var title_f0_26_416="Visible vessel GU Endosc";

var content_f0_26_416=[" <div id=\"graphicsToolbar\">",

" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=GAST
%2F61604&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=GAST
%2F61604&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Gastric ulcer with a visible vessel",
" </div>",
" <div class=\"cntnt\" style=\"width: 318px; height: 322px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAFCAT
4DASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwDlba2Ms9wD2OP0rUtbUDKt8pxxV8WqQy3HYs4x+VJNHsQFvvjtXzUpXZ
99CFr3KqRgfI3JU8GkjU+WQOmakJBfdyqjrxViONliwQMnpSWhoVmiI2479aesTgE5G01KAQJNw4AGT6VL5
QSFDuOGOBxTuNFIRjCKv3RRJH8rBavLEEIX05qJEIZ89OtFyluV5IxhgFoEJKqduMVZEPzsd3B6VLEjHC9T
6UrmNSdiokWeDU8dtgFh+NXIoA2CR1q3BABuUjjvTucU6jexmRWnBx3pRaAcHtWtHBsDEj6U9IA67sc9TRc
53JmStqG/DmnrDlmb2rQMIBwO9BiADnpxgVV7kS0Mw237sHueKSWHKKp7VpCPJAoMS8569qVxXMv7NudV9a
qS27KrL/dPFbZiaHDuMHHGOaSSHKRM4AG7L+wqou2ozBuoP9V5f3hyazp4sSsZOua6KeMG4k28Kfudsj2rF
vuEMnVAdpI7GqTNIoznjw20dDVeaIcp1xzU7ylTk5x2NPTDAPjJbg1Y+QoeSWGBxVe6QxsVxnIHNaTja/pm
opQcEOuSOc1S8xWMZgNvlkdar+QMHd/rBVudj5mQtQM4WSVW6sOKotJmdKhY7pPvDpUMi/Luj6iroVlTlct
mopV2JvA+TvVLQpozSh3qT/FyaiuEImDr92r4QZ3E5RhnNQXKlYwAMhuhqkzOSuZ7K3nZXoVqntIcknnmrs
inz1CHIK8VWMJZuvK9ea1TMZJldxlP9qothC7j1zVsqCCw6jrTNu5cnv1+lUnY55IrlSmAfuNUTqDnb0HFS
leqknHakc5GCMHp9atMyZEOHP0psfC/NzzUmMyN7CkjA28HJq7k2uz6cuGUTXPH3WH8qpPG053S/L6Va2Ez
3IYfLvHP4U4Lk4+96E8V8/otT6u12V1TCFSvPanugbbk4Iq0o24DDk9Pao2AxkjmncpIQqGB44HX3p8RUqp
Ycb+KFwGHJI7ilAwifKNpbOaGx2I+ImBbkkGolXbvcjgrVicDeCee2KcUPlcDOQBikRKSiQxQYXrk1etoCU
JI/GpIrbcy44BFX4YSEA9Tinojhqz5tiusICLxzUwtxvyeM1bWEInPODUphG4kHP8ASocjAqMgBxTNuAfer
ckfpURjJNWmZsrBPmzTXTirmxQVVmAZugJxmlEasSAVLDqAelPmsS0Z+zANIF7mr8kG1ckVXdP50k7hYrgf
xHmopBlt/p2qS5kjhQGV0jUkKCzAAk9BUUjhR71auNK5J4c0yTX9Vax05ftEkXzSO3/LsD3/ABrm/EaWq69
faZpsnmW+nfuriVejyjGR9K77wBeNpl3NbWQjhF6QJ5T1wM9D68muN1a3s4/E+o6bpERg0u0kLEHnzHwOdx
5NbNRVrGkE3Ua6af1/l+JzjRbewK1WZfLYsDwe1XZla4lKwH584CCqlymCYmO2ROStCex1JLqGRIvvUU3yQ
gt1zTLSQGdY24LGpdSWQK67Bx71RlKFpGLdHMgKjiq+0Ncc1edCkIXGS397jFUzEyyFhgn0qky1AZLhXqq2
HRkx1q2qNJl2woHb1pixk4bbgntVXBxM9g0agAZA4qnKSzBjwF7VqshcszfLg9PWqskXysQN248j0ppmUlY
zSA7FlQf7NQ+URk7Rz1q+0eJxtVdoGMZqlcp5bsfXnGelaJmM0U9vJXsajbkEDoKtMQApbgkdKoTSBQUPBL
ZzWsUc0mISBmoj8zZUAketKzYTIGWzjFMMZK9cN/SrSMJNCZ3LIVUYxzSxqXUEADHFMPovyr/Ec9aVcqMEc
duaomL94+p2UGa5UjjcP5VGYyTxxirsiZubvjChx/KoQN7/ADfd7V85c+yUdCDncE6k96QYV9pGal43MT8q
r3pZF2/OnzGqQNEDMHBAXHrRGx+ZHGFXkU8jgZxhu1GwngnOapGM5WEQCRRnrV63i3ALUdrbjGMcjHPrWtb
W/VlGMdqeiOKpO4W0G1DnqOKvRQDlTxxmnxxZPNWNgHUZFZtnO9WV0j+YDGQeakCZ4AqcR8ALxinrH+VZ3C
xTeLimCEelXnXmmlOCcU+YXKcZ8QNOuJdMttQ02F5tQ0y4S5ijjBLSDOHQAeoPT2rnHsNft9Dtb6KG8hl1K
8kutQWBGM0SsP3a4A3YAAyAM16tFFubNWSgC1qsU4RUbX/r+mYyw6nJyv8A1/Wh4rfyeJgumfPq10wiCtGs
EluXPmMNxbaQDtxkPjpnvTt3iT+29RFut/NlbhoXkVoo4yAdg2sNjc4wVPue9etzRZaoTB14raOKVvhRm8M
19pnjcdrrd1axJcLqU4+02sjRz20mY2D/ADEMRyMdcZAxXeanbOgyorrEtwB05xUF5aLJGeKU8RzvYqnR5O
px0TyKvBIqjqErGN/4SOSff1rcubfyyy96ybxA6/MAQOo9RQnd3O2C6nORz/ZJFnxtJOA3rUMp813uH+
+3f1qTVreQoAo2gHKj0qERnygH5atOh0pXIbGPzrh2xgp3q/eqercZHWrGnWvlxNIy8NVPUn5jUZ3E9PSne
7M5LmloYkys0hO7cBUSqFKE54BBq/JGjzeW2QO59aYEZQftAAbsKpaGqRVEQKqq5ySTRt/0gkD5QtXpI2jR
XwN2OPWqrqCoIO0nriquQ0UdoMfPXJqpJiIsT0PArWeBVYdNuM1mXi4jLsuRnhfSriYTMm5EaMGJO89azb+
VQ2S1XtSkCxqf48ce9YDMbiYhzgjtW1NX1Zx1pWJJ5RJsJ7DioGxJvZvvrzinFNzAYxikZcSEfxY61stDkd
5PUhJ3Lx94UhYbQSSXqV8DgDDetR7Qp49KpMloiIXPfB60o56HgU/b8zj2zSIEIG4npVEpWZ9cGI/aLtXIw
XH8qrSgEeWvGO9X5QPNuQBnkfyqkwKv0yMV8xfU+1jsQTqGRdv8HLe9QSM6r8pBHoDk1JOcKpj4weaiG1WL
r941pFEVLIcoXZkHJP6VNboc4PfvTIogF/2nPNaVrCGAX0rS1jhqSuSW1uQME8g/nWtDHhie2OlV4YgxQ45
FaBUb1Pes5SOaSHBdtTomRz2pNgU/MM7elSjhQwGQ3GKxbENXGcnvTzjGKXyyp+Y5A5ApwXIyOhqWwRFt5o
KcVLt5qRUzU8wMihTAp7CpgMCo2HIFS3cSK5QGk8oU/PA+tPXqRTUimiEJ2phj3I3qKslcYNSWkQMxB6Gt4
O5lPQ5TUrfzF3KOR1rmr+2aTDJnjriu0uIWS7lTsSQKx9Stfs9vJt6nkgVvGRrBnEXyuXIPIAqtZwefKB13
HFalzE0rMsI69avWOnC2iDtwx4B961vZHQ3ZFO5TyIhHj5axr2Ikecoz2Ard1RWjzGPnI5FVLiIraoCOT1a
pvpcmG5hSp5QUyKCX6kdqhQJLMAcs1abwiP8A1x/cmoETbcPGEwxHNaJnTaxSmKTzFFJEoHy+lVFAERDgkg
9qt7XUtuACxnv71G2A7OnQ8EGrTuZzRVlGV65B9Kzrj5g8OQWAzVyYtGd0ec+npWZdERuzr1I5rVaHPKLZz
Grz7mCR5z39aoqA23kDHOe9TXjb9SZgeBUQCqc45NdUdEeXVfNK4OMybulN4Z255AzUjqC6A/jURC+cSPpT
MyIkGMt3phHc9xmpNm1mHY0zbuTGcFTwapEsbn53/wB00tuoYdBSOCWz0PcUjEA5i6dKtELc+v3O25uQOoY
dfpVFnCOQOc+tXJSPtF0T/eH8qozDB2jv3r5nS59tHYqTsGVtufl5PvUbLlVC/e9+lPC535/hp6KWjGBzmt
Y+ZzVi3aIH+Y9hgVq2sOGzx1xVWCP5OPata3jwoJ/vUSZwyHxIN3A4q6IwSB3pIYx+VTqMHNYyZABcNhevf
NSouDnj2pVXJagcJg9KzZNwAHXOT3pemeu3NKqrjjmndBgDrUslsQAAA0/oPelYZApxX5RUNktjByOaiz98
jipG9u3NRu25AO5ouUiE9gOaehBOQe1RSeinBFKuQoIXn1qb6mrWhKDnacHAPNW0UhxgdaghVtwxyMZq/Eh
K88EV0w2OepKxmy2itdF36CsbUbMyySYB2kYANdO65ye4qrOodAQMEHrWyYQkcYNMjifKAA991NMasTHgEK
M4/wAK1r5QJTk5NVEUWxe7dMpEB+Z4FXH3r6m+svXoc7ZW6T+ILWzn+/dv5ca+rHPFWfHuh/8ACK3FrFdyx
k3RPl7TwPrXp/gTwilk7a3q6K12x8yBGH+oXH/oVcJ8VtUg8aJbR2cRh+xTMfNfDbiOCOK3lFRSbdm+nl3J
o1lUxKp09YL4n562SODuUYHEa7gDjD8D8KrTofKmlGROelX7pfPeNl3JJF1xyD+FUbtkaVovm3Cm97HoJOy
uUVg8yEmTI3Y3A8ZNVZl8y4WNOWX14FaErYC784XjFUWwGkK/f7VS0FJGXdsySyEdAQPYfSuf1KdUhmfd26
Vu3qk7A7Yycn864/xLMsl35EY2qvU1vTV2cteXLFyMyCMPlmPzsOhqQAKBuwQKTIFwgUZUDr60uQZD8nANd
TPHsyMKcujFd55XnjFRMo2jaRuxzU5dPOLbeDwKrxgPvAGCOaaAVjhFz170xkyMEgZ5GKXBkTHTFNxtQ7j8
2MCmTYYxL4PAIODToAoLemeM0zA3Y9RTgv8AfqkTY+uZAPOus/3x/KqZHXbyO5NXnA827z/eH8qpTfJ93oe
tfNNan2cX7pVlG7Kx9Dwat2qL1PTFQomGBHfrVy2AKmM/eHNbHJVZftIgY8NkA1pWyBkQHIy2aq2y5CccCt
O3T5UNRJHHIliTnHrU/lgHAyaIR86n1qwqfOx9KyaMZSsRuuZDjOTQyBUJHJHY1YCfvC9NYdTUtMyUiJcEq
MAZp0acmkHQn0NSgDOc1nJA2Nx83NOxycfrTj7UgB3EnvUWJuRsqjJyar/x59KtMmaYFxkUFxlYrBFOc9+n
1pQhC7ec+lS+WMfQ5p6jcd3elbW5bmPgAyAv41azlOuD7VFEo2jH3iaS4JSPA+9mr5jnfvMJD8wIx6U25X5
MDG1upqGdmIjK9M81YuQx2jPGOa2jK5VrWOdvogAWA5zxVe0UtqenpdLvtHlHmKenBBGfxrXv0Pl4UZzWec
7xCOjD5z6Cqp1OR3fQ7IbXR6H471T+zPDF5PEQZWjKxgdyRXhjxzWHh6K4lwZ7hiTj7qknvXRX99Nd3YgWY
yW8K/dY5zVHw3MuqeB/F9xeKq3loh+yBuqHaeg78gV6EpSxM51EtEr/ACTt+b2FgcJ9Uo2et2r/ADaS/O/3
mD9he0nVmyJpk4dvusf9msV9u5hNlJGzg16F8QYGufgLpGoRttvFghd3UcsSPm57c153cXizJDvXOEAJH0o
lCUZOMt1/w6/M7KMnUg5dm0/VMpzh0GZeYx0PrWe53OZiAB2Aq/OWcxR5/cZ+asu+JElwE/1adKady5LuZl
+SxDKAULZJPUfSuM1NvM1GUrgxAdT1rp9dl8i1MivtjxgfWuLIYcElvM5rqorqeZjpaKALIqkkE5x+FLkog
KnO7rntSE4RSE46VG0hJK+lbnnMW4YARhD8vXnrUQkQu24kZ7iqc1xgkEZxUElyzJjtWqptnLPERjpc1pSq
kBPu4zmmyfcR2HzZ4HbFVYJDKoU9cdasZPlovXmoatobRfMrocVDdgMc0RdDkAnPekcfMQTjinRfdoTLUdT
62f55rjHABGfyqnIePmIx7CtBhiS5HfP9KpsNoIKhs+navnLan1qehFCACNoJHc+lXrRMEnHJ71Uhj2ZwTg
9a1bYYKgDJxWvQ5ajLdrEVHB6+taVumGIPTdVeFVbBY9OlaFuh3nHUnIpHFNk0CDZ+dTqPlwB2FNjU8f3uc
irZXaoIGeBU2OKctRCnymo3ThcYFWyuVOOajkj3AKc1m1oZKZSMeDz09KeqgjI7VLsxwM0Adc1mzTmuNAz2
pdmPvdD0p688AcU/A27ev07VPLbQhyKyodxDDjsaYI/mIq0Fz8p5x6U0IQSSMVPKUplfYV5xnmhUzk7SAal
dfl64JqWCNSAGYgetDQ3OyuQBPKQEZznPNEgEi+9SzcPhQSKrtlJc/pWcpctkEddRxURlSy5FWlQeWzNhsj
io5zm2GwZyaXf5a4XpjmiMuV8pDvJFW6UGFgFHHesCVGG6WPllHI9RW7ezAWuR1JrKijL6ha2sYLm7JUbe3
rWsW5TtE7aGkW3/AFY51o1jtZpoBh5jyT2+lc1r8c06HTtIkCtcDypJzzgtxj9a7zx5YQeHrKCK9lxFK3Eg
4APoaxfA+kzXGrw3F8IU8M+W7Ldu2BK+flCk+
+a7aEJVHy212fy1t66Ho060PY/WVt087fr5GT49vTc+H/DvhG2MsLabGiXq7v8AWhVA3ZHqRn8a5sxIYMQD
CjjnrVzMlxruswXUPlwidxCDnO3PDH6jFUiGEYOcNu5x6V0Oo6j5311/A6I0lRiqa9fv1KlwMwuPugDkd6w
59yQmNyd5P5/Wt672/aXGDJuAwV6ViTIUnnZ/nwPlx2q4u2hE0ch4rn3xxwAD1x6VgnhEyeVFXNWkaadnzy
GIxVRF2sfM4yO9d1JWieFipXqNdhiyF3DY+RBwPWqVzMBHIx4J4GKtspJUD5QB09aytTkDPtXoO1bQXNI4a
8+SDkUgSTyacBupCOtCHBrrPGW9mKjMjggmtW2lWVcscEdqzQM0+JjG4rOa5kdVCbpvyNNFLkBu6nk062Ox
SGGeetN3ecqAEKdpzUtsNyY7jiud6Hp09ZXPri44nucf3h/KqjfKOO9XHH+kXW7kBgf0qjIcZOM98V8/a7P
q18I+Mbht6Z4rTtMvKo6AIRms63Ifa+MAHkd62LPHljPdTWnKclQ0LVFG0H860LcZyw6iqluPlXPYcVpWyg
vwOKLHn1pEsa8D+93q2qEimQoMA96sxg59fYVLR585CbcdKay8ZHWpgvGD1pAvPPSoaMuYrFeaYyc49as7c
t0o8rnqKSiWp2IFAXjtQoAZqnZMdR+NQvjsOtS1YadxighiRUmCWPuKRAQDUiYVCT1xUSVhtlJh+nFSQcnb
TZRhAR9KSM4+tZmj1RMFLuR0wOtV3XduU/nVtORnoOhqFh+8xj5TWdSF0TF2YyFwFCv0PSq9yjKhGckmrki
KoDEZC9hVKds/NzntWDvsaw1d0Zl1MTweAvajw3KLLxRaXdxzbybox6RkjGabeoeXqCIj7Mytn5j/AC9K3w
tWVKoqi3R6HKpU3Ho9PvNr42SWs3hkWjqslzK4MY6n6/rWH8NpP7T08eGURfsun7JMvyRnk8fUn86y9buJb
+7Lxgu0EZYbudoHaquhatH4a1V9atpELzjF1A3VlXuv5V7NCqp1pTeik9fwt+H4l0sJKngfq8dZLVf4v00N
b4s+GU0UjXoEaS3X5ZkHUDtXnUarJC0kYyDzXsvxY1SLUvhZNdoZYLe7VSCwwcE5H54ryGOMR2ytF8kQAyG
6mqqU4wnKENl/lf8AU0yypUqYVOt8Sbj91v8ANmHIrPkx8OvQVh37lY5yeDtPSuju9u8tDwT37CuN8WXI0+
0kdwSzjAANKN5NR7nTVkormfQ4NnVnlkOSFY5/Oo1cMxldSV7UxD+5dmOVJ5VevNPTbsCMxwegr1LW0PmnJ
3b7gdwheaQHy8fJ9KwG+eRiPrWvqU5SIRA5T+H6VkKMZJ6e1b0lZXPOxcuZqIlJTutCrzya1OO1xyHFOJyR
TADTlzmkaxb2LtqSX/CrtuBg4BrOtyVJPqMVqWUZkJVWKkAEk1zz3PTw+p9cyf666PqR/KqUqgIX74xVxzm
a59Aw/lVY8qa+f2Z9bHYbANqxn+
+cVtW+AEH+yaxIiCRu+8pytakBB2sc5ArQ5qmpuW5J4A4AFaduMDJrJtjuA659q2rYfKo6/WmkeXiNC1Au4
Db1qwg2njrTFAB6Y+lSjOO2KGjzZO47buOaXbnpSj0qVFGMdqzcTJuxGEwOlIU5we9T4o25pWJ5iCVNq4PI
qm6gcAcCtFhldtV2iGCMc0rGkJ23Kqd6JD8lPVWVjnFRyHnFYT2NlqyIR5QmqhbDVdldo4vl7nFU1UF+elQ
1Zm8Nm2WowSwQdxmrDJtGQMmmWpyxc/eHAq03ysd2M5qam6OecmnYpSJ8hz35rPuh8px1Fad1tBPBPFZs0T
DBJ+92rmb1udFF9WZN0zFdpqqny/fODg7frVi7I80A8Y61FdkJbtOMDy+eeaqF07nqw2S7nLy3BTUrXRrbd
9u1KYRM/wDdBrQ8beF4/Deo+HBLMWtLm5WO5kx7jj6Gl8MxWUnjW11PVP3drAPOSfdgCUZABHpiofFep3Pi
DWZ5dQGba3bFtH/BjJw2O575r2qPs6SpuSu73founz6ff0OznnHERjB2ioty827pW9NDvvi3dWy+ErjS7cJ
9pkQJCgAwmMflxXjqQMLRFztU9Qa1ru4fylVpTIccMxyfzrNvFCBRku45Ug8VUqnPKU3u3/wEY4PDfVaPsU
76t39bf5GHqMUYm8pQfXivK/HV99t1aO1j4SL72fwr07UpS73E7ECSFcjHA6V4xJO15fXl1IQGYkE9q3wyv
LmfQyzGo40lBbsrEEnbt3KTxjtUm3D7gAAB3pE+4VVvlX8CarXkggh7729TXctXY8RtRV30KGoTGa69gccV
BIvcdKcpw+T1PWlf07V0rTQ8t+822RdDS9qUDijGeBVEpCjnipVTiiFR3HNWimFBxgVnKVjppU76sjiXFaU
LFQCnXHNVo1xHkD61btAFJORgjIyM1jJ3O6jGzR9aOMTXS9yw/lVfoDVjAae4B9f6VWIxknrXgv4j6qOw1V
/eKe1attg4FZMY/e8d+talt91QP7prY5qht2Y54rXtW+cCsm0HCn2rTtz82aqx5WI1NeLDKPWpsZGBVe3P7
sVaPIGKbVzyp6MRRzViNarquThasx4I/wBoVLiZTHYFIBUqgHjuKRuR06VNjK5CFyc0x0yTirBHFNZeSanl
KUim0Z5qsI8Pk1pmPNREY+XFZSjoaxqGTeLkewNV8bRV29G0/Xiqjx4TmsWtDtpy
90u2K5X3zmi63CSVuy1PpkebfA67qszx/wAJAqJU7o5ZVLVGZEG4xNJJ17fSsXV7zE6xRHEj8AeldDdogU7
TgLXNTQxtK1wf4ORWEabZ6GF5ZS5mQyeV80lw33BzTr3R729s1vYgFskXfnPUd6brcG/TzCjqk7jevPPFbU
utLqngq5tI7k299Hb+W37vhuMYH1x+tduHox9nOct1t/Xl5Jvsm9DplUqQUJ0+rs/JdzgLaGPUNT+x6URPN
cLnyiflJ/vD8qrXEscep3On7993bYEkZ6irHg+JNCaDVLW0FrqMVu0EkRYyfLuJwM/nVaeGMaxfaimRLqDB
nYjof6da6nBJ2Xnf8LWPZtarKK+FL53v+VtjPZJC05ZfmP3VrOu5CTsRtuRkVtXcRXf2VF+7/f8Axrn9QkM
SBl+89C2HfmscZ461D7NpMsEZIMhAdx2rzZI9qsinjOTXR+N70zXwtY+e5rCdi0SZ+/u5xXoYePLD1PEx0+
epy9hjsu1HcBQvAx3rG1Jmefn7vatJ2ZmIJ4B+UVHewebCAR81dMHys8yvDni7GOBnJ9KXORU6QSAjGNydB
QkLuHyQMnJrfmRwqnNdCBFywHrVpIwMgLuanrCqjIb9KnhyWA3AZ45HWolO50U6NtyFV+ToFqRVJwpOR1qx
GokSTeCGHBwM/SnxRSO/lxqob+Lnp9fT6VDdjpjGzIgAgyfuNxT4AoXMjYPQfSlnx5jbThUHXH3jSQxloFM
frzmp6GsFZpH1sy4muOcHP9KiPZj9Km5Mt3n+8MflTG6KteI9z6VP+vkVYsCYnPy55PpWvZnhfTBGayY1zI
x7bq27Pb5Yx2reK0Oeqa9pjb+ArThXgY61nWgyuRWnb9fxq7aHk13qX7fovpVuM8HP4VSiOPyqyp4NKx5tR
EijuDip4shl28mq6VYSixhIsrjcxzR/AB3qNugxUg6j6VLRg0I1G3NDdTUiD5BSsDdkN8vHaoCvzknrVxhk
/hVWfhqzkkEHcytSG7BX+91qtjpuFXLsZ4qPy9wFY8vQ9CErRSLNmxRQwHy5qxITKNy8gd6ZGhS1Ax1NSLE
VgOe9M5pNXuZU8JmfCH5e9Zxtle8WND8sZya6CSERx5UHceaynUw2lzMSAxBAzUOPY7KNV7I5fUZWvNS/0c
I8gyiZHNLfD+z4o4oU868IzPFnoD6GqMrP9sE67VlU/NzwRRcyR3WXIzCpyMHnd3rqglGPme8qduVdERF0G
jXUSyq+omUmG5wdsKcfLIP4j16Zqi6+XZ7XH7yQfvM9/dfQGrM0pMKbABKTgA9Me9VdQGSMjEkY+b05oe39
drf8P56nVFW+
+/8AXkZc5CWa73PlDhWPUVy2r3Ajhmnz+7jHJ9K6DU7k/YhGxHJyK8y+ImqrFALK3OHf72KIRc5WQVJqnBy
ZwzyfbL6eZ2xvOUOOuKq7mWdh1LNVjJSGNQQFXgkU9IP3uAu3HO71r1LpaI+fk3Jtvcgih8vblS7DJPtUrx
7oy+dnoKmwFYEHG81K6gNgNxSb6gkZy25Pz7SHUcn1NRvCqBWHzhuCfSr6j5/UHrTWjBJQY9RnpTUmw5Sp9
mKSBG25PT3p8cBa9htWTLzMEQAcknpirmmQWsmp2sWpvdJpZfNy9uoaT/gIPUZrotY1rTfs8sGjaLbKtvcL
JZam5IuVwONw6dapbq+xMk+iMweGLyy1uHS9flGhHBlNzcoSAAMqMDk5pfG2p6Xq0unnRdPfT2ggEV3KW4u
pB1kA7A+hq1468Wat4xudNutcuI5by0j8tLhQFLfgAB1rlmLOXY5Lk5Y+9TFyavL+tXr8106ERg27y3GSHz
GbZhV7Ie3vT7fcw+T7o4z6mo4g3mPkdqbAWwdj4GelUXHWR9fTKUnuDjgsP5VCBiTPUYq9KuGut3PzDH5VU
k+RVI714z3PoYSuiioKSOM5Oc4rZscKqqTy36Vksv8ApWc4FaUDhSpIzjvW0djOqb9p8qVpQkA57VkQthcH
vV+CXgA1ojyq0WzVjap1bIrLjmwQDU6zn5celFjhlBmmhHFUo/EWj+R5/wDaVp5P2n7Fv8wY8/OPL/3vali
mIxmvKIvCPiFsaMNPT7H/AMJN/bP9o/aE8vyc7tuzO/f2xjHvVwgnuzjrJxPY9J1Sy1eCWbTp1niimeB2AI
w6HDLz6GtAHnFeKjwlrsNpZi70yS906PWL+5utLju0ja5SU/uXzuCkLydpYdfaqOoeEvEt34giu4LO/jtUi
tfsSW9/G76eYwN8ZZ3GckEllDZBx2pulF/aOfW2x7wepqvo+q2WqLeiwnWY2dw1rPgEbJVAJXn0DDpxzXIf
Djw5daUdUvtYS5Goz3tzs8y7aVRbtLuTCbii8Y7A+tclYeDfECeMpbmLSprQnxK+p/2p9tQIbMqA0Xlq5Yl
8EcqO2TxUqnHVXFJux7Yen4VTuDzn0rwuw8GeNE1K9uZNNu7Frqzu4Ln7DfxIjuzAxmMlyx4ycvg54+WoF8
FeLx4c+y/YlSBL9JXtFmRJrqEIRlwJWiyGIONwDdTjApSox/mQqbd9j2ubkgD1qxDH8oGK534b6Pd6X4VtL
PUhdLNEXCrdSrJIqFyVBZSR06cnAwM116qFGa5JpRbR0Sq6WQyXgIg7U9huUKewpAuWLHrTlHXNZ9bmTZHI
CWVuMAYx61zPi+Rbe0WDkGU/e7LXSXuSqhR05rjvGdyjtEjkbemDRbY78ujzVomDKhO1WI46HGM1WkASVCf
l+n+FPuHUsoycY4Lf0qILvDgnLAZG7rWy0PqI6K7IWQP5ycsTyO2Kz74MYADKEUdf4i341eluVWWApE5B4Y
9qxtSmjhldExhycjstNmiZha3cRrEZwNqRg8E9eK8VvLo6lqt1dSsSuSFXHSus8ca4biV9KtGzk8yL0FctA
pVjGpHzV1YeDguZnm4ytzv2a2RXCLhQqkj3q3FEQTtflepIzmn+WwCnIKDg1OkeyJ2PUmtrnEV5FUb2C89g
aSCM+WWcjPpip9mXIPQUMOcdqNykU2xliByxzj0qMxMXDbse1W5cJ2qq+4MDnjPNNMAYrv3DJXGCBTUzEgV
RgN8p78U+QqAQBgseKg80qyluR938aLX0E0KXVIWXaAAflJ5xVXJXdk8sM59TT5Bi3fccsTxUUhJjUD7wOc
+1WlYnYbKWRDITgkYxTbc+VGNxB3c9KSQlvv8AK0QYC4cbvSr6Ga+JH2fJGPtF1gfxD+VZ1wmcjpitiYYur
n/eH8qzXG5zu6V481ZnuUZdfQoTR5PTJ28mrNuTsANSAAM3Hygc0BN5yvFVF2RpLU07ZieTyccVeiasy0bG
4e1advyB71onc4KqsTrk4FWoFwMmo4lGelWVGFNWcNRjjxgVYjYoq/WqxPzgVbUZApHNUV0Q3F2VXr0qTTp
MRZPeqGojDCrVqcQUtwdJKmjVjnBIFWBcBVx3rHsnJlJNTTuQx9M0WOaVFc1i8brctV1LPJxTIcOuT2q/B5
YGeM0nC5jKLhohYYmwMmrATFOVhjinA5FJ00YNsi2gVFM+B6U6d9hxVO7fJAFYShymtON2R3MpKtk/MBXn3
iG7M2ox2yN8xOT7Cut1S8EEexz9843V5b4jvvK8S5B2og5b1pJa2Pey2lyyuXLudlAiikKsD8xx1FR3N89v
HHJYxo0fRhnv3rJub8S2qOThZG25A561HI6QWQhJKgMWDbvve1a2PbfKkWJrvzZXKsY0zyg7V5/8Q/EP9nW
6WWmufOlJDsOTzmtHxT4jitbcRW2POdsE9a82kaSa7LznfKxzk1pTp80k+hy4iuoLkjuV40EKMjDcz8sTyT
UkEWTwMMB1p7RFpSy9B1qeNRFLKfaupNWPOI44v3bBFyM8ipSgkfaeAO1TpmKAMvJbNVomDAs3XNTsJK4yQ
YPGM9yTSBl6Pk/SiXmYDaTUci4brt+tUiraEdww3gf8swOBVSYNs5POePpVorvmZSc96rFt4cnovFNCk+Uh
Lb29x0b0phASJtxyxPB96WNSVJ6JSiPKgk/IDn8apLUiTK2/aNpHP8R9aid9iuc5J71MSWt3k7FsfrUMoVu
F7VdjNsYFOCD6ZFOs/lUg/WmE7pDjstSWgyCT+tUStz7XuF3Xd2PcfyqjswNn41ryx7Ly6ZuhIx+VUJ0COp
/OvLmj1qU+n9bFFwfmY9G4pzD90Mf3TSy9QP4d2T9KRe393BrPY6t0SQghF29cDNatm2cc1mIpGCOhFXLYh
eCTmtIs5qyujZj/AIanUgg1RST5VAPTrU4YGMkHmtkebKJIWxPg1fi5FUGXcR/fq9Adm0N071JjU2KWojdI
AKljbCBe9R3Z/fjbyDQw/eDb97HShFbxSLFp8p/Gn3Jy1NtxwWbpUczEnA+9VWM7XkWbB90bZqypYISKp2i
sFzj5e9acSjyTTSMKrSZas+bct3qWE5TmorVttvjuelSw8LiiSOGe7ILgF5FI6rzWbczZlfJyQa1rthHCcd
T0rk76cW/2idiQqjJJrnn7p1YWHOYerXC3dzNbF8LGN5rybUrmXUdWuFhbIV8Zro7/AFV7mK+ng4Z8KM8cV
gWASFMIuWlPzt6UoRsfT0I+ziyeO5aGAhuYgMEeprmPEWupBZMrHbIx+UVra9dw6NpzT3LFYj9zjJJ+leWX
d5NqF0096gAk4QA5wPWtIU+d3exNSv7NabslluZLiRZp1+hpv+tmXJ3AetRwhvMZN24L2NXYUQxNlTkcgV0
uxw+bFNvuKFugPQ9KlWNifLK4UUsbNLAyt93sKtRMHjZwSVA545pAyiF8xyqNkAHioYY/nwi7T3NX44BsYj
Kq38XcVFO6wWZDvGr54ycbvYepo8kNMrIG86buQcB/7tRSYCvk+a3Td6VtLpt3bahZQXlncwXNwu5LeSMq8
o7MAeSPeqGsWbWk9xDPGYZw2fKHOOe/pQtRKV9jIVVjlCvknqCO9RmP/WGSMCIkEEVZIZmLMAp6DBzUmlWq
3/iGCwll8uCUH5j0z7+lXFEzdjHmc+YI5P8AVnoaJpFwIm+8TwakvodmqXto7DybdygcHI49DVeddyj1jPJ
NWlsZsbex/ZkBl+YnpULN8q44cjj6VI8nncPlgBVVySBkEc8fSqSsQxUZQ0xb/WN0NFsu8nzOcVE3yxAnOT
xmpLYlJGPbAHPrVPYcNJJn3VcqGluD6MP5VRnTchB9K0CMSXf+8P5VSl/1QHpzmuCaZ20mZky/JtPUVEwwg
+hqzcjLbscVA7fKAfQ1zM74u6JIfmT6Cpo3x1qnGxUj0I4q0p+TJAB9qE7Cmi5FMFCsRnNWlmCsDjisvdsb
GeKsRykrg9K1jI5p076m2rAvkVaVulZdpKSTnGRV9WIIOK0uedUhZ2Gz8uPUU9AC249uKrmT98wFPR+2O9I
HF2L8QypVap3B2ylT96tG0Cs3BxxVbUowh8zHA4JpvYwpy9+wtvIRAAOuea0ovmiI9qx7Bg020k461qwSZZ
lGM0X1sZ142ZbhP+jD1zU0bYXNUvM2w7QBwaljmXywDxQ2ckoMW/O0BvbpXn3jy4PlraKduTuY+2a7+7dSU
BPBXrXl/wAQiftj5fAXgEdTXPUep6OWQ5p2Z55Lci4WUJ8qqduPXFFnIFkQAZzWaz+bLNkeXGD/AAck1Ml0
sFjdunOxDhm6j3rXbY+gmrHD/EDUjqetpbh828R5UfU1z1wdsp2f6vgAVCjmdZ7h2PnSOefxpwJMSCX5SSR
kd66ox5UkeXOXNJ3LQCq6Op+Z+1XvOcIMDjpWbGQhibutWlcmLOT1yM0mBdtnzJg9DVgIREsZ3LIerKetUr
Z9kZc4LelSNII5VD7jjkUmK+pr+ELC48T66NBsXRL2RHdRL0IQZbn6Vg3q2+owzW9u6TwwtnzApV43+ppZp
2a5WYMyMvQqdp/Mc0kkryNLI4HmSj58cbqfmtw5Xe/Q7bSPiRqFh4k8O6rdWq63qlqv9nQJKfnKyH+92bjA
PvV79pm2tYPiHo17p8uNYvbZPtmljkxjn5mYfKe4x/s5715gEDJiZQyDrnjntVvVLu51OeC6v5WuZoo1hjk
c8oi9Fz7VXNZRXZtv59P8zGdC8+ZO2hVm2R3pjt/mjBwX9aitp0gv0nlUsi7lyPSprl9iYznB6+tUN7ROBx
5fUH0NEbpGkldMjuSA0hLJ9mkclUxyKgmlYh0OxnzwAOgqeUDDMWJJ53GqDSbZdzDcTxVRRDs9RpkZUJxjH
HFQ7maPPVQe9SFSqlc4B596glc7G5JJPStVqZu4rEsm1OSOakh/e89OMGoR8u7cdrFe1Pt2IQdM47UxR+I+
85U+e7+o/lWdOvyCtmZcyXOBj5h/KsiY4JVuD2rgkddCVynKPk6ZPpWbIRu59DxWhOW8skcFfTvVGfACsAC
cHNc73PSpEZbYC59Bj2qaBujMevSqUjEKSTkEDiljlHljPJFZs6HC6NU4dM/xelLEexqnbXAZAScseM1YyQ
ygHr3oTZzuNtDRtm+YnNasbgxqc1goTGOvBq1BOydckdhWimcdWlzaosq+JmNTwSAqW9Kz88lt2c9qltmO5
s8L6etNTV7GcoaGtb3Pk/Me9XwVuIHVuh5FcsbjbvEjHAPGe1XbW+Kxcvle3NVzrY56uGfxLcv2SmOVty+w
qdC0MjSHO01JY3MEqAnrjqapaxdARkIcKB2rKVXXQwXNOfK0Tvch1HOPmpj36iLA5wa5WK+lljcgtw2Bmnz
XUsaI54UfeAqnUTR2fUktGdE2o7i+4/Io/WvNdXun1jUb+OIHKHArea+jdmkSY7Txtz3rlJ5fseqSSpIUEh
+ZRUxV3dnZhsOqd7GHJZiCYLHzKeGX3rn/ABKXg0vUGRfmwQwHauzWRJ5ZHmRYXBysg4JrK163E2j3TCNRu
U7zj731rRuzOqWqaPFoQDbRHpjJP50+XPmJtG5TUNuSYmQnOGYfrViLKMMHtxXe1seOPVQ0jEdxwKcjNJuX
btVe9RJI0ZIPDE8GpyxC/N/F1FSykySIMYS0XzY9KXfI0244algzGmyM7M+lPt1Xzwoxg0gvfcjkYs2cjOe
lSkF433DDAcUxkWK5YgAjsT2pBIQXLknIpdRjMBrTYDl2anb9lg6H7ymoY2/ucc53elNnO5gATtP3vemyWw
kIWPkZLjNUSCQe/bHpViRj5zbSTGOhPaqzsy5KDB9B3qkRqR3pHlKqdqqMVwCRk9KnnIVd4GSf4fSqsqHYT
uIPXFWkTshCPl3Oce1V5AWYMBjHapmkBt9zKG29QaasgUkyDh0+UelWlYzbHXWxmDDhgtQQkEZRT70AEswO
GOO9JBKwTaTgg01oTT+NH6Cy4Iuj/tD+VY90AeT1xxW6VBW6X/aH8qx7lcnGOFFcM1rY3w8tTMlXZEWbk+l
ZrfKDnkEH8K1p1Ity/esqcbMj+9XO0evRdyizAoynGQKqiT5SvQ1PcId24elZ8jhZCTwazaPRhG6LLyNEgY
ZwT+ValvcbljGQc9+1YPmMyrk/Ic5qw0vlRxMn+qU0mjOdM6pRvX+tKrc4Ix9ao2V6mwhyByMUW19v3CQdG
ODTucDpy10L6P5bZcfnSySMFDjgZqFJVmkK5z7U6JgzNA3BxlalIhxtqxlzMjZU8Mf1pkc4i2qozxVLUJDH
Io2EsOAahXe7ADpj5jTsdMaKcfI6C2vw0bYbDDsKbPfG4i2OAGA9ayIn2qVQYHdqeki7wpI443VlKN9TJ4e
Kd0iCO5iRXUs3D+lLdXTRFXbLQN1PYVQ1iNraXbj923zZ96hgu/NVoZP9SRTTujdQTV0WdUjSPyZ7Tlepx0
rDnCXd+8hzvI49K11Ymz8lPuA8Ad6zNQjZY0lgGJF6L61pB9GEVbQoyI74tJmAdTuB9fanXBM9neR4xiIrt
7in6whe1gmRCJRyx7iobeSNU81SzNJ8shJ6CtXqrh0PB7Ybbi4U/wALtn25NPaQoxweG4U9s1PrkP2TxPqV
uOEZ91VyAEVTyAcj2rvvdJnkPR2JwGV1EnJPTFToCxIkYZHQ+tVyds6OTkAVLGyyFiRgL90Uh2Ji22EsPve
nenoNm0EjNIB+6GfvtUW8iJtg3sO5pMmxJMSyuhBOSPmFV5GIl2plqdG7C3POWY9BQxxhkPzU7alPTQjmbI
Qnjb1UUOWVQY/unqDRxvyfvGkYkBhQQ2Ry5I2KR8/IqDcWJbIyoxt70jEbg3PyjHFQRlVlL4O5j61dibiSP
tGCpLn2qvnYp3/Mfap5WYpKzjDA4qDbiFWJ4P8AOqRD2IhhieMA9jULuxUqQML0NSj5d27vULMQoBGeeKtG
b0Gg7ssfTBxSwfMx3dO1N5AYZxmlt2AzxVCi7STP0Nj+d7sLwc9/pWfd/wCrboKsW0v7+6U8fOBn8KhvcAh
H6GuCW5pTVpW9DKusG33DOOnPrWY4BwWUnjtWhefvIfLTgKaozgfKofDYOawktT1aOiM6QYU7vXP0rD1cbF
Dr0zjAreukOQAe3JrBuzut5iRyr8Vm9D1aGupHA5bdER1Xg9qklbdaRwR/M+ecVVsW2EmVuv3amuJSlo7qN
kin71SzWa1LdpI5yJckgj7tWra5ZbtYpOU9RWTDK+yGZPuN1rSiwjmYDcpxxTsZyiupowTLBqyoCTuGfarF
3KVv4irAFqpzGLdFcEYk6AVbuUEpiZhhgOKTVjjcbNMsz7ZCVdc8Z3VWSI+YHUgoOgqwrAr7Ac0sBUwsY/X
itEr7GabirFa4JDEYADCs/J8wREEBQCCa2JofMjDN1HNZ1yjSTKRwBUyjobUpJ6Drh/ttnLC2DPGOPpXNgs
kBJBBBxjvWreg25FzGxyDhvcVDqASe3W4gHuRXOvdkkVFcq0IrOUpDtZ1L5yMHtVmX97iWIBmi+8tZcmTE7
RLiRlGz65rU126h/wCEa0230whdQBH2s+2eauSekupE9JJd2Zt6ctJKGYRsOFPY9/wrEkm/h6ADnHQ1pTyB
YzDndxnNcvqNxhn52hQa1W1ietjzjxRIZvFd24+73qsVAYkZKkD8KjnlM+q3Eh6OSAaImc71Hbg16KVkvQ8
ierfqT7NxCjOfXtUyL86L0I5IqGKQtKsYHPrU7fJKZW+90pFLYeXO8NgnsAKcCqrKCDtfpt60Rg53fjQu2W
LcnBpCuVIy1vCVk5Unr3peQPlIyadMS+FYc0zflXYrgr2ov1G9dSKSZTKgXOVGCe1ISQ3zEEGoS2QJMYJom
Y/KfWqRmxr5ZmVGwAagc4lB3HinGQB2HeoWcZORzVkizy7gSw4PYVWY/uwBnrx7U8gsh9qgUnZ7ZxVpEO1h
+N20N+dRyHJPGArY5pwYj5PxzSO5HIXKnvTM5EMhDNkAn6Utvk56D60rbWGVODTVO9iR6Yq0THc+
+y4E12q/eDj+VS3BFwqsRyo7VWJBuLrH3t4/lT7OT97hjla896s63HTmXQp3o+QjgfTrWY6xyRk5AI4zW1q
wWFuRw3SsAgxxsuM5rGe53YZ80borXOBDzICe2BWHqrERtsj+XqTW275V8hVCgdTWHqozDIAxyR2rJo9bD7
6mTCwQRGTqckj0p012ZEuIpAPJ25B71XygaBpGy5B4qFZDJc3ETjC7Rj86SOmRrWqsmmRt1kI4QelXrSVZr
dUDFHGTtPUms/SlcOBK25Y1xgda0dNhWSYYUrknr1q7dTGcklct6gT5FkWx5rPyB0xWnC+btipzjAIbkDjt
WPO+67kQ8mFdwqXSLk3LyseOeTSeupjKF4X7fqabO0Ezqillb1qxbjyrcvj6j0qMEmESKw2g9asIQ0gVT8j
DJ96uOhySehOUDQo5PXtWXMm+Z1kJXbyMcVfypJdm2xDge5rNunBuME4omwop3ZXlVZLV4nGWXke9Y29pTh
SFUAgge1a8rOr4Vf3Z4zWEhV5jGpwzEisLXZ1QdmxJWKW8TMTndwR6Ut4uXkZQqsy5yO/1prsv2WVOoiOM+
9VxKZLc7jhiCBVWve5nIoSzllfeQNq4+Xi
uR1+4K6bcHj5lIB71uzzAzuuflAwfrXHeJLnFlOM8Y4rWnG7RjUlypnJ25O1NwzyTx161IC20nIClju9cUl
ufKjDqNx9KRcMWYnG7qK9B6/I8nfUsrsyrHIHY1O4Kuw69DzUCZKKGHyDoanDMWYqMqoGTUMq5KSQQQcbuC
KbOCCuzj1xTXkSUoynCjrT94G5mqRXKt0xDA5+VSOR1pjkO0jgnPT2prhvMXfnYxpWIVpEXvVWHcgMbHaqg
lTyT6UyUDAycBfWnNJtBibO89MelN3g4Axx1zTSIbIhtLbmH3hkVEDnd5wAA6YpzyK07BcYHTFRHIB39M1Z
LY3cUUkgYJxURAAYD7pPepJWVo1B+6DTW2vKSOEH86ozbGHHkkn1xUcsnyKiHCjjmhm2xcdM02VsoMYHNUj
NjHxnaCNvcgc06MqOoI9KRcrkPjmnRgEfMwJpkrufdEbMZpwcg7x/KnSEqwK1VNyXlu8DG1hn24oe48wAL6
V5rep68Vc0XYXCLu5I9axr5GWRgB2NXrOcI21zluw9ag1IszHaOcHiiWppRThO3QxrlBtAPcc1l3w+QqnOG
rTllyMYzgfN7VQ2j94SflY5B9awmz1qV1uc3coPtO58AKeKpwy5up5T2GKm1Ys2yMdVY5P41SgP72VG4JHA
9aUWdL2NPT7lbdpHlJxIcda6K0kVwqTtsbrGc9a5EOsqIpX7jZ+tb6f6Vb7xlnUAIB1Bq7q5jUV1cu3rOPM
mKhZtmD6EUeHW26Vl8B2OR7iohJLNYrb3Kkz+vc1HpzfZmuI7jIUHCZ/g9qnuZ/ZaOmtnVSncHt2qxLFukj
KHCnnA/lWXZyskYXGd3Q1aaUpHGqOPNHX3q01Y5ZRd7otK4mLsBgIfunpVW42mF5wBmplIeIs/yYIJqrfyK
F4IEbc57VMmKOjKFxIcAOcAjIx61gxFAsgJwwbg96vzTB5T5jAYGEB71hCZWMiyHZIG+6amNrm6ZflcLEzq
OMYPuazzJshDHuasPIGhIH+rx196z72QC05421SWhgzHvJFF1Ix4yOAK4vxO5W0Ibq3SukeQvI2fmJHBrlt
azIkivklOfpW9NaowrP3eUyU/1KkHnvT9hAV0G7P3/AGFNhGFPc+lERHzfP97ggdq6+p5xaA2urIfkI5B5o
3K0YVHPBJOOM0kXyyY/g9TUbAJLvGArHj0qWMsLtUgkDHpSTEqu5OSe1McM7hei+tNL7yWU4x1HpUg9SFvm
IDEnPv0pkxQSfKCTt9adJtEfByWPBFQHAxwxIbn2FX5huJOzvJGrKFOODnmo5gxk+8AoHJApofeZN43EfdJ
7U0DbCcluT2qkrEu4gMQkDK2QBg8U0D9yy9cnIJNAiwwWMh0bknuPrQdu7Y4ZQOhp9CCJ1AiJJ+cnpSRqd2
DwQpansN/mIOWHINNU5iBcHGcbqoy7kSjGWfo3QVG33GHvTpmDnA4UdDTWLMhY/TNUkSxZMYU9Tio4wpHfN
AbKnPOBREfl9qqzsSmuZH2VojE394CSRjv9KvPwBj1oorzpbnr0tiWH/Wg96nuPvmiinHY36oxLj/lrWZKf
kWiis5Hp0zlb4n7dLz3qhCf9NFFFKJ0vZF6P/j6X6VeZisI2kj5h0+tFFN/CZS2NIk/aU5PSp9W/49Yj3PX
3ooqEY9TR0zmCPPpV8AfaIeKKK0RjMdHzNMO3pVPUf9QPpRRUVNjMwLr+H61zsn/H5JRRSplIuW/3MdsdKz
NZ6uO2DRRTnuzOXxHPxff/AArmNZ/1lx9KKK3h8RzVtmYik+U/Pan2P+pB75oorpex5SLY6tUbfdT60UVma
R3FmJyvNOmGJjjj5aKKEORDcDECY9aqj78n1oooewkVz/rKmb/j3NFFUZz3IY+GbHFNk/1g+tFFBnLcb/y2
b6VXj5iA7UUVSGV3pZPvoO2KKK1JZG/3jT4+g+lFFUZPqf/Z);\">",
" </div>",
" <div class=\"lgnd\">",
" Ulcer in the gastric antrum seen on endoscopy. The visible vessel appears as a
small protuberance in the one o'clock position.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Eric D Libby, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_416=[""].join("\n");
var outline_f0_26_416=null;
var title_f0_26_417="Diagnosis of adrenal insufficiency in children";
var content_f0_26_417=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PEDS
%2F60520&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
%2F60520&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 656px\">",
" <div class=\"ttl\">",
" Diagnosis of adrenal insufficiency in children",
" </div>",
" <div class=\"cntnt\" style=\"width: 636px; height: 406px; background-image:
url(data:image/gif;base64,R0lGODlhfAKWAdUAAP///wAAAIiIiLu7u0RERCIiIpmZmd3d3WZmZhERE
TMzM8zMzO7u7lVVVQAz/3d3d6qqqhFB/4ig/1V3/zNc/6q7/3eS/
+7x/8zW/5+fn9/f3z8/P8/Pz19fX+/v7w8PD39/fyJO/x8fH0Rp/7+/v93k/5mt/2aF/7vJ/6+vr09PT29v
by8vLwAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH
5BAAAAAAALAAAAAB8ApYBAAb/QIBwSCwaj8ikcslsOp/QqHRKrVqv2Kx2y+16v+CweEwum8/otHrNbrvf8L
h8Tq/b7/i8fs/v+/
+AgYKDhIWGh4iJiouMjY6PkJGSk5SVlpeYmZqbnJ2en6ChoqOkpaanqKmqq6ytrq+wsbJWAbW2t7i5uru8v
b6/wMHCw8TFtbPIybMBynXMzdDRps/Sb9TV2NmY19pp3N3g4Yrf4mPk5ejpfOfqXezt8PFu70sCBJMBA3f2
RvTy/wDNGSFgS4ASfvmMDCCXkMpCIQ+ZRGTCj4BBAA3RZETCr4i/gCBDZvlGAAGAhQuSdDwycUvLJi+ZWBS
y0UxNIyuHfBTJs+cT/5ImASQwIKBWgZRFa93Ld8CWAgYFjC5caCBhg1oJiAgokCDA06a1nkYNUODhAQW1TG
6NKtboEAYBUg5JAMFe1VpV0QYwQIQBwQAJmuozUACAga4BBCxEexRA0sZXASOwdeAxUlv3PPrczHkKUMNxE
6R80GBBQoT6hDSFEHHhxXxbD+AswADqRQCrWzNrYPKA6NgMhsZUIOBAAQMLslZ8bXArkYUMVCckDIDAgyEo
ATQoLRoA6dg69SUfXfp0ZiI7O6vfTNKWgbtGqTteOmDB3726wyMIWqRjSfvu5TcWXh0dFxNpCEBQgAANzFf
da4MVRsQDgBU3XWEDoEXAAhFtBf8fWfuhN9gtx0mYE03rpagiegPxN94QpqXUAH0IKAAAXAZAdxI1sBUgW3
/3+GZAjTfiF0B0D/GmVWYGHllEcoU1kEBz91hHU4RHmNYUXwRIKARvESmAwItCgEcTBACQmWZc2p2n04pwr
vfZEEkFYNJkXtE3QFdRGcAAYxMl9FdWdNrS4J5k7fUnWWbpFUBlTPrJWBFTAgDBow7eVRWW2NmiVliF/XXU
QmHJVqdJgwKAZ2WeqhqWmyjGKatP6ZVxYiIxfVHrrLyCs+sYtyKSqxe/9mqsNMXKeeyy8CSrnrPMRvsKtFb
MZEWwUxBEAKmpBUKttOCm8i0V1laR07BLQJD/QHTEOQikHuOGK+8o8UpRLhXYRtFRAt0KUu+8AHfyrxFgeR
VdZIlhRBgCA4zFpV4mwaeWmw+tZbBfWAlmmI+5LHhPw7UIwA/Ie2GkF19n1cJbZlaGMXDAMF/y8hGrgTdTA
A0KxZe61X2MqRBVMXAuM8AJ5yRuF7prnlC38TOUpVkl7NyMQzR1gNVizBzz1pFoLQSAeIX4IEb6FFzLATNZ
bYCjkD5HdKTeVagxdR2Zh3WZBJj9aNLHEWHRA/yB4TXXhC8yOJE4blXbgmQL8fQQaT9awHWXtt2pu31/vTe
XhdWtj9NN3/P4lRu3+RxXcrlc+OqoDI5on4smwHhDJIdq/5DVjz06NOY5tpqUAp1ntjSiiY08VmFJp4yzEA
rAqivr0JMyuCjB9St49NiDMn0oD9hIxvbZh48H+OqQL/75cpiPjvrot88G+
+LA7/78Ns0rP/34qy7v/fn3z4UxAAygAAdIwAIaw38IVBH/EshA9y2wgRAM3wMjSEHWTbCCGNzaBTPIQft1
8INXMKAIR0jCEprwhChMoQpXyMIWulAXMNugJmS4Bxo6YxoxBIgN87DDOfTQGjn8xw/tMEQ4FPF9QZTHEX0
oLhwGbImQgGIcpLgGKp7Biq7AouGy2MRSaBEVGuBArDigAXRwQAQZ8EAAPJABEYixFGdM4xrb+MZPxP9RjW
x0oyfuOEc9MkuNG8hAADKwgTWmo5AfCEAiN4AKRCoyAIwUhSMXCYpJQhJcHcBFB9QhyFtkABWdtMUnRRHKW
ozSE6UcJLg4gIs6okMEthCBKmBZC1mSgpYBsCUocKlLaRWyFpFUBwhsAQJVDLMWxSTFMQOQTFAss5nSCuUp
06EBW5QxFdWsxTVHkc0AbPMT3fymtBL5AXlkcpOrOOcp1DkKdsprmNBUBwkCQAJWzLOeprgnKfQ5r2qKUx3
oZEVATTFQURQ0XPgEoUIXytCGOrQSL4woDJMg0YqW0CMWlShGM8rRYTSioy+8IUSV8MV5aIYS3CjpFT86Uj
qoNAr/73hpFU+KD5q2jqUoFWlOKRqLlLb0TaqQaT9+mj5LxLSnNu1aUp24xZ0ykahDhYVPnRqrLja1pi7dg
nESFoZ7/YSkSGURFnL1kpvgxHm0WKoXvIo3t00BXVgQqlqjwFYkmPV7Om3CX/hihAeg9Qh3LcJDrFVXJhxV
qnNdwgL0sqCyDsCxFPkrFabKBcKEZQD3qhjFPpKP/FyPEe8w23WOUNh+WE+wz4ArTPOq19sUoQGuJelplUD
Y2DrhsFmo673ydRDJrlSsUPBNUBhE1pTO9l1boKwWLsVXBNjDtu6CSHo8+zzQKgFrGcpZEUrrkeNKt7pPfc
JMFgOYBcCnYE8h/69o8PQzALRrCA14AFXcQwCIQQG3UqhTA9Dm2uUsqQmdfUa+LOuVARQlZ4w7jFJSd9/Eq
sR7nUJLdwKMG0d1Cy4MpovFnlIdpURntcDVQny3a1/NnmRAROAZjI6Uj+Opl8EjwSkS7mYaBigPVfZlXHAg
oLwAzzcsUJEKM5R3nQ1/2LCslYlBplIdVLk2N4IySU1I02ShcIgZhPXZjwAM1ik8oDFowyx0d+tb1Lb1CMw
VgnMFkICnLQguaGJAA/gKYqBCQQCB25E+SkK2JAmvX8QxDnKU46PgEIU2f4LuEpSbWzoLgQBaNnGlWoJhwl
SmQRTWc5X/J2OatTcfSvKNff+0TB3qUK3PXJUOa1K7mwYlx8CFHt2ik7yE8T4jRDMBm5HULGXrqYsoCuDZY
C8SuS0jmadToAuJ0+KgmdTJTVSmk41abBQjE2HEWlnQut6c6sk6mCNe+q6qev2QzG0EQQpiEO/EhmcpMBoL
SvLb7R6lWexygzgKGBJsUS1usSW30wT7WY0HtJdiVy/fADD3Y5+h6959N3MEIArcuJxVKNia12ND3K7HjRE
0USowbD4Ulkdb7K8i293G7tmO2mYR03zOTTxDwD32nemiOTri/aFNAhCQ4L8g4MgNDrETfJMz4t6a3K1eU7
+gpJ1KFejQi1N0l+28XK46t9iSbg432Gz/kjanJMBIOro7AF4E7IpJO4EruQAUQKjtKD0iGu9d2LXjatjA7
dQnL6p48QJ3J5+ETxsP0aqufQ8c7Qg0BZ93yqcOWCrIemy4q5IA5JMTOFvnMF9f+Jkz96U8Oycprv3TaOtc
VShkKCyKETuFF8CWmlSqcrzrcAAIAPTbfnsKbFaKmJF2ABPfBS1PSsiXr7Sosoid09ZNgtku0mP+8r5IF2G
9VzL9OkUBash6KTLc+DXrilM1qlL4ctm2VezlxMh01x5KcggF9tgP4VIXWbOEoqKYDd3ovaTHCFTlmjWyZ2
FPtQcGEFBm+ud9WGVXVcBeCOB8kZdxr9If6+JeQZEP/8X3dBCoe84BGsWBMNqVf/zXfVR3Ch9YelugAKM3R
bT2CPjVCu+mgrf3CSNYgAeod9/3gtJjg4fQgjeYfDOIgkigWvYidQKRdyyIg8ilLwRILEkVWJsQg9/AW4Ng
Q+wAhHQlhFFAhSRohKGgg5GFe0k4dkLHhFaAhU8wLNTlbmQHhVjAXUoWdOGlEAPDhvqDgNWyZLXgXVWEh56
hhXTyhUf4WyEohnRghuPihGc1BnKIfG+IWhJmXhG4duTVGL9zGUrxIIcRHWvnGLbAIQ6DEWOBJzbyEBJDhH
y4XQaBf2PFalUgiI9mhSSYLEaGXgywWCqTbV3BYZGBi0D2Yt4Whv8nozHQUV/MdmMP0iVbcYsM0Ci2sHBRk
QCRcR3EaGTHI4suhn21UGQFwBYBmIU5OBvaKHOPJl/TJ4lh8XUn4yp4AR8GYBFdEo1joQB6gSYzcTwwVor9
94NRlnB80SQyUh4pIXOmgSb+1TfH4XJzsTNRYxA8dzWZBjRHA36NV4dCoYemV4gU6YH4Emt0VjMQlm1Rt3b
sIjIcRhxMxmd7GIbNURiChyp1twChJhr1ZSqI1li74T0+lnD3UBVohxu/oZEvAWXf5XavZnN0eFV0opFWYz
XZsR3nB45SE25EQlgKIBsvuQCx0RQKKXlEMDmM54MsIXb2oCCH5xglAhFl2Wz/VCKW8oE0t6AxniOKbFOUE
YlazfiM6FgyFoEnoeJhU7EXiWInYcGWBlONFXaNZKmNdnWO7FgA7MUlBjF9JQORMoiEQlCQ92EAB3AVCNeH
j7Yft+CZntJ3vRiIWLInWGMte0Fw63gR/sEwzKBwEXFxqvl0EdFwAsJXEWeBczkOh6iPDwI4Y+khEtIwjUM
3iGE7rViZtyBxpLMcDKCAXWlESSCawdEuYTImbDIj50c1M1GdBmGQjuNoS8NvXAl7uymZ0qUPBZCT1xCVj/
k5iEaSXJUwC6kxqpYfQskvRAlYzZEVMUkE7okRKXmesBgpcXeU/yUkICltRyaaJ0mapVMd/wqQMzNROfGWn
A4iJElSd5o3NkkSOLTpJHGnIxuqdBaId9xoCE8INw3THde5nfSxMavhHaFCchdxoUrzcpboJGfHZgEohdN5
fA8QgaTiFaZSjui4nmPjHRGoibXAiW4xnhSWO4uXotwYm3boGMc5NgnBbq4ZHjlqm6oIcczpm4ClDwvhfFr
qFjfDKUuIL5FSfUThHlphKF9CpwjjcBz3oK/IKZeSGvdxO2xjLfp1eNIXFR16cc33dMUnp41qjQGgfZXJF9
wndIiwopPKPJlRpFPppAqQeaUjKoWhKdayqH+GlsrDmNoBXUBqcReBhTi6pPVDimNpazM6fG1KllEXKP86S
jYj6iQl6nInCivCh5y3ipxJI5kxKJeTyRHnkYjRlSXtBQcDiJ7dyATVI251EBzb2KpOcCkfplp/0anv95Bl
sILidnGiyqWAypc80qudBXiSwiiQKqm+Wak6IRVLuq65upZhuH9L4BseJ6v1gFZF6orSyYNK0D2XAwje2oP
2aAfVileW6oIVu4NGqVQGKAnougpcqLDNylS8WYNA9H/UQJwbG7Gc8LFkAK1/eGwhaFpcQIZeObKkhbAw8Q
40i4Yp6xDU4FxfwDh8aq1BdXs7Szq05YomFq0wa6VIqwVHm7T3mLHyBrU6uysu+7Bj+AzBUaUmRatFe7Fu5
W566LL/HaGG/ypbM2tFhogELrsEcBW1JreIRkCPJoMXJ2YLQJMZk6gwqipddWmYo0h/nvp1CwO2Tsu0biC3
ZjaWtie2Q1CNVGEZCWcUC8BemQlk2lEQRICK8ZWmnmJtIJi4kImZCRGM9kVkhXmH5WYQO0YyxWFfWxEW8Tg
2dnsEfbuY0XmtpJVjrqthXGEwm2swz+WXabIgsqiMdkKWtFsL8mgQt3ueCcsEXPmUTDOWwbYm/7gUHahpSq
qTQxA0D9KU3Du6RMuZcsC4Y8uzMQuH0vWd3RFtlXkdpzGSIuMjBEtlfCYaS7ufXUkP1ruS1dGS+TkADWCTm
ldqhVEpnceTVukj/1ipKloZuSe4YtsroV7bviqaBJC2cgqsq7axoMSxFWgaF2VBBEBZlVdJnxM8v4iLREnw
nK1yIfaWJoQiH8RZE1h6eGtDGZY4nMijhx1bNZ7COEqZKM5omIjyNMWbcgqWMLkoNMHbFmQhe7RXdtlHlsh
ImMrTvW8Kt6qIeEYhw8zWpZ8pNvfya2snbG+zeY7GrABcmoGBKahJGLhpx1fyEAdnuls2m6fqnNBpBDiMnO
Z7qRyseHvsLiXBXnbSEQuRAKMlppXrHp6DlmS8vMw6vUcgvmeXNE7HDA8QydkZo2Mrm5RDxwIAo42zuxqMv
kZMbwnxvcxQKZdIwqQ1eiJ8v/
+7KmDxOXluUcCKYxv4mYQsuyNzZ8Opw8lSJpAcViYzGVttVhnOeHiZ6H7/u2icUl8UahAWyqFCWXNs5zi3g
aOVvBzKrKVHpspy2LY3+3xrRyj8oKDN7C5TUSm/upPouzQWcc6ZXLIzxli9Vjq/N8up07c6/AwXR6VjY9BC
zMqurHg7DLo/ojt/dXobwshX15kO2m5beceteZsU18pvcX2Fkhapeidnk6exI7TwVXgl8xDJ0cgTd81qKx9
/+micq7qHmmlw8aqIEbuUUc6Sd9Kr2h9Ius7+l5xY09NlYqfDuxeOzAzJwTDyqrwU3ZxDDdAvPFNbAAEd6Q
UMzL7S2x//3sNnRdF7CJ2lTrcu/ACer+Vc8xzPRoOJz/xaHCrXcnd4KEqEy0qg+fWsCKslz9GkXcCtMQayc
NukaFuzjJ0Hk0GuYn2+X9MVrjl9aJ2cD7HEfMEPJyIqMkLJdlp8Vlx7qluoj7q6Xpy2PbgrAgs5QniwRWCC
65DUSCDbZzbbPWux/RwGCnCR6HsFi920Iavbias9tI3Y/gyxkAsHwd1bWlDMiQDdnsDOHJuCb9sGiTjEVlX
cq3wG6vvFTqAt+HhFvh1Cx021yV21TdDcXZDdDn1Ty/20ZkCFQCjdUNOtHeqFhpUad8Xe7x2FUKXJ6r0H7r
3V3UW275PfcfWCrLi2//8W37/9leZCgA3R4OYNWiDVQtYtuxbhl8xWEfYFoHQqjMtb2u9Yu41piY/41U5bK
xYOpth8BY61tGllqZFojng7isVbFYEbqWLcG3qxX1msvNBoYcrrxdJdMATWGBQGjvrYl3NKFqlTMAuYxUOA
uaVbjB7TFCkBHSTzxv9dhDDoti1py+F7JBWhZUcQlVoGzBDMwgBqI/O4j2A+3CItszBV3u6g4Bces0uJaQN
65lJcwurJnkQQNHhXwMHKLwecx7shWfZ9ItWreU7eJPBLHv9FdzbcLxU+oP9ZESahJE+jYiGdDH2df65NE2
Xaw2fjX3dTJltabGQq1Gtaxc5GAP9iOdZ3vrr54OTWQYvLk+VM4RSzGORkI4t29YmBadWaB+LDGOI0PbbOk
TSsftW1mqXVLmiRe8fldsew+Zp1/opPwA+XjHQSPKkR8SHhpps4B+NJQ6gfM8cM2ZaPqwyn7oamaCnWXp5X
XXKqRqOQ9yjfbGB/nDcBgCa4+ruoCLn+cGrDzpCV0ZFSEzXdwpEiQsQD6xEK+eaa5/DNXiVt3hvdEe0N28l
Ywu+WE9GvecqZeR4DH6ygxqF+xtfjzp7sYu7OsSd6qiZa4T0Djx4e9+6sySRKqjORvQzGTVqce7ZG0e+K5z
dGYayPUtoFL3vZuKRDuo12XtwK95u9oZl8cbr/e1Mfl5m5CJcPDWdX8Kp5346WvKea5vsNnCobSUOlUY3ZR
NP0VxPkqkvkx5somtfFylrzq6uqFLZVbKenTorJk20nqiviYx+qQ+
+QqVE7c2vqSZ8IpaXd8MWhJzbyztw4w9frNmJ4oU/6RcIXey2lHS/zbVxssUry2poHgl3qWy8K9w6IAqMI4
PrC/iB9aJEazdPUeGsLJxyviRLlJYP8fTKRB/6WUt16Hx/we+/Dsu+4dgDb9c7d032pGc5RjR1FYX4E2Xqm
y+WHs7rr0a2yAe4vb5BQXJ3eGrvbS8Cwaj//3M+7+b+yhgwEAOGQWDQekUnlktkUBpxRKRE6tV6x/8sqcpv
1fsHYLmCMHZTDQ0KAkB2j03H5FT63F+t3vTe/N/b9Av+UAAUN5d7CzvYgEhj48A4l7Qon6SwxtTIHNy3zKu
fW2ugGjhaNDgoCBMISwU7vBEbd8AJsb3FzdXd5e31/gYOFbzvjQIv3jpOHmZudn20J92SPGh+XCFj/So1gi
R5mCbmlqbwGVKMPFGwfABbWAxoAGmwVGN5t5YfU2Q9uDWgh0ySQIKKCm5QdbKWQDCZqbsYR8TakgTYtEblE
ypKA1aIG8hYkGCBAwRCSjxQIIHnkozuRDwMyLCeTJhMNHJ4I4aChpp2bOQHs7KknYSBAAm4tyEagAIJ/AAj
AQ/8AgNqABAESGPBnywC6AguoJs0GwCvYABHPEeMXAIGBWweQBvg6z1YCp7YOkBtSVIi/vIsKAISqlZ4CA3
dtIThQWLCQwEIIGIApZmjDypeFeAiwIUOADBsCeMAcRjNnz6BFj07DN9mSBWfVKMg7BEFJAm3OwG3DEYABR
5PJPng9buyQAu1gD+HtceqBBEpZhQT7oGKB2WQwHnGFhTfSeSCTUy1w0oiAAkRaDgduhfWh9qoPdcjVAT4Y
+bjo1wfzntKSrkSKE+AquaBixS9Z/HpCNwAYQKyt89QQoMFbpgovQcBwMWAst25paqq9suNkLy84XAeAtdq
JKwCA6OFKxcb/ToQnxXAuGYo//fbgIBeccMRCR1x47JEyhfoYLsITA4AAgAfOG+vA3VgRkAFq3EIJASMhE6
BKABSoMKLuoGjgwyxdAksI865LkonthGziRj/ebFMO0GzZQM4r6Nzszih+skwogY4SS5s15GrSwAAWtAorg
KhZq6mwbIHOUS+JKBGKtRANkEKo6gLgruu002hPvRTiQIQMNPMgAxGCHDWTzmzJwNUoYPVs1iVK6+yz0AiK
89Yk2Px1RJpA+yAAY+0UFhNjP1CWCWadReK+W/IDNNo7glXWVzlqjfVaSUAIAIRvkQh3XHKH+PGWVovZ9tt
s9Qsvo5pEuEUEdA3RIACe//AlQl9+
+80z2V77XWgmLIorLor1mJhI3lBrCteWcwveg4SKibi44lplLcjda+GNQmErGGYvxINl0tcWgDFu2eU9oD3
o42jhbTEBSBUwq6sMx1JxgbhyXjIpCtNasUCmUARgEUwH8M0Wi4atSb5qX67a6jDMJfJqKbJFU4jXwEKgjX
jILBBLsD0dW8kzR8kKgEagku07lwbwaJSzCGhn3ppICEBjOaEJXPDBn6mF8MMJp+lfrbd2IlsExvxP6fOSS
1hLCHuD8Bzx2Jqyja3eKu6xwQAT7KwB1iHATJRporrNmQEX9XW+GYJdW9nPtO7rAMBqYGxu8s7ybN7nCSer
lf8AcPvIuYfzCLxxxBSxcaKmjxqo2KvfO3vtLSuC0JuBNosbDjWMMqnwGRjQnpDYKtrQvmRUGooFVFlnAEL
nwn371bYPuT7bZ4U4AQ6QgLnQn7D4UkAFQqM12fMffMqwQAlOEID8w0wFCVajW8EOg/E6oAc/WLEOfmGEJC
RXAhHYwExMZBo0Goj1hjIy/ZXQRhccDQ0RMqQNqjAJazjUyazAQiecomREKCLEYCi5QFiOCTJkXfeqhkMNV
qYOokCGE9mjwwDyEAlMQZQ/gDgFITZhjEg4ovSgmDlDYLGHUJvh1qSYRRtWwxGbeAgbuaZFV3GwiWIjABg5
xQYGnOEMbkH/x11KAjp7TMRninLbUgrgFWo8IClJOyPuxqBEnC0AbkN4zTWEYLNNkmFn/8gGA76ntKs80o1
PjKNMXpnHOZbHhZK4YyvlmMstUg8bCDgDUkZSAAYwICW/fAIrEGAdQPYlSd7AUvJY4RtUyo2IaqMISF5SS2
DhToloExsDeNcVuOgjd7Px5tj0YbkzgJI30sRjBG8YRrbpUSF9qsKfaoIG0EmmHjp7lBDOoIoEtKgdSSPki
uKSPyQlJiqJWWgAFglRrKwuhC9swuiuUDS9EQGcmCMQgxKAOTdx8QgEmEqLBgC5M/lyC7B5yFmU8g9vKDFB
ZDhAcarJOQQwYHSRuSTr/zKJOcltLiWGQUBFiKBSIQyVcsAbFCsoyZGaZ
gqX14OhUo3CjYdpR55U0eaaepKr0/CqJ3CgxjnJQE6AwqYAbXAL80RiTOksSa13xA2i9tFM2JiUe1E4Bkat
oIB2QACvRlSASJ6gJkPKElt9XGgwhzkeWLj0biktCTgN4MzwdMcROA3AIyaTlfSc5axbRWNQPUk831HFLsl
7jhF15w7V/g4yelPYa5wTpc7qFpRW9S1W4dRVKnT1p0hs3XyoaEa3aq6pRTjFWEoHmcxWgUO2EOktkXSAmH
LlFMB9ouOkgNGkUcewSc3ZOXpLFgEolQ1tUABTGNufXgrBKaUgFAEG2f/SUry0bldRxXSL0MhVAqQ4xJSLL
NJXDwZYsg0/DVZ1VxE+2ZaCSUZIpYSTQ75snMGhjiQwK5D6xqSOKZD4Ja9JSrIPeMjjvvnl8FtguuJRhgec
FE0ABMxTv0e0KKLreC0MGaIuW7ALlsqVbe9oK5EqQDdMzzvFXMuTYichqjYMWlF3SfzdkUYBo+kRCdzENg+
ooc4pblynVR6xihuPR6Rg5SW6FCDcB8okfelNYxqxap5hpgTMbQhxKGehZ2IKwJjYecJIUnzktBl6CClJhQ
FCIp4DpE8y9uASofdK4lg2QWCXMesoMIyR53bkUvGDhYpIzD6xHeoAivovlvsKXi7/N6anBgAnBPLmGxsrK
X1ro2+GSFlm88R3DpvOZ0VVA88R0+ZD6711rn/smMYodb2T1eoAFgNRAzCV0UKgDgIgMB55PCQwiGlfFYBr
7CVwzNMnpKcSuvy8eWQlJDcjQgLaERJf9/pMJVlRSKbUZosWu3/IviEa8yxMnoKY3gmwN0UCrXDJtnRt4TE
P2lYrr5CcpwHdGUVgyLNW+mr6MjFL7rvenQR04CV+rLWScwe00d483B+vacyw/UrSq8354Lgz9/1sgV+Xcy
nLa2Fx0PNLG7yQ9imhLgJvCJsXcrNIpugmeWWy1m6UT3GPOqeEcMlYwQeWEQ9gb6zB0aXuJSxO/
+sgSzn2zp5VM3SBhYQdEwNaFAAm5QIpgnkrUJXgsBCZ1ttG+xo8xqOL3ND3q769c8vUvoS/nVxmZkeCw94+
uzcHNw0svE0duWRp1In8CX4PVh7IPlwkpO82fWktVfTxkMUvmlSOh/z+Mi+J5BA+Cpjn+qj4OIQz+BgsGO6
K2NDhxQTkpSzdPlpgNmWeq0R0csQgQs0f88lutNT0mAy8RF8Lm7yzQqKGH4JvEoS8AI9i9mGu/eMxFvk9qX
v3ljcFz2PtBzbi0YiNh7/B1sq+roR4woxsoMKt2ApqjsP5ogJUqkTQJg6a5CfASqIqBG4CEwsXvC8JCAkqv
ERA8mIsVv9BPLynHXomy+ZJfnDB/5TNcexvCVJP9/yKgmhQcHLOiPopbhxqLbJMLhKjHiAD6YZvohDDH+AB
RhQpv4iv+qJBy9wsC5gIG6pqZBjmjIKP9CCH2yqH1LJkQhxKXorDAOABUe6IpS5kDFYOUXBr+/ai+wCPA60
OO5RKBEtBk0CHQHBu/dZqNtxvm9AOROQgBqWA/97PD0XoBncnbNqg9XIjepyDokYwmQ4AjAStmDKN0UYwD6
9PrwRQAn1Pl66AEL1nCqtKDwvRgrBwAJGM0ZgsS7akSxhQGxYw6holKxYBTJTsGoJHAagpxSbLDWEI9eKQt
CSO/OrwulKs15wj9mL/j/0Kqw/76hh4L6PUDhTkbxKssVKYq0CyKw1hhLIOjdpYauQw8RiJYLuuzOrO8A/R
iCI6xfi88ZRSycO4saSkwquYEApyDKLs7P/2Q8nI0em4cdQmJRbPxLrI8BbkYREsJanIyTdO5Hv05heX6vS
+jxzPwsAOzNA0aTxoYyHhISVSsP1YsB0J4QgBaZ0aii1ihB1a0hbqBgo8steKRgB4kHMgCh6UpGeSQta27B
B9UtFWa8oWAwUPDR+xAwIxDSMrzhxp47LSkRxx0QkHrpwScdEMUJ0+Szmiabe66K4WBN8mEE0ozbgITiGKC
07Y8Qh4CkZyaC0z8TxUSqUIADwW/8DLBqABUux0oOA//oM3Qqk5ngNN/AGZFlEAnikoqzLtEPEgIQosiBJT
QAUcDa3FYO1TYEOTXC0qPWUqGpIqCxGrtNCpyCSqbLKwqKqLWA1B8GoRps4sDQIt/c8Q8E87gi6DQLPs1Mg
qEqQ4VqTWRocvQQp1tKKwyCJD+Asfs0GTFPMUt+4naebdvEYokyx46lG2csvlegb0yORJJNA7XtMkUXF6ap
PygEwc1Chu0okVom608tLJqoAk7A0w54HEkpMasiExoXMx3a05U+j3ghArZmx8uGLDNoUex+LPupMMEdAHk
RKwznM8G6c8awgunZKwgOcWDCR+6McHY1IIwP9JGxRlFSTzPg8TUohnP53T7fzzV1AIE+psCjRxRU0IPgTR
CRiGQstKPBdmFkQROyWCOzEhG+OvMZ3lRYciLhBLRY2Bq5rgRwMxTnJ0LXeUSovAOXyN/17MjQSrXYx0CiB
UCjRqSL/0giwPSXcp7lSviUpRD260CaY0N2cpQoGSSWctC7o06jzBSKH0TS2sTZ3U+Y4ITbtu834NLxJqAV
CpLqrLLSHjHg3qLFbEB9kCCJPQYY6vaAjsHqtrKuJ0L2qwBnm0YIgUC8Qrfk6s38xrAdArqZ7Ci9hAoEAFF
Gn0InXv2oitTOsDOK5Q9eaKOtZpeUoKLPGy0CJRmSxEr/D/QB/cBm4Y0TgfsJZwSIqusRNK9QrijW76TMwk
oktG8AiqrPXcohQ8MiaesAtT6fwGxDysq8SUUC7M4gi5sfwAgmmUbunkdZJ6kk6rsqNwMB8I5RZu40OW6RB
4VecyExfOwzSv80+7UTAiw9qQEqYCFsBU7w5T0y/E8C0+VQbJdOd01Qkwqtae7QF07d547caMaEDeZ9QgQT
EN1M6sEwMrEdN6Rx4y8WZEMEo4bi8jYvd4Fh/VZFTfTz65gUnA4qZw1QOZ6QW94GAN9QmUBMrOMVP0RkoAh
NXcU2L5q8owS/CEQHkWNBUGi0FhUxCoFY5C9qIawz3nDdIc7unyTWWZ/0lJKqwVG5ZWDbE0sWLMUodV45Aq
xpEEYSM36FCNgvNncfU/qIFdd0pOYXM8lIpudZNpkeRk6FWVFsWr+s4HB8olOxUp+bVGi+BTUO3FPJMrFJQ
b/SJSAZG/NtNiAZEJ3+dAEHJBiFZNdS9UedcGW1RkcSFphg4Wg9QlAcS6WnbJAJU/zfK2jJMiWAq0ivEUYB
E27tYY1cht96Ip1Si0vlGPzqyOnnd2AxYmuSBo2+k3CqAUOrCteqMLotVK1zYKYhT4PrZIk+32YBbTHEoNr
EtR16FJhPAW5KZD7At7/6NDVSEiMNMcEUx9eotQzQ0gxHZN+epyueAYpwp3XZYhx/8Qd0f3ZatnWl2mWmv1
dn7XHN7A8tYQAKegC/iNKkqCSUpBaY/ScgFptVTvL3lL9pR3AmfRbCEXQK2GhPW35+r0XOMAbBtGQ5t0iiC
SmcKGQmajcggWNpYUEP+DHn2YTFzzdqFWd9V2T494TvvlWo8097IA16zV617BfEEIG0sYgjoBFjbHY+10h4
gY7uTLDkTSCqLwfvE4iduuFdgXEGABAbTBX0E07/YOF/quIvM4d+dPjXGkV+UgiwdxedFWkMnFnnSCZY7NG
MzuFNJnNoxWCHjxEUYPA0lJkpX4hEeRZGaTTfeYeTVPjMPgLpri46ZrCVXkRXjyMclAXnXZKAr/Rqx2JTUq
NPDQwSbjRxaQomL7cl3d9RQ0xDjWayq0z7m4D5Zx2UqhtP/AYJyHmErNWQnS8oXdmIRKwf0CowNN6pksB63
iMmo7uWCmxRZcZ5SVgD7x0jxwdRFmtmapd23Cd5AucLIMKJb3tgkaFZJuslNBB/mCTlYhZS7otVHZ+ZZLan
lFMUed9pw7+utoL56tTpMsZzTTs48HGV2ELACIjCb6oKbIAmIlYxYKFwpQhw0WQBwXIdIOlStaGCBLD5xl2
R9V81HzwhGjLX4P8H3JFTFfi7zuOZ1tb5I/2paXQKRJ16URYb/OwyosFnLo2bYQc7Y48gJd2D0wptPM+AgA
//p5YEJNvEFMlHIRHkBvYnglePEvfPGb31erSboeRSdDNhZRRwFvl1Nh1zpvU5hGNZUbExVFX+Q3fWnAvCo
lKxVR/3dRBTSp9daQT6R+bDEOfUbDzIeYM5Ot/5GMC4bd4rob1pXB7vWt8AcyBzh5zCSKkWQBbqouJlKw/y
6cC9s6iyN6jKNs4ULKuNBsou2xZzZXI7tZdZaqp6MB6FkbDDB9PaczwRs2frUBgtWhJXSM5RhjTK6QMwECE
i29CdsIVBt+OPZ2VY2xV5slW/t9zS+yH/pKc+GmtERhVZq7axg1E2X58CphO0Ro6DP/2hq9Xxpfsm62+zO+
74RQjaCC8/8z2s76hjnru9VTasvECIr6bM8bZGG7YNjOwp/TvPV4tIXPKyg7+pKCfJKDi0cBQw8VLohmU0S
7pMnTk/tl8tgbX9AYhWV8EtYZxl97hIkc95DhRqZxSOUpyf9zyQ8BS2PzmKMoyqW8jfdjpF3whtEzqU0YrO
e3RzBZwt16yns3znvBo8s8Gc70yte8kun8kpdBzv3cGcAcvhlTyxFUFkRqr5AuVWX4+mTMMiU1eGMsHwbUu
ENYz7W8nDn5LFm0jN8SyT3auxuw7Gp2WxVUh8VjzzDNwA9N/ewZzx3nz+Xckr2AChUSReXGylzbyQuV0zMh
zdv5vzexigV8G8SxZE//1jimrdkGtxyzzTBYOshX3DzvgArPIxVUAkK6VIY1mbpd9GWMzdfxWddD3ImIMbI
YDm4fDtBMYnopzswvTq2rHNzBXX4RY1P7d/xgKzCHbeEcY5tlnY8JuddJ1aMLfRvcdXiLrtF3u8eZjismHd
oFXdqnIFzB0muo3SX4qX8Tes8z3NutRU7GuSjm/denPH9JhmVZl8o+hNYdatiqzFOA7dItHX+91Am8Sw8Cu
Y3ynJKznKZNXgr8wW5rlwyLMd/XXZV3im7Vj9v3hAT4pQqcHl1AOShEecKT4OanPdPLBsPld+aNwAOqPuKb
eRCRN+UnzcfKNXeM3tppLkWZ/k70/0UFUsAzWOBe0EWZUaPTmQC4wqeTdqe3RKnFSCkeJeTCcjDkOb7bj4A
D5GOmrd6f01RY8mRi+mWfA6CfHx9cx+ScakycBKCuYqtm06psYvYqwwzxZb7nhWBX9KTmXTyXhWXucSHsnS
WmHZ82o0A0t7GoDkNBsUocWfGpHPxyAOp9/BvFe8JPDVEDQMBYbqFjxPz1hWTkv6Be+Lli4FrvlwCrMK7BW
svhKGo6lZIV0Tq1uh+ygV3XZUL556VvYN0Xfj7yhUVi/GZjnt/19x4XRiIHjQQIHgUAsUgIBBKAY4DAAAQG
RAPSQBAMkAEEQIBULJaCIrlcDJjTZrRaHTAUEP8HBZL70C4EhURA8WQ6ZdElhN0hLczVkRUgDQE+taWxAWi
AfGgFZERucnZ6foKGnomSlppCnaaqenogsazCxnpefsiSTtrmxuJ+8nIGNBA1cB0QBkAU6TEwFAgoMyhgRS
1xHRcNAxSHEWURPUeH+mZsIG3onqP3pq9H+rK/l3VkwtN/ggSA1Evq86/dhksBwEiLAT1bGAggQIQAgobeE
HQD4NAgAmaYDBSJ6LALF1DuAHCQx6EfyVQfS8I6idIWh1orS2oIoGGlype6aroBKKxjmQQFFRYrWGBZM408
AfjEZibLk2fNwkXyMNMm1XaYrmLNqnUr165etVZNRyIsv7H/NMmyw7nPY8BEh/j0Qagl2BIkgdg0ZADXj9s
AB4pAC+DILiR1aA+HVYt4MePGKR3bUlxGcqiEjClDzmxSM+fOnjdhXmn5VGhUukYjLv15dU7Wk7/Cji17Nu
2sZGrjzo27jWqSqEuV7u3a9PDiUI0TR076tvJRrTtlyVKw0QIGTJQQoLMlm/YHXQow8rNAezAvgrdl0yKnu
8d/zQ2/jz9ZufD3uOofPik5y5gFhAA80ABTRgSzQAALNFBgAgPocYBeBSlQhH+F0OWNQgAkCIB/AXUSnC2/
LYaffI2JSFWJxt0Xn36fRESFFkPckcAYVxDxRgEYLfETETce0EAfBrjY/wgZo924EI4dumfKbyAC+IaE2jW
DVRZ/SXThGRy2gyVzI77HgQgZtOJBBiKM5NqJxaVoH28ssjGhGQYeQCMEfmVoIIMXFulNAW6aIUCEGBY4jS
ceygKiXgRcWExHAtA12pREIGBljVq6QWmNXMZHDi0BmDPcmZ5u2dyKnkTUhXpZKMJEAGO45R2R01VhqiIS8
rEeEt7B194acDRE0BLacWGZeU2UYUACB/jVxZ9lOJpslWQgoEWPXzAwHhLDSOsPps1lcJUmoKIj6EJjpMKk
J+Ze6pyoa+ZCY35J3lYhpBESEGgeBNjZhaRLeEejAEclcyGqWuw7jZ9PROPnbZYmt/
+tcSJoIQKKvDXCcBs0iitGJOgOue+4m3Cc5icYOFCyAyNgUMYFDkSA0qi2uIsWoZMFJABcjpD7RkJwWEgGs
i9+l0azVEZKs0SYyOGjAhhlHKrDxt2DRD5o8oaRzcBhGbOSHmu8Mdfpgu0JyRQAgIIDZJP18tMNDyqJFMgi
I4TGcx6QkIFhNCCpwgDoBUExjTYqsLNF34bMwX0OYc1aaxcXExJTgSsJRnA+Yi0w1iGB3Rh9xOovdR03ecg
AfPik79FVBAnrnrIS+xzbm4wNwMotU+DABA5UEEHLFpwcgQMn3B5Byr6XPAEAFZxNAQUjOCABAMynnOt8jL
/
+i9sLNTL/GBJjWBZtH5I+BWkwA2gHjukAPPostEhMW8WwGHlPpdPUsyZPB8jpB38zQ0HjzLIDfmxVXdCcmw
IEOsUhZQzGQoikEECv/vwnQPkK2fw4ETsT2A4AtStZ7nbXPAD4rgQYPAEZQuAAFCCvZBRAHgVKcLLjLG4VW
nuXKDAzw9V8in79IEEAzEI1N1BnI/
+a1tKaJCONTWNKVwiSYEBHETjVqG4KsZmQaMTEGw3hfDHEDMlMNoELaNAB0dMdAHjnPN9dAHnG453JKqDGI
pjwdhWAobawRoYb0kF+w8rbVa6QRYGQq2ecMNfMPHHDz+RQh/y4H/6qlgz+hS9oRKDc5qQg/7cr8IlZkvLJ
EW3GQLgByBHeyeTdMPS15HDxbGWo3Rg9eEYHpNF2EnihHN9IhFk6IAQ1ZBcsZjg68wkhDHEKiKD0UIRIatF
rMZQe4xKpyGeqIn93JMz7BsYFjFVMY8M6SkL0Qq3RJcFqCmECeADgIlhtx3sKOKXIxKZKMrCSCGQ0Iwhhqc
YL1C4CtXNjBolwAd85j47Ty0gU3qAFPwjiPFCQgo+2VwYENIBnSEHGGmr2x0j+bAtu4YKxtqeegepKh86EJ
knhVdJ2huWfLdul69AnwCLALQt4C0YUGtQ1IvRNL1JwltFY59CA7SQbhCAArpKprpDSb6TP1A1Tm2qbtP+U
1GlKPcUsLWDS+UVkAaoyQESMGYWNaI2JXChdRfV0zECebyBVIF8T7rXMtilyqiJtJFSjGja58kNtLp0X394
QEQVUg0GQRCtRuREABgjhbQQgpkXPOqQ/KaUMw9gbSJm5NrxSD7N1XYdmHYPSibU0IuBkBFcP+pcoBCYBGD
2QY72n0UmZdUdo9Y9GteMXci6AtgArZGbtKovOpgOvwF0oSghZwVSgcRUkM55Aj6uGUrGGt8307S7oyllQQ
NeOpnDXIcugNeMedRXJVcVyWfrWNmQXkbdwKnvbGxvqPga019VH00LR3XNx7bPIhaVy+4nUyjpsuJuBb+QK
HC5JDET/nXvVQ3ie0FCEFhQOn5vGIzCUOVmBAQoSJojnREc6jHS4dSANTRdL5rwLME93sOTdBCJggQvcLpc
VmF2KUxbjk5WgvM0Nb4A7I2AC/1YVbERBESqwQbJt0ItVJcI+l7PZ24wBAQU4ALIG0I0GPehw0eBPGQrgnZ
ryL2FTniRriwaMj4khX0Q44gIxabD8OrcTJGvZ7V55ATY6wAJydGEIZgeAWTKXCHXW8X/jPKIfmwLRQF4Ff
kz4OyKYrYV/tmoZP/jnPDMZd06er9FGE4Ur48kArt1CRBjg2sAKsSE8kegAEhcQ7gpAoumh0m1jnUXwhs0T
JbgxLOOJRnrW02Sw/2TZ8TIoAUfnmdCWzXWPOaPoRQ/YFCzUHRhP4AATmAHYSw7jHBP9Dne8eVKg3hGECtO
iwwIAsAt1ijPGrCHW5o24/BqXmhM4QOsIoJTxrmP1IlHneqJY07+29O2w7U9iq3HOl7aAsuEqCfdCPOJa8D
G0cZiKOv87nmXQtrA5uOngXs/TVkbDqyy8Vja4JQ7ErfB1MBwGQZ0zxAsAZ+lopE4489iCvqMAGktgQp6v2
NIwNlkE/PzGGNeO4f5dtssqDmCne/YULhQ22QqebUtvu8nefvJJDW3xtDldA2ViAwcgB/XLULWfJkRBpEsw
aSJwnNJaB863qatfA9vk2Y1pxf8GujWOAHjg7FE3hQm7zTsSGlmFRYh7prtNd66T9O5mkhnU5YEJRgoe7fI
FuW8lH13KO50DVylT5kNkXc6TIr3YO2VqvB6KgLfM2mKkL+idTo5ylJ5Epz9wKVQPgQQ8ob71zbvTgE2KWT
rPbGu0NBn8HBmqiD1dZYd2t5Dwrdy3fvO8T707OKZ5Zp+Cd3NEHqVpbxO+
+50cgYc2LbD//cys8Ly5CE2rJ77RjFKBoReexoMZkND/DEu+ABB33IpLSQcd4QLy0RjLpAyefRGxARounYz
JUADyAYAJOBrZkBEGMA+OLaDwXGAGAtqlBVS/LdJVYN6i3cPUuB8NlYItlYH/HMmCBVhABaLM082fKBxRN2
CDNoicTU2KlkmDFDBEvTnERgiDgowcWuVKAjaPnwEaCxUBFGaQDC4Z8o0NGMlTy4RA0Y0QFU5AFvoTtXWh6
9GD6GEC6S1aTJhdCybGOcjgDJZM9JhhNIUCsvxFN6iVzlzIVx3FVyGNUcga+hwLTwkEjhBAaT1e2CggwtlO
wJkYGAKAFWIa8m3bFpaYChmdLGFaEdzO7ZSfCfLD7XHK2fmQG4IdPNkO7nBgyYyA2zlgeZkA8USABFJAJjo
P74yA7xjP0HGQL4bAHNGgDdIh+OVgKHQSGkTW+YCZ/NSUHxAUpCBAvf2KvADKu43cIiZH/yO2DAwiT5+xzA
WMICVaFRaejRaCEBdGgNsdXDfajhgSQYmxozGSRPXNAyriY0nwQpJVQBdewAhJYTw+IsvMYxwKpCvVEwb8m
6DhDp8VQfzx2/Z9govQAQGyj8jVRRIQV0P5FV4ECx4AwJxoSavsFbw4oQRs4gTYojC6YhVq2hV+EAYq3gZ2
4EC6o/HI5DvVTqDRI0m0Xz4CZV6t0uxl4jnWpASUl+y55BztmrDd2Qex0ngFm8mgY0udg959gvfZYc5pRu0
QWR3SwwpmhsSRZVkGZXhpXBfOY5HlEqH9kwM0Jbb928A5Dyst5CReG9MFGWQUA0VdJViiRaRF5Euw4f9YRt
5Z5prGtWLxrORylVgtAgAG7Jxkng1dhhEG+CLuZOZKtUPddR5gGiZZnKLuQRNW0sfu/eVncuXkoaJpkoRra
t/nQV5pgiZkwKZn3Kb5nWVuaqNEssMNDZ9QrqZshkNZGicSPB9tIiZvXtVNvERw6iYUHOd0goV5UdxeogSq
WIxv5iNzWid3ikJ06Ax1YI5GXkF5JoBr1c2EaQdG1N+qbBSjveb7OVtyRsIevpQa3JcamA8ZzAlPWE6UXMU
BmpNaeKd6xaZzpgKXFZCAoNu4DOA0NCgUcM8QHFFQacNWCmf24aZ9boLqmcF+psGChCgBAJ9QLUrgnAGOUA
GSLCf/airoKZwb0MTIjIxBjRLXFeXolPHUHh7J1m2oC15ndUEHG5jHnqBn6hgCayXDFyyA9/xReixAkVAW6
NQIixooYkondVKnZ8pom/xHGVCShPiFNWTSjtpbUBFpkNbekMYXJ3RDgw6g
uyAQmYaBmWmJwggLwAjSlk6c9Whp7uFHqWyTNYmBocbPNqEpOMGnbckPkEZnm9Yndn4oGugojroLRRQGq7l
al2FC3UQpUF3pFGRpoJbegUYqPRxob6RQCZZAB64jnpWM8LwT74SiXjZnGsRpmJIB5RTVmh2JvilExgAQUf
2NN6joqBaoi5qq4KFqPXRW9JnG9KUiKcSYLslO/xeOH3PZUuxU2q063JtWqjecyke5CBXFxZA4qbyJTxEYC
/qUD7mghpMsK6A269k9q6rWA/plgvpJ6ieoVJONkBl0a6124o593FzdK77anT5YnhakYFWoRgRmkPGxJXMV
5cEWWrTF1cIyrGqe4egJKSggWzjOEgmVQcGija3mKqQqrMdWXL7Cw3CRYqf8ayeYDbbW2QVo6/Fwaz95K8t
+ZxlIBcJeFsw6ncx6KT3Y4/VVKyiAIhF8IwC86qyyo8rCncYuW0gEgBoyq2OoHojaK9ICGZeabVP1w0+OrG
aIw+3ZLK6axHaGQnZ9GsmNExPyEtnqbemJJYcOaSVcghY4bf+4zp/cYpc7QJeIDufeMi58FabfTioPsVcad
JQA9Z9bOKh0HOmTSot5ZJiNHIEUDGBGQRgdrE7d6kvqJNGD1mbjui79jObTTiolWAImDO7XGkFRCeG+uRQE
UQhxlZKZ0cUR8ml6QIBMXSPqWoa7EK/8ve7zQi/uxqCmpYHsFaO+lsHfleKOsRW+jJqUHcmMCsk0cKq8jQ4
e9upWdZWrjZu7nK8hLm70yu/8mqBBkoHyVVoJTiGxxWgZcK3Xjq0ZTBY0CoOVZBWvQgEyCCu7Zoc1OlBfKW
K6BVb7FlUDWyX9YvBVnu0GOxUOMqTjkQH56WNUtGEAY49CcaQBYC6hflT/oq6ruIhkGYxWR37BaWWjZZxTS
Aan0mZwd8bs08me78yRBCIlBVpgTmpgyyzmK35gyiDxCFpg63bmS2jl1uRtD2MxpRIYL/jCOOLOkplQCcBk
EVMAOpKRP34hBL7jOY5h0ZWhB/dmP/SlLszxBWfxHbssfHHx1TmPHPHaF1di81xiOhZlGTuiSmrsJ2qtKA5
tb+HxI3PsFgPYkjFPBZwsGYwxPKYjAKjl/t6kJsvjYEZyUkFyKcdxwx5XijWZBIrRGIfgTCpxTT7gTb6yTi
5d/BrtAxAwKSjuoBguen0ED5uys9LXLxuSiHkoI6OEVzrvKQvVX1RxGmDMdmoldMJp/zAPczYT7h1iQqhWS
ofI7e8VxjHiMkkIZjPnKgL8Ki/jrXZxnx1rczz3JCegby/8sjUbVTILczkvWwFQ1PICiznBRax5JBKN3CCg
h+lkhyL0xQC0qER8pOgMhHuqFTzLszYLRz1LqUtZhEJFwUM7xEDsiXpuLkwRhOe+HK8k7D7PcyNDAZUsr0I
oUVGB9DVVUnRQA+ggikv1SB86tEfWW+n8nr2BKEtftB6fQkY1EUNgyFF42ULV9CJ8mRRMKFAF77Bao0kZ9a
cEM0zf7ax17wJE9TQbhU6zil/kyUd7pKwpdZnmITYfdVwrcxtoNCHioal9lFpLI14rAvl2M+iUL/8+4+5WJ
/Mx/fNXa/QwTMkc2PRClTVQ0Qge1kndUhlgBfWPJqNFyzUkZzT8godCUAHCTLBfMHZoS3ACawgCWzW8Dasx
TzE/y66GPhSuLO9Zx8nnHEECqBtZFzRk2/aUcg4RJoG6BeB7DgFFwvVmy3NnA02Bvg2UBFZd6LatCAYXuPC
sCBJKs6vLcrB7FTYRFMOjyodRK/dhQht5c5oZ6PI4q0h5L/cPLxp6y7Z7m7J8o54kKyd9D7N9g6dd1UQ0g0
IvL61+c3aiya1gn4OAXzEqtwGAf4KCX3MeE/gd9wY+15fY4lef3lE7b6x/gwzrsbOJTHh9GzhouDYoaCWEo
3P/fqsBg8UF4RBVQq1OhQ3L3S6QspicEpS0YNTBF+yVa/0oaIx4KeNClZmTIwR0Q5schEnHV11IjJMceKQr
R6LV/amHZdAciHHPuta4kQ/gXL9si0/Zg+AhHiJvgnxDvllDbR/iIQLhhAqQlFEZ6hbBA2/zkPdwkZOvI8g
0nfi0EHLZQpW5X1zZmPuEzfyF1vQgIYyGZbAZ8LnZneLLmitE80pxszV4qInBA3DB+qaaRLF5QkDAECChjo
abY5PczcAtnkOvnksBz0Q2WuMIIJbrlWx6p9stuYEVWvlooxNAPdcap4K6TBeiePN3/wqNprfaf/wVArDbA
tOIXoDDmyPw/6lTtjXITZouOKtjMBeDGM7M2mQzyC6XShLtQRiMm5sPFhks4944OvdAuprjzaTP+0IoQFYf
Ozm3uKanm+DUcEY6wekUwFcDyIlmpI7ntRSIXDeQ0xD4B3uLMrfPLy94LrjjIXDTgf6dnK33u2GllQEEhmB
UuaPqFpZ/mDatK5ReSAzDsXmDgk55fCcs403ZwgNw+KVL/MLiFcx3AjMEeS4oBa7hNyjocjRGAhMowKPOCc
RDa85jMV4V/S/YBTog/V/UccuzeJg7/cTDd9m6/NZz/XmLfS44eNOBPf3mu74jNdmDuIiffdjH99h/SNsT3
9vLb9p/t4erwnvm+lOUOf95kK6DacGW98HLtad82n30dvfi70bcq0ICeMe4+b2fmwHcIHqaldmwVijiJ37n
Yz3aqwL6Sr5t54mGbNWuB/are3PLev7Z4/2hrUJmL+9H9nSdRwgD6MxgLfCec37re/7rj/cquAgjmA6q5NE
K8wFphfxTaDfvz7fv2z3wt3csGFMq+PyAQ//bS7+aqIJ5kGiiTT32Zz/Yb/
+6ZP34dyfjqz+XLtXXo78PN2v5v3Y/IHh/v7/7yf8Id+wpwBoQAIRDYlEYGBgHAeHS+IRGiUxp1XrFZrVbb
tf7BYfFY3KVWkan1dbz2k1udwmCL1IZf+Pfe37f/wcM9NITLPwjNBT/RIRiIAgISDB4DDCYAwgoeER4VACQ
FEJAuBw4mFRgyMR0OlB4fAAQKMg8rUu0vcXN1QVc3PXd6v1NCy5aYhiyBLAMoEMoOCgd+AQIHR0qhXACcGp
oAFhIGIg9YIisFUZPV18vJGZfd3/vih96gKRLXk4SIDiSpqqGZIGjRwa0OSlgQAgBA/yEJDwnT+JEihWFcF
BB4hIAEio4WEyHUSOTjh9BRtyyIMABAq+U0bHjcNQSaApEIUHQiQElY9uYdPuGRCbEBv2AnUSaVKkgEQGaP
l3q66lTp1GPalmiyVNBfbCM2nGUwObMBJgoMWhVYFWrAK+GKgzHhZ5VunXtAsgw/
+lRhru28url21fKXHUQjF4VnFixVQ8fJn3wsDhQ48eRJRchbDfzZc6dC62YtMKzH9CPRI/eiHqKatatDWmY
pMH1GtiPZKPeTDf3bN69q2wIsMF3GuDCVe+WNyDBgSjIhz/3nSJACuhkpFM/fihJIZlPnFcHz9p4+DDjcWs
3tJO5d/Lt3b+HPxgKK1deBaxElopApuWwHhVYYJOCEjhGAAWWWMKAVAC8hC2FlINEIQLYEoW+AEQRQgE62I
uvQw8/9I0QoMARR60iCOhHkiQKEACcBQB4wBs7AIAooSU2HKKAV5iBJQEAEqDDAAJR9OmABipM4EVqcMQMR
CefhHIxQv8gUqahw5ChQ5s5JJmkAGu8gsBLbRgQ8EJraMLvEpboKOWAVAoChcnVoqRzDL3uxDNPPffks08/
/wQUUCMCJbRQQw9FNNE97YRiRKGuXChLKuZwcQoIhChHQ5+EkOSYsex4wEsge2yEzZWONEJTDutkdRAP8fg
Ovu8IsdAtSF/aFNf7tBKQuQcIzNXCAm76LwkIzbGkTQvxUw+KWFt18tnLYIXWDEYLScaM7b7obtBqv8VCWs
moBXdVMMS9AoIAjmFj2y6UW8/ccuedMz5y6R1i1tnQxRc8fhO7t199Xfu33+f+XSATb3Tz1uDUwvhXGzVmF
KNgh3vLrIFJFjbCESX/r9D40ix2DaAB5nby8giFtoK44ZRKJuI+l7rYyccn7mNS5okGVkPiYdw992J6N7NH
TiJaYRfkAES+ItQXWdpHgbguWXkalI6wQoCyAiCAOZU49m9mLmouopUFcI65LTRQzrdqKhTkBOjmru35X4p
bFrpconmsOawFNH4EAsC5JgcSv0k+hSAeE7B5iASYzlGAaqjmFLmAb4YZnAIY+DptsbcgG/Oc1S7DwKkpqR
wAdVdGwGhn6Y4ilrJOQZCSXRV4cYA3qTGKqEd83JXBIbg0c4okCCKAgRhj7sTavMHdmw6y7/OmrKQB0FiA6
WEOGcbihWAcs3ibWFe5Y/DEu14o/zJZbxMDOueyrFfghlldBe4ngv5TDIfkRY3P5lH82tK3ddHPG/YgQFkW
Fr4isGhyqGNZAz4XLthBIRYMQIUAbhSUFyGgH6Nyggcf0pBnCKFSyzNCp4x3QbQIAAI+EmEDXNek530regA
gm7qqty5YvOkBOeTe0r6RiiRBwRxEKBPqIGg1V9GQEZAYgsy+phIvSTEAnXCfujgxBJXQAodQpB72AgDAFm
EibDuZRBepQYmi/WiMP2oc+RhgvkvcqUrzqODNjEIABGhDQU14Bn5C2DsDTG4rXcofW9Lkj8lJbieGeYCQP
ja3GlbrhkDcIefAOEAo6lCMKxOCPUTBwHqYiP8lLxSZgSjHsh/N0HnqewL7QEGJr3lSZiRzhSc9NwRMipGM
tuSkzXDZljaaDQpJVMgSf4IhxAStCg45QCS0oRL/fZAO9+nhNiIxDhMW0Qg6Ut0iR8FCFmEvEuCIIyUr2aq
MbayX1hPjFYMZTm+A44qD6xocjVAmBAjpGmNU5jeAJReXWTBzCdjc15bQCSs2Twi65OIV2dXL/
+FsoWeEYlAc6j06GJOUOHycEFQZUHVtqHWtfKUzpUAyb0jsdi/iUisA4KYrIut3/tFKFP8jTrA8InmkAsBY
2LBOaFksHQ9wZUqx9syt5bNz9pDn/N7kQpgVQX8UHSPaoNqKH2bUE1P/LeYbP+pPIZRCJW4TaVMHAI7ryau
JK70Vw4jKKqNqpqBPQupQK5a1uFqlrnOd1qvuOrQ8juavgJWSYJ0osMJ65rCIBdguskWEyUJMblm4HGH36g
ef7eKxkO0LcuyxMpqAwigsHR+WYtaPyvpDLpel4GLFUI7UhqixVjhIMDqri8+C1q5fKAeRimRaGDEIak9oL
a4GBdvBMFevsBxCK9rHTBptLF6VwJQZj5CyclSxquXsQrdWmwuebWG3UjgvLnrrW7l6QUhtGi7vfgQ5KExI
Kw6xxIICNIkDBO9FlBiWfr+ER9k2QSwmpS5EWLK5hazMdNsJ3FaqyDiFgJcL4hVG/3m3kQoB1Mo+elELE4T
0CHz4dI5xAHAfU6EQqGa1ALM7BvJO3IokNeKmuoMTdNkrKzC0BFdZmUQ/xFnfemaVtUwCpx1OKCOw0WhHzl
Xqw5DYgD9SI8GgDGk02eVADHGtHwrYTw+1lsH1/WcB0fhqKTRxLIXgVz/8YY5ZLrRFEdIomQ7acI5ft1nH4
WhE4YiFsajgBB+LdHMt7GxVzfHCSzCNnAJgoYYQpIw+8hB8CmG0jnfsntyo+T/xFeERpZAM2x2ZTJO4SRKI
Z0Y7nFord2vmUolQDgiUIwmGtLNqH+ASY9CRGY9jURU3lwBnJNXJaP6jTEYlJAbgN0V2KCePnP8BDZwQ8hL
XFBWm01lgApd1kVRiiExyu41WECBAGJJcopPg6Uf0NxMIaPYeQ4HuSoNCFPYAErt5uukP5UaVIM1GmkQYqn
UTYK13s4S6+ntkFX7qUpXKl6p5+Ckoy6fAqxYFrqk03x8pCZlU2wSkhY1T17n6QsiuYj/gqyb8SipS1pBJt
UdoDQXpu7b5quCohOAocRilJz470qPVfeknbFPl2zw0i7RhSJVEE5Tc5jd5cmNhBDSgtPJdoyYWfqJJXPPI
wsp4u0mW6pmyZVgDJmiBC20MjStkwaprHq1F2glaEigW2azuNQe6FU/dREJVbN6oxtzyXHUl5iXSZjJVnW3
/IqhEbhqGEDM8LBO0qIIJBGGQjIeeZ0yUgxPN3thCTLz0SmsFx9rFedTtZYgDgeRyZo1cEk9fsmPIkFONMy
sEs3n3rdDB9tcwuyhu5yV79rEs5iC8lmCyj6+QYhbmsMMfT59yt3Z7HRiGg+pX36HM0szSYShHWynS+sFaX
x3Yv632D6ZYTUMv/YFVP6fZn3qDafg88W+PO9KrBYQbu2IVj632s6H3Gxf8yz8s2D/McpfkQgNYuxopqwMA
vAIHrJv/C0CVYo31MsCdQUDn6D8+oEDzg8Ao2L8QfK12AYMEDBcJtD/D2sDwiIMyeZDd4Yf7MJLPW6j+qS5
M+K8FpJCd//u8WOAEtrgUNvswFaEEeUIdGeQ8JrAQ6hpB/UMEEwQGCUxBD2RBO1GULeTCLtTAF3wHQsgJlH
KCQIMFWpA0sEiwJ6OsfqAJA/EUkaO2ZrAmT7A7E9mga8M7UOiEBHgFbkCSSeq+WPqPaQgIPDs9CeGHZ2ALK
gMIspOxBWjEUZDER2iyHDGzJnyJMAOcU4iFWTgGAaNCAQTDUvSFONCa/4CvMjSKJKo3KzM5slOtNnHFw/OK
lVsJcTuD6JswVRQkJngT3YvCDkwdK9NDrfkRbVMGBWCOohieRxynQ9OQf/MHaqwCcAKhy2PGM4zDcSiHp0u
yLDTFcVSHNsCG4kIpbP+SCTgcAtJrOFl8uTZhR5FqPq9IR7vzuV1cvHMMlXRcpj0jxXZ8G2i0AzTRizWZuW
IMiAFoJAS4QQVQvId8Ol7ip1W8PJPSi9YhpFhEO4sjx488Ra7DBC+JKSbojsExiEcEO7RLFvxASVt0CCPUx
Yj7KmX4D5LcqbLjL+iSwmOgCVYgu34UNeVyRvKpiVR7tCjyEoq5uzF7xr7zR+WaR3u0s3fsSHUCyay8hS9E
B97DSlmrgsrzkrD4lGLhvLHcEAvxBrKERBMjGcV7S+xhkpUsSeWKp1IboZUcRfrTyr5sB97Ylan5yhFEivA
rR79ETEWYP7DEF65MzI90TIsYRPf/e8zK3IPIrIjJHEDL5MyJWUzCTAMVFAMG9KzONM0ywEyK0EwyEM0wIE
3eOs3YhBgvpM3atM1HKL/QNKrXJC/Z9M1KqqscLCL/uoRUEJDm0TwkSEIF8aAfJJ4KUaQk6ETx88zftM6LC
U41XDI9nLZoiDQN4pFLWBgiuTq+a4DmEQo09D8+u872nJfstLdVW0rmYyR6k5gZackDMABFcpOVwYmM7IPU
dM8BvQv4tDKIc63DEzp9jMeVACeF47mpDFACpdCi6gPSwykziYl6TE6axBV53KkDSBizkM5JmMg1ENAKVVG
kSFE/aLq/XNEYBZEWfQMgW8/qlNEc5TGHoVEdU/XRDMPOHxVSfwnSITVS2+LRI1XSfSnSJXVSw7rNKJXSKd
WTJ7XSK8XSLNXSLeXSLvXSLwXTMBXTMSXTMjXTM0XTNFXTNWXTNnXTN4XTOJVTiQgCADs=);\">",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" CNS: central nervous system; ACTH: adrenocorticotropic hormone; CAH:
congenital adrenal hyperplasia; AHC: adrenal hypoplasia congenita; ALD:
adrenoleukodystrophy; AMN: adrenomyeloneuropathy; PRA: plasma renin activity.",
" <br/>",
" * ACTH resistance is a characteristic of familial glucocorticoid deficiency
(usually caused by a mutation in the melanocortin 2 receptor [MCR2]), and
of \"triple A syndrome\" (Allgrove syndrome).",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_417=[""].join("\n");
var outline_f0_26_417=null;
var title_f0_26_418="Heliotrope eruption in DM";
var content_f0_26_418=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=RHEUM
%2F73090&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=RHEUM
%2F73090&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Heliotrope euption in dermatomyositis",
" </div>",
" <div class=\"cntnt\" style=\"width: 360px; height: 232px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCADoAW
gDASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwD0CG586VJrd+AdjR9D16/pjFa0MscSl4fMKNliGOAG9OKwznzZY1Cie3
kL7McuP881cif5TGQ3lSEMhPr3ryW7H3NSmmSid7iO3IXypoSTjuy5/pWgDFFMz2shVJAAWcZKk9ax76T7P
cLhfMJXeGUYUjuM1at5I5oY1JfyyMhXHHrj65oSuROF4prYsTKlrMlsFQk/MHfnI9j261JCXdpY/wDVMRt3
t0PGTzWSJHnjliY45+Uk524/Hj6Ul9cO0KwW2HlCjgnoM/54qloHsm9L6/1qWv8AR5JWWQAsB2Gcj/Peqdz
E7TkSnEa8owJG4+ntSuRuSQK7KSA4GSy+9K/nCKTf8ka/MuPvcetPyRpZxZWOCVmkCrnP7sA8f/XqjDbLPL
sBWzhcFpAeHY9z6DtTr+7NvE0mY2wchGbBHrzXL3xnJW5mkldSS2xEwFB77ev4mtIo0Ub6Jlye8VJ5fsNoW
hTrdMOo9vWi6vbZlWJndoWAZijEkfU9Pwrn5tftVfPkXF66Hbs6J+IzVeTWt0To1hKJQuVV2Cqnpn2rVIxq
SjfU211SJSTEtsApKu0jBPl/Hk1h694n0tJtsUkIl6EIpfcfoOtcze3dzrM3lwiOf+GTyMJFGP8AafGSfYV
k3UsVnMsNiRdXecE28eAv/AjkkfStIo46lW+xvS6xeyStHJ5wDnKlUEbY+naqU8LwL5/2u2ilY4RmTzZPpy
f5CsC51W5gk/eS20coyDx5jj29/wAarPdXU/7x52L8HzZpNmP91ep/Cr5ephKrbQ35L+Q27pKkJJ6loFVm9
8mqcurTIqvtt9+Nmwoq4A49Oa52cTK5aV9oB+
+wK557E81HPdNI+WuGf1ZlJ5/GnymE6tjZTUiLnzrlX6fIIG27fcipYtUwQSFnQDb8wCsM+46/lXNPLESSX
O4nkBKWbBdVhjDFgPuKSSfx/pVWRzyqpm7fyMYyfLmQhtwPmFsD3GP5Va0rVEMDpdRpJCx+ZkYhvxXv9a5l
UuEViYpkZedpyuPeiO5mM4k8yRT0LkbiP5frRYn2p2kU8D7fs/kzkjABkKlR/vDH61ZvNO2r9uklnsGdcql
2QQ3HXeuePqK5Q6Xeyobq0mV7V2wJQQvPv2B/Gprme+W9Z9R1C4kmwEdXbqAMBeOKOVFqo3samdSRRI1q1z
ARlpLUhww9WAyKuQXk0SC2eRbiNydpkYrgdxuJIA/OsuxntkC+TchZGPzR73jJGOqn8xgg/Wtq31jTLm6ht
9TtG2/xTWxIdRjnjJB6dV59qVi1LsNPNu8ENxPJA5Li3uVDMD03I3f061GNVmEgElwszrHkCRtrYPY55+mc
10L6HDLslsLy2u7djuCTExl1x0B7+mCM1FNaPOsUkIS1IzhJRuPIIySf4ePTvS5bFxqPoc19ulmuJZleaC6
A+V1BYEDqGwclfcc+1TWurSXEyNFAstwm7zI0YESLj0xhh+Z9elPJEkyrrVp5IZjsmhzHGffcv3fyI9qbqH
h93jt7hL2Jd5PkvNgE46YkXgjPQ/yp2KcmyGxupCLuTSICOjPZBcnOf7v+HIrU0PXVuZCWYjCkIHO7Htk9R
jPB5FY1xDfRXg/tmK4WT/llc2pBaT2PQN/Os6ZJIGnuPN89CyqZUXy2z1G5T0P6imawqNHqpIESSW7duR1I
/Okgu5HgPkNukRsryOnTn246e1cNZ69mATG53uvAdv4Rxy6gDB5xmr8Os20UjMj/ACudrqX5B/vY6/nU27F
xndHdTTRytIRJ5kJJyzrgMcdPwOeD6H61nTD5XEeNqnk46g+hrNhvfMdoyxZN43on44YZPHGKu3DH7Kvktl
FGGYjBHP5n9KnlHy6GfcsFjMiNwAQV78dKzb1d2Vi3M+QyEgqDzznPbHFbDtFJalg2117cHtziqORvADASK
pMffnr/ACND0MJqzMrVCGt1SAF2HLnjn2xWW1yWgQTKSEHy44/Wp7xmjmbeGQOMNkg54qlMNkJJznOME/Sq
SJSsQSDBTcMFh+v0qEgqFIyeehpS+8ZBJx831FI53xA7t2DjGOKoTZSm+aY9SDUDfMD+tWnAMoxkcc+xqtM
D5n60zCZf8JA/8JXoipjd9utwufXzVoqXwhj/AIS7Q88f8TC35/7arRXvZPLlhL1PLxfxI+o40jLl0k2XUR
B3ryXAHcVZgYzzMY1fk7025wp7gf4e9UUnSUi5uFkgaUBDIhwQ3+0K1oitvZpbtMi7WPlyIMLIcZ5/InNfE
ybZ95VdgN1K6vCArbOufvJ/9eoI2wZIiWwfunOFLf3sUOuGaQRgXJILN03D19xUN9JNIm2PAUYw7dj9OtLz
RnFW0J5RJBZB5GTMYwRjBzk88damurhRCjsysY124Uc/Ws23mui0rzMqnj5c/r+NRtOVuGkQgh+UA5+vNVH
a5oqd3qXvM2/vUmZI0yxDDLAentWXf/a3LNp5Lhjw85Kp+A61eDqSzKq4I+Yk8k/4VTc+fHMCsihm5zwD7g
+lWrkPRnL3MQhnUzyvJO7EBy2EHchBz+ZpddVZY1QzyyyuQFtQ3ykerY6/yqzcQvHJ9pnQqEBVA3Hlx9j9T
3/Csi5uJXinneIQK/AYn5sep/LOOa6IjvzGX9ntLOQvPPuuCflSLjafRAOtY8sYvzu1BZo7SRj5dlC2Zp/e
Q9l9gauwQIrPc3MhLTfN58jZdE9AO3/16hnu7e3kEkcpMzfIhhiJwoPvWqOSrruZGsRXX2Y2JgjsoIxu8mI
/Mw/2j0Rf1NZMOk3HleddTC1svT/Vl1+nXH1610ayQTymRlZLFH3SPLy1y4PB/wBoCmardvKpub5Jfsa8pC
6hd57ZHYex5NNPoccotmBNZ/6GZrS2tbOwGMSyrh3GeoB7e5rEup4o2VbWWO4lPJMYJK/8Cx/IVsXts2pTm
91YywW5HyQxIWdvoOgFS/bzY2LRWFqlvEwwGmUmTPZsKDz+NX0MZKXQ5dreZsNIsmT/ABMhI/M9ajeJY2w6
GU+jNtP5dauTyXMzb7iS7nIPBztAquYJGYGCMgf3gd369Ko53T7L+vyIN0S5XyVB/vHcDSh0GWEvzAjCgsM
j60/7JeMC4tpWTON2zj8Kvabply8kjy2Mc0ew485yqoSOG4649KLmFpdF+BnyywtGoS0KOvJk8wsTQbiSUg
vMMrwN5wcfWtiLQ9ScqyeYi4zuigKg/icZpW8LamcH7LK2T9/OQT/L9adyvZVH/X+RnrcSRDypVSRcglGOV
P5dKfcvYOy+VayQMR80bM2PwJqzJ4bv44/M+zycnBWPB/PmmvaSuywz2080/O1cuzDP0/rRcfs5roSJZo/l
/LNZLksJpMyKMdMFRkc9xV2SGRZE869t7x5f9WZsqzHPaTj/AMeNVI/DurW6PNJp03krwSdqsB34zmmPFPt
ZIYbaVQCAIgshK/7QxnP1oK5erRq2Gq6hZzypFJ9oMh+e0kQq4wMZU9/pyDWzpfiHT5wy3UctpNuxslAZFA
HbIyD27Yrig6QApq0N5KOCgEhRozjuGByOlX7iKG4ffDqMvAAxdTKp6cDnsD3zQNR10OzvDcROGsjD5G0O8
Mb70II7qx/UHrWdcnTbl2juIzo87Lkk8wTEH7rL909umDXP2N/qsaiCzlhlfIfyo5dyyD/cPGR6gj8amn1M
xWRi1HQ0JYY3OCNvuGHb2OaT3NE7GgFvLRDHcxb9Mkb5ZogZ4QO+Vzlf6d/WkuVjiKmV1jJO2O5jffE47KT
3X/ZJJrFt7yKyOFeRLd+dscu1h6bWxhgM9Gz061csdfaC4MSyQywMMK06bcd8OQMfiR+NFiua2hUu9MXznM
UqQXGQyrINqEH0I4/kfUVlzPPp8hWRWibG0g8o49D7eh/Sunu3SJG821ubaDBIdF862IPfjlefT8qw55LaU
bbmR4oWOFmgO9PxU4wOnTFCJlpqnY2tC1e2lgEcruJSQvzfeGPu4P5846/WukN5HJbF4kR0lGwsSGAI4OR6
Hr7fTmvM7jTbmEGaEC5t16tHyNvb6fhV+x1SdIVlQyFBkCQfN+Dj8ev607XNaVZ3tLc9Al3x5WMb43wu1s5
DcZBPp15qq3zRy/fyB0x19SfTFZ2kanHcxyKWEbrhWicfdbtgdcZ6H8KsxXuxStyRHtOD/dyR69j9fTrUtG
spc2xS1CMR4kBZmHCseay5t0rNyBt4I29O9bl9LEFWPHy9MZ4HH6ViXYcFfm4TOeMZzTRle5RmGyTKkBcZ2
g5p9u5G7bsClCpLLkHj+dJcrsyuV3cjhgee+cVHF8odSRyMjBoXYhsiKlt2Bz357VWmXY/HTtmrT5UqQTz2
P+FV7jk/MMe9NGUkX/DbE+KNIYcAXkBz/wBtFopvhxXXxBpRhBeT7XDhcdT5gwKK+myGKdOd+54+O0kj6ph
Uyyq9tNHOoO2XcvcYwRn/APXV2NtnAVhG+VdF5wP8KzyIY/OUAW0gbzCY+Rz6/r+NTQsi3CzKzLGxIkVDkf
UDPWvgJdz7ySuWL4XIhtlk8tNpzDIBw691PpVbzFSX7reXIcSHO4Kf/r1euBNFHK9s0b2pHKt8zYPTgisUB
5JT5KO9oRktGeE/D+VC00CmlJF4wZk8w87eAVbPH0qrdBIVTfGVHcDpimWMkW9S88juBtUhuD/vClnkYO8M
khZskgEYBGfWrKSalYpzb1Mqx58tQSef1zTo5SsJVpWZgvLHg1N+5lPmRMM8jGePyrP1CTcm5IxvY7WAwci
qj5BKSl7pRvw15I+
+USWqjJVRje3Xk+lZV1HHLGN87OmduH5wO+AKv/aAqNbyKflPy/J0BFZt1ve5VixWNOAMgbie59q3WhmRPF
iEyLGWVj8qP8oCjvnrWLe6e1z8s0wHmozmJWIyBwAT1x7cVqXk+xMzKSEIPzNnPv3qm120riSJSmSMuVxkD
0z/AIVabMZK+494oLcBowBKi7FAXJAxjCjtVL+zkmuBPMwkkxxzwpPoO1WDKykASEBsjbkH9acFU4YDD9yT
iqVzJpEbRqbgyzyBptgXnAAHAAA7Y9qrvp6PvbZES2ckguT+Z/StFCXHMXBGTgfnz+VTx26yRgiN9n3mBPb
1x6e4pNsnkSMiLToWaPzEWQr9wuB8g9h0H5VfXToi+fLTPQNkE5/Wr8dshJMgaOPkkKRx2HX+tWYo3Ebebv
KFgPnyAMnnPGOc0c1twVNdDOXTFHzSeY2MHgZGP/106S1RE3tGrsOQetacUbRx+dj902VLBwdueMHnNSB4B
IyzyiEjG0tEGU8jg+nHNTzMtUUYay8K7MZI8DAVOh9O1attbyXEeZWjjC/8si2GcYzn0x9KbJZ26sZozhT8
gniU7d307cH8akt0vIl8uS8W4iiB2BuMA8nBJyPw70+dnQ6FOS00J7vSormBHktw6RnJ+UKcH2PXHrimp5F
rDJAcrCpBC7AoPHBI6VJzJFmWZIi4A8zGY8AnjcOQfYik8xp5P33kzsn7tbhAN20YxgkZxzg560+Zoy+qq2
pm31pb6nkRWgdccN/qxnrk45P4VXHhvQbJH88wJcD5iQcbs5zkknd2610zqoaPDuqsTjJCg+nLDleOpxmqE
kSTTyJBJbHGScEYCfXHP60KbJ+rRaMXULHS50aIRSzW/B221sYy314x+tc/d+FbaUK9jpdzaAnISVd6keoB
OB+f0rvfLkN5FA8sNtGwwJLo7VfjqTnAHbHSqUmr2cpaHfukQkMYo2YnHTP+elac/c55YVrU4ltChmiYQ31
wr9WSQISCOmCMceh/xrHvdN1Jdkb6piFgDudmKBR03A88fjXpkZgmQtHo8DuG5dwMj/vrP5Ad+elMurU/Zs
xQWTRyMC8UcSr06ZYjnr04HrmrUjH2LTtY8yXS5VjWUQW13atgM1pe7CT7kgkde49KoS+HpTMBapNFuHQyp
IB7A/KD74r0W60Rbs+bHptnbykcOyo+7H4Hj9ahHhi5ELedqchklU/u4I0jwPXkE/n19KE2RKknueZ3en32
k4O1kHIO+IDJHptY5+tQSRyuD5tg24874w3/ANcGu8m8GMzblnlVkO13llZ2I5O0BCOfasi58GxQ3Eafa4N
8h+SNoiCT6YL5/nTuZOm9l/X3nIrJdWQAiaZVzxEwOD68UxLwqwdY/KkPGUyNw9Dxgj/PNdu/hma22sslug
B4IYIOe/C8D6ntXPXtpaKWDahG75z5UStICe5JzwelMzdOUfhZRF5HsUM0eR93dlHT6MP6/rW1pWswt+6un
jdm4Ej4IP1GeuOKzbe2aQqbdnlQDLDYpcfgeD9M5q6thDMVi810nJIVZIEUt7dOaDWPNu/6/E15bS1O52ih
xgsUCLgd8d8fpVS/sYwIhHEoXbnKrjjr/n6VZs9JW3KqPKTCkuAnQjvlcc0y4MUJjDSB+oGTjP4GgoxrhPL
YYb5QMj3HpUAdmkPPBUnj61YulYSMGyFXHQcVAqABFBGTnnNBDG+YDJg8Y/Woi5bcxz1qWeGSFombGGBIOQ
f/ANVMckCQkZz+VMhmp4SEY8T6QHcoftsGG9P3i80U3wwzL4n0eZCodbyDqeMiRaK+gyaMpQly9/L/ACZ5m
Ma5ldH1hcRRRyW90xjjuc7N8anaeejf4VbtlSe6DMI1eRg0jwkfIfVV4GOlR6ZcGyQvcwzkJMC0ZQyBlPTn
0qbUvssV285DWwuMgBBkAeoGMgnHTtXwjaPsXdy5fx/T+rlaaFC4E00YkDbQ0ak9+jZqjPaukryWzB8jMiA
4KnHUetXblpMNJDbqZGHALA7xg84PQ/59KptPIFX/AEYFnbaRt2upHvmhWvc2pqVtCNoF+Xb5eCuRldpznP
btVW4eSFT9oRRGWwsijI9s+makkkXJkuAfLJ+UE/d9eR3qKS5hmd42Zl6AqwJz6Hmrsacr33K7bJpFUOyvn
PycBvwqldbFcJulMoXAyMYB/Q1dmifCyxuJZV5+c4IP4Vl3TtJId+5SOSoOQM+/SrijFq73Mm8kduI5lcc8
4yf/AKxqhcPhWVo97DgqecVeuw4cbHAQHJBGay7iclyBySeFzk4roSInOyKgJLnc7YwdoPY44GfSovLLyL5
oPQkjuPU+1SyMRwzKWzkKnzOf6frVSe6aMNxt7DIycjsB/j+tbKJz8zm7IvhRFH5jo/AzjBG3PQ5o86Riot
bZXeT+FVyzYHIz1/LFYs96JmLSKzBsDAfOTxnkiqJ8ws4SPc4GfkbJx7nPWrUUdVOgup0ct6FxlIsKmfk2n
88Hnr35q1Z3keXEsRYtjkKAVPbqMg9+2a561kWTzhPbBZSAYzkqRgdSDyykDt+datiXuojEJZTcIPMREYOJ
B/F1Oc8E456Gk4mzpRSNWYOsayGNzvfy1Zk4Zh2z68jilFxIsTBHwCMDy2yo7dOx96ztI1CQ5tm+0SI7GVR
AFO0DILHPt2xV03UEqhp4uSnztGNmG5wVxnIwQTkZHTvUSiS48ujRoSXLyRR/aIYwcAeZCow2Oxxxnt6ikM
8LeaYZhGQQMEZ4xnj8j71izXSWyc+VIjRMA7fePPXA5znIA/pVqExOkXnDzYCB88TgSOMgkHsXG707fWp5B
ci3JLe+uY5jCQjq7DKqduR3+X6dDW1GhktpxbzqAAGaBziQgf7XQgZ79a5rzPMto7WRtoD4TCDOf59voK0r
a0nICxSxS7BlQjgMo7/KcEn0puNypqL12JpLuKJZBsRJHGXbGRnPXPJI6cVQa3mmk2weQSXOXXALNjI5yO3
c9KvRXI89JtQklZ1wQhiC+YOwLdPY/wBazjPp8UzKJHhl4BRCCAd3UH+LueKcUbU20tDpbWMGEJ5lyhjZTL
vBdGP8PAPIzngZOCao6iUmdJPKtQiHIjhXLsM856evT3qgmrfZ5mMM9rcbG2K0hLZ7Ejv7cVVXUmlhIF1Co
WTaWXknjghj0UcD8/Wny31M405J3Ll0jb2e3Nxb3JlI2KMKiH7q7iTjr0JIAqOzXMwiBEoMvzYYqm7GOWOM
fX0qkt00rrHGpRUQtHmTauR36ZJOcZx+NNF0gjeVpGIkyygScDAG7dnBP5H+VKxTi+WzNe7uG+z22woh5XE
KAADOPx6U1rwSyIyhwin5WKhs+uQevSqen3UJE0Ra2SIgFmyWwOuVA+8eOlS2RFwBJF+8PLcKRgjn04FK1m
cs4xW6NAiMbQVdVK5DOpG4diT2z+XpWVqF1DboFW5JOS3RW5PqMZ//AFVoTXJAPkM2Sc4UZ49c8Vi31vDNI
ZnTzBnqMcnr0rS9jljBN3ZFeX7AB3voTuXgIjBz25XBA/zzXP3lxHIClw1ztztOLIkY9sn+ldQHeJFETzY+
8QhJ9qqtbwmXzHhDEn5i0YY/rTvcxlFnFzw2U26OzsJrhF5kZhKfp8uFQf8A1qaFazgkWexlIyMRCVYkT/g
APP1Oa6m9mSMN5drlf4QOMfTt+NURNezLG0dugC9H3fzHBzRfojL2VjCnllCJ5+klFXksyEFR2Bwuf8fpUD
IkkLkS+ZCxysZhm2scdM4NdJILhWUyQySsTwiuign35yfrVLVLe3ZmMlvNA2AftHl4z7Eg+nvVEtGTaXTWk
QKsjBePIl3Hg9dhOOcdjn8KvT3sc0fybsJ1Ujn2BFQHzyQYRLJGrYIl5Bb/AH+uTjvmmXV3ATC84kgkAwxZ
McfXoaYmkihdR/xCIrx0HApsbBcyBR8pztPNWLy5t3t9vm7nzx1Ax/Kq0BVRIG6HoQeKZm/IbcY3YIGOvTN
RnhBjnNK+7auGAHcYx/nvSQ58w8dqRn1NPwwpbxToigKCb2ADI65kWin+GmX/AISPSnZWbbeQnCnBP7wcZo
r6PJIydOdu55+N+JH19bS3InaOb5LMKMSqQDznA+Ye2atxRyPP9me6tppiD5bSpjOOxI79u+awbe9ujeyR3
EEc0CLwjtlcYwO+Px7Vr2l4r2UKxW62d5G2A2ce2Tk/yNfBbn1NalKOy/L7+/qUL+O6eeaSe2gDQsAsUA2j
GM8e361jzG3CyySKybivAY4BPJ59a3pUjljNzbyRu67mlTlRjIxwcg5yfy96w7mb7STFF85T
H7vbnAx3pWR10HdW7fIqyoDIkkTOoY/KhG8EYqrFcNJugZgFQ7lG3jPrxx0/StCxjeUSy3e1BCMtjAdR0BA
4B/CnXVlCFAaIgtnDKMHPvjrVJ6nRzxXuyMq6OcHy8gcAhsfiayZ5xErLyckDAOP1rVv2FrwzfMOcdce1c3
duHXILMDz6e/51vTVzKW3kUL1y0pPyrk9u3NZc0uM+VnGMEnFO1CcO3DEgH8qoO4RhluccY5AHc12QjZXPM
rzcnYsGUBlL7m5+70AHvj+lQ3BSRXIClQOgB69uoNQTT8qOCdwXGc5/GtCG2ZwHXzGyDzgcDvj6VXqZ0/dd
2czeJtZmVDgNkFV5J+gqC2ujDJbu23fG24jqPxH+c1uX8TZcRqWk25PHIOBk/lzXPztl1adnfBO5MY2gdOe
e/tWkXc9elO61L9vOl47i7m8kkEKHJ2J+ABwPf3py3DweY6iM71Kh2XchXPXJ5z71kRzkKq7lG0H5sc5PY+
tTG5H2cRBt5BO0En93nrjsQf6U2tS3M35UljZXgcNGhYhR8zQ84+YjAPt6/Wrul3sJgMPlSecZN6vyQgxhg
w9MfMD7Vy1lNFHG7O7AEDocH6j1x2q7HdjMU/mZw2HRSM7u5/EVDRm5M2NSELyyiGARKuMEElnA6kd+cE+3
TpVCzglkuIlsb3/WN83mrsEeTxuPfjBOOB706O5E0cbyy7ckuylMsFB4C+p5J7CtD7O5ljV8x3OFYKcbcY6
Z6Z6cUtivaWVmWo1miiLzwRSlV8oSKx+ds9VIPPueOtXIZbtBCWjmjUxgo0QyXUE4HPQE+n/1qhhjLTgyXM
cRQRp8gPyjbjBU91/rjPFdNZWsC2UnmzxQqsgd/kHnSMoBJ4OfmyOAR3PUcw7syqVVFGYJomECuGjG9vMja
NdmwjlQ5+cN19h2qi7WZwSreTHn5rcpgKM8upwSf9rj1rrLewvry1abbdpIo3JCyrLG6rhpGfPB4I9+B71h
+LIYrJorbVxb7pHDQzPZMn7r+9gEMqEY6BiT1IqomdOsm7XMBvOYxiGQ3LlFXaGDYJOFXA44GD65PWok+zQ
wAPbv5+C293C8HoB69z/
+qq7yNEhMKJCVfKJkktu5XCHIUc56/rWXNeMdkbg4XO35c5z7n+tW1c6HUZ0dwklvHF9odt0sIYDzDuHGNr
Htj09qzGuEQws7NF5gK53AkgdcDr178dKwri/lLMFMYUY3KgGCe2OvPqR6VUNwrTeZPEZd3Lb25b3pqAlJ2
1Z2QmsrVbcQwvJM48xw2F/3AMHIBXBI4Pb0pg1WTynUhl3ksBt46849hXN/2jG0uRvION7TMWYgcc49uw/O
o7i/XkRswXdyANqgZ4xznpjrmjkM209zqFvX8kBJCVXHPTH4mn/2mojRIGXccBj3JPb9elcXJfu5x5mRkcZ
wPanrcBynmBMerZwD+tJ0yHZ7nZLdqcqS3mEnAB5HbOD60klyoi8vaeG+Zicj+dc3aXsSGQkBSQM+3Xv/AJ
71aku4pYNmA0WcnA6+3+fSo5Wc7WproUfdhnLYxgA4FJK5Z9ke10zuXacge/pWfZXBKHHyY42j+L06VYmmD
naFQOTzzgn6jv2o2MnuUxHbsztLG0ig/NkEkD69B9PpVW7t7Nnw0Ea98upfjHGFGefyrQMUu0D5jzwcAfjz
imhJdrAzbivDEBsdPX6U3KxnNJsyEsrV1cR2Eh3fKrMgTd+HX9M1UguWjXyYo1aT7pSPOM+pzx/
+ut2WATK3ynaxIOCRux645rLNqvmvEIyicMqDA+uTx6CqTuZ2RnzxsD+9CgsMbccCqQh2t3Cjk8/0rQuLJC
TuiVew3NwKqiPaVY42kkADnFUKUSsz4LAgH04pUz2yT2waa6Eyd8dMGnQMqSYf8MUmc/U3PCRK+KNCKjpfQ
Hg8n94tFHhmTZ4l0eSLIK3sJHpnzF9KK9/J6bnCWnU4MbJxkj66srS8jupoo418lVA3Bgwzk8AcfjUlzpyf
NOIVfcBvw2MrwDjJ6/40AwNsSKQKAMMUf27r6/rUIuEsrYFFklCjAZZCxAzzke9fDPTRn0t5uV47/wBeYTw
pA0zW0DXEUZBYJ/AMjkAgepFY03lrf5UCBpJAqN0zzxn0rSld0YzQh4wwDMp5Hy9yPr/Oq00qXAWabYwJLB
QcY9x+tC7HTSvHfX+vuJo7hlIhjVSN25GOAzDHQ9se3fFZbyMgMRdlxkDOSAenApNSf91HLCwwp3EIMevAz
2xWYbl3UOXGMHcr8BQT2/Sqs2aqnZXKt6ihSDgPnoRmuY1MBFKfNx0A/rW/eTFllZMIQOAOpFcnq1w3zBy5
IXjjJrqoxMpyZgXMwkkKs5Azgkc4/wDrVnvKPOMe4nvtHI/GqlzdIZmbeyMD820cVasV+4yn8VPTNdbTOap
GxYjgknmVIVJy3BHBxW3pkIknEE25JFJ3MnTbg8gdz60/RrAXU5UsqEgYAOMdO/IAzWhrdukYiMjhbu3Ysk
4zuwMbQwPUADHQccdhVW927MYvmlyGLe3CNd2e9nVgRHuQZY9e2RnOQMcdK53UY5kMzRmJ8jY4jbLgZGcZ/
AZHUH61pa9dxTTI8FqURgQVMh+VlwdqsRlTw2M5yGAxxVDxPJZreRSaZKjW4iXACMpGUHDqxJ3hiyswOCVy
OMUQVjsj7tihZyo1zEGSHZHE2D5eSRg/eAIJbPHXI96oySHZ5fVAc7en9KaZDEwK7QSu3+8Gz1PP1H5UyA4
kTzAGQNlypG4j0yf0471qU5t6lma58wKGkfeTuf5hjjpjv07GnxT75PujfwMjjHTn+tVISoLAqpZsYLE5Xn
t/9elUbnCLnfx05zQOMmXob8xDY7DGeflznv8Akeh9qtWl7czDy422qV2zSyPgD3+nNUJoZFIkG9mBy+7BA
/WprSaVVmYIqIAytgdc9OPrx+NKyZotdTr9E1G2gnhkjtftkVvE8kqO7RiVBwcnPQZ7c8110Vvrd2h1jE9t
PBGZ7eKaMRSzRgZMqlyPMAX+Ibmwoz2J870fVbw3Fvax20UiQsTHD5eTubHAyc9cHAz9K7PT9d1jT5I5dTd
pLZ40Zru6sGn/ALPb5RtRGOMopwAeCH4qHFEVKct4/wBf1/VzpNNvdGk8KLPqkM1xcWM8bXbrMyrEzFgu9S
hQL93LMGYscDPGOK8b6pYwGK2tLnT74XcPmz3FujSTQux+ZN+FGBnhQAFHBBr0rxXMNKluxod9ZbNXtdpOl
rItxesWKqFLboVweSFw2GYALjNeL+J7S5SOW8m1dZ7stukhkuTJLhhksScZPXP0pxSMsPFTvPZf1+pQuLkR
biod4AcpOy4+Yj5dxzyeM89BWcbwfaMFkIYgDj5Tz157fWmyNNdXXlQh5icgJIQ2eMZx0zx+lUAFUnzFLMR
nrxir5UbyjroWZbwPAsGyIBSTvXh2OeNx746fSqhlGRliR/FzwfSiTLYYpgv930x04pJhheV43YBJ54p2M3
cmeYySGdgA5VfuKFGBx0Ax2qAyZdnTAUj+L5j/ACpgXJJkYYHUDqfpSSSRkHEcg4AHz5OemTxSMpNoRXIcH
qRnANT/AGklCshDDPT0qqzMACMDI7Z6VGMgZAOP60GbmzTimZQzIQEHysWBIH4/hU0NyGgl3CRmz8pUAAe5
9B/jWOJJANoJ2k5I7Z9atwy7QyDPJwDnHP8APJ/xqWiFO5r28rqu2KVdpG7AfG31JBH9asrNHEgaM7um4jg
e/XvWTNdIzmGJEVN7P12j8ecduP61XNyqhVU5CZw3bGfap5bgnc623uoiQUmVNnJIbdz9etPN1HNHtBX5eA
T3z35PrXKCeQOqjDFhyMA4FacEsUewE7i5B3Asuz61DgRKBoMAYl2EnuoDfzz/APWqBlCSZXcvygbV4Geef
WpRKjc2ucKDmVupOeeO350942aRZJS3UYb3A559fXNJC5TPuYC27cQ8mM7CMYHqT3+lZtyihmAC7ecEHmtW
9aMsfLHGe/8AhVDywxbfuAHXjg1ohyjpczHQxqxyGYj60qQrIGYn94F3exqaZCvGeDUZhVY1JJ3HsKDmcNT
U8IqZ/E2kRjHzXkKjt1kFFHhJQPFGkfw5vIRuPQfOKK+gyaUlCXK7anmY2ykrn1c0cBnWeNGG4hlbeFOeM4
GP0p0vkeQ26TaypzsXGGz/ABD/AA9aruI5VhMih2Q7sv8AL29RUU8MhHnFQIsDCjB2t2LCvht9T61K9rsmt
ixaaVvm81M5b+HBHNQzxxIS6dBneqjIB6fSmvJGTtQlXI2nBOCeM5otpyBiUrG8YI3f3wemR+lTYtXWqKci
FDtHMe3C5PAOQeP1rKutsYZYQMAHKlQCQa1JN2wLjdn7vtxWTfoDmPbnB+bnitIbl3u9TNmGAd5wVXH3sDF
cvrMMUsRyZFxjp3NdXdjyoGDKd/Q9DiuP1KZv3hf5dqlQuDn1yK7qehyTu3ocfJZtLK5ZmBxySOMVLYbGZR
FLhM4zn/PFTOcsvmAmNs5Unnr0rPlmME6bo+M5wBj6CujVqw1ByO70UCzgubiWY4kjCdSoYAgleOvIB544r
N1W68yUNCWaTJyefmGOm09Oa5+XUnmQpIiooweGbnjgYHrzS3ckc0LIMrs+64Zhkn1BJ/TH40NO1mbU8MoL
me5BKLmX7RHH8+CZJFLYIK8c5/CpILG9vbW+ezGY7WIO6F/uLnuDjALfdyPvEDqwzWuNau1mhfz33wR/Z0l
wA2whgVJA+bhiOc8cdAKZPr9wdXbUPM/fuuyUn7swPUMB2PX2OD2GKSZz1Z32H6fpsN9fQWkl5Bbpd4ZJC2
5ImK7lVyB3zjA6HryMVXu7OKxmvbS5nje5tZWjVofmjmwdpKsOo6EE9R060+/uQiTnT1dLG4kEsSN/AVOdu
c9cEdPUVV1G4eSGDMdqgYDBSPawIGPmOPTHQkHg9aZipO9xkiqlrEyzESOzhkUg42hdpI6gHLflx3pVX/R1
dZt0u4hkKEbVAGG3d8knjtj3qrIpEzYyoDYBk79uTjHr6VNPHLp93cWtwFFxbuY2CMrruBwSGBwR3BGQeoq
i1UVzTW5KKFlAZDwAvGfXP0q7D/pBaYHYXHzFsfNgenesIzFyqbQoHQngY/CrdncSRngKBIMkZ69s/Xiocd
DfmutDbOlzSR7yVderOrAr/nitGxurjRo1itJdSi8yMpPGJ2VJeSVyg4Kj0Oc5PQ1nWc7TIwCFifmI59Dxg
9auxvO0JkijDheDmUfOCeMruzjg5I/Q1F2Q69tJFzUPGWqSTWBSZ9Pt7DHlpa72Usv3WKsxGQOBjAHYVyet
aze6r5TXs4kkGSDtRcZ+gFdNbahrbaidJ07QIZL+CaRJYbe3lmZT93Yy7ioAPQ4BBzkmsIahd21vcI8MyXB
JQyvGF8kBcFFUrgcYBIwccVomawnFbIyJ7tp3zIqyHAXCoF2gYxjHFQTyiQqcZXGACxOB7d615tM1GGe1hF
vLC+5VhXzFVm3gMMnPcMOvQGsNoycbSrEAkjPTrxk8dqtDdRPYGfjAbCgfzqGQqf4Rj0FJwevejHXI/Cgxl
MFII+bA6kbTjB/wpARnOAMeh6Uh25HJA7kDOKI0UyKGyOR6D9T0pXMnIlnwZZAww+47g3Bz/SoCA3Tj6GlZ
Au7J6HHBHrUGMnjJoIlIlZFjXkfN39vak3MsZZR0YD2Bx/OhYZDAXUMIi2Cc4BIGf6/r71HJH5Z2vkdiew6
cfh3pGMpWH+YDnJYk888c1IMFQxOTnODjrVfI3DCjAHUHr+dOxkjI6/pQTGZctnwwZlG1fmIJwDz0/wD1Vp
wz+ewVsZCg84wR7VihyUKZyoPTHQ1NavhzkHPt/Wk0brU6jS4RcSgqCrk/w8ce/wCFW71WWYbCAFxwOn/1z
WVb3TW0QVJefQ5IGf51f3l1XzDvJwRnOPx9qyaZShLchmiV8uVBLdywGKouqJGwVhkZBJNaE7BSuYvmA/g9
KpSmSZiSVVQfwFUvMbi2UpAmcEfvPU9qrElsoADk9RVqQMJRwhyOmKpunLZIHsKoxlE1vCzg+JNMTkhbuEl
R3+cdKKg8K5XxHpjpkAXcXX/fFFfR5HG9Odu54WY6SifUkVysiTB2LFTkfIcfQ85BpDjygBgA4+XP86yLuc
R52OCR1A7/AIVL9u3o8jFIyFAIzzn1Ar4VQ6n2bptaosXUwjnjjZAqHneM5H0Hp0qvfTuj4YhT1VlPBz6VR
nummiDgNhOG688UsjqLdSrK5frzk/8A6sUcvQ1jG1rkE964mKIMsMZH4+lW7lxKpfAC4xuzwaw13tMdj/MS
Ovb2HtV23uN0Z3vjqRmtOWxFaNtUR6gFj+aUseOM+vtXGayuS21mKkEBvT1Ge1drelJowjvudByCOn0rl75
QBwC2DkEAce1dFPY4JSOXnjEMRnZCQqlT3wSP/rZzXOvGzlQzbygBIIOTXaagnyhIeVYFSFXLevA9B1rnr+
LZOJ3JEckZyFB6dDj2FdEJHVQehRgttzhWcRlW2/McHkEg59eKlsIfOgYt5jDBJ8sjK84+b0/+vVYOJFtiF
DeVtWXBPzDJwT6fL8v4V1GlQWgEohy0bP8AKhGD7DI6DB5x+tVN2RpUmmrHOS6NBNHJkTpJuI3KwZemcYyO
cj/PSufe3KKPJaQjnIx+teh6jBHJGzRs0OdqOqArlefXr+PvXNy2LzNhg6xgbf3fG7Geeevfp1xSg+5wTox
etjlzPNANpbKDOFY9M9cCrVleQBY/Mj3zAkeXJnbID06dMeh60SQRLu+Qh+wUc/8A1hUVxYS28QeaGRFf7p
KEL+B71eqOCUKtN6PQ0Lqea9SWSSQZO0kYCgEcBcDoPTj1qvM0hCC4L4TCICckAdgKzWedP3nmP0GNxzn04
NOTUJ90bMVJjA2EDaVA6Yx/nNHMZfW4xdpKxs3EYivFjtJAyNErAy/KFJXJXLehyM8cikimjW3hYplc7XDZ
5bOeMdBjA796o2t+HnVppHTndhvmBJOe/XnPrU1wktowZVxCSHR+GXPTgj3qtOh0068ZapnQaRDcahII7B7
ZpOdttK7ARLgktvPCgEd2HJHWoJbmWK423CukiZ5ZBuPYkjo3+c1n2+m3s9xI9uh3w4ZpImBAJ6EkHIz245
/Ougsr+1ls4jqEpe/LkrC6earMMgFlbjGepGDjp0wTlKdSzF0bxlr+jW7W+i6tNYxTSrLKlttTeV4HGMdOo
Awe+axrnUNQ1G9b7Tc3M91PLuPmPlnYnOTz1J71LJaG7WGGytGEiJhpRuBkzn5jkkEHHBGBj3rNS9ltmIZU
laP5RHMu7aR6A/8A6utFik4rVLUtzZFnCpgRgS20gqT975vu89cY3Z9uKzp0MUzI6ncp5A6im3F0bjylmCA
RrtARAOMk8nqeuMnntninLA8ke2JJTkjAwcsewC96ZXtNCW2sbm6sL69hVPs9mEactIoI3MFGFzlueuAcDk
1ULEsNpViTgDqc1feLyvDtvcpNKgkLwyxFGwxyCGVtoGOxGScoegIpLuNItDtd91A8xlkAtoRh0xjEkjYxg
5woBPAPTujPnbIFRY55FvVnTaxV0C4IYZ4OenPbGanuJLZ2lFvFcJbhQqGUBmHXqRgfjioLvUp7tp5rorPc
ztvluJCXkJJ5OSevA5/+vVN3CceZz14PU0CdVLVks7733Y25xyAFB+gHFQEA45wM96EYuELOrMSRtLcr05O
eg561dMPlBSbRyxYoZCwdGbHRcDGR16k0rmXtefYijuCsPlg5EZLKAOcnhsHpzgevQYxULhywUtkA8Ac/j7
9anKEAArtA6cdPWjYxfcW5PGcUGipN7kEcLbC5GUBAOfU56fkaeqY6rz6+lW4oS2wF2I9ByB+H51dWw22wk
cO0bEqDjPIPH04/+tSudFOikZIUnOKVW2vg8itaTT2WMOV+8Mjgjjsah+wlT83J7ep/Ci6NvZW2IYtzYJ4V
efQ1pWkjBl8wkZ6kenb+tW7K0hjiIZQ0mcMOuKkuIVCrsdVU8kqNwH1xU8y2NY66DHkkfaqp9MDk/T9aVU/
d+YzHdjtyRTGeVAhV2IxgEjOPcVbjk3ho/L3Nt65HPqce9JuxlUVjFuY2VssdrZ4ycHFVmiyiuxJOTnPatC
5tvM4XIwO+M1RwRlctgHk9qsxkibwydvijSgehvIef+BiipNCCr4g035QcXUZyOv3hRX0OSpckvU+dzRuM4
2Z9CmVSWITEgOcnvzWfcSSC9M25AHGTx3p9rcSKz+aVdgTg+gpWEbZLZLdxnNfGJWZ9w3yNjI3LoG3eU2cA
qeD+FVEuP3eVXB/ugZxj/wDXT3BUg72bpxjvVdiTGCDjPGehBoSLTTJo5QQS6FiDjcOBiprpAEVypLY4OSM
H+tZiS4nIKjJGGX1/+vVxxiJXibcuPuseQfSmZ1FZkvlOUYGQo/foc/lWHqscuWKgKRgkjAC//rrXSVtjsQ
yjPBC4yepFQ3cY8tzhvmGQpGc+1axemp59SNpHGzyNGUe2n2SRvvjIXlSD1zUGot9puLsrAIWmYyKsfKJkk
lQp5xk+v1zW5eWTrLCURRGBtAGNymqs1iyTIyAZ/iQ9R9PrzVqVi4yS1OLFlHG6szgfMQR3c9uOw6frXQW1
w1rbH7KxjkI2Kq8Fu5U+2cfUcUX8ASZpADGeTg/dJPXHpVXcXd081UkkGEZlGd3QKD0HXitFLmG58xJdXpl
dVx5mECu7Acnj5QB2HT1FUZm3XTLNFMvQtGqhCq9eM9B9elTMl1byw2sojlaMBxE7cp8p2ZPRsA7h+vpUEU
qSwybrifbl5GyCTKQOMtgZ5/Xt3rVJFWTRlX4LX7vAxLltxDgMTjoOODj8uKuaKlzc3UEEhS8tthBgkcv8u
DxgdBnnHHIFQvDIZzIZF8xk3ufu7Qfb/wDUOlL9u8m4YQoVkGPKdGwV78nHPGOO1U0Y1qd42sYWtxRi8uFt
0HkxuUUJ3Ycce2c1klTyAfb2AFa9xA0pDuyjc2AQQADnvVCZMbgoG4nbx2AqZI8bEUHe7K8QBYOy7o1/hbO
D7cY6+2O9KJWUFI8oGOSqk4HoOTyAB3q6Y1CqqE+WoBORjL4x0yfz/SqIG6RtvTk59B/nFS1Y5J0nC3dl/S
dU1Gxu1uNNnlguYgSskJKOBjnp29qsXWoypFbysqi4k/eeavXqcc5PXGSOOvpiqcEAiUtPGWUxHad2AGxkc
+ozyKqLFvcquNwjLfkM/nxTu0VKVWFnfVmtf61d6s/
+m3LzNlm+cAcnnoOPp+lUEkw6ndtI5GeKhQMoOD8odT17np/WpThNUZZQDGsp3LGRgjP8J5HfjrRzNlLEVE
kWY55HKojquGG0dApPTk/Tuab9qkld7h3kcr8vmb2yCc4OfzqtMgVGjVWDJIcbjn5D2Pv/AI01PLZkHKKGI
z6Keh/CjmZUsTUbsyzLODGI03BepUf59ulQmYqPlQ9D16VG26KQEDc8bZwRxV69S3jnZbYFrcnzUZj8+GA+
Ujpwc84H+Bdh7apO/Qqr5khBiLYPcf56Ui26srK8hSYMApYjaw7jdng/zqWzcQTLwH2vkZOB7qfTNa85gmB
aEEI3yypgAhcjAHOXIOT9APwBwpe0V3uVNM2z3CWk7WtvKpwXlc7WPQEbQ2e3TIPX3q2IipeOSNY2XCsFOc
89c+lVZYY2icOk88QGElIz07McZGBx6fSiBLiPZGz5TIILHI9Ovbj/AOtQd9BTjpLX+v61LqWvzJtDyHG4+
4H9P0pXt2jbb8ob3B4z/ntU6zzRxyQOzIufujAzn+8R1+hzjNWlic7RJAQw4Ax3/wAfrSbsehBGdbR4Yg5J
zgEe/wDOtqxgGApfAkwxI6Z/qPaqy2rNKrOMEjOAMZrc0628vYXR9hGeOwxUTl2HKy2JZIDHM0JVeRuDRnI
wenP9KpTWKL8rY3N0ZRyPYfyrSMDrgAnPUEH/ADmppIFeJHZ9wBYDGAc+h7nrWSfUpaG
G6tAVBJOegXJPPrTL2Pzot4IWTO0fNgEe9aTR/KjKfmA4zxjj0Peo2iR5ysZyD1DEVadhp2M2JtgIXqvB9s
+ntVmPzcEBVyBxnj9atNADPECpVUG3nnj+VVbhXkR0QhoyRzgHHtihvUyqO6M6QskhAGUz37VWuipLAgnPU
jpVra7Tzb0URgHb14/Cqk4/d7SRg9M1omYS3I9JLJrVgynJFxHg4z/EPzop1hiLVrNnB/16EHP+0KK+hyZL
klfufMZ1NxqR9D3IOftDeWAR0OfSoZWZDmIgP1Cg9aS9dXLqoZSGPPQg1QaYK+FbOcAnNfIpdz7+SbLEkrP
gl8HnHaoY7jYArqWP8RHHHrVee5i8tYwDjoMHrRLiReB24xxTaHGLtqiZ9rqZOAh9OTTraUliEAaPGGx3H+
NUgwjXklY2BGOvPrj8KWCY2825Tt3feK9/84pNFyTaNhZ1dGzCxjJxng4PsP60TjMJIJAAyWJ5J7fhTLeWN
rYLsLsAANvbPrTWZUDeYrZPy4JGAPpSTscjhfYr5V1ARY2YnJY9Rx79eapXEwXYGXGB1UZ5z3HWp7h7hI3z
slBwcY27QPT1p9q0g2s2MkfPxjb/AImtEZShbUx7uCG64UqZFG7ofT/Gsq6gZCFPzIeo2gjkV095ARISyKo
4bJyP5dvasu6X5AzkkMThQMn2/OtIyMeTqjCuLN7yRlRkQklvu/MxxnGR/KqS3BtPMiGwSygFZUJ+6cEj0z
kV099CJFcxDdxmRtnJHqBWPe6eZnBBVU34Uxg7lzyP/wBVbKRVOfSRVmCOTMFeEblWJACwBAznJ5JwB+dVJ
YZbuO0gghKxMcouSzM/Tv6nsKnuoFgs4t8rAlmZt/cgjGMeuSM1KtzNGgW1DLvDxwySjaoww+6eh4A+maq5
u46aHOeUzOgiJyBkv02HP9PU1G1kysyq0bMgI3I2RwMn8f5nHpWtFZIt20U3yhCrMR1xxuOPxHtT75BaXY+
yoqKzFY3J4j5wGz6455+vSquYTpRkzm7ltls8K+WCisx3LgjkcZx1qtHB+6wMA5AxjOf8/wA639U08eXA4M
kguJvmlfq/JJJ9+KWSzMTqUVWh52g8dMZBAPHX9fXNLQ5PqvNO77FCVUMVwyvMgABUHByf4snPHHoDn9ax5
k2XDsq7UbONw5wa6xrNN4WSILtO2VDkAkYwM9s8d+9Vtd02MWUUsVxI7qrqYnQ4iGQQFPcHc3pyvPWkzLFY
ZyV10OckjaJVJBGVWTBHUev6VqWyLqHiCWMsVNwhjRm/vEBVye1Jb2y3EqiQkH7K+dvPzLnAPpTtItZrjUo
EiHzyoVGTjdk9Md+gGKRzRw+qXmv6/En1mydYvtDbPtCHZOoPzcAAgjpwy4z6561nJalWcKFljJygzyRgt0
9MA59MV2NhbvA85jRWhVlMsckYZQxJBXHf+vOKzRpO9fII8uWEBVKsWL5bKkcHBG5eM8j8anmR0Tw2tzHmt
EnsEmhLCaIFZEKj1657/jTtORXslaSMkQS+WT5ZKlWHIJHccMPYV0mk27bGjkV8yp5cn2dih3qCVJB/hKjP
TnaO9RW+mPa3iyqXeFso5jBAjYY2Nz/X+lHMhqglLmRjXmlG1v7dN6SRXBUK6NnGTx1x+uPetgaXGIwYsrO
E/eIArIuc/Lg9OOepxk+hFbcmkiW1ubO8dYyDlF24xk46HBypHQZPTpU2n287xedcqryxAK7O3mEMB3BOcc
fhxjip9obwpqL0MK3tcK0zKkZHGxQVxgY7cfj3pi2kUN35vk+ZDnLQj7pGOvfHr3/Guh+yrPMVQIzqfLwAV
JBP8X58du1OltprefdcLhw20g/fHb3/AJUlUdzpskYcelwOgW2NwZNoI+UMCSQCADjpn72fyoWO4WRxLIwY
EqwLE89Djrn61uCNoRLJAxRgpAfaZFyRgjIHBwevGOOM1nRWBe4854AxY5K5wCPpnimnfcal3LVoQ6EnahB
zuYBhwf8A63etGGGUlmKRtGP+WqZwc9Pp/Kq8FiVGF3Ek5C7sDH547mr1lAgRD5nlOP7w5z7+9ZXMkr6lmz
LNsMm3BJ5IyP06U27gjKOssexsfex0x6j1461ajbahUjKkZUrjn8P88Gk858EuCQBtdwOgz6e1NqxrG99DI
kt28gOjHqCP4t3r9DVUW21lEykvk/Jj+RrXlRdpDKcDkAfqKoXLSebGMlgvzAkcn0wTz60K/UbuVIwWdwhJ
BPC8HIqO4UJhgrsucggY/Op2CF5CoGWO7B5IqCc7GRkyVA5x/wDXp3MpGTcv8+wYGBuz3IrPnG7aWz/n0q7
fbXb5GIIHBHQcVRYknkHA9Bz9a2S0M5KxFZEf2hbEZciVSQR159aKZZSqNYgRT8nmLz+NFe/lHwS9T5bO1e
pH0PcdQRfNlLtkhiBjkD3qgbMuZx91sAn39xWvdRIt0ykgEOfYtz/Oq9woDOmcJ1GD+dfKWP0BzadkY9va+
ehCtnY3U8c1dWAxBUdAMAZNFu+QELAFW6Y4qxLlmDK3O3nNOTuW7vRlSeMN0GeOQTwKzVyjmMhgvTOMkVrb
SrAFiSOD/tUy5tAF3JwxJOT1x2pJlQtsxlnAXnWKGVF5IDE4BI5H54/OpnLEkSmQSDsw5zVDzHWXymGGI/M
VqCZ3jiiuMyqCWDMoySfU9/pUvRkyi7lIyo07w3SyovUZGQD7n0yRWlHAIcIGkCDhcDOD/P8ACmEq6ER5ZS
cqMnDdf61Yt4JWBEUbsx42qe31/wAKpM560brTQGXdGNxCk8Hf+lZV/ajIcbywPLADmt1wJY+UCN94c9T3O
fwNQpLCdyqUQ4xgj9RTjLocyjZXOcRPIPUFT1B459Kp39uWhAyoJJH3sD8fc11d5p0MgRkIlBwdw5IPQ/jW
ZLasiOpVfKU9duSPp6j2q4yIst0crPYmK4iedDjAJDndkHoRxkcVD9ilVZo1txLah+QGzjB+
+nof6V0t1A5Ztq4QkEbWJCj2PXpVb7MtvG4Dsy4ITbjPPUE+/wDjWl7msXociRNBckwzncqsM7cgqeo5/Lm
mKrXMaxylkQoSc8jd24J7+tbM9szNG6FBGgIOeeBzg4696atvH5ZYOo2jeG2k4z6/yq+bQ25TLvILiaGCMq
jRJENgI5zjHHpgc/zqeSAx2cAUrO7ZViF+cZByobuF546Z6cVLcGMShlHyf3PfHUCpEucK7qCFKgBc42nPY
dxjvx/iOTY1TII7GOOFG+0QymMbnixtEibgMgnqeenUYPpWj/ZMUkQlkJj0+fALKu5kBHykJncc9D9Qaowg
pMjyRM9soBx0JBJ4zzg1oQTq2IomMkAb5YpfvJz+HzfTrj2oZEqbOfi8PrBdyRXErqFGI5oiHRlPqR6jvU2
gab5eyR0XeHeRkfqnQA7TyQAO3rXSWCKyef8AZzNbkmOY5YbiCCMtj5SPX8+KvW6TQGX7SvEK7V84BjCrHK
n6HruXoenXnNyZi6KRBHZeffxKzx27sQEkmXcmcZwxAOB+Bx39RHJo0v8AabJIqwSTRssiM3ysR05GRzzjn
A45Ga1LOeKIECWKMIyk/Izq5z2I5B+hHtVxf3KqUtImtpQd/lnCSZGAy9djD1GP9oeubJlB7GW+i5RLi3Tc
S4SbgHHf5lzuBDZ54PoecVcksoZIlnuo/wByZQBdWuGUjPKkHG7g5CttPPTrjeig3RLckyyQQsEe6QHzLfP
QMc8rx0I68g9qdbF4Y5LwNGJAuFngk8kTkc7e6Fu+1tpOOM5zSuYSTe39f1/SMCPSbSf5YkVpoiQn7suCow
cbANyHtjHupqGeyt7CSWW4D2sDxgJLD+9iB4xuweRjPcnnnJGK3JZLeITNqNlO0kS4ZI1KNC27JyBho+/zA
Mue3PEE0xijhaKZ8zEeW0yqfPHcFhlWI6EHPrwae4LmT1MqeeSSECdLa6hBIUxAZX6HGQPYgD8c1VWRbg5i
3ebjDK3O/wB8H/63StVYvs0xMIa3aQ+WcHG7PZgTwD75X27CGf5HxLAgGMFCuCD1/wADVbaMp26FAWzO4Ey
CEjIWSLJ+nv8A0qrHE4uSUbcynK5GSMd8jn/JrSVMKGWQhSf9U54P0Pak/s87uAd5zw2TjPP5UX7EpW3K7x
mSRW2IDjJYdf5896siFkjzJ90fdduuKIohHGJCEdujq4O4fT37ZqaO3aUPJB+8C5JjZhnpztz3/wA4pXW5t
FdClJGY1JgmUYwdu7p7kf4VA88qSgMwG9QSzrxj3+lTpMkkW6Z+QuChxx26kcf/AF6ikSdo9iYVV+fGAdy9
8enfv3zSNlFrcimuGgEhmEqgDB44YeoP+etVWlillBTOz1OTtz0GalkSVIDgnyyBgbs9vX8MY/yaiJEYm2N
uVumTyvoR704g7DXjZWzI5CjJGR3P9aqyMQW3D5Dzj3/lThIwmWOZnKsCeBnP+HSiUvLGUVVDdyrEg/SrRl
IyriRXmDLCOfbrWc6u8rMAVzzk559quS7izRhlzkMAOv4VVlfcwUjDDo3rWyVjCWhBAVXULRzkASKScY6EU
UkUcpuopCmFEq/Nnoc0V62XzcYysfL51b2kfQ931OYM02wbSGIHPTms977ES/aCE3fIp9TgnH6Gp9RkEk0i
plV3Zbcc9apnK5RRwehPSvnbaI/QnDWzHWhDIXZQSWwcjpT1JCb/AJcgHAFK6FUwHAQdaguJWDqY1YgEAFT
j/PWjyHFc2xbdVaZQAOQMip4428p8KMHtmoIOYzvBJGBz1qwrKrktu3fdx2NQxbaGJdq0N1HhdwIwSB+lbN
ouE2NsCYJKnOB6YxRcQfvNyoWIxweBUM0nlMdgJUjLAe3X6UPU1aU0kTxkNL+6cKcjcp4FSvOISAXMbnAUZ
zk/4VQn81Y4bvYypIOGzww6cEVbiCeSGcBldQ3zDke/1p8pjKCLnlvIiMHCCU7g6+o4I9jVA6PAt6ZDI5lw
U+Vzkd/pzzWlbSRJCkbYx3yB9etRK8xuASG25OSV5KnmpvbYxtJXtoLHALZXMeWhxyX7E0qxIsZLsiqTg+5
9v/r5qy0LxAFWA3DaFzncfxrMlMlwJAFIwcqp704y7mCpc+ojwGFZWhjOzjcJVyAPXHb2NYt3Zu0zBAjQPk
goeF7j6/SrkK6j5ii0mHzAlkk7Ff4cdc+nFMme4WXJQqSNrpJ8qgjjntWinY29g47O5Uayhkttwc/aFBAPl
nDH0J9+cGqyWYNv51srmRMrMikEYxyR/M10FtEYZxIjC3bjY8ZJAJ5H09xSx2McLRShnV35ckcr+PcGr5rm
XM4M4XU9ImZfKjHzueAGGD3x6Z74rMNldLbmaPgE4fLDcoHqPbg59816FdWYSUG5TbBJzFKuCoOeCMdPpWf
cW00dzJPbxiZhgsJVDBsDowzzx264q1OyOynV5lqcjZxXk0koh/hXdJAzcyDByQO/rj8e1PijkktxlcrGx3
xhcNCc+vTHSty+tvPigmtkw6uNrxDJjPpyc4+ueKW0hWZt+TbXEQG4uT87E4IyOnXjPHY1d1YvTcdp9/NLF
LBO8a3GAzLKfL8wAkHnocg9x9OvOvABdTxwQN5LbWWGB2xt4wYyzduhGeCOuDzWW9qJ7SWIW/lS2zErv7Lg
YBUgHOeCQSOnfmrUTs5j0+7hKaguNssmB5qYyAcng+h6HAzgjJzMpU1uiM2c9qysFhEqckqw2yDO3GM/eHO
VPOOmRWxpBm/tGFrGUWt7z+6lGIps8HGfl6H17kGm/ZLqH7O7FblJSNok+5Ke6N3Djpz9QelXra0F+vm6W8
7IHJe3mXc8LY5U8fMOOoAJ7juYZhUaa1BbuMXaxHdpd+jMTsXaFTsPXGc8HseMjAp19aQW0P2qa2EMkmfLl
tFPkS44O4djyMjkDPK81dsMXt5a29/dyQ3wUR29243RlT0Ug5yvUYyB6g1nX1nLp2oSRCSG3lErIokdvs7l
egyB8hOCCDwOnFSc6S5rL+v6+Y2zaVoo1SI3ClSkSOpWRQeuxxncB6A/gKVEiSMy2yJPAwzJAqbf+/id+/z
L06+oNqOJWmmjmieylEiu1ow25Yj76MpxuHUHPI9atXMUDwsJpyl9vxHcrlUk4xkn+FunUc+tOxjUfvWRiv
cS5xNtlgiUSIsrAyqAOMSYyyjHB56dBURCXfzqwjJwR2yOvI6Zq0IJ7SZo7hDDOG+9tDZz3I6emCpqWI5hk
E9uXTjE8f3TjuR9MfnQm1uVKHYy5Y1ZSqRkMD0U7ce/Tmh3aWBEWdjHGcKGQZX8P8P8K1Z4Bb2q3UbLcx9C
0bHch9R6Efl9KpSOggRnH2m3Y7QV+8vt6H6fl7puw4q62KNyxhG2dAGIDJs5Bz+v4VC8UUxVlb5l4AdSvb2
7/X9auSMnkll2zwvgIQMFT6DHQ+oNZ58oxlot0u05eMcHH9D78/zFVqzaC0H3Qj2xxzhVZjtLbPm/EdDVC5
E6Jw6AMPMEn3lyPft6Yq+s8T3EUUk0ckTPlZJH2gZ4BYjpj1wMH2qK/fy5zF5e0k8h1yODjr0zSNEmnYzHb
bGD5TgkZwrcHg8gis7cxLMBhgcdQpPpx/hWrcxALsB8xSPlQNwq9fy5zn1rDmnaFzKMMT8hVm4wRkY/zmqS
uJoHkLTF8F8fw55PqMVWnuVQ/uwQo49CD2NJKzOscuOhycrggn6/l+NMvpgWWT/lo3DBScj8a0S1MZLUoTN
ulYZ5B55zVbzGVj5i9DxzVuVoxCTIpDHnk9R6Y/KqWwSS7cH2Pr+VamM3caqiOVGZiAzggD0zzRUT/LOhOA
Mjj8aK9DBO0WfL5zb2kfQ9yfY11KvORzgd6pySRKi4O1uuWPX8au3ksIvZWyqlm54x+NU7xJEkG35lOPcV4
SufosruWoyxumZijplQeG7kVJdsFRgvrkj1qKAhmdUIXaeRjioHZ4nZyQ2V+tJGNmpFyxnd7c7x+8HSrdtc
kTqGTtyR1JqlBJvhV4+o5Ge/tVln8zcyqEccYx/WkNPUvXExYqxZEB/LBomjWOBpAec4PqO+c+lQQQBI3Lu
MY64ByPr/AEq/ZgFSJtnlNyhfgD2JqbWNNkZ9rbR5UlD67fU9jV+2iSMGN13CU5UEZK/nxj2p99ZlY3kj3M
wHSNegpsEgEUccobKp8z4wcE8fgc0nK+qCWquWlWGEOzbQSB17/SozcoHj8tdznLYGSAPaiP5pvLkQ7cE8n
nHbj3prNIqymNcKozGeuT7j0qWupglfcekzPEVuokBb+
+4AAPOQcdarZhW3+0LMTFu2senln34/HOKmUNK8ZZSQACU9/pVbUUS0aQwMyu4AyhOcHrx0Pbj/AAqoe9oU
oq9iOWe3Z9ixqW+8WQbgOnI/HmnfZo9RLiEqwGFCyuMnrwoP+RUEd3EkyotrBPvKqyk7SwxwOOh96PITc+4
uFZiUZDyMH0NU/Ivkt5E1lAYNitmS1flUkyAD3Bxj25q1tV0CgSIgf5kZuByMc9j9abbkxxCO+X92WJM4XJ
IPZse/etGK0dFR423SMDsXIbeD7Hrxn6GmpX2OOqrO7KrQLBE8M6A2ko+VVGcN1H0/zxTEd7TEF5EJbSTHl
hyNpJAxk+vowOR+lW4tggChVyPvRMOB7jHJ4pIsyo8MKGRdvzKPv4PPI7+xqr2MfU5+4h8248zTU8uWMkzJ
KCC57ZGcMeeowTj8akGlwX1v9tiV4Zht82QtujBPUsOuDketbvkoI4y6YLP+7u8dD/cbHSriWM5Q3OnB3EQ
JZlBPlN74Hpnr+oqnI09u0kcjd2Uc8MMUTSR36Ix2l8q+BwUY9eP4ckHtUsBhu41s9ViiWdRsKOTGAeMMox
wx5yM4P6npJ7SG9JlitotrD99aINqg/wDTM87W9Oo5/GrK2FrcQkSh7oG2HkvEw8yIjJKSKcbsYHTJ6EZ5w
+a60KddJambaWrafCI72RZLC64MpUswwPuuv5DI5HYjFWpNPMc8d1DqHk37MDDdByQBjklh/rFHQsPmQ5yK
y0uLzToTY35ItJ2AMituDDqDjs4yecZ/lVzTWOn5OpI1zp5YhyJCCrHBVuCPmAwcjG76g1DMpwesk/8AgiP
BBrE2L0Ja6gyllJx5dwQSSxPHUg8jkY6UxpN1ktlqUSW2o5O2dhmO7weVkXn94OQGHXvjvevII5Jj5B+2WE
m50L/f4wNpGchlB4bvg9eaZbPBNbGC8C4JDW8xIAyBgLKOqH3Hf1HSrmD79Py/rt/SrWNu0dqLa6hMlip8x
bbdmSAHOSG7LznB+U/nTzDHLa5ElspH7oXMiExsxP3JVH3PTONuTWrHdtbzeVem42Ro6278NNGMAk7gP3qY
PvwcgetK6WGOOa/sI1kVSEurdD2HXdH2U5+8OAc8DOKhgoybu/6/r8zOU3HNpd20riIsVhJ3PbjqVQdWTA+
6Ce5GOaRdkMLyxPm1cHhQdoH8JzkspGeRz+Pa1fuiPEcJJbOd1tdxEkqeoBxg8HjP3lPHPSqax3Fqq3aGPA
OWO4YcgYO9eoyeNwH1prQ1UE0QefcQXSyRhVY4xKFBSUZwM+ncbhjrj1qEwJcSuyKkd6P9bCVwGA9u46/Tp
1xUjD+1I54rSIW7I/meXGx+VjzwOhyR056dDVVR9rt9qllvxn92q8EAZ3Ajn1yOh4IpqzNVT07GPqBmhupJ
oYVt+QXRclW9xz90/jilnREuRBJNF5in5JY8FTuAIDHuD79Oh9p7uVry3Xz1QXEWGLjIZxnv6kZ6+g5qlFF
H5LqwWQY7D7nPUeh//XVWNVHTUr3ESmYjyhC7dVBAVfdT1weBgihm3xpGXGApxuJODxjP0x+WKL6MwyiJkd
ivCMBz7A+oNUpJQYVbLx7T8zN19RgVXL2H0uLHK7IQ4hWNj8rOuO3T3/zz1rD1uEOVcmNU7sSdpI5xgZP/A
Ouunz9shJkRUlAHOzcp9/asm9to7gSYBJOV56j2FUnYzcrM5v7SXYxgsy9OWycf/WpUdNjlwWZV+6RkYPcZ
5yKbLA8CtuBXdgAjkelRmJsKsZV8ryc4J9h61rp0MKnkQyMZGBLqAeNvTPvzUKTSIEUADHcdfrVtoGEOWO4
YPJOT34xVNRGVLEESdB3yf6U1sc0ncjkUFtzcPweeKKZIoQ5Yt97uKK7cK7JnzWca1I37Htd5GsqqHOBjP4
YphyIGV2Bx0I9KZJu3HzF3IyqQRzjgVUkEjOIQ20jHy+teO0fojWt7j0kwG2AbhSeaZN29c9gKi8rZIf74O
CBTY2b94ZDgA9vT3pWMZyRctCHK+S3ygf55q8uOHByMHv1rKjKW8SiMAq/IweB70yJ3M+AxUK2AM0mru5EP
eZuWMg3JACxYgsAQSPz9avpZyXdtiVvMRGGQf4PT+v61QtGAIZQSx6ADkmtPTHFtJ5M33ydzDHUDms31Nb2
ehala6Jji2yKm0qGBJEgHBOajndbeG3XyUYSruO0EHpgfX61taNO9+bxHjXy4YmZJTwV568fl6VnrC9yrof
8AR44iMOf7gP3gCe360lYqMk/datYz5DeNM3miKLcvyqD82QM/gajW4nllXySMDk7urHvjPUV0It0MBleUS
eXt3Fv4+vOR0qJBkyW3kJI7LuBYZHtz707ohTWuhQmdxIsgRjEoK4VsOG6Y/rzVaxtbYjzN0kgyzEEng9uO
xPrWvZW0cMTfaNiySsVDPwOe2Pr37UG1SJ5ZLc4I+9tO/OPU8fnioTaeglJK6RnQLBcKq+XMoU/N8q7lX+8
G9vQ0yJbuK2lCyrIACyHIY4J7+1XoggHnxJMJG+YsjZAzwPmHT6U9hNEYpIDHNFG21kHT8R26Uug+bWxSEi
SWbzLa+WVO1vLYsFbPTnoMetXYiwiRUnSSJHGx8jbk9s/wN9ev5Gi4B1C5iliMccoI3hQyg+m7k/n7+lUZJ
IVuo7fyXhuJeNpIKnB65q4vqZuKkaDGUypvEYUAsWUDc3Oeo7/Xj6U+O3YXG6wkxLg4feAcjk49/b8qntJM
28cMwG
wHCMFAbHXB9hjp37elNeNpGiZcBGk/hJCS5PH0rRbnM10JSYJJnw5QSLgxnIDEjGc9+ecH6UtrLJbTwmUyR
Rg7S8YJKg8Z46/U/SobxpZfJjiJdImJEbL86dyR6559vpUkN26xtGwMlqzYiYAkR8k5HdT+ntVXIdP3S5eW
8c3lXdoIracAop8zdG5HXJP3c8cHp61G5hnjWRkZVBzOqoS8TEHBwRyOPu5wRyCORTY7mZSvlOsW3ck8rLv
R1JwrOgHp3HOO2RUt4rDN3YD7NMCUlReR16ADkrxnHb2otqZctrJmbdW8jQyRuAyQqWbY+V5I+eMgZI5GRj
5eO1RWthGhVfNRI5Yy0EzL5kY7FGxk7CM54yp56YNXlvrJ0W4FtJbXgJaMWmQsbbceYAc5B6EHqKbpkcSab
LJ5LRxXbFHIyFSRTyBn7pP5g7T61TZblJR7FSO0mtJluIgYomJAKuGRTjld/wBOR2xwexq5LZiURkxqJY8B
j0JB6bj/AAhhwM/n0qxb289tez6Xeuu6ba0UkQDHzMHYwwMEdQcHv3qq8hSJ7y3Vlltm8iWFgcSD0B6cjt7
AVAk3LYsraWupWkonWVzENsShfniUNgqozxg9vrjtnKjEn2WJ0eE3MBEcV1G2FlXptkHuBjPH55rYt2u7pG
v9NkU3UGJZYBFgurdNqkkFccd+6n1rH1W4trhjdoI7YSsY7iILjy+eT0ADDrj/APXQyqTd+X+l/wAOSW7Cx
jdo7JJdPmjLXFq4JFsxOCyjsvIPGPwPNYZWU3o+yF5YMh1VlyyZ+UNgdugJH41rR3X2PXVi1lzJDOrRSOgy
ZVYEbx7g4OPT1zVKW0EBeCaFHjl+aMIcndxggdtw7cZ9QRS2ep0RjZ37/wBfeUAYfIlbZm4iYCSNicMpIBB
PpnnPUEipM20uoxKxeaN22KX4Zv7oPYtyKoSzRJA7I68g7d+AxTH/AOsf5NRrJauYs+W0mzzASD1H16NwPy
rTl1NHD1GTRCFZI5sqeqsTjLd+3pgVlyXMkYkKooRhhggBVhjnAHQ8d63dRuYbxiQoReX2EZ4x7kmsK7BLF
k2owxlvbse2KtLuODuveRVvZrgzhhIHG3AVu6+uT6dM0KwV3MsgcSYB3cEj146GiVlB/euRsGV44+nPbqaa
m2SVZlypYZXaA2/jO39aJdhTtYhuI2tvMkSV9uMHsAPXnp2ouow9v5keHH8W45/+v6U4yqZD9sQiP7qgqVJ
9selV2AEj72xETgADkD/H396NTnmzOupWi37cMScqG9fX3HFZpn+URyIoUEsoHGAa0lYeau87o25Xd1X6is
m9JaUqVAAJKnn9Pb2rWNjCViq0w3FSCCO465qtcg7mdWAOfXrUsz8jYMsDy3ce1QynI3OAFI2598VRzTdiK
6kYQEs2cjODRVe5ZvsxLAkAcHPFFbUpWR8/ma5px0Pbba58+MIiYO1cZ75AqhM00d1GNmVJ5OeRRRXDuj7+
T94lLeXIzuxCn1qCSUPL8mNp7etFFRE5pERcIyhAdi9jVyyZJI2lVchCQRgn9KKKq2hUXY14f3aI4Xkc5B6
d/wAKsWitLfxTpI5cZUP6Fuv86KKxlsaRd0dMZGS3lS0AyYwAFYkvyOfoOfzqW6sL6coytGlunDgkMHYDHA
7L2/GiiskzOc3Ts11L2lwfYrhY72UqsnRkUFlyepHTGemaddSpvuCbYRRs4WIFfnI9wO/40UUXZmlztSfUh
t7eGVy1y4BQhzGTyOnGO35dqum1iuZYZ4mcLIpTD4QnJ6Z4AGKKKJOyM6jcVzJ/1Yxr6yCvMrQlJFP3WlID
IOh4/oarzwzTTC5UmO48za5U4IPQBh3/AFooo6WOinNuKZfW3AnCM0WVBO9oypIOOD2+lQXtpDqGZJXjS4g
KhkfGH/2l7Z9R7UUU0ZptO44m5eV0lSOaE/IAAOCCDxjqKeDMIGRi/wBkc/Mo4GSOGI9v6UUVt0IvdrQe8a
G2+QgyBuJkflMZHzfpQLV7aIlsNHMo3bWySfUkevQ+nWiilcTdrIiaRIlW3jklChScSKAfQqDzkdD79vayy
rdrDJCpW8jAYJvBSSPHGGH8Weobn3NFFaW0FUjZXM7UI452V3jL7xgi3QlgevAzk81LCk2n6c0rwG4hV182
M5DDuDnrnBwT+fUUUVNr6ilo1Hpf9TevLiPWNOFxbTDz7biLB/1uATuCY9ODjGfTOarXMI1Gwsrrb5Mqq0U
7RLnlfvAjoHAywHUgE5BoooRhKPs3aPR/5mU/nW9yj2axo6gspO8o+0kOSM52t1OCCKq6hNJewk+XFHJvV1
wfmYjA2gngkYyPUc9aKKHodUbb9TP1GaQvc2N15YmhfYlzEw2yqM8r7YAxjnt0qrcSR+ZGIJoppIJsbt4IP
zEfiOPxGD2ooqopNnVBe4mZ16yXyqk1uilJDtJbDAEEnn/9fOMVQlleUxjC5hVgJFfLFccEDt6UUVomWtCg
Z5GlVpYWB4wVYcHPX68GrheN5jnlgNpUHAyBjkUUUbsKiRRm8piIkBTy2G1h1X2HvUBViVm3qoIwfmwc/wB
7H+RRRQc0u5BMJpJESWNGfGct1/8Ar+tRPOELMMuyDByuOnQn6UUUN6nO9TJuYt1tuj39z16DpzUdyI54Qw
dQxUbiTwrZ/wDr0UVcXoYSd0ZN4hi2hSGZQDvU/wCfeqbkH5WY889aKKpO5zTKl2zLbyoOFAP8qKKKo8PHf
Ej/2Q==);\">",
" </div>",
" <div class=\"lgnd\">",
" A reddish-purple eruption on the upper eyelid (the heliotrope eruption),
accompanied by swelling of the eyelid in a patient with dermatomyositis (DM). This
is the most specific&nbsp;cutaneous eruption&nbsp;in DM, although it is only
present in a minority of patients.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of John H Stone, MD, MPH.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_418=[""].join("\n");
var outline_f0_26_418=null;
var title_f0_26_419="Seizures in children";
var content_f0_26_419=[" <h1 id=\"patTopicTitle\">",
" Patient information: Seizures in children (Beyond the Basics)",
" </h1>",
" <div id=\"patTopicContributors\">",
" <div class=\"rcTop\">",
" <div>",
" </div>",
" </div>",
" <div class=\"rcContent\">",
" <table>",
" <tr>",
" <td>",
" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/26/419/contributors\">",
" Author",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/419/contributors\" id=\"au1329\">",
" Angus Wilfong, MD",
" </a>",
" </td>",
" <td>",
" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/26/419/contributors\">",
" Section Editors",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/419/contributors\" id=\"se1864\">",
" Douglas R Nordli, Jr, MD",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/419/contributors\" id=\"se6945\">",
" Timothy A Pedley, MD",
" </a>",
" </td>",
" <td>",
" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/26/419/contributors\">",
" Deputy Editor",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/419/contributors\" id=\"de8764\">",
" April F Eichler, MD, MPH",
" </a>",
" </td>",
" </tr>",
" </table>",
" </div>",
" <div class=\"rcBottom\">",
" <div>",
" </div>",
" </div>",
" </div>",
" <div class=\"patTopicTool\" id=\"patTopicToolTop\">",
" <a class=\"toolbutton findicon findInPageLink\" href=\"#\" title=\"Find in
Topic\">",
" Find",
" </a>",
" <a class=\"toolbutton printicon\" href=\"UTD.htm?0/26/419?view=print\"
title=\"Print This Topic\">",
" Print",
" </a>",
" <script src=\"file://w.sharethis.com/button/sharethis.js#publisher=357881b8-
c7e3-4c31-b7d2-242aeb1528e1&amp;type=website&amp;post_services=care2%2Cfacebook
%2Ctwitter%2Cmyspace%2Cdigg%2Cdelicious%2Cfaves%2Creddit%2Cxanga%2Cstumbleupon
%2Cblinklist%2Csimpy%2Cyigg%2Ctechnorati%2Cmeneame%2Corkut%2Cmixx%2Cfunp%2Cfresqui
%2Cmister_wong%2Cfriendster%2Cfriendfeed%2Clinkedin%2Coknotizie%2Cgoogle_bmarks
%2Cyahoo_bmarks%2Cfark%2Cnewsvine%2Clivejournal%2Ctypepad%2Cbus_exchange
%2Cpropeller%2Cwordpress%2Cblogger%2Cblogmarks%2Cwindows_live%2Cfurl%2Cybuzz
%2Cdiigo\" type=\"text/javascript\">",
" </script>",
" </div>",
" <div id=\"patTopicMiddle\">",
" <div id=\"topicContent\">",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" SEIZURE OVERVIEW",
" </span>",
" </p>",
" <p>",
" The brain contains billions of neurons (nerve cells) that create and receive
electrical impulses. Electrical impulses allow neurons to communicate with one
another. During a seizure, there is abnormal and excessive electrical activity in
the brain. This can cause changes in awareness, behavior,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" abnormal movements. This activity usually lasts only a few seconds to
minutes.",
" </p>",
" <p>",
" Seizures are frightening to watch, but children rarely suffer long-term harm
as a result of a seizure. Fortunately, most seizures can be controlled with
medication, and the risk of seizures often declines as a child grows older.",
" </p>",
" <p>",
" This article will discuss the most common types of seizures and tests used in
children who have seizures. Articles about seizure treatment and febrile seizures
are available separately. (See",
" <a class=\"medical medical_patient\" href=\"UTD.htm?19/5/19540?
source=see_link\">",
" \"Patient information: Treatment of seizures in children (Beyond the
Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?38/35/39473?
source=see_link\">",
" \"Patient information: Febrile seizures (Beyond the Basics)\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" SEIZURES VERSUS EPILEPSY",
" </span>",
" </p>",
" <p>",
" Epilepsy is not a specific disease, but rather a tendency to have recurrent
seizures over a period of time. Seizures that occur when a child has a fever, head
injury, or after taking drugs often do not recur and are not considered epilepsy.
In addition, what appears to be a seizure may actually be something else (eg,
breath holding spell). Having one seizure does not mean that a child has epilepsy.
Many clinicians require a child to have more than one seizure before diagnosing
epilepsy.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" TYPES OF SEIZURE",
" </span>",
" </p>",
" <p>",
" Seizures have many forms and symptoms can be mild or severe. Seizures are
classified according to the child's appearance or behavior during the seizure, and
the pattern of electrical activity in the brain, as measured by a test called an
electroencephalogram (EEG). (See",
" <a class=\"local\" href=\"#H8\">",
" 'Electroencephalogram'",
" </a>",
" below.)",
" </p>",
" <p>",
" One of the most common seizure types is a convulsion. This may be called
a \"tonic clonic\" or \"grand mal\" seizure. In this type of seizure, the child
loses consciousness and may stiffen and have jerking muscle movements. During the
muscle-stiffening, the child may bite their tongue, causing bleeding or frothing at
the mouth.",
" </p>",
" <p>",
" Other seizure types are less dramatic. Shaking movements may be isolated to
one arm or part of the face. Alternatively, the child may suddenly stop responding
and stare for a few seconds, sometimes with chewing motions or smacking the lips.
These may be called simple partial or complex partial seizures depending on whether
the child remains aware.",
" </p>",
" <p>",
" Seizures may also cause \"sensations\" that only the child feels. As an
example, one type of seizure can cause stomach discomfort, fear, or an unpleasant
smell. These feelings are simple partial seizures, commonly referred to as auras. A
child usually experiences the same symptoms with each seizure aura. Sometimes, a
seizure aura can occur before a convulsive seizure. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21912?
source=see_link\">",
" \"Overview of the classification, etiology, and clinical features of
pediatric seizures and epilepsy\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor2\" id=\"H4\">",
" <span class=\"h2\">",
" After a seizure (postictal state)",
" </span>",
" &nbsp;&mdash;&nbsp;With some types of seizures, the child may appear to be
awake during the seizure, but is actually unaware and will have no memory of the
event.",
" </p>",
" <p>",
" The period following a seizure is called the postictal state. During this
time, the child may be confused and tired, and may develop a throbbing headache.
This period usually lasts several minutes, although it can last for hours or even
days.",
" </p>",
" <p>",
" In some children, the postictal period comes with other symptoms. For
example, the child may experience mild to severe weakness in a hand, arm, or leg.",
" </p>",
" <p>",
" Other people have difficulty speaking or experience temporary (partial)
vision loss or other types of sensory loss. These symptoms usually resolve over
several minutes and can be important clues about the type of seizure and the part
of the brain that was affected during the seizure.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h1\">",
" SEIZURE TESTING",
" </span>",
" </p>",
" <p>",
" Determining the type of seizure helps determine what testing is needed and
which treatments are most likely to be effective. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/4/14409?
source=see_link\">",
" \"Clinical and laboratory diagnosis of seizures in infants and children\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor2\" id=\"H6\">",
" <span class=\"h2\">",
" Medical and seizure history",
" </span>",
" &nbsp;&mdash;&nbsp;Parents can keep a log book of what they observe during a
child's seizures, which can be shared with the child's healthcare provider.
Questions to consider after a child's seizure are listed in the Table (",
" <a class=\"graphic graphic_table graphicRef53593 \" href=\"UTD.htm?
13/2/13356\">",
" table 1",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor2\" id=\"H7\">",
" <span class=\"h2\">",
" Physical examination",
" </span>",
" &nbsp;&mdash;&nbsp;A complete physical examination is important in the
process of evaluating a child with seizures. This can be performed by the child's
usual healthcare provider (eg, general pediatrician or family practitioner). A
neurologist (physician specializing in the brain) may be consulted.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H8\">",
" <span class=\"h2\">",
" Electroencephalogram",
" </span>",
" &nbsp;&mdash;&nbsp;An electroencephalogram (EEG) is a test that measures the
electrical activity in the brain. It is performed to search for abnormal electrical
activity that is commonly associated with seizures and epilepsy and allows for a
clearer understanding of where and why seizures occur. Even if a child does not
have a seizure during EEG monitoring, important information can be gained.",
" </p>",
" <p>",
" EEGs are not painful, and there is no risk of being shocked or harmed by the
test. Some children will require EEG monitoring while sleeping and while awake.
Parents may be asked to keep their child awake for some part of the night (eg, put
the child to bed late, awaken early, and prevent sleeping during drive to test).
The child should not drink or eat anything with caffeine before the EEG (eg, soda,
coffee, tea), and the child's hair should be washed the night before the test.",
" </p>",
" <p>",
" Before the test, the EEG technologist will measure the child's head and make
small marks on the skin with a pen. Approximately twenty wires will be attached to
the child's head and face with glue or paste (this will wash out after testing) (",
" <a class=\"graphic graphic_figure graphicRef55691 \" href=\"UTD.htm?
38/57/39824\">",
" figure 1",
" </a>",
" ). The child will be asked to lie still and try to sleep, and the
technologist and parent can remain in the room with the child during testing.
During the EEG testing, the child may be asked to breathe quickly (hyperventilate)
or to watch a strobe light. This can provide important additional information for
the physician. A typical EEG takes approximately one hour. If the child is unable
to sleep, a mild sedative may be given.",
" </p>",
" <p>",
" After the test is completed, the wires will be removed. A neurologist will
interpret the results of the EEG and communicate these results with the child's
healthcare provider. A repeat EEG or more prolonged EEG with video recording may be
needed.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H9\">",
" <span class=\"h2\">",
" Other tests",
" </span>",
" &nbsp;&mdash;&nbsp;Some children will need to have further testing. These
tests may include computed tomography (CT) scans or magnetic resonance imaging
(MRI), which provide pictures of the brain. These tests are not painful, but MRI
requires that the child lie very still for up to one hour; most children who are
less than five years old are sedated for an MRI because any movement can blur the
pictures.",
" </p>",
" <p>",
" Blood tests may also be recommended. These provide information about the
child's chromosomes and the level of chemicals and substances normally found in
blood. A lumbar puncture (also known as a spinal tap) may be recommended for some
children who have a seizure during a high fever or who may have a metabolic
disorder. The test involves inserting a needle into the low back to remove a small
amount of fluid (cerebrospinal fluid or CSF) from around the spinal cord. (See",
" <a class=\"medical medical_patient\" href=\"UTD.htm?38/35/39473?
source=see_link\">",
" \"Patient information: Febrile seizures (Beyond the Basics)\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" PROGNOSIS",
" </span>",
" </p>",
" <p>",
" The long-term impact of seizures is small for most children, especially if
there are no underlying abnormalities in the child's brain. Many children with
epilepsy have normal development and a good chance for a normal life. Some children
with seizures will have difficulties with growth or development. This risk depends
on the underlying type of epilepsy or cause of seizures.",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" SEIZURE TREATMENT",
" </span>",
" </p>",
" <p>",
" The treatment options for children with seizures is discussed separately.
(See",
" <a class=\"medical medical_patient\" href=\"UTD.htm?19/5/19540?
source=see_link\">",
" \"Patient information: Treatment of seizures in children (Beyond the
Basics)\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h1\">",
" WHERE TO GET MORE INFORMATION",
" </span>",
" </p>",
" <p>",
" Your child's healthcare provider is the best source of information for
questions and concerns related to your child's medical problem.",
" </p>",
" <p>",
" This article will be updated as needed on our web site (",
" <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
" www.uptodate.com/patients",
" </a>",
" ). Related topics for patients, as well as selected articles written for
healthcare professionals, are also available. Some of the most relevant are listed
below.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H3498776579\">",
" <span class=\"h2\">",
" Patient level information",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
materials.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H17229106\">",
" <span class=\"h3\">",
" The Basics",
" </span>",
" &nbsp;&mdash;&nbsp;The Basics patient education pieces answer the four or
five key questions a patient might have about a given condition. These articles are
best for patients who want a general overview and who prefer short, easy-to-read
materials.",
" </p>",
" <p>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?27/56/28546?
source=see_link\">",
" Patient information: Seizures (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?11/20/11586?
source=see_link\">",
" Patient information: Febrile seizures (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?18/0/18434?
source=see_link\">",
" Patient information: EEG (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?42/40/43650?
source=see_link\">",
" Patient information: Epilepsy in adults (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?37/54/38754?
source=see_link\">",
" Patient information: Epilepsy in children (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?8/47/8947?
source=see_link\">",
" Patient information: Closed head injury (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?25/42/26274?
source=see_link\">",
" Patient information: Arteriovenous malformations in the brain (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?2/44/2754?
source=see_link\">",
" Patient information: Myoclonus (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?19/25/19859?
source=see_link\">",
" Patient information: Long QT syndrome (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?12/4/12355?
source=see_link\">",
" Patient information: Fragile X syndrome (The Basics)",
" </a>",
" </p>",
" <p class=\"headingAnchor2\" id=\"H17229121\">",
" <span class=\"h3\">",
" Beyond the Basics",
" </span>",
" &nbsp;&mdash;&nbsp;Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are best for patients who
want in-depth information and are comfortable with some medical jargon.",
" </p>",
" <p>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?19/5/19540?
source=see_link\">",
" Patient information: Treatment of seizures in children (Beyond the Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?38/35/39473?
source=see_link\">",
" Patient information: Febrile seizures (Beyond the Basics)",
" </a>",
" <br/>",
" </p>",
" <p class=\"headingAnchor2\" id=\"H13\">",
" <span class=\"h2\">",
" Professional level information",
" </span>",
" &nbsp;&mdash;&nbsp;Professional level articles are designed to keep doctors
and other health professionals up-to-date on the latest medical findings. These
articles are thorough, long, and complex, and they contain multiple references to
the research on which they are based. Professional level articles are best for
people who are comfortable with a lot of medical terminology and who want to read
the same materials their doctors are reading.",
" </p>",
" <p>",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/4/14409?
source=see_link\">",
" Clinical and laboratory diagnosis of seizures in infants and children",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/28/18888?
source=see_link\">",
" Clinical features and complications of status epilepticus in children",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/2/1063?
source=see_link\">",
" Clinical features and diagnosis of infantile spasms",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/11/6328?
source=see_link\">",
" Clinical features and electrodiagnosis of neonatal seizures",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?32/62/33769?
source=see_link\">",
" Epilepsy syndromes in children",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/23/41335?
source=see_link\">",
" Etiology and prognosis of neonatal seizures",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?3/9/3226?
source=see_link\">",
" Febrile seizures",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/28/30154?
source=see_link\">",
" Management and prognosis of infantile spasms",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/50/30505?
source=see_link\">",
" Management of status epilepticus in children",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/60/35783?
source=see_link\">",
" Neonatal epileptic syndromes",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21912?
source=see_link\">",
" Overview of the classification, etiology, and clinical features of pediatric
seizures and epilepsy",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/61/43994?
source=see_link\">",
" Pharmacology of antiepileptic drugs",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?0/0/13?
source=see_link\">",
" Treatment of neonatal seizures",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/32/37386?
source=see_link\">",
" Overview of the treatment of seizures and epileptic syndromes in children",
" </a>",
" <br/>",
" <br/>",
" The following organizations also provide reliable health information.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The Epilepsy Foundation",
" </li>",
" </ul>",
" </p>",
" <p>",
" &nbsp; &nbsp; &nbsp;(",
" <a class=\"external\" href=\"file://www.epilepsyfoundation.org/\">",
" www.epilepsyfoundation.org/",
" </a>",
" )",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" National Institute of Neurological Disorders and Stroke",
" </li>",
" </ul>",
" </p>",
" <p>",
" &nbsp; &nbsp; &nbsp;(",
" <a class=\"external\"
href=\"file://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm\">",
" www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm",
" </a>",
" )",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" National Library of Medicine",
" </li>",
" </ul>",
" </p>",
" <p>",
" &nbsp; &nbsp; &nbsp;(",
" <a class=\"external\"
href=\"file://www.nlm.nih.gov/medlineplus/epilepsy.html\">",
" www.nlm.nih.gov/medlineplus/epilepsy.html",
" </a>",
" )",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Epilepsy Therapy Development Project",
" </li>",
" </ul>",
" </p>",
" <p>",
" &nbsp; &nbsp; &nbsp;(",
" <a class=\"external\" href=\"file://www.epilepsy.com/\">",
" www.epilepsy.com",
" </a>",
" )",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" International League Against Epilepsy and the International Bureau for
Epilepsy",
" </li>",
" </ul>",
" </p>",
" <p>",
" &nbsp; &nbsp; &nbsp;(",
" <a class=\"external\" href=\"file://www.epilepsy.org/\">",
" www.epilepsy.org",
" </a>",
" )",
" </p>",
" <p>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/419/abstract/1-5\">",
" 1-5",
" </a>",
" ]",
" </p>",
" </div>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Feb 19, 2012.",
" </div>",
" <div class=\"patTopicTool\" id=\"patTopicToolBottom\">",
" <a class=\"toolbutton findicon findInPageLink\" href=\"#\" title=\"Find in
Topic\">",
" Find",
" </a>",
" <a class=\"toolbutton printicon\" href=\"UTD.htm?0/26/419?view=print\"
title=\"Print This Topic\">",
" Print",
" </a>",
" </div>",
" <div id=\"disclaimer\">",
" The content on the UpToDate website is not intended nor recommended as a
substitute",
"for medical advice, diagnosis, or treatment. Always seek the advice of your own
physician or",
"other qualified health care professional regarding any medical questions or
conditions. The",
"use of this website is governed by the",
" <a href=\"/home/terms-use\" target=\"_blank\">",
" UpToDate Terms of Use",
" </a>",
" &copy;2013 UpToDate, Inc.",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <div id=\"patTopicRefHeader\">",
" <div id=\"patTopicRefHeaderHeader\">",
" References",
" </div>",
" <div id=\"patTopicRefHeaderTop\">",
" <a href=\"#top\">",
" <img alt=\"\" src=\"./../images/top_arrow.myextg\">",
" Top",
" </img>",
" </a>",
" </div>",
" </div>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/419/abstract/1\">",
" Proposal for revised clinical and electroencephalographic classification of
epileptic seizures. From the Commission on Classification and Terminology of the
International League Against Epilepsy. Epilepsia 1981; 22:489.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/419/abstract/2\">",
" Berg AT, Shinnar S, Levy SR, Testa FM. Newly diagnosed epilepsy in children:
presentation at diagnosis. Epilepsia 1999; 40:445.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/419/abstract/3\">",
" Berg AT, Levy SR, Testa FM, Shinnar S. Classification of childhood epilepsy
syndromes in newly diagnosed epilepsy: interrater agreement and reasons for
disagreement. Epilepsia 1999; 40:439.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/419/abstract/4\">",
" Duchowny M, Harvey AS. Pediatric epilepsy syndromes: an update and critical
review. Epilepsia 1996; 37 Suppl 1:S26.",
" </a>",
" </li>",
" <li>",
" Freeman, JM, Vining EPG, Pillas, DJ. Seizures and Epilepsy in Childhood. A
Guide. 3rd Ed. The Johns Hopkins University Press 2002.",
" </li>",
" </ol>",
" </div>",
" </div>",
" <!-- patTopicMiddle -->",
"</div>"].join("\n");
var script_f0_26_419=[""].join("\n");
var outline_f0_26_419=[" <div class=\"patTopicFancyTop\">",
" <div class=\"rcTop\">",
" <div>",
" </div>",
" </div>",
" <div class=\"rcContent\">",
" <p>",
" Contents of this article",
" </p>",
" </div>",
" </div>",
" <div class=\"patTopicFancySpacer\">",
" </div>",
" <div class=\"patTopicOutline\">",
" <div class=\"rcbBottom\">",
" <div class=\"rcbLeft\">",
" <div class=\"rcbRight\">",
" <div class=\"rcbBottomLeft\">",
" <div class=\"rcbBottomRight rcbBottomRightBottomOnly\">",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a href=\"#H1\">",
" SEIZURE OVERVIEW",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H2\">",
" SEIZURES VERSUS EPILEPSY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H3\">",
" TYPES OF SEIZURE",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H5\">",
" SEIZURE TESTING",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H10\">",
" PROGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H11\">",
" SEIZURE TREATMENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H12\">",
" WHERE TO GET MORE INFORMATION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" GRAPHICS",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" FIGURES",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?38/57/39824\"
title=\"figure 1\">",
" EEG PI",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" TABLES",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?13/2/13356\"
title=\"table 1\">",
" Seizure diary PI",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>"].join("\n");
var title_f0_26_420="Isosulfan blue: Drug information";
var content_f0_26_420=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"2\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Isosulfan blue: Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?19/62/20451?source=see_link\">",
" see \"Isosulfan blue: Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F5577185\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Lymphazurin&trade;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F5577187\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Contrast Agent",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F5577217\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Lymphography: SubQ: Inject 0.5 mL into 3 interdigital spaces of each
extremity per study; maximum: 3 mL (30 mg)",
" </p>",
" </div>",
" <div class=\"block dor drugH1Div\" id=\"F16160052\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Renal Impairment",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No dosage adjustment provided in manufacturer&rsquo;s labeling.",
" </p>",
" </div>",
" <div class=\"block doh drugH1Div\" id=\"F16160053\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Hepatic Impairment",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No dosage adjustment provided in manufacturer&rsquo;s labeling.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F5577222\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution [preservative free]: 1% (5 mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Lymphazurin&trade;: 1% (5 mL)",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F5598929\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Yes",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F5577218\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" SubQ: Single patient use only; do not mix with local anesthetics (in same
syringe)",
" </p>",
" </div>",
" <div class=\"block scp drugH1Div\" id=\"F5577208\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Compatibility",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Compatibility in syringe: Incompatible:",
" </b>",
" Local anesthetics (eg, lidocaine)",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F5577188\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Adjunct to lymphography for visualization of the lymphatic system; sentinel
node identification",
" </p>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F5577198\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions Significant",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" 1% to 10%:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Dermatologic: Pruritus (2%; affecting hands, abdomen and neck)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Local: Administration site swelling (2%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Miscellaneous: Hypersensitivity reactions (2%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Postmarketing and/or case reports: Anaphylaxis; body fluid discoloration
(urine, serum; may lead to falsely low oximetry readings); skin discoloration
(including blue urticaria)",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F5577193\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to isosulfan, triphenylmethane, or any component of the
formulation",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F5577194\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings/Precautions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" <b>",
" <i>",
" Concerns related to adverse events:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" &bull; Hypersensitivity reactions: Hypersensitivity reactions, including
anaphylactic reactions (rare), may occur; appropriate equipment and emergency
medications should be available during use. Competent personnel and emergency
facilities should be available during and for at least 60 minutes after
administration, since severe delayed reactions may occur. Risk likely higher risk
in patients with history of asthma, allergies, drug reactions, including previous
sensitivity to triphenylmethane dyes.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" <b>",
" <i>",
" Special populations:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" &bull; Pediatrics: Safety and efficacy have not been established in
children.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" <b>",
" <i>",
" Other warnings/precautions:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" &bull; Methemoglobin: Methemoglobin levels via ABG may be falsely elevated;
co-oximetry may be required to accurately assess.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" &bull; Oximetry interference: Peripheral oxygenation measurements may be
falsely depressed due to discoloration of serum caused by isosulfan blue; (peak
interference 30 minutes after administration; minimal effect by 4 hours postdose);
direct determination of arterial blood gases (ABG) may be required.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F13299549\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" None known.",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F5577202\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:0em;display:inline\">",
" There are no known significant interactions.",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F5577189\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" C (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F5577190\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Animal reproduction studies have not been conducted. There are no adequate
and well-controlled studies in pregnant women. Use during pregnancy only if clearly
needed.",
" </p>",
" </div>",
" <div class=\"block lac drugH1Div\" id=\"F5577192\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Lactation",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Excretion in breast milk is unknown/use caution",
" </p>",
" </div>",
" <div class=\"block fee drugH1Div\" id=\"F16324129\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Solution",
" </b>",
" (Isosulfan Blue Subcutaneous)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 1% (5 mL): $714.00",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Solution",
" </b>",
" (Lymphazurin Subcutaneous)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 1% (5 mL): $754.83",
" </p>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F5577209\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Following subcutaneous administration, isosulfan blue binds to interstitial
proteins; these proteins/extracellular fluids are drained by the regional lymphatic
system, resulting in concentration of the dye within the lymph. Bright blue
coloration imparted by the dye permits delineation of the vessels against the
surrounding tissue.",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F5577211\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacodynamics/Kinetics",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Absorption: 34% absorbed in 30 minutes; 69% and 100% in 1 and 24 hours,
respectively",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Protein binding: ~50%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Excretion: Urine (10%; as unchanged drug); feces (~90%; via biliary
excretion)",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" Hoskin RW and Granger R, &ldquo;Intraoperative Decrease in Pulse Oximeter
Readings Following Injection of Isosulfan Blue,&rdquo;",
" <i>",
" Can J Anesth",
" </i>",
" , 2001, 48(1):38-40.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/26/420/abstract-text/11212047/pubmed\" id=\"11212047\"
target=\"_blank\">",
" 11212047",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Kern KA, &ldquo;Sentinel Lymph Node Mapping in Breast Cancer Using
Subareolar Injection of Blue Dye,&rdquo;",
" <i>",
" J Am Coll Surg",
" </i>",
" , 1999, 189(6):539-45.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/26/420/abstract-text/10589589/pubmed\" id=\"10589589\"
target=\"_blank\">",
" 10589589",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Sadiq TS, Burns WW, Taber DJ et al, &ldquo;Blue Urticaria: A Previously
Unreported Adverse Event Associated With Isosulfan Blue,&rdquo;",
" <i>",
" Arch Surg",
" </i>",
" , 2001, 136(12): 1433-5.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/26/420/abstract-text/11735875/pubmed\" id=\"11735875\"
target=\"_blank\">",
" 11735875",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Sprung J, Tully MJ, and Ziser A, &ldquo;Anaphylactic Reactions to Isosulfan
Blue Dye During Sentinel Node Lymphadenectomy for Breast Cancer,&rdquo;",
" <i>",
" Anesth Analg",
" </i>",
" , 2003, 96(4):1051-3.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/26/420/abstract-text/12651658/pubmed\" id=\"12651658\"
target=\"_blank\">",
" 12651658",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 9039 Version 28.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0504-61.55.141.10-46FA143880-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_420=[""].join("\n");
var outline_f0_26_420=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577185\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577187\">",
" Pharmacologic Category",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577217\">",
" Dosing: Adult",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F16160052\">",
" Dosing: Renal Impairment",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F16160053\">",
" Dosing: Hepatic Impairment",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577222\">",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5598929\">",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577218\">",
" Administration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577208\">",
" Compatibility",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577188\">",
" Use",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577198\">",
" Adverse Reactions Significant",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577193\">",
" Contraindications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577194\">",
" Warnings/Precautions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13299549\">",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577202\">",
" Drug Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577189\">",
" Pregnancy Risk Factor",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577190\">",
" Pregnancy Implications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577192\">",
" Lactation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F16324129\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577209\">",
" Mechanism of Action",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5577211\">",
" Pharmacodynamics/Kinetics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9039\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9039|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
title=\"Lexicomp clinical abbreviations\">",
" Lexicomp clinical abbreviations",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_patient\" href=\"UTD.htm?19/62/20451?
source=related_link\">",
" Isosulfan blue: Patient drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_26_421="Buccal SCC resected";
var content_f0_26_421=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=ONC
%2F69202&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ONC
%2F69202&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Buccal SCC resected with 1 cm margins",
" </div>",
" <div class=\"cntnt\" style=\"width: 396px; height: 264px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAEIAY
wDASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwDiX0+RZJHZwbaNyVXdkFj6VU1T7Xc6eYoV8yEDL7egpdTUB2it5wu1iB
F3x61q2tyX0+K2sbKR9Ql+QJjOD/sjvmvuJR0Vz52MrHIadb6jpsqyW05jdjtEZbgj0NST6pO91i/Vkycbl
6A59q35/DM0GoRJqlytvPIN/lxuGYHPQ9gai1KzEMDpJJGduQCRnd9K5HTTlei7fkdHtLL94r/mS3U1ndKj
rtns1A3FT8xPvXG6pYM80t5aK9um4+Xtzx/jWimkyRTxNa3GwN8x3DAFTXGsXCrHb3qKmz5VZRxjvis3NJc
laNvPp/wC4wfxUn8tL/8ABKukeJnEsdprMm0MMefjr7Guge1jt2eVpfOhZcqV5C+mayL3QbW/02SZJ43lHR
M9q5m3vtQ0QtBMHls34xnpVKq6a9/WPf8Az/zFKmpv3dH2O1S9ub6f7LbOQzDGCMAD2qe+1C4tLWOyu2kjV
T90g5qDRtRtZtP83ZAdpwGB+bP86uy2s16ySmSJ1cbsv8xx7muqMlKzWxzyVtGhdOtrHfG8cvnzSIDt+6Ax
qtfw3NnfvCyhtvBUvnmmRfZIpHWOORnTOZPXHt2qBJknjLSKyMGyODyK0SaIv1L/AJq2nlxzbQzH5mByFFV
4ru8hu1uIpSIVPyIO5+lJBGJ7iMSxSbOoI7n3rTv5rWSLy9hgJJLSnnHoAKm6Wj1BrtoP0acjVUudVjfBzt
eP+H3Iqpql3JPezM8+LboMnJ/Gowy2unmNJXbzBkswwR7Cqmm6XJJG0b5IlOQo5JPqaNU+awaPS5rabb2k1
u0lvcGWReqOePw71U/s+OeZ5ZzM0JU7WjOBu7fhSXUcVkjWiR+SWO3IOWJ75NKHvIdJbe37ocI+3gev4035
u1wSs9FsVZVa1XZDdSFycbS3QUq3ELvGkqyuI/vMvSoLWC0uOXnUyEfxtjJ9q0YrZbW2fbPthX7z5BwfQCi
S7Mfw7lae5e61BTbgxunEe48UxUltrrzrx3Mz8ZDfzosopo7tZrRHmZskeaAcj3FT38+QpLpJMfvKF4X61T
d3Ym2hIx+03UZZV8kfK0q/N+dP1V7MPFFZF9vcHhiaLKT7MguLl4tjnCeT8oz71VSKRpZ1MitKTuD9QBRFW
d30CTvoi5bY8zZKpuI4wSIsng46mqUksjJKMYDfdZsgfhTLaS6svNmjKsG4Jbgt7Y9KksIm1gu8s4WTdiOH
+v0ofLcfmSwapcTyiK/lIaNcB2549jUcscp2yxzQ3Eb8NGCdy/hVyK3Mds8YV7iPdh5FTIX2qvLFamaOW1t
5gkf+tZ2wCfb0p67JCVviZavYrWDTrcWN5M2/l4ZFxtbuKpWUgN7HEUZ2Y4KdV/GnTmOeSTzV5I+Ta+CKY+
n3ENwkty4Kgbht/wDrUlordR6bss+IIYYxHHpwRUX77KT859Bmo4bqTy1CpJFcRDAB+6R6GqfmCSQTwmMmN
v8AUluT71dvtUt7iGOCTdEerFR1quV2XkRffzC0lYXkRuYI542Jyp6+/ParcTF5ZHhh82BMhYd3IPr61BBb
R2swaS485ZEzHsPA9mrOsrue01Q3ESM0WcNtP8qGrptblJ6pdDUtbF4GN/5gk/vRO3P/ANardvFJrDv5Mca
wpwEB71Vnfz7CSHTpVUN+8cNwRTdIe4ZQj26sCpHm27YI+tFrJ33Je+2hahln0m4VrNxIA2JIycj8O1MniW
4uprmIm2MQ3eS3BJPoKo3kXl2QlSRsK+cBs5P0rSRHntPMupo2n8vcgVgcL7n19qNnfqGyM6yvHN4YC5YTf
eV/u1q3Gkx2wS6t1/dgcKGJBPrWJal1Z2hTz484bIrUm857Rfssoj5z5BbJ/wD1U5tXugitLFKPWU+3K14Z
Mrwp7Y9Ks6pdvfXSSpcGNOixYyuPaoIhavqO18usfzSIo4J9M0Xi297K1xbM8TRnCpkYxSaXxWsPyTFtltR
eBwGikXlmRvl/Ksy/eafUgE/f5JxnsKvpbQQ3Urx5AZR8h7mrNg5tLszSeWy4wQmNyj0oS0uF7NpFOB54o4
xNeNAN/wAsQJqZHT+1CFnZ1j+dXXn5qL6VLi4EsiRoq/dU+nvVmOCz8zzLUCMEYBB4JpME0UZtQme/aS98u
cykHeRgritXW722msi+nw+XcvjzHj4Bqg1q1rNLshRxGfvHnJNUiwku41WBjIT+88vgChKLafYHdEulfbmv
VR5I1RRnLAZpk95dzzSOAcZwCO4qW/iNpMxltnjXbghT1HrmrGmTXD2aGE2qoOMPJg0c+nMlcair2ZCumJ5
y3Vw5WN8sN3cVb0/et8LrS7kfbEH7vY33c8EfWrlxGvlok5lneRQscWck+h+ntWTHorl2u5JVso06MDt5HY
epqLcys2F7dCfUT9muJZrxXkuictI56H0A7mq1tdcLKFjnLHhT1Qd+KvxbruJWYtcgHEX94tVqQ2VjZSwXE
KJdT/ekZhlMdh9aT91qKQ9HdsxNZkN2qGJFihQYHzZ5/wAaLPSX1G2XdPCAPkBc9Cewq5Dp0L2u/wC1LLEv
CQqMlj6VUv7gQ2fljZGB08tc4PpmrcVJcq2EpOL8yhqvhm/0maaNJopEAydj7lwecZqpFPHfRra3nloqjbg
jDVuW15cLaxpuVSRnDL8zZ+tQzaJZ3Ukf2m9QzS9Ioh8wJ6A9q4ZYedL34P5dP+AdSrxn7s/v6/8ABOKutK
v9NuWu9LLlFbJKg7D9a19F8R20w8m73W1yThgTgN9Ku6ld32iTNpOoO01nESoKgZUVk32h29+he1YFCNxJb
pWMYyTfsdH1j/X/AAxq2mrVNV3N1DdiUuqN5IGSyjJK0st1JcSIqBWQnhF+9getcxpuqatoi+QZTPYSsELP
xjnHBNdrYnTv7EuLhMmeVhsbGCi+9ddOspy5WrS7f1uc86fs1fdEd75JtFWNvK2/ffd1PvVzStNjvdNjlOp
RFkb5I3GNx+tZOn2U13HsWXEDMWO4Z+pqxeWVw88NjaQOQeFEXU+59K0np1tbqZwTeiV2xNVSa5mWCFVkIO
Pk5Hvz3qTTk+yyrALnE78cPjZ65ru/CfhS60+wC6mYU3fKqqPmGfU1pjw7osMcQt7GJpkPLN8xPqTXmVs6o
09F73psethskr1vitH13PNL2zxIERJ7p1O7zB90/QVoG01HVoIbS5s7lbJM7AsfA9frXq2l3S2ChYLO16/L
viBIqw2q6nOrbXEQB6IoFedPiCf2IL53PWp8OUr+/Nv7l/meP2fw91Nxm3tpSN/BdCDj+Vaz/D3XZIp5f7I
mdYxlVQ43fhnmu1vH1EIXed2Vecb6wY9X1V7kNFcTxMpwAGIOK8+rnWLkrKVvRHrYfh3DJ8ySdv5nf8DnRb
WCWJhupJoNSVijW4UhgfU+1YV5pqWKiS4ncrKc7UAJYeuPSvUY9HbUpfOuo98jD5nbkn8akbwXpk5xPD82M
daUc7x8U0p3XnYuWRZde8oa+V/8zzRIJfsMFz9kxbSEqinBbI4xtHI59a0fD0Vy1zmPSjKGJDGRQNjdOcV6
ZpHhiy0xWSBAUfhs88Vr2OmRWybIIkRPYVjVzPGVvinb00HRyzB0Phgn59fxuefx+G3msJEu1jW5zldoU5P
oT2FRSfDdpDHdteW8MhGDDahuPqSa9SFnGuWYLn1xVS4ljhO1Wyx9Kyp4jEU3eNSX3m06FCro4J/JGDaaS9
lZQWtskSRKQWyvLetaH2K3Z9rww4x0ZRg0+e9WEbpc49q53VfFBRyligJ9TUScm+dydzWnQ5lyQWiJdT8Ie
H7yRzPp5jnxkNbkrn+lRWXhHRpLVocTMMZ2mXkUWGsXM0IeY5Y8HHAFatvdcBkTDHgmumOMxcVaNV29TmqZ
fh3K86cW/RHG3Pw4sJZ2lt7toMdF27s/jXPat4V1PThN+7imjYELKo6D6etexQzRsdoYZ+lWMo6lcAj3HFd
1DOMZSspSUvVfruedXybCVW3ycvo/02PnjSo5LXfDdRFlbncP8altLIXc08hd0CHhVNexa94YtNSjbykFuz
cOVAww+n+FcFqXhW+0y43aYzxwSHa7Nyo98+le5hc8oVrxq+5Lz2+88HF8P4ilaVD31+K+X+RzMjttkjliI
hxhXPc+5rU0yePSdIkxArzyY+bdlQKyp4bmxn8u8JVpDtTI+WT8T2q3qNt9msQpKRt1IRtwJ9q9dNTtyu9z
w5wcHaaaaI8pdBprVTDNGc4HKn8KkuZlhtkE+3z5RgtjAWqFtmC1RwssUrt8rZBUj6Vcu7xmbyb23hlhVfl
2ggk+pqr633It0LmnJeadbGMJG8TfOsoIPPrWSLgvcOLlm35/1g4I/wDrVsaczwaRM0QMMMx2pGxyCfWqF9
btIIrbCw3ROWLnCsPY0LRtyBdLFlbK5TTxPA6yBmIYjqfrVKy+zu8jfaXR14xsyAa0bmW9ttDaB2hZgMBVP
zEeoqWxOkLohZmcXqfeRxgsfb2rNt2/yKVkyibiRGWKdlIYffA5A+lTWZgtXd2haRMZR88n8KzJY45pixSQ
bh8smelaV19p+xRqZE8sJgNtAOPaqcXfcOayK9y9rJOsLuylzuKuP0zVa7VrS68oMsUbjORyFqW4BuII4/s
pcD7kpPNPktYIliEdwtxK4yEUbip9KXn1CyH28y28Bkiu3ZAcP5i8fhVcPJbfvrWcu0hOAMVq3V9DBZRwS2
0OdhD+YM5b19jUFrp9nIsdzbSxmRV3MmeFNPfdCtYW9ma5treIRvFO3yAyHgmo4vC7ICpbLA/N83epbhZbo
29zZXSXUjcPGV4T/wCvTp4byB9p82EkbtoNJPoh2a3LuiawsWszPcxwS2xG3en3oc9xTNZSO/dY4CxRcsVI
4xWfY6da26T3THbJnbGAcgnuagW2uriPaG3+aclt2No+lJRV77Bf5mnpukCzijvGulifYXwM4QdgPc0w2E1
9atI6Q4kbq/3gv94k9qbcKlyyWpvI7aOIZLzN/rCo6D69qvXN8uoaZKFRoY4k/euvOecKAPSm7oW7Miz+wR
zmCC4fcoO8scDjsorWt7E2xjkeyiCxr5xUtnI9T7+1Y+naLHdXIUPEkir5kjSHiNff3qeSPzrqOKLzHjIOC
ucBf73vTkk3a4J7OwlwINRvGuYnMYHBbOW+gFM8qWyQXSkITkB3xk/Sq82kw2TvJeXMsAwWibbgv/Sq1nNb
zowuRJKynPl7jkj19qLJoNUPhW0uxPCrObyYZWaQZB9R/wDXqjf6JNZWq3GnuFfB3ozhh/8AWrrrJri7tkj
0LSVSY5Rpl67cY25/rWzofgWSC2K63cuI2O/7PF/U152LqYekr13r0S3PRwlDEV3+5Wnd6I8l0m5g1ORbC8
srppSTkQqWBP0rr/Dvw+v5GmGoXLpay4EcQY7lA6ZPbivQGmsdPC2+j2iIoPJROSfr1NbVjFI8QaRSC3OO/
wCNfM4vNZz92GluvU+swWTQpWqVVdvp0+457R/BunaVsikdxET8z/M1at34d0txtsCTKed544rfsrPzHO4u
MdcnirRihgywZcpz9a8uderU0lJv5s9mEIUvgSXokec3uiamsgWOWYpnA2ksKRJdR0j5pSZIhwSwziu3n1q
EoUiZXYnGFqFtPGoqwuDsRucAd+2awcnF76nbG0l+9jocgNW1FnabzW8sY27VFbVjfXjQ4kYLPnIVwAGH1r
dk0u2Nm0cmw4GMKvFczFMvnSxYDxRHaGzg/hU+0mt2U4UqiahG1i4dUIG24h2MTjk5/GlsrWO6kaRSpAOci
uXvw51EJHIRGfmG481NbXraZceYs+UI+ZPWrjVUtJIidB043hLU7h7l4yF4wBjilhmOQc5Yda52LxBZzvif
dHxxkVof2lZCAyNPEI+/PJ/CuhQT2ONza3RsLepu2buT271eguHKhIkdnPPAzgetccuu6fHMGiKn/aPPHtW
vbeOodPEraeoaeVDGfNTgA+hosluxyU2vdjc6KSGUwkl8nH5Vzs0MdpctLqF3FEvUKWGTXn+oaxqDzyPLey
iOQk7QSFH0rHu7h92ZH3dBgvyw+h6Vm68Vsjrp4Cpa7lv5HomuXcN9Bts7uFvYOM1xqNFBO63M0ayehbvWB
JfSRtiNJdvU4Xp7Zpo3edvkiZBjndzWc8Qt7HVRwjinFS0N+DUVt7gbpB5YOeDniut07xBpTvAt1MVhyN+B
zjvivPmkhlURiBQ2f9Y/HFXEsY5E2eZAzn7gVuRVwrt9DKvhI299tM7251ux/tScaWZJLPd+73D5se9b1vc
pNaKduPc9q8YYTQXDKGwQeMHmtGz1u6ij2STyYU5KseCK0WIj9pWOeWXSt7jv+Z66k0WMMwI+tK8SuGw2Ub
oa5zSLqC8gSePByPmGeQa2baeMEqfmT09K05b6nDJ8ui3C70yC6geKaKKSJhjDrmuD8QeA3wz2DmFwchGBK
H29q9IjlAI+YsnY9xU74lj28H3row+Jq4WXNRlb8vuMa9Clio8mIipL8fk9zw/X7mawsYLe501kuR8olj+4
R7Hua5+eI3Dq8Jm3YG+OTqx9q9z1XS4Z4SrR5X0FcDqXhuOC6d4N8pLZySf8ivVjxJOCtOnr3T0+7/gnlvh
SlUd6VR27afmctrCXK20UamRDGcCM8EfhVjTHeL93foVOMhnG4Y9q2LrTWuVaC4lkWZ1A3nnH41Cnh1obFp
4LsTuvHzdq7cNn2Hqw/fe6/m1+B5OL4dxFCVqXvL5J/wBeaMO/tDOzTLeKEJ2kD7w/CrUOhXVrpouIrhLku
MhXYAgfQ9aS/tkhkt43RoS6ZeYE7SarXUdxceWPPZ3QYU9cAV7FOrGtH2kHePc8SrRnQl7KatIdepHNFAoW
6jljH71NuBn/AGTUWoTPcNDaWztNKRtUMcYFXra7ayUNqcbTxFfkMbZ5PrVS5skuALiASIikZbPLZ7Zqk+X
VmbNkTWkGipAI5odVVtkiOu4bfUGs6CGJJTJGB56HJ2ghlHqfSrd5a2Yhtore4eO5f5meRsgZ6A1E9nHY+f
FqUHl3MfWaKTIkz2+lCdvVi6a7Et/YyXNxC0DRyeYpcsDuZMf3hVZha20qLexyAMMO6DGKh067No1wbW4TM
w27SpJH40lzcXbW8QmILA7mwc4FWlZ26E3ui8vkecZtPh/0RMYycnPqaZda5drO4LBSD9aeb06naBLaG2tT
jaxT5C2P4iKzra3aVGKeXIFYruLdam11aQ9E7lrxRchpngSRVlR8uyd/p7UvhS7mVJQbEzQ7gHmJ5x6Crxt
7e3eSfVomjt35WNgAxXtj61m/23dRNKtvFGsBQxxKBygP9femnePLFD831LN62n63rkKNi33uI2b+GMA4zT
dTQ2upk6fcJC0B2xsvKvjv+NZ5l+yWwBjAmY8n/wCvVVZdRnuUC42RnjK/L/8AXquS3oJO5tQiG1hee7hkZ
rgHdPnAT1Huah0nVl0y+kNpK19Cw2hGyrdOB9B6U25c3SxW99OEi3cKi/eJ68V19t4Pt4JVXT5pXikbd5rL
tfZ6CuetWp4eN6jsmb0MPVxMuWkrs5may1HWIArxNJOG4YnCqD2xXU+GPAVtZyfadWdpJiMCJThQPQ12mn6
RbW4jjP7pVHGG3E+59614kt4m3Iu4Y6sa+Yxmc1Kq5KXur8f69D63BZJToe9U95/h/XqZdhYxWIxZRpEo4w
KS9eURtGGzv4zW/avC4Y79kg/2QRVO9uYJUxMiKw43J3rx+Zyd3ueta1lY4WwQwXMqSo4aOTnaM8V2+j3MF
0CsUb8HBZlrJ0/SC6yTSu7PI27eDg47Ctizhe1jIihGfUtkmuBt3setUcZx21NQRoRyQHHYd6zdTt0aBy6k
KQQQatR3DZyQM989RWX4gvfKhBRgZCeVPcVTloYU4yUlYyStnpqQiKwNzuyQw6itK2k8+NpMNDHjO1z0otH
VoCIYnaR+WIBwPxq35aRw7JXEYxzuqIp3ub1qq26me0yFHQOFGOueDXOXdu0QZoXT5v1rb1eVIYsW8SyuTw
O5FYsLXEs/
+kRwx84AdTgelE7bF0U/iWhhX9rPKFkVRhRjNZxSRZMhQ+O2K7SSWMy+TNbjdnAaPv8ASqmraY1oLa5KAQz
5AORk49R1FZJ22OyMuaykcvdNKmJMshPYAYFVWVfvXTEx9SFHNbV1FbPKu35MDlvUe4rIvFReV3bM8Hp+VC
qO5qqKasMjtY3ZBG7r82MNwDnvitptJkg3rKyMCvysWGAfrWdi3kRGRyj+nY1f05o5fOtpTvVl3xEnI461T
97Rhfkejsc7qYe3CpOAeflZWz+FTW0iTPEskARjgK5GCD7n0rqL7w9p7eFrLUTcyvqC3TLLBj5RGRwfzqvL
pf221Mo6oAAPapkpR3N4VaVW9+ja7GNLaXc8hURB5AeEi+Y5+grLnjlik3SJIG9XBFeveDPD2j+ULvVbu5t
JAMwywkKUb1Pf8qpXvhyz1LVLiKxl+1pFktMxJ3H19fzpuDtzGSxdOM3C2i620+/Y83067tpdQjjv/Oe2f7
ywY3k44AJ4HNQ3M8Yu1EFsbZEcFctubjsTXa3/AIWupi8Nppwd44y7LCADgdT6msXTfDUl9mSInG361Klf3
bamn7t3qc2hTF5ZyTs1wzruB5Vec/4VDqNzatEoiQnHRjwa6i3+G2v3kB+zWbzkxGZCXVSy5xlcnmuLj0y4
Fy8N0kkTxNhhLxj1yOtaWa3RzQnTqSfJNO3bodD4I1NY7o2s77Q/Kk+tejZjQKRjnvXlsulwRXYFm/mkJvL
gYB9hW6qXiWZaa5ZU2/KC3SuiniFGPLJbHBisEqk/aQla535mRcFBmMdfanlxnejbc9sf0riLLUtSjgSRkj
kQcAkdaW98S3idbeNRnnBNa+3pvW5hHBVr8tk/mdk10N3zKcjrtpjLDKSSMhuvvXPaRqUWpkrvAkB5HSt0x
lFwhP41ektTOzpuz0ZTv7JBblY1xnp7GuffSQ6SFGeGY8FlG3j+tdLKxVwC4J6kU55UYrE5HIzjFZSh1R0R
mpq0lc4DULW6trIidTc25GBK38Nczdts
mjXcUWX5WI4r1WSOa3LNEUkRufLbkD8K5HX9LaeOSeOFJAp3OAMbfw6V2ZdmMsBUu7uL3X9dTzszymOPpW0
utn1X/AObuYY9ORDbqzyPyhk6Y70k8s1+iLdRPbwIuR5R+VzWVqhuIz5TRs8echlOa07R7i2gt0KwowOdzA
guD/Ce1fdUq0a0I1Ketz85r4aeHqOlUVmvxKs0k8jKsmI1A+U4+bFWpWuXRbd3WVWGeRg4q7BeRE3M17DN9
qY4RGUFSKy44HuppZZ2EWQVL4PHtW0X1MJK5tWeoWQsJIliQmM/K23qcVjSqkk5mtZBJux5sPr9KuNby3Nv
GkMcZECHMqnAf3bNZGnStaXJkhkIm3DAC5B5px62Bu+rOnisLC4Qi+uYrKQxl4twPH+ycUmmRPZWoiihtLh
M7hIJcZz7Vz+rW17eTLLdkK7sTtZsA/4Ct/SbGC+skk/srcV+QtG5wcd6S0V07ia2TKKwQpE6XFwzvGNzNI
2SF9B70y0vLKSyZI7NUaKTeLqVjk5/hx0qSe3TU52QNChDMxYHAA64z3NRXXlLZJItpJLJG2FH8AHv6mi6s
LuaGnyQavcqzpB9nt0I2sBj3PuaoXVpf3kqz2kscUYkCxKGAx6EirdvpckESX8sCIsu1X2g4hDHgkd8daiv
42t7ye0tb+N7NZAjyqCqyAHrzzzU80b6Fe8h2naZqUJF3qEZJllCxPjOeeSO1eqaYHnddwYEAKqj0rz/AEK
4ee8Z70lbaAgwouWGfb0616d4edpLJZGhWNieo53D1r5PO8RGVdQb1SPt8hw0qeE9o1bmd/l0NKG1VX3OTx
6nmrTRW56KSfeiIr1dSfXFOlmhICiPbt6kg814bZ7Fr7joZkjjCG3iYepHNZmpRxGGVxEAfbt9KXUb+CR9k
SiIj+IdDVCWSSOJmdjIo6gelS5GsKN9Tb0eOO6iQw4aIgdDWv8A2fJbOyvHuRWxwc8/UVwnhH+14Jro26qL
QtuSNu2ep9hXQJ4xl0m5Sa6tjKFzhQeN3b8qzg0t2KvGbk/Z6+Rb1FfKSSZUCgDtXJ+Y5Vrm6TfJk7Ex90f
SpB4kbVFmIiZIsk5buaqSXcjsI4IAPLOTK5B/DFKbRtThP4WbOn3V2sXyKUjI4HakmKOS0jZJOfvcVzF/fT
mGWWW+eGGM/wAHyhj6e9c9LdXl7JI6XDvAgJGe+KzU+xusG73vY7Weexhn82a4UgDGwmqeqXa3sTJE1rJnu
jDcM9B82P0zXELHNcJuSUk8Hsce1SS24tkZWmLMw+6Knmve5usPyta3Zry6Xq1rPKRZXcfkqJGfONo7Gs03
TELFNdNwS2Cd2D9KzZB5ShZriUSE8KrEgD3qNhHbP5iJGdpzzzz7/wCFRZXOv3upakuJJZgPvY6E9aj8q4l
cmXy0DfwkEYP0rX8I6xbW/iG3vdbhE2n7y88USBcjtjHocHHGcYrsfFur6JqemC/aAedNKSJXwGJ9MDt060
407xckyZYiUKsaXK7Pr0v2OFk0uA2KmHapQfO2ckk1Ld3D3DJJM6iToNihcfQDgUzQdYn07XoJo3Q2s5MLg
ruUKwwSR3A649q0fGGn6ZpeqLbaVfreRPGrGcLgMx6nHb6UopuDlHY2lZVlSmru2j/P0M+zvnEotL91SOT7
knQfjWv4bZhqn2VnJjYd+4qlcwRqJYDa/aGKqYphJwueTx3449qgjjmgZfPyXQfKcnIFDqWVnuHsXO7jon/
V0dzdWLancpFEjRLGSASww34VW0mefw7czPqIVYpG2k/1qPw3rlusCR3UMpkVv3ZVC5b8q1ZLvRWtL6bVZJ
NsiEwJ/tjoMe9aKKeqepxzlKN6U4tx/H5GXqWuvNeyXOlSKphHyuvzEgjBGP8AGrXhTydT0a7mlt54ri3BZ
XThDk9CMcfpXFTWcs9xI+kiSGKXG5BXX6NpdzF4auE1C+mWORWVI0/iI7EjmlG7ZrXhCFNJO23r/wAEzU8U
6tpmqxSWd6saWp3CJgTuB6jOP0qPxTruh+LLWXU7eAaXrqMBPGWPlXKDj5eOG+uOB1rNtoBaRz20UxaKRg7
I/wA25gMZ59BVO7iCnYYl2nocdaTxDtyvX+uhpDAQcueOj6NdvPubEd3p1kZYI7iO4jMYzLGvqMn8jxVbX7
6OWzt0h8loi3zeX94HHfNYQH2e8G0EQuv5Edarzysku9sNG3HHY0KqpKwng+WXPc6Cyv8AzkKyqI4gdgVf5
n3qtqn2cQ+TFveQnPXpVLw7Z3uua1Dp+ntEhmYgyXBIRABksxAOBW/4t0e28MXUdtdahHKp4klg4JUjsD1F
Plk1e2hnKVOlVUOb3nrY4uS5k0XVYZ4yVB/hBzXq9jqkEthHceb8rAE5PSvLNWs0vIIp4LlZCDtMZGCB6it
qDctisDL8qjH1rqw7cU10OXGqNVRbevU79Z4LoCRNrejCmQwq0jAEMeoPpXIaTLPbgpyIz2NXbGZ7Z2ZZDg
tkqTnrWz11ZxL3G1GR1CW3zbiTj0FJLBHtYI0aD3GTVK3nkmO2Dv1Oav2VvbwXKyXA8/uRnqazcblurpqc7
rPhyxv0PmxsjN92SH5W/wADXF+JtPu9Pe1tboyvZs2Um28+mCema92voLa80wSQYidOQuP51zep3Edtp372
MOX424/WuvBY6eCnzLWPVf11PPxuChmVPklpLo+q/wCAeXajp8ml28DRSPLJNzDHPjIX1rK1B5JIxZzRzQv
Gd7BuMn6Vt+LbGWWVZbCNXd8D5icxY/uj0NZsl/l1GpW06TIvMrHcGYcAk+ntX2+FxEcTTjUhqn958BjMHV
wdaVKqtvufmicK1tpCxzX5cyc/ZvJyPbLA1UfUbU2UMUFsoniyCRzknvVaGQ3csf2O9WKVnxtnGFb8e1as2
najZ20y3dgqPJwSgyHBPDKe49xW+kXqzks7GXHptzeQSyIfPkxkxM3JXuV+npVm2muNPgSDT7iVoQM/fI5P
Xis93hs9TS33TC0Q5kmjU5z3AH6V0c1vaak/2iyjmjtyMKqgtjHqfWnKavrsNJ2sjJsrKzMgRmkiiDEPKx4
z6AU+9maO2GB5Vq3zKEGWkx3qzZXjXEgZosW8C8yzNgsOy1SsrwXE0scbRISedwIYjPRahK23QTu2Ni155V
nt5Eu8TbfMVT/rMdM+wqzcW9ibXyIoZGkZht3vgIMd+2c+tQ3t+sEk0elFTkAGVlwW+lUFvyEit5YGhU4Ez
qMlj6irjS15mJ3asj0LwOEsLeWGby5IJMFmY5IIzxn0rv8AT763+yeeqsyL92NRya8s0SCIubONwsZIZRvD
4B6ZPrzXa6dBcQtt88FB03DPPrX55mCnHEzb7s/VcFCnUwtNxfRfkdNHd3Mjb3UIp6KB0qeG6CKWmJAz/dr
B1HUrmwmtonPmK6b2YDBArWsWEsBlzzIPuscg/SuLms7G0qWl+gzUmtrgDZJ+I71z2owy26JIsrSxMwBAOO
PetyS2GcoAPY1G9spgcEAtnpim3daFQXs7X2NewZI7OORzhWGM1mazBBfM0IUAE5LAcj6VzF/rN1p8qxsrP
bpyVxyK6Tw0Td2aXEjA+Y2RnqKxcvslPD+zXtWxIrCO2iysfAHRu9ZmpjyNzQR/PkDnoPeukvrXbJEzSSAc
jC9PrXD+Kb6dYZBbMse3I3F+T9BUSk1ubYWDqy0MXxTLBHCN7jcByue57gVi6JqUkaHZG22VsIuDyOlRWWm
XN9dGa4dmY8sxP9K6qz0aFGQJ94DIB7VEZa3PTrclKHs3qEVkLezUxMqysMiIcc1mX1j5kZluZFEmciKPlq
u6kHtXyod+2KjXS9XnVHtLYgNz5jsAAKOboZ0qckuduxl2Fgt8sn2QsZ14KP6+9aTaHELOMzhfNPbOR/8AW
rMjg1PTZ7k7oQXOyRg4OPerN/bXkUciK+GXuh+9TjJJamtSneXuvQde6dGYD9mAhOOVVq5+bzRgSPui/wBo
HP0ro1u7N4LGNrJo40A+0SiTMjnPJGeBx0FZt3EZZBGT5luPmRl4Yj3pN6+Q4QS6alK0upLe9WKzi3sy4Ab
+A+tdRp8c8pheRQWBJkBHX2FcuYfJV5mScsG/dyBeGx1Ge/auo8O6g04McR2qQdzvnMWP6UkubQqVTk96x2
AstGvo/tUdxJYFzjyfLMiR8euc1zl28ryt5SqUX5RJt6iul0Jr65jLMluyw/KMjIfjGTWObG7m1DL3CJEDl
l6YPpTnFWTSMKEuSUlKV7d9f0v95Qt7ybTPMubWUQ3ceDHuUMM55yDwRjNathpFz4nkS4v76GBY2ysUKjLM
e+ewro9Q8HxS6MZY7uGe5Me9k37GXjJ68HFcD4bvbrRfOgfbKC3+sXkqPpWkYuCUZHPKpHE81SjutDqNVtP
sDiKT93Nyu+M9fcmsO4s1gt/Nivi0oOWAJ/WtFb621G8MLGaaONhhsHc+f9ntipdbfTRAdq3A+U7RGnzZ9D
Sk7vQunJwtF7mfpyQT3QV4JJJF544DCpdWgs7fIuj9mhmb90znIhOeucZIqw+rW0enwtbR3DBPvpHFiQepB
I5FcJ4m8RHUHzIjvsOEQqeD7mp9mrFqo3PshZ9RijmkdYvNEi4AIyAc/eH5VHf3n9pebcRJCLgfOyIFjU4/
2e30FUre2WeHdcu/mfwKgwF/CqYs5Q5h2K2TuLMcEfjVRi0ipVeZvuW/t16BdSQyvaNPH5EkcOQjpnO089O
BUWt3mteKrg3GpzxzyBQiNwuxRwAFHAHtxTraAFts8jGMHGFbnFaRshG6mBz9lwSuOtW5zSs9jCcafOna0u
9tRllpEj28MklwHnjGGVMnA9Salsb+WG6WO5tXniQ8qCRuHrkc1o2N4sECGN1dW5AI7+mKS3ubn+0Y7gwtF
Hg8gctWtGbkzhxcXCLuvTUsyajJdS+Za6f9ljGAIwNw4781p6Hd6Vb3SLq+mpJGWw8jO2R74BxVG41K7mBW
GPyh/Gx6moLZv3yCZ1VM8swyPyrra+Z5sLta6fM6u4ltbC8kTS3DW8o3LzuKj0zWro9kbq4ieQfKevzdfeu
VaOESmSzulfefuxxlVHsM1s6cblV2ea+WGAB1NQlcpystGdNqK2tuQkPGT1BrlPE8oQR7U3r0A962ZAIbZ2
Y7mAJAz0rhtb1lDeWm5yp3H8B05FY13yI68HFzloc9cC+hvEeKQrcxyLIuGKnjuDWffu8UtzCA9xf3J3NE6
gqvOcius8SaZNDapd8Ns6uDgEdiK858a6ilhf6c8E4lMqEs6vkjB6V62Q4lU8Qk9paP5bHl8RYdYnCOfWGq
/Jr7hbdN94IUjEflk+aXH51pjV795ok+2utqU8oq4PCZ4H9a0tMnn1jQoppIbeMKfLVto8yU+
+P51i3luY5Q9yBc2ocBwnBHsDX297rU/POpLodheSa+iTTt5EjEq4AJbPbnuasRXljulS6vDYyRuU8kITjH
fIqO4jkhiH9lF7m1J+UyDa8Z/un1PTmq73cUWI7nTrUyqMEup3H3PrRGKtZf8EFLW7I9XleW1t4Y1Y7SWyD
wGNT2dk8Q82W5RUhJxIF2u2Ryo9etIbWe7d0aI2loFBMmC43fh0yc1Qu2ktJ4CqzSpGerfKCR3WkmvhJ16F
oLaxRSXbB1fcFigJ+Zsd/p9K6LTpIHia41K2eCGRNojRMlAedwz3qj9n028CXVrch5oVBYOhVkbHIx3I6VS
sIr64nkmkt5JtNVvnZpQhGfrRJ3V27ISVnZI0vCPkx+ITBG4cZYgegz617HY6cSm/btLdcmvEfBwvLDxzbh
hFFplw298YYZGVBB6gc/jX0ZaLGV2llZu49a+Bx9OVKtKM3d3v8AefpOAxUauGjOCstvuOZ8YWrRaE1+ir5
tsRn3UnH86i8P3qyb7cqEZMFV9QR2rpvFMNpdeFb6JZishhdZF9Dg4IP5Vw+iAyaVYXyfeiARiB1Hqa82qr
O56mFmqkXCR00ytIcovPeogCCfrVyaZmtY1UJ5fXIGCc+tVkB8wcE1cYhd8upZitLW5BF3AsinqP8ACkTSL
G2G2xhaJc7iA560+IgOAauYxzWnInuckpSjszNu4JZIjH5rgdjnNeYeJ9Fv7G58+dxLbs3ysOMe1esyvg/L
gnHSsjU9Mur60dFmRecqrLmsatFNabnVg8bKhPXbqee6XDLJKikFY+rn1rrrS2CIzKASozUgtw1sIZoPKuk
HRfusPUVS1S6ubC1UW6HzHONxHSsI0+Xc7KlX28rRJrHTnv7dLtYxISSNgYcVoLbTQwyRPJ+7HzKNvA9aj0
SZoAvnAhj93bwPerurmeWOO3t23TykBiTwB70Lltclykp8j2POBdCbVLuGOHfHyFcjP510KQSvEkSoXfAHA
yWFah0iGBjbCNUKN+8cHqT70zVfEYNhBpVnDbxi2JIlT75PfJNZKHWTsd0q/tXFUo3/AK3MbUdBmjtTNNay
QRryXxt6+34GubNrGko3TNHE564yV/CupuhqOqQiKW4O12B3O/DEDjOeKyhaxIwhkUeexKqDzz9aTsvh2Nq
bbi1Nq/kULrWdVXQJNAW4STTPN84AxjIb1B6j/wCvXOqXhkTZ8pXjr1/xrqte0e80G+eG7IkliUZjX1Pb3r
Ej2XMReJVHmDJLL86t6CrlKT0l0CEKajzUkrPXTr5mlo/iy/0m1lhgaBgDu2yqQSPYiun8H+KtO1a8mfW7i
CxuEXMSlcqx9j3PTrXns9n5DLJtMjdeT1FVmswqS3BZHdAT5fXirjU2b1RjPDRmnFXTfU9X1HVrRX/0nU4b
uYHK+SOn0FRafYWOqWss1pIXnB+bAwV+oryuC0bzoZdjBSQfnbgfjW7azTW92z2105IG1ZIWIok1LVrQy9n
yK0Zanbto97pdkb77TBbluUQn95Jzjp29a56YkTLPe3ag+YuVVsMAe49en8qNQ8UC+hCamPLuIlCo0YOG/O
uRCyahdSBWG8nhjyBUyprSzNKM5JNz39Oh1XjXWI7fWwmmahJdqUUtKxHp0yPTvXHfLIS2xWlPzYJxV6PSP
KMKsgeUnjB4T1roLTQ4gMwuWuJCOSuef6CrWu5HMoKyOWS4QExxv5bg5OOrfSr+ki41K2nlWyeaUvgBBjHv
Wongu6vtVF0FdLRiRJ5a4z7D0rr7HSb6zLQ25FpB/AAQcVrTouZzYjGxpaJJs8wnjNleF7uJoZQOIyODUdp
c3t1dJb2CswkbHljp/wDWr0jUvDpuZQ19m4kz8pxg/SrenaHJpt0k1tpsETKOC/zc9zV/Vpc25lPNqfs7ct
366f5mBbeGrq0K78GQcnBzitGDSZmJEknOOMmtuS1u3ycFjnooxTf7J1GXkfuweld0YxirI+enUnN3kzGuL
Jk527hn160QRW6K3mhC2OMjOa3V8L3EhVp5yR1xmta18NWqjMr7iOwFA1a25zejpJHC8UUMQL8bt25gPYdB
XQQQyfIWjRFAxnua2IrC2t48Qx4HbApqbJJfKDIMdS5wBUuy3NE29kcprN2I4ZIZcrI3+rKnr659ua4jUdK
+0p5iNuePj5Onriui+IE9nFqEEa3AeSMNuRDkHjg1ztpqs6RPHAikkbjn/P6VxVGm9T2sMpRpqUNzUfU5L7
RJ7WVNp8vbk9iK+dPFNzJP4inHRYX2KD2Ar2HXPEUOj2dy2oONzY2oO7EdOK8RnupdU1N55VBkkbJCjpXoY
Gk1K667HiZzXiqfslve7PQ/DkgktYozIsLyOMtuIAzXTQx2emS3H2vfc2zfJErgnzM9SCOODXIadZSraxNI
D9jc7Sy8nd7jrXe6fYq2giGC/eazjDGNJMZL4yQPb3+tfeReiPz6aV2jMsrWae6UWSR72yI4C2FJ7Z9x71d
tNMs1hxqtndzXuT5jQ8qD6AjrWFLBcy2ySW2Rbs2J2jOWX2xXYS6ta2myHRNSMVkqLhXiO7djnOe+a1lF7J
mXNbVowJNSupZIdPgto4pdwjjhD4wf7xPf61NqGkW4hge8ZhK+WDq+/eR2Rew9zVbTtKe6maK5tzcBDsEu/
a2WPygHHXrxUSWEh1dyJAXhBQmeUYiHTr+lSpJ6J7D5Wnr1L1nY6fqU9z9glwLdFZY2wk0hbGQq+3fFT+cL
OJH1PTpIoCDt+faSPU56A0+z0171o4bK6sLtoh58s0TAPAAcdTgn6VW1WK41O9ntpJJJntyGGTnaBzlmrN2
k9WPVGa2rRS6rbyxwKsgPy5yB16fTFemWniSzVLZpZpAuMM4BH4V5lY+HNU167l2LHD9njaUzSvsRgDjCk9
T2rtvDcNoNT+waxbCW1/vLJj5scc/X86+V4gpxvCS32PseGqn7upCWy1sdsfGemWmnXVtPObiCRCqZG7kjg
duPU1V0CdW8NpLaCNYJImyoHAIyK891KzMU8wtlxJCc7GI5IbGAO/4V1Pwwvxc6RPBIMW4kIKn+HPX+tfOS
j7uh9VywhaUep0+g3iT6VH8wZlJB71cWdAWAxuHasjU9Hl0J/tNmyyWM5zhG+4f8Km0lPtEW5WyrnJbu1TG
UlpbU6akISTqwfus0km3soU5z3Aq0JikQGSW9TT1jJwFXAqJ12k5rpimtWcE0pbFdS7OS3X2q3BFwS3OaiA
wc1YikAAyRVpGcojbuzjni2yDIHoazjYiUhJl3ovQNW4gFZesa1pWlKf7QvIo37JnJP4VnLQdOM5PlgrvyK
jac4OIcBAcqnQ5qtfzCG6jluEa3aMYIJOG9TT49TttUt0Ni8lwJj99PlCD1zTp9BW7gK3VzcyIwxt8w4rnc
ebWJ2xl7N/vtPzKkviK4ike605bdGA2lnRWUgjHTHXj9a5uW2k1CZ7m2tXgjRsNKBlSf/wBdbieFhb5W1u3
2g5WOX5hntzVeDSb1ZZ1mlZblnLqi8o3f5RUVINrU7qNWjC7ptXFuorjymtCkjSEZcbec/SsW4sNShBa4gc
jIK4+Vh74rsPC1ul9cTf2rcNZXMbbVZgcFs45wK27nw/dXtuXU+XEI2leVyPmUZ5HOecelQqUqi5kQ8dGhL
klbz/4Bxl1FaXels9/qcceqrCcC5ZiWwBtUcdxwPpWBd6YNGRoSYrrcQyOhOA3qp6HqRVtrOTULB7qbVUjt
La4JhspSQzuwxvTPB6YPPao7z7UbW3tuRbD97szxnkZx60ScbJ217nXThJPl5uu3+Wi+78ShBbPqNvMjHa8
fIG3OR7mmrHbWFhLYXWmxtNM/mJfhzvVcYMe3OCD19etdJp6W9hA115kqyuDGEXgYI5LN/TvXO+JfIu7tEt
5N8WclwcjOOgpU046sqTdZuCul939fqYBgigmlaKdvLz0HX6CrEIkcN5I8tjz0zVmQRRSKj42DGQewq491H
Dcm1t2QHPzbQO46Z9KfPqDpNrTUwJbWRpXTed5GcZz/APqrS8P2E1uss7IuCQAGPP14rY0y1MkV1KbKS7hO
1GZM5i+bIxjg5wRzXTP5V6rpHpbWKxSBdhIBGBg7h2boTTa0uiJT5fda0+Xl8znrS2gWaWacld3RE6CtXT1
iDMwTAxu+92pFtor6/ltnW6SI5QG2i3szkcKRkYHBOfau40bwk0Ni+
+RD5X7pZsYLAgEKR64NVCnOe2xzYmvRor3nqyPR4YWsdiFzFksGbjOe9XLuzhismLFSMZBFaJ0+OKxYH5MD
gdjj+VYlxcpdyKiMBBHwD6mvQp3grM+fqP20m4jdMj2Hc65YDgmr0xfbtwqk8nNZkl4YptkSgD+8apPdXNy
WVNrBeN2K0Tsifq/M7yNVp/LPBVsDHSj7axk4TAHqetU4Lok7ZFX5eMVJcSNMFMEKwqowzbixc9jz0ovJjd
KnF2sXftq+WGbaoB5wKry6ykWWbhc8sR0rOuo5kWNwscgJORu5BHfGKqXmo28aEPCHlwSw3cD0ye1ZTnJHT
Sw0JK6R18GqRQWZuAIjhScls4+oxXj3inxE+oajLLF54gQYVEONx9Til0+O51KS5KtI6r9984B9hz0
qrrzppdo9oY2hYSBpEkTD8dM55HXNZyfMrs66NOGHm1HV/kYdpe+Tfz3N/FG5kjZUEucBscE45rNtL25hja
4ba0pIGG6MPWrEN9FqkoS7ZVhjkOcDHyjsa5rxd4utobh4dP2S7BhdvRcep71cKLmloTVxtOjd1HY5zx5cM
+qCF3zj94+Dn5j/APWrN0SFmvUNuhkkB4B6fjWbNLJdXDyysXlkOWJ7mvQ/CdrHHp0ksoKxxAF2UZI9q+hy
rDqc9NkfC5ni/aSlU7nU6fpU1zYvHIhtrqJfMmDdAnqvrVN7640bUYblj50ca7ViYfIV9CPeut0iQy+FBqu
oW6JCWMVmok+d29TznArmWO/UGiZTeNjdI6qSoA7Yr6mD3TPm3vexYa1a5lS/tYHt8gP5MbZBJ7U5b7TZWk
a+e4tZdxAjSEMAPrmkaGWyit5tLuopImGRGHO5G/2geKZ9oubj510mJ+27zAMmk3rZbDhG+5qebLprzyNGq
mSPYmTt2N3P5/jWdDoY1eGKSK4jilnl2JsfmTHcj09zVnV7SaV0uIImmsyhEcruCgC8ZIHT8aj0uG7t7Vrh
Ci27LsWOX5cNnnaDywPtUxfu6PUXW7Re1c6dp1wbSyljinSEILqULzgdMrxntVa3vLu10U2zSLJYXDB3MJG
+Y9MMe2PSq4Wb+2xFMkEtzKoBgYDkew7GtG4s7Gyge3sbdry6372hjf5Y/XBxyenahK2m4N9TLuSl+7RzTS
29kgAWGJi2D0OB+Pr61veHtNuNPWLyboXdjIhEa8EHa3I+ozXM2twZbK4aG2C38bZZ5jkKp4Hy/XAzWnpWo
S6FbSNq9h+
+J8wzoNxYY4UDICjvxzXLmNF1sPKnDftod2V11hsTCpLRf5m7qkBmeSRI0KsNwwcsvPb3rE8EXZsdZ1Gwnm
kSJ3Yp9D9a0X1TStWtzNp0pSI8lg2GXI6Yx1zXO21jdZXVJ54ZXMjR+VgmQouMN6AfrX5+
+ZOUZKx+l88ZRjKLPadIuxqdrFp9oixXNuN2JeFYAdffNTaBC8Rmim2h45GU7enWsay1efXLnSNl4kZit/J
GzAKqvYk8n8af4auJHklRJDLIzlg2fv571jZJ3NqXNKEovTr+Pc7UsoQe3tVWQh24GB0qRc7AG4aopCVTOe
a6ehzRVmIycUqxfxdh1qITEMARnPpSmdc4IIFCaLcWWFlAkwCR71z1x4W0m8mnmu7fz3kOSXY8fStoxzTEi
JRkDruAqIO8DFZRzjsc1EoxnpJFwlOnf2crPyI7K1hs41ht4UjjUbVUDAAq+ZEVFXOT7VSEzswBXA75qSJS
T82B6VrBJKxz1FJu8txw2+bvUEgdQaZfM7gPC22QfdZe1OPBPOKajEj5cUSHBW1Oat11efWNSuLhrGNk/fq
rt5Ql/vBR0JHp70+41DVWUwwGAx3CrxcR79p6/L6dK1NY0oatYTWs5+RxkEHBRuzD3Fc1oY1nTZI7TVIUnS
EkJMCQWHb61yThyvQ9SlKM1dpadLG346mu9Z0e1udRjtLVrAfukghKgn8zx6CuLgi1UoLo6bPLC/zGRTv/A
Bx1r0E6zYraiDUVkHmEKCUzzXX6fa2ElqyIQTtAj2/zxTdFVn8WplHHPBU+R09L6dreR4f/AG3bP5kU7Fec
BGU/rWXfFHA+zFkUc5I4Jr2Xxp4P0/VdPMscO29hUlZAOWb/AArzbw94bGqarjVDNHZRkbzGuTnPI/pXPUo
zhLlfU9LC4zDVabrK6tut/u7nN/2JcTQrdTyyOpHBxwKgt4m0+4zJHFNk5w2cA/hXsviuXwpZ6HLYwXV7FI
Iv3EWAzFie5xgD261xOh6D/bEUa2LyTaqZwos/K+Vo8ZL7ycDnPFKpQcJJLVmtDH+1pOc04x81b5/8HoZ/g
fxFceHk1SCezW7e7jEcBuOYoznJYr0Jx0//AF1csvEtzqPiC9W7mije5bKpCMRqe+0ds16rf/BvTrwRy/2j
dxSoyuFAXaMdR/8AXrf0zwd4P0Ly5LLTYmmDbhIC0r5z6kmulYas0ot2SPHq53l95VIRcpy7Lbbv6dDjPCV
mt1rBSNrWSSNP3jTgFYlII3dRlueK3r8NbFbW089oYus8oXaW77cc46da6C60zTrvUU1A6ZbrLECVkK7W3e
+OtZOoSKsMsk+GRFOMHGTXTClyqx5EsX7eop26bef6/gYt9qE8ar5kh2EjaoAP41hXKbicHavbHGazb7Xv9
IOxCxBxiqT3V1e4Y/u4wPugc1Em5aI9KlTVNXejOhCu9ts3Ii9Kks44IMxiZSw/2qzbSLdBiTLuemTUrRLG
V+Q+5HtWsadlc56lVSbRrWcMlxd+TDGJJJDhF/vVoR2jrZPPJAVTftUBSMN9c/T1rHsNTjtJbeYEI0b/AHm
GR9cVk+OPGt1ChzO8kpUxxkgDA9T6n3rRvlRgqc6s7RWhk+IdeQXEltbSOAj/ADOhwW9QT2FUbOzmvWdbp/
Is4ZP3sRJyCeeTXJS31imnW5jkme/kLmZWACoM8YOck9c8fnVT+3TpVlLCzom/5gzHjP8AWuezvdK56clyx
5Yux6HczwxQSPaOsdqP3ahf4sdSf5V5f4o1aa5mmNzKzyucPLK+449c/Ss/xB4wuL20xb5WL7gCDbv9gK4X
WLy9R2t7i3ktcjlJFIYj8a64YfRSq/JHkVc0jh1KFLV9/wDgkut61JdH7NaMUtk4ypwX9zWHinxRPIwCDrX
Y+EvBMmuTSQmdIbhV3Ir9Jf8AZHv+ld1DC1K/wrQ+axOKu+eo9Wc1pFu0s4fYzIvUgdK9R8O20mnRi4Ijur
ZoshGXjJPRhVnU/Dv9jSQ21rEDfxINzIm5EPueQT+laEN69pb2un6npsiRofObkYlc9OQOF9ua+lweD9hFJ
a3PDxOJ9rtoO+y6f5cNxdRTWs8hJjtVfAk+gP3R71pWWoWVtY6h9uQ2Esn7yRSTuKZwI1PfPc1ja/qdlqF0
0bpJEPLGbgnHz9BtPoOOKu2bz3Vstl4mU3NvbQs1rcBQxJ7Dd6d67ZPuclupCNQne6S5iiifTok2/Z44x8o
9/f3NVmhi1R3ujq0FtuOBEsbDbS6feR6PDJMbkRSPzFHtz547g56CuibS9P1BIr3ZZ2huUEhglYKUPTAGen
FVUkodPuCKcloxbDVIIrZ7fVrCO2vYE2yLHHs81gflOzgYI6+vFYGoM+r38U010Ib4u3lCPG1MD5QfT0qvr
9xHJGxsRciMyBZJD842jgjd16VTW/mB/wCJWi/ZScDpvYDrmphFLbcG+Z36GzFGqrK2ogC6i+SO6jX5ORyS
xwSfasm8ml0+7kfQ7m5uXA2vNtKqec9PTpV+51o3FvFC2nhJ1x5Ub/MkfqxXqxq7Po+pW9iJPPmCxr9qa3Y
jZCpx19zgHHWsJ15QkotaM1jCL9643Tlg1eES3EzyyHiVkQhs55LY6Csq9uJY9RC2ULahaQOWMfODzyDUml
XdnPM8VhJc+dIPMvSw2w7RznHX/GtFY30jXYrG3Vns42zOYvl+VgCcMe+PypxmpN2J5EtWYVxpjSeZdaba3
Gls3JjuCPLyM4APcViCz8V30CQW8piV2ZTI8oiQ9DjJwB2rsdQms9bedL+f7EIsmBACxYdgSB1rOuBE1t5d
zby3cZCospkOC3cgduMflXPXy+nXfNUjr/X3/idlHMq9CPJCdo9hvhu7u9MsTb3pl81E+Q4B3epz35rv/Cl
8ltBBJbqTHjcwzkrnqK4bXVkhjhCTSXKW4CbpBjykI+UH2xU/hrU1s54rgyEQP8rpj8q+PzLCRpVWodT9Cy
PMPrFBSnutGe5w3yzRI8ciMMetPklB4ZsHuK4KLVIEhNxaty5J2Z+X8Km0n4mWTaPEmo6NeLeW7uk00SgxO
m7hlJ74zx7V5caj1T6HqVKHLZwTdztIypYgtk57Va2DcM4zWHZ6jbXqJe6bJ51i/KsByPYitCG7Ek2d7FM8
EjFPnWxnOnLcvbDnpWdeX1tbCR7osqp6VoNcxDClxWTd7ZNSKyvClsQMvJn+QHT/ABolKy90mjG795FrS5h
e7JPLMQYZUPwa1jAvKOBux2PWuWtdTjk3Rrw6Hj3rrLeNp7WK4bCnGMnitKcuZdycTB03d6IqvZDyiqliff
vUSw+WcAEH0rS3EgAYz9KNjbsZBPatLJGCqPqRIg2beTmmXEQKjCZx1z2q4u5MADBPXilaENk55NDVyFOzu
YU2nR3AXdEGUdj0qWWfUrXVnvA0To/Jh27cem0jpWpLGFGR+VQSr58YR8n0PpUuJqqvNurobL4stwkkdzFN
C6rliyEgfiMiuW0i5vm166uI2YWV4S6uibkz7elaE01xp9wDtYjp9RXXeDdQt71BausflKDwQPlGeR+tLl9
q1d7DnNYWnKUIXTOJfwHaX0nn/bZwxYs4AHJ/HpXV+H/DWn6GrTWnmtPgfvGfJ/Ct7U9FjkjlezJjkj+Zdh
+
+uao2VnBLA63kszIw2sofb/Kto4dRd0tTiq5pVrU+WUnbsaole5s1N1cKqLgjruJ98n3p63SMqm1t5JXHyK
QNq5/3jxWZHZWNtAlvZQuoByA7byfxP41tR3RmijjIRYlIUqAf8/hWyg1ueZOcb+6tPuMbxC2om1tds8UMc
soBCHcSoGSM449OK5jxDe+RC0UmAjjGK6jxJAP9DniKiK3A3AcDLZGAK4LxVKs16jHLIpxtFQ46nfhJJpaG
GYxJah4I1GDjPrzUsUQRVycAjJ5qg0ywjbESgXJx2q5byNNDncB3U46U0kmdc3K1zShlSaAhcBlJFdjp8Gn
r4R1RZpbc6gqfMZf4eARt9/cd6840q8F688UMTgwH55P4c5qe+n+zs1xPFFIoVgVkztwR1z6iqTVrnNVoyb
5L2Zj6hrkempIjKfNKgqjehHU15bruuXOrXxdWDJH8oA4yfaovEuqYmmSGXdO33jnO1fT61a8IWKSPHLIoE
e3lmHQmuec+WPMz1lCKl7OHzM46bq5Q3Ekflq3TuavaX4LvtS1e3iusSblEn3hgJ3P4V6wNug6KpEtnNE5I
RwN7AkD1rkvE+tR+F/Ct/qbxquo6lut7cIccHqcdsVzU5TrVFBv/AIY2reyw+HlVcdtr9zzjxj4gstO1+90
qx061utJiDwPDOnJbP31cfMrAgYI9wcgkVysMeqX1uqSvcTW2RgMSwH0z0rsfFieG/E2l6Bqfh+aWLXjCsG
q2EqswLoMecrnqGx05I/Ct2PTG0qwgd1lgR1UiJD98n1PYV9ZgMD9Z9+ei29bH5vjMX7N6atnO6P4ZKQ/bH
QTW6YBjVh8jHoT7V32g6b/ZdodTFy0ttkwvNCgdom/uYzxkdDWZoEVul4BqMf2e4YARxudkTJ6k9zWxq+mT
6bbSNZhra3uRuS4kYFpR6BRx+NfRU6SppRjoeJUqubbkLYXU3iTU3tIIZYtLJIk8qTayqB1ftk+tQ3lrJ4c
LQ3TzG3mOIYphkhOzE44BFQ+HJYRG11bYhuQwV4ydq3AHqOoOcH0NLfX8xvGupJmu7iQnd5oGxfYd8Vpy3k
0ZXstSrqdtapYQSMolachoxE24Rr6FR3NGo6jbQpFplhDObQ4MzOp3n6DsKv2K2iTefoYtvPxmZJGLJET/A
BD6VFqM0NzbqiSmycHb9qVQfPz94t3A9PaqSaHdXsZslm0cM4h+z3UCY2mRwSB6L60QBDEpuZmic9EZgdo7
CtCeyGmqV1qNJrQR4iFk2MMMYZh9OaoQTw3gaWMpDHuIRWQZK9icnrSc1FXuPlcnaxpeGYVilnbzJ0tpSY1
gUKPtBPoGzj+dWb2wt9Kt3uY7YR3KOCoAwqHHTPc1Wv8AS77SrnOtskcCvvFvJxOpIzuCjp+fFWBqY1Ji/w
DaAmgt0EaCbBkdehCDp75PNTbXmWqYPsipp99p99ZzzzSmz1dGYiVwWEg42qM/d6HkZ61JeXN3Y20SX0rXE
cYGUQ4QZJONw+8ef1pNMvY1neC/haTTfmJkmwxGOm0gdfxqlqN3DPK81mxWFG2JFtIjIAGdrH+Kpsr2toN3
+ZetrfT9RjkTXJPsE7IWhlTC8dg6jn6VHeWjRpbwWiMzpFuKMxARs/eJ/KmadYxzzy6vYTSJNCpDJfIW2gn
GRgYyOvOKtQ/a9av/AOybZ5pLiUbnkQcNt5ySeccVCjZuV7Ip7KNrnNLZ3sE7ymWC5uY2P+ik9fU/rWnHNb
Xmgm+u/tB1FpDCttFtWNFA6kdc1u+IdFg08RvJItxfjLC1iiIMK5HzykeuPujp3rKtIdQ1YTWN1F9o1B8vA
Q5WGCEDLOB0/wAMVhUnLl5uhcYq9jEi0a7u2hh0/UFlnuG2m0QnAPbOeOn5VHbwvbvJb3BVTE+xyDlQavxa
XFoLSTW+sGZ5Lc7iuUJJPKLxk/Xoe1XdJjXXdMnt9OWNri2AkllK4Kg/3vWvPx2FeLp3WjW1z1spzH6jVs9
YvcraTdNaXPmSSKUDYyegrs4dff8AsptOeUCzlfzRHHgqTz6dDXmK6qQ81vdRsm0gtGV6+49q0Y4olBuLOS
RCoDKifMD6g+lfI4jBtSfN7sj9Dw2ZU6sF9qPc2bBde8KTSXOnzynRpXOVKFkTvjPTvXXWPi2G/htvMkSOa
LOWXjOexqt4b8YG10C8lS9tV+0xG2lgG1ZPMOcHyzkMm3HzYHJrnH0q3e3XULB4BKSQ8MW4lMcZYYwM57Gu
WdNxWu53UKkJybaVr76npC6ipiE5likUDJCtzU9jcWdxNHdysxyNvll8Iwz3FeSvevZXcUV67w2+MtJGN7H
6D1/Ki38Qy2czNbTtLC/zbJB0+o9fpUqMnqbunTfup6n01psnh/XGe3tNNgttRkTBYJgEd9pHf6/nVyy0cS
abdRq8jG3kMakrnd/h9a+cbLxfHlZYHubaYHrG5GPXBHNdBovxE1vTEKabqC+Szhykihjn057V0QrRXxRt6
HmVsnqWfsKnbR3/AD1PYtRsBZRK32iNn3D5AMEcZ4z1HvVaEhjyAPevPNP8dQXMrrfuEn65PI/Oug07xHDd
KDaFJpOu3fj/AOvVOrEylgK9ONpa+Z2NrazXRkECghFLMSccCtmw0GCe33PdbpWGQI8YX6iuS0/xbfWEEtu
unxzKW3ESNjP04rlE1u/try5kS4liEuXMQXIT0wT0o9vCNnucn1DE1eZJqKW3W53up2slhO0MuD6EdDWO8o
iIY9Aea5pfFN/LZymeymu7jICzMdoU55J9ararr8zo0iWsnnvyyjG3p2FL2ykro7KWCqR92f3nS3ha+uEWI
KV6dRVJC2kXkV421TuCv6YJ6/hnNc5o/iKC5GLhmt51xlZBXQ6s4l01GkO5evsc04tS1Q6lJ03yPZ6HoS69
bTrMIVUsnKyL0YY/kawpb7yrhpGRUjkP3VzgGuV8OXKi2tlDkxkFAx9j0/SukjMc6lW6j1rsi+ZJniSoxpS
a6Gib2PZvZ8FRgGn20srBZU+cv1A44rEMahTE4O1gdh/pUdtfNZzAZJj6FSapy7kOkre6aepXTTXYUkmC3b
BGOASMdfx/WsHxBbCKPzRjbjj/AArRvdTs3sLh51cYyTxncPwrJj1YXls1jd2xkbblS4wJUxw3+NZSkkdFG
EtGlojg9Y1q0batosktzkqBGuV98mrPhpr26tpIbxViYkquBjArqDpVrd6UjpbQxupJTyRjI9CPWoNKtXad
kRk8rAxtIOPWkm29T0J1Iezaitu5s6FoS2dk+6XduGWx/F9a4L4wPLpljpqxtshu2ZW46Y5r0q1f7JH5bNv
XPXHSuF+Knh+58Ry6cbdgREzLtz0B74qprljocuGqc2ITqPQ8RubaFppjZWrzfLkEDJJ9TXReFWuVWGGKz8
wSny3idTnPU4/DvXUL4O1TQEtXW2jninkEcjRtholyMtz6jNdRruqaT4X0u5uoiVt7ddxAA3nnH48kCuWNO
VZcr0PVq4ujhfeg+a/3fPqZf9h22lWN9fa9cfZ9FgQNJG+GJbsB6E9K8c+LV9Hriafq+iTPNoBTyUhEWPsT
j/lnIcn5zgnPcdCecW/ih4ruvFum2k1hcyQ2DoBPYuwDLMvJJ9VICsp92HauX8FaLq187JZStFaXeIpV3EL
KAQcMO4BAP1Feng8Dyy5aa9WfLZnm08SrTfu/mangvTUtV8+5gdZ3HyPtJCj19zXbxn+0L+LTLcXTxvgsD/
y0IHoOmOeaW/isvDaQ20F/FdlvlklRWAjHcfN3q1p8dzpkV1rWj3Sz2UqiB2kO2ZUbsB746jivuKNOFKmox
/yPiKs5VJuQ600hXE8GovHeadaggySShfK/2Yyfvc9hWHdu8sfnLcyzWtr8gmkbhfZR3rodcvre+e0R4pIL
aJAQkS5CDHRj39c9az1S3lUm3m+eNtz2Tk7ZR2I961hfcyb6EsN7ZjSI5poo7m/YssLoNjhf70g6GqKN5Vi
6zRpcpO4JlBBZR/dI9Kl1j7OiQzz4bVHP/HrtIit17ZP8WasW2sR6hdW9jc2OnadcH/Wz2ybFZB0AXJ+Y/r
U3srRQ+XqGjWy6fZf2lZzxyWSybpoZrc4BB4Vmx0J7A1TttRt9V1y+uNSMUQO51ht4tke7PCKvYelaXiJYJ
Ckf28q7JsjtihRAQMjPbJqjbKk9sWv9OC30G0pNGcKgHdgRhu1JNLfcdrky2x0ax+dd93dDeVY5ESHoAO7V
Vmk09ZCILeQ/3/tC4bd349OlPlV305r1rqeS3hcKr7SwLHJwBnjueOK2NIX+07U3mowWlxLIxKyzSFGZRwO
PwNPzZK00ZT17U7t75Y7iFLuWJNg3KWJPdieuT1qj/ZtpqRD2lutnfQDe67ztPP6fnWlrKX2hMllcTlUKsV
vYHLpOpHRSPrg1V064udP0soxjMRczRs8e55TjABHcenpSXwrkK1TfMQ6vqF+peZX2KR5TtG/lxhf9le4q9
YXkqi2j1CaG7tGcMkgXEMbEffdBzn9D1qHRtQstWaZdVae6c/6m1RcPv6ck8Ko49+ak1K/TR7i7h0Wxj+1O
FVxIN6gY6KOhHuetRKKva2xSk0tWaPiGeygt57OC4Sa4k4maN9sWfbHb2FV4LzVdRuAdXtIJryCMNHe2rCJ
0AxjO3g8dKxzd2eqWLsz2tpqIYb0nyOP9njHv+NX9T1qHTdPtrXSJTHlld5lPzOQMEdORzx2xQ1dJJa/11E
m1fsZ0d7PeXV3dbx5QciQsS+4gHAAPfryfWp9HvJJ72K31KH7LZ8vaK427nPrIf4fUfhVZ7u0ntZbrDQTxl
REYSE3YPO4DnqRg1uafPfaXaTXN1drfrds0kkbpvEWBkv8AMCdwFZOV7ou1typa6ZfavfyR6PbvfTW2S00o
+TbnnH90cnk0l3pa2sVxqWtRNZvIQbaWFhGrc9cdWX0PQ1o+HNRGjyyfZ5Ptdtc/PJGCY5pc/dUnuBnOB1r
L1TWP7T1Zbm6eXUVDiN7RYcCNF/hAPTHI4qK2s+VP/MdJPluQm0tp/Kv9buLmOzdzILryN8h+X5V91JAHJ4
61hXFz9mcPFDeW1tIDiQx4BHqRXqGlvaXMK2trfO9t5Z2298h22UoBwf8AaOOh7e9ec/Yrm41XEUYkIZkVp
WJ3EHjjHP0rgxGAjiZ3mvL+ro9PB5nUwceSnZ+v5aMzZNOjlUXFtNEwPBO7t6020uJ7Uxy5bylyMFsB/rit
G50rRL8w2mo6bNp12ZXM11bykwSZ+6uzHy4Oe561leLfDFspa00a4uDDB97zckM3+yBngV5NXKKkbq9+x7l
LiKF78jXfXQ0ZJZb6FTNIVQfdKooIz6kdenenXlmltBC0c8cxIO8BjkEVkW/h8aBYebrks7yXEAktxE+cZ+
6SPTjoafo3iiyjtbi2vDBKsgx5hX5wR0we1eRUw9SDtY+gwuZ0qsU20r+f9WJ3glSETRkKwPbtWVeajcR4k
DqUI6g5Oat/aUllkFhMT32HkVQvI3nQjcAu7cQOx+
lTHzRtWqy5X7KWoy38TXkTATDMfr0NXX8UT8yW7MoY54z+lVVWCaCeYJZobeML5czMXnJPVQO4H4Vji2bEp
jO0g5CZrRU4S1kjhljsZS9yMm7Hap8TtcggWCK7mKgYBY8/nUI8ea07lQ4lBwPvHIrjYCdzCQA7hgZ6irn2
ZlI2RuM9DT9lTW6Mo5hiqmvN+FjptS8QeI7xPKW+a2tgvEcLY/M1Qsp9WEqLBql2bhzjy2Yk/rWhYRvFbpH
qBEMb4IYjINa1zpmnyXPm6ffr+7iVxkjqfQDuDng1i20rI9FLnak5O/qRaTc31vrSWXiR5VEv+rl7K3r9K9
M0vV7ma2SzvJo3VWEYIHzHH9K4vUtUXUbOKz1IQPNAo8q4hUgjHY+ufWrPgzXdPW5MOoyKlxG+5efv+9Zu7
dzppztDklr2PR4IFhZZGuHijZ94UnADf0zXT2sqzgFf9YOtefa74q0yK0lgmYnzVIXaM/jineC9dmudPjYE
u65VSTgsB6/hW9KaUuVHJicPUlS9rJWPToivAYfrWfrdnuxPBwe4qlBr1sFBaQRtn7r8U65vvOiJicZ9McG
ut6o8dc0JFCK4aGDb52H5BDevpWdZObuUpeCWGa2+ZJVf5WP0qzqV0RuD28cjbDKMHAKqu5sH1A7Vn6peWd
il1fRB3giSLOMcBlB6dhk4zWPIpM3jieRPzNPSdUnhvpLeaMy2g+aOZVxjPVSO/wCFV7rTbe016K7sb2e3W
VixxGzJuPUEDoPrWfL4gjt0tkSItdXdsLuCFDkumWB/EbTxXO674xulhuLizlhzazNDLGQQVYFRyeh5Yj/g
JqlQUvdI+vOLclomerM+1QZXHPdelQ/abO1czXMnCjcMnjjvXlV/4vFzr2m6ZHq89vDrFvZtayrED5cjy+X
KDnryG57YrM8J+ItN8VeIW0CVWe+LvDbPfsMTq7DejY48xQMp2+8O4qnT5dzn+sq2nU7/AF7xgJrSa/tLUX
WkWu1p5g2EVGbbuBH3vmAUgdyK831LWLLS/Hl/Y65Ob3wxr9uPsV+pB8qJyQP+
+ctG/cFc9sHj/hrrmqvaa54XWRpNMv7GceW67vIkXEgdB2O6MZ9fqBi94U0iN9Fey8RyK8ErNNpz4JWGY8E
kjojYAI9Qp7V0UsLOs/dXu9Tiq4y3xPXoYmqeFzpGu3Vmk6X3kErDcR8K6j+uK6XwklzA8DWSPFcEmNZN4C
8j9DWzYpdeG5zaavbCGK6O2QgAsYyAMIcH8aku/ImcWGniSKJ2Xy5HTO4jsAvODX1OEwsaMNNfM+exWIdR2
Wi7FS40q6ub6S0LTXE8KkylwoQMMkc+/wBeam0UNZXKNOjtEwO20aTEbvjHP+NSZvmeDRtZWdYopNysG3B2
bHG0DknjBzVjxBFDbo8d1bmLVFYMI2k/eIAPu46c8emMV39LS1v/AFc43vZFC61C4itb2W5j8i7IYGMKVji
UelU/CF5cWk8l9ZRwXcp+Vmba5QkdSp5Ix3GPrWha/wDEzshJcSLNdyt5AtmkPmg4zuOf4QKsz6VceHtOhh
soTHHP80zhC8k7EkYAHIXPTPWs5uo5JaWHFxSaV7karbaqwtbeORbt5S9zO7fwe3oOtXLrRRYrPdTh1ESB4
llI3SqOhwf5VXghsfJk1OK5NndH5JbQptYsD02+mRyKZ4hury/1Rp7y4WS5uNhEgUjGBgBQKtLmlZEN8q1M
eSNtQtG1G6SKOBH8pYhzIW9SoO7v1rQtb97fQZbSRVgMpy6OzFin90enNSvbb9SRxBNHqcR3ecAAgK4ycc8
fWqmvWsxtzNdzCRbpzIcjDO2Tkj2prXUba2ZPZ2pmuYJ7FXNmiGUQefvaIYPccdeSMVasbGO5tlm1G50+2u
G5MeSvHqRg9ai0a3xp6w2jPJpNu3m3GyEmSPPBZwOoHrVi+8QwC6kWGzconyh5sbnx/EaVn8w6k2iTJFPFa
3CtcLMROjSMsaTEdfmPG0YPA5NU7m8a912e4sZ7e+ljbkt+7Q+u0cZFTW/nWlnOukWEN5IpZjPPguR3KqTx
nnjFRaXpsesWFxc6elvALdVjuGuG3SPI2T8i446Yz+tQtLt+ho7MuusOo273Emm/2LIoAuJ1cFJB1ynHynj
sec1Q8QZ09I2UzLGgV4VY5dF/hyelRXd7Mojiv2SO0VwptmGN3qf0xU2sRvFaNei68yGRhtgmi+cLgc89u3
X+dVFJNNkPXVHR6Xp83iCzg1e60y1j3sFtoo12veNnngdACOSTXPappt5DrTtZ28lxe5KSfIfLhb+4Ox7DF
aVrpGjizttRsZJ7DUHctBZxzmWZjgY4CgAZz78+1Q6VJqmjXjyusiOzeYtu8m4Svz8xXrkY/OudJ7/g9P1N
G03oY7aBqWrvNb36JaXdupAugoRA2QcSH1/PpQ8Or2srOMaksTbRcwr+44XlcYA6dRWtqviCPWofst9bSWV
hJ825gWYNxubjuT/OpIblrS2Gi+J4HMVsPOtLhiyvKv8ADGoBHPPfmuSrzRnzfgbw1jYgiSC+jfUbCJ9LuH
xGYt+ftDcf6rJ3KfXHHp6UkVq9to6W0EElrdy7zeTscOgXooHYc9utS6tFHdtarpKtJeRAEmPMTwyA4CoQf
mPcdyfSk0qQ6naXlhe2Uw1K3kaS4vZZT5+Qf9UF6cnp396mNS0k0rv8gcLxd3YZa3Uum6M6TxQy2ewyedCf
nlJ4wSal8NbPFNm4khtldZAkSByjyHqAAOmO54qPWJws4WKOW5vAcTxTSYjjPZVAxzjrUWkPczJJqcmlfY0
hQpJeITEJGPGwE+3XFdk9VzVDCGmkToPElnLbaHKNNe0jWNjG00C5WdickA4wmPrk1yyf2XdNNtnGnxwKEh
tLhz5krYyW3Ac85pJbe7WwjuHErW0+WiiUbQ4HfHp71HE2mSRNdXE5e4VlVTnaVJ7L6KO7VhiKKhBzgbUan
PJKWxX1W/sr1/s90yxbiFeUbxkAcFhzjPTin6v4G0S1hn1TRzDdR2mHUJKJA3uV+p4HtViWyke3imuWtIrS
MlBHbjMkhzyAT196p3ph0/VIRLPI82FVbaEbNq9FDE8EjP8A9evOqRVWH7y/mdlCo6NROnbTa/8Akcp4l8Q
3GqJDBbaDYWcsIKtNb2wheTnqwXqRnH0ptnZXc9tbrdyxu8gLjYOSM9Pr1rpPEGmSW1zEjBn1QgmRI3zswe
7ZPzcfSny6vY2L6Tc3uhvIUyrRlyfMPTdkEEH2H/1q4a2AjCleCdz1sHmU6mIXtGuXr0Rk2HhaPVrj7NZ3y
Lc7ifLlKopUDOAxP3ieAPpTvFPhO10e20640zW4NShuo9zoiFZLd+6Ov1796nvr20u7aX+yvDeoC5jxJcXU
kmfKJ4wEAwFz0B59zVG31fULG/fULXSpLm2hwhF18mXIOGYA5z3wOOK82NCt/KevVxeFbup6fIp2lnnnzIp
ATwNpXp9amkvLKKRlGpxK3TahJGe9ZzeGpGhS5utQUyzMd6RSBiCfUVfHhXTLZUZGk1EEgNtBTn0z7V1Qy+
rJ2ZwSzinCPuRKV9eQNJEseoJM5HzDkbfb3qrJfozhYAVcEfMoJBIrrtR8EaZolrDcNJ509zKvkwANuVcZb
Jxxg8Z5qrbeHpbe4k/s+4tbKVE83y7mZRvPoG/pVfUai2VzFZrGT952uU7HxBCZT/afnqixtta2iDFnA+XI
JGBnqetZN1qLzXCXEcYZ/wCMsNuK3b+7uLiSOTULaG3bbnzIkG1z1PI6moYb+yu7V3uY40QHaQRgZrha5bp
x1PWhWlVtap6bDLDVElnSPUFZUdgGlX5sZ7V6d4ceDzY7aOaJwvCrnGR6n/GvEdSC/a3aBBHCRlcE4PuPWt
TTfEEulrGS4kkYYdWXBA9M040opqUVY2jmk5p0q8ttme63d6uo6HJJp9ogWORgzSjcx91PX+E/kazdJjk1O
WytLPWriBJrhoTIqjhyoMYxngFgyk+nauK8M6/Ja2t60EUQguHjdoWkII6glSOn3vetm01GFdF8QrApSVIl
lghmcBcl/LYxygD5gJM8gcgVtWXJonucc5XTaO58MaENR0Wc6jPcwiC6n3QSNuEMrxtGwB6lcgHB6c9c1cH
hlNO0MJeWxlkl0+O0cs4PCSBw2PXArybwz4iurLU9Wt9OuLmWW6sZSYr0lvMmjxNuJH8RWN19yw61fv8A4q
6hqmmR6anh2aCF1ImmEhfblCpK8DjkHHtShSnNNxTZxzqRi7Tdj0ufxB4c03Vxqzm1vLlLe7eG1Chmx5csm
32Gc8+9eEaTft4i8K+JWu7uK1u5r1Lo4HJDE7sfiRV74e6Zq3iDxMdUvYmXS7SCWOQscKQ0bIBnoD82efSm
WNpazXF/Fp8ZNoJPJSObHmsexIHb6cV24bCTnOzVvU48VioRXuO6K6eEZZp9PuhqlzdafbNsjcH5ovmLAKM
8AsWP4k1oJoGlWPiW2+1KzTi6jlaZZDtjG4EknGCe9dN4AW10o3/9q3LWWpRKQmY8sUPG1O2T3PYVbitb/X
muLuWZ7aygUxrcx/JjPVVXq7EZFfRwwVGKfu/1/X/DHhTxVS697+v6/wCHK2h6vp/h/VppNVs1j1CSVlkv4
IgEuoSSMY7EgjLDGe/cmnrX2Ge9lsPD9+gXaDJcBcqT12jj5VHTJ6mpxpVhbPMupXTOpQlEkB8wADqQe544
qSz0yD+yraWxjjmvdQk/cWcEh3bVyP3n1POOuK6KdCFH4dNjOdZ1HqWfCwuLGyu7zUNPt7y1t0LLJuLpGT1
OM8nA4HaoJ792s01CGEiS6VkgsYJCDs6FmPX8M1NrB1GztrGwiuLRbeIlpRA3y788+Zn06YH1qe3NojXuoW
en+ehiMbO4Gzfxl4mDDbz6Z47VouWPvW3Mmmybw1JD/ZMj/wBpWtnOoM00bphrUDgKm4Es3t0HWsyK4Or3k
KeG7TNyjmQmTLO7D+KQn+eamvpprHT7eK/tjPNMf9InjCkwp6ZA6+5qTQ5ItNtJ5ZtRFxo9zJiaOywJp1Ix
tBIwAOM5x1py2bW4orXUzTp88d3Jd3BS0VOFnibKq3U898ntUN3Z6oFbUJGMABDx3V0hVpSOdqjp+lbF3s1
6y3uIY9PZm8m2M4QxbRwAMckj8zVW5s7y6vE8vU/tUMUYGy4OwIuPu4I9OM01LoFr6milxb3ulw6hq1vbS6
hIfLiQQYmlOPvvgA7e1ZOp6bqCXXkXkUifaM7LuIkRIeu0HtgcYPNQXUr6veNDp0IgWMFVkJyB7FsDPpnij
w5dRWzXK6ldXi3e5fIt4pMwyP8A3juPA75z+FJRcVaP3D0bvJ3FsrO9stPlhXUHkkuSqbThnbGTj19+Ko6d
qscDXLai9y0oQxWyY+
+TkAn0x1xVea7mj1szW4NzeQsyiRGJUEg9Cv48itu01W91XTkj1LTtPd7OMqLxF2ZUnOZMcMR07H61U4tJw
3TBdJPco24Tw5ZG3guo7jXbpP3zYykSnoPQtVjQn0RbST/hJNJv72/MhPnQT7EK4GMDn3qpex6bNbyXFnCU
igGJJlyN755AU+1P0m91Oe1J0mRI7RGKqkhXI/P61MaVoWu/vs/wBzd7ogh36M73c1m9ypZgDvA8psccjOc
V0nhW8g1iSebzkgvdgwpARMAYLt2LYzxUGjW8eqrMJ7uC2tLFSFtIsCaQk54BP3e5Ynism/ubeaSS1mlSzg
zhWt18wE9Muw6Vmmp3vuW7qySLV5p8NzqDvYW8+oWYUt50zfKwHGenAzVjTDcxROjWSx202A/2zIMQHOVdu
x71c8Ma7Pp2g3GnxaXFf2KMZBJExRWk/vSN3x2XgVjXOvXN/d4u7srcEhijMfJO3kAjqB/hVtuV0+nmQltY
lmW/bVVuIGigMZLRyqC0arj1fqPStm0stQvvDq6nq2pW4s7Q4Wd1+Y88AdyeDWaJrrxFqNtb38wtLwLu3vL
+7n6kbR9AAAMds1NqPiB7qZJtf+yTQ2eIVtwQiqMHACKMduT2JFYuUm/T+vxL5VayIdXe81yedGUFbWASoJ
PmLAYxkqOM5HHA/SpNG1+a7uXj1drZ5kbev2kqBESCCSTxtGc+uadYaVf6o5uPDyy2+HG1ImXManP33HRRj
jP4Umo2/wDp01rc2xuGH7uS5O0FccHGRlyD3rCrCM7xtqu3QuDcbPuZ2qW017fSrpV8I5YmUsUXG5SM78jg
Vq4WO0stQvFi068LF4JoSfMmYHO5hk4A4A6VN4HtF0e/Ona3/wAeEo87zk3Hzk4wi7cfMfftTr8jxBf3lvN
9lVVy8MAj3vHGo5QNx82O1TClyqzexUp3eiMvUrGS0uzDe3TXDSkN9oiXKBj/AHiOePX1qzq2qaZHp1npIe
S4sbcYmNxJgzSHuMHhB+dVdG0+4gimFs8k1mrAmF/lJfrtB7cc4FZ+o2FpbxyJetJLdFQzJCu9I8nIBbPB9
RzWrdmlv/W5CimjSMJnW3s5JDAHYeQ0jEtEh6c9lHUVk+MtP/suFI1RBHuI81iXLsezdQMVt6bDc2eoyOFa
dGhGWllCNj+EbT1xjp/OsvXrS/tWtH1iGBTOf+PeSUeZtPO4qMlfxrKclPS5cU07lS0j1o20cdwIrmK0Ty4
wWwEXrxt78kk1WjtpdaciW1BAJDSoPmA65JPWtW8sbS4002egPcBo+XLsMS4PIB67eRVWHS7i9uGg1O1uLE
R7zI4uNsKAD5cDb1zn1zXOrp3eiNtHtualloyw6VEf7Q8mGT98qzZI2g4BPU+pxVPR9HN/Ld3FzHd3VhE4W
Rmk8sS98IxBwRx2OaqyWE9y0x0eaa/s7Z0WeYPnd7qOp57YroZ7qW30tL2LMMSyNEgQYEY5zuz/ABnn8Kpp
STS69RKTi7v7jDtdPvdJuLmS3vxLPclkayYiWY5PDH05xz1qO00+U6hJYvPFb3zIX82SUIkeDk7i3BPbHHW
k0PTP7RMk7wXkUkTGU3MK5IABOefp060tvpanTriS5iXU7ieRTDMrFXxn5gFOM9R245rG7Saia6X1Ca3tp7
tbXRLl5InQJPdCAbpnJ6IvXAwKgTTpruxWK5EwSBiI3gGdzlupGetO1PS30e5iE8/2SVuFhik3hWH8L4HHv
itjTPEFxaxSwXKGKW1ffbxwSfIhPdB6+rE5rWnRafMupnUqJq29iZ7TUYNQEUV2uqanOnkRQPGocLt6e3Hb
rWTYWlgqo+sRi2nglJcSgFWUHG1ccnnjP8qja3tdU8uW5+0WtxNISsyNlU7ckAd+9WYtMuYo7m41B47myjB
jiuZGONwHQcHJ9hW6pRitWZc7ZSazW9dp9AgX7PHlpIAMOg5JxuJzwM8VlXNmuo3ENvoUVy9xATIZCcOD67
egAp4nCXNtOLo2luHx5ynLL6kgcgfhXa3VjGdIN7y2sSEl4rZz88WBhpMY2A/rWE6FOpeLRtGrOnaVzzLXb
K6tr+NDNBbwxxYLMpdFbvnIOCazvsUcrJE7xPMVHzq3Bru7ixjudPaO9miinQ5EExwHPPyrtxgYx+I61d8H
w6fp91Y2d1aaVa3W04aZC6Sk5wzZ6njgA46d+K8+eXJT0kd1PMGo+9G5yWiWt7E25lQ2cZxJJ1Kj1rtNI8R
Wsnhq+0NdH1PW9B1F3WGMwCILdAD97FIGJyOCRjBHBHNc/wCIIornUpFsHQxMSzwK+0N6naOn0rUuDd+XBf
LYrpNt5RjV4G2mQAYOATjJ6H1q/wCz09a8tF2Lq5k5x5aMfvMA2rRamJ9MttVF5bOEV/OXcjAcEqAc8D+92
rQMEU5FrZXDtebgPJMLb3GB067atWGpy6S9rNKDDDNEfKlYbmKtkE9wMZOD2NdvNFbX1tHqlxZQ2kohaa3O
nOBKIiMbp2GAefT5utdNPDUqC5ov5nFUxNWq7PU5rVLrUoNLhsdPszb6YCJDHlSHkH8UjY+Y47VaIttW0m0
u4rcwa2WZDHZwbIyOzZB6/QYFZu6afVwsFtLqMO4oJ45PkwOpUDjHvWl4X3WM9w9va3e90MLQ7toVs8lXP3
R7AZPrXowgmlJ6s4nKxPdalpv9kR2Go6e8SbGjXVEkKlpuOuQdyKc5xjr1qXRrXXrKNoJoYJrGKIyx3UiFk
gU/xjHJPI9etcvrN/fPIlpd28JtA5aPYCFUHqAx+nWtPSGNhaSS209zaR6jGbdN0xMZx3YDJ2jFJ1Y0oO27
BQ57XJNPMt9eyPZojPENzz3TjLH1weK2tHsp9RW7vtNtpLK4t2ZL2+jI+yhWABABHDH29qyNZggbS7eyu54
7RrYBjMMeXK574/iB+mfWpfP1ptMjhZ/K0i1cO+ITHC0hzjOPvEjpmumNRVEtbGMochJrFlHOltPsik0wfI
tvu2TSserc9Rx1NVLLSZZHjSBw0ds4dtNdipJPcH3qTw+39q6vaTQSCe484x/ZChBY/wAJUenPr26euleQX
WnQXlvooVtRL7XmB3MZDnIXH0Nat8uiZC10sZPiO8124aOVwHt4WI+z24/cR54weeDjvUmjada6fa3V/qNq
0WqYDWdujAoBnl356cjGM5NX9Pli8RQ/2az3tlJZg3F+koA87AzI7MTk8gAAiuc8TQFLSMu7H5i0cajLRpn
5cntx9KmKuuRFvuxk1/exakLZ5ltrm4XcZVRcLnovTj8K1vDUkVpayjWESWyBaSW8Viz3HpGMnjnqRWhosW
k32kw2ENyJ7t/3lzdMC0h9II17k926CqHjGARTqNNb7aLUBXtFOY4ePuE4G49ckfrSalfllcV09Eiy+mPrl
o+o3kax2pJhtbSBsYwehA52jue9ZM/2fw3G8qBdQnVdmxeUjPp+XrT9H1WW3a4/sFpdOEsQFx50YkWIZ/hY
jiiTT3iQSQxvJDMPMNzMwIc9z71aT2ewna5NeWTfZrO50ryrq9uoBNOlq5CW6Hsc9eMZ64qS51U4itfOieF
YhFOBwJGx1zwCRx+VTeGtMtr3Tb68gmlt44EZbifG1Np52gnrn0HrWTdWlslo97eJKIkYbI4DuKp0BYdsnA
yaFy3alrYL3tbQ04NGtJNLuLrTNSimaMeZNZc4A/4Dxzz09K2NG0W4j06GTzIbBJx5qQyR72APfP1BrmrOy
YF7uxeVGjwRukAVDnPzHGD9OKe1nq07tPdWk13JMfM81ehB6VhWg5aN/ka09Hp+pkzSFgj2ywiMko0nVl9S
aks9X1G3ubUWcjJHa5jVLhd0bIxJZWwM7TuP51QeddH1OFYYGuI1dXd1TIPOcc9j711kln5lhc3cc8Nqk4E
j26kN5XorY+6W54rOUFLQtNw95GLquqO11c2OkW1vEsx3+Vby/uQ3tyc/jVa2jhVQsMTSagq/v3c4ZX5yAp
7dvwqVdPvZbiWSBIQiDe8cLDeF9QD1rVlv7W/u3uLezijazCuRcDEkh9X9fpmnBcrtuJu/vFrwLcafa2txJ
fSXEF+MkXGwsYl9I1HfrzxjNQ6faXNzfXl7ptjB/Z8GUkkulJO4g44HVu4HPvWXqlzBcvFJN9uG4lpWRAgU
n0x2rR8OeINQs7J9Pgk+22SlmgdyB5bsclicYLcnk1bg9WluQn+BNa6RdWEkrWEn2S72h7mxV9pcb8Kp5Gc
5BwM1BJeW1z4ikfxBFvmncKIUcny88ZLdtvHU0k2nJM8lxOtw1yTuM0L7mXIOCD68Hg1oaRaQQaRcwvcJP9
qciKUx4mkUDoc/dXOck96xnpeSevki072TRNK1hZ29xZWF6hurgiOW/kLSRxqvRYzy344xxWRepJcNJZy27
W6RZ2NC3BY8kbu5PvXPXmn3bKTayINz7THC4Z8j6fWu0sdX1bRbaJNb0SN5YhshjdVVUQjJITqznP3vSiL5
dFuJq+o6S1nawtdLt7+2ae1jOFQFM7s9cdX5wSM9qzNItLey051lE41FJSksMZyN/wDeLH5R6AfjUd19q17
UoHaWS2MpCKsIAEOSeG9OOa0WmSO+gg06Bb7T7dSFV
lyzzDq4GRu+hNEoSezDmS6GHLdalBdummaiY7mYHfJNgo/HYkfKQOKjtI3s7aO+v1ebUJiWUqgcSYPqT065
P5ZqmumXepahNC0ksYfLymXCRgdyc8cdK39Wvr3TLSOAKDDMBGzJH96MHr0yv0BH61nKjZ2Nee6MfSLyKW9
FzNdxxeU6A26gr5mSeA2CFHqT17V0FvqjwWF0dStppZLk/MGQhEIPUYzkDsKuW9lpMGiJdpZzT2m3YmbfzG
TactIxA4PsTXNW+rXFvcebHcfbLURgZ5JtlY4yE6Z9cZrKLetinFO10GjQahM8iGa5ihlKzSS7dqwqCRux0
P5fSnT3SxTxwGzkGjJvJvWVy90w6deAfy/lV6KGO30u4gtdXJS4kErJvyJBk7dx6k8/dHTPNP06c6bBcyar
Dm0VhG1thQZMcjacnaPVsVNaCqOze44TcL2WxlyzalOtvqkEk9lDG4EMBjzF/s5HfOD2rU8Sa/fxafD/AGg
sTapLJ+9kiTCxJgALgcL0OQK2tZ1G2sNHjluxFLe3S7oijBlVc/cX+6o7kZyRWH/bF7o9m0OoaGmoregukj
9Fyc5BA59vqaclJJcmlgjyyb5lctW02liWD7Ct06woHVnOZLmYgkEbR8qj0z2qpf2+q3kMWIbYIMyMrqA8x
bHynaSc9cA8/niqemPexwyxMDZXEgO6Lyh5m3tg9R19qm1JbTRwLhxdx3O5MWyT7jnjDHGMHOcYrWMVL3re
hm3b3bkOjvdy6rcCOzC2drEQ6bymCQQMEjvzwajvNcvtQdINWj26bAGMduvyIp6ZC9zzyetdvrukJdAz2cU
iO8CNKGbCxAHKmU9Nw9M1yEiaffanHY3M0huiCftYUhi4ydxBPToPpVJ39+1v0E9+UsppItJ5xc6fFqFndb
HWaN1UrFweF5w3tVTV420z+0INFlu4LeVg01pcMpcIPu7iOT16YFaFzqy2+mv5MckesqUjmeGIKigfd2FTy
Se2Kp6d/aUcd1NaXqXssrcwT/LIrE9eRz6VcUybrdl+z0yzufDI1PXL1Y1uyQlyAFCuGGUGRzx3BHUc9qy7
+2tvtAu9XMqadHOLcushd1HY9CAPp+Vad7YOI7bSSIjdyQs81stwDFEyZO/n7vBPA689ax7PXbTS0FjBbm+
eb/j7t5YgkUjAkAA53cA5yMc1zTi5Sv5/gbQaS0Ib/T4xAt3YLbCENtR8F2lAPbvUqaheXZMGoys8UvDWqs
qbSOBhc5/rV/U7K20SKWS0up2hYcXABEfP8MYPcc5OTWRcXNjqtwobT7iNlCpDdLIWYkf+hHnsM0/cjbn69
xLml8J0M+lf8IraTxQ6pZXrTJlLS6tzKbRD1PzcLnOQOT0OBXO20MOqSyxaYrWxRMySsVWPPqADwKS8leO+
YG/fUYCoEhkViW6YHOCTVVo5yY1vLNVJG4b28uR1J9B/hWKTcrQd0av3V7y1Ou0W6srHS4bKS1lt0jzJc3L
Nxdt1CRkdFqO91RtfjkSW+8qIE4giUtgDoM46fjmqmq6TeaVaS2c888zFA8dlLMHaCM8jOOM89BVW0uJDp7
totvm8VP8ASVaMEKpPQDsOO9dlKq3scs6aTsja1AzS6jE+p28twEgX7F/Z6lY2UcZbdyP05ri9UZLa6ljj8
y4VD/q1OFUemPSuv0rWdLh8OSi2ttSt7iVz9tl8rIYHpGpyQF57kEehrD1ZVuxbT6S1vYrbIVkhx9wA5DM/
O/OT79q55Tm5c1tNv+HNoxjazev9bFzTZNHvY4Qs3mqkYaeJgwUE9Ilwc9c88UzU9Xv55HtoBLJbQ4LWkUz
OgK5AZlJOSAcZ7ZqtpmiW99o9xqWpSw2qp+7WQOFaYk5GyPqfr0GaSW3k0mzgubZJoxcBiE2kuydMk+nPNa
0qnv3ZE4q2hrLqJ1LVrY6fp8mlXvlbfMjAwCTyeO+OM1BqWnxaZOItQkeOUDzRchyxYkZGMEe9Og1uO1sI7
GaNuQVluAf3xB/hHPSm/Y0+wRXdmn23SC/khJPkljOTyQDya9D3oNdjn+Lc63T9LuZRpj2FlFc3dxE5Cvu8
x16CRyflAxzgH61jSx3E8l5PayRzJEQLm8kOYyc8IqDg+mOaxoX1BJrjTdNvmmklAEsSj5ig6Ln+Yre03Xt
O0i0trG/0ycSWTtNHCww9zO/QtxjauBUU5aOwTWt0VbjRm0y+gvriO5015UDRInySS7hjKj+FTzVLxLok+k
z2yzEl5FDSR2pVpIyx4ViD1I9cVoTXy6lqbHxVfOZCFw0TGQwYHA/ujGMYyMV0mlXVzpl/q0mq28MrxwtLF
qMjB2EbABtgAwX646Y703UnGz3dhqCd7nKXNxZjT7fTjLeLHL813cbfmPH3dvPT8KcDPf3elW88v9oaakfk
xRxp5cigHABXsxyPrmqExhu7ryUk/s+1nDRjzDsKr2Zz0yR3q9Y3F3p2pQ28Lw3/ANngCW7o+4Fv7ysv3iM
nBJx/KrfkSloE9ilkxtbm3d2U7lt/OZo488DeOmR/Sjw9DcW+smTV91tYSqInniTdGF/vMB1PHHvzVi+JvP
tYu/tFnpkP+rjyrO0uP4jkdeeAePSs6xEdlpE80t3NDDI2yC2Z96u2cbiOwHrRpJW6hruJ4mlsr69ZbGG4h
sI/lto1PLAfxN6k8mrEemXupr576tYqRhdssgiZQBwNtU7q9S20+KzEl3FqNyf38/kZXb6KQcgewHP4Ypmj
+G7y5sxLazSPGWOWwSSaJSUVa9hxjfc6mL7CtisstxaywXKGUJaBcxfN0lbqORkKMEVix3EpuE1C0+yfYo8
xtBCgJC45O3vjrk96zja6TZtLd28kv2aTPlQ9S59XHpVy0SzQxTXWLGPC7tmUl5PIQ+mOuawhBqPvLVms2n
LR7F8NYT6WsT3UFvaOoKRJGrzSkEnMjfwDnpWe93aFgGtls7c/uxJu81pcdMnt17+lSanbWEesTrpTrJp7g
GAbf3kuR0z0B96bot25F9p1/DJbabIu9k+z+cx5yoDgfLk96TcY2/r+v61EoyZoWrafPfXE10ZbW38wFYY5
gdw/HqM1Bq1y95bW8FiIkSAl4oIwpUjPWTByG9iKry29rJJGLuSNkJJ8mFM7BjgEsRn6VB/ZkcQhubKGfTL
qBA+
+STfvOeoAHAx61KfI+YduZWsRQ6Fc3dq93cb4Sg3SSM5QLnoP16e9N1DUZpCHvWa5TAQMg2jA6dO3860tSa
91HTWN2kU5ZtqtAxK9PvFevWqlnA9nJHbz3fkwFUWdGQSAp1yBjg1rCXOrrUhqzs+h3MPiPw/FpGdMtczpm
OARwHapwP3hz9453YA+prkLOfUBrVxdWbi61CWHyyLtMgZ/uE9DxSJeWraqgube5tdHiUlFjG5unyk98E4z
WPLe6rd60i2cqmaN8xKiY4B6HiiFGEU1+YOcm0+h1WpSWVppcdolowudgfDrtLNk5Zz/ACA7Vztmt7qNyI7
a7s7dhu/dsGJYjnAwCVJ9eOlbVxa6lqGtWVhcTRS6jdShTdRg7fMPJUnoNvP5VuX32HwtHfXMWJdRybewjZ
MsuOHmfPfOQAaHa3LHcF7r5nqjGvI7hrOG0l0mRLqfBQn/AJa4yMr0OB6Ee5qvFYX19qthaXer3YtR88jTO
NtuowD36DseM+lVoJvEMHn6hDdvfzzoGabdvaNe6k9V4JzWvDbrDgPBPPqV/h/IfGTnodv8K+mahxlblf8A
X3lXSfMYE0R07XZbgPLHpZDBLiKQj7RzyGZT909x3FOjh1m51NdW0rTbOGxt8Sm3t5FQsM4xycnPPHJ61IJ
r7TtQfSNQQTw2xJNrEQxU/qDz1p9xfzQ2sz6MUtJJmWGQw4Und0AA6D/JrFULq0berL9pZ3ZY1TVvtd4jpY
Q/2vcLuIj2qIB0AjUd8dSRmpH0BI9MlvZ7yed7UfI4ZmQhjygG3OcnPPHWqelhbS5WOTTpZLpMCOeFw6tIR
jByCOlMmg1J1ltFllItF5RJRtj56nB6c9fenGgkld2sDm7iaXYWutw3UunK1uIl2iORPMkkfGSoX0OOOlM0
O9ezcTOHgjgcmNGyFDdnbgnb7CmaRftJqAtd7xXZI8u6tBiRT/tdAV9+1VvEd1eRIIry6iu2gfaFUALjOSc
9z71FSKUtXoVF+7ojp4NV/wCElla/SSG21OORncyLlGJHygN1+lZ0FjDf3lq87X1trit5ryeVuiGMbWB65/
DFYmjedbE6hti1CFY9rQhcmEk9SpHP1ra03UpdSW9urnUZIy/KISEMp5PL5AUcYxS57LTRA4O/cpeIdavUu
bfSrm8cqZsyMo2q0mer+uP0rqDbafYaDHLqM8UrXCAhGI8y4YNghcDKqPU8msqKeaCyuYvEelJeWF0iyQyW
mCyP2Zj1OR6/WszyRcXEL3N41xLAmI4xn/RgPuqxAOM1UWpK0hSVtUaWlala7byzvdPiiQYaC0YhBIMnLF8
5yOPc1FBLHodt/acAaS+lZ0t3ZP3aDHDLySzdeoA46ntPoN9b+I7yPTL+D7ZLtcfuo2OGBOHkc/w846cYFN
1mwFvpbJaRRTrHN5ZvHb5kwOUQZ5XJ/DFTFWdgkurQltaWfiGCCH7c0etLHuUkEmVsE4AXP8u/PSn2zx3Dw
jxFpdrHZI7eZdQQsJPTCnPzHI7+/NYFlujkFzY2Nxb3iKQ+FZUmQ8EHByARx6Guu1jxjPe6YljY6aLJGHzy
vteRRjlEUfdX36/nVS5p6J/8ASSi9jjdfS+KWsk0N9Fo1vceUyy5YRjg9Poc/jXT6nef2Q9taQ6dZxXUh8y
1ulGJbeI/MAQDgNjnPvVHTNPv3kluILlvtq7Y5o7sl1YHgHa3AAAH6VLrumJe6tZaTp6p5u1VdypSN37Abj
z14GcDNcsqMZSSnqbe1aj7pjwzSaBJd6raRxXpuVxBLtAWE55YpzzjpzW/Zx28tmuoTbb2Vk2/bDJgxAg4R
Om5h3rI0eO1sdbuPt05torSORJBMu7e442qOhOemOB1pviy+N5NYNpjtHeqd8UES+WIfm+XBHVzwSRjmmo2
lyJfcDd1zXM+fV9PtbqaCCCRmaXP2ibIx6lgPT8a6y0Nnc6dPdnULSG0RsBbeUfabtm+XaoHIX1z2rnI7aG
SztjqtstrBMx3z7S7BuegHLVPb+EZUv400qW4Fw5DpHCn72T0yn8PXvVuM5L39ifdTvDcmvruK11Kex1lmt
bKVCxt7BsqAegLdD0H61N4b1Cw0YXFrqemWusadGwltikgUBxnHmf3hz0PpWNqNpc2Go/ZpsSXbTbngAD4B
6g+9dNqek6VZSz2vh028moToZXmwTHCO0SE9T05/KnVpWhypbihUXNdso61qMOszzQX9hFCAdwRYSrR5P8A
Cc84AGP852dMuza2Vy1zcR3F3HtFtM7KfIjA+YMuMhsAAZ4/GuRubhvsYtlm/s29jG12bO6UnqWboBnoB26
11Gm+KY7PS7ca7pUM1tGhjEMbbTcnOQzHGSAeeDz9KuhC1PktqiKrblzX3OQ1+xeXUrhkhNtzv3joSecccd
Ks+Eb+PTy1vLB5dxP8omdd0a5/jI/pWn/YN5dWtvfXJQXly5e1tY2I+Qj5SVHCqOeT1qtcTxWEr/YUU3jKV
nlRBiNgf4a2puSlyxWvUUmnHUrXsdjcagkNi08dsPvSBdrls8sepP6fSumt572WB73VLv7RbW+BbbIlWVyp
woztBzjGeM1dgk0/U5f7P0GZZi+ye5uYw3mkqNz7lYDC9c4Paue1/W7q41k3aSTRxQSEQGH5RnPVUHAOe9d
EXzvVaruZSTirJi39pb/2HFdQzGbVb53lnRgT9nTPGc4O/OT3zUtrfSQeFLS2+ySSgzt5s8n/AC1PG0AZ4A
9Kp6JYXniyWNZJMgzYyGCSuB6gdgO9N15LzzbOOXzJbGB/Kito3wHA6sO3/AqpffbUHrodF4a8MJqunnUdT
aG4eaRzBDIdsYVfvSSE8BR0A6k9Kq6vrUDN9n8NtHDOhKmfiN5T3x6D0wc+tVYdPh1C/eDTzdw2oi3srOFU
tnhOCck8cDvx1rJuLSKd3uJFlmw2WlbIZmPOFB7+9KKU3d/5E6x0OugOm6oskV3LNb6Vpscbx2ssYM09ww5
wOvJzk88VzfiVJLi9khjhjjmljCtDBuCxYP8Ay0J6njPPtmtfwkjamVudRvLZbgSNHaI3M8KBTl2I5wAOM1
XuJv7WuYYrCeG10223K0e4EzqM5kKjnJx/KiKSbG7lHRYxZtHbXsjxzuBHG5bK84BAI4z1rY1UppN19ha9a
JoVCmK2mBWPvtJ7tzyfesKSaKDTANURltncGGEHMjKAQGz0Ven1rattMWK2hfY371BIMup46DknJ4FVJqIJ
cz0HWWnRRv8A2zEJLayVdvzR7wZemUU9c/Ss/VrG4js5Hu42tt5V1L4dj3yw6iiipUmJavUrIGsbd7bV4Uk
MpBhuQd0SL3O0dTzVvULmODRYF0j90xB/eICJHHTI54Hcj3NFFFPWKkXPdlC0tbWaDzLG4ma8jAMkVwQF3E
8lAep4rQu766u9Gj0+5Me0MzsU+aV26fOfoBRRU3vKz6A1oWdKOr2dulrB+
+sGOChULIhwOR64z/Oq+qwWVtLKJLiRp1GEjVCSx9Se30ooqoK83bQTMX7fKjCC9jljERLbiPvZ5AIPfPev
QbjSbeLQ0ube5hL3SgRzpgSTcAmND0AU5BbuTiiipqO0o2/rqPeN/QwbSC+uZYdLbTI7WInzftEkhJXn7+4
dOakiSygv5Y5Q00SBprqcuGkkwcbF64Oe57UUVSfM15iSvd9h3h29SDVPNFi9qETfbxSbn+0yE/LnsFHU/S
mWzX8urXCwCP7Q8nmXMrMWYjPQnsPpRRV8qleTWpN7aItXVpa6dpr6le2UjlpSloyuwkkYHLEsT93k/Ws3/
QI7eSfUoZTNuG20jyqpuGQWJ68YooqIvbzb/DQ0SunfyHW+pvp2lGG0tbg3EwO5QR5cC56gf3sdzVJ549Wt
riO2kNnqM2PNjVAVl545x8vbpx1oooaS1FEvR2GnRyNceIUuLWZ1MPk2Uu0vgDkkDGCRnHfis392msWlvrc
MtlaIrhbswh8oVIHykfNngA4B+h5oorJ0IzVn1LjUadzVvbW0g12DUo7g27sMxwRj/WHsXJOADzxWVbTW8F
tqTXNpFHfM6rbpAxCyDqxLY5wccce1FFckqUUkkaxm27sdqNneaClzA1rOl1KoaIMCvlA4Jyo5zz/F2rOtY
heoyaWlxBqLAJLAFJ+0HPoM98de9FFXTiklJCvzKzNnTBbWavcXsL2DxJiOe2nKNOR1UjuOlW9Ba61LVLf9
27FG82G1lfAkc55B7KO/eiiqUndt9DNK6Rp+JBciRba2geG6ufmm1HZiNW5yiN0AGPrXOxXL6Bpd5o2pabM
mpzvgX0bAjZjgAjtn0ooqqLUnZr+kVKKiQS2cljarE96LiG4y8wMhOWA4yByPateyu7TxDCLLVlvb0CI+TK
luA0AXgfP/AHc9c0UVC95tvuD0Q5bb7PaQf2g0N1pqQtHG623zSNn5inc46bulZLaQ+qW1rfNbiexgyGggw
Jwn+0OrD35ooquVRXP1vYhSbfL5G/I2m2VtaXMVykuqOuYYEXelkvuT0bHaqWlRSaDe3Ot290L/AM1CvmKz
qUPfOO/bHv1oorflv8yNtTfXTtKS3EcUim8eLzLq5g+Yb2GfLVj1wOuO5rh/F1iJpYLiBUs7Tcq7TuLIF43
E989fU0UVxwvKV2+p0WUdEdhpuiWk+hm6uFt3VYi9tcPJvAycL5gz14YhRz6iuZWadXLW+my39lFKomm2Yb
GCCuBwAfTPaiiuijFO5jLe5uw2MlohvdIc2mly2ySXRunQMuTho13c5B445xWFcuFb7SkcVpYEnZM6hNwP0
GW/WiitKNpNylutAmrWS0TNLRlgMiXaW4W4lDJGY8xecCOXftsqnqUcNxcSRaVFFLMr/vZ3Y7VbHBXjAXJO
KKK2j8RnurkLaZJBGLrWJRDFICFnhXY8g7gAdvrxS6jptwkdrNEl1c3VygNrETl/KHQ//WFFFS5tIOW7uNT
VLyw02ztoIAbhZmnkYAsQ2MKOT26/WmW07agknnRtYX1uxmRrYbkz2DJ/D9aKKuUUtQ5nsW54rTS0km1hB9
pkw8CCPmNG6Mx/oRmptHVtMd445rO/WdC5u7fJEcZIJQqeuemMD6miioell3GvhchZtckv9Q1FhCrXF8NrG
ZVEcIBBGxP4QMCqFvaadKrH7TcQuGIcQIzIW7kY7UUVooRj8JPM5PU//9k=);\">",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Neil D Gross, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_421=[""].join("\n");
var outline_f0_26_421=null;
var title_f0_26_422="Initial evaluation of the hypertensive adult";
var content_f0_26_422=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"1\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Initial evaluation of the hypertensive adult",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/422/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/422/contributors\">",
" Norman M Kaplan, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/422/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/422/contributors\">",
" George L Bakris, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/422/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/422/contributors\">",
" John P Forman, MD, MSc",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/26/422/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Mar 6, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Most hypertensive patients present with a modest elevation
in blood pressure. The diagnosis of hypertension is made in this setting only after
an elevated and properly measured blood pressure has been confirmed on at least
three separate occasions. Two aspects of the initial evaluation of hypertensive
adults deserve emphasis; first, there is a need for more accurate measurements of
blood pressure in the office with the addition of out of office measurements,
either by home or ambulatory monitoring [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/1,2\">",
" 1,2",
" </a>",
" ], and second, the assessment of overall cardiovascular risk is important,
particularly in the large number of patients with prehypertension in order to
establish appropriate management [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/3\">",
" 3",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/4/43080?
source=see_link\">",
" \"Blood pressure measurement in the diagnosis and management of hypertension
in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/4/4169?
source=see_link\">",
" \"Hypertension: Who should be treated?\"",
" </a>",
" .), for a detailed review of the definition of hypertension and the specific
individuals in whom therapy should be initiated, (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/27/41398?
source=see_link\">",
" \"Malignant hypertension and hypertensive encephalopathy in adults\"",
" </a>",
" ).",
" </p>",
" <p>",
" After the presence of hypertension has been established, an evaluation should
be performed to ascertain the following information:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The presence and extent of target organ damage.",
" </li>",
" <li>",
" The patient's overall cardiovascular risk status. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/59/39866?
source=see_link\">",
" \"Overview of the risk equivalents and established risk factors for
cardiovascular disease\"",
" </a>",
" .)",
" </li>",
" <li>",
" To rule out identifiable (secondary) and often curable causes of
hypertension (",
" <a class=\"graphic graphic_table graphicRef56130 \" href=\"UTD.htm?
41/38/42604\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?27/21/27991?
source=see_link\">",
" \"Who should be evaluated for renovascular or other causes of secondary
hypertension?\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" The patient with severe hypertension (eg, systolic blood pressure &ge;180
mmHg",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" diastolic blood pressure &ge;120 mmHg) requires immediate evaluation for signs
of acute target organ damage, and possibly immediate treatment. The complete
evaluation for potentially contributing causes is usually delayed in these
circumstances until the blood pressure is brought to safe levels. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/27/41398?
source=see_link\">",
" \"Malignant hypertension and hypertensive encephalopathy in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/11/18614?
source=see_link\">",
" \"Treatment of specific hypertensive emergencies\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?27/37/28246?
source=see_link\">",
" \"Management of severe asymptomatic hypertension (hypertensive urgencies)\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" THE BASIC WORKUP",
" </span>",
" &nbsp;&mdash;&nbsp;The features of the history and physical examination
described below are directed specifically toward hypertension. Additional features
may need to be included for other indications.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" History",
" </span>",
" &nbsp;&mdash;&nbsp;The history should search for those facts that help
determine the presence of precipitating or aggravating factors, the natural course
of the blood pressure, the extent of target organ damage, and the presence of other
risk factors for cardiovascular disease (",
" <a class=\"graphic graphic_table graphicRef77599 \" href=\"UTD.htm?
17/8/17549\">",
" table 2",
" </a>",
" ). The patient should also be asked about the signs and symptoms that suggest
an identifiable cause of hypertension (",
" <a class=\"graphic graphic_table graphicRef56130 \" href=\"UTD.htm?
41/38/42604\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/14/23786?
source=see_link\">",
" \"Clinical presentation and diagnosis of pheochromocytoma\"",
" </a>",
" .)",
" </p>",
" <p>",
" One important consideration is the duration of hypertension. Simply asking the
patient \"How long have you had high blood pressure?\" may lead to a misleading
answer. Suppose, as an example, that the patient says two years. This should be
followed by the question: \"When was the last time you were told your blood
pressure was normal?\" In some cases, the patient will not have a blood pressure
measurement for many years. Thus, the patient may have had undiagnosed hypertension
for many years.",
" </p>",
" <p>",
" Another important consideration, particularly in the patient with severe
hypertension",
" <span class=\"nowrap\">",
" (&ge;180/120",
" </span>",
" mmHg), is the history of prior treatment for hypertension and nonadherence to
antihypertensive medications, since this is a common finding in patients with
severe hypertension.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Physical examination",
" </span>",
" &nbsp;&mdash;&nbsp;The main goals on the physical examination are to evaluate
for signs of end-organ damage (such as retinopathy) and for evidence of a cause of
identifiable hypertension (",
" <a class=\"graphic graphic_table graphicRef69470 \" href=\"UTD.htm?
13/39/13948\">",
" table 3",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/22/21859?
source=see_link\">",
" \"Ocular effects of hypertension\"",
" </a>",
" .)",
" </p>",
" <p>",
" The various pulses should be palpated and the abdomen should be auscultated
for a renal artery bruit. The presence of an upper abdominal bruit with a diastolic
component that lateralizes toward one side is highly suggestive of renal artery
stenosis.",
" </p>",
" <p>",
" The 2008 American College of",
" <span class=\"nowrap\">",
" Cardiology/American",
" </span>",
" Heart Association guidelines for adults with congenital heart disease
recommend that every patient with hypertension should have the brachial and femoral
pulses palpated simultaneously to assess timing and amplitude to evaluate for
brachial-femoral delay characteristic of coarctation of the aorta [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/4\">",
" 4",
" </a>",
" ]. In addition, supine bilateral arm (brachial artery) blood pressures and
prone right or left supine leg (popliteal artery) blood pressures should be
measured to search for differential pressure. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?32/15/33013?
source=see_link&amp;anchor=H2#H2\">",
" \"Examination of the arterial pulse\", section on 'Unequal or delayed
pulses'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Laboratory testing",
" </span>",
" &nbsp;&mdash;&nbsp;The procedures that should be routinely performed to
evaluate for underlying causes (and signs of end-organ damage), as well as
cardiovascular risk are [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/5\">",
" 5",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Blood chemistries including electrolytes, glucose, and creatinine. An
estimated glomerular filtration rate (eGFR) should be determined.",
" </li>",
" <li>",
" Lipid profile",
" </li>",
" <li>",
" Urinalysis to detect hematuria and a",
" <span class=\"nowrap\">",
" protein/creatinine",
" </span>",
" ratio to estimate proteinuria",
" </li>",
" <li>",
" Electrocardiogram",
" </li>",
" </ul>",
" </p>",
" <p>",
" If there are abnormalities in the patient with severe hypertension, an attempt
should be made to determine whether they are new or were previously documented,
since the patient with acute changes generally requires more aggressive blood
pressure reduction.",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Additional tests",
" </span>",
" &nbsp;&mdash;&nbsp;Additional tests may be indicated in certain settings.
These include:",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h3\">",
" Serum Uric Acid",
" </span>",
" &nbsp;&mdash;&nbsp;Hyperuricemia has been found to be a precursor and possible
pathogenetic factor for hypertension [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/6\">",
" 6",
" </a>",
" ]. It is not known whether the presence of hyperuricemia or its treatment will
influence the management of hypertension.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Limited echocardiography",
" </span>",
" &nbsp;&mdash;&nbsp;Limited echocardiography is a more sensitive method to
detect left ventricular hypertrophy than the ECG and is considerably less expensive
than a complete echocardiographic examination. The main indication for
echocardiography is to detect possible end-organ damage in a patient with
borderline blood pressure values. It will also identify some patients who would not
be treated based upon clinical criteria alone [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/7\">",
" 7",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/34/17959?
source=see_link&amp;anchor=H8#H8\">",
" \"Clinical implications and treatment of left ventricular hypertrophy in
hypertension\", section on 'Indications for echocardiography in hypertensive
patients'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h3\">",
" Ambulatory blood pressure monitoring",
" </span>",
" &nbsp;&mdash;&nbsp;Ambulatory BP monitoring is capable of reducing the costs
of the management of hypertension by rapidly identifying the 20 percent of patients
with \"white-coat hypertension\" and by ensuring adequacy of therapy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/8\">",
" 8",
" </a>",
" ]. However, most third-party payers refuse to pay adequately for this
procedure. As a result, the main indication for its use is in the patient with
persistent office hypertension but normal blood pressure readings in the ambulatory
setting. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/60/7113?
source=see_link\">",
" \"Ambulatory blood pressure monitoring and white coat hypertension in
adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h3\">",
" Microalbuminuria",
" </span>",
" &nbsp;&mdash;&nbsp;The presence of microalbuminuria is an early manifestation
of nephropathy in either diabetes mellitus or hypertension, and is associated with
an increased incidence of cardiovascular disease. Testing for microalbuminuria is
at present primarily limited to patients with diabetes to screen for early
nephropathy. The value of measuring albumin excretion in patients with primary
hypertension without diabetes is being increasingly advocated [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/9\">",
" 9",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/16/20745?
source=see_link\">",
" \"High albuminuria (microalbuminuria) and cardiovascular disease\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?41/49/42777?
source=see_link\">",
" \"Microalbuminuria in type 1 diabetes mellitus\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/33/39449?
source=see_link\">",
" \"Microalbuminuria in type 2 diabetes mellitus\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h3\">",
" Plasma renin activity",
" </span>",
" &nbsp;&mdash;&nbsp;Although the plasma renin activity (PRA) may provide
prognostic information [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/10\">",
" 10",
" </a>",
" ], the test is usually performed only in patients with possible low-renin
forms of hypertension, such as primary mineralocorticoid excess. The PRA may
provide guidance in the evaluation of resistant hypertension [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/11\">",
" 11",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/55/36728?
source=see_link\">",
" \"Definition, risk factors, and evaluation of resistant hypertension\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h3\">",
" Workup for renovascular hypertension",
" </span>",
" &nbsp;&mdash;&nbsp;Additional testing for renovascular disease is indicated",
" <strong>",
" only",
" </strong>",
" in patients in whom the history is suggestive (",
" <a class=\"graphic graphic_table graphicRef56130 \" href=\"UTD.htm?
41/38/42604\">",
" table 1",
" </a>",
" ) and in whom a corrective procedure will be performed if significant renal
artery stenosis is detected. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/17/31001?
source=see_link\">",
" \"Establishing the diagnosis of renovascular hypertension\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h1\">",
" ASSESSMENT OF CARDIOVASCULAR RISK",
" </span>",
" &nbsp;&mdash;&nbsp;As well defined by data from the Framingham study, a number
of other risk factors interact with hypertension to determine the overall risk
status of each individual patient [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/12\">",
" 12",
" </a>",
" ]. The presence or absence of other risk factors can influence the decision as
to whether to institute antihypertensive medications in a patient with borderline
values [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/422/abstract/13\">",
" 13",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/51/37685?
source=see_link\">",
" \"Cardiovascular risks of hypertension\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?32/54/33635?
source=see_link\">",
" \"Patient information: High blood pressure in adults (Beyond the
Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?36/32/37380?
source=see_link\">",
" \"Patient information: High blood pressure treatment in adults (Beyond the
Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?9/8/9347?
source=see_link\">",
" \"Patient information: High blood pressure, diet, and weight (Beyond the
Basics)\"",
" </a>",
" ).",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Among patients with mild to moderate hypertension, the diagnosis of
hypertension is made only after an elevated and properly measured blood pressure
has been confirmed on at least three separate occasions. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" The evaluation should determine the duration of hypertension, the presence
and extent of target organ damage and the patient's overall cardiovascular risk
status. Among selected patients, secondary causes of hypertension should be ruled
out. (See",
" <a class=\"local\" href=\"#H3\">",
" 'History'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H4\">",
" 'Physical examination'",
" </a>",
" above.)",
" </li>",
" <li>",
" The physical examination should include evaluation of end-organ damage. The
various pulses should be palpated and the abdomen should be auscultated for a renal
artery bruit. The presence of an upper abdominal bruit with a diastolic component
that lateralizes toward one side is highly suggestive of renal artery stenosis.
(See",
" <a class=\"local\" href=\"#H4\">",
" 'Physical examination'",
" </a>",
" above.)",
" </li>",
" <li>",
" Laboratory tests should include blood chemistries (electrolytes, glucose,
creatinine), an estimated glomerular filtration rate (eGFR), a lipid profile,
urinalysis and",
" <span class=\"nowrap\">",
" protein/creatinine",
" </span>",
" ratio and electrocardiogram. An attempt should be made to determine whether
any abnormalities are new or were previously documented, since the patient with
acute changes generally requires more aggressive blood pressure reduction. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Laboratory testing'",
" </a>",
" above.)",
" </li>",
" <li>",
" Additional tests may be indicated in certain settings including a serum
uric, limited echocardiography to detect possible end-organ damage, and ambulatory
blood pressure monitoring to identify patients with \"white-coat hypertension\".
Microalbuminuria should be determined among patients with diabetes. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Additional tests'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/1\">",
" Shimbo D, Kuruvilla S, Haas D, et al. Preventing misdiagnosis of ambulatory
hypertension: algorithm using office and home blood pressures. J Hypertens 2009;
27:1775.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/2\">",
" Mallick S, Kanthety R, Rahman M. Home blood pressure monitoring in clinical
practice: a review. Am J Med 2009; 122:803.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/3\">",
" Sehestedt T, Jeppesen J, Hansen TW, et al. Which markers of subclinical
organ damage to measure in individuals with high normal blood pressure? J Hypertens
2009; 27:1165.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/4\">",
" Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
Management of Adults with Congenital Heart Disease: a report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines
(writing committee to develop guidelines on the management of adults with
congenital heart disease). Circulation 2008; 118:e714.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/5\">",
" Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure: the JNC 7 report. JAMA 2003; 289:2560.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/6\">",
" Forman JP, Choi H, Curhan GC. Uric acid and insulin sensitivity and risk of
incident hypertension. Arch Intern Med 2009; 169:155.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/7\">",
" Cuspidi C, Lonati L, Macca G, et al. Cardiovascular risk stratification in
hypertensive patients: impact of echocardiography and carotid ultrasonography. J
Hypertens 2001; 19:375.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/8\">",
" O'Brien E, Beevers G, Lip GY. ABC of hypertension. Blood pressure
measurement. Part III-automated sphygmomanometry: ambulatory blood pressure
measurement. BMJ 2001; 322:1110.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/9\">",
" Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European
guidelines on hypertension management: a European Society of Hypertension Task
Force document. J Hypertens 2009; 27:2121.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/10\">",
" Laragh J. Laragh's lessons in pathophysiology and clinical pearls for
treating hypertension. Am J Hypertens 2001; 14:603.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/11\">",
" Egan BM, Basile JN, Rehman SU, et al. Plasma Renin test-guided drug
treatment algorithm for correcting patients with treated but uncontrolled
hypertension: a randomized controlled trial. Am J Hypertens 2009; 22:792.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/12\">",
" Kivim&auml;ki M, Batty GD, Singh-Manoux A, et al. Validating the Framingham
Hypertension Risk Score: results from the Whitehall II study. Hypertension 2009;
54:496.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/422/abstract/13\">",
" Vasan RS. A risk score for risk factors: rationale and roadmap for
preventing hypertension. Hypertension 2009; 54:454.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 3849 Version 6.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0604-61.234.146.186-8AB89F2CF9-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_422=[""].join("\n");
var outline_f0_26_422=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H15\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" THE BASIC WORKUP",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" History",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Physical examination",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" Laboratory testing",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" Additional tests",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" - Serum Uric Acid",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" - Limited echocardiography",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" - Ambulatory blood pressure monitoring",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" - Microalbuminuria",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" - Plasma renin activity",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" - Workup for renovascular hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" ASSESSMENT OF CARDIOVASCULAR RISK",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"NEPH/3849\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"NEPH/3849|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?41/38/42604\" title=\"table
1\">",
" Features of secondary HTN",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?17/8/17549\" title=\"table
2\">",
" History in hypertension",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?13/39/13948\" title=\"table
3\">",
" Physical examination in HTN",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/60/7113?
source=related_link\">",
" Ambulatory blood pressure monitoring and white coat hypertension in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/4/43080?
source=related_link\">",
" Blood pressure measurement in the diagnosis and management of hypertension
in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/51/37685?
source=related_link\">",
" Cardiovascular risks of hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/34/17959?
source=related_link\">",
" Clinical implications and treatment of left ventricular hypertrophy in
hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/14/23786?
source=related_link\">",
" Clinical presentation and diagnosis of pheochromocytoma",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/55/36728?
source=related_link\">",
" Definition, risk factors, and evaluation of resistant hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/17/31001?
source=related_link\">",
" Establishing the diagnosis of renovascular hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?32/15/33013?
source=related_link\">",
" Examination of the arterial pulse",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/16/20745?
source=related_link\">",
" High albuminuria (microalbuminuria) and cardiovascular disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/4/4169?
source=related_link\">",
" Hypertension: Who should be treated?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/27/41398?
source=related_link\">",
" Malignant hypertension and hypertensive encephalopathy in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?27/37/28246?
source=related_link\">",
" Management of severe asymptomatic hypertension (hypertensive urgencies)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?41/49/42777?
source=related_link\">",
" Microalbuminuria in type 1 diabetes mellitus",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/33/39449?
source=related_link\">",
" Microalbuminuria in type 2 diabetes mellitus",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/22/21859?
source=related_link\">",
" Ocular effects of hypertension",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/59/39866?
source=related_link\">",
" Overview of the risk equivalents and established risk factors for
cardiovascular disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?32/54/33635?
source=related_link\">",
" Patient information: High blood pressure in adults (Beyond the Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?36/32/37380?
source=related_link\">",
" Patient information: High blood pressure treatment in adults (Beyond the
Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?9/8/9347?
source=related_link\">",
" Patient information: High blood pressure, diet, and weight (Beyond the
Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/11/18614?
source=related_link\">",
" Treatment of specific hypertensive emergencies",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?27/21/27991?
source=related_link\">",
" Who should be evaluated for renovascular or other causes of secondary
hypertension?",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_26_423="Leukoplakia - buccal";
var content_f0_26_423=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=DERM%2F81049%7EDERM
%2F72711&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=DERM%2F81049%7EDERM
%2F72711&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Leukoplakia",
" </div>",
" <div class=\"cntnt\" style=\"width: 432px; height: 324px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAFEAb
ADASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwCU8xnpVNVPm8+taCrkYxxiovIy4rxGrn2EXYcI8pkUipz0q3HHhcc0jJ
tPQU+Vk8xGkWQc07bt6VMuAOtBGc5q0iecFHy+gqJ0284zUi8CmFvmAp2KTFJ496gVVVsgc+tWCOKhcUrGk
WKxyKEYAdaYd2OKTaSKdh3Q6SXd3pkY5ppBByakj+goSK5kloWYzgYJpsvOaQdKRmx3zTM+YYGA4qRHx6Gq
rnkkDFNWTkj9aNi73NHzBt60xpAW255qsHytSKwPbmi47ki8U4cnmkHTmjp3pBzIcobzM5+X0q0p5NVQ3NP
V+aRJYJ9+afH0qAHqaljagluyLCYY9OKkxnpUYYewpC57UWJuyTAGaYpLdsChTkYp6LwM9KEO45G4pT3Paj
binheDRa4uYiUnt0qRWPekCEr1o24p2HzXJFlI+lWobsrjmqBFKO1LUGkzeivwe/61ajvAW4Irm0JU8GrUD
NnNWpMxlSidRDc8jB61pRzdOa5WG4NXo7o9utaKRzVKVzo0KMwYgbh0NWFfjtWPbXOAM4q4k4yDxVp3OWUL
MuE4zkVA5NJvzkikLZHWqI5RFzyQDUq4x0pIvwNTEDHApAyEL8wPpUm7nINB6UADHpQIY0mT07U3zMc0rKM
imnH40XCyAHJzinZGfSmghV96bv8Aai4WCV/SmKwGOv0pJMk5BppGTkHFK5SR4wPu80kRy9SlOM0kadcda5
rHsXJUHNOlXjGOabCeeR0qwBuPNUkZN2ZVVPXtSlCc9atFRngCmEcU7E8xXMWQMAVGU+bnire4BcAc1XLHf
z0osioyYZAHFN2g4yaYzDPX8qbvORikXqSlKjx61Kp4NDJ1pi5iAgU3JB4Ap5jbpQU4x0wKLD5yF5sDrUSz
ZOM81Hc4APNZ7TbCOamWhrFKSNjIZeSKY20dKy0vPU077Se3WhNMVmjTVwF45p6y8fLWWJmxzU0MpIoC+hp
LNwBkZpfMBNVFyee9SAHrjFFieZFoMMjNL5g56VXDc4p3FFgUyx5makifng8VXwCOc1IhAI5pWK5k0XY2bP
PSnbuuarrIBj0pxkB+tFhItIfSrEZ9Kz45eamSbHamhMu7h+NPQ+lUGlBPOalSbimKxc6dqRsfQ1AsmcVKr
flTEKR70KMDnmlH60pA4OcUrBcdt9RUikAAZ5qDdg4NODUIZaRsA1LFKQwqhvJFPjY5FMTVzbguDgDNaEdy
MjJOK5+J+OtWEmA5NUmYyppnRLcA1Ksv5VhxXNWYrg9zWiZzuBuQvxVgNkY7VlQXAx2/OrKyg0zFxLZOKMi
qyy9elHmj0ouLlJGYDvURf5s5qOSTI4qDeQPpSuHKXCwxwRURfB4qBZSQetSD1zmlcLEq5binBBn2po7U8n
HcfjQI8dwApBNIvtyKMEjNPjG1D/erA9QYsignPWnecM5FQPH6mnxoBjrRqEorcn3EkYHaojuLf0qdQNuaY
5A5q7GdyMRk9eKUQlgTUUl0Fqs+pDkA0ropKT2LrW4xUTRbT1qo2p5HAqtNfFsYpNotU5s0GdV70n2xB1NZ
HnNJ0poV93Jpc5p7C+5sNeIBwKrzXygHBqvFHzlznIqtcQqxOCaHN2HGjG+oy6vQxNZMszMcgH8KtzwkAZH
JNQqmzOD17Vk5t7nQkorQreawOG/Crtoxc8c1VeNs/d4q/pafvBuGBSTdzCvL3W0W/IOzIp1urEitmK3UxD
HNQx2+2XOK6eU8pV2ySCAkDjNW/sfyg45q3Zw5xmtFbcFc4FaKF0YSrSTMA2pZgqKSfahraSNgrIVPuK7Dw
9bxC/IlC5K/KW9a1vEUULWOHCeYGG0gc0Ki2m7i+tNSscGloWWkexbsK6K1gG0cZqd7dcDjr7UchaxUkzjZ
LeRTxUDCRTzXZyWKnOAKpy6XnmspRsdEMZ3OZSUhhmpVmye+K1X0wBsYz+FVZbAgnAxSUWbrExZCsmTU6MK
rLayDJ7inBZFXkU7GvtYvYuI+DgVOr81lCfFSpdelAXuayyD8aUuCODkVnCfPQ09ZRigRb6njNSrjvVRJBn
FT+aMdaBtkxHvSb9uKi8zrzSA0Ai0JSBxzSiXLcVAM4pUHGT1oAvRz471OtweMGszeOR3+lI0mBxTuLlTZu
QXXPWtKC4DVykUhyOea14JTtGTQpGVSmkbwnHanCXPHNZaTe9W4ZOnPHvVXMXGxbPPPaoyOTTwwxgfpUbHq
KoyGgdhz61PGeKiQY5pQcGkDLGflxR1zUatkUu7IxTRLR5QAT0FPWNiKR7qKIHcQOKoz61DHnDVlod2r2Lx
j5Gaado71gza8D901Tm1d/UkGpc4o0jRnI6WSdFU81nzXmc7elYi3ckjY5ANTIcgnOc1LqG0cNy7kr3BkJA
PNV3YkkYBHfFSsn7ssE+XOM57+lQyARoWI6djUNs6acEgj+dgB1x61cuJ0eeGeO2hXy1UNEclXI7ke/fFZs
YZG3dc81Os+STs+bP4UKXQc4X1LDIIndkP7pjkZGPfpUYkyxyahdjI33lHbk0w29xtDDp3A7U2SvMurN2ya
a8o5xUKRsi/O29+RkNxRHHtYl+R7mhbWJdkKwMg4HFAt1GCRye9W1iLKQBgYzxU9nbNIdzDCj1qlG5lKWl2
UTagr8q5P0psUTW75YEE9BW8UjEWVOPTHU1lXETtMWY5PX605JLYzjeejNO2mygx0NOPLZFZ9lPtTa4AOat
iVT06VtGXMjgq0fZs2NOnGQM1uwMHUDOK4SS7aJvkyKv2WrcBXbJOAADjmrU0nY55UJS1R1kikHI/Oq5897
g+YSYwMAH1rN/tgK7I/yshwQfUUHWIyy9BmtOZMz9hNdDobcjGPSryAEdq5m11aIseRmtaDUomHX9aV0Q4S
W6NFhntTSg9BVb7dF69KVr2PH3v1qJCUWSPAGYEAZ71HJaq1NF7Hn7woa/iAPIxREHFkD2SjsKoXluuCR0q
a81eJBww/OsO41mNnK7hV3iaQhUeqGSWpLEgZpgtCD3yatW14jDPBFWTNGRvOBRKnF6o2jVqR0Ml0eMnPSm
CbHJqzeToxxkYrJlkAPBrFxOynUb3RsQzg45q0rg4Oa5hLwqev4VchvsjJOag2ae5ug5FSR8msuO7BABIzV
yCcHHOaYr6GiuQMGgnFRLMpH1pdwPegSYpYDmo3OacSKaetSy0x8LY96vRSn1rOBPsalRzQD1NqGbjFXoZs
AVz8c5HpViO496pMylC50CzjHBp5lHFY0U+e9TrPkHninzXMuQ1Vf5RSt6+lZ8cuenariNkDNCZnKNidDhc
g4pSwApm7imSE9ulUmiLXPlm/16+lkOwYz2NVV1OTdi4Zlb0NbVzpXmISFIP0qGytVZza3SA56E1yOEkz1K
deNr2FtJwQpHJNaEI3YY+tVZ9Dltjvtw6jrxyPyqOKea3x58fyE43joPr6VLTjujphUhNXizWChjlT3qwQU
PtUdmiudy8rjtU+3cRkHFI0T6CFyVO0dOpqCWQuBvwBWjDCmwk9O1VZIjvORx2zQ9S4yRWYkKVLYGKkihdx
u5waljtUK5cnGeMDpWzHAqwLgEjGfmFNRZM6iijINscdgfrU9nA4ydzY7H0rVFoAg343HpgU6C12AsM/TNV
sYSmmiksKs5CL8w4JJ600WcgkO8J5WfXmtPyOBjgemabAnzgYON3SqMlJrYS3sVjj3ZBPqaVgzI2wADua1l
h3ZHr7VCIVVtj/AHcVdtDJSTvcybqNnThevGQcVSmykexgWK8VvOqhSM/MD09qzZ0DEknNRJM0g11Ofd/lO
AQ2c1dtnbCEHI7io57YGU89asJCI1XaM0K6Z0T5Wh9yvyluKz3wwIfGD3Fakx/dDfwfSs2XZnv9RVyM6a0I
mfaAquT61KrkHIbJ7CoGiYycdPWpkg2L8zZPaiN7lSikVvts8bkKxyTitG31WdVGWyawnysue56iraNlRtH
FJSaLlRi1sbX9tXHA6+1TtrEwQHPNYkR+cVJI5KkAd6qMrmEqEF0NFtblQFmIAFULnxBcuRs71n3KlyF/hF
VCNrgAHNDkCoQ3sXptQuZj87Yp1t5kjbsk496pxDecN+XpW0oSOFVTGD3ohHm1FO0FZIntJmUgZ+Qd6uTSA
Kvznb1NZIPld+tPDebHt+Zpc9c8AVpz2VjL2KbTJ3kY/MpPPGTULMxbAHXvWxLcFtFtLAWihkkaRpe7k9vw
qrbwxhj5wJPPfHPaptroNSSWqMyYFgFQYI6k0+COQxuwZVVBnk4yfQe9OkYl2GAMHBxTLgAKCvGKj1NHtYc
J2H8WSfSpk1EwvtckEdQeDVDTfEE2gail5arE8kZziVAyn8DWB4q8QS6trl1fopRJm3bSSSDSlOMVe+o1Sl
KVradz0O11RXABYVpxXIYAg15Np2rMgDSHC10+n64jAfNxRGV1cznDkdkd0kgPfNP3DqMVz8GqxHuPzq0NQ
jOMHFWY2ZqEgUgkwTms77UrDIalWbNSy1saJkJNSxOcA1npIeCKsRuccYpWHc0I58gDPerMc3asczFTipop
wcYponlN2GX1NXIpjnPasGOYEYzV+3lz1qjOSNhZCaduJHNU0fAzmnNIMdapGNjzBrdWQ8fWsXULJRMrKCO
etdPJCVz6Cqd3D5kRXoRyK2nG6OeE3Fj9LQSRrFcjDEY+tPvvDcbqZIcAnqD0b6ipLCKSayV0P71P1rX0u7
EqssnyuOCD2NPlTVmZ88ovmicM+lvp6vcWyv5a/wCshPJX3FOhdJolMfzA8giu7uLQODNGAJh37EVyl7Ziz
kN1CFFs5xIo/gb1+hrnq0OXVHp4XF875ZbhBauYwSnyntT3syWXgkemOlXIpiyBQO3HFWQkjKN2M9+1YuKO
xTaepnwWC78BlU56E1pi3Mcm2T5dvGKXaAuCATSIm7gg8dcmiLJm3LUHXui0MOACcCp2Hyjb29KRPnGDzjr
xT3ZHQjRDggDr1q1DbKo37ehqO3b5/mAGOea0IZVwwHQ1asZyuQXEixxAjOT6VQbLLuI6VbuXU8Z3H6VREx
XjHB9aGVCGgwy/wgY/rUbQnIyPmPNWMiTBA5qXbtXLHJP6UJXKbS2MW8hVW+7k96rJnBU9e1asyli/Aqs9r
vGTwR0NKRottTKkV9rF2J7VRkAReMnnrW09szMQTnNULmAgEYwQenrWbR007bECtwDyfrSTFi4PYelNlUiI
dcDtUUR3bhztpqXQr2a3GGLcxOOc5pUUA89T6VaVQMDOc0hjUPkYPtVNEuXQVFxjJ4qJ/vkk/KelSvzgCrK
QK/D4wvQVpGJhOVikscbgkZyKrzWxRsAkr1yO1ahRcnH5UhICheOatwTMlNozbC3ElzszwBnNackCjAVhx0
qvGFim8xTgmre4suR17UoJRVhybbuQbAccZPvVyzA2yb22YGV4zk+lVFY461PEcjIz70uoPYsiQHYU3CZDn
fn+QpgclgD0znNRvP5WTjORiqEty7sQTtAp8yRHI2XJ4j5rEbcYzn1rOvJFRTgmo5r8JAw+8+euelYlxduz
EsSQaxnJI0hCTepDdEs5ZjkH17U/xA9tDaWQggaMrAN+5t2WJ5I47+naoGcStgnAzyaq3LG4lO4fIDgD0Hr
WUNbmtR7amaRNKQoOW64XgD61YFxNblVAI/Go2lEUjLgGmKzyvlBuk7e1aJIx1foa8OsyrgKCQPWtm01RnV
SSRmsK3s/LCyzOAOu31qxHMVl/dJn61aVtzNyv8J1sN4xBLHjtitO2vQVBz+dcOLueM/Ku7PfsKlFxcKw+b
IPXFX7vQi8up6HFdKQPmGasJcDsc1xVteuqDcauwamOBuqXEa1Oq84nuKfHJkCsKDUFY8mr8M4K8GoZojai
k6E/pV6K4CgYNYUc+RjNWEl96VyXG50Ed0eOasJKWHWsBJavW8vHXmquZyhYq3VpsJOKzLmIc8V1NwinIxW
TeQAZ4rtseTGRkaJKLe+MUg/dvWrqWnSRSG7tuMDlf7wrEuf3UqSY6Gu605kvNOQ5ycU1qrCqPlakjBsbtZ
UIPOeo71Df20TK+5d0Eg2uB6VLqWnNaTmSLIU9hSB8w/N6UvJlJpPmiYGmxvDNJbudxjPyn1Xsa3Au2PPU4
rMeEf2jbM0qQru2NI3QKemfx/nXSapZxWU5giuY7kpjLRjg5Ga5eS10emq/NZsyGyVJx1qORmhXCgsc9fWr
zw7thyeRwKbPCg5OePSsnE6I1EVVdyAcHr0qxDMEUqRhuDmq6480heR1p+CSRt49acRyS2Bly+cZJOfrTx8
q8nAPvSbii88+g9KV2BwcnPWi3UCe3aA+YtyJMFTs2kcN2J9qp3Uaw3BiL5dDgZwMjryOf51K+GUHOzjH0q
O0hZIxHcBX2JtRwAvfOT61S1JejuIyFSASnIBwp4FK3IIxzRIcyA54HekzkEinIaEUAg5AJ61CUJYg9KnUH
JcYz60jYUEkfrUoaWpB5eFxjNVbi2UqTjJPetEMHUZ4qKRNxAByadjSLaOfktSG56HpVaS12n5V+tdJNaBw
Djmq0lvg4xn0NL2Zsqxkx2hwOP8A61NnQQg/3j0rZFs6nJ6AVVNv9pm6jK1p7OyMva3dzLhjZ2ywOatbWVu
wGM1djtBHwuTnnJp7QKAd3pxVRjYznUTMuRtqlj+lQ+ZvUgAZqzLFujPUVFFFjkggUne4laxG0Qx8zAGp1Z
VQ4PTjHrTJIi5GBgVJ5P7rjrS6juupCowoB71KjhSfSkKjaM54qtcP8pANJXRaVxb6VQcKeKxL29KZXlifS
i+uZXdIIV3OeOO3vViOxSC3PmNulYctUu8noKpUhQXvavsctcalJHIRIrKD6imC8Ei/Kd2T61d1OBXLhQMe
9UtC0tp7vziP3UZ6eprDlbfKVDFxkrtWLMAynON2cjNI8LyLsBHzGt5bSJD5khAGPTqaiEG6QyAAL/DnvW6
pcqsYSrczuYU1oNuxI+R1Y96ns7WOFQz8MeMVpPHtlUsGZuuAOBTZ1RNrMpBznFHKr3FzN6DVt0kA35I7Cp
1t4/NwBgY/Oo40lkGYxgeprTW2GEJPzdDWi1Ias7XKgtiEx/D6VItuDjB4FaRtlCcH5vSmkbAMrV8pNys9q
Am44wKzmULMdmSK1Lt2aI7RxVGIYU5HzUpNbDimtRkd8Ulwc1rWOotxyay3t0LB2GDTCsiy7oz8vas3E1ud
lb3gYZJ5rQhnDAciuNhmdRyavW9/ggE1nKNhrU6+OTPQ1bhkIxzXOWl8HHBFakNxuA5qQaO8lhBU4FZt1Bl
TxXQTxnBOKz7mP5OleifPJnG6jb4BAFX/AAnemMmJiTg4qbUYeCQBWFaytaamrHgE0tmatc8bHeahEs0TFe
4/KuU2NEzI3PNdVby+ZDuHTrWBqAAu2UcA81UjKm+hz2sKfs0wx1UkY9uam0a5MltGG64703VQdxHHK4qHS
CVtk4yBxXLPSR7GGs6bTOjRcxgk8Cqd0/pnPvUsU+Y8jHA5zUTsrNyBg1Ei6d09StAh5PvTwpLA5wM1KqhV
IyCvakJQD61KVtzbmbFcLvByMiljjLsCO9QqcS8jOatghV4FG5TukNljAByOnPNQQuo6k46YNWp5AYMjt3q
hH8zZ49fqaezCKutSVuW4HBpCncHj0ph5cY4xzU8a7hnP6U2rg9BoDZz26YqJwGKhOgHJNTSA7iuM+9OiTB
wQKl66FJpakXlnBJ4qWC03qCDzViOEuOuKsb1hTC43etaQhrqZTqvZFaSFYlw2Koz4aQ+WR9CKnlLSMfmOa
rwwtv3DBA61va5mm1qV5be4II3jn+6Kkht44htA+bqTVyPhsnke1EkQZy6DAoS6jc3sUZsKcYqCSMv8x+6K
vOnByOaqTsQo4JoYkyrOE3KD6VVEe6UAZwP1qfBkfA6nkn0pQpQL2NZspKw1o9qEYFRhcYHpUkjkggGrelW
j3M8caffkYKMjOKe7BaK7MS+BiG3ox/Ssy4+WEk9uldB4itDbzupbLKxBJHXFc7PHJcSKqnA9cVnUXLe50Q
qLkUuhJo9vGsMk03326Z7VS1GXcGKnp0q1LZOgUAt09axr20n3k20+G/uvyDWTq2VrHmz/AHk3Nsghie5LE
8Ac1tWUEVvYAEkE87V6k1haIt7LeyefGI44h82DkNXSwBPszSMMnvWtNLcaTtcrzqpGzb97pnsKmtollkCk
YRRgZoiVppVaQED+EYrS8jy4yx+8fWtErl7LzK00SRxlUwXPSo4dJdistxgk9quWsBMylyCPX0rQkj3nauc
etOyluNXWhmSWIDqIxhR1prWjNgpnArehgUR5xk9+aaLUtLvBwPSnyoFIxkgePG4Ek9M0SwFRl/yrclUMwG
ORVa9VSowc+1VygndmFJGWjbAxiqsUI37j1HWtgxGRiB0IqpJbG3Dd81m0ax7GdMQxIHShYyMcZrRithxwD
mrYt0xjAGKSTepTsjHlTcAFHNQeXsPzZrde2CqTVfyA7cihxuK9itapcgRusT7JG2RsRwzegrbF15Fz5LRy
xOgCukh5Dd/wp81tb39jaq9xNbvbJ5RAhaRTyTkY6HmsjWrszakvliUJFGkQaUYdwoxuI96znCy0FCfM7H0
DMnNULpP0rYdT6VSuIep7Gus+eTOav4eDXKavCUfzB1rtr+PKntXM6pDw1JnRTZo+Hr0SWg9e+ar6qT9rjx
WNoVwYLh4mPB5rQvpN94p9qG9A5LSM7UMtcYGA3vUsWmXVphZBGSFLMqNwMZ71VuJwtwZv4I2AJ75zW1Jfm
8xJcn53AXAGQqjuPesXZvU9GipRjoVIWJQbVxmlKMo+cjA706E+g79qJxlCPXkYrJnXFDTKixgMvzZ+9nt9
KiEhZwc8dcZpJASgZh35ApVVVJK8f1qGzZRS1J41LSZHSrO0IueD9KgtTjknA9KuBUIyT05ppGc3rYim2hP
mXFUsEsWHTpU9zK3IXkVDFGSAORnmmVFWQDg4659BViHauQTzjv2oit3kcDaWXPQHn86tSaaYioGWJ/Q1ok
7Gc5xWjGpCSQVBJ9qv/ZofKXLFXHJ75pFHkINnIA5q
GWQADLZ74rRR5TmcmxJIgrkAnA5AqCXnqKe85Z+wB4xTmjJxhh707XKvbcrKvyE8D3NEaiJflGdxqRioOMc
dyKVnjABUZ7CrWgXuQhGEhxjJHGaWPKDJP/16a0nLlR9D1zTY2LrlgPYelK4Ndxly20FhyPQ1RkZdwIxzVy
Ybxt7VRdcSY9OlQ2OKEVVjUtkDPTiq0x3vnHyinyls4boKSIFmJPQVLfQtLqQJA27d/DXS6XCtnp/25nYyK
SIkU4IPds+g6VmuyLb8jDdsVFBNJIBGWYR9xnitIWRnUbmjK8WTvdzxsieWWPIGTn1P1o0+x2JuYc+lXrwo
9ym0AleB7VeEQSPAwccE1E1zSOetWtBQRi3kG5cAc4rndR06ZgkkbtHIjZR8ZXI9q7C6XapxWS0DtgsAcHo
axlSUpWM6UncyouUfcTu6tgfeJoiiP8QOOuKu7VM2EHFWIE/eBWAC9a25eh1LuWrWNPJWSQYC9BUVyPOk5O
EHpVqQBwB2HYVHGqsxHbPAqpPSworW5LawIV4JA6VchhG7BqeGFfJGFGKl2KFHPNNIL3I2jCt8vSjyQRlRT
TKYmwRuFMlmbaeoFVoNRYFI0Ry45PSsmVlUkE5qzPIyxjJwDVQIGOTScjSMOrJECBAR1pzW6zqN35UxY/mG
DV6MA9BzilcfLbYqi1UNhRzUws9yjsasRABuQc1PjOADTVhSbM57It9KgkgCdAK3Jx5cfvWajyxXKyBA2Dk
BwCPxFOSSIi3IsE3Eun2a2eqQWgRCHi80qc5PJx3NYOrWkrXRa4uRdSYGZQ+4EemT6V0bapKnW3s+f+mC1m
ahI107SskaEjGI12j8ql6hGLTPc3WqlwnymrzYIziq0voOtWeCYN8nymuZ1JPlJrrb9Mj6VzuoR/KaTNqbO
NuMxXIdeOatedlWkLfdpl7Ed3uOaoSSZBUHAJ5FZydjuhHmJboExwoD8zt5hrRjwFUA9u9Y9tKZrsydQPlH
0Fa6FSMnr/Kudu7PVhT5YpFuEKwGO3arUcahT69hVSA5xzirC8BueaEhSViGaMqQSQD6VGBgYbjHQ1am5UN
np1qusay4znNKSRcdieILtIxk9cVaQM8ZKrhQO/f6VFApXC4/OrIQAAsRntQkZTZUWNg3PXripoYgY9y554
pZHy2Bzj9K29EjiSGaSch9uAq446f0raEbuxnWqOMeYi0qxZ1d1xkccnFXjAoXccbveqdw/mSKFyFB4C8VJ
I3lo65LEjjvXQrRVjhleUrsSdRIhCBBx2Gf1rHMBL4kJ+U1fjuCGEbDbgVJJEu4sTwBn60tzRLl0ZiXcWwh
s/QGoBJgfIx561cmAcrh8gt93HQfWop7byxkDknis2tdDpi01Zkcaysp6kU4qwj8pwo5zv5z9PpWhAmEHTp
z6VFMhxgjNVbqLn1sU2gZQqqVUYwTSGIqoKdMfWppSxIK8jvSPJvHBxU2DmdittxnBzVSRA0/BPHPFXRjdg
c/WqFyWSY7entQwWo26zjnGaS2jJXJ6Dk09cvw3WtHTltVuYl1BHa2J+cL6VKV2OUuWJmyKZpAq8JTljJVm
XtVjUEgS7me1Gy3Zv3a5zgdhzUjOsdrjC5Iz9a2trZmEp6aHNeaReMGJODiteCXdEO9clLeqNUuYXO1wwb8
xWpbXyqnJFc8JrmaMa8Gac8oYgcEE9MVUvpgvyxDLHgD0qITmSQt2HQUoyr7vlya3vbYdKnyrUrxx84YYfr
zV1AOA6jgdqesIchnIyKWfCsAMkn0qTo3IZA+07RjPQ1LbWxUgnr9abKrHaWPTtVyAYjDE5J7VO7NUrIsQO
SjIc5HShXZfpQPUcU05AJqrgog8oxkCqtwXZdwPy1YVlP3ulMmCk/L0Ip3Ha2hnzr5gyTwKWNMpkn8Ke6kZ
FPtlJyDUGi0Q6GMgZq7Eg2ZPWoPLK421Mm7GP5U0Jq+ogB3VMikYOOak8tFiBz81OjUkDNWkQ2NZC/WmiED
IYDNWSQi+9RbHkOc8U7mVisbKaaSMQws28kLx1x1pl7EqyiA2xhdMBssTmt2KY/YiRDOWSLyN6r8ignls+v
PSqd6okvOEZVjVYxv+8cDqaLEqbbsz1Zun1qGQcYFTkCoH4PtTPDMm9X2rn9QUENjrXTXmDk1zuooQW4oZp
A5G/AVjurmLt/mZFbBPT3rqtWGN2RXLwpO1y6Bep4G3msKux6+Bjd3fQvaTESB/d6citiJDk+nvVCyUoABW
nAeecj0rGx6knd3Hxq2TkYHXigMdxwckU9+SNuSPWgKAeBzTsZ+YifNk8g+lORMnsG6irEKK4yhzntinQwM
Zdu35+uMUKLJc0T2Toq/6REXQgj72Oale3PkLIBhe/tVvS7ZSzi5U7R0BFaDQ77d4lAC5+X1H/1q2jTvqcc
6qTOfjUYIPQ+var8AZLZoe4bJwc1Yt7JY3/eAMfTPSmBVF4X6K3rVpWFOfNohjw4A2kg5wParKQjk9T704R
5I74NSlTtPsTwKtLUwk7mfqcXlPFMi8fdxVOdpJVQkYQ+hq5rTE20AVeN3NKYhJGoZcKBxipau2jSLtFNlF
VRXJK8HrTbw7IkzyoOM46VZeAc7CW+vFRkDaY5AcEYNFnsWmtxIyMDbzTJRuQtnGOtViGtp/LZiykfLU7tu
TaDtHp61Ll0G1rcrrkIQ35U112jAB6c0rcPz9OtLnJznikiipzv5OBVAszyknBWtC5wsbE8E9KqxwbVBPOe
al66FpqwijDA9z0rVmEdm9uZIpTcrkzRS42Y6rjFZiRyOXYKSFBb8BRdmdLgJPE0LBQdp7gjOc1cdCZRuyL
U5CYgVGPmqOSR3j4IJ+tQ3cxkO1PXrVhQsUPGCxHJoi7yMqzVOK7nIalpAk1FrqVyXwAAvA/GljiwyjBra1
BgOp61nWIM15hRwD1rBpRnZERcqi1LuAkGADu/lTxEdm4cnrU08flvh/wCKnKNqADpW7VkarXYjj/0h1w22
rflCL7xyarIuxyR1qxEhd8k546VKZs4kgj38gZqQJvIC9O9Lny4zjiiCTb84wQaeg4ppEh+T5QM0jvuG0Dm
nbt3Kjmo1G56CkraiPEvllicGqbOEQ5POa0bkAJg9azJsHC4xQxwV9x4kU8mp4QCcr0qBYsAbgMVatwCOBU
jaVtCSQE4x1qRBheeKZyGxSkE96oErlqBEKksaa77ThfwqGNWUZ7VKoB5J6VVyHHUey7lBJ5qRWAUYNNOMD
nimKyhqZla5sxSQTWvlm4jiIhMexyRzuzmq160c9wvlsXCoqbz/ABEDrVyFrlrS2FikbgL85KqSDnvntTtR
fdFKziL5SgUqAPn/AIgMdRVHPszu+cc1C479ql5xTCMg1VjxzOvDzxWDqOWBNb13nnNYd8QEJ7Umi4HI6wM
I1ZmnXkFpL+
+ijm3rsyhwVz3z2atLWn2xsetc/ZRhvmIBOc1hN2Z7OChzp3N9IhJIzxRbd7FgB2HYVp6fYtOdzKVjQfMTx
VSwYiCNAFBBOGHU57V0tvBLawyRTqhUruxwSPxqoxTNqlRxVkZ0mn4i8yFwYgcMCMFTTrazgljZRv8AMxnJ
x0pLgSLFtVyVbDHB4p0IwysOooSSexN5W0ZVEUkUxSNdxHQjvVqxWRpzI52hfXrV0HzASo+XPWoo8pMQvU8
ijls7oTndWZf3LsZuuBUkcu+BcdagLbomC9+tR6bKAGBIK9DVt2Zz8vul4ZJOe3rVKWB3uNo4CjJrRUqQDt
IP+cVBtJ8xs8tQ0SpDFfaACMEdMU5TtGXxhu49ajeM8BT847U5M55GOxpoTIr9F8kZI61Crs6BW4x6VJOyy
KY0JJHeqyGTG3aN1KW5aXuj2ySMdB7VA7ZdVjIyOSad84fy3Iy3OaiKbCdp/GlctIjuow0kZbHQjJqBgR0/
HFW5QHAVucjAPpTUyCYzg46+9S1cadkUXG05xknpUeSiFn+76VauU2yEgA4qhfNhAp6nmpeiNI66ELOZZuT
wO1SNMmFVuvT6VTDYDY61BM5BTHBrNSszf2d0asZlHmeTCJcRsTk4Cjuff6ViXNw6sIwWYAZOTnHsKkmuGR
GdydoGB71m207y5YgFmJxWk5aWCnC15MuQSIjBpc8DOB3NMvLxxyEwvoOtW4LQFi20n61Hf27FR8tTGMraH
n1pxc9TDv7mOUgJlM8DcauaDbeW5aQnA5qjNAPOUEZwc4Nben7WhckYBNTCD5rs1g1yXRLeBZGJB+UdKajE
BdoBJ9acyqEJJ+gptqpJJIIrWRpTjoT7BjDj3ptv8txhalk+YUgQqA3Q0maR2LAj3A7x8ppggAclThamLHy
qYuAvPSm7DjcBhRRD98kDihQGJ5wKCuzJB5pGltBs8ik5PUVRDhpACKmlyQT3FVFUswY9vSlJ2KjHQvMdy8
YFOiUquQOKjibcOlWWf92FGKYrW0EDKc5P0FIgPPXFJHGGYE9amcbeBQPyJEDOoAHJ4oZNpwaS3LbuDVqRV
IBbqKtLQyk7MgQZyCaQrt5GacEy2V/U1Iw460ENmvYCBIYv9FWVnhaQOcnLA8r+VU9aZBcjZGIwUVgg4xkd
6lh8qG2t28ueVjlt0b7Qpz0471BPGs0zSlZF3f8APRixz9avocy0ldnpRApkntUj9hUL9Cao8Yo3oyD275r
A1E/Ia3rzoa5zVHwrDmkzSBx+vvhGFZWnjCgHnJq5q7iSXywSG9qbp8TA7SuGz3rmnqz3sEuWm7m3o0BnnI
PCLhj7j0rpysQBeI/Jn5Qew9xWNo0BjtnmAbOdvStuONPL3xquSCdpOCK1grK5nWkpSK80GEDsVJlUMoXtU
drCXZgRwo+Y1IAVWHnGQT04o2EOxiz1wTTfclS0sSW4K7l3EopwKLiILtdV5yBx3qRECR5GffNOJzszjAOa
EQ3roOUDYcDBNY7MYroqpwG5xWwW+YHGM96wNWzHcK+f4sUqmiuXRV3Y6Wzl3wAk5xzg96JXG4hFy3X2FUN
PlcxY6LxU/mYUk4yTzV30MpQsyRP9YSck+tQSILiWRg3yg/nT2IZxnoexqNGw8qA8BjSEl1EUBHHBxTGYsQ
PfilPReep5pXG0gKAXP6UMpFeT5ZE3HnB6VG/v29anljAjYnl+pJqFlwOSMGpKQijLbiQFHNQK6Ft3Qkk5x
ViYbjsXhRyTUDMgPPTpSY0QTqcnLZ6VS1IqWQLg7V5PvWjOVdwe2AKxbpv38g5GDUz2NaSuyDkn2qtPlJBJ
J9wcVaLfu9q4yfSpp7YS6e0nyiNdocscAZOM1kkbynY5i/uvPkVEPyA8e9aGmW5eQBenQ1n3EC2+oGPKOFY
gFDkH3FdFpChUz0PWlFc8tQxU/Z0kkaDIkYCpis+/fBPcAVcupOM9s1lXMuVOeOMV3PRaHg7syHYNNg8t6V
pWeIoAG7msyEZkyeoJz71rBcINwxkcVzp3PUpx5YJMfK2eUXNFuzD5Txk1JGoWI54NMVQ5HPSmzaNrWJgyh
yGpYiJW2sOO1MSHBO7k1ZtFG/6UIp2SJCqxptHSolO44IqxcHacjmoolBy3egI7XGlQoypoJyAf0pGzu46U
HGKRZFcgBOKprkIQOlS3BIGKZjC1Mnc1irIngUeX3zUoU4qO04XnrVgtgetNEvRhCrcnPNB3M+D0qSJsDJH
NOQAt7+tMhvUcibcelT8NnPXHSmo2Qe1RhsHrirMnqKw8t8DHNIXGQCaVsYznmkjk8qVX2q2D0YZH40xM2I
rgNaQLDfrAQuGQbhznrx3rP1B5BISZ/POB8+Tz7c1J/aRQFjb2uP8ArkKydR1Mzux2onbCDAqrpGEYPmPYM
gjNRP0oY4/ConYAHnFUeIUb08HBrlNZn2q1dFqEoVDzwRXA+J70RxOQ3NTJ21N6MHJpI5+S9H9rL/czhj6V
1tvEjkHaGA+6RxmvPdO/0idnYHcTXd2MrLBGGwTtAGDWFKV2z361JU4pLc6GFFhixGzBGwzA+tTwsm4ZBA6
ZzVIHeFj53DrntUruyuscSF5WOAo61uzjsWJ/9YojHJPTNSRxeVwxDMeSRUUDPvWRlVtoIxTvPBlIAKH0al
bqxeSJy2G4XAqGTAKkYyOKaHzwT0pk7M7mNMDA5JpCtqPZiTwenpWXqeGMWP71XTtUrycdMZ4qneqMAv8Aw
sDn2qZ/CbUtGjZ091FkY9nzbgd3tjpiopcFvm9afYBpI2K9AO/f2+tVpD+8Ktyc4pp6GdveZNEVEgB+8eaR
cJLKrDo2fWiNVPmyDlkKrj0FIV43g/MeSKGwE43kk4571JgZL5/DvUU43xD1HNCfd3c80XsTYeq7kkyeoqA
xjOWNSO2A201XmbJAHIouNJkUsmCwTPNV5FUIB3NTnrnHeq9wxZ+owOlItISQrg46nvWbqBUzLt4IXBNXGV
iV5AAHNZeovmXjJKjBxSextTWpDvCMFOM45NVbmYPIEZuO3PFNuZUQ/MwLVj3EpLGXnagyB61i3Y64w5ieV
wZpHAyFIQEdPrXQaXIzbduM4zz6VgaZbS3qqqjAx8zYroYLNIIwoBJA6miEW3dHJjZRXut6hfS4+UHp3rPk
dcEscmrd0gVegrAupSsoQZ59K0nVcHqcEKansXIgHlyOhNakjK6IMdKzbJSSSO1WWZzgKAPemnuzvUdki05
Ty8McU6J1MeFFV3hJTLnJ9BUkSsnAGRSuy+VE0Rwx3dKsRgAlgcVXU7pACv1q6IlUDiqWoSdiGR2NOjBxkf
lSSjIwo+tCBkFD3K0sPP3s4qvJjd0qb7x5prDYCT36UMFoVHUM+TRIoyAabuLyZp5BJOai9zUkhAGe1OQ/P
zTI++aVSAx5FNE9Sw3PSpYVY+
+Kiz8uamhl2jGOKpGcthWLA4q0tsDbFyRk/pVRWMkoAHNSzyukewnAq0ZSv0KEjEHg9KfFcKsgZ0WQKc7D0
P1qMsDn2qhPLsfvj1pbamlr6HRxh54fNFjYJGwLDzJCpxnGcZ6VzmuAxX8kZSGJgBlYSSo/E96vR3aGGzMs
EpSRHtS4IAdT0xnuCfpWdras18EEckYiRYtsn3sAdTilJ6GdOLUj2tm68/jVO5f5eCKfNKAD6fWse/uxGjc
/rWx4CVzP128CowzjFeU+IdQ+1XhhjOVB55ra8Ya6I90aHLNxXF2ys8vmMTknNcdad9Ee9l2Ft+8kdVolqr
xLsI3+hrbMn2QojHfx970rmbGRoCGU9Oea0FufOPz8E88U4ySWh1zg3K72N201JZJSJm5OAGP6VrRHDiQyM
zdASeRXG8rz+tWLa/khbIfI9DVRqW+IiVC+sTt4bghcLyO+ajnIkiKvwRyD6VjWmqxlcshBHQZ4NW4pWvAf
mCpnrWnMnscjhKDuarqipG0TZBUE/XuKhaRgWY9W7D0qMqU/1TZx1HrTGePdln2EdQaZKRKCGB596juwXhb
AO0ckfSoRcttbaAQAc/SrFq6yx53A5GPpU76FpOOpq6LcF4JEh48xc/exjAPeqF1gyq3Qd8daj0+U2dxtdV
dOcL2INPkBd8sMdzRfQlrlk2hSHs7+SE5YOoOO9TksDyOv6U6K4dddSVSoUxgK78jgVJfKyXBB4J5+ooRLe
qGbFCnHJxTLfAiPJx704t8jDGew96YpUWynIOeDjsaAsQyuN3C01Bk5A3e1PkwVIzjuOOajMmNoXv1pFWGN
jd83T0qAxj5ian3ctgDP51DOfk4OM00CuRYDcViayypuPTLfnWsX25x2Fc1q9wrxE5wyt0olsdFGHvGfefv
WG0ck8mq08cjbI4wRuYLkc5/+tT4Dvkya19MiSW4Ei/OYhwB61g1c6Z1PZq/Y1dPtUtLZUAGQOvqaWRuf65
q1FEzjLjFJc2wdMcCtkmloeFOopSuzKuFBHJ69Oawr5B5gOefSr9/DLCzBGIUjvWOsjs4idV+U8N3IrmnO7
tJHTQjqmjb01SIyxB5HFT7NzEelRWjEQ4x0FSQsGGB1710LY61u2Sp935+McVIqkc7sj601lVF+fnPvSj7m
KZSbZNbkCUk1YZiwJzUFttL89andjkhRxQtCXuQPlhlTyKkRj5fNHC9aMgr6CgsUckZNFyuIx3+lR/LvHNE
8ozg0n2GlqVUOCafnjJPNJtByRRuOMGhFvUegyetPKoGHzc+lMjdRkNSRgFyecUyS4iFhkdBQX4PqKRJgi7
QM8VTuZ9mfU88UzJXbsWUl2Hdmory4OzJPGOM1kvdkvgE0ye7LR4JwadynTs7mjaOJEJLZqC8jMnyxAtIfu
gDOazLWVwzYztJq7G0gYOrMrDoQcEUubQXI1LQvQWi6laWn2gXcLRJ5fyQF0dck5Hoeas3yb7pf3ciKkaxq
JBhiAOpqaB4LOytfNuNQV5E37IpAFAycYq3d2sZWSWKe4kZFRj53O5W6EH+lZvUlPXU6m+uljU81wPinX1g
RwrZbsM1H4v8AFEVlG4Mg3Y4Ga85+2/2nP5kr5BPAp1attFucmEwfN78tiR5Jb24MspJJ5q7EmF4OKnt4EC
jGDVhYMcisFFrVnsKatZEcT7RtJyKnQMG3K2eOlIYwcg9aiJeHoCR3NUilZmjHPuwPzBpxRtwIJx6VRRwxB
WrsUp3bWH40biatsTxMV6nitOxvWhJBBKGszggMOacjn2PtSV4u6M5JTVmdKl4j7RETknkVK/lliZ/mzxXM
B2VwyueOmKv217vGyXOSetaqpfRnNKi1rE2ogqKVzuB4BxziqMDiOcqNxXOPrQ17HGRls89qriTdO7jjuB6
UTktLBCL1udBj/VtjG2pHfIDZ6msqG+c4AwasRzl2w3A/lT50Zum1uaBkK+Q56MMdenarV1PuSNnbLIuw57
Y6CsuQq4Kk49D71WNxJIojY8A5PvTcrE+z5texqQylyMjDDsOlKygMwHAPzVSgk8rBAycetOa7eRyDGNvrm
kpJrUTjroWnICFj0NV2xy5yQKUzCWPAOD6UrttUYBxiquLYqSybFZgAMVnxTtJKctkVculD5APBrFeQQzEA
gDNRJ2sb043RqSsvlswXrXJ6v8rhUUZ/i5remkPkEhgUPSue1RGeQyJkk9cGqqPQ0oKz1K0WUIyACBXV+Hr
RUgDrlWlOWzXJaaxbUFR1LDBOCPSu0tJgY1LcGop2crGWOk1GyL5XJIQ5rLv5Jl+VWwOtaEdwi/dIDYIzWd
ckOxDOD9DXRKKeh4ybTKjypJGRKeRXPyKnn/umDc9RV7UoyCykkVjwARSE547muWaldXO/DW5jctGIQZIz7
VYxjLLgDvWehGwHPbtVqJtyEbq1TPQt1LanODnNSRtl/mOBUCZCgDqaQRlZQXPBpjsi2QFfcCcelTmQkfL0
qqjoX2g5FTEY6HpTRDQp5OWbiopJDkr29qZI2WVQeTzQyYYbTnPXNDRSdgiGW60TEhzxxTIhIt0x42Yp0j7
nO4YHY1PKUnqOVgU6UxWz16U1pPyqJ51VccA07DLR2KuTULTBeQeM1UmnJj61TkuhjGaLijE1Wucrnr+NZ9
xdFiQDyKrNcfIQM0yKFpDk5pXGopakbysX4FTRI0gHBqzHaAEEitCCFQKVwlLsVraDYPWpgp6VbEeB2pVXn
HFTIUTTsmFvZwLeTRkOC0UbQCQqM9cnoM9qnn89XeKSUSJKVkLgY3DHy/Qe1V7aaNoo47m2Wby+EbeVIHoc
da1mgd50aVVGUUqqjhVxwKpamMvdep853rXt7ctLebjk8D0qS3Hlgbcg1rkgjBHIqFogzZCiuTl1vc9NaK1
ieyv3TCt0rbgv1IxxzWCirHg1ahZGbpitIt9TOUE9bG6soccGnAnaQelZq4T7xz6VZW4AwB6UyLdiy8QwNv
FJvKjkZxTElBPXr1p5cDjqD3FA0SRzHIG7FWVfLc5xVAggbgDUyycDPPuKYnboWw5PC9acGIPWqqkgZGRml
EnODgNSsKxbBDDcOCPepo5mYhWOD7elUNxBBzQ0u1xjnNQ9BqNzeH+9wOetWYpsLkgcnp6Viw3AG0Ock+ta
NrK
rDBwvPX1FVF3M5RtubKurRgggHGaguFEYDqeP4qgAYAHzAUJ6YzSTFpPlUjk4FW5XMYxsycSfKNx985oEm/
I3bfam7FRQDyR1yahY4UH9KjULJ6EwJ2hwcEZ71ZW4ZkAyDkdQKzfMDH5XBFOaVowdpGOlUp2FKFy84Jb5u
gFc7qhEFwdmTu5Oa2vtSeX83X69aw9amilQMFJK9ee1VUa5bio3U9ShLekxeUchT39KjldSu5WyPrWVLOSW
XJ+hqWzWWadIlOd3HFZRqN6HbOnyq5p6TazT3JdAdgGNxroEtJEHJzWhp1slvbIigcdav+WNowRn0rrhRVu
ZnhYjFOUrJaGIqAA7wc+tUr+23JuVu/Y108lruTpWVqOn5gb95t78U3F2MIzTZy10zKCGJH1rFkLb+5BNdK
LMzMvmMcDiqusWEcO3yyOTUyg5Rujpw9SMZpFW1yF65zV+IER8kVmRnacd6vqSqgMck9KiJ672LgYgAntT8
iQA9KrM5KfWpUJCD1q0Q2D5U5TqKsQvujJY81EzAKfWmiQKMHrRYm91YnPEm4YI7U5XHXFVZblFTHGfeq63
uEJGDnpTuhqLZoNJk+lRXMyKvDZrLlvDtJzVCa6YE85qHM1hSua0lyoWqE9yC3NUhMzg4pgV5G71Lma8iTL
kk5xjPBqOONn5qeC1LgZ6VqW9oqr0/Gk3czcraFC3tSx5rYtrcIKfDAMdKsrHjpQkYydys64PTinR/pVvyg
RnANM8v5uBxVDTQ0HORU1rGvnKZkZk7hTgkfWpEhyOBWhY2jTTpGuAWPU9qWrYpSSRYt1sB0tZ/wDv7n+la
pKyOrIpRQoUKTk8Uy2trPoHmbH8QUYNXHg8hgAdykZB9RWqVjhlJNngslqozxUQt8nArWaNBnmoNnXHSuOx
9EigbYjNNEBzwOavtgU1etMTRFHG7DBo2Sx+jCrqBe1SbFYHNUkYSjYoo4YEDgjtUsMhXq34Gmz22clOGqu
u8H5h0otcjY1kdSOCOe1NjYCTZ2NUoJMfXNT7hIfeglGgylcd/pUcmOM8GoYp2ICN94dDUkhzzxnvT6CXmC
NuYrkdPWms3ADHvVeQsjFlHWnHbLGex7VLVzVaEySlT1GR0rU0+5BB3DkmsJwTHlQC1SWsxU5P3unXpUJ2Z
TipROwhPmZXPzHP5UBRG4y2cHr2rMsZ+g5yO+avyMhhLeorV6nE04uxZa4RucnJ/SmO+MEjKn0qCJl8oZP5
0SMFTJyV78dKkWzsSGVApDAAHofSqczN3Y8dxSSlEJy/3ulUp5sx5+8O2Km5pGPYmN2qyYJO7tnpVDUZcFi
MY64Heqs12VbGCwPHFQSToFw3JHvTvdWNOTld7FUOGJPbrzW54chAnMh7cCuelnEYcggKT0rZ8M3KzRYRiS
TlqUU0ycVL92zu4pVCj5selD3RU5Bz+NZyqCn3jQYiVwrE16PPaNj51xVzUF8BCC0nPcVUvLhZIjmTtx71i
XHnRSkMMioZJDsK5+btWSmy/ZGhLcRooCDLVj6s7mEu34VZghl25HJrO1ppFQIVPXnirc/cNKUPfRRhlJck
1dSTdgn8Kxlk2N7VKLnHfpXMpWPcSujaWXnnFSyT7QOawXvgFwMnFQvevIdpJAqlNC9m2zde9EhwTwKqm9b
cQegrHa6YHaBx600SO54zUuZqqVjYkug2cmqn2lg2AeKgSF3I4NaFtp7NyalybHZRKsjyTcDpVmGyaTGela
sNgEXJ71dtoNpxt4ouQ59jGWx2tg1ajs1HIFazQDIJXmlWL2oIuVYogtW0xjpS+SwIG2pFjPpTQnYAwAo35
HH6UpjJ7U5IeR2NVqTZDQ7KMYzU0ALcnirEcC59anjtwDkA0WZDkkLbpkjg1r2ULCRGjB3g/LjrmqdrHnHJ
ragiIUbc57Y61pFHLVmWYlkBy1opb18s80lwXZv3gIb0IxilmhupGz0J6jfgk/TNNCOjlZMkjrnrTk7HOrP
U8lktUZiQABUD2Q6DrWi54puNynmuflR7qnIzJNP7jmqctsUaujRTt5wagmtw+ePpScOxUazW5zwDDOaBKc
8E1qSWZ54qpLaFc/LUq6NOeMiuZTnPWmtIr9etJLEy54IqqWwcEc0c1h+zTJpYznclNSXLY5DUqPxg1E6Bj
nvTMnTaL6vhQc5qTfkctx9azUaVBnripA+RlenfNUmZOLRZlI7E4qus4SXBzg1C87I+c5XvVOeXLFlHvikz
SK6M3VdShycE/rVSVvKnAXJz1qpb3e8Jv6iiaffKSp6VErWKgnGVjoNOnJXbnDVtBw0WwHjoea4a2uSJ1yc
e4rbs75vLJyCO5PBNNSM6tPW50K7DGQCeOCx4FK8qgZJ+X0rFN8vlbcnIHftUrXKeVj73HPFVe5g4Nblh2W
Y/iSOf0rPnlVBjHtkU2S5QBwuOOorJuboqgB+b0Oahm8Exb59pOTknpisyaUh9rSE57+lOuZUeNvm2t7GsW
adwWD8gcZFZvQ6YRvoaUkwDrk7gK6rw7GIrcOv8XNeerc4YDBIJ6mvQNLkP2WLAGCK0pO7OLMI8sEjqYG3p
ipxGwGVJqjZNjGOa1Y8AZwK7VqeBN22IZIDIvzVltbqspIBwOtbxbOSo6DtWVf3KqCpGKHG70FGTI4Z0U81
FqeyWM8Cs9ph2PFQzXmF60S2szenTk5XiY+oxuAfKXNZfmNjDcGtW7uWZSEPWsxIN7ZJya4m0fQYalK3vDV
duBUiRu56Vo2thuGSK2LbTRjp0ppNm0nGJjW2nu5G4cVq2+lc5xW1bWargVdFvgfLxVqJxzrdjJhsNv8NXY
oAg6VopAu0A9acIlC02jPnuVEjHfpVuGAH6Uoh54GKnhTHA60Jdwb0I5IDjOOKhAHStSRMx89azZIyGOKqS
sTB3EYAjrSKOKaVb61NAgYAnOalPUt6D1jyAakWIZzUxUbAfanRDc/4VoZNiKCGHGferEIDA+tTJbs3IFSJ
EY25HWqsZSkmSwREDOK1LV/JKsQDj3xUNuoKj/CrsKKkqMwG0Hnig5JyuQvHAGyZJFyehTmpJn3MpVSAFAG
epFSM25jHOwdSfvDnH0ousb1CkEbQMg1L2IW55A5JcgdKXbgU2EEvnrVhgGU1ke62VVdzJweKnJI6ioCu0/
SgS89aExuPNsT7gM5qtIS54WnlvXvThjHA60CskUpYQwPFZ01p1OOa3Nm5vY02SNR6UmrmsZtHMywMDwDUa
hl+9W9PCvtVSW3U9s1nZo6IzT3M0TY6iglGyOnepZrcqCR0qlIGHSi7Rp7KMtido0YcHmqVxavzsNSbmAzz
SfaGHU0c4vqz3RSnEyQ5VfnB6CqKXTq5MqsAa3POBHzCmvFFKv3RSeoeycehnC4DHhvfNXLa+8vaCeB096V
LSIHPHHSg2ak5WlZkSj0sWBeblHmHrzkVMt22GCnj+EmqP2DeMnI+hpTbSBNu7IHNGpDp3Qk12Y1+
+CD/Oqst6Eypb3WpZ7NnULk1UOnyEktnjpSsy4xVtSGafzG2twSM81TuSGwccj9atSaXO77gMccE9qUaVOQ
BngetKzZbstUZUbsZkXHGa9E02ULFEPYVyH9lP5i9wDXRW26NVHoKqKcGceLpuqkkdnaSgIpz0FWVvVAIJG
fSuXivCqAA01rlmOQa6lVPMWWyk9Tr7fVooVcOTzXO6ne+dM7qcKTxVFpWI61C4Zumal1mdNHLIRd2Nec/w
k0zLuO9Sx2zE5IxVtYcAcVm5N7npRpQhsjNW3ZmHFaVpp+cEirFtAGfpW5awAAHFJRuKrVtoVbWz2r0q9HH
hc+lWRECOOKVowFwta2OBzcmRRlRJuxzVtORUSRZ7VIFKnB6UJ2JcUyQnjoaj3Y9alAzTTEeSOae4JJEkbZ
ANPVwrdKSCE7eRRJEc8Ckw0ehY80baqtgtkU7YwAJzQAOpFO7YJWGMAB70RMN3Hao5T83y5qSCFic4pO42l
Yu7dyDAqS2hPmVYtId2ARWra2XOQK0ijmnUUdCWwtsoCcVNdWnyHAyalhUwcHpUkkylRitLo4nJ810Z0H7v
hhj2q6jhgMdTxionw2emaSAKsoY8etZt6jlqiwUQnBbB68LxTWRgSuBipkQ+arfP8oAwBwfx9KSXGBjBwAM
0GXMeNWnUVZY8Giisj3ZblC6cqDg1WhYk5PU0UUM3hsWU5IzVkDHFFFMynuMfgcVExyOaKKRUSKYdKqkkNR
RUPc3gQTHI5quUUjpRRSZ0Q2IJI1IIIqm8a8cUUVmzriROozTTx0ooqRscjE96kMjKhI60UVRFRaE8DFo1J
6mpCARiiirOcXYEUAZxUigFRRRTiTIXaKYwAOMUUVRmxgA9KTrmiipLQq/eqZPmGT60UUIch+MGrVsiknI7
0UUg6GlHEgXpQ0a56UUVRhF6k1oi56VrwKNvSiiric9bclPy9Ka3OM0UVRiizABtpJlAPFFFBHUegGasKMA
0UU4ie5YQAKDinqoL9KKKZJDdKOccYqn7ds0UUGsdhyovmDitO3iX07UUU+hlUZo26L8vFa9qfk+gooqkcd
UWQevPHeqknyniiikzNDUYkc1IvFFFSUTLxj3p45U5oooMpH//2Q==);\">",
" </div>",
" <div class=\"lgnd\">",
" A white plaque is present on the buccal mucosa.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Leukoplakia",
" </div>",
" <div class=\"cntnt\" style=\"width: 324px; height: 432px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAGwAU
QDASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwCe4keNA24lhTLNvNVi38PWpJkEsIxxzUlsgjiYBfr615Ku5H1N7Iarsm
Mg4qVCoVsjJqIZEmCPwIqyqHYMANnvitkjCbHFESNSpGcciqUpwrMD9cU+4cbWC5JHP0qtP8sYcfdAyc9zV
mDuZ11F+8DMeByDUIcKoI57VcmG9Cynk9jWc7FIgFHensCY53CrnnJoQsCxY8VA7GNRuOe/0o+0B4SAeT0q
E7s1RL57IpwcnNOeXKZJxjrWO0xMpUnaw9atlg0AOTkdaHc6LJWJWm+UEdKm80vbgkEHqDWbK5VBt5GeasJ
cbrcHsOKlHRHYtwysz8+lWo1DZzzjtWXGx3AqeOuK0Yc43gjJ7VaRpcuwSFCA34VYnCsQyjBqBoz5eWwCRx
RExGA3Wr5SVrqhNxWTGKvQjdFnFUWm+cgrx0qzDIVX5eaFEuT0Vi0XCR/MBVRLkE7duM0stx+5IcHdWWSfN
BzjPvQ4kxTe50X2g+T93gCqumXCrO4f1qFZ8QFTVSOZVl96Gti4R0aOjlu1KthD07UmmzRoCZAQSe9Ube8x
GRt/GnxSq7KDwM0WJ5bRcWdCqWr53EZNTLZLGVMb5B6gVlpJErBd45q9FdGLhTkUXRhJSWiZDetILgJCnyi
qt1PJvCbcVoy32WJSMEjvisW5uXklJ2kN7VJpTvJ6odceZGAQetUpZZ2ZslsHt6VZE5xh+agmuBhs+lRI2V
+xVE7htoNDMwA3VReQsxfOD2q/bR5jDSnAYUW0NJJJXGvcErhelQFzgE+vSq19IIp9itkGlklEmxRwRU2Fy
2V11L8bHGc8UkrsFzng0iyJDGBuBJ7VXNzubH8Ioasc7V2TRzgDnk024KkAgc1SDqZyx61I0oc5U8CkjKdN
dBH3MxI6UVEbhgcACiqRz8h0MUe1Du9elBIBz29u9QvcHdjn647VL5zLGNw/d4zSj5Dae7EC5ywxkHuakXB
DbGOegI7VExKRZxktzj1oih6Lkq3Vj71a0M5ah+7jHBwAMEnuao38qvENvKg5NWJELK3IGCeaqXODjy+/XN
N3ZkVJJFRQWJwRnmqdxIAy5JwelOunJJUYHbNUZJVdxkjzAcKhOKYWGXcjFwcjb125qmZJgBIinbnnHNSXz
iNdwifYRyWI4rKGqbQIiNmOCfUUKBpA0/N3OHcYY9D7VJHM0AcgFoGOORWBc3gQgKwIHTHpTxqrSQrCzHyw
c496aizdHRqA8TmMhl/lTIZFCFXOPSsZblduFk25PNPa52tjeHHsaLFpvY3IDk5JxU6yFJAMnbWHa3K5BLj
8604rqELkupP1oK5+Xc6VZ4mCBSc471PG6ruPBz3Ncyuowqf9aox71M+s2+zAkXn3rRPQhy10ZpXDfNkfdJ
pwOB+7bishNatmAiLpnPBzR/akO8rHIpx6HNSaKqtmbky+ZEHXkVQKM5LnIK9KbbX7tEfLb5B1oE4wWLZBp
2TKjVsWA3yfMeBVVJQZv9kVFcXSlDzxVe2uAc4FJ26G9Kppc2HeRF3AZWrcM4MGSSGFZqzgKvf2qGScl/lO
BRsaJ8+hpxXebgFm4Fa5vFchUJrlEwWJ71ftJCjZJqOo5widOt3Gibc5b1NUJp8ysFxms5mLOW3H86Zh2bd
uPFDM400tS7JOF+R+p71nzyFzsQk1BcsTLgtmpYQFXPVqi12W7QVya2hHRxyKuS5KYxxVWKVT94gVZjlznn
K1okYSk29SkbNZWL45FNkgEKZYc1Y84Rlwvc02Xc0RLipcUh88na5jOzvN8ucVcnjEdoGVvnNSwwKPmPU+t
LLGH460+Uc5p6IoIxEIz941DM7Q27MD83arVxtGAMcVUaQFyuMis+UzcrleCV3jDMTk0VKrFRjAFFTYxOrW
CQTMzOD7DtVqRQybVHHHHvSwoBkZxRJz8uM85qoxsc8nd2YRIznBb5AOp7VEXVpWHJbOT71OZRGw2854IxV
Vn/enYwAIzjvVshpsjMm35T8u459ap3bMd7KAwHTFLdO28EgY3VmXNyYo3w3ViAM00S42KN6zeWWD8jnGKw
dS1WCNFM0a7VGfvYJ+lGt6p9ntpW4LqCAAeprzXVL2a4kbzCVGfu10UKHtHdmVasqa1Rf1TxE85YW4dRngs
2SKyWvJ5G3NK5P1qmT2pVODXpxpxgrJHlyrym9WX2vJtvMrk/Wovtk6nIlcH61EkckrfIpP0q3DYFhmTI9h
TfKtGNOb2Yg1O8Y/61zTxqF6zcSuPpVxbGJBnrikW2UncpIA56VneC6GiU+rKwur0ZzO+Kcl5e9DcPj1q4I
UI4GWPUYpy2m3Gcfh2pXj2KtPuU/tN0T80zkeualD3JXPnOR3q5HbqTwOv86UQMD93PPOORU3XYn3+5RE8o
BLO+at6NqUtjqEcsrM0efmB54p7wZPzLn6CozCApOCBRpJWYve7nuXh2xt9R05ZrORZEcZIXqK0n8ODyxhM
DvXhuiavfaPMJNPnkiPcZyD+FeseFPibDclLfXlEDZA81R8p+tcsqLQOc0tDTHhgODlCapz+GymTGGUivSt
MurC8t/NsbqCVT2Vhmi7t1ZWynHWsXAUcXUi9zyaXSLyPkEmqjLLE22YEfSvV4tPjlJG3APrXI+IraO2kkb
5doHOazs9kehRzKS3ZzSlccEVZSTOFB4FX7PSVmt422/e5FJc6DInMbsM+1S01uehDM4PcijcJ15FNa5weB
xVaSwvIsjhwKo3ElxECHib8KDohiac9mXvM3OWqaKQovPNYsV8ucNx9am+1AgbWzmiJo5p6F12y+f09auox
SEHuazEl+YE9OtWpbkeUMCqXccp6WJrdy8uGOauzzfIEx0qnYpkh+xq3cKqAMzDJ6CqSZlOSuRSkeUGHFVS
5VC2eTU0hZ1AxxVWf5eGbgUWtuQ5LYjnP7kseSapswVCR1zTru46LkY9qo304WEIpIPc1DSM+Yczl2JDY7U
VnqWA5c/nRUFHqGdmTkZ64qUSRMRuO0N+OaqSAbsLnOO9I4VfmPVeAKLmDiOllVQowQC2QaiuWVXQock/yq
K6zIUCP7CopCI3Ck5YjAz2qiXG2pRvpSdxcYUNkAVzup3Qt4mkOCBuwCa3pyN52sDjOS3TNcF4xuA0qQqMM
xyfpVwheRm5W1Oe1CVr2638hewrA1QFbjBJPFdOICqqxFc5rybLsH1FenQavZHBioNR5mZfU0+NWdgq5Jpv
etrRLbGZWHJ6Z9K6JyUVc4aUHOXKi1YWrxwjcAM1aWPAHAFTCIgZUbgO9WoreNVbzcqSOOa4pVL6nrQw9kV
BAu49SB+NSLCq43rt/u8dasQqU2eU4Izk5Gakk83rlSAc4Xio5y3SSKRiO4blDKfSp/J2jG3r7VcjLbCFU7
jz8wBqWGF5ARg8djxinzmUomeY8K37tlYenApVtWdBtJCnkmtJrQum5flBHHqfen2ljKysRtbHXLEGjmJcV
a5hyRyRt83NHkg4L7io7GuhmsWCgqN2D0H8qqz2owoAPPIUnmnzGejMryw4PbHtTXQKwVh8w9avpCyb2SPI
785FII1kO4KwY8YZafMS4lW3ubuzcPaXEsRzkbGIrpLHx94gtU2Le+aoHKyjNc8sDbyvGfc4xSNbAvt2kye
5o0YnCLPQtM+LmpWqFbiyt5RjGQcGsHxR48fWLby47UwlmDSEtnI9BXJSRso2lPYGqzxMc8c+lNU4t3IcLa
o+lfAl5puq6VA8U8ZcIAVzyDiuin0xWztHHavkuxv7mwuA1rLLC/8Astiuy0v4jeILFVAuvOX0kXNYSw7vd
GTjK90e2z6X8/K81UudEBB+Tn6VxWk/GJ1kH9qacGU8bozzW+3xZ8PSlAY7iMnrlOlZyg+w05oivfD0LNho
hWFf6AIGJhOMc4zXYw+L/D96pZNQiU/7fFY+ua7o8cbFr6AAg8qc0RpXNViasdjzjWfEC6NdiJ49+RzU+ie
I7bUWO44I/hrh/F16uo6s88Abyx8q8dRWNEZLWbzIX2kfrXUsNFx8zeGOqRep75BeQ7V2MMU17pDJ834V5L
pXiAuyx3DmOToGzwa6KG+uGZcMHB9DXPKnOO52wxilqdzPfKsW1TWNeXRYlATuNctea95F0YX7dcdq3dCub
G7mRZZN0jd+wrNwl1NI1YvZ6ly2tmbDOc4qK7jRlUsfunmrV7fRpK0cJEgHAxxUG1JIwed38QPSolboHM3q
zPkcbsIuFHTNFXIoN6ZVCwz1orPlY+dHpMkS4IXBXrVHKkhWbkDirUzFV+UnBwMGo2t/3oY4AI4GKS8hJ2K
iJtZjkE5wDVW9UGXgjBU8itFkwOi59WrOuF80LtU/KOT0zzV7ES1MY+abRiCRgEEjHNebakXa+k8zJIY8nt
7V6ZqEKw/aQ6HceVX61w+t6ekNlFPGxaRywkBGMEdP0rajKzBwvEhdd9smK5bxLFyrgcjrW/HMREmT2qnfK
ssi5GRXXTfK7nPVj7SPIc9p1g0rLJMMR9cHqa6NFwqlUUL0CjvTI4S3QVft4djqDhgOCfSirV5jbC4VUwgX
zFJWM789c4AqVIzJLtbbtHLetWHBT/VjjH51GIRtGTyetcvMegqegGNBlUYlew71PDA4JJKhT3Y81JHGqxD
I+X1I6VLHZOuHUqY2PfrVJ3OeaSJooY0HOM9qsJFGoX5tu7klj/OpRZE2fnCPO07WI9aS1s2mG8OiKv8ACe
c0zikr6gvQb0X5c446inzKfL80goQfXqPrUqIDgJFlu4FOWNR8rKGUn7p6CgwasV1gZlJHIPIyeaj+yFd+x
ULnrjtV5rY5BHCA54p32dpSrQIcnPJemtxWM14mKhJFJwONoxioHt50JDtuzwFwP8itcQD7hUGbOWJPIpzW
fnEs28Y9OlMlnPssQmwNvmN2PGMU2S23AP8AKH7mty9WJF+eAeZ9OtVrQxtOFZQgfpkcZ/pU82tilB2uc7N
BvO1ASw+8B296ryWU7JvTDD0711lzahbsFFbe3GV/xqmTKJj5g2N03KOKrnaK32OV+zHJ8xGU+tQgOCAN2R
1yK6u5ZkjYeUsinq2D09ay2hJJaJiPTPerVQhxuZjJkjcS34dKY0JDA9ia1C4baJflx94quajltUb5oizHu
MdKvmJUTPMZViCcj1HemtHgZII+vNXRAQoOCBnkUjRBzgjaM8ijmFymcyEjIxg1Vlg/dj5ck1ry24XdvXBP
QioWi+U4GfxrRTJcLnOSQEsMZHPXFSfabq2bYZWGOhBrYlhDgBj+IrPnsC7khiEHTNaKaejM3BrVFX7Qxfe
zFmPc1p2N2yEMjFWHoaxHQoT6A1JDNt45qpQTQRm4vQ7bTtQeYDEmG7k1u2k8suAWx/WvNVvXilV0OPWum0
bVo5nUPJsbPOa8+th3HVbHq0MVGouWWjO0VioxuI9gaKox3tu65Dj8TiiuHU6LXPW5QG2hRyO9QS7id8jZI
5FWlQNMcDPy+uaikiwW5JTHNNkFFWMrn5flBGBipnj2RgsOCeBVpVxF8oxjp61HK28guMgDI/rU3sCVzmtb
AkY7QQ4BJxXJ6tbeZZRxtJvlyxI/u967vUI3ZmMfRh19K43XQ0ON/I3EEirhKx0xgnE4WfKjYBznFNK555N
WLlN16yKDgHOKl2gccceldnNZGUKV3cigiJTdjitizW2jR2uA7Hb8u3jB7GqcSt5ZwAFUdu9WLAqC/mq75X
Cgevas27nZGFkS2UReQM20RnIHPNTyRjcTghR0pLYGI/vMqSMcipZJkaVY4ufXNTy9xyeuhIqKYAD36HFWr
dVQqgVWZhxViO2QRpvwGHJBP61PHDECJMgGtOWx585XKpjWOZfMYIjEszf/AFqDCqyrLFGTjnaDjJPfFaoV
GQBlBx/FUc8G7lFG0jkA8ge1NrQxtdlKQwyEuQwAPuM1bj2siiNVUnsynkVTjtwJC0b7lPIyTgVb2sh3Rqw
Jx82eoqUKcFsI7iCQB92T2GMCpA5X/VL82ORnbxSSqhUEqSOo560hw5J2AHpmnqZuCBC21n2hRno/WpHiLM
2WIPbBwKaFCkLNuGfXoKjfzwf3ZQp23cZFDdjLlI4gqM6FzIw5A6n86imuVNuI3ttuWJLHkipGRJArhQrZ7
HmpGaObfHL8xbkFuopehXXUrR3OdmJVKKM7WGD+dWiN8BOIizc8mohp4a2DxkLnPHvT7VIyMkhjwCW6ihX6
hJLoVhvlgEYVRuP8Iqs1gBvV4VXuGB6VpJgSHgsq9CD1omVj/C20+hyKEzNpmIbKOMbWXIP3iO4qvLbCLa8
e/wCU4IHpW1cQuCvlSoEPB3ijytoB2gY6tnINFynGxz6wIS2OT1BAINNNpuchcBc9/WtufykxkktjPoMVEy
klsgYPOf6mmpEsxfswPmFjhx29aqNZMGPykZ79s1vXDwqjJhXbuSOazncvGu2QhSccc59KtSBXMqSFUbCoc
dQfQ1WaFWJ3gY65rWG1HyyAHndkZFVZEVs9Fz+Rq1IrlvoYlzaRupxw3XOKwZ1aGUqQeK6yZNpJxxnFZ2tW
iPaG4T76dfcVvTnrZmFWm7XRhbyxFattEUVGI9zVHTofOuFHUDk10Eke2Pmrqy6E0IOWrJY5sIASc0VGEyM
iiuXkR6qkz6ScsHBBIGKa6lmkySRjAGKmYqzoTxt9OmaZtJeQhufavMZaHBuFGDwPTrVW7VwzY4I647cVM+
5mBToO9RkF2c5yCMHIqbmkEUZWO0ZDYxjIHWuS8UQqbVsZHzEge9dmo8kjyuTz972rlPFkm2AjOGYZIx61p
DY6IvU4IWxHzMR0zkdajSLDEt+tX1KuW4PHpVZwTJljXRccdywifuyAeT2rQ0eNRI0hYFlGVx2qG2g82MlS
enXGa2PD+lkrLJIxCDGR0zV04tsuco8upYitft6BXUCPP3yOfwq/YeHrS3kMwQyEcZdulSLKquFQDHt2q9C
XYBT97rXWorqcNRzto9CHUtP8+2RUQNz94jHFZsVshcLjJFdTAZMuCowBWCRm5kY4wGxgVFaKbuY0paNMqg
ybiEQbc4JJqXYx2FGw/Ix14qVoU4YzBATkjHQUkawOzLGSZezZrE2sV1WMcKNzDsRgUzYVIIVSOpZjWiE84
7o0YyLxuxUTKCMxJyeuB0pENFRhksCisDzj0qSKMBlKKc+3SkUs0uJFTjpkYNSxr1YrtPYg9fxpEygx0kCu
qjGcc4FRC1AUsx+UngHkinN5iHdvJJ4we1WlBdAw2K46kjIo3Zi4NamTJiKYlVKd/XiqksqvJhSoBPWttt6
Ru3l7Y+rc5/Ssh7BZJCYpY2RjkjptpNPoOKT3E8yVcBZE2gDawPGKuR7Nm5oyCBnI6fnVdNJe1kwHBXqQBw
BVh0SJlCvx0x2pJ9yZR10IispPESFR0GMZ/GmRReWx3A7mPQZ4P1q1uUg9No4zg1GVXkgHHr1z74oSsFmxr
KMgNkg84Izg1VuEkClThfp0xV5DHJG2Hye/PIpjfIQQBx97ND1FZpmekLIuMmRMZIf19qJVQp8idRngcirB
khj2/MqZ6AnofenQKspLKqcH1pLsTNPcwAkJaQy7lZBnaxxTbmzWRS8coWZTwijqDW1f2a3WC3ykDOcdKp3
VuVYSKYwAo4HBNXsJamMR8myTazDqrDH5GqhUlCV3+WcjkZ59K1pFWRjj7390/wA8d6zZg0UjIsgZM59AaO
Y2jEoShGX5Dj29KzNZ3Jp0m3kNgcVueQZWJgC5HOD1rNvQDBKrDgjkVtTlqKpC8WZOgRfKzHua2JkyhqpYA
Rx4rWEX7kepqqsveIw8PdsZyZ2jFFWpICrlfSis+Y6eVn0HO6xfM4JIPAoSQE9DuJ6CoLhGmkjwTtXls1Zh
Y7cKcFepNeZfWx0cugpyJAjbio7Ad+3NO8tRFuBxgc89acIiW3A5LNyBTrhAY22Zx2A4oSE3bYospeQrtHX
hvU1x3i4ArhUO/ofSuzl+UJg/MDziuQ8bzCFTkd+QK2gtBqbvocjGmzKHknvVWdQXyPyqcbtvmHgtVlbULb
h3I3t0rW19jqo6u7Oj8KWeyz81+c9Bit3CkqFX7ww2Ki0rZBpyBeGx1xVlYkngZWLAnkEda74qySOSprJtl
D7NulByQPT1q6eAAM7+3t71FcSB3CQt06n0q3aRh4WGdoHQ5qklcznLTUktPm8xdxMmRkVBqNqrfOibWXg+
hFJDJhsocSVdtIkLsbqYqMEj5e+OlJ66GNrO7OedgwyoLOOwqeILOjoFEW3uBzmmamFi1AmBRgHcR2q1aXU
c0wBVhLIRnPA4rltZ2Oxr3U0Q2BkkaXyzI6j5do4FJcBLUlirEkfdX+tasrKY5PKZIyeCoNZ0tum5TO4Vc8
YGSaTVtEZxfM7srJa+dM0qx4fbwpPX3qZISwyACB970+gq2kCK7eYAxK8AE5AqOGEbWKrg+uORQEtRCETBK
EEfxD+tKIi+GBCkd+xpWQvhZNxHdfX61Ir7V2PHuAGQB1ouc849ilcROg2MQc9dorMcxNcZJZW+7gdRWndT
7eCDtJyGPG3PaizhtkZyAjzHkMp5+lArNLUiiTOQsjOf9rkAUlxbtIo3bcd9g6VedYpMAIx7AkY596hmPlZ
UxscHs39aGkTG/QoOm3jbz6YpohBy4Dqc45HQ1YIzgMQo/WoHjMbkqGyTyS3B/CpsbKJGsIWU7hlh1Cj9aW
TaxIG4cenUetSO+AORgehORVOW5SORVdjuI4A6j6UnoHI5bEFzbxyrv9MEcf0qNf3BKKqkg9Aasbt4yu9l5
B7ED0qNmZiuB82cYHUj60hOD2K8ssgmHlDzFX7wPOPpTrgu0YI2x46nGSanNqr8qxQrw2B1FSM3zBDcJgrg
bh/OjUHFPZHMzoxAdcSK3G49VqBSiRnZgPj5ged1a97GWnykaoVJHyjhvwrCljc3DlQVB+8KDWCGhjCQygg
HnB6GqVwBKZARjJzj/CtCNNyAOx2A4x6VBdweTICp+U9Paqi7PQuULrUxYxsfa3Y81u6apmkBP3F5FYcqN9
rKnvXU6dH9mtwTjJFaVXoc9BWbQ2SEeYxIxk0VOq+c
N/TNFYXZ1HsW7fgngbe1MQBWI6jg01ATgdFz37VMq7ixUZA/WuS1xItwsEKMp+Yg5BptwQTgHGBxjrUcEuS
Pl+denFRTSMs+OMjr3rRGbWpRn3Rs0gz079OvWuX8UmOZgZTnvz/FXR6jMDGVzsIB5rgtXM1xdMX4RR8v9a
uK6FRfMykHVmJ2j0AqWJmlkUEZwQBxUUcZyc5z0FdL4Y0ZpJftFwn7sfdFawi27I9FcsKfMzes2iNuiOCDg
cDvV2OylnkCp8gPb1q7b2sETCdYx6fStaBomuUxtQk8E16MYnj1a1r2M6bQIT5WV+VTiRauXelWyoohwpA4
HrWzMIRbnEqkqeazLyZX8tYV3MOS3tWiSPN9rObOcudOAuQQSrbc8emaJYpI5NpbfH29a1XJe6UEn7uCPxp
lzGpl3MhVvQVFtTrjUd7M5rWGYXcbLEFTaAARw1CW6RqkhiZn3Z+StPWdGnu7aOaGYssXLKe2ar2qLB+6lk
YAfxKPWuapH3jthUThox6ASxljFhc5IPFRNKkoPyx+3OOanCH5iXdtpGO3FOmSHep2B0x0xjn1NQJWIU5wC
5B65HGf/rVHOH67huGTkNwaSU7C2LfzWPAw2cD0pGCbFaXLODg7RyPwqWzRQYsTSI+5xxnOT/SpkAlk27lP
pk8k1AIFlEhRlG0bgd3P0IpluHlA807FbgGgmcNLlS/EkTnJzH0ZE/xqKExqVCQbo+qtnGfr71dNj86gMyo
W/Mf40iWsDM5hZs5IINTZi921hwu5YgxCnBOAh5b65pJGDplzgn0PApQcqvmOAy8BSM8+tI64j3gAqDyR2q
ieRFIjyykmYx/eOCTSFt0Y3Ieem7+lPkKuGKSPt/hz0PrSDBgOYXVs5Ddc0F8pWkUD5lxuHYjmqs8BaRZFf
A7hhWg6ARlnJZccMO3pmmkOqA7gYxjOR60mrlq62KLJsdduTn7oHf1qRYEbzfMDeef9WwJ6en1qR42jY4Us
pbls8VKsUrSK6Oykc7dveoC3Uz4meUeXIWikU4z2NPkIVWa4jVkXgcfrWhBEJ5GkkX94QaqC2TH3i0mehND
Rm7dDPKRNExUkMOVBHSs65tnJDopbnNbskKsACzKue4pjxmNFJGSDyfUVFnuTe2qOPuInWWQMMdyKgm/1Qb
dkY/I10ep20ZlLYwMckdq52SMoXAIKNVJ6nRB80SmYg00Tn6GtKafzZUhj6dKyp2aPaSe+K09DjMkrSHnFa
Sfu3MIazsam0oAqNhQOKKl+zSMSSD+FFcvOdyps9ZjRWbnAzzgU1ldCSDyTgD2p1uMEM6naeRUoO6QsWCgA
4NSldHGnZkEAZZckll71UunKyNnqenbPPetXaMllOW9Kw9SkLcZzz3qkrCvdmRrl4sY8pWAkYkKAc4rDe3M
is7kkAdSKkup0uNQcRLwny5qWeTZGEByzHArWEerNqML6Iv6F4eW6aP7VJsU88da7mPS10+JUjO6NeRzya5
6zljEUYjLHgfSuktpQ9sudx7V6NOMUtDCu5tq+w0oGjJXgHjFWNGspLm9QlMopGQfSn2o2FnTAOCAOtaPh+
dVuyJIyQRggVocNaTUGkM16yiSYiMbB04rFEex9gkPyjFdP4jObgBF2oRkZ6isdrZMKy8yMOTTOejJ8mpl3
kosXabIcsMDPY1Ss9RF+7KSRIT8o9ak8SQMIEXeFJPIPasy2tHhSCZJSsu/KDHHWuacpKdkepSpU3R5nubk
lxcW9uUKKVmO3eewqsEhMLb7hQ2QMHqa09Stne1RAhYswY4GcCqdjp6z3cscpSJVRmLOMj6fjTqt3MqVrOx
GIdLXEc1xO94SSdoyoHbFRMMgjynLg5APHHrT5ILiCzBiKRmN9u44yD6GmyI4kjJkaVjySO/8A9asTdepm3
SkM223Z0cY3ZxtPqKY7IjMyu7Egb8CtSYkIx37PbHX6VSnMZAVVBY8ttP8AM1LRvGfNoyKUQuRISTngkD+d
QFvIhdpBn0A5x6EU77NKxXypWXI+ZPWo7h3UrGYjvHG5TRcGuhHFLcZWSMSOmP4j19cVaUy7wZGVIyeVByR
SKNzIry/vDzjup+lRxsiOQyHzkBySOGPrTM5IlkBLfu2RyvOG4z7GmsXfMgT3wv3W9qSTeyAkjIx86j/Oaa
zyFG8slY88MPX1xSKUdCJkWRAwj2KTyD0B+lJmWLZ5RfCnJHUAe1XFLSqqOwOzoDxkVHmSJsrGQG4ODkD0o
GishALCVc7l4KevqRURUN5ayTFUYYzj5TT2YGdQWXzccheoNS2STW25iBcROMFHGNpPepTuW42VyOFN2Sjr
5edjKP0Iq0sCukZ5IHvyaSOGF3LtGyMT+VXIUTBUfKc8DtVKN2clSViE2zIjBBwRwfSs6a1kRCTy4PDVuFw
IGXjPQ00LHsBb7xq3C6MYza3MDyGC7pEyCetR6hF5KR8HBBFdB9i/dNzlVOcexrP1lVMCKBx2pOnZMuMrtH
KyhjdP5i5jZcVzuowlHGFIxncvbPrXU3aN5bkH73H4ViXzF4e+4HB4rmWjO1R7HO3sZe2DLkEMARW/odnL5
MZC4DH86qywBrVmxndx+tdj4YtHkREZMdM5FKrU92yNKVPlk5GxZacy26gxEnr0orsIreeKNVhKMmOrDNFc
9kLmb7feUI3x0z09amL/ALsA4qhDMGBI7jHXpip3kwhDnAz1rVbHKSrIqAqC244II9e9YupzJHbSNtO8Asc
1ceTackcZ4IrF8RTKLSZkbbxtye1UhSWpzlhKJZGcDGSTwMVowLvlaQruCjIrM0/D5K9M5GPSty1KxxMTwT
W6VztoK2xt6Ou+Bi+Ao4AArbsXbmNfl4yM1jaRdJHbNGQFbOS1aOkzC5usKc9ccdq7IGNaD1ZqLG8TZJJB9
60rI4mU8546VNZW0cqNvzxyKfb2xabcMBs8CtTyatRNNE2oAXDqCO2Mms6S1niYNCS+TgLW1d2jxYctnjJ9
qISAC3TAzTOSNSy0OA1qRm1vZeKVSNAdh71bSOJ7lfscTP0Bj+8FB6n2xXS3GjQ6yZSQPOGFVz1FRabpN7Z
6pcsYXggC7QV6Sfj6Vly66nX9ZjyWWjSK8cl/bi48pEfamB6+1cxHatJI7XErqxBYhmxmu3uTJDbXMgG3nH
6Vh5gNolw8Qf8AebAp6/WpqK4Yepa77lO2S0khH+jlOCWJB59xmnyXem+StrEJY5Qf9dN1bjkACrElld3ER
uIZHWMfL1yBntTzZRQK0d8S0gHysi559M9qxOlSj1Zluj+bB+
+gQNyFcZOKrXaSS3LNhHwccgKv4Crs9ozQyt5KAEj976Z9KyntxpbxS7zIQ2dsmSOal3R1QEuFMEiLv3Dk/
wC7/wDWqOW1Zj5jndIw4wOKu6nDcwuyvAjqQG8yP5t2e1ZyzCTYJhIgXjd3X2oHq9irLbyx7RJIrBj/AAjB
Aq5ubCqX4x0I5z70zbJIPLC7oQdolPWlvYZYo1xIN2QFBHzEdzTHu7DXBZNpRsE8gHGPelBWORntiwjKgES
9QfwqdEJ3GXkHjceCaiEcTo2W2ydQhHWkPS+o3O9czlIiF6jvUErYSR0kDRlcEg5x9RVswggB5FkTquO3tU
G5IpxJAQu47XOOnFJlRaT0Ks8ieYi2/lmVSMMgznjvU1tczqzxXcwgB+YADIb2qNYozNJ5TeZkDLjgjPetS
C0tHsFD4edWbr94jtkdqlRYVJxS1RXncqjFiWZsHAHP40W9wrsu4bO4J71LK0WAIsbsc1mSKFmwJtu7PJGc
H0FbQRy8qmy27Eh3JIyeo9Krz30iMPmX5RtGBz+NQxynZuZuAelPjjFzvA4Hf0qmr7GsYRW5oWt4RbNuOSV
6+tVb9fOtUYdduaagaFooSOH5VsfpVidF2bV4wcGqs7WZkklK6OdkGw/NkqvSsq7jVmLDGR3A61vXlsys5Y
nnpWMrBpmiPOeK4qq5TrhrqRNAjRqrDaCRz+Nd94Ts2eQiRQw4GfSuJijF00cKlc+Yo5OK9V0Ow+y2ifMnI
7tzkVyPUUqnLA1FiCKFBOF4oqwYyoXK7SQCRnNFJtnImjhY3AzhTux+FF3IQgH61Crll5GT04p1zITE6lcC
tFsbdRTIWtwWJ29K57xI4ezaLdtDYBOOeta08jNGQBnjIUVieImMixDaFGRx3NaIh6tIZpcH7gFVwAKuiJm
AOe9FpgRKoznvir8MSyH2WulI9Cj7quXLZIkijZ+uTnFaFlFEpBhlJZhlh02n0rNEq4Knb6ZrT0OCS9umEY
+VOCcYFdMfIyr6RcpHc6Ro8r6WkqswZueTUsGm3W4yIzYU+nFb1i6wWMUDHtjrVm2lyjRuMKDxitWz5SpXn
zN2MY/aIYNsih9w71XYL5Z7MRgg9K29QuI3UKoBKjGaopHGYpDImGx8pxQRGWl2Z+iKwmCLy7N64rVur7N0
+N32eMfdzkg1XsLdFRWc5DAnj1qBWZHlWJflZiPekwaUpNi2Qt7ppFc5DvjBFc94ujWC/W1t42jto+dpOQW
9fauhW1KrvjYLKnz5rkry+kvLqXcmSzHLNUTOrDK87rYfp8c0sai2ViOju3CD168UspEltNL9piFpCdrOH5
b3x3FZ19CTHGiM6xYyI1YhSfUj1qQQwToqx2ySXxO1Y9vy4rndz1Y018Q2+gs7c7re7Hl4DqVJKufQjsaYD
9qiLywLGhBClz8pP+NUr8zKfLmRNqH7idsVYtyLiMGZdkZPGOaXqbNcquytbXkmjwTQXQEtm/MRAwVY9PqK
pzOtxJK80ZAOH6dK0JQ0SkEebtOPmOQBTJJrbymjk89ZzINgCboyMc5pom6ve2pmvH5rCOCRFiYjPv6UXMD
earQz75fuhGGAB6irEdvtfCYkUnIDDGTTLhgGRVdguRztyT7UmtDaL1IZXuZpVMrruzucAf55q7Gonj2Ou0
D7nqfWkeydIlnxIsbEFSRyx9cVNJY3Jja6uI3aIYZ3XgKOx9qCpSTRXRY42j8uFpFXOQOo96p3UUks0kRDe
XwcY71cEslvFuty3T5T1yPeojLcFEm8rLA7sjpnuKZmm0Q3cEFrcR+UMnaCxUcKKtwmL7Mk0csWVJ3Lu5/W
oZWMkMihf95vUelOmSNYkj2JkgdBTSFPVakEpjIJUr5hHSsuVJFJ8yNgpP3jxitmW1AaJFUBsjkVZvbWQ2+
yJdwxzntVxgRCag7HNyfKvTB7Yq3pyY5IYBeD71UOVZRJ9wHkZ6VMtz5bbY2yG4+tClbU6ZRclYvHNzKVwS
F79MVUZ1F05dyoXsPWrtiJEtjKy98DPYVQvoyieYfvN8xHtTm9LmcVeXKRyTho/nILHua56aNxfBjwG6Vft
ree7mYxj5Qe9XGtgq7Z16HOe4rmmuZG7gqeiKmi2Ie6RsZH3iM9K9MsgVkQB1TapDE85rhdOjBviit8oGfS
u60dRtXd8xz/ABdvWvPehyTdjZgjlkiVo2yvbNFSw7FTDKRg8UUjn5zzSF8EZ49aUnIOWBbsPWqauA3Xjrz
UzlWUMSd2cV0JHTLQZdNgYVgBXP3LPc6qFwTGnOPetbUJlijbDcBe9ZmlKcGVzl3OSa0iiqEeaVzZtUCAcd
epq2HSHJ4ANVIjnPzd+1XvswEKyPLExLbdgOSOM5+lbx1PTjFJai6bGbu7jjC8Me1em6JYQxKZAvyonPoTX
N+GbGMfNEuW7HFd0ihbZUjADEYK11wjyo8HMsRzS5Y7Fe5uIrGyW8uiwjU4Kjue1X7Gd7yzFwi7EPQe1VNZ
so9RtFgecxR5DEjnPtVyymhtLcW0bhkQYB9aptnkSUXDTf8AQikRnbuM81eCYRVxnIq7aWyTOvfK5oaE5dY
xnFS5HM6iehlBTatJMIi6YwQO3vVezaOZXePILMSAeuK6V4khsZC/GRzXM/Z/MRTEdhJPShMdOSkmT7PLsp
5nOVCnGfWuMldTDJcMirCDy4HA9q6fUphFo00M10qyggLHjls1xk8IS1dS7EF8hc9frUVGelgoJ6vuFhF9q
trq9lkjigjB2h/4vYe9VZLm0mn2wCUSkA7ydnPTipTaRXPkIkUwl5ZkZsL+VS6naI6xRi2WD5MM+cjB7msT
1oqKZVtoA90IJDEkgbaRvwW9jmiZvMMkECgN2PZcUl5YxxQ4WIyuACjd81VLgRgTsVHTpx+NIbjfVDlLWaL
HcIvOSjDnf9ay4r3UY7ww2zlIyDtYgA8+hqzdSqLmPzpS0fZVbOB7VUnltZbiKSCRoE3bQz8/Umhq5UY9Wi
e23hZPNbDhs4B60+KcpdpLAoj8tt4ZxkE/TvTI0UqyRuJPKJO5R96pEVriNBDFgK33n7k9qXQtInkuZrmZr
ue681V4VOAQPQDsKk81I45FQ3OyRQGQ9Cc9PcU4C3tg9lfC3hkVSyunzmRvTI4qaafdbRqSECgFTj5vpmmZ
y9CoqyBMxgLjnpnAqAzzQQSpDMPKkbLgjjPtVq0uYrZ3e8EwtXTbtB+bPbPtT44bxrRryGKBrQ5Vgx+ZOep
FFyXpuZ1n56yq7xF7YncSp5zU/NzdKQqgKeR0xS6a7IkgdMx5Iz/dqNAFkeYt+7J6Crj2FK9yeIM7uJFO8H
qPSrU83lwmJyNzD5QvX8a1tJhhvoo4xhXxnp2qSHR1xLLkEb8A+tbpHE6sVK0tDgbq1ZSGkixnOc9BVSGFR
L8oJU9T6Gup1SBZ55Y0bA2nI7msyJDESFUMCu3PoaxlGzPUp1bw1J5bVGhUNIVUjPXrWLeZuJ1VSemMCtG8
juAESIMyevpVaIwQI4ZT5nOWNOburFUI213ZEJVt0CZXjuBiq9zcGeNgMBx6dxVG5LPMArcntVuCPehVmAb
oc1zOfNodlSnGEbvcn05AZ1lXIZvlx7iu10KEyEnD4zjI55rkdLX/AEzYq5TBOfeu20J22YHBBxgV589JWP
JrOzdjooJCsYU8Y45opsRjVMM3I9KKRzHkEvOMDoOagmYhc9vSrUhAO04xnmoLlVUAqRzxx2rqsb85kakTP
AI0YbifugdhVqzUCIZycelUIh5t4xdiMnaMe1a8MWxcjp3rSKsj0MLFEoz1XoatwJkqvvUVhElxeRJLKII2
bBdhkCtq9t7a0vxBb3HnpnG/btrWmjtnNR93qdxoEq22mglQrHpkda0EkZkV9xyx6DtTLaNEsoxywGBjqM1
cxhPL8tQ55Leld0T5Oq05ORXLhpSjsfz71u6Lp8T2m6UZ56GsOSB1dW2jkitpbvyLVQnzMR2ps5K12komH4
h12fTdWS1tlIUAc/4VuaNqsltcq09uZYZFBJ/iWsnWGgeze+nj3TRcqMVqeDtRj1azlmkQI6fL7YqJdh1Yp
UVJR20ZqalqVncW0gjkw7cBGGDj1rItCxYIAMA9anv9Phngdhw3ODVeEy2Vo6NHvkbG188gUI5oRjb3TO8R
6NLcyyXMbAiPBwOmK5O/dS+HiJHGSO1eg2cclzHLgtyD8o7+1ef3btA2FjJw3KnrUTPTwMnK8exZheexty1
vFFdM67uh3CsdLZr2KaYag6Ocb4h256DNdNbPNJa3BhCx7EB3MNm4dx71mXka3FqZ0heKNejMMhj6D/GsWe
jSla9xLaK5jvxK8MBjij3OrtguOmcVm6rdhUISGMI5529varFtGbOWSSGcGZVzifnzFNZRabzBLgPHuyVxg
MM84NI1ULyuypHDALkw3SicygSo0PzEHH3at6bbSsVkNnHNsOCjcbsnpST3AijkEVk5CHdE6nGznmlF1qEV
tEpRIod27MfUE+pNCaRUrtWQ6QssmUj2bWJAPIB9PenxtYQ2nmzSXFxd7uIiv7s56HNSRuZNPMdtb+fLkqM
cnHck1KsFpcrEjyfY4z94scg4HPNDFH+8UobWOS0Z3kRJEb/V4yW+lWFhztVurH5Per9gsI2RrAJIt20OG5
YHvWreD+z28m3ZTJ8ynK5Kg/560kjOrV1sYCyhbgW80aZ5HzDmlvBNEFa3VvJI2nIwKuvsBUXHBbpJjJFNs
onY7GmcxAkgN0P+FUkZOXUxowfKkUv05IFSwsn2RYIcsG+ZsjOT7Vbv4kRWOV+YZH0q1bwwi2iijAaY4O9T
xj0q4LUbmrXKsNw9rHvRSDjDY7Vu6dePdxmJSqsqbsHjA/xrLls5Ym3q3B4IPSrdnDtLSwjBQfPj+IVsmYV
IxkvMwnhM2rzbmYEd89KaYwkrr6t+dWGkSO6lbvK3TPSoby3MdyjTP1XPHSpsdce3kQ3by48uIqM9z1NZLW
j/ALwPkE881rGyT7X5rS9sjmqt2zRyMFYsDUzV9zqoO1uU5aSJ4blm5KjnNP8APO0txzzVm9lZiSKoSoyqG
UZB5xXBLR6HfV96Opv+GpPNiaUqdxf5a7TSkZYgTwwOcDua5fw5aKsShu3fHSu2sLc4fZtIHOa45e87nhVG
ky/BbvIm8jk0VNGrogX5vr60VNjG7PG327y4GQT0zVWdiy4C55qZ5V3A5xnjpVaR/lPHTnNdl7lsxBcFGZ3
4IcgKPWt6CX90hYZJrnrZgsuJV37zuB9Oa3IpA5+Vc+laHs0LcqNnSY9MubO7FzJOup71FsFB2EdwfetfRN
Fvry+uZI7YulkN04LAEfnVbwObYeJLBLmy+1s8ygRhsf59a9L8ZyWWn3kR0a3jlT7Qj3zxjIHzcKcfyrWC0
uZYnEzhV9lDqvkHhq1utQ0kXt1dx2tnbsdiSLy/fP0rVh+0S6a8ltayGJmzvZew9DV7xZcWeq2Nnp1hIkk0
0g2JF/AAOc46CsdvEutp5Wl21jHBJbIEmaQbsgcAgV0ps+flGVZcyVt9H0RaZPKEMl8fJUyBWZhkA4yBj3q
3Y6e91C0nAIOSAe1czrWlah5lpcp+9jB/eKG5HvivR9GEJ063K7VnZMnHBP1pt2OXEJRgnFmLcaan2fym25
9/SqukomkeZGi5gl4lRRz9RWpIrsWZSz7chsLwPxqBGSa4RIxtZiBgc0bnNGckrPYSfYbFWjmV2xwqjBHPe
n3Cx3VvAYz8wX5sjOD6Va8u2t0YzIoJJHA/nWRp9+sGvGwZSkUih4yRwaGRFc13HpqST6o2i2xeO0WZ88gc
MM968zjMl1qgupWIV5CxUj5Rk9DXf+PdWjsw1haFWuZsNK46oPQVwhkc/wCjW8bSSON2UHQjsaiWp7eX0mo
ObWrLz3UkjCOOEyRnOZAO3oKntZVsfLEkUjx52eS4wCx/rUdlBetJ+
+AQnMjFOAB6Ypl/Fc3P75LxJEd8oh4KPjqO+KzZ0tK/LcoahFBaSLOqB5t+3ys7mUH36CqrWIeJ5pVZoUIC
xt1QZ9ql1iaR7eJrrMcyfK7AABwO5NRXF9fvAfIi/cSYRljOMj61LZtaXKrF26WCy8v7GqXNrkZK/dODnBJ
6Vj/vbm4nmndUjdsErnC+g+lK1pPEkUF3ujeQhvK7bfU471em229g/wA6b5B5ZSReg/vUwS5dLlCNZNPeaW
0kf7PIpRnjPX6GrOlWltbwhbs/KQZCGOTz60y4jkaWSEH7TEdrbYflQcdas7LEtHBfQtGVxyp3ZHrSsaPYs
6VZWtxYy3VtKjEFsQCQhk/2sValura7t1ABgu4oxhQp/eEH/PNVoYYyk8lhcRrGDwUHzbabcJMEJE4DHAXA
+Yj1oOeaUpXbK1+ZXciNdjJ61XiuIvOVfOx8uXwPStFbdpBKnICgAsx5J9arvYWyxnCg57jrVJajvFKzGX+
oi8DfInmZwdowKv6BAGkXYck5BGOazreyjnRhGVSQccfzrS0JXsw0e9pJEPDA1tFWM6qXs2oFnU/9EdBN8s
Q5LY6fWi5uFjtNtq6uZBkuPWpJ1nuLcveKrR7idp71n3CReW3kfu9vQDpT1MaUU0kyhew7YU2ABmxlqp6k8
kkscfO0L8w9qtwiW6XyGO14zkDpkVn3M7QTyF8cLspt2R6FKLbsQThriUQ52oowD7UtyphRBJyOzetQLcDO
WPzL0z6UzU7kmHY685B
BHasHNI7o03dIg1C1R1Lp0I6D1rKu18qMBWHAzWh5+LbBJ61RvAJSqLn95xxXLUaKqXUXc7fwrEsk0AIJXY
WwD9844H411GnpmKctGy7csGycA+lc74dtebdJH2COME7evA/nXRrcxSqAXumxjG9xjP0riR4lTVlxd7qCx
ycY60VJHzGuMdO9FRzCPEZh8qHt0qvI2Fw3TOKvzIJYdvTHJxVApnIJNdttRS2OcQPFeSpu6NxnuK2raePc
VTqOtYupK0WpA5wr9D9Kv2rbsFevetGexgrVIJs7Dwnq76LrKX6xJMwRkUN/DkYyPevTL6xb7PYaBY2+fOC
3st2TtMmecH1xmvJvDk8SatYxXcZeB5AJNoySPavc49Ea98VRxGRo5LWFJtoY/IN3CH8K2pJWOXMZRp1FJ9
r/AHbGtdQ22g6xpNyo8u18p0YhOc4zyfesfw1czXWsXVxDKsUt25IEgyNoPvW3a6jf6nrF2Ugje2s5XiXJw
CdvU1z3hm8gg1KZpo/MCowUoM/Nmt49WeIk3CXNq7Glq8uLuQGUyMTglOBn2rW06NrzTo/ssaI6feJOC5/w
rD8SXVtYXyRxskhkAYKuPkHvXRaPMl1olrIocNuIDRDBAHrTexzVI2gpWILi4vobV7VlEin5VcDke3vWdbX
F3DPFJOnyqCq7Rg+2a6O78tLYSgsH/gPYD1rKmuLa622xlRJs+vNNMwjNvSxI0cMjxOH3uMBoT1Ld/wAK5D
xCuofarieaOSERvldvQJ7V3kloqNbsh/e95QMYz0zWF4mtb+HTZTNcSXC7vmC4yU/
+tSbN8NJKat10OKeS2vdSdVkkct/y1bgn39qoaJZ391qSxW8uUjJ3yA8hQeefpU0skU4tFs0eO6LHeTyNo7
Ae9b+hx21iZy0rxxzRsySIQM46qQelZSZ7rl7ODshbmC2ijEltNI0ZO5jKcFR9axfEd2tvLZJFBNKFGcINv
mE9OfSo71ImvGuZn862KkHOTtHYnFR6he2clsiKQCg6qCApx0qWxQp2ae4/RrJ7q0lur2HzoCGwAMqp7D6Z
rPNqEa5VzIqom9UVsBSeh96u6a93c2UkMRIhQMWZR8q8Z4rPt7TzLgGS6eOF2Vv3vOQB1PtSL+07vQjC3dz
Kl1K5iQLudnbG5R2FamoXy6jFaCKOGOJcsSQScAdDVazs5XgjuLq8VbeB2XY/TBPPHvViweJjcqkLpbFvMV
ugwOw9qaKdt10IkjKLGloWlyRlcYG3OSM/SrdzYWqTo8KFFLkqrtk9Pu/SqM2qQpc3LxqzQGQDyy2cr3wfS
pUhaXUojCTA5+dGDZVc9qLjcZJ3e1h2mSW5Mqc2zqSQu3KsOu32qSCBLx0uInjZiCwhXnaM9DUl/p8sUTW7
mN1zvSVDhhnsarMsLOpkza3cQ5KdGb3qSdJapi3kp85nSFQSNp2dvp6VPZLFNIiIwAQfMx7mmxWzox3FW4L
lz/EagkmzIrLHgk/Mg6VcHqZyhdWiaF6kSxeZbPjBwcU2JxHkxL85PUVH5mMqiKivzt9KlupY0t4fKxljlv
WtzFQfwsv3ckbacCRyox9ayooljtFMvJJ3Yqf7T51uE2cgg4HpVW+md1KMu0AY9qd7Do0mlyoefKEyEbQSO
SBXPaxAkiyHOH3EgCrjysMYxkelZd2TNcOEPOKzlLQ9KhScZ3Ma5ZQ4GcsPSmSt5kG3ncD3pl3F5chBAznt
UloA6t61xN3dj2Jxio8yK6Z+zBgMjNVrhzFLCV4bzFx+daMgCKyEfKOmKzmI/tWzjI3K0gGKzmcGIn7rPSN
FMa4la7EUqkqF8vP41oXV+HEkaXkbP02iHBP41gwBIwMqQ2eD7VrabZCc+YxVXHzEk4rj5nsjx2lfmZt2kr
m3j6jj0oq5CBHGqjtRSsZcyPEYpTsKkY461Wnj+Y4OTjPFTREgLnBz1J7UToAhKH8679xnLa8drw84bJ4qb
S5ASFJwcdKm1mFHtfMOSUPX2qtpqRoxlkYYPQdxVdD1cvklGxvWrA3EarIsZ3D5yeF5619FWEt1odnJd3mo
WN1eXke4TrkBgqfKB7mvn7wtpUet3N3FJcraQRQtK0zjI9h+NS2Oq3Om3awowmhiU4VjlemKunLl1ZrjcJ9
aagnqt9Pu1O+8Nalf31rf20Op/ZFVTKdpxvZz90mut+HCvbaDeX7ojlX2IM7mVQcMxFeOaDO9vrNtdyDnOV
XGQxwcDA969O0PVLxvDyLZwkRpA6yMcKWlYkYJ9K3jO5x4/COMeWHW3kdJ4os7K48PRXOnRIXkkw0xGDxmt
DwFdx3GivAxysDjJU9c15Uuv3S+EDBcXMZxOf3BQhsHuG9K3/h14ksoLmCzkLQyTErnPDHsD+NXzJ6Hn18D
UjRa3s9D1zUFSeE2+5kJ7hc/hXnWt6ZJpepQXYImhdxuBHQ56YrsJ/ENnHbuzyf6SMgQZ+YEVxXi3XLe7Sx
E7PFKHGY1PzAZ5YjtTWh5uFp1JT20/wCAd3rF2LawF0y/uo9p2Dq2egrjvFF7PqkKGCWSNZm8tYF/XNYnib
xaJbddMtA0h3AiRj1Xrz+NRxaoLhYvPj2uFKqyggpgdMDrn1pN2O3DYGVJKpJa/oVJ4xaIjxvmcHGEOTG3r
itC/srddKS8kmnlMx2spAC5PUj3rNspWuTJDZqTuGShBJGO+fWrlw0stpaBWBiUnYX6luvSs2z0pJ3VmZ7y
Cw+1i3iZIZVXAkf7vpxWGl5LdJJG0UYjyB5p6D1rR1GxdZ7g3ih5ZMN5u/KrmrOl6XYyWdylzMqy2xDxrn5
JF7rWbZs5QguZ79zoNF1Wzs7WGzhXzIYN0lw6rw5P/wBasTxRLZzxQNp0aRLKxZQhydv+16Uun3BtLaeG2T
ZFdyMuI49xIx9zPXFZ19AXjt3bekuAnlRqMEA/eY1SehhTopVHNle7dogTI4mb0PA9OBV2C5JgSKaSSGZYy
VYc7h2C1Uktkt7qWNZElUEAvnIHetiS3jlkmnRxNhPlCrwDjt6CkmdcuXZlOGG3Jd3HlxeWAqnlm9al8si6
ge1dmVFyBjtnoPetf7OzabarJAhngUlk7D8aiurSPEM0RALHOxAfl+n+NMwc7uxXsXe5uponlYuTypHQ+ma
nu7aVTNHKiRuDvULySPerGiusUshWErK7fM0jdAe9Je3+3WY4HZVDscv97AxxUtk2lKdooXTxLNaBrjHnqS
DxwB2p0uk/6K9wQTIDz71LZtCLXcSwbkH09sU24nljtynmnB/i7YqonLNzctDEul8tsnO4VnK0vnEIGZm5I
7Ct6yhjmnbdIxTgHK9avRadbx3ImgRgAOARWy1NlVjTunuVbS2VNPkcsd4GeKzbhy0Q8zk+1bcBSO8aRVZY
mXDr6GqYjtp5Z5BKuCPkXHVvSmxU5WbbOfnXcxKpgnjk1FLbq8uD8m0ckVuTWXlXR3DeI+54BrM1S1LO/lS
AOPmyP4ayktNTvhUTdkZ/iXw/daXbxS3MRH2hPMjHfHuO1cvHM0K4DYJ5rsNd1a+122ikuZMz2ieWNo42+p
rkjb5G7PzZzXJUWuh34Wc/Z2q7+RLvLxgydx1qrp1uZ9XgkU5WL5sevapi2Y8k8jio/D8ry39xtHKIF/M81
nN+6cWLasd/pECT3SCblcEqo4LEDpXR29tGIWWSPaUj8x3zyG7L+Vc3oUQluE3sdqqW+XqcDOBW3MqzmRUV
o8wrLkMSM+9c0drnjyu5WuWVnIUeXyvvRUEJAjA6UUkhuJ5HCp8vrznGKUozcfhioo+xU/dOcVNvzkHgHnJ
Nd5W5nX8ZEUqlfmK8AVi6dbbpFlc5RevPeuoCK8ZLEZHPHpWI0K2t6wO4pIdw9jQux0YWo6c7GrbQ20KTl7
lU/d7wu7Ofbin+HreHVdSWC6uhaxquQ3UyN2UViXRjiQoi5dj+daXh67Szmld7eOSUxsoLc7M9x71V9bHtx
bcHJPVm3cWF7pd8hnRoZIiCjZ5+or1HRNT0HUYrLQL+WJ4ZYxMLiI+Wwl7qx7nmvOtQu7M6Lp9paXquZB5s
ssy48tv7gPXFS6JpUd3pFtdC6+UTNHJgY8o9mz3FXezsjkrU1XpJ1G01+fc9d1fT7DSPBVzpuqXtjcMoLWe
4BGx2HufevFo1lvLyIRL5UmcLzjmuhi/s9tOu4Lp2v9SZ/KhncExxpnGcdj3qZ7SO2060tZbaJGO5fO35Ln
PDDvV7nNh4/V4yUm22/lsai3mtZU3OowR3Sp5YZ1HCjuTj9aS20mC90Se7muW+2q+A69ME8kmsW6ijuGi3M
oKARugyobB4Bpmr26w23k6fO+
+SUeZEhIAzwFHrVykyY0r2SdmaNpCEzJAgnhSTZI5HLYHY/TmrsEq2lus8bGd1LKibsOM9Mj6VlzC40qzNj
dFYyF3EI2O3P403Rrq4nuM2kG6P+/J1IHOanmLnByvJbHSXNlqUcSXS3NrErRFvIiPO3uT/ACrn7iKeeNBb
rI2DtVhxye2K05mbVp4tnmCV85w2M4549uKrQz+YwCoY57fLgSNtV/8A69JmdLmS13G6jut7YxKiESIglVh
lw3pSwWcZsILiaVROH/1GMZQdefes1pI3uDKzkM5+Y4OPzqxKIrbTzM9xF56OcxdTsPTmpbNJwdkiO6ka1a
aCEEzswkSUSfLGD2HrwcUwXHkFEIkkVN2QeisRyfesee9bzMKhKLxgjmtK1kmni+0M2QoweMECoUjoVPlV2
ieCKwlZZ1nDAYUox+83qK07y6SDO2Ly9pwj4xn2IqPRJ9MjtxbJa+dcFt+ZBwfati7WIRQi4PmANhmYcIfS
qT0M5v3kpJmdY6oUIlLNNldj+YOF57VYF6J7ovGmVQDkfxewqNobswKkVsZAp3BgoAKZ7mpLKWGcSNcKtsw
clAvQgcce9K5Eox3SLUIMqgOqvBnHBwQff2qrfQJHftLIzyoBgGMZORVue5SaMLAVVUYl1Iyzccc1Cs6xXU
bbvMR1w0AOCG7ZobM4pp3CO6Z0FvAjyR4ypZen1qcW1w8Qt3Rd7Hp1xS2azMGkERhUEjJ7g1oWN1DaXSST7
pGPyr9e34VUTmrStflQ+30+PTrYSXBOwuBt75qZ7uCTzzEuBHwCataxMsjsku0quCAORmsiQBbaQKQoYYBP
Nbcxxwj7T3pblI3W+SRnAHYgfzplpo8bBriAhnLZKmo9Jtzb6mJLmORolO4jH3hW0t6jyTXEMSoCSdnZVpc
1zsq3p+7A5HVluowwjYHPBxzzVe2uhHDcqLfzZCnzyN8wUdiPTmtq6Avb9lSRIg/K+hPp9apXUb2MWr2jXB
tiFA2YyZcdRn05rKTtqdkJJxUWtTmZb6e3tLyO1Kj7SoWTjJOOwrDRWADvkEdc8Vo3DHAMRO5aqMTLDIJAC
SOa5dWz0r8sXYozHYr5643DFaHh2Jbe2M5XMkx3Vk3D/aNsMY2vkKDXU20aFY1UYIGB9KzqvojysVN81mb+
jIJruNS7RAAsXH8OBmujQpcxOPtjsqDJ/dAZFc/pqvHPELQJ5hznd0xjnPtit3HkwuyfZVXaGbZklhnp9Kz
itDzp6sjdfIdo2I4PBHcUU1pPOcuynJPbpRU+g1fqeQRqA3161KYwx77TSCILjB68mplfGzjvXaNMjEQxtC
7ffPWsjWIZJLcmLIkj5HPX1rdkcmUEgZI7VDcKCzFF57e9Ju2pSetzjYpcsMAtgdfStC1mxImEIU9feqOqw
GwumQErHJ8ykdPpSWcpLRh2yAc1o9dT2sLW547nRrF5iqgiLBjwo5rRs5WsgiG4IiY8xA9/eoT5DWMtxHcC
K4VlCQKCcjud3arb2Aky8B84KgZpD8uM9cZ60rW2OtVObR7HV6TeXmkJHDFHMJJcs0LqrpISOefpU8esPbX
TXF9pyG4VNkAABQDuPrXOWGranHaLDBNi3hyC2wZX29TWpZi9uooL+aaCUfN5RkPIx1JFaxkcVSik7ySN21
W3SyfzYBJd3T+ZvU7liToRj1qF7GCy2Stc4uEdWKhOntz3qHUbh4p0tftcWoEoJN1uD8pxwPwNVrGaeOWea
f7PJcKBv88ncw9verbRzQhK3Nf+v8ia8khu5ZGv0jgunJO1s4U9gauWixWccclxMoPJHlD5QOnUetUDCjNG
bpWljly+wndx7gcitLSrEmyJgQAPwC5OMelSty6nKo2JJL6CKUC2RY2RS3nE5xkfyrFW2lnls573bHEATtH
LSc5BP8qu6xp8UUkUolVmYbXjUdvU1Cbk20ETSJEVVvkZV+Z8HpUO99S6aSjenuRXNvHKJGtZYkQJ5mzPyo
M9PrVO2Fu8LibLBFIbcOvoc96kubtrslP7OEBYMWcDBOehIrNeWZ4pVUAJHjcRxkdKlyRryPls2aLTQXNzd
XB2MPLG1mHJwuBio4gJrmMbsAoOFztf2quFR4EicMgB3bwcD6fSp9PdrYiVY4wV5DHoOetLVmkY8qdty9bS
lLrC+W7w/MeMEY7fhWlHq8+oRznyTCJT98jgj1571WuI5nukuFgRvO+cuE25wOQKt28jS3WyWDdtbCR79rD
Pb6U9jOSi1exTjuNQNuBayM8DLtkJbhuewpZS8N+iiRQpHyA8gH1rUmt7jMUljDHGDkSITyo6cjtWXeLFBc
mBJUR0G7c/PJ7CpFCSeyRchllZ5vOx5+weWQv3vY1Z0+8uJ7qOSW3iWSJgFUc5pbYSPbW9wkpl2nOD1Ptir
unyNDdNKsCLC4APmLyGHamjmm1Z6Fk3ZdZ4nRdknz7QeYz61SktsSWqDfIrBTuU9yehP0pplcaxcEJsjYc9
637zVraDTYIbe0zE3IlfgsRxnFWkckr02lFbk2sWjae6wiNI4WTd5zNu2gdT/SsKzVriSVoXJ+XcqgD519R
U+ratLf6ZDp9sU826kK5Y42gVi6OskmqRRo62kkYIZ24AI6nPpVXHQpNU25vU3bi+gtrSRTA0ThVV5Q3ILe
x7Vmz2cmnsZncyWk3ETjgOMdabrlrF/ZZlN2JrudwJCHzhRWTrWqzSWEenLdrNaQMDFhcE8Yxmp5+pvSo89
uTZ7/16k+pu+nR29vZwtLLcIpdmXLK2c4B7VX8Sar9qDWkkASRCCC4+dWxyD61b1jVLqXw9At1Z4mVx5NwB
wyY6A+orltW1JtT1HzpFUSjCvtGFIA6/Ws5SOijS5mpSWqvczpZcOc4X1zVF50Ckg5U5zVrUdjwvtGCO9c9
cysZ4LaH5nb0rJ6M6Kk4qN2aOjoJ755QT5UIwM9ya6uyUIN24NngZrDsrEQJHBEWJYZc+9b0cfKx4+VR2rC
TbPGqS5pNmppXmfbEMamVipUqDjII5/SthQ0VtuMYLpGY8iUEbc+nrWZowUXf3iBsbcO7ccgVNttvLIihnD
ngbiMD60LRGDd2W45BsGCR7UU1VTaKKVhM8lifcmO/Sp7Y5JVz045qlattQgjgmrUSl3BHWuq5US3swFzxt
7ilI4V27mpguI8gZI7VGZTG+HUcnH0qhrUxvE1h9pswYVJdG3CuRtp5Y5HAAz05HSvSynmbhnJIz7GuH8R6
Y1lei4i/1Mx59mqk+h1YapySsyaykLNknqORXQw3WwZnUPlQqEn7g9hXJ2Uu0qy9Qfyrdt72VYZDFtMj9yO
n0o2PZjLmOgS7UwnyQDMr5Sb7rD2x0qzFAI5DAtytwzZy0PPXtzVC307+0LJpLN4jHCAZVkcIxJ54HenJLC
beKK3t2iu0fbJMr/LtPH6VSYpJO6XQ1LKPzL+OCJGERwzjJUuR1AI6VsagJbZnNvDLbQS8qjMGzjvmqF1FP
ZXUMNvfW0rxLuEkJ456ge9It5JHcqLho5Ijne0nIwe2e1aK3U5XebUlsLA4juor0TSi5DBnfHTPbb3rTfU5
Xt5J9u0KxjJzg5Pfb2qQwCC4ikfyUWL+NXBB9M+vFc9JBdyXlxJYOkjTqQ7tyCM9vSolJx2KhGNd2kb1pbz
3qRmDETO4G6UfNn1+lQTXMUM6rNAbq4DHaSflD56kCoo3kWxSGSeRMsAQo5J9M+9Wnlt4keExSRSKDvG3JY
9s570XuJaOwy7kd7hpJpIhI+WcBcAY6CoLd7MTSG4VkiMbozD1I44+tVpp2ltSZsbmPpg8cVXktkndI5ZH2
nklBzwKlsbgrWY5mjhcpDKZGxlldPu+1WbWRFgZ52MkeR9w5I/D0qvArO8ckUYeZOGZzx+NX5bB4pHukYhG
G9lJA3evFTr0NU1sXoLu5WJo5lDRMu+MkkHHtUYiaaSTdva6JyjbsZH1pumSyzf6tGcgHy0D8gf4VlXWqMJ
pCTvkBHyj2ok7aihBylaJpQXcryTRvI5hkYIeTu4q9NNErziCDzdwEZlZRhRVS1MV2iFSiySDO5uNhx6Vd0
5JAxRFJcKfMGARt7kUt9SajS1asSuXsIFPl+ZCTxKhwAOmcURSSSX5t4GkLD5lL/Ko/PrTp4V4WxuCyOMss
q9QOf1pYJV1NWmu2Mcif7OAB2xTsY6ctzc05Z47hZUMPmBdpSTkMao3RvZNSMb4DuxjwqfJjOTT9PltxcRS
SmWcZ+5GOFPbrVl9QtZtZe4hldI0+QtjkNkcgduKq5x6xm2lfQqXFvJDPa3MoJgtnKBkXOCTwR681fuBY3A
1G7kypjtVzEh+Z8nkfWq2p3N1p9zNb20wCStnEuNrd857Gs/Tb27t/EVw0IQzmMFSz71Ax0J9DROQ/ZynDm
vsu5egudGSDUJbi3c2Z8t4SQVKjoeT6d64e9uYWuJWgK7CTgD0zWvfG9vbRXv1jNtuZ442yFY55ArI1m1iN
jDcyPDHcykgwxrjYo6Gsnc7sPTjTb63LE2s20mg29pNvd7eRmOTgBSOMGsW6W1icSWM3nKRnPrVGRtrKQu4
E4pbhlQsIx8o60r3NnTjS+Ez768MUEzyH73aoPD0EizNeXCEswwg9B61Tnzf6jHbx8oh3SN6Y7V1NnGquMZ
wPaol2PNxdbmdkaFquV3YIY+npU6yNHyzYwcZqC2bdI4OAMZz704AOcnBrJnEjd0PaT532wQygkBdpJHvWy
1zshdWv1lJH3dnX9KxNHt1aAsZ4YySRtc4NWZ4FWBmFzbtjsrHJ/Smr2IktRTdgH5RkUVlNcqh2qeBRSsVZ
HnltICQv61oWWBvJ5rIsCHVWHWtK2cJcEbq6XoyIPQ1kbdLgHapGaR40lOST8vHSmW7AuAegq0GKucKOuDT
expHRkF1E7BJYQeAAQKo69YHUNMlih4mxuGR3Hat+JpD8hQhTx0pGtirbQTycg9qWzK5rHk9vcOTtKgAHB9
RWslzL5Plqo2+/aq/iLTxp+tyKSPKm/erj361FCSGzuyOwNat9T2cJUUoo39LuRCxUsFLY2kHoa2iPLRlcF
JyvzMGzuzXN2CqiYjBaU8EkcCtK2ncxz+bGDKOFYnkUos65RTd0a8Bf7NGVVtjHncfl4q49qZoPPmuYXUyb
fs+ef949sVh2dzGAEvXnSA/xR8lfbFX5JxFOvkOrozYjZsKSMfxCnzJmbhJPQ0nDQJGk5AiJB2A5DD0NTwG
OeHzoFitE8355A3CJ7ise9ikIilE0cqtxJGG5U9uKbAsSQyxoG+Yg9eB+Hem5dhezXLfqa0pt2Z2ikkdlP7
uToCfXFWEuoTAFIElw3yszHGD9axJZ4EUhZRGwHy7gfm9fpTmfzrGEFsEHqVx+FSpa2HKnom9jSumHBkcOM
EKFPGT6U83stkY4lCOjxFQ55IB61QZ/KuQHRXg2jGP4T7VdgtrBIGEc0nnPIGcMM4GOB+dC1MppJW3LMEAj
jWYKzEnaQeFYVaj3NGC5VgxOA7fdHofaqcQaS5VQ7mPoNvQH8aZZWq+ZMZsK/JLuThTT1J5Vq2zW0CcyalJ
NMRFsXYp+6F9h7Vo2trDNLNKtohAb99JnI2ntj696pWV/GsYa+g8zIAPycnjgjNaKXMKForMhX8rLrGMkg9
PxpW7mFXmcm4oyrqxtbfUlliANuSSFXo
TnpntxW1EYmSR4WkdUXcGQ/dB/gOetJcXCPbQ7Ld2hkXaz7APmx1A9ai0m9H2eaIhYECkcgncKdrEylKcb9
hIRJdXWy3INvPwGY8pjrmqm57C5+zxRgp03H5s1rRfZLm18uOMEI+75DgkH+LFY+pSRWt28QuDsf5cnkqaQ
6c+ZuNjQg1W4Nu1r5Q2hSoKx5Jz3z61NqRtoEgjMDx3IOzcAf3gPXJ9azo5Glu2isZdw8vy+DyxxnPNXCzS
LHBcvLNIsZMbKwRgf9r+VDM5xSlczLzWUuZp4W8wxnCgsuSCBj+VZQMumTlJHkjjkBBYHOV7ZrT1CJoZZPL
uGVmiD7ZEBw2PUVzZluYpGM7htw4Y8/lUSO+gk42jsOu3uI12PKZoV5CBs9eeKzr3y5QgKPGR23U24IRjKC
+DzsXsabHei5tAzRbGB9cmovqdLfKrojEiqeM5Hb1rMvp5VSX7OBmQ9c0+W42rI7lcAHHPNM0mLzYUuLjkg
kqp/nik3Y4MXWUNi1pFglrH8oLzPhnY+tbKgr8p+8fQ1FEwaNWReD2q1EcKXxwfzrPfU8dsRTsbYPvHqTVl
Y8uuD07etV4V82UnPTpVmEjzMKeB3pMDY0XyzcqpRWfa2wN0LY4z+NXL6eR9PkcRxJEYCWkVANrg4K/jWVp
/lyXgRxuG0kJnG8gZAz71SkctZ3xuIHjWNfMVyCu1s8Lz1z+dXFWRlPcqNI5PyjiisWXUjv4OKKOVEczOW0
e5JjAPpW3EdxDnjsa5TSpgGEZ69a6W2k3DAPWumrGzIpyNSFwqozNyDxWur7iSDnIB/GsS2cFORnnitS0cO
FUcMag6kX42lKg5wOmc96teVIYvXA/yayyjxkgNuU8/SrtnIQjLI52OOD6UuYqS0uYPi3SRf2jTni4tgSAO
4rg7byjj97g/54r1kYAPDF1OD7j0rjvG2g+Uv2+wjjXj97Gg7HvVxfQ3w9b2bszFExCGNWJz3HUVft7oxj9
8GZm4x3ArAtJ/mXPFbFrdLsDIMsOAjDlj9aGrHt06qkjobaWBhNtiZsFdrt1XA5XHTHvUk32S8XaWVXB+ZQ
Oc/4VhfaZGmSUTvBISAozkVdW4zcfI671bJ+XnNK/Q15Lao1kz9nSNI8kDZnPX60lvFP5T/ACKjH7tUvt0i
4URuSTy+f6U6Oa5+0HlduODnPNFwUZWNKNDKqx3O0O7/AMXAX6mrMV6DEPLVSyn+MZTI/wAazILh5IGDoQR
8p3UxLhVtykSlNp+Y5yDntTuZyV9zobGa1aZnuQg48wIwwr+oH0qNWiN28ka4jfghjgIK56V1aWBlLSdygG
3gVqWsvmw7NoDZ3KDycUKRnKlyvmNyAo0Db2DJEM5C9R2/GpBKyIsnltMJsgKFB59MVkWXyyOJJGAPDJnOB
7VPegzRR/Z5HRkYbXQ42mnKTaJ5FzWZp6ZcxXEokMEq+UfLZJuhOKfdPbG6R9Pjlhu8ZPl8qR6E9qoW0sqo
63TGZ5PvAdz659asi8e0uvMtVWN9o3FVG0dgKS21FKNpOxfivJZLuFLUiBzjAkbgepGamUkxK87uiRuw3IQ
2PqPesZ9SRNyqIriUsWaQ8npyMUqXMDyj7KG8oIAT0O6kQ4PsTXV4USJ2T94vJKnBPt9KSaR7m5SVrYRI4y
CBgH2qrJcQTT/e+YZDdxTnul8oCRmjWMbgCchvSmXbl2WpsXs0cFq0kCJHKG2qgJzj1FZNrPJcW0glf5Eky
XH3jnrzVV7xri1adYMxwnyxhsHOOpHWqraoEcRSW2PMUAsBgGk2uhMKTUWixeSt5wYXRYMMEZ+6PQ1QlkjD
Da455Az3qK9ItrnzNwWNlGFPrWVPcEy+ZIhIUdV7CobN1ZIttMzCXzBhevXrWdJfxKuYTgOdoXHJqi9xcz3
hgsnSQdSQPu/WtK20xbdlJ+aTrnOTmpbsceKxKjohlrpse8yXSbmJ6dhWmE2ttUAKAP8A9VP2MJQSoPGTQ7
KpwRndyah3Z5cpuTuyTeONp2n0qUy5UZOB0FVYwZPlIxuPWrJRScnog4osQyzbnqcdB+dNL4XAOM9/Sq80z
7flAAI/IVSmn2oVD5FIV+pordRTTwwRW888vzbhFJgtxxj0xSalBdTQMDpmqO4HyeZc71U/TFY+m30dnfiS
YP5ZVk3IMsuRjI9xmoL6WLS7e4827uX+1IIl3W7oqZIO8k9SMcAVtThc5atS2xk3Vwy3Dq6sjKcFWGCDRWP
4i1tb3WJ5rcu0RwoZhgtgAbj9cZorp9gzm9oUY9yyBxkEV0mnThkyvORWHMQjH0qXSrgRylWPB6Vc1zo1j7
rsdbCxJABwcVo2sgxk8utYttKPlJ6+vrWtCyLhwcE9RXIdcJGrApkBwcnGfpU8JDDY+V461lxSYcMOB7GtJ
MFVKjBxik0brYeX2IGG4uDgj1FSuqvmRgZIGHzDutRqmJBubBHTP8VWrdgGIXjPDL6A0rg9jy/xBocmlXDT
wvvsnc4IHKc9D/jVG2umViVCsPQ16pf20LhobiESQPkZI4NcBr3hieykkm01TNa43YH3h7D1rVTvozpoV+T
ciEolOGAx/KrETJHllBDtwWxWDBdtgdj61sWtyhx3qZK257FKspI0ELxpgybiCWPf8KvRyggOpxkcKazfNj
Rd7AnPHyc04MCWDLmMkbeeaSdjo+I1JGbywwm288gjg/8A16hLOj4KgqwILfWovPUs4LKVxxkYNODNNbfMc
Kp6jtn2pXJ5WkNhhcXJAaRY41O3A6+taVtcJNEBEfmJwOMZrKhtp5HmcZIiAYDfyQfSrKTFLhFMZQdQcYAN
NPqJroa9ifJU+YV8xm42jnHvVuKeG0hcyMIyQQ2cnJ7VhF55XkEUqh84yB3q8MGOJp/3hxgj1NNPsZyjfVl
+5kgeJWS4CTH+EAhce59adZ3GX2JICqjDN/XFUg/7naVUKeCMdveqs8iRy+ezNuwR+7HP0xQ+44wTXKasxV
ZEYbUHP3WHOaSWdJpFht1VGxghTjn61ls0DhZtpU7eR6GmBZri6Aj+SINnJHQ/4UmVyW3ZcERhtpEiYJKvz
Eg549KaHjaFBguqnc2TVOS6YSyQA9Mg44BH1qOCTMWH3EMPXoPShPoDva9zbXUYXRoDbfZ4wN6bR/FjBJPv
VGa7t9qxSSkNnKAnpVYSR52xhfu4AycYrMvZUw8jFSR3NP0OVuKY7UdUGUBjLnPc9KzxHdX0jhGEcDMATnr
60WMJuyZmb/Ryfu+tdBZxZYFUC7Og7AVlKVjhr4r7MBtlaRWcaiFAhPU45NXU7tyB3J708hnOQoVAOWNJNK
FiBOOBnFS0cDbb1GB28suRj0FJEvmkvIcAfrUMTTTZZiPmPQVZCGMHBG0frSQPQlLIvzcDioftKsp7qoyTW
fdXDTsqISAOOKlcrDGEIGep+tWiG7CS3BaMkkgds1RnuFVGJPHaodQvBkgYCjtXP6lqW1NgbJrSnTcnoc1S
qjV03WIotWVppVhARgkrDIjcqQrH6Gql/d3Nrp2pDVdTt7mOeEpFClx5xeTIwwx93HJzWJDpGo6pB59pHG0
WSMtMiHI68Eg1ZsdEvdMtdWuL+KBENlIinzkc7iVxwCT2NejCkoo4pSbZyrMc/wD16Krsxz1NFdFjM7a4hD
g461V8vywTyGFXy/P1qOQBhg158JW0O6Rc0ucugJPSujtSuAC3HWuQgxDJuJ+U1tWtxwCp+X61nOOt0XCZv
qV+ZQRx3q7ayBYxuLZ9RXP+ad25R1q/Yzb4iDwQaxbZ1Qlc6NGDWxLndk4HtUsToY9ki5dTwR1rKt7n94u8
ZBHOK0oSpZWIGD6mluabIndmKFeQFIyD29xUQj8sSOsfyg/WrEmxn+br1Vv6VGxnXDR4KjILLSsI5bWPCtn
qLNPbkWkx/iAyrH3H9a4670+/0mUpdwtsBx5ifMrfjXrYaNogh/dyHrn7rVU8hN7bwNpb7uOKtTdrF06soO
55fa3ijAU8ehrRivI3VS2FI7+tdZqXh/T7xGeSFBN/ehO3Fc1d+FLiIlrKYOvXbJ1FDaPSpY9P4gMu7dwGI
wQCMD86sW86pIxKKq4yw9fxrIks7+1IElu7A/3DuFRpebJSZI2SRRjB/wADSsd8MRTnpc35PsizKYy6KQTG
dpwaeWjcoTIXjI9OB6Vlxak2FjPzjHyh+30p8d2kjHcTgfeU/dz60Gi7mlAZPPDCRQOp44I9KsCUSyqN4AH
OewrME5/5ZOwUdeAQaVZi0agON2M8gcGi4S1NUyHdtBbk461VLsJGefaEA7nr7mqQlk8sq0pDk8EVHNckx7
HYsO+Rnmh6iTt1NNbsSg+W+VwM44BqBrqcXTKJlVD91QeprKaZrdtivtQ/wkZ4pk7rJ5bZ27eVIpol1FFms
8yhcbyu7jaTnBqk93IHMcowT8oK1nS3sheQuVGeahgW6vWC2yOwzneeAKq3c5qmIUVuXJ71Y0EaZdiNq4OC
amtbGW4+a9yy9RGDwPqe9aOn6TFbIGIDznq55JPtWokRVfmwoHGaylLseTUxDmyK1hVYgpQL6DHSrKkxgc/
KeMjvSIq+ZwCcfjmlxtYllBJP4CoSMX5jhLvTagI5x61JKiEZblsYFJCvJ2KTj9KljjwSHbn+lOxDYghW1h
BGN5qndTbsRYxnqafdXPl9TkngVn3Fzt3c5Y07dCJSHK6RMcY4rMvLwLuZjk9arXmoLAj7m561ztzqPm7ie
nat6VFyOapVsS6lfs0je9YM0zMSScmknnZpDk5qux55r0adNRRxSnzFi1s7rUJSlpazXDgZIjQtj64pNQ0u
+sFDXtjPbqTgNJGQM/WtewuYZ9ATTxqa6bMk7SsX3BJwQMZK9xg9eOaf50Gmabfxy6wmoNcwmJLaEuy7iQQ
7FhgYx25rS5JzG4D0opRbseetFVdCO4lXmojVpgMc4NRMB2ry0z0GyCTDLin2c4hYK3K+tNcCoZACp45rRa
qxPmdDBOdvrV21uACM9M81y9pcspCyNgVqxTg42nj1rCcLGsJnTI/8S4xn1rQWQeWMnmuZt7nIK5rUiuOAM
ZFQjpjM20d9gIY4HPPQ1YiuI+GIbb7Vkpck8HG09ialWQduR9alo00e5pSKWO5CGT+56/Sml3U/vMsv6j2q
sbkKFC/K3vU32glSpwHbk57/AEpDsA8p9xLFT7CoZ43AU/dHUN603AXnkN7nrUxkHlgbSD/snINITVimRsO
x9vI+8DiqV3BBOh+1RJKnqRyPxrQlh87cxiLD24xVYRTJlACV6lW7UalJow5fDkEzZs5JIW6jcdy/Ss6bRN
Rti2EWZQOdpx+ldmzgIC6DAHpyKhMiSEnkA9xVcz6mscRUhsziRJcWm0SW0qY9AcVWN6m9nC4LcZr0AlUjZ
Y8MpGcng1XMMDrzGPcDHWmpLsaLHTWrOFTUNmMPnHTPJoN4ZdxyWGMcV250+FpCVtUGBncwHFNS3gSUgpHj
P8C80c8ewfXps4yOaWbMaRySYHG1TmrP9l6hNGilBF6Bzzj6V2rCKN8xKVJ6gVDh858ssx6e1DqdjJ4icjB
tNBjgG64YTyf3SOB+FbEcIRdoAAGBwMCrMVu78O+0dMDqak8gRjLfMQeF9qhty3MJO+7HQ24KB9y5PcVXn5
JC/hU4fcu0thBxxThGqxqQNx9TRYhabkSK0ahep7+1EUW+VlBwD1PpT8jG1zg4zgVUaZiTtOAKVh3NFZFt1
2pyo6k9TVGe8DM2Tn6VSnuiXHJx9az7q62uWzyKpXexk5It3Vxl9xPToKxtR1AKrKCDjvVO/wBSGCFPzVzl
zdNk8kk811UqDerOSpVLGo3fmHJJxWXLITxnmmyOW6nNRsce5rvjHl2ORu+4px3prMB9aArOelWYbRmYEir
em5JpaF/ZD2Nyuo2ZlvI/njJuGjWUd146N6etWT/ZU1u6waO8MrDCubpm2n1wRzWxoumpb6It7BpseoXLSs
j71LiFQBj5R65PJ9K0FgW8069lu9JisfIi3pcRxtEN2RhSDwc1k5FHJrZqFAoq4T60VF2LQs+YWFISKgIYZ
xSBz3Nc3KdpI5qNsYpwb1pj4qkJkZAPGOe1OguDC+0k4po+vNNbA5aq30YjVhuM8hiTWla3R2g5/OuZRijZ
jP1qc3IYjBKnvWcqV9TWNSx2MUyP8rPyelSx3DxHrkdK5SG4ZcMZK0ra8yvPBrCUGjeNQ6NLtTES549adHP
lcg7h9egrIS5ATHUGnJKoIwcCoaaNVM2vtbMhyOAOtNF8QVwMDuRVAOGYAHH4075GbBXBFFmwczagu1Kk43
A8cUq3IL525PcmsdWZDhMEexpd8injIH1prQFJGvNICW/dkFhxgcVVZioAWNHPoRiqyTsxI3c+5qwJOF3uA
e+RRa4+Ykj3SRsjRAOOetJLazuxZNiJ7HmlWZfMzgMO9TCZicIiAHmlyoV2irHHKpCs5JA6daQQyhiCQFPP
Srjyvj5tv5ZqFgS+5yQvbPSk0UmMEOGyDkdD2qXKrDtAXd2xQiByzEnHoBUTyhMCNCz5656UbCvdhKcqPl+
bGTVZYz/rHcnPanSOXl3Z+p7USTgkZIwopWuwbsPTk/vOlMllJCiM4x1qo96zEjIHvVCa/EbEAgCmjNs05p
/vEcDGPrVC4uE2kKcYqhcXpPO7j2rJu7/OQpwe3vWkYORlKpY0ZrwIpyRWHfX7Fj83WqN5fMCfmGfesmW4Z
jjNdlLD21Zx1KtyxPcksSDVN5N2SeTQUZz/AIVPDaE9q6tInO3dlZQzeuKsxWxbGRV6K0GQDVtIwvFS5gV7
a0UcEVcSJV7UAhelNLkms3rqB0Oli2sLCK+uZr5GnkaJPsjhCoXGSfXr0qe6sp5xdvd3s95aratcWs28lXw
QOQe4yQRWBBe3f2OSxhO+GVt3l7Nx3eq9wfpT4tR1DT7S4sSZIoZ1IeGVMde4z0osFyqH45oqEE4op2Yrl8
v2NAVT6VoS6eScriq0to0fauc6udMrlOTio3BxT3DqeBUZk4ORk09R3IicHpTWOfSiRwaYDVjJFwOlIxB+9
zTO9IxpoB6uwOVPFTRXbowyDj3qoDg0PIWwD0FDinuCk0a66hu5DGrUV1kAk1ze4L608TOcAN+FQ6KZSqtH
Wx34XGenY9xUhvi7kg9+pNcvHcMo5zUqXQP8VZOiWqiOqS4Ocq35VaF4AvzEkdK41L1lf7/FXI77cMt19qj
2TRXOjpxdxlR8vPqKspeBo9h27eoyK5eO9AHysakju1Zidx496lxaLU0dTHOD1CjPcVOkyA4kY9O1cmt9wQ
G6U/8AtLCZY/rSsyuY6v7ZHGxUNlT+dRveKxJRj7Vyn9pxnnOWpv8AauPlU49TSsyuc6Z7xpJMM+B3FRz3q
RphOcdq5s34LZ3HJ71A2oMDy2afIyXURuy3skhAGFHWq014qkjdnFYhvl3lpHyPSqlzqQdzsUAdquNFsxlV
RtSXRYcH8apTSqMsxyRWPJfOe/FVZJ3fIUkg1vGgYyrF6fUsOVU1kXlzJI/B+uKkWAk96lFqOpA5rpjGMDn
lNyM/y3kOWyanhsznBBrQESqOgNOBC9uKbkyCOK1VR0qdUVelNaSm7zjNJ3YExYA9aaz1EXyeRSBu/pS5RE
m/nrSbuajyM0DmnYR0+kxlNEd7fzfPlSVyYTh22lQFB64GSxA68U5I3n0Apd+fuMcsgE5JKlMEOueQDnaR0
JrG06/e1jMTxiWAsH2FipVv7ysOVNWrzUmuYnjiiMSyY8xmkaR3x0BY9u+BikMy1BxRU4j4oo5hWP/Z);\"
>",
" </div>",
" <div class=\"lgnd\">",
" A white plaque is present on the tongue.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_423=[""].join("\n");
var outline_f0_26_423=null;
var title_f0_26_424="Role of lung biopsy in the diagnosis of interstitial lung
disease";
var content_f0_26_424=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"3\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Role of lung biopsy in the diagnosis of interstitial lung disease",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/424/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/424/contributors\">",
" Talmadge E King, Jr, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/424/contributors\">",
" Section Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/424/contributors\">",
" Kevin R Flaherty, MD, MS",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/424/contributors\">",
" Praveen N Mathur, MB, BS",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/424/contributors\">",
" Andrew Nicholson, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/424/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/424/contributors\">",
" Helen Hollingsworth, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/26/424/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Feb 14, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;The diffuse parenchymal lung diseases, often collectively
referred to as the interstitial lung diseases (ILDs), are a heterogeneous group of
disorders that are classified together because of similar clinical, radiographic,
physiologic, or pathologic manifestations (",
" <a class=\"graphic graphic_algorithm graphicRef77345 \" href=\"UTD.htm?
42/30/43502\">",
" algorithm 1",
" </a>",
" ). The results of clinical assessment, laboratory tests, imaging, and
pulmonary function tests guide the decisions about whether to pursue
transbronchoscopic, thoracoscopic, or open lung biopsy, as outlined in the
algorithm (",
" <a class=\"graphic graphic_algorithm graphicRef69044 \" href=\"UTD.htm?
17/14/17632\">",
" algorithm 2",
" </a>",
" ).",
" </p>",
" <p>",
" The indications and methods for obtaining lung biopsies to evaluate ILD will
be reviewed here. The clinical evaluation, diagnostic testing, role of
bronchoalveolar lavage, and histopathologic patterns commonly encountered in adults
with suspected ILD are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/20/22856?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Clinical
evaluation\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/18/16681?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Diagnostic
testing\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/41/25239?
source=see_link\">",
" \"Basic principles and technique of bronchoalveolar lavage\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/36/16968?
source=see_link\">",
" \"Role of bronchoalveolar lavage in diagnosis of interstitial lung
disease\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" INDICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;When the results of clinical evaluation, laboratory
testing, imaging studies including high resolution computed tomography (HRCT), and
pulmonary function testing do not allow the clinician to make a confident diagnosis
of a given type or stage of ILD, lung biopsy with careful examination of lung
tissue is often necessary (",
" <a class=\"graphic graphic_algorithm graphicRef69044 \" href=\"UTD.htm?
17/14/17632\">",
" algorithm 2",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/1,2\">",
" 1,2",
" </a>",
" ]. The evaluation of ILD leading up to lung biopsy is described separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/20/22856?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Clinical
evaluation\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/18/16681?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Diagnostic
testing\"",
" </a>",
" .)",
" </p>",
" <p>",
" Lung biopsy is helpful in the evaluation of patients with ILD in following
situations:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" To provide a specific diagnosis. This is especially desirable in a patient
with clinical features such as age &lt;50 years, fever, weight loss, hemoptysis, or
signs of vasculitis; a progressive course; an atypical or rapidly changing chest
radiograph or high resolution computed tomography (HRCT); unexplained
extrapulmonary manifestations; or pulmonary vascular disease of unclear origin.",
" </li>",
" <li>",
" To exclude neoplastic and infectious processes that can mimic chronic,
progressive ILD.",
" </li>",
" <li>",
" To identify a more treatable process than originally suspected (eg,
hypersensitivity pneumonitis versus idiopathic pulmonary fibrosis).",
" </li>",
" <li>",
" To predict the likelihood of response to therapy before proceeding with
therapies that may have serious side effects (eg, cellular nonspecific interstitial
pneumonia or organizing pneumonia versus idiopathic pulmonary fibrosis) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/3\">",
" 3",
" </a>",
" ].",
" </li>",
" <li>",
" Rarely, to diagnose ILD in a patient with hypoxemia and pulmonary function
tests strongly suggestive of ILD and a normal HRCT.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Patient preference must also be considered. Patients with minimal symptoms,
signs, physiologic impairment, and radiographic abnormality may prefer close
observation over several months with interval repetition of pulmonary function
tests and HRCT, rather than proceeding immediately to lung biopsy. Other patients
prefer to undergo a lung biopsy sooner to obtain a definitive diagnosis and clarify
their prognosis, rather than watchful waiting.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" TYPES OF LUNG BIOPSY",
" </span>",
" &nbsp;&mdash;&nbsp;Lung tissue can be obtained via transbronchial biopsy
(TBLB), open thoracotomy, or video-assisted thoracoscopic lung surgery (VATS). All
are subject to potential sampling error because the disease processes causing ILD
are often patchy and the sample sizes may be small.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Transbronchial lung biopsy",
" </span>",
" &nbsp;&mdash;&nbsp;Transbronchial lung biopsies (TBLB) are obtained during
flexible bronchoscopy, using biopsy forceps that are passed through the channel of
the bronchoscope. TBLB is often the biopsy procedure of choice when the suspected
ILD is likely to have a centrilobular location (",
" <a class=\"graphic graphic_diagnosticimage graphicRef75540 \" href=\"UTD.htm?
20/38/21088\">",
" image 1",
" </a>",
" ) and when a diagnosis can be made from small samples of lung tissue [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. Examples of such diseases include sarcoidosis, hypersensitivity
pneumonitis, lymphangitic carcinomatosis, eosinophilic pneumonia, alveolar
proteinosis, and infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4-6\">",
" 4-6",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/29/16858?
source=see_link&amp;anchor=H9#H9\">",
" \"High resolution computed tomography of the lungs\", section on
'Centrilobular nodules'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/20/22856?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Clinical
evaluation\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/18/16681?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Diagnostic
testing\"",
" </a>",
" .)",
" </p>",
" <p>",
" TBLB is less likely to be helpful when the pattern on high resolution computed
tomography is indeterminant or suggests an idiopathic interstitial pneumonia (",
" <a class=\"graphic graphic_algorithm graphicRef69044 \" href=\"UTD.htm?
17/14/17632\">",
" algorithm 2",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/23/4474?
source=see_link\">",
" \"Idiopathic interstitial pneumonias: Clinical manifestations and
pathology\"",
" </a>",
" .) &nbsp;",
" </p>",
" <p>",
" The equipment and technique of flexible bronchoscopy with TBLB are discussed
separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/50/43816?
source=see_link\">",
" \"Flexible bronchoscopy: Equipment, procedure, and complications\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4657761\">",
" <span class=\"h3\">",
" Safety",
" </span>",
" &nbsp;&mdash;&nbsp;TBLB is a safe, minimally invasive procedure with an
estimated mortality of &lt;0.05 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,7\">",
" 4,7",
" </a>",
" ]. Pneumothorax is estimated to occur in 0.7 to 2 percent, although rates up
to 10 percent have been reported; less than half require tube thoracostomy drainage
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,7,8\">",
" 4,7,8",
" </a>",
" ]. Bleeding (&gt;50 mL) is reported in 1 to 4 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. Additional information about the risks of TBLB and bronchoscopy in general
and precautions to minimize procedure-related bleeding are provided separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/50/43816?
source=see_link&amp;anchor=H12562876#H12562876\">",
" \"Flexible bronchoscopy: Equipment, procedure, and complications\", section
on 'Complications'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H20485052\">",
" <span class=\"h3\">",
" Specimen collection and diagnostic yield",
" </span>",
" &nbsp;&mdash;&nbsp;In patients with ILD, the location for TBLB is generally an
area that appears involved on high resolution computed tomography (HRCT). Of note,
it is general practice NOT to perform bilateral transbronchial biopsies during a
single bronchoscopy because of the risk of bilateral iatrogenic pneumothorax.",
" </p>",
" <p>",
" The optimal number of TBLB specimens reflects a balance between the expected
diagnostic yield and the patient&rsquo;s tolerance of the procedure. Usually, four
to six TBLB specimens are obtained [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,8-12\">",
" 4,8-12",
" </a>",
" ]. The effect of the number of transbronchial biopsies on diagnostic yield has
been examined in case series, although the data are influenced by the underlying
ILD. Among 244 patients with diffuse ILD, the diagnostic yield was 50 percent,
based on five to six biopsies [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/8\">",
" 8",
" </a>",
" ]. In a series of 24 patients with interstitial lung disease, a total of 118
biopsies were obtained (average five per patient) of which 78 percent were of
adequate quality and gave an overall diagnostic yield of 74 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/13\">",
" 13",
" </a>",
" ].",
" </p>",
" <p>",
" Larger TBLB specimens are more likely to yield diagnostic information, and
toothed forceps typically provide larger specimens than cupped forceps [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/12\">",
" 12",
" </a>",
" ]. Specimens that float are no more likely to be diagnostic than those that do
not float [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/12\">",
" 12",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H4658609\">",
" <span class=\"h3\">",
" Ancillary tests",
" </span>",
" &nbsp;&mdash;&nbsp;When performing flexible bronchoscopy in patients with
interstitial lung disease, endobronchial biopsy and bronchoalveolar lavage (BAL)
are often performed during the same procedure as TBLB although the data in support
of this practice is limited. Transbronchial needle aspirate of enlarged mediastinal
or hilar lymph nodes using an ultrasound guided probe can also be performed during
the same procedure if the appropriate equipment is available.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Endobronchial mucosal biopsies can be helpful in patients suspected of
having sarcoidosis or chronic beryllium disease. Four to six endobronchial biopsies
are usually obtained, preferably from a site where the mucosa appears erythematous
or from the first and secondary carinas if the mucosa appears normal [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. In sarcoidosis, endobronchial mucosal biopsies are frequently positive
and may increase the diagnostic yield, compared to transbronchial biopsies alone
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/14\">",
" 14",
" </a>",
" ]. In a series of 37 patients with sarcoidosis, endobronchial biopsies had a
diagnostic yield of 24 percent and increased the yield over transbronchial biopsy
alone by 8 percent. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21914?
source=see_link&amp;anchor=H39#H39\">",
" \"Clinical manifestations and diagnosis of sarcoidosis\", section on
'Diagnostic procedures'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/45/22234?
source=see_link&amp;anchor=H14#H14\">",
" \"Chronic beryllium disease (berylliosis)\", section on 'Tissue biopsy'",
" </a>",
" .)",
" </li>",
" <li>",
" Results of BAL are generally not diagnostic in ILD, but frequently provide
supportive evidence for or against a diagnosis. We typically perform BAL after
obtaining the TBLB specimens and avoid performing BAL in the same subsegments as
the TBLB. The role of BAL in the evaluation of ILD and the analysis of lavage fluid
are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/50/43816?
source=see_link\">",
" \"Flexible bronchoscopy: Equipment, procedure, and complications\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/36/16968?
source=see_link\">",
" \"Role of bronchoalveolar lavage in diagnosis of interstitial lung
disease\"",
" </a>",
" .)",
" </li>",
" <li>",
" Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
requires a special bronchoscope and is performed under general anesthesia,
typically with a laryngeal mask airway in place. It is performed to evaluate
enlarged hilar and mediastinal lymph nodes. The bronchoscope for EBUS is different
from the standard bronchoscope used for TBLB, but general anesthesia and the
laryngeal mask airway make it relatively easy to change bronchoscopes and perform
both EBUS-TBNA and TBLB during a single procedure [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/15\">",
" 15",
" </a>",
" ]. EBUS-TBNA has a yield of 90 to 96 percent for the diagnosis of
sarcoidosis in the presence of hilar or mediastinal adenopathy. The technique of
EBUS-TBNA is described separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?19/32/19976?
source=see_link\">",
" \"Endobronchial ultrasound: Indications, advantages, and complications\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H20485060\">",
" <span class=\"h3\">",
" Limitations",
" </span>",
" &nbsp;&mdash;&nbsp;Transbronchial lung biopsies (TBLB) are a few millimeters
in size and are subject to crush artifact. They may miss ILD when the disease is
patchy or be nondiagnostic when visualization of whole pulmonary acini is needed to
fully evaluate disease distribution. Among 651 transbronchial lung biopsy
procedures in patients with diffuse pulmonary disease, TBLB was diagnostically
helpful in 76 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/6\">",
" 6",
" </a>",
" ]. If a specific diagnosis is not made by TBLB, surgical lung biopsy is
usually indicated.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Surgical lung biopsy",
" </span>",
" &nbsp;&mdash;&nbsp;Surgical lung biopsy specimens can be obtained by video
assisted thoracoscopic surgery (VATS) or open thoracotomy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/16,17\">",
" 16,17",
" </a>",
" ]. The specimens are substantially larger than those obtained by TBLB.
Reported diagnostic yields vary, but are in the range of 86 to 92 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,16-18\">",
" 4,16-18",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H5485310\">",
" <span class=\"h3\">",
" Safety and contraindications",
" </span>",
" &nbsp;&mdash;&nbsp;Reported mortality rates for surgical lung biopsy range
from 0 to 6 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,16,17,19-21\">",
" 4,16,17,19-21",
" </a>",
" ]. Estimates of morbidity vary widely (2 to 19 percent), which probably
reflects the varying severity of illness among patients undergoing the procedure
and different definitions used to define morbidity.",
" </p>",
" <p>",
" Relative contraindications to surgical lung biopsy include [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/16,17,20\">",
" 16,17,20",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Radiographic evidence of diffuse end-stage disease, eg, \"honeycombing\",
without areas of milder disease activity, as biopsy of end-stage fibrosis is
unlikely to reveal an etiology.",
" </li>",
" <li>",
" High likelihood that adequate-sized biopsies from multiple sites (usually
from two lobes) will not be obtained (eg, in a patient with associated pleural
disease or emphysema).",
" </li>",
" <li>",
" Severe pulmonary dysfunction manifest by a diffusing capacity (DLCO) less
than 35 percent predicted or the requirement for supplemental oxygen or mechanical
ventilation.",
" </li>",
" <li>",
" Serious cardiovascular disease, advanced age, or other major risks for
surgery or general anesthesia.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Pulmonary hypertension, mechanical ventilation, and immunosuppressive therapy
appear to increase the risk of death and other complications of surgical lung
biopsy. Such patients are evaluated on a case-by-case basis to be sure that the
procedure is likely to reveal a treatable diagnosis.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5484649\">",
" <span class=\"h3\">",
" VATS",
" </span>",
" &nbsp;&mdash;&nbsp;Video assisted thoracoscopic surgery (VATS) is a minimally
invasive form of thoracic surgery performed under general anesthesia. Single lung
ventilation is usually employed during the biopsy procedure, so the lung being
biopsied is deflated and respiratory movement inhibited. A rigid or semi-rigid
thoracoscope is introduced into the pleural space and forceps for lung biopsy are
typically introduced through a separate small incision.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5484684\">",
" <span class=\"h3\">",
" Thoracotomy",
" </span>",
" &nbsp;&mdash;&nbsp;Open thoracotomy, also performed under general anesthesia,
requires a surgical incision of 5 to 6 cm. Single lung ventilation can be used
during the procedure, so the lung being biopsied is deflated and respiratory
movement inhibited. Alternatively, for patients with more advanced lung disease or
those on mechanical ventilation who cannot tolerate single lung ventilation, lung
biopsy can be obtained through a thoracotomy incision without deflation of the lung
being biopsied. The thoracotomy incision allows the surgeon to palpate the lung
texture but does not necessarily allow biopsy areas of the lung remote from the
incision.",
" </p>",
" <p class=\"headingAnchor\" id=\"H979589\">",
" <span class=\"h3\">",
" VATS versus thoracotomy",
" </span>",
" &nbsp;&mdash;&nbsp;The choice between VATS or open thoracotomy is typically
determined by the expertise of the thoracic surgeon. Increasingly, VATS is the
preferred method in part because several retrospective studies have found that
morbidity is improved with VATS compared with open thoracotomy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/2,22-24\">",
" 2,22-24",
" </a>",
" ]. A prospective, randomized trial comparing the two procedures found no
difference in morbidity or mortality, however the study was small (42 patients) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/25\">",
" 25",
" </a>",
" ]. A separate randomized trial of 61 patients reported reduced need for
postoperative analgesia, shorter duration of chest tube drainage, and shorter
hospital stay with VATS, but no difference in diagnostic yield or complication
rates [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/26\">",
" 26",
" </a>",
" ].",
" </p>",
" <p>",
" Specimen adequacy and diagnostic accuracy are the same with both procedures,
although it is technically easier to obtain multilobe lung biopsies by VATS than by
thoracotomy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/22\">",
" 22",
" </a>",
" ].",
" </p>",
" <p>",
" Open thoracotomy is occasionally required instead of VATS because of severe
pleural disease or to provide more definitive control of bleeding in a patient with
a bleeding diathesis. When necessary, patients receiving mechanical ventilation can
undergo surgical lung biopsy; an open procedure is generally preferred in the
setting of severe hypoxemia [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/27\">",
" 27",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h3\">",
" Specimen collection",
" </span>",
" &nbsp;&mdash;&nbsp;The optimal number, size, and location of lung biopsies
depend upon the suspected diagnosis and the anatomic distribution of the disease
process. The clinician should communicate to the thoracic surgeon any specific
concerns and suggestions regarding these issues. High resolution computed
tomography (HRCT) scanning may further assist the surgeon in selecting the best
location(s) to biopsy. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/29/16858?
source=see_link\">",
" \"High resolution computed tomography of the lungs\"",
" </a>",
" .)",
" </p>",
" <p>",
" In order to provide the pathologist with adequate tissue to evaluate the
pattern and distribution of disease, lung biopsy samples are ideally greater than 4
cm in the greatest dimension when inflated and include a depth from the pleural
surface of 3 to 5 cm [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. Areas that appear completely normal are avoided as are areas of severe
disease; the latter tend to exhibit end-stage fibrosis (ie, honeycomb lung) without
suggesting an etiology and are therefore unlikely to yield useful results.
&ldquo;Honeycombing&rdquo; can be identified radiographically prior to surgery or
by inspection at the time of surgery.",
" </p>",
" <p>",
" Biopsies are obtained from more than one lobe of the lung and from areas of
varying severity, as several studies suggest that this improves diagnostic accuracy
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,28\">",
" 4,28",
" </a>",
" ]. In 28 of 109 patients with usual or nonspecific interstitial pneumonia, the
histopathology in at least one lobe was discordant from another lobe [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/29\">",
" 29",
" </a>",
" ]. In a separate series of 24 patients, the diagnostic yield was improved by
multilobe biopsies in a third [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/13\">",
" 13",
" </a>",
" ]. Among 15 patients with chronic hypersensitivity pneumonitis, sampling from
more than one lobe helped to identify hypersensitivity pneumonitis in two patients
who had chronic hypersensitivity pneumonitis on biopsies from one lobe and usual
interstitial pneumonitis on biopsies from another lobe [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/30\">",
" 30",
" </a>",
" ].",
" </p>",
" <p>",
" It is controversial whether sampling of the dependent segments of the right
middle lobe and lingula should be avoided due to nonspecific fibrosis that may be
present at these sites [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. However, several studies have found diagnostic yields from lingular and
middle lobe biopsies to be comparable to other sites [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4,31-33\">",
" 4,31-33",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H4658163\">",
" <span class=\"h1\">",
" PROCESSING LUNG BIOPSY SPECIMENS",
" </span>",
" &nbsp;&mdash;&nbsp;Biopsy specimens are sent for histopathologic analysis and
also for mycobacterial and fungal culture. As the sample size is small, the
entirety of the transbronchial biopsy specimens not sent to microbiology should be
processed and examined.",
" </p>",
" <p>",
" Frozen sections are generally not useful in the diagnosis of diffuse
parenchymal lung disease, but may be used during surgical biopsy to assess whether
an adequate sample has been obtained or when malignancy is suspected.",
" </p>",
" <p>",
" Surgical lung biopsy specimens are gently inflated by injection of formalin
prior to sectioning [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" 4",
" </a>",
" ]. For diffuse parenchymal lung disease in nonimmunosuppressed patients, the
routine initial stain is hematoxylin and eosin.",
" </p>",
" <p>",
" Special stains are performed as indicated based on the clinical suspicion or
initial findings. As examples, staining for CD1a is done when Langerhans cell
histiocytosis is suspected, and special mycobacterial and fungal stains are done
whenever granulomas are noted. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/63/21497?
source=see_link&amp;anchor=H5487023#H5487023\">",
" \"Interpretation of lung biopsy results in interstitial lung disease\",
section on 'Langerhans cell granulomatosis'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?32/14/32993?
source=see_link\">",
" \"Patient information: Flexible bronchoscopy (Beyond the Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H20484825\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Diffuse parenchymal lung diseases, often collectively referred to as
interstitial lung diseases (ILDs), are a heterogeneous group of disorders that are
classified together because of similar clinical, radiographic, physiologic, or
pathologic manifestations (",
" <a class=\"external\" href=\"file:__www.uptodate.com_contents_image?
imageKey=PULM_24076\">",
" figure 1",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" An approach to evaluating immunocompetent adults with ILD is shown in the
algorithm (",
" <a class=\"external\" href=\"file:__www.uptodate.com_contents_image?
imageKey=PULM_23646\">",
" algorithm 1",
" </a>",
" ) and discussed in detail separately. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/20/22856?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Clinical
evaluation\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/18/16681?
source=see_link\">",
" \"Approach to the adult with interstitial lung disease: Diagnostic
testing\"",
" </a>",
" .)",
" </li>",
" <li>",
" Indications for lung biopsy in patients with ILD include atypical clinical
features (age &lt;50 years, fever, weight loss, hemoptysis, signs of vasculitis); a
progressive course; a normal, atypical, or rapidly changing chest radiograph or
high resolution CT scan (HRCT); unexplained extrapulmonary manifestations; or
pulmonary vascular disease of unclear origin. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Indications'",
" </a>",
" above.)",
" </li>",
" <li>",
" Flexible bronchoscopy with transbronchial lung biopsy (TBLB) is minimally
invasive and is often the biopsy procedure of choice when sarcoidosis,
hypersensitivity pneumonitis, lymphangitic carcinomatosis, eosinophilic pneumonia,
alveolar proteinosis, or infection is suspected. (See",
" <a class=\"local\" href=\"#H4\">",
" 'Transbronchial lung biopsy'",
" </a>",
" above.)",
" </li>",
" <li>",
" Transbronchial lung biopsies (TBLB) are a few millimeters in size and are
likely to miss diseases that are patchy or require examination of a larger area of
tissue for accurate diagnosis (eg, usual interstitial pneumonitis, nonspecific
interstitial pneumonitis, granulomatosis with polyangiitis [Wegener&rsquo;s
granulomatosis]). (See",
" <a class=\"local\" href=\"#H20485060\">",
" 'Limitations'",
" </a>",
" above.)",
" </li>",
" <li>",
" Typically, four to six TBLB are obtained from areas of lung that appear
involved radiographically. If the lungs are uniformly involved, the lower lobe or
both upper and lower lobes are biopsied. (See",
" <a class=\"local\" href=\"#H4658609\">",
" 'Ancillary tests'",
" </a>",
" above.)",
" </li>",
" <li>",
" Ancillary bronchoscopic tests such as endobronchial biopsy and
bronchoalveolar lavage can help improve the diagnostic yield. For patients with
hilar or mediastinal adenopathy, endobronchial ultrasound guided transbronchial
needle aspiration (EBUS-TBNA) may contribute to the diagnostic yield, although
general anesthesia and specialized equipment are required. (See",
" <a class=\"local\" href=\"#H4658609\">",
" 'Ancillary tests'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/41/25239?
source=see_link\">",
" \"Basic principles and technique of bronchoalveolar lavage\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/36/16968?
source=see_link\">",
" \"Role of bronchoalveolar lavage in diagnosis of interstitial lung
disease\"",
" </a>",
" .)",
" </li>",
" <li>",
" Surgical lung biopsy specimens can be obtained via video assisted
thoracoscopic surgery (VATS) or open thoracotomy; the choice between these
procedures is typically determined by the expertise and preference of the thoracic
surgeon. Open thoracotomy may be preferred in the setting of severe pleural
disease, a bleeding diathesis, or mechanical ventilation. (See",
" <a class=\"local\" href=\"#H979589\">",
" 'VATS versus thoracotomy'",
" </a>",
" above.)",
" </li>",
" <li>",
" In order to provide the pathologist with adequate tissue to evaluate the
pattern and distribution of disease, surgical biopsies should be greater than 4 cm
in the greatest dimension when inflated and include a depth from the pleural
surface of 3 to 5 cm. Ideally, specimens are obtained from more than one lobe of
the lung. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Specimen collection'",
" </a>",
" above.)",
" </li>",
" <li>",
" TBLB and surgical lung biopsy specimens are sent for histopathologic
analysis and also mycobacterial and fungal staining and culture. (See",
" <a class=\"local\" href=\"#H4658163\">",
" 'Processing lung biopsy specimens'",
" </a>",
" above.)",
" </li>",
" <li>",
" The interpretation of lung biopsy results in the context of the clinical
setting is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/63/21497?
source=see_link\">",
" \"Interpretation of lung biopsy results in interstitial lung disease\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/1\">",
" Poletti V, Chilosi M, Olivieri D. Diagnostic invasive procedures in diffuse
infiltrative lung diseases. Respiration 2004; 71:107.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/2\">",
" Halkos ME, Gal AA, Kerendi F, et al. Role of thoracic surgeons in the
diagnosis of idiopathic interstitial lung disease. Ann Thorac Surg 2005; 79:2172.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/3\">",
" Nicholson AG, Fulford LG, Colby TV, et al. The relationship between
individual histologic features and disease progression in idiopathic pulmonary
fibrosis. Am J Respir Crit Care Med 2002; 166:173.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/4\">",
" Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline:
the British Thoracic Society in collaboration with the Thoracic Society of
Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 Suppl
5:v1.",
" </a>",
" </li>",
" <li>",
" King TE Jr. Interstitial Lung Disease. In: Textbook of Bronchoscopy,
Feinsilver SH, Fein AM (Eds), Williams &amp; Wilkins, Baltimore 1995. p.185.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/6\">",
" Ensminger SA, Prakash UB. Is bronchoscopic lung biopsy helpful in the
management of patients with diffuse lung disease? Eur Respir J 2006; 28:1081.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/7\">",
" Pue CA, Pacht ER. Complications of fiberoptic bronchoscopy at a university
hospital. Chest 1995; 107:430.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/8\">",
" Descombes E, Gardiol D, Leuenberger P. Transbronchial lung biopsy: an
analysis of 530 cases with reference to the number of samples. Monaldi Arch Chest
Dis 1997; 52:324.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/9\">",
" de Boer S, Milne DG, Zeng I, Wilsher ML. Does CT scanning predict the
likelihood of a positive transbronchial biopsy in sarcoidosis? Thorax 2009;
64:436.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/10\">",
" Halme M, Piilonen A, Taskinen E. Comparison of endobronchial and
transbronchial biopsies with high-resolution CT (HRCIT) in the diagnosis of
sarcoidosis. APMIS 2001; 109:289.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/11\">",
" Roethe RA, Fuller PB, Byrd RB, Hafermann DR. Transbronchoscopic lung biopsy
in sarcoidosis. Optimal number and sites for diagnosis. Chest 1980; 77:400.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/12\">",
" Curley FJ, Johal JS, Burke ME, Fraire AE. Transbronchial lung biopsy: can
specimen quality be predicted at the time of biopsy? Chest 1998; 113:1037.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/13\">",
" Vansteenkiste J, Verbeken E, Thomeer M, et al. Medical thoracoscopic lung
biopsy in interstitial lung disease: a prospective study of biopsy quality. Eur
Respir J 1999; 14:585.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/14\">",
" Bjermer L, Thunell M, Rosenhall L, Stjernberg N. Endobronchial biopsy
positive sarcoidosis: relation to bronchoalveolar lavage and course of disease.
Respir Med 1991; 85:229.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/15\">",
" Nakajima T, Yasufuku K, Kurosu K, et al. The role of EBUS-TBNA for the
diagnosis of sarcoidosis--comparisons with other bronchoscopic diagnostic
modalities. Respir Med 2009; 103:1796.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/16\">",
" Lee YC, Wu CT, Hsu HH, et al. Surgical lung biopsy for diffuse pulmonary
disease: experience of 196 patients. J Thorac Cardiovasc Surg 2005; 129:984.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/17\">",
" Lettieri CJ, Veerappan GR, Helman DL, et al. Outcomes and safety of surgical
lung biopsy for interstitial lung disease. Chest 2005; 127:1600.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/18\">",
" Flaherty KR, King TE Jr, Raghu G, et al. Idiopathic interstitial pneumonia:
what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit
Care Med 2004; 170:904.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/19\">",
" Kreider ME, Hansen-Flaschen J, Ahmad NN, et al. Complications of video-
assisted thoracoscopic lung biopsy in patients with interstitial lung disease. Ann
Thorac Surg 2007; 83:1140.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/20\">",
" Sigurdsson MI, Isaksson HJ, Gudmundsson G, Gudbjartsson T. Diagnostic
surgical lung biopsies for suspected interstitial lung diseases: a retrospective
study. Ann Thorac Surg 2009; 88:227.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/21\">",
" Carrillo G, Estrada A, Pedroza J, et al. Preoperative risk factors
associated with mortality in lung biopsy patients with interstitial lung disease. J
Invest Surg 2005; 18:39.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/22\">",
" Ravini M, Ferraro G, Barbieri B, et al. Changing strategies of lung biopsies
in diffuse lung diseases: the impact of video-assisted thoracoscopy. Eur Respir J
1998; 11:99.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/23\">",
" Zegdi R, Azorin J, Tremblay B, et al. Videothoracoscopic lung biopsy in
diffuse infiltrative lung diseases: a 5-year surgical experience. Ann Thorac Surg
1998; 66:1170.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/24\">",
" Tiitto L, Heiskanen U, Bloigu R, et al. Thoracoscopic lung biopsy is a safe
procedure in diagnosing usual interstitial pneumonia. Chest 2005; 128:2375.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/25\">",
" Miller JD, Urschel JD, Cox G, et al. A randomized, controlled trial
comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung
disease. Ann Thorac Surg 2000; 70:1647.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/26\">",
" Ayed AK, Raghunathan R. Thoracoscopy versus open lung biopsy in the
diagnosis of interstitial lung disease: a randomised controlled trial. J R Coll
Surg Edinb 2000; 45:159.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/27\">",
" Patel SR, Karmpaliotis D, Ayas NT, et al. The role of open-lung biopsy in
ARDS. Chest 2004; 125:197.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/28\">",
" Flint A, Martinez FJ, Young ML, et al. Influence of sample number and biopsy
site on the histologic diagnosis of diffuse lung disease. Ann Thorac Surg 1995;
60:1605.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/29\">",
" Flaherty KR, Travis WD, Colby TV, et al. Histopathologic variability in
usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001;
164:1722.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/30\">",
" Trahan S, Hanak V, Ryu JH, Myers JL. Role of surgical lung biopsy in
separating chronic hypersensitivity pneumonia from usual interstitial
pneumonia/idiopathic pulmonary fibrosis: analysis of 31 biopsies from 15 patients.
Chest 2008; 134:126.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/31\">",
" Miller RR, Nelems B, M&uuml;ller NL, et al. Lingular and right middle lobe
biopsy in the assessment of diffuse lung disease. Ann Thorac Surg 1987; 44:269.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/32\">",
" Temes RT, Joste NE, Allen NL, et al. The lingula is an appropriate site for
lung biopsy. Ann Thorac Surg 2000; 69:1016.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/424/abstract/33\">",
" Ayed AK. Video-assisted thoracoscopic lung biopsy in the diagnosis of
diffuse interstitial lung disease. A prospective study. J Cardiovasc Surg (Torino)
2003; 44:115.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 4379 Version 7.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0505-197.136.42.3-9C20EB8C63-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_424=[""].join("\n");
var outline_f0_26_424=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H20484825\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" INDICATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" TYPES OF LUNG BIOPSY",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Transbronchial lung biopsy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4657761\">",
" - Safety",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H20485052\">",
" - Specimen collection and diagnostic yield",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4658609\">",
" - Ancillary tests",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H20485060\">",
" - Limitations",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" Surgical lung biopsy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H5485310\">",
" - Safety and contraindications",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H5484649\">",
" - VATS",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H5484684\">",
" - Thoracotomy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H979589\">",
" - VATS versus thoracotomy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" - Specimen collection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H4658163\">",
" PROCESSING LUNG BIOPSY SPECIMENS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H20484825\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"PULM/4379\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"PULM/4379|ALG\">",
" <a href=\"#\" title=\"ALGORITHMS\">",
" ALGORITHMS",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?42/30/43502\"
title=\"algorithm 1\">",
" Classification diffuse lung dz",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?17/14/17632\"
title=\"algorithm 2\">",
" Approach to patient with ILD",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"PULM/4379|DiagnosticImage\">",
" <a href=\"#\" title=\"DIAGNOSTIC IMAGES\">",
" DIAGNOSTIC IMAGES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?20/38/21088\"
title=\"diagnostic image 1\">",
" Nodules in pneumoconiosis CT",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/20/22856?
source=related_link\">",
" Approach to the adult with interstitial lung disease: Clinical evaluation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/18/16681?
source=related_link\">",
" Approach to the adult with interstitial lung disease: Diagnostic testing",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/41/25239?
source=related_link\">",
" Basic principles and technique of bronchoalveolar lavage",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/45/22234?
source=related_link\">",
" Chronic beryllium disease (berylliosis)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21914?
source=related_link\">",
" Clinical manifestations and diagnosis of sarcoidosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?19/32/19976?
source=related_link\">",
" Endobronchial ultrasound: Indications, advantages, and complications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/50/43816?
source=related_link\">",
" Flexible bronchoscopy: Equipment, procedure, and complications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/29/16858?
source=related_link\">",
" High resolution computed tomography of the lungs",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/23/4474?
source=related_link\">",
" Idiopathic interstitial pneumonias: Clinical manifestations and pathology",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/63/21497?
source=related_link\">",
" Interpretation of lung biopsy results in interstitial lung disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?32/14/32993?
source=related_link\">",
" Patient information: Flexible bronchoscopy (Beyond the Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/36/16968?
source=related_link\">",
" Role of bronchoalveolar lavage in diagnosis of interstitial lung disease",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_26_425="Primary coccidioidal infection";
var content_f0_26_425=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"4\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Primary coccidioidal infection",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/425/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/425/contributors\">",
" John N Galgiani, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/425/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/425/contributors\">",
" Carol A Kauffman, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/425/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/425/contributors\">",
" Anna R Thorner, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/26/425/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Apr 26, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Coccidioidomycosis is the infection caused by the dimorphic
fungi of the genus Coccidioides (C. immitis and C. posadasii) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ]. Most infections are caused by inhalation of spores. The clinical expression
of disease ranges from self-limited acute pneumonia (Valley Fever) to disseminated
disease, especially in immunosuppressed patients. The concentration of cases of
coccidioidomycosis in the United States is in the southwestern part of the country,
where the cumulative incidence of patients requiring hospitalization in 2002 was
28.65 per 1 million persons [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/2\">",
" 2",
" </a>",
" ].",
" </p>",
" <p>",
" The clinical manifestations of uncomplicated primary infection, specific
diagnostic tests, and management strategies for primary infection will be reviewed
here. Complicated infections related to coccidioidomycosis are discussed elsewhere.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/51/39734?
source=see_link\">",
" \"Management of pulmonary sequelae and complications of
coccidioidomycosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/55/17271?
source=see_link\">",
" \"Coccidioidal meningitis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/11/26807?
source=see_link\">",
" \"Manifestations and treatment of extrapulmonary coccidioidomycosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/21/21848?
source=see_link\">",
" \"Coccidioidomycosis in compromised hosts\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Coccidioides spp are endemic to certain lower deserts of
the western hemisphere, including southern Arizona, the southern and central
valleys of California, southwestern New Mexico, and west Texas in the United
States. They are also found in parts of Mexico, and Central and South America.",
" </p>",
" <p>",
" A substantial increase in the incidence of coccidioidomycosis has been
observed in both California and Arizona in recent years. In Arizona, reported cases
of coccidioidomycosis increased from 21 cases per 100,000 in 1997 to 155 cases per
100,000 in 2009 [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/3\">",
" 3",
" </a>",
" ]. Total new cases reported in 2011 was over 16,000, a 37 percent increase
from 2010. In California, the incidence of coccidioidomycosis increased from 2.4
cases per 100,000 in 2000 to 8 per 100,000 in 2006 [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/4\">",
" 4",
" </a>",
" ]. Inmates of two California state prisons have been disproportionately
affected by coccidioidomycosis compared with the general population, with 180 cases
recognized in 2005 [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p>",
" Possible reasons for the rise in incidence of coccidioidomycosis include
increased construction activity, an expansion in the immunocompromised population,
and immigration of previously unexposed person to endemic regions [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Risk of infection",
" </span>",
" &nbsp;&mdash;&nbsp;Estimates of the risk of endemic exposure to Coccidioides
spp are approximately 3 percent per year [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/6\">",
" 6",
" </a>",
" ]. In addition, a telephone survey by the Arizona Department of Health
Services of patients diagnosed with Valley Fever in 2007 found that the average
time of residence was 16 years [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/7\">",
" 7",
" </a>",
" ]. Thus, even persons who have lived in endemic regions for many years may
still be susceptible to a new infection.",
" </p>",
" <p>",
" The risk of exposure within endemic regions is seasonal, typically being
highest in dry periods following a rainy season. As an example, periods of high
incidence in Arizona range from May into July and then between October and early
December [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/8\">",
" 8",
" </a>",
" ]. In contrast, the central California valley, which rarely receives
significant summer rain, has a single peak from late spring to late fall. The
estimated number of infections per year has risen to approximately 150,000 as a
result of population increases in southern Arizona and central California [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ]. Based upon population sizes within the most highly endemic regions, it is
estimated that approximately 60 percent of all United States coccidioidal
infections occur within Maricopa, Pinal, and Pima counties of Arizona and 30
percent within Kern, Tulare, and San Louis Obispo counties of California. Cases
reported to the United States Centers for Disease Control show similar geographic
distributions (",
" <a class=\"external\" href=\"file://www.cdc.gov/mmwr/summary.html\">",
" www.cdc.gov/mmwr/summary.html",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" MICROBIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;All isolates within the genus Coccidioides were formerly
designated C. immitis. However, based upon DNA sequence analysis, two species have
been identified as distinct [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/10,11\">",
" 10,11",
" </a>",
" ]. Isolates from one species are geographically distributed predominantly in
California and have retained the name C. immitis. The other species is distributed
in Arizona, Utah, Texas, and other endemic regions throughout the western
hemisphere and is now designated C. posadasii.",
" </p>",
" <p>",
" The spectrums of diseases caused by the two species are indistinguishable, and
clinical laboratories are not routinely able to determine species. For this reason,
it is simplest to refer to all isolates as Coccidioides species.",
" </p>",
" <p>",
" Coccidioides spp grow as mold a few inches below the surface of the desert
soil. With dry conditions, the mycelia become very fragile, are easily fractured by
even slight air turbulence into single-cell spores (arthroconidia) approximately 3
to 5 microns in size, and can remain suspended for prolonged periods of time in the
air.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h1\">",
" PATHOGENESIS",
" </span>",
" &nbsp;&mdash;&nbsp;Infection is virtually always acquired by inhalation of a
single arthroconidium. Within the lung, an arthroconidium changes from a barrel-
shaped cell to a spherical structure and then greatly enlarges, sometimes becoming
70 microns or more in diameter. Enlarging spherules produce internal septations,
and within each of the resulting subcompartments, individual cells (endospores)
evolve. After several days, mature spherules rupture, releasing endospores into the
infected tissue; each endospore is potentially capable of producing another
spherule [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ]. Organisms grown from patient specimens show a reversion to mycelia on most
laboratory media [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/12,13\">",
" 12,13",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h1\">",
" CLINICAL MANIFESTATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;After infection, a wide spectrum of manifestations is
possible. It is estimated that less than one half of all infections comes to
medical attention because illness is often subclinical [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/14,15\">",
" 14,15",
" </a>",
" ]. The proportion of infections that become clinically significant increases
with more intensive dust exposure. It is presumed that this represents higher
arthroconidial inoculum exposure, as occurs during archeological excavations or
desert military maneuvers [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/16,17\">",
" 16,17",
" </a>",
" ].",
" </p>",
" <p>",
" When illness is clinically significant, a subacute process known as Valley
Fever with respiratory and systemic complaints is typical, often lasting for weeks
to months. In the great majority of such infections, resolution occurs without
specific antifungal therapy. Future respiratory exposure to arthroconidia rarely,
if ever, results in clinical illness.",
" </p>",
" <p>",
" Primary infections due to Coccidioides species most frequently manifest as
community-acquired pneumonia (CAP) approximately 7 to 21 days after exposure. In a
study from Pima County, Arizona, 29 percent of patients diagnosed with CAP were
serologically positive for coccidioidal infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/18\">",
" 18",
" </a>",
" ]. The most common presenting symptoms are chest pain, cough, and fever (",
" <a class=\"graphic graphic_table graphicRef69260 \" href=\"UTD.htm?
35/12/36043\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/19-26\">",
" 19-26",
" </a>",
" ]. Hemoptysis may occur and suggests the development of a pulmonary cavity.",
" </p>",
" <p>",
" Fatigue can persist for months, and the frequent complaint of arthralgias has
contributed to the alternate name of \"desert rheumatism\" for this illness.
Cutaneous manifestations of primary coccidioidal infection include erythema nodosum
and erythema multiforme. E. nodosum is much more common in women than in men and
often is the symptom prompting evaluation for Valley Fever. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?12/52/13130?
source=see_link\">",
" \"Erythema nodosum\"",
" </a>",
" .)",
" </p>",
" <p>",
" Most routine laboratory findings are unremarkable [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/27\">",
" 27",
" </a>",
" ]. A common but nonspecific abnormality is the erythrocyte sedimentation rate,
which often is one- or twofold above the upper limits of normal. The peripheral
blood leukocyte count is usually normal or only slightly elevated. However,
eosinophilia (&gt;5 percent) was found in approximately one quarter of patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ]. In occasional patients, eosinophilia can be striking.",
" </p>",
" <p>",
" Although initial infections usually have a respiratory component, standard PA
and lateral chest radiographs may be unremarkable in up to one half of all
patients. Common radiographic abnormalities include unilateral infiltrate and
ipsilateral hilar adenopathy (",
" <a class=\"graphic graphic_diagnosticimage graphicRef76967 \" href=\"UTD.htm?
4/56/5001\">",
" image 1",
" </a>",
" ). Less frequent is evidence of a parapneumonic effusion [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/28\">",
" 28",
" </a>",
" ]. Peripheral thin-walled pulmonary cavities or nodules are detected in 4 to 8
percent of all patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/29\">",
" 29",
" </a>",
" ] (",
" <a class=\"graphic graphic_diagnosticimage graphicRef51795 \" href=\"UTD.htm?
10/49/11027\">",
" image 2",
" </a>",
" ). Rare cases of empyema have been reported [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/30\">",
" 30",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h1\">",
" FREQUENT ABSENCE OF EARLY DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;Given how nonspecific the symptoms, signs, and routine
laboratory findings of primary coccidioidal infection are, many, if not most,
infections are not identified because clinicians do not consider the diagnosis. As
an example, a cluster of 21 cases of a flu-like illness with rash in the majority
of patients was noted in a church group returning to Washington State after
building an orphanage in Mexico [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/31\">",
" 31",
" </a>",
" ]. Sixteen patients were symptomatic and sought medical attention but the
diagnosis of coccidioidomycosis was only confirmed in one case.",
" </p>",
" <p>",
" Although this cluster was located outside of the southwest in an area in which
Valley Fever is not common, low rates of disease recognition have also occurred in
endemic areas. In Arizona, the number of cases of coccidioidomycosis reported to
the Department of Public Health from 1999 to 2001 averaged 1900 per year [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/8\">",
" 8",
" </a>",
" ]. This number is less than 10 percent of the expected number of illnesses, as
estimated by several methods [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/32\">",
" 32",
" </a>",
" ]. In a study from two medical centers in metropolitan Phoenix, Arizona, the
number of patients with CAP tested for Valley Fever was only 2 and 13 percent,
respectively [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/33\">",
" 33",
" </a>",
" ]. In one study, the clinician&rsquo;s workload, as measured by number of
clinic visits, was directly proportional to both the number of cases of CAP
diagnosed and the number of cases of coccidioidomycosis diagnosed (",
" <a class=\"graphic graphic_figure graphicRef65388 \" href=\"UTD.htm?
32/52/33613\">",
" figure 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/32\">",
" 32",
" </a>",
" ].",
" </p>",
" <p>",
" A prospective observational study found that 16 of 55 cases (29 percent) of
community acquired pneumonia (CAP) in Tucson, Arizona were caused by Coccidioides
spp [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/18\">",
" 18",
" </a>",
" ]. In another study, 6 of 35 patients (17 percent) with CAP in Phoenix,
Arizona had evidence of acute coccidioidomycosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/34\">",
" 34",
" </a>",
" ]. A similarly high proportion may be evident in persons who develop CAP
within the one to three week incubation period after visiting an endemic area.",
" </p>",
" <p>",
" Some practitioners consider the failure to diagnose early coccidioidal
infections as an insignificant problem, since many infections resolve without
specific therapy. However, identifying coccidioidal infections as early as possible
has many benefits, including [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/35\">",
" 35",
" </a>",
" ].",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Allaying patient anxiety by arriving at a specific diagnosis, often
simultaneously dispelling the fear of cancer",
" </li>",
" <li>",
" Reducing the need for additional diagnostic testing, some of which involve
invasive or costly procedures",
" </li>",
" <li>",
" Eliminating empiric or protracted use of antibacterial treatments",
" </li>",
" <li>",
" Reducing the morbidity of less frequent but progressively destructive
extrapulmonary complications, most of which develop within the first several months
following the initial infection.",
" </li>",
" </ul>",
" </p>",
" <p>",
" For these reasons, the standard of care for management of this disease could
be improved by a greater attention to early diagnosis. This approach is emphasized
in the 2005 Infectious Diseases Society of America (IDSA) guidelines for the
treatment of coccidioidomycosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ] and the 2007 IDSA guidelines for the treatment of community-acquired
pneumonia [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/36\">",
" 36",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h1\">",
" METHODS OF DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;Considering the diagnosis of coccidioidomycosis is an
essential first step for detecting most coccidioidal infections. Because exposure
usually occurs within an endemic region, it is critical to obtain an accurate
travel history. Even brief exposures, such as changing planes in Phoenix, Arizona,
have been sufficient to cause infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/31,37-40\">",
" 31,37-40",
" </a>",
" ]. In most cases, the incubation period for onset of symptoms is 7 to 21 days.
However, for patients who are immunocompromised due to AIDS, solid organ
transplantation, or lymphoma, reactivation can occur after much longer time periods
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/41,42\">",
" 41,42",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Culture",
" </span>",
" &nbsp;&mdash;&nbsp;Isolation of Coccidioides species in culture definitively
establishes the diagnosis, even in patients with relatively mild pneumonia.
Although fungal cultures are usually requested only in hospitalized patients or in
those with more extensive disease, there is value to early diagnosis as noted
above. Direct examination of the smear with KOH preparation or calcofluor white
staining is also helpful.",
" </p>",
" <p>",
" There are two disadvantages to culture. First, growth may take several days to
weeks with subsequent delays in diagnosis. Furthermore, the propagation of
Coccidioides spp in the clinical laboratory represents a significant health risk,
since secondary cases have been reported in workers opening the plates for
inspection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/43,44\">",
" 43,44",
" </a>",
" ]. Thus, laboratory personnel should be notified when a sample with suspected
Coccidioides is being sent for processing. In contrast, specimens for culture can
be safely collected by health care workers since coccidioidal infection is not
transmitted person to person. Coccidioides spp are listed by the CDC as a select
agent. Special rules govern its handling and storage. (See",
" <a class=\"external\" href=\"file://www.cdc.gov/od/sap\">",
" www.cdc.gov/od/sap",
" </a>",
" for further information concerning the handling of select agents).",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Serologic tests",
" </span>",
" &nbsp;&mdash;&nbsp;Serologic testing is helpful for making the diagnosis and
for monitoring patients on therapy. (See",
" <a class=\"local\" href=\"#H96096634\">",
" 'Patient monitoring'",
" </a>",
" below.)",
" </p>",
" <p>",
" In patients with primary infections managed as outpatients, diagnosis usually
relies upon serologic testing. Commercial products are available to perform
screening coccidioidal serologies in any general clinical laboratory.
Alternatively, reference laboratories can carry out more detailed testing. The
details of the laboratory diagnosis of coccidioidomycosis are discussed separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/27/13751?
source=see_link\">",
" \"Laboratory diagnosis of coccidioidomycosis\"",
" </a>",
" .)",
" </p>",
" <p>",
" However, regardless of the method chosen for detecting coccidioidal
antibodies, three general principles guide interpretation.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Any positive serologic result is very likely to be clinically relevant. Most
patients lose serologic reactivity within months of an infection unless residual
lesions are evident or infection is active.",
" </li>",
" <li>",
" A negative serologic result lowers the likelihood, but does not exclude, the
diagnosis of coccidioidomycosis. Although most tests for coccidioidal antibodies
are very specific, they are relatively insensitive, especially during the first one
to two weeks after infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ].",
" </li>",
" <li>",
" Repeating tests, if a first serologic test is negative, will improve
diagnostic sensitivity [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/45\">",
" 45",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Histopathology",
" </span>",
" &nbsp;&mdash;&nbsp;The diagnosis of coccidioidomycosis is occasionally made by
identification of spherules in tissue specimens. Staining with hematoxylin and
eosin, periodic acid-Schiff, or methenamine silver stain will all demonstrate the
organism, although silver stain is considered the most sensitive (",
" <a class=\"graphic graphic_picture graphicRef75250 graphicRef55301
graphicRef68068 \" href=\"UTD.htm?39/36/40522\">",
" picture 1A-C",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Polymerase chain reaction",
" </span>",
" &nbsp;&mdash;&nbsp;A real-time polymerase chain reaction (PCR) assay was
developed and tested in 266 respiratory specimens and demonstrated 100 percent
sensitivity and 98 percent specificity for Coccidioides spp compared with culture
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/46\">",
" 46",
" </a>",
" ]. Sensitivity in paraffin-embedded tissue samples was found to be lower (73
percent). If these preliminary results are validated with larger sample numbers,
real-time PCR may offer a rapid and safe means of detecting Coccidioides directly
from patient specimens, including fixed tissue.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h2\">",
" Skin testing",
" </span>",
" &nbsp;&mdash;&nbsp;Reagents for skin testing are not currently available [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ], and the utility of this modality is limited in patients with severe
infection due to anergy. Skin testing is more useful for epidemiologic studies,
since dermal reactivity remains present for life.",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h1\">",
" RISK FACTORS FOR COMPLICATIONS AND DISEASE SEVERITY",
" </span>",
" &nbsp;&mdash;&nbsp;After diagnosis, the presence of complications should be
assessed with a careful history and physical examination. Risk factors for
complications include:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" HIV or AIDS",
" </li>",
" <li>",
" Immunosuppressive medications used in transplants patients",
" </li>",
" <li>",
" Glucocorticoids (20 mg or more per day of",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/43/38585?
source=see_link\">",
" prednisone",
" </a>",
" or its equivalent)",
" </li>",
" <li>",
" Lymphoma",
" </li>",
" <li>",
" Anti-tumor necrosis factor (TNF) therapy",
" </li>",
" <li>",
" Chemotherapy for solid tumors",
" </li>",
" <li>",
" Diabetes mellitus",
" </li>",
" <li>",
" Pregnancy",
" </li>",
" <li>",
" Preexisting cardiopulmonary conditions",
" </li>",
" </ul>",
" </p>",
" <p>",
" The most significant of these risk factors is major suppression of cellular
immunity, as occurs with HIV infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/47,48\">",
" 47,48",
" </a>",
" ], solid organ transplantation [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/49-51\">",
" 49-51",
" </a>",
" ], and high-dose glucocorticoid administration [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/52\">",
" 52",
" </a>",
" ]. Coccidioidomycosis first developing during pregnancy (especially during the
third trimester) is a significant risk factor for severe, disseminated disease [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/53,54\">",
" 53,54",
" </a>",
" ]. Diabetes mellitus has been associated with more slowly resolving pulmonary
infection and residual pulmonary cavitation [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/55\">",
" 55",
" </a>",
" ]. Individuals of African or Philippine descent also have an increased risk of
extrapulmonary complications [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/26,56,57\">",
" 26,56,57",
" </a>",
" ]. Although there appears to be more serious disease with increasing age [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/58\">",
" 58",
" </a>",
" ], a comparison of patients younger than 60 years of age versus those &ge;60
years of age did not detect significant differences [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/59\">",
" 59",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/21/21848?
source=see_link\">",
" \"Coccidioidomycosis in compromised hosts\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/55/17271?
source=see_link\">",
" \"Coccidioidal meningitis\"",
" </a>",
" .)",
" </p>",
" <p>",
" To detect extrapulmonary infection, careful review of symptoms and physical
examination is usually adequate. Extrapulmonary infection can be found at any site,
but skin, bones and joints, and central nervous system localization are the most
common [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/60-62\">",
" 60-62",
" </a>",
" ] (",
" <a class=\"graphic graphic_diagnosticimage graphicRef75408 \" href=\"UTD.htm?
39/62/40930\">",
" image 3",
" </a>",
" ). Active coccidioidal lesions typically produce regional symptoms. These
include local discomfort, swelling,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" ulceration. Any focal abnormality of this sort that has developed since the
onset of the primary infection should be a source of concern. These physical exam
findings should prompt further imaging or sampling for histology and culture.",
" </p>",
" <p class=\"headingAnchor\" id=\"H630889929\">",
" <span class=\"h1\">",
" MANAGEMENT",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H630028667\">",
" <span class=\"h2\">",
" Uncomplicated infections",
" </span>",
" &nbsp;&mdash;&nbsp;Otherwise healthy patients without evidence of extensive
coccidioidal infection or risk factors for more serious infection usually do not
need antifungal therapy. However, it is important that such patients be followed
for a year or longer to monitor for the development of complications. Therapy can
be considered for certain patients on an individual basis. (See",
" <a class=\"local\" href=\"#H17\">",
" 'Whom to treat'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h2\">",
" Whom to treat",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with severe illness as well as those at greatly
increased risk of dissemination due to immunosuppression or pregnancy should be
treated. In contrast, the value of antifungal therapy for patients with
uncomplicated early coccidioidal infection is not known because prospective
randomized trials have not been performed. While it is clear from older studies
that most patients resolve their infection without therapy, it is possible that
some patients might benefit from treatment, either by shortening the course of
illness or by preventing complications.",
" </p>",
" <p>",
" The possible role of treatment was evaluated in an observational study of 105
patients who had primary pulmonary coccidioidomycosis and who were seen at a
university-affiliated Veterans Administration clinic [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/63\">",
" 63",
" </a>",
" ]. Based upon severity of illness as assessed by the attending staff, 54
patients were treated and 51 were not. Treatment was more likely to be initiated in
patients with elevated symptom scores. There was no difference between the groups
with respect to overall rates of improvement. Among the untreated patients, none
were subsequently found to have complications.",
" </p>",
" <p>",
" However, among 38 of the treated patients, eight had relapse or progression of
their coccidioidal infection following discontinuation of therapy; the duration of
treatment among these patients ranged from one to 24 months. A possible reason for
these findings is that patients with more severe illness are more likely to develop
relapse. These findings provide no support for treating patients with mild symptoms
of primary coccidioidomycosis, but emphasize the importance of close and prolonged
follow-up for patients with severe illness requiring treatment. (See",
" <a class=\"local\" href=\"#H96096634\">",
" 'Patient monitoring'",
" </a>",
" below.)",
" </p>",
" <p>",
" Given the absence of definitive data, it is a matter of judgment as to whether
an individual patient might benefit from therapy with available oral antifungals,
most frequently",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/15/20730?source=see_link\">",
" itraconazole",
" </a>",
" or",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/12/16586?source=see_link\">",
" fluconazole",
" </a>",
" . As noted above, patients with severe illness should be treated. However,
opinion varies about the most relevant factors to judge the severity of illness.
Commonly used indicators include:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Greater than 10 percent loss of body weight",
" </li>",
" <li>",
" Night sweats persisting greater than three weeks",
" </li>",
" <li>",
" Infiltrates involving more than half of one lung or portions of both lungs",
" </li>",
" <li>",
" Prominent or persistent hilar adenopathy",
" </li>",
" <li>",
" Anti-coccidioidal complement fixing antibody concentrations in excess of
1:16",
" </li>",
" <li>",
" Inability to work",
" </li>",
" <li>",
" Persisting symptoms for more than two months",
" </li>",
" </ul>",
" </p>",
" <p>",
" In addition to patients with severe illness, treatment should also be given to
those at increased risk of dissemination due to immunosuppression or pregnancy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H14\">",
" 'Risk factors for complications and disease severity'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h2\">",
" Treatment regimens",
" </span>",
" &nbsp;&mdash;&nbsp;If a decision to begin treatment is made, reasonable doses
are 400",
" <span class=\"nowrap\">",
" mg/day",
" </span>",
" for",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/34/33312?source=see_link\">",
" ketoconazole",
" </a>",
" , 400",
" <span class=\"nowrap\">",
" mg/day",
" </span>",
" for",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/12/16586?source=see_link\">",
" fluconazole",
" </a>",
" , and 200 mg twice daily for",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/15/20730?source=see_link\">",
" itraconazole",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ]. Of the commercially available azoles, only ketoconazole has been approved
for the treatment of coccidioidomycosis by the United States Food and Drug
Administration (FDA). However, the Mycoses Study Group has published descriptions
of large prospective clinical trials using either fluconazole or itraconazole as
treatment of coccidioidomycosis.",
" <br/>",
" <br/>",
" Fluconazole has fewer drug interactions, whereas itraconazole has less of a
drying effect on skin and mucous membranes. Both fluconazole and itraconazole have
a lower incidence of gastrointestinal side effects compared with ketoconazole.
Ketoconazole has also been associated with decreased testosterone synthesis and
gynecomastia. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/4/36938?
source=see_link\">",
" \"Pharmacology of azoles\"",
" </a>",
" .)",
" </p>",
" <p>",
" There is little information available about the value of newer azoles, such
as",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/38/17002?source=see_link\">",
" voriconazole",
" </a>",
" or",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/60/33737?source=see_link\">",
" posaconazole",
" </a>",
" , for treating primary coccidioidal pneumonia.",
" <br/>",
" <br/>",
" An",
" <a class=\"drug drug_general\" href=\"UTD.htm?42/53/43863?source=see_link\">",
" amphotericin B",
" </a>",
" preparation should be considered only in the most severe cases of coccidioidal
pneumonia due to its toxicity and problems with administration.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1895250\">",
" <span class=\"h3\">",
" Duration",
" </span>",
" &nbsp;&mdash;&nbsp;If treatment is instituted, the duration of azole therapy
for uncomplicated primary coccidioidal infection generally ranges from three to six
months [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ]. However, there is no consensus regarding which factors should guide
decisions about duration of therapy.",
" </p>",
" <p class=\"headingAnchor\" id=\"H96096634\">",
" <span class=\"h1\">",
" PATIENT MONITORING",
" </span>",
" &nbsp;&mdash;&nbsp;Regardless of whether treatment is instituted, immediately
following diagnosis, patients are seen in follow-up every two to four weeks. During
the weeks to months following presentation, respiratory symptoms (eg, cough and
pleurisy) and systemic signs (eg, weight loss, night sweats, and fever) typically
markedly diminish or resolve. Once such improvement has occurred, intervals between
clinic visits are usually extended to every three to six months for up to two years
(especially in those who are treated with antifungals [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/63\">",
" 63",
" </a>",
" ]) to document radiographic resolution and identify any evidence of pulmonary
or extrapulmonary complications [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" 9",
" </a>",
" ].",
" </p>",
" <p>",
" Fatigue and lethargy associated with coccidioidal pneumonia may persist for
many weeks or months, far beyond the resolution of all other symptoms and
laboratory abnormalities. The protracted duration of these symptoms resulting from
the disease itself is compounded by the resulting deconditioning from reduced
physical activity. Developing a structured physical rehabilitation program is often
helpful.",
" </p>",
" <p>",
" Serial serologic testing for complement fixing-type anti-coccidioidal
antibodies should be repeated at least once several weeks after the initial
diagnosis, since a rise in antibody concentrations may be associated with
progressive disease [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/64\">",
" 64",
" </a>",
" ]. Although the original descriptions of this test noted that titers greater
than 1:16 were often found in patients with disseminated infection, this
correlation is now less reliable due to differences in commercial assays. Serologic
studies may also be compromised in patients with altered immunity (transplant
patients or HIV-infected patients) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p>",
" Radiographic abnormalities should be rechecked to determine if they resolve or
leave a residual nodule or cavity. Determining whether pulmonary lesions evolve
into residual nodules is also useful because it obviates the need to investigate
the etiology of this radiographic finding in the future. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/51/39734?
source=see_link\">",
" \"Management of pulmonary sequelae and complications of
coccidioidomycosis\"",
" </a>",
" .)",
" </p>",
" <p>",
" An evaluation for disseminated disease should begin if a patient develops any
suspicious skin lesions, severe or persistent headaches, or new joint effusions.
(See",
" <a class=\"local\" href=\"#H14\">",
" 'Risk factors for complications and disease severity'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Basics topic (see",
" <a class=\"medical medical_basics\" href=\"UTD.htm?13/19/13617?
source=see_link\">",
" \"Patient information: Valley Fever (coccidioidomycosis) (The Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H907830\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1895484\">",
" <span class=\"h2\">",
" Epidemiology",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Coccidioidomycosis is the infection caused by the dimorphic fungi of the
genus Coccidioides (C. immitis and C. posadasii). Most infections are caused by
inhalation of spores. The clinical expression of disease ranges from self-limited
acute pneumonia (Valley Fever) to disseminated disease, especially in
immunosuppressed patients. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Coccidioides spp are endemic to certain lower deserts of the western
hemisphere including southern Arizona, the southern and central valleys of
California, southwestern New Mexico, and west Texas in the United States. They are
also found in parts of Mexico, and Central and South America. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Epidemiology'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1895492\">",
" <span class=\"h2\">",
" Clinical manifestations",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" After infection, a wide spectrum of manifestations is possible. It is
estimated that fewer than one half of all infections come to medical attention
because illness is often subclinical. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" When illness is clinically significant, a subacute process known as Valley
Fever with respiratory and systemic complaints is typical, often lasting for weeks
to months. In the great majority of such infections, resolution occurs without
specific antifungal therapy. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" Primary infections due to Coccidioides species most frequently manifest as
community-acquired pneumonia approximately 7 to 21 days after exposure. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" Given how nonspecific the symptoms, signs, and routine laboratory findings
of primary coccidioidal infection are, many, if not most, infections are not
identified because clinicians do not consider the diagnosis. (See",
" <a class=\"local\" href=\"#H7\">",
" 'Frequent absence of early diagnosis'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1895500\">",
" <span class=\"h2\">",
" Diagnosis",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Considering the diagnosis of coccidioidomycosis is an essential first step
for detecting most coccidioidal infections. Because exposure nearly always occurs
within an endemic region, it is critical to obtain an accurate travel history.
(See",
" <a class=\"local\" href=\"#H8\">",
" 'Methods of diagnosis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Isolation of Coccidioides species in culture definitively establishes the
diagnosis, even in patients with relatively mild pneumonia. Direct examination of
the smear with KOH preparation or calcofluor white staining is also helpful. (See",
" <a class=\"local\" href=\"#H9\">",
" 'Culture'",
" </a>",
" above.)",
" </li>",
" <li>",
" In patients with primary infections managed as outpatients, diagnosis
usually relies upon serologic testing. Commercial products are available to perform
screening coccidioidal serologies in any general clinical laboratory.
Alternatively, reference laboratories can carry out more detailed testing. (See",
" <a class=\"local\" href=\"#H10\">",
" 'Serologic tests'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/27/13751?
source=see_link\">",
" \"Laboratory diagnosis of coccidioidomycosis\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1895508\">",
" <span class=\"h2\">",
" Management",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" After diagnosis, the presence of complications should be assessed with a
careful history and physical examination. The most significant risk factor is major
suppression of cellular immunity, as occurs in with HIV infection, solid organ
transplantation, and high-dose glucocorticoid administration. (See",
" <a class=\"local\" href=\"#H14\">",
" 'Risk factors for complications and disease severity'",
" </a>",
" above.)",
" </li>",
" <li>",
" Otherwise healthy patients without evidence of extensive coccidioidal
infection or risk factors for more serious infection usually do not need antifungal
therapy. However, it is important that such patients be followed for a year or
longer, to monitor for the development of complications.",
" </li>",
" <li>",
" Patients with severe illness as well as those at greatly increased risk of
dissemination due to immunosuppression or pregnancy should be treated. These would
be considered complicated situations. (See",
" <a class=\"local\" href=\"#H17\">",
" 'Whom to treat'",
" </a>",
" above.)",
" </li>",
" <li>",
" If a decision to begin treatment is made, reasonable doses are 400",
" <span class=\"nowrap\">",
" mg/day",
" </span>",
" for",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/34/33312?
source=see_link\">",
" ketoconazole",
" </a>",
" , 400",
" <span class=\"nowrap\">",
" mg/day",
" </span>",
" for",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/12/16586?
source=see_link\">",
" fluconazole",
" </a>",
" , and 200 mg twice daily for",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/15/20730?
source=see_link\">",
" itraconazole",
" </a>",
" . Fluconazole has fewer drug interactions, whereas itraconazole has less of
a drying effect on skin and mucous membranes. Both fluconazole and itraconazole
have a lower incidence of gastrointestinal and other side effects compared with
ketoconazole. (See",
" <a class=\"local\" href=\"#H18\">",
" 'Treatment regimens'",
" </a>",
" above.)",
" </li>",
" <li>",
" The duration of azole therapy for uncomplicated primary coccidioidal
infection generally ranges from three to six months. (See",
" <a class=\"local\" href=\"#H1895250\">",
" 'Duration'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/1\">",
" Saubolle MA, McKellar PP, Sussland D. Epidemiologic, clinical, and
diagnostic aspects of coccidioidomycosis. J Clin Microbiol 2007; 45:26.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/2\">",
" Chu JH, Feudtner C, Heydon K, et al. Hospitalizations for endemic mycoses: a
population-based national study. Clin Infect Dis 2006; 42:822.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/3\">",
" Hector RF, Rutherford GW, Tsang CA, et al. The public health impact of
coccidioidomycosis in Arizona and California. Int J Environ Res Public Health 2011;
8:1150.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/4\">",
" Centers for Disease Control and Prevention (CDC). Increase in
Coccidioidomycosis - California, 2000-2007. MMWR Morb Mortal Wkly Rep 2009;
58:105.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/5\">",
" Pappagianis D, Coccidioidomycosis Serology Laboratory. Coccidioidomycosis in
California state correctional institutions. Ann N Y Acad Sci 2007; 1111:103.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/6\">",
" Dodge RR, Lebowitz MD, Barbee R, Burrows B. Estimates of C. immitis
infection by skin test reactivity in an endemic community. Am J Public Health 1985;
75:863.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/7\">",
" Tsang CA, Anderson SM, Imholte SB, et al. Enhanced surveillance of
coccidioidomycosis, Arizona, USA, 2007-2008. Emerg Infect Dis 2010; 16:1738.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/8\">",
" Park BJ, Sigel K, Vaz V, et al. An epidemic of coccidioidomycosis in Arizona
associated with climatic changes, 1998-2001. J Infect Dis 2005; 191:1981.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/9\">",
" Galgiani JN, Ampel NM, Blair JE, et al. Coccidioidomycosis. Clin Infect Dis
2005; 41:1217.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/10\">",
" Fisher MC, Koenig GL, White TJ, Taylor JW. Molecular and phenotypic
description of Coccidioides posadasii sp. nov., previously recognized as the non-
California population of Coccidioides immitis. Mycologia 2002; 94:73.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/11\">",
" Umeyama T, Sano A, Kamei K, et al. Novel approach to designing primers for
identification and distinction of the human pathogenic fungi Coccidioides immitis
and Coccidioides posadasii by PCR amplification. J Clin Microbiol 2006; 44:1859.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/12\">",
" Sun SH, Cole GT, Drutz DJ, Harrison JL. Electron-microscopic observations of
the Coccidioides immitis parasitic cycle in vivo. J Med Vet Mycol 1986; 24:183.",
" </a>",
" </li>",
" <li>",
" Cole GT, Sun SH. Arthroconidium - spherule - endospore transformation in
Coccidioides immitis. In: Fungal Dimorphism, Szaniszlo PJ (Ed), Plenum Publishing
Corporation, New York City 1985. p.281.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/14\">",
" Smith CE, Beard RR. Varieties of Coccidioidal Infection in Relation to the
Epidemiology and Control of the Diseases. Am J Public Health Nations Health 1946;
36:1394.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/15\">",
" Smith CE. Epidemiology of Acute Coccidioidomycosis with Erythema Nodosum
(\"San Joaquin\" or \"Valley Fever\"). Am J Public Health Nations Health 1940;
30:600.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/16\">",
" Crum N, Lamb C, Utz G, et al. Coccidioidomycosis outbreak among United
States Navy SEALs training in a Coccidioides immitis-endemic area--Coalinga,
California. J Infect Dis 2002; 186:865.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/17\">",
" Perera P, Stone S. Coccidioidomycosis in workers at an archeologic site-
Dinosaur National Monument, Utah, June-July 2001. Ann Emerg Med 2002; 39:566.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/18\">",
" Valdivia L, Nix D, Wright M, et al. Coccidioidomycosis as a common cause of
community-acquired pneumonia. Emerg Infect Dis 2006; 12:958.",
" </a>",
" </li>",
" <li>",
" Lundergan LL, Kerrick SS, Galgiani JN. Coccidioidomycosis at a university
outpatient clinic: A clinical description. In: Coccidioidomycosis, Einstein HE,
Catanzaro A (Eds), Proceedings of the Fourth International Conference. Washington:
National Foundation for Infectious Diseases; 1985:47.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/20\">",
" Goldstein DM, Louie S. Primary pulmonary coccidioidomycosis; report of an
epidemic of 75 cases. War Med 1943; 4:299.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/21\">",
" Colburn JR. Roentgenological types of pulmonary lesions in primary
coccidioidomycosis. Am J Roentgenol 1944; 51:1.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/22\">",
" Willett FM, Weiss A. Coccidioidomycosis in Southern California; report of a
new endemic area with a review of 100 cases. Ann Intern Med 1945; 23:349.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/23\">",
" SWEIGERT CF, TURNER JW, GILLESPIE JB. Clinical and roentgenologic aspects of
coccidioidomycosis. Am J Med Sci 1946; 212:652.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/24\">",
" TAYLOR AB, BRINEY AK. Observations on primary coccidioidomycosis. Ann Intern
Med 1949; 30:1224.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/25\">",
" Werner SB, Pappagianis D, Heindl I, Mickel A. An epidemic of
coccidioidomycosis among archeology students in northern California. N Engl J Med
1972; 286:507.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/26\">",
" Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive
survey of a reemerging disease. Clinical characteristics and current controversies.
Medicine (Baltimore) 2004; 83:149.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/27\">",
" Yozwiak ML, Lundergan LL, Kerrick SS, Galgiani JN. Symptoms and routine
laboratory abnormalities associated with coccidioidomycosis. West J Med 1988;
149:419.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/28\">",
" Merchant M, Romero AO, Libke RD, Joseph J. Pleural effusion in hospitalized
patients with Coccidioidomycosis. Respir Med 2008; 102:537.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/29\">",
" SMITH CE, BEARD RR, SAITO MT. Pathogenesis of coccidioidomycosis with
special reference to pulmonary cavitation. Ann Intern Med 1948; 29:623.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/30\">",
" Crum-Cianflone NF, Truett AA, Teneza-Mora N, et al. Unusual presentations of
coccidioidomycosis: a case series and review of the literature. Medicine
(Baltimore) 2006; 85:263.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/31\">",
" Cairns L, Blythe D, Kao A, et al. Outbreak of coccidioidomycosis in
Washington state residents returning from Mexico. Clin Infect Dis 2000; 30:61.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/32\">",
" Campion JM, Gardner M, Galgiani JN. Coccidioidomycosis (valley Fever) in
older adults: An increasing problem. Arizona Geriatr Soc J 2003; 8:3.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/33\">",
" Chang DC, Anderson S, Wannemuehler K, et al. Testing for coccidioidomycosis
among patients with community-acquired pneumonia. Emerg Infect Dis 2008; 14:1053.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/34\">",
" Kim MM, Blair JE, Carey EJ, et al. Coccidioidal pneumonia, Phoenix, Arizona,
USA, 2000-2004. Emerg Infect Dis 2009; 15:397.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/35\">",
" Galgiani JN. Coccidioidomycosis: changing perceptions and creating
opportunities for its control. Ann N Y Acad Sci 2007; 1111:1.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/36\">",
" Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of
America/American Thoracic Society consensus guidelines on the management of
community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/37\">",
" Centers for Disease Control and Prevention (CDC). Coccidioidomycosis in
workers at an archeologic site--Dinosaur National Monument, Utah, June-July 2001.
MMWR Morb Mortal Wkly Rep 2001; 50:1005.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/38\">",
" Desai SA, Minai OA, Gordon SM, et al. Coccidioidomycosis in non-endemic
areas: a case series. Respir Med 2001; 95:305.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/39\">",
" From the Centers for Disease Control. Coccidiodomycosis in travelers
returning for Mexico--Pennsylvania, 2000. JAMA 2000; 284:2990.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/40\">",
" Chaturvedi V, Ramani R, Gromadzki S, et al. Coccidioidomycosis in New York
State. Emerg Infect Dis 2000; 6:25.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/41\">",
" Hern&aacute;ndez JL, Echevarr&iacute;a S, Garc&iacute;a-Valtuille A, et al.
Atypical coccidioidomycosis in an AIDS patient successfully treated with
fluconazole. Eur J Clin Microbiol Infect Dis 1997; 16:592.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/42\">",
" Vartivarian SE, Coudron PE, Markowitz SM. Disseminated coccidioidomycosis.
Unusual manifestations in a cardiac transplantation patient. Am J Med 1987;
83:949.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/43\">",
" Johnson JE, Perry JE, Fekety FR, et al. Laboratory-acquired
coccidioidomycosis: A report of 210 cases. Ann Intern Med 1964; 60:941.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/44\">",
" Stevens DA, Clemons KV, Levine HB, et al. Expert opinion: what to do when
there is Coccidioides exposure in a laboratory. Clin Infect Dis 2009; 49:919.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/45\">",
" Wieden MA, Lundergan LL, Blum J, et al. Detection of coccidioidal antibodies
by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera
from patients evaluated for coccidioidomycosis. J Infect Dis 1996; 173:1273.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/46\">",
" Binnicker MJ, Buckwalter SP, Eisberner JJ, et al. Detection of Coccidioides
species in clinical specimens by real-time PCR. J Clin Microbiol 2007; 45:173.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/47\">",
" Singh VR, Smith DK, Lawerence J, et al. Coccidioidomycosis in patients
infected with human immunodeficiency virus: review of 91 cases at a single
institution. Clin Infect Dis 1996; 23:563.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/48\">",
" Fish DG, Ampel NM, Galgiani JN, et al. Coccidioidomycosis during human
immunodeficiency virus infection. A review of 77 patients. Medicine (Baltimore)
1990; 69:384.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/49\">",
" Hall KA, Sethi GK, Rosado LJ, et al. Coccidioidomycosis and heart
transplantation. J Heart Lung Transplant 1993; 12:525.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/50\">",
" Cohen IM, Galgiani JN, Potter D, Ogden DA. Coccidioidomycosis in renal
replacement therapy. Arch Intern Med 1982; 142:489.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/51\">",
" Holt CD, Winston DJ, Kubak B, et al. Coccidioidomycosis in liver transplant
patients. Clin Infect Dis 1997; 24:216.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/52\">",
" Rutala PJ, Smith JW. Coccidioidomycosis in potentially compromised hosts:
the effect of immunosuppressive therapy in dissemination. Am J Med Sci 1978;
275:283.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/53\">",
" Peterson CM, Schuppert K, Kelly PC, Pappagianis D. Coccidioidomycosis and
pregnancy. Obstet Gynecol Surv 1993; 48:149.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/54\">",
" Wack EE, Ampel NM, Galgiani JN, Bronnimann DA. Coccidioidomycosis during
pregnancy. An analysis of ten cases among 47,120 pregnancies. Chest 1988; 94:376.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/55\">",
" Santelli AC, Blair JE, Roust LR. Coccidioidomycosis in patients with
diabetes mellitus. Am J Med 2006; 119:964.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/56\">",
" Pappagianis D, Lindsay S, Beall S, Williams P. Ethnic background and the
clinical course of coccidioidomycosis. Am Rev Respir Dis 1979; 120:959.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/57\">",
" Crum NF, Lederman ER, Hale BR, et al. A cluster of disseminated
coccidioidomycosis cases at a US military hospital. Mil Med 2003; 168:460.",
" </a>",
" </li>",
" <li>",
" Johnson RH, Caldwell JW, Welch G, et al. The great coccidioidomycosis
epidemic: Clinical features. In: Coccidioidomycosis. Proceedings of the 5th
International Conference, H. E. Einstein HE, Catanzaro A (Eds), National Foundation
for Infectious Diseases, Washington 1996, p.77.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/59\">",
" Blair JE, Mayer AP, Currier J, et al. Coccidioidomycosis in elderly persons.
Clin Infect Dis 2008; 47:1513.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/60\">",
" Galgiani JN. Coccidioidomycosis. West J Med 1993; 159:153.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/61\">",
" Stevens DA. Coccidioidomycosis. N Engl J Med 1995; 332:1077.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/62\">",
" Drutz DJ, Catanzaro A. Coccidioidomycosis. Part II. Am Rev Respir Dis 1978;
117:727.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/63\">",
" Ampel NM, Giblin A, Mourani JP, Galgiani JN. Factors and outcomes associated
with the decision to treat primary pulmonary coccidioidomycosis. Clin Infect Dis
2009; 48:172.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/425/abstract/64\">",
" Pappagianis D, Zimmer BL. Serology of coccidioidomycosis. Clin Microbiol Rev
1990; 3:247.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 2460 Version 8.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0503-200.131.240.2-EA0AF42627-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_425=[""].join("\n");
var outline_f0_26_425=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H907830\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" EPIDEMIOLOGY",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" Risk of infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" MICROBIOLOGY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" PATHOGENESIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" CLINICAL MANIFESTATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" FREQUENT ABSENCE OF EARLY DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" METHODS OF DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" Culture",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" Serologic tests",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" Histopathology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" Polymerase chain reaction",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" Skin testing",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" RISK FACTORS FOR COMPLICATIONS AND DISEASE SEVERITY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H630889929\">",
" MANAGEMENT",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H630028667\">",
" Uncomplicated infections",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H17\">",
" Whom to treat",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H18\">",
" Treatment regimens",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H1895250\">",
" - Duration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H96096634\">",
" PATIENT MONITORING",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H907830\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1895484\">",
" Epidemiology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1895492\">",
" Clinical manifestations",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1895500\">",
" Diagnosis",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1895508\">",
" Management",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"ID/2460\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"ID/2460|DiagnosticImage\">",
" <a href=\"#\" title=\"DIAGNOSTIC IMAGES\">",
" DIAGNOSTIC IMAGES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?4/56/5001\"
title=\"diagnostic image 1\">",
" Pulmonary coccidioidomycosis",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?10/49/11027\"
title=\"diagnostic image 2\">",
" Coccidioidomycosis chest CT",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?39/62/40930\"
title=\"diagnostic image 3\">",
" Disseminated coccidioidomycosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"ID/2460|FIG\">",
" <a href=\"#\" title=\"FIGURES\">",
" FIGURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?32/52/33613\"
title=\"figure 1\">",
" Dx coccidioidomycosis by Dr",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"ID/2460|PIC\">",
" <a href=\"#\" title=\"PICTURES\">",
" PICTURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?4/21/4438\"
title=\"picture 1A\">",
" Cocci lung stain A",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?5/57/6040\"
title=\"picture 1B\">",
" Cocci lung stain B",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?29/26/30117\"
title=\"picture 1C\">",
" Cocci lung stain C",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"ID/2460|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?35/12/36043\" title=\"table
1\">",
" Sx primary coccidioidomycosis",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/55/17271?
source=related_link\">",
" Coccidioidal meningitis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/21/21848?
source=related_link\">",
" Coccidioidomycosis in compromised hosts",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?12/52/13130?
source=related_link\">",
" Erythema nodosum",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/27/13751?
source=related_link\">",
" Laboratory diagnosis of coccidioidomycosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/51/39734?
source=related_link\">",
" Management of pulmonary sequelae and complications of coccidioidomycosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/11/26807?
source=related_link\">",
" Manifestations and treatment of extrapulmonary coccidioidomycosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_basics\" href=\"UTD.htm?13/19/13617?
source=related_link\">",
" Patient information: Valley Fever (coccidioidomycosis) (The Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/4/36938?
source=related_link\">",
" Pharmacology of azoles",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_26_426="Idiopathic systemic capillary leak syndrome";
var content_f0_26_426=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"5\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Idiopathic systemic capillary leak syndrome",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/426/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/426/contributors\">",
" Rajesh Aneja, MD, FAAP",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/426/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/426/contributors\">",
" Scott Manaker, MD, PhD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/26/426/contributors\">",
" Deputy Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/426/contributors\">",
" Anna M Feldweg, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/26/426/contributors\">",
" Helen Hollingsworth, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/26/426/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" May 30, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Idiopathic systemic capillary leak syndrome (ISCLS) is a
rare disorder characterized by episodes of severe hypotension, hypoalbuminemia, and
hemoconcentration [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/1,2\">",
" 1,2",
" </a>",
" ]. During \"attacks\" of ISCLS, profound derangement of the vascular
endothelium results in leakage of plasma and proteins into the interstitial
compartment [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/1,2\">",
" 1,2",
" </a>",
" ]. Episodes vary in severity and frequency and may be fatal. ISCLS was first
described by Clarkson in 1960 and is variably referred to as Clarkson's disease or
syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Approximately 150 cases of ISCLS have been reported
worldwide [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/3,4\">",
" 3,4",
" </a>",
" ]. These have been diagnosed primarily in middle aged adults, although cases
in children as young as five months old have been reported [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/5-9\">",
" 5-9",
" </a>",
" ]. There is no apparent gender predilection.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" PATHOGENESIS",
" </span>",
" &nbsp;&mdash;&nbsp;The vascular endothelium is a semi-permeable barrier that
controls the passage of fluid and macromolecules between the intravascular and
interstitial spaces. Dysfunction of this barrier leads to leakage, with loss of
intravascular fluid and protein into the interstitial compartment. The resulting
intravascular fluid depletion can cause hypotension and impair the delivery of
oxygen to the tissues. The capillary leak is often severe and results in
significant hypotension and shock. Cells and platelets are generally retained
within the vasculature, resulting in elevations in white cell, red blood cell, and
platelet counts.",
" </p>",
" <p>",
" There are many causes of capillary leak, which can be categorized as
follows:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Increased hydrostatic pressure within the capillaries can force fluid and
protein through the endothelial barrier and into the interstitium. This is the
mechanism of capillary leak in heart failure, renal failure, hepatic venous
obstruction (eg, cirrhosis), and lower extremity deep vein thrombosis.",
" </li>",
" <li>",
" Decreased capillary oncotic pressure may fail to retain fluid within the
vascular space. This is the mechanism of capillary leak in conditions characterized
by albumin loss (eg, nephrotic syndrome, protein losing enteropathy) or decreased
albumin synthesis (eg, liver disease).",
" </li>",
" <li>",
" Increased capillary permeability allows fluid and protein to readily pass
through the endothelial barrier and into the interstitium. This is the mechanism of
capillary leak in many medical conditions, including sepsis, the systemic
inflammatory response syndrome, acute pancreatitis, anaphylaxis, snake bites [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/10,11\">",
" 10,11",
" </a>",
" ], and certain infectious syndromes (eg, Dengue hemorrhagic fever,
brucellosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/12\">",
" 12",
" </a>",
" ], hantavirus cardiopulmonary syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/13\">",
" 13",
" </a>",
" ]). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/20/5449?
source=see_link\">",
" \"Pathophysiology of sepsis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/21/18778?
source=see_link\">",
" \"Pathophysiology of anaphylaxis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/44/31431?
source=see_link\">",
" \"Principles of snake bite management worldwide\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/34/18985?
source=see_link\">",
" \"Clinical presentation and diagnosis of dengue virus infections\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" The mechanisms of capillary leak are discussed in greater detail elsewhere.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/34/36393?
source=see_link&amp;anchor=H2#H2\">",
" \"Pathophysiology and etiology of edema in adults\", section on
'Pathophysiology of edema formation'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Hypotheses in ISCLS",
" </span>",
" &nbsp;&mdash;&nbsp;The pathophysiology of ISCLS remains undefined. A small
number of hypotheses have been proposed, but the evidence for any one theory is
incomplete.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Monoclonal proteins &mdash; Several studies have found that the majority of
patients in series and case reports had a monoclonal gammopathy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/1,14-17\">",
" 1,14-17",
" </a>",
" ]. One study noted that plasma levels of paraproteins increased during the
acute phase of capillary leak and decreased during remission [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/18\">",
" 18",
" </a>",
" ]. The paraproteins are most often of the IgG1 subclass with kappa light
chains and are typically identified in the serum, rather than the urine [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/15,19\">",
" 15,19",
" </a>",
" ].",
" <br/>",
" <br/>",
" The role of these paraproteins in the pathogenesis of ISCLS has not been
determined. Paraproteins are probably not directly responsible for disrupting the
vascular endothelial barrier, since studies in which healthy endothelial cells were
exposed in vitro to paraproteins from three patients found no detectable cytotoxic
effects [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/15,20\">",
" 15,20",
" </a>",
" ]. It is possible that the paraproteins are an epiphenomenon rather than a
pathogenic factor.",
" </li>",
" <li>",
" Elevated levels of vascular endothelial growth factor (VGEF) and
angiopoietin 2 at baseline, with further elevations during attacks, were noted in a
series of 23 patients and in smaller reports [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/3,20,21\">",
" 3,20,21",
" </a>",
" ] although not in others [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/22,23\">",
" 22,23",
" </a>",
" ]. VGEF has been implicated in other disorders, such as sepsis, although the
source in ISCLS is unknown. (See",
" <a class=\"local\" href=\"#H18\">",
" 'Acute pharmacologic treatments and novel therapies'",
" </a>",
" below.)",
" </li>",
" <li>",
" Endothelial cell apoptosis &mdash; Contraction of endothelial cells due to
apoptosis (ie, programmed cell death) during attacks of ISCLS has been proposed as
a mechanism for the increased capillary permeability. This hypothesis is supported
by histologic changes consistent with endothelial cell apoptosis in muscle biopsies
obtained during attacks of ISCLS [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/24\">",
" 24",
" </a>",
" ]. In addition, serum taken from patients with ISCLS mediated extensive
apoptosis and contraction of endothelial cells in vitro [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/25\">",
" 25",
" </a>",
" ].",
" </li>",
" <li>",
" Involvement of IL-2 &mdash; The proposal that endogenous interleukin-2 (IL-
2) may contribute to the pathogenesis of ISCLS is based upon the observation that
patients who receive high dose recombinant IL-2 therapy can develop a capillary
leakage syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/6,26,27\">",
" 6,26,27",
" </a>",
" ]. Furthermore, increased IL-2 expression was demonstrated on the
perivascular blood mononuclear cells of symptomatic patients with ISCLS [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/28\">",
" 28",
" </a>",
" ].",
" </li>",
" <li>",
" Inflammatory mediators &mdash; Several inflammatory mediators have been
studied in the pathogenesis of ISCLS, including leukotrienes and tumor necrosis
factor alpha (TNF&alpha;).",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Leukotrienes, chemical mediators produced from arachidonic acid metabolism
within leukocytes, may increase capillary permeability in patients with ISCLS. One
study found that leukocyte-platelet suspensions from patients with ISCLS contained
abnormalities of in vitro leukotriene production, compared to normal controls [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/29\">",
" 29",
" </a>",
" ].",
" </li>",
" <li>",
" A small series of three patients reported elevations of TNF&alpha; during
episodes [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/17\">",
" 17",
" </a>",
" ]. TNF&alpha; is an inflammatory mediator that can increase vascular
permeability [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/30,31\">",
" 30,31",
" </a>",
" ]. One patient was treated acutely with a TNF&alpha; antagonist, with
apparent benefit. (See",
" <a class=\"local\" href=\"#H18\">",
" 'Acute pharmacologic treatments and novel therapies'",
" </a>",
" below.)",
" </li>",
" <li>",
" In contrast, defects in other factors and pathways capable of altering
capillary permeability (eg, complement, kinins, prostaglandin, coagulation,
histamine, serotonin) have not been identified [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/14,24\">",
" 14,24",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h1\">",
" CLINICAL MANIFESTATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Attacks of ISCLS usually demonstrate three phases: a
prodromal phase, an extravasation phase, and a recovery phase. The frequency and
severity of attacks varies significantly among patients. Some individuals have a
single attack in a lifetime, while others have several per year. In one series of
25 patients, patients experienced a median of 3 acute attacks per year [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Prodromal symptoms",
" </span>",
" &nbsp;&mdash;&nbsp;Approximately 30 percent of patients report an antecedent
upper respiratory tract infection (URI) or a flu-like illness with fever. Nearly 50
percent report other prodromal symptoms that precede more serious signs by one to
two days [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/32\">",
" 32",
" </a>",
" ]. Common prodromal symptoms include irritability, fatigue, abdominal pain,
nausea, myalgias of the extremities, polydipsia, and a sudden increase in body
weight. Women may be more prone to attacks during menses [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Extravasation phase",
" </span>",
" &nbsp;&mdash;&nbsp;Capillary leakage develops over the following one to four
days after the prodromal period. As this occurs, the triad of hypotension,
hemoconcentration, and hypoalbuminemia develops:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Hypotension",
" </strong>",
" &mdash; Intravascular hypovolemia causes hypotension, which is generally
defined as a systolic blood pressure &lt;90 mmHg, a mean blood pressure &lt;65
mmHg, or a decrease in systolic blood pressure of more than 40 mmHg from baseline.
The hypotension can be severe upon presentation. Hypotension develops in nearly all
patients and its major consequence is shock, defined as reduced oxygen delivery to
the tissues due to systemic hypoperfusion [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Hemoconcentration",
" </strong>",
" &mdash; In the series of 25 patients, the median hematocrit during attacks
was 60.5 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ]. Another review reported a mean hematocrit of 64 &plusmn; 9 percent and a
mean white blood cell count of 30",
" <span class=\"nowrap\">",
" cells/mm3",
" </span>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Hypoalbuminemia",
" </strong>",
" &mdash; Patients with ISCLS had a mean serum albumin of 1.7 &plusmn; 0.7",
" <span class=\"nowrap\">",
" gm/dL",
" </span>",
" in the same review [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p>",
" Other findings that are caused by capillary leakage include generalized edema,
ascites, bilateral pleural effusions, pericardial effusions, and cerebral edema and
encephalopathy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16,25,33-39\">",
" 16,25,33-39",
" </a>",
" ]. There may also be symptoms and signs related to the hypotension and
systemic hypoperfusion. These include cool and vasoconstricted skin, obtundation or
restlessness, oliguria or anuria, lactic acidosis, and diminished pulses. Acute
right axis deviation may be present.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Complications",
" </span>",
" &nbsp;&mdash;&nbsp;Compartment syndrome is a serious complication of ISCLS
that is frequently reported during both the extravasation and recovery phases [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/34,35,40-47\">",
" 34,35,40-47",
" </a>",
" ]. It is caused by the leakage of fluid into the muscular compartment, which
increases the pressure inside that compartment. Fluid resuscitation may exacerbate
the problem. Compartment syndrome can lead to rhabdomyolysis, with moderate to
severe elevations of creatine phosphokinase (CPK) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/42,43\">",
" 42,43",
" </a>",
" ]. Renal insufficiency or failure sometimes follows. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/57/8090?
source=see_link\">",
" \"Acute compartment syndrome of the extremities\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?31/55/32632?
source=see_link\">",
" \"Clinical manifestations and diagnosis of rhabdomyolysis\"",
" </a>",
" .)",
" </p>",
" <p>",
" Another complication of ISCLS is ischemic end-organ damage due to prolonged
hypoperfusion. The most common injuries related to prolonged hypoperfusion include
acute kidney injury (ie, acute tubular necrosis), ischemic brain injury,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" ischemic hepatitis. Each of these entities is discussed in more detail
separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/54/12138?
source=see_link\">",
" \"Etiology and diagnosis of prerenal disease and acute tubular necrosis in
acute kidney injury (acute renal failure)\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/56/19337?
source=see_link\">",
" \"Hypoxic-ischemic brain injury: Evaluation and prognosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/8/18568?
source=see_link\">",
" \"Ischemic hepatitis, hepatic infarction, and ischemic cholangiopathy\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Recovery (recruitment) phase",
" </span>",
" &nbsp;&mdash;&nbsp;The extravasation phase resolves after several days and the
recovery phase begins. The transition can occur quickly and is characterized by a
decrease in the amount of intravenous fluids that are necessary to maintain an
adequate intravascular volume.",
" </p>",
" <p>",
" During the recovery phase, extravasated fluids are recruited back into the
intravascular space. The patient is at high risk for intravascular volume overload
and pulmonary edema during this period (even those patients with normal renal
function). (See",
" <a class=\"local\" href=\"#H21\">",
" 'Ongoing management'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Chronic forms",
" </span>",
" &nbsp;&mdash;&nbsp;A small number of reports describe chronic forms of
systemic capillary leak syndrome, in which patients present with subacute edema and
monoclonal gammopathies [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/48-50\">",
" 48-50",
" </a>",
" ]. In the series of 25 patients mentioned previously, two patients developed
what appeared to be a chronic form of the disease, with progressive generalized
edema and pleural and pericardial effusions [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" DIAGNOSTIC EVALUATION",
" </span>",
" &nbsp;&mdash;&nbsp;Most patients with ISCLS initially attribute their
prodromal symptoms to more common alternative etiologies, such as a viral upper
respiratory infection. As a result, patients typically do not present until the
extravasation phase, when hypotension is present [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ]. Since hypotension requires immediate intervention to prevent the
complications of prolonged hypoperfusion, the diagnostic evaluation should take
place concurrently with initial management. Resuscitative efforts should NOT be
delayed by the diagnostic evaluation. (See",
" <a class=\"local\" href=\"#H14\">",
" 'Stabilization'",
" </a>",
" below.)",
" </p>",
" <p>",
" The diagnostic evaluation is the same as that for hypotension or shock of
uncertain etiology. The first step is to try and determine the type of shock,
thereby narrowing the differential diagnosis. There are three types of shock:
hypovolemic shock, cardiogenic shock, and distributive shock. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/62/6120?
source=see_link&amp;anchor=H3#H3\">",
" \"Shock in adults: Types, presentation, and diagnostic approach\", section on
'Types of shock'",
" </a>",
" .)",
" </p>",
" <p>",
" Distributive shock is initially characterized by warm, flushed skin. The
jugular venous pressure and central venous pressure may be normal or low, and
peripheral edema is unusual. However, patients with distributive shock can quickly
develop a systemic capillary leak that is characterized by falling jugular venous
and central venous pressures, as well as new generalized edema and hypoalbuminemia.
The edema may be exacerbated by fluid resuscitation, since a large portion of the
intravenous fluids will leak into the interstitial space. The skin frequently
becomes cool and clammy during this period as blood is redirected to the core
organs.",
" </p>",
" <p>",
" Patients with ISCLS similarly exhibit hypotension, low jugular venous and
central venous pressures, generalized edema, and hypoalbuminemia. Thus, the initial
differential diagnosis for a patient with ISCLS is likely to include typical causes
of distributive shock complicated by a systemic capillary leak (eg, severe sepsis,
septic shock, toxic shock syndrome, anaphylaxis, and certain drug reactions).
(See",
" <a class=\"local\" href=\"#H12\">",
" 'Differential diagnosis'",
" </a>",
" below.)",
" </p>",
" <p>",
" Clues that a patient has ISCLS, rather than distributive shock with systemic
capillary leak, include hemoconcentration and the absence of an identifiable cause
of distributive shock. In addition, patients with ISCLS are more likely to present
with generalized edema, while patients with distributive shock are more likely to
develop generalized edema during fluid resuscitation.",
" </p>",
" <p class=\"headingAnchor\" id=\"H20828386\">",
" <span class=\"h2\">",
" Diagnosis",
" </span>",
" &nbsp;&mdash;&nbsp;ISCLS is ultimately a diagnosis of exclusion that is made
when a patient manifests with one or more episodes of intravascular hypovolemia,
generalized edema, and the diagnostic triad (hypotension, hemoconcentration,
hypoalbuminemia) in the absence of an identifiable alternative cause. A monoclonal
gammopathy supports the diagnosis, although it is not present in all cases.",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h1\">",
" DIFFERENTIAL DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;Several disorders may mimic ISCLS, including severe sepsis
or septic shock, toxic shock syndrome, anaphylaxis (as part of systemic
mastocytosis or in response to a specific allergen), and certain drug reactions.
Hereditary angioedema should also be considered since ISCLS occasionally presents
with acute cutaneous edema without hypotension.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Severe sepsis or septic shock",
" </strong>",
" &mdash; Sepsis is a clinical syndrome characterized by systemic inflammation
due to infection. There is a continuum of severity, ranging from sepsis to severe
sepsis and septic shock. Normal levels of serum albumin can help distinguish sepsis
from ISCLS. Sepsis is described separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/10/24744?
source=see_link\">",
" \"Sepsis and the systemic inflammatory response syndrome: Definitions,
epidemiology, and prognosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=see_link\">",
" \"Evaluation and management of severe sepsis and septic shock in adults\"",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Recurrent toxic shock syndrome in women",
" </strong>",
" &mdash; Toxic shock syndrome (TSS) is a rapidly developing toxin-induced
illness that usually affects otherwise healthy individuals (typically young women,
but children and men are also susceptible). Patients usually have fever,
hypotension, and cutaneous findings. The skin changes are variable, ranging from a
sunburn-like rash to erythroderma or a maculopapular eruption. Other manifestations
include chills, malaise, headache, sore throat, myalgias, fatigue, vomiting, watery
diarrhea, abdominal pain, and orthostatic dizziness or syncope. In menstrual cases,
symptoms begin within two to three days of the onset of menstruation, and in post-
surgical cases, approximately two days after the procedure. The presence of skin
findings, a history of antecedent menstruation, or a recent medical procedure is
helpful in distinguishing TSS from ISCLS. TSS can be recurrent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/51\">",
" 51",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/52/8010?
source=see_link\">",
" \"Staphylococcal toxic shock syndrome\"",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Anaphylaxis",
" </strong>",
" &mdash; Anaphylaxis is an acute syndrome resulting from the sudden release
of mast cell- and basophil-derived mediators into the circulation, usually due to
immunologic reactions to foods, medications, and insect stings. If anaphylaxis is
suspected, the patient should be treated with epinephrine and fluid resuscitation,
and a serum tryptase level should be drawn as soon as possible. Tryptase is found
almost exclusively in mast cells and basophils, and is released into the serum when
these cells become activated. Any degree of elevation in serum tryptase suggests
anaphylaxis, although a normal level does not exclude the possibility of
anaphylaxis. In contrast, tryptase levels in ISCLS should be normal. Patients with
anaphylaxis have normal albumin levels, as well. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/62/38888?
source=see_link\">",
" \"Differential diagnosis of anaphylaxis in children and adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/54/40809?
source=see_link\">",
" \"Laboratory tests to support the clinical diagnosis of anaphylaxis\"",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Anaphylactic attacks of systemic mastocytosis",
" </strong>",
" &mdash; Systemic mastocytosis is a rare disorder of excessive mast cell
accumulation in one or more tissues, most often afflicting adults. Patients present
with sudden episodes of symptoms caused by massive release of mast cell mediators.
Symptoms include flushing, syncope, vascular collapse, and anaphylaxis.
Mastocytosis \"attacks\" may be precipitated by triggers that non-specifically
activate mast cells, such as exercise, alcohol, emotional stress,",
" <a class=\"drug drug_general\" href=\"UTD.htm?24/7/24698?
source=see_link\">",
" aspirin",
" </a>",
" and NSAIDs,",
" <a class=\"drug drug_general\" href=\"UTD.htm?19/31/19962?
source=see_link\">",
" morphine",
" </a>",
" , opiates, infections, exposure to iodinated contrast, and",
" <span class=\"nowrap\">",
" medical/surgical",
" </span>",
" procedures. Serum tryptase is constitutively elevated in most patients and
is an important diagnostic clue. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/1/6170?
source=see_link\">",
" \"Clinical manifestations, pathogenesis, and classification of mastocytosis
(cutaneous and systemic)\"",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Drug reactions",
" </strong>",
" &mdash; Certain medications have been reported to induce systemic capillary
leak, although the precise mechanism is uncertain. They include recombinant
interleukin-2 (IL-2) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/6,26,27\">",
" 6,26,27",
" </a>",
" ],",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/13/23767?
source=see_link\">",
" granulocyte colony-stimulating factor",
" </a>",
" (G-CSF) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/52\">",
" 52",
" </a>",
" ], interferon alfa [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/53\">",
" 53",
" </a>",
" ],",
" <a class=\"drug drug_general\" href=\"UTD.htm?31/1/31769?
source=see_link\">",
" gemcitabine",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/54\">",
" 54",
" </a>",
" ],",
" <a class=\"drug drug_general\" href=\"UTD.htm?5/39/5753?source=see_link\">",
" sirolimus",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/55\">",
" 55",
" </a>",
" ], and",
" <a class=\"drug drug_general\" href=\"UTD.htm?39/1/39958?
source=see_link\">",
" acitretin",
" </a>",
" (a systemic retinoid) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/56\">",
" 56",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/12/40138?
source=see_link\">",
" \"Cardiotoxicity of nonanthracycline cancer chemotherapy agents\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/32/37384?
source=see_link\">",
" \"Differentiation (retinoic acid) syndrome\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/28/7625?
source=see_link&amp;anchor=H552584207#H552584207\">",
" \"Interleukin-2 and other immunotherapies for advanced melanoma\", section
on 'High-dose IL-2'",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Hereditary angioedema",
" </strong>",
" &mdash; Hereditary angioedema is a rare disorder of C1 inhibitor (C1INH)
deficiency or dysfunction, which typically presents in adolescence with recurrent
attacks of cutaneous or gastrointestinal edema. Edema may also affect the upper
respiratory tract, leading to life-threatening airway obstruction. The swelling
gradually worsens for 12 to 36 hours and then subsides over a few days. Unlike the
generalized edema of ISCLS, the cutaneous swelling of hereditary angioedema is
localized, usually asymmetric, and most often affects the face, extremities,
genitals, or a limited area of the trunk. Complement component 4 (C4) is low during
attacks in nearly all cases. In contrast, complement levels are usually normal in
patients with ISCLS. Hereditary angioedema is reviewed in detail separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?33/4/33864?
source=see_link\">",
" \"Hereditary angioedema: Pathogenesis and diagnosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/52/19272?
source=see_link\">",
" \"Hereditary angioedema: Epidemiology, clinical manifestations,
exacerbating factors, and prognosis\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h1\">",
" TREATMENT",
" </span>",
" &nbsp;&mdash;&nbsp;The management of ISCLS is extrapolated from the treatment
of septic shock because the clinical presentations are similar and there is little
direct evidence from patients with ISCLS [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/57\">",
" 57",
" </a>",
" ].",
" </p>",
" <p>",
" This section summarizes our approach to the management of ISCLS. The treatment
of septic shock is described in detail separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=see_link\">",
" \"Evaluation and management of severe sepsis and septic shock in adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h2\">",
" Stabilization",
" </span>",
" &nbsp;&mdash;&nbsp;The first priority in any patient with ISCLS or shock of
unknown etiology is stabilization of their airway and breathing. Supplemental
oxygen should be supplied to all patients and oxygenation should be monitored
continuously with pulse oximetry. Intubation and mechanical ventilation may be
required to support an increased work of breathing (caused by compensation for the
lactic acidosis that results from hypotension and systemic tissue hypoperfusion) or
for airway protection (since encephalopathy can be caused by cerebral edema or
hypoperfusion of the brain).",
" </p>",
" <p>",
" Intubation and mechanical ventilation are described elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/30/11754?
source=see_link\">",
" \"Sedation or induction agents for rapid sequence intubation in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/14/36068?
source=see_link\">",
" \"Advanced emergency airway management in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/55/1912?
source=see_link\">",
" \"Rapid sequence intubation in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/12/22726?
source=see_link\">",
" \"The decision to intubate\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/7/18552?
source=see_link\">",
" \"The difficult airway in adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h2\">",
" Assess perfusion",
" </span>",
" &nbsp;&mdash;&nbsp;While the airway and breathing are being stabilized, the
adequacy of perfusion should be evaluated. The blood pressure needs to be assessed
early and often because it is the most common indicator that perfusion is
inadequate. However, hypoperfusion can occur even in the absence of hypotension.
Common signs of hypoperfusion include cool and vasoconstricted skin, obtundation or
restlessness, oliguria or anuria, and lactic acidosis. Patients with chronic
hypertension may develop critical hypoperfusion at a higher blood pressure than
healthy patients (ie, relative hypotension).",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h2\">",
" Restore perfusion",
" </span>",
" &nbsp;&mdash;&nbsp;Sequential rapid and large infusions of intravenous fluids
(20",
" <span class=\"nowrap\">",
" mL/kg",
" </span>",
" over 5 to 10 minutes) are indicated once it has been established that
hypoperfusion exists (unless there is coexisting clinical or radiographic evidence
of heart failure) [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/57\">",
" 57",
" </a>",
" ]. Volume status, tissue perfusion, blood pressure, and the presence or
absence of pulmonary edema must be assessed before and after each infusion.",
" </p>",
" <p>",
" Hemodynamic resuscitation should target a central venous oxyhemoglobin
saturation (ScvO2) &ge;70 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/57,58\">",
" 57,58",
" </a>",
" ]. Other reasonable goals include a central venous pressure (CVP) 8 to 12
mmHg, a mean arterial pressure (MAP) &ge;65 mmHg, and a urine output &ge;0.5",
" <span class=\"nowrap\">",
" mL/kg",
" </span>",
" per hour. These values should be considered guides and adjusted according to
clinical factors, such as whether the intravenous fluid boluses continue to augment
perfusion and whether there is clinical evidence of hypoperfusion or pulmonary
edema. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=see_link\">",
" \"Evaluation and management of severe sepsis and septic shock in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/8/26762?
source=see_link\">",
" \"Initial management of shock in children\"",
" </a>",
" .)",
" </p>",
" <p>",
" Crystalloids (eg, normal salines) are the intravenous fluids that are most
commonly used because they are inexpensive and readily available. Colloids (eg,
intravenous albumin, fresh frozen plasma) are alternative intravenous fluids that
normally expand the plasma volume by increasing intravascular oncotic pressure.
However, they are costly and their effectiveness is probably greatly reduced in
patients with ISCLS because proteins with a molecular weight &le;200 kilodaltons
(eg, albumin) leak from the intravascular to the interstitial space during the
extravasation phase [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/14\">",
" 14",
" </a>",
" ]. For this reason, a trial of colloid is most appropriate as a rescue therapy
for patients whose perfusion is not restored by crystalloid alone. Intravenous
immunoglobulin (IVIG) is another colloid, and appeared to decrease the severity of
the episode in two case reports [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/36,59\">",
" 36,59",
" </a>",
" ]. Red blood cell transfusions can increase the intravascular volume and
improve both blood pressure perfusion, although transfusion does not increase the
intravascular oncotic pressure.",
" </p>",
" <p>",
" Intravenous vasopressors may be useful in patients who remain hypotensive
despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema.
There is no definitive evidence of the superiority of one vasopressor over another.
We prefer norepinephrine, although dopamine is also a reasonable first-choice among
vasopressors [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/57\">",
" 57",
" </a>",
" ].",
" <a class=\"drug drug_general\" href=\"UTD.htm?38/36/39488?source=see_link\">",
" Phenylephrine",
" </a>",
" , a pure alpha-adrenergic agonist, may be particularly useful when tachycardia
or arrhythmias preclude the use of agents with beta-adrenergic activity. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/35/40505?
source=see_link\">",
" \"Use of vasopressors and inotropes\"",
" </a>",
" .)",
" </p>",
" <p>",
" For patients whose perfusion remains inadequate despite intravenous fluids and
vasopressors, sequential trials of red cell transfusions and inotropic medications
may be helpful. This strategy has been studied in septic shock and is discussed
separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=see_link&amp;anchor=H12#H12\">",
" \"Evaluation and management of severe sepsis and septic shock in adults\",
section on 'Additional therapies'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h3\">",
" Additional considerations",
" </span>",
" &nbsp;&mdash;&nbsp;While the perfusion is being restored, a central venous
catheter (CVC) should be inserted in most patients. A CVC can be used to infuse
intravenous fluids, infuse medications, infuse blood products, and draw blood. It
can also be used for hemodynamic monitoring by measuring the CVP and ScvO2.",
" </p>",
" <p>",
" Insertion of an arterial catheter may be helpful if the blood pressure is
labile or restoration of arterial perfusion pressures is expected to be a
protracted process, because a sphygmomanometer may be unreliable in hypotensive
patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/60\">",
" 60",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?25/51/26424?
source=see_link\">",
" \"Arterial catheterization techniques for invasive monitoring\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h2\">",
" Acute pharmacologic treatments and novel therapies",
" </span>",
" &nbsp;&mdash;&nbsp;There are no established acute pharmacologic therapies for
ISCLS, although case reports describe several treatment modalities that have been
given to small numbers of patients.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" A case report found that the combination of",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?
source=see_link\">",
" terbutaline",
" </a>",
" and intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?14/19/14648?
source=see_link\">",
" aminophylline",
" </a>",
" (with a serum target",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?
source=see_link\">",
" theophylline",
" </a>",
" level of 15 to 25",
" <span class=\"nowrap\">",
" mcg/dL)",
" </span>",
" appeared to be beneficial in one of two patients, and administration of",
" <a class=\"drug drug_general\" href=\"UTD.htm?28/6/28776?
source=see_link\">",
" infliximab",
" </a>",
" seemed to help another patient refractory to terbutaline and aminophylline
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/17\">",
" 17",
" </a>",
" ]. All three patients had received terbutaline and theophylline
prophylactically. However, since TNF alpha antagonists such as infliximab have been
shown to be harmful in some patients with sepsis, this latter experimental approach
should only be considered if sepsis is believed to be unlikely. (See",
" <a class=\"local\" href=\"#H22\">",
" 'Prevention of future episodes'",
" </a>",
" below and",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/16/29960?
source=see_link&amp;anchor=H11#H11\">",
" \"Investigational and ineffective therapies for sepsis\", section on
'Augmentation of immunomodulation'",
" </a>",
" .)",
" </li>",
" <li>",
" A series of three patients described successful acute treatment with high
doses of IVIG [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/59\">",
" 59",
" </a>",
" ]. These patients also received IVIG monthly for prophylaxis. (See",
" <a class=\"local\" href=\"#H24\">",
" 'Other treatments'",
" </a>",
" below.)",
" </li>",
" <li>",
" A case report from Japan described the use of anti-VEGF antibody (",
" <a class=\"drug drug_general\" href=\"UTD.htm?2/20/2377?source=see_link\">",
" bevacizumab",
" </a>",
" ; Chugai, Tokyo) to treat the acute phase of life-threatening ISCLS [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/23\">",
" 23",
" </a>",
" ]. Despite low plasma VEGF levels, the authors administered intravenous
bevacizumab (5 mg per kg of body weight) over a 90-minute period. They reported
that urine output improved and blood pressure and CVP returned to the normal range
within 48 hours.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h3\">",
" Detection of compartment syndrome",
" </span>",
" &nbsp;&mdash;&nbsp;The muscle compartments should be carefully monitored
throughout intravascular resuscitation for signs of compartment syndrome. The
tissue pressure needs to be measured if clinical signs of compartment syndrome
develop. Fasciotomy is indicated when tissue pressures are within 10 to 30 mmHg of
the diastolic pressure [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/61\">",
" 61",
" </a>",
" ]. Alkalinization of the urine and diuretics may be required if the patient
develops rhabdomyolysis. In the series of 25 patients, the development of
rhabdomyolysis correlated to the degree to which albumin declined during an attack
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ]. These complications are discussed in detail elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/57/8090?
source=see_link\">",
" \"Acute compartment syndrome of the extremities\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?31/55/32632?
source=see_link\">",
" \"Clinical manifestations and diagnosis of rhabdomyolysis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h2\">",
" Reassess perfusion",
" </span>",
" &nbsp;&mdash;&nbsp;Patients should continue to have their clinical and
laboratory parameters followed closely once the hypoperfusion resolves. These
include the blood pressure, ScvO2, CVP, urine output, creatinine, platelet count,
lactate, Glasgow coma score, oxygenation (ie, arterial oxygen tension or
oxyhemoglobin saturation), and ventilation (ie, arterial carbon dioxide tension and
pH).",
" </p>",
" <p>",
" Although the lactate level often remains elevated despite restoration of
perfusion, a rising level is suggestive of recurrent hypoperfusion. Evidence of
recurrent hypoperfusion should prompt a renewed effort to restore perfusion as
described above.",
" </p>",
" <p class=\"headingAnchor\" id=\"H21\">",
" <span class=\"h2\">",
" Ongoing management",
" </span>",
" &nbsp;&mdash;&nbsp;The transition from the extravasation phase to the recovery
phase can be recognized by a decrease in the volume of intravenous fluid that is
required to maintain the target CVP. When this occurs, the clinician's focus must
shift from the treatment of intravascular hypovolemia to the prevention of
intravascular volume overload and its complications (eg, pulmonary edema). In one
series,",
" <span class=\"nowrap\">",
" 10/25",
" </span>",
" patients developed pulmonary edema during treatment [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p>",
" Nearly all patients require diuretics (we prefer loop diuretics) during the
recovery phase to avoid intravascular volume overload. Patients with renal
insufficiency may require ultrafiltration.",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h1\">",
" PREVENTION OF FUTURE EPISODES",
" </span>",
" &nbsp;&mdash;&nbsp;No prophylactic therapy has been conclusively proven to
prevent future episodes of ISCLS because the rarity of the disorder makes
controlled trials impractical. However, in a series of 28 patients followed for a
median of 55 months (range 1 to 161 months), all five of the patients who did not
receive prophylactic therapy died, compared to only 3 out of the 23 patients who
received prophylactic therapy [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" At present, we believe that there is enough observational evidence to warrant
a trial of combined prophylactic therapy with",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?source=see_link\">",
" terbutaline",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" in patients who have had an initial episode of ISCLS. There are also an
increasing number of reports of apparent benefit with intravenous immune
globulin.",
" </p>",
" <p class=\"headingAnchor\" id=\"H23\">",
" <span class=\"h2\">",
" Terbutaline and theophylline",
" </span>",
" &nbsp;&mdash;&nbsp;The theory that",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?source=see_link\">",
" terbutaline",
" </a>",
" plus",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" may prevent ISCLS is based on the observations that both agents increase
intracellular cyclic adenosine monophosphate (cAMP) content [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/25\">",
" 25",
" </a>",
" ] and that elevated cAMP inhibits capillary leak [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/62-66\">",
" 62-66",
" </a>",
" ]. Terbutaline increases cAMP by facilitating its production of cAMP, while
theophylline blocks its degradation.",
" </p>",
" <p>",
" The most compelling evidence for treatment with these agents was a
retrospective series that evaluated the clinical course of eight patients with
ISCLS who were followed for 18 years [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/35\">",
" 35",
" </a>",
" ]. All of the patients were treated with oral",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?source=see_link\">",
" terbutaline",
" </a>",
" (dose not specified) and",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" (serum target level 10 to 20",
" <span class=\"nowrap\">",
" micrograms/L).",
" </span>",
" The patients had a median of six severe attacks per year prior to being
diagnosed with ISCLS. In contrast, the median attack rate was reduced to 0.2
attacks per year after receiving the combination of terbutaline and theophylline.",
" </p>",
" <p>",
" Many of the episodes that occurred while receiving therapy were mild enough
that hospitalization was not required [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/35\">",
" 35",
" </a>",
" ]. The one patient who continued to have severe attacks, and eventually died
of shock, never achieved a therapeutic level of",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" . Breakthrough attacks seemed to correlate to subtherapeutic levels of
theophylline in two other patients. Sustained release theophylline appeared to be
the most effective formulation. Adverse effects from sympathomimetic stimulation
were frequent with therapy, but improved with minor dose adjustments and time. A
few patients received glucocorticoids intermittently.",
" </p>",
" <p>",
" There are additional reports that support the use of",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?source=see_link\">",
" terbutaline",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" to prevent ISCLS [",
" <a class=\"abstract\" href=\"UTD.htm?
0/26/426/abstract/3,16,17,44,47,67,68\">",
" 3,16,17,44,47,67,68",
" </a>",
" ]. According to one review, theophylline and terbutaline alone or in
combination seemed to be effective in 17 out of 50 cases [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ]. Dosing of terbutaline varied among the available reports, but a dose of 5
mg four times daily is at the lower end of the reported range [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/32\">",
" 32",
" </a>",
" ]. Some patients require higher serum levels of theophylline to avoid attacks
[",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/17\">",
" 17",
" </a>",
" ].",
" </p>",
" <p>",
" Reports that",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?source=see_link\">",
" terbutaline",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?source=see_link\">",
" theophylline",
" </a>",
" prevent ISCLS have not been universal. In a series of 13 patients with ISCLS
who were followed for a mean period of 6.4 years,",
" <a class=\"drug drug_general\" href=\"UTD.htm?14/19/14648?source=see_link\">",
" aminophylline",
" </a>",
" and terbutaline did not appear to be beneficial [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/32\">",
" 32",
" </a>",
" ]. However, serum theophylline levels were not used to guide therapy and
treatment was usually discontinued if patients had recurrent attacks, potentially
accounting for some of the differences in outcome.",
" </p>",
" <p class=\"headingAnchor\" id=\"H69665446\">",
" <span class=\"h2\">",
" Intravenous immune globulin",
" </span>",
" &nbsp;&mdash;&nbsp;Monthly infusions of intravenous immune globulin (IVIG)
have been reported to reduce the frequency of attacks in some patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/4,59\">",
" 4,59",
" </a>",
" ], although not in others [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/17,69\">",
" 17,69",
" </a>",
" ]. In the series of 28 patients, 18 were treated with IVIG in doses ranging
from 0.4 grams to 2 grams per month [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/4\">",
" 4",
" </a>",
" ]. Eight of the patients receiving IVIG had no new attacks over multiple years
of follow-up.",
" </p>",
" <p class=\"headingAnchor\" id=\"H24\">",
" <span class=\"h2\">",
" Other treatments",
" </span>",
" &nbsp;&mdash;&nbsp;Other therapies that have been administered to patients
with ISCLS with variable success include glucocorticoids,",
" <a class=\"drug drug_general\" href=\"UTD.htm?17/22/17767?source=see_link\">",
" spironolactone",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?35/50/36649?source=see_link\">",
" indomethacin",
" </a>",
" , leukotriene modifying agents,",
" <a class=\"drug drug_general\" href=\"UTD.htm?9/18/9514?source=see_link\">",
" verapamil",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?31/39/32368?source=see_link\">",
" cyclosporine",
" </a>",
" , and Ginkgo biloba [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8,16\">",
" 8,16",
" </a>",
" ].",
" </p>",
" <p>",
" Monthly infusions of IVIG have been reported to reduce the frequency of
attacks in some patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/59,70\">",
" 59,70",
" </a>",
" ], although not in others [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/17,69\">",
" 17,69",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H25\">",
" <span class=\"h1\">",
" PROGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;The fatality rate during acute attacks of ISCLS is not well
defined. Early case reports often described fatalities, although better supportive
care and more widespread recognition of the disorder have probably reduced
mortality. Patients who die during attacks tend to die either of flash pulmonary
edema during the recovery phase, or of ischemic organ failure due to hypoperfusion
during the extravasation phase [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/3\">",
" 3",
" </a>",
" ].",
" </p>",
" <p>",
" In a review of 50 cases of ISCLS, 70 percent of the patients who survived
initial attacks were alive a mean of five years after diagnosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" 16",
" </a>",
" ]. The estimated five-year survival in the series of 25 patients mentioned
previously was 76 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ]. In the series of 28 patients described above, five-year survival was 73
percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/4\">",
" 4",
" </a>",
" ]. Some patients with monoclonal gammopathies will eventually develop multiple
myeloma [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8,32,36,50\">",
" 8,32,36,50",
" </a>",
" ]. However, in one group of 25 patients followed for variable numbers of
years, none progressed [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/3\">",
" 3",
" </a>",
" ]. One group has suggested that the prognosis in children is better than that
in adults [",
" <a class=\"abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H26\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Idiopathic systemic capillary leak syndrome (ISCLS) is a
rare disorder that typically begins in midlife. It is characterized by episodes of
severe hypotension, hypoalbuminemia, and hemoconcentration. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H2\">",
" 'Epidemiology'",
" </a>",
" above.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Episodes of ISCLS usually begin with prodromal symptoms, followed by
hypotension and edema. The hypotension and edema are due to fluid extravasation,
which typically worsens over one to four days and may be complicated by a
compartment syndrome. The capillary leakage then abruptly reverses and the fluid
moves back into the vasculature. During the recovery phase, the patient is at risk
for volume overload and pulmonary edema. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" The diagnostic evaluation is the same as that for hypotension or shock of
uncertain etiology. ISCLS is a diagnosis of exclusion that is made when a patient
manifests intravascular hypovolemia, generalized edema, and the triad of
hypotension, hemoconcentration, and hypoalbuminemia in the absence of an
identifiable alternative cause. The diagnostic evaluation generally occurs
concurrently with initial management. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Diagnostic evaluation'",
" </a>",
" above.)",
" </li>",
" <li>",
" Initial management of ISCLS is aimed at securing the airway and correcting
hypoxemia. This may require intubation and mechanical ventilation. While the
patient's respiratory status is being stabilized, the adequacy of perfusion should
be assessed. Patients with hypoperfusion should have their tissue perfusion
restored using a strategy similar to that used for septic shock. This begins with
the infusion of intravenous fluids to a goal central venous oxygen saturation
(ScvO2) &ge;70 percent within six hours. It is reasonable to simultaneously aim for
a central venous pressure (CVP) 8 to 12 mmHg, mean arterial pressure (MAP) &ge;65
mmHg, and urine output &ge;0.5 mL per kg per hour. Intravenous vasopressors may be
useful in patients who remain hypotensive despite adequate fluid resuscitation or
who develop cardiogenic pulmonary edema. (See",
" <a class=\"local\" href=\"#H13\">",
" 'Treatment'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=see_link\">",
" \"Evaluation and management of severe sepsis and septic shock in adults\"",
" </a>",
" .)",
" </li>",
" <li>",
" After initial resuscitation and stabilization, treatment should be
redirected toward the prevention of intravascular volume overload and its
complications (eg, pulmonary edema). Nearly all patients require diuretics.
Patients with renal insufficiency may require ultrafiltration. (See",
" <a class=\"local\" href=\"#H21\">",
" 'Ongoing management'",
" </a>",
" above.)",
" </li>",
" <li>",
" For all patients who have had an ISCLS attack, we suggest combination
therapy with",
" <a class=\"drug drug_general\" href=\"UTD.htm?29/31/30200?
source=see_link\">",
" theophylline",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/55/12151?
source=see_link\">",
" terbutaline",
" </a>",
" (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). The purpose of such therapy is to prevent future attacks. A reasonable
regimen is sustained release theophylline (dosed to achieve a serum concentration
of 10 to 20",
" <span class=\"nowrap\">",
" mcg/mL)",
" </span>",
" and terbutaline (5 mg four times daily). Intravenous immune globulin is an
alternative preventative therapy.",
" </li>",
" <li>",
" Among patients who survive an initial attack, at least 70 percent are alive
five years after diagnosis. Some patients with monoclonal gammopathies develop
multiple myeloma over time. (See",
" <a class=\"local\" href=\"#H25\">",
" 'Prognosis'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H21224979\">",
" <span class=\"h1\">",
" ACKNOWLEDGMENT",
" </span>",
" &nbsp;&mdash;&nbsp;The editorial staff at UpToDate, Inc. would like to
acknowledge Dr. Joseph A. Carcillo, who contributed to an earlier version of this
topic review.",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/1\">",
" CLARKSON B, THOMPSON D, HORWITH M, LUCKEY EH. Cyclical edema and shock due
to increased capillary permeability. Am J Med 1960; 29:193.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/2\">",
" Marks J, Shuster S. Disorders of capillary permeability. Br J Dermatol 1973;
88:619.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/3\">",
" Druey KM, Greipp PR. Narrative review: the systemic capillary leak syndrome.
Ann Intern Med 2010; 153:90.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/4\">",
" Gousseff M, Arnaud L, Lambert M, et al. The systemic capillary leak
syndrome: a case series of 28 patients from a European registry. Ann Intern Med
2011; 154:464.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/5\">",
" Foeldvari I, Waida E, Junker AK. Systemic capillary leak syndrome in a
child. J Pediatr 1995; 127:739.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/6\">",
" Karatzios C, Gauvin F, Egerszegi EP, et al. Systemic capillary leak syndrome
presenting as recurrent shock. Pediatr Crit Care Med 2006; 7:377.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/7\">",
" Onal H, Aktuglu-Zeybek C, Altun G, et al. Capillary leak syndrome in a 5-
month-old infant associated with intractable diarrhoea. Ann Trop Paediatr 2007;
27:81.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/8\">",
" Kapoor P, Greipp PT, Schaefer EW, et al. Idiopathic systemic capillary leak
syndrome (Clarkson's disease): the Mayo clinic experience. Mayo Clin Proc 2010;
85:905.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/9\">",
" Piastra M, Pietrini D, Conti G, et al. Sudden shock from capillary leak.
Lancet 2012; 379:976.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/10\">",
" Suchithra N, Pappachan JM, Sujathan P. Snakebite envenoming in Kerala, South
India: clinical profile and factors involved in adverse outcomes. Emerg Med J 2008;
25:200.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/11\">",
" Nelson BK. Snake envenomation. Incidence, clinical presentation and
management. Med Toxicol Adverse Drug Exp 1989; 4:17.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/12\">",
" Erkurt MA, Sari I, G&uuml;l HC, et al. The first documented case of
brucellosis manifested with pancytopenia and capillary leak syndrome. Intern Med
2008; 47:863.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/13\">",
" Chang B, Crowley M, Campen M, Koster F. Hantavirus cardiopulmonary syndrome.
Semin Respir Crit Care Med 2007; 28:193.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/14\">",
" Atkinson JP, Waldmann TA, Stein SF, et al. Systemic capillary leak syndrome
and monoclonal IgG gammopathy; studies in a sixth patient and a review of the
literature. Medicine (Baltimore) 1977; 56:225.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/15\">",
" Zhang W, Ewan PW, Lachmann PJ. The paraproteins in systemic capillary leak
syndrome. Clin Exp Immunol 1993; 93:424.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/16\">",
" Dhir V, Arya V, Malav IC, et al. Idiopathic systemic capillary leak syndrome
(SCLS): case report and systematic review of cases reported in the last 16 years.
Intern Med 2007; 46:899.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/17\">",
" Dowden AM, Rullo OJ, Aziz N, et al. Idiopathic systemic capillary leak
syndrome: novel therapy for acute attacks. J Allergy Clin Immunol 2009; 124:1111.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/18\">",
" Treatment of systemic capillary leak syndrome. Lancet 1988; 2:1496.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/19\">",
" Dams K, Meersseman W, Verbeken E, Knockaert DC. A 59-year-old man with
shock, polycythemia, and an underlying paraproteinemia. Chest 2007; 132:1393.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/20\">",
" Xie Z, Ghosh CC, Patel R, et al. Vascular endothelial hyperpermeability
induces the clinical symptoms of Clarkson disease (the systemic capillary leak
syndrome). Blood 2012; 119:4321.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/21\">",
" Lesterhuis WJ, Rennings AJ, Leenders WP, et al. Vascular endothelial growth
factor in systemic capillary leak syndrome. Am J Med 2009; 122:e5.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/22\">",
" Nagao Y, Harada H, Yamanaka H, Fukuda K. Possible mediators for systemic
capillary leak syndrome. Am J Med 2011; 124:e7.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/23\">",
" Yabe H, Yabe M, Koike T, et al. Rapid improvement of life-threatening
capillary leak syndrome after stem cell transplantation by bevacizumab. Blood 2010;
115:2723.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/24\">",
" Johansson BR, L&ouml;fdahl CG. Ultrastructure of the microvessels in
skeletal muscle in a case of systemic capillary leak syndrome. Acta Med Scand 1979;
206:413.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/25\">",
" Assaly R, Olson D, Hammersley J, et al. Initial evidence of endothelial cell
apoptosis as a mechanism of systemic capillary leak syndrome. Chest 2001;
120:1301.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/26\">",
" Schwartz RN, Stover L, Dutcher J. Managing toxicities of high-dose
interleukin-2. Oncology (Williston Park) 2002; 16:11.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/27\">",
" Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic
administration of autologous lymphokine-activated killer cells and recombinant
interleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 313:1485.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/28\">",
" Cicardi M, Gardinali M, Bisiani G, et al. The systemic capillary leak
syndrome: appearance of interleukin-2-receptor-positive cells during attacks. Ann
Intern Med 1990; 113:475.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/29\">",
" Rondeau E, Sraer J, Bens M, et al. Production of 5-lipoxygenase pathway
metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease).
Eur J Clin Invest 1987; 17:53.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/30\">",
" Vadlamani L, Iyengar S. Tumor necrosis factor alpha polymorphism in heart
failure/cardiomyopathy. Congest Heart Fail 2004; 10:289.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/31\">",
" Lejeune FJ, Li&eacute;nard D, Matter M, R&uuml;egg C. Efficiency of
recombinant human TNF in human cancer therapy. Cancer Immun 2006; 6:6.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/32\">",
" Amoura Z, Papo T, Ninet J, et al. Systemic capillary leak syndrome: report
on 13 patients with special focus on course and treatment. Am J Med 1997;
103:514.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/33\">",
" Chihara R, Nakamoto H, Arima H, et al. Systemic capillary leak syndrome.
Intern Med 2002; 41:953.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/34\">",
" Barnadas MA, Cister&oacute; A, Sitjas D, et al. Systemic capillary leak
syndrome. J Am Acad Dermatol 1995; 32:364.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/35\">",
" Tahirkheli NK, Greipp PR. Treatment of the systemic capillary leak syndrome
with terbutaline and theophylline. A case series. Ann Intern Med 1999; 130:905.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/36\">",
" Vigneau C, Haymann JP, Khoury N, et al. An unusual evolution of the systemic
capillary leak syndrome. Nephrol Dial Transplant 2002; 17:492.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/37\">",
" Bertorini TE, Gelfand MS, O'Brien TF. Encephalopathy due to capillary leak
syndrome. South Med J 1997; 90:1060.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/38\">",
" Claessens YE, Joly LM, Cariou A, Oksenhendler E. Acute reversible cardiac
involvement associated with systemic capillary leak syndrome. Intensive Care Med
1999; 25:334.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/39\">",
" Lister G, Hellenbrand WE, Kleinman CS, Talner NS. Physiologic effects of
increasing hemoglobin concentration in left-to-right shunting in infants with
ventricular septal defects. N Engl J Med 1982; 306:502.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/40\">",
" Sanghavi R, Aneman A, Parr M, et al. Systemic capillary leak syndrome
associated with compartment syndrome and rhabdomyolysis. Anaesth Intensive Care
2006; 34:388.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/41\">",
" Matsumura M, Kakuchi Y, Hamano R, et al. Systemic capillary leak syndrome
associated with compartment syndrome. Intern Med 2007; 46:1585.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/42\">",
" Dolberg-Stolik OC, Putterman C, Rubinow A, et al. Idiopathic capillary leak
syndrome complicated by massive rhabdomyolysis. Chest 1993; 104:123.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/43\">",
" Balcarek P, Frosch KH, Quintel M, St&uuml;rmer KM. [Systemic capillary leak
syndrome causes a compartment syndrome of both lower legs and a forearm. A case
report with a review of the literature]. Unfallchirurg 2005; 108:770, 772.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/44\">",
" Doubek M, Brychtova Y, Tomiska M, Mayer J. Idiopathic systemic capillary
leak syndrome misdiagnosed and treated as polycythemia vera. Acta Haematol 2005;
113:150.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/45\">",
" Navarro C, Garc&iacute;a-Bragado F, Lima J, Fern&aacute;ndez JM. Muscle
biopsy findings in systemic capillary leak syndrome. Hum Pathol 1990; 21:297.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/46\">",
" Prieto Valderrey F, Burillo Putze G, Martinez Azario J, Santana Ramos M.
Systemic capillary leak syndrome associated with rhabdomyolysis and compartment
syndrome. Am J Emerg Med 1999; 17:743.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/47\">",
" Sabbadini DD, Peressutti R, Di Silvestre A, et al. Systemic capillary leak
syndrome. Case report. Minerva Anestesiol 2002; 68:929.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/48\">",
" Rauzy O, Adoue D, Arlet P. Chronic systemic capillary leak syndrome not
requiring treatment? Am J Med 1998; 105:360.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/49\">",
" Stirling CM, Boulton-Jones JM, Simpson K. Progressive oedema in a 30-year-
old. Lancet 1998; 352:450.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/50\">",
" Beermann W, H&ouml;rstrup KA, Will R. Systemic capillary leak syndrome. Am J
Med 1998; 105:554.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/51\">",
" Andrews MM, Parent EM, Barry M, Parsonnet J. Recurrent nonmenstrual toxic
shock syndrome: clinical manifestations, diagnosis, and treatment. Clin Infect Dis
2001; 32:1470.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/52\">",
" Rechner I, Brito-Babapulle F, Fielden J. Systemic capillary leak syndrome
after granulocyte colony-stimulating factor (G-CSF). Hematol J 2003; 4:54.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/53\">",
" Yamamoto K, Mizuno M, Tsuji T, Amano T. Capillary leak syndrome after
interferon treatment for chronic hepatitis C. Arch Intern Med 2002; 162:481.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/54\">",
" Dahan L, Ressiot E, Cournede A, et al. [Anasarca, a complication of
chemotherapy with gemcitabine in two patients with pancreatic cancer].
Gastroenterol Clin Biol 2007; 31:1143.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/55\">",
" Kaplan MJ, Ellis CN, Bata-Csorgo Z, et al. Systemic toxicity following
administration of sirolimus (formerly rapamycin) for psoriasis: association of
capillary leak syndrome with apoptosis of lesional lymphocytes. Arch Dermatol 1999;
135:553.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/56\">",
" Estival JL, Dupin M, Kanitakis J, Combemale P. Capillary leak syndrome
induced by acitretin. Br J Dermatol 2004; 150:150.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/57\">",
" Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign:
international guidelines for management of severe sepsis and septic shock: 2008.
Crit Care Med 2008; 36:296.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/58\">",
" Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the
treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/59\">",
" Lambert M, Launay D, Hachulla E, et al. High-dose intravenous
immunoglobulins dramatically reverse systemic capillary leak syndrome. Crit Care
Med 2008; 36:2184.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/60\">",
" Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for
hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004;
32:1928.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/61\">",
" Whitesides TE, Haney TC, Morimoto K, Harada H. Tissue pressure measurements
as a determinant for the need of fasciotomy. Clin Orthop Relat Res 1975; :43.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/62\">",
" Casnocha SA, Eskin SG, Hall ER, McIntire LV. Permeability of human
endothelial monolayers: effect of vasoactive agonists and cAMP. J Appl Physiol
1989; 67:1997.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/63\">",
" Rippe B, Grega GJ. Effects of isoprenaline and cooling on histamine induced
changes of capillary permeability in the rat hindquarter vascular bed. Acta Physiol
Scand 1978; 103:252.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/64\">",
" Sigurdsson GH, Christenson JT. Influence of terbutaline on endotoxin-induced
lung injury. Circ Shock 1988; 25:153.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/65\">",
" Svensj&ouml; E, Adamski SW, Su K, Grega GJ. Quantitative physiological and
morphological aspects of microvascular permeability changes induced by histamine
and inhibited by terbutaline. Acta Physiol Scand 1982; 116:265.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/66\">",
" Shimura H, Yamaguchi M, Kuzume M, et al. Prevention of reactive oxygen-
induced endothelial cell injury by blocking its process. Eur Surg Res 1999;
31:390.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/67\">",
" Hiraoka E, Matsushima Y, Inomoto-Naribayashi Y, et al. Systemic capillary
leak syndrome associated with multiple myeloma of IgG kappa type. Intern Med 1995;
34:1220.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/68\">",
" Kawabe S, Saeki T, Yamazaki H, et al. Systemic capillary leak syndrome.
Intern Med 2002; 41:211.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/69\">",
" Hollenberg J, Frykman J, Lundberg LG, Forsberg S. A case report of systemic
capillary leak syndrome (Clarkson's disease). Acta Anaesthesiol Scand 2010;
54:649.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/26/426/abstract/70\">",
" Gousseff M, Amoura Z. [Idiopathic capillary leak syndrome]. Rev Med Interne
2009; 30:754.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 3919 Version 12.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0503-190.102.30.19-4C5AE98573-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_426=[""].join("\n");
var outline_f0_26_426=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H26\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" EPIDEMIOLOGY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" PATHOGENESIS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Hypotheses in ISCLS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" CLINICAL MANIFESTATIONS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" Prodromal symptoms",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" Extravasation phase",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" - Complications",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" Recovery (recruitment) phase",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" Chronic forms",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" DIAGNOSTIC EVALUATION",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H20828386\">",
" Diagnosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" DIFFERENTIAL DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" TREATMENT",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" Stabilization",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" Assess perfusion",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16\">",
" Restore perfusion",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H17\">",
" - Additional considerations",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H18\">",
" Acute pharmacologic treatments and novel therapies",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H19\">",
" - Detection of compartment syndrome",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H20\">",
" Reassess perfusion",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H21\">",
" Ongoing management",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H22\">",
" PREVENTION OF FUTURE EPISODES",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H23\">",
" Terbutaline and theophylline",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H69665446\">",
" Intravenous immune globulin",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H24\">",
" Other treatments",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H25\">",
" PROGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H26\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H21224979\">",
" ACKNOWLEDGMENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/57/8090?
source=related_link\">",
" Acute compartment syndrome of the extremities",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/14/36068?
source=related_link\">",
" Advanced emergency airway management in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?25/51/26424?
source=related_link\">",
" Arterial catheterization techniques for invasive monitoring",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/12/40138?
source=related_link\">",
" Cardiotoxicity of nonanthracycline cancer chemotherapy agents",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?31/55/32632?
source=related_link\">",
" Clinical manifestations and diagnosis of rhabdomyolysis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/1/6170?
source=related_link\">",
" Clinical manifestations, pathogenesis, and classification of mastocytosis
(cutaneous and systemic)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/34/18985?
source=related_link\">",
" Clinical presentation and diagnosis of dengue virus infections",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/62/38888?
source=related_link\">",
" Differential diagnosis of anaphylaxis in children and adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/32/37384?
source=related_link\">",
" Differentiation (retinoic acid) syndrome",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/54/12138?
source=related_link\">",
" Etiology and diagnosis of prerenal disease and acute tubular necrosis in
acute kidney injury (acute renal failure)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/51/21306?
source=related_link\">",
" Evaluation and management of severe sepsis and septic shock in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/52/19272?
source=related_link\">",
" Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating
factors, and prognosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?33/4/33864?
source=related_link\">",
" Hereditary angioedema: Pathogenesis and diagnosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/56/19337?
source=related_link\">",
" Hypoxic-ischemic brain injury: Evaluation and prognosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/8/26762?
source=related_link\">",
" Initial management of shock in children",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/28/7625?
source=related_link\">",
" Interleukin-2 and other immunotherapies for advanced melanoma",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/16/29960?
source=related_link\">",
" Investigational and ineffective therapies for sepsis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/8/18568?
source=related_link\">",
" Ischemic hepatitis, hepatic infarction, and ischemic cholangiopathy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/54/40809?
source=related_link\">",
" Laboratory tests to support the clinical diagnosis of anaphylaxis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/34/36393?
source=related_link\">",
" Pathophysiology and etiology of edema in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/21/18778?
source=related_link\">",
" Pathophysiology of anaphylaxis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/20/5449?
source=related_link\">",
" Pathophysiology of sepsis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/44/31431?
source=related_link\">",
" Principles of snake bite management worldwide",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/55/1912?
source=related_link\">",
" Rapid sequence intubation in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/30/11754?
source=related_link\">",
" Sedation or induction agents for rapid sequence intubation in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/10/24744?
source=related_link\">",
" Sepsis and the systemic inflammatory response syndrome: Definitions,
epidemiology, and prognosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/62/6120?
source=related_link\">",
" Shock in adults: Types, presentation, and diagnostic approach",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/52/8010?
source=related_link\">",
" Staphylococcal toxic shock syndrome",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/12/22726?
source=related_link\">",
" The decision to intubate",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/7/18552?
source=related_link\">",
" The difficult airway in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/35/40505?
source=related_link\">",
" Use of vasopressors and inotropes",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_26_427="Risk of nausea and vomiting with emergency contraception";
var content_f0_26_427=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PI
%2F77880&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PI
%2F77880&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Risk of nausea and vomiting with emergency contraception",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" &nbsp;",
" </td>",
" <td class=\"subtitle1\">",
" Percentage of women who experience nausea",
" </td>",
" <td class=\"subtitle1\">",
" Percentage of women who experience vomiting",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Estradiol + levonorgestrel",
" </td>",
" <td>",
" 43",
" </td>",
" <td>",
" 16",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Levonorgestrel (alone)",
" </td>",
" <td>",
" 18",
" </td>",
" <td>",
" 4",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_427=[""].join("\n");
var outline_f0_26_427=null;
var title_f0_26_428="Causes of microcytic anemia";
var content_f0_26_428=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=HEME
%2F59035&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=HEME
%2F59035&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Causes of microcytic anemia (mean corpuscular volume less than 80 fL)",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Hereditary disorders",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Defects of globin synthesis",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" <span style=\"color: #ff0000;\">",
" Thalassemia syndromes",
" </span>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Thalassemic hemoglobinopathies (eg, Hb E, Hb Lepore)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Defects of iron metabolism",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Iron refractory iron deficiency anemia (IRIDA)*",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" DMT1 mutations*",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Atransferrinemia*",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Sideroblastic anemia",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Acquired disorders",
" </td>",
" </tr>",
" <tr>",
" <td>",
" <span style=\"color: #ff0000;\">",
" Iron deficiency anemia",
" </span>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Myelodysplastic syndromes (MDS)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Refractory anemias with ringed sideroblasts (RARS)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" MDS with acquired thalassemia*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Sideroblastic anemias due to drugs or toxins (lead poisoning, alcohol,
drugs)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Copper deficiency",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Zinc deficiency",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" The two most common causes of microcytosis are shown in",
" <span style=\"color: #ff0000;\">",
" red",
" </span>",
" type.",
" <div class=\"footnotes\">",
" DMT: divalent metal transporter.",
" <br>",
" * Very rare causes of microcytosis.",
" </br>",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_428=[""].join("\n");
var outline_f0_26_428=null;
var title_f0_26_429="Diagnostic criteria for Carney complex";
var content_f0_26_429=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=ENDO
%2F83442&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ENDO
%2F83442&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Diagnostic criteria for Carney complex (CNC)",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Major diagnostic criteria",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Spotty skin pigmentation with typical distribution (lips, conjunctiva and
inner or outer canthi, vaginal and penile mucosa)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Myxoma* (cutaneous and mucosal)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cardiac myxoma*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Breast myxomatosis* or fat-supressed magnetic resonance imaging findings
suggestive of this diagnosis",
" </td>",
" </tr>",
" <tr>",
" <td>",
" PPNAD* or paroxical positive response of urninary glucocorticoid excretion
to dexamethasone administration during Liddle's test",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Acromegaly due to GH-producing adenoma*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" LCCSCT* or characteristic calcification on testicular ultrasound",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Thyroid carcinoma* or multiple, hypoechoic nodules on thyroid ultrasound
in a young patient",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Psammomatous melanotic schwannomas*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Blue nevus, ephithelioid blue nevus*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Breast ductal adenoma*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Osteochondromyxoma*",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Supplemental criteria",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Affected first-degree relative",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Inactivating mutation of the",
" <em>",
" PRKAR1A",
" </em>",
" gene",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Findings suggestive of or possibly associated with CNC, but not diagnostic
for the disease",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Intense freckling (without darkly pigmented spots or typical
distribution)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Blue nevus, common type (if multiple)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Caf&eacute;-au-lait spots or other \"birthmarks\"",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Elevated IGF-I levels, abnormal GTT, or paradoxical GH response to TRH
testing in the absence of clinical acromegaly",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cardiomyopathy",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Pilonidal sinus",
" </td>",
" </tr>",
" <tr>",
" <td>",
" History of Cushing's syndrome, acromegaly, or sudden death in extended
family",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Multiple skin tags or other skin lesions; lipomas",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Colonic polyps (usually in association with acromegaly)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Hyperprolactinemia (usually mild and almost always combined with clinical
or subclinical acromegaly)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Single, benign thyroid nodule in a young patient; multiple thyroid nodules
in an older patient (detected on ultrasound)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Family history of carcinoma, in particular of the thyroid, colon,
pancreas, and ovary; other multiple benign or malignant tumors.",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" CNC: Carney complex; PPNAD: primary pigmented nodular adrenocortical disease;
LCCSCT: large-cell calcifying Sertoli cell tumor;",
" <em>",
" PRKAR1A",
" </em>",
" : protein kinase A regulatory subunit 1&alpha;.",
" <br/>",
" * After histological confirmation.",
" </div>",
" <div class=\"reference\">",
" Reproduced from: Almeida MQ, Stratakis CA. Carney complex and other
conditions associated with micronodular adrenal hyperplasias. Best Pract Res Clin
Endocrinol Metab 2010; 24:907. Table used with the permission of Elsevier Inc. All
rights reserved.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_429=[""].join("\n");
var outline_f0_26_429=null;
var title_f0_26_430="Patient info search strategies";
var content_f0_26_430=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PC
%2F71366&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PC
%2F71366&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 528px\">",
" <div class=\"ttl\">",
" Three strategies for finding trustworthy information on the web (with
examples)",
" </div>",
" <div class=\"cntnt\" style=\"width: 508px; height: 314px; background-image:
url(data:image/gif;base64,R0lGODlh/AE6AcQAAP///wAAAIiIiERERBERESIiIru7u+7u7t3d3VVVV
czMzDMzM2ZmZpmZmXd3d6qqqp+fn9/f3+/v7w8PD19fX6+vrx8fH09PT8/Pzz8/P39/f7+/v29vby8vLwAA
AAAAACH5BAAAAAAALAAAAAD8AToBAAX/ICCOZGmeaKqubOu+cCzPdG3feK7vfO//wKBwSCwaj8ikcslsOp/
QqHRKrVqv2Kx2y+16v+CweEwum8/otHrNbrvf8Lh8Tq/b7/i8fs/v+/
+AgYKDhEgBh4iJiouMjY6PkJGSk5SVlpeYmY2FnHcBnaApn6GkbqOlpaeoq2aqrJyur7JesbOBtba5Vri6f
Ly9wE6/QgoBCy8EAQfBQMPMz0aqD4sKMgkBDyvFxy7JyyUHAQTQNM7k5z+x4eM019kq28jK6Drm9Pc46uIj
CwHu+wL8AWiQTFzAQ8cOBhAAQEEBccZIFEPE8MAAcd6SIQBAoADHcQQPjVPQL8CAjf3c/5Gzh6/lDH3sAJT
EBtDfuo0iVAZ0AOAhgocK4pkoNu4aQ28OFjZY+PHmiAIEDhiIOPPdM5Yus7qAyS9AtXUAAiYAwADRWJXXEk
0bGXEEgrSHDvSr5q1YgQFRP5I1Gy+csrnosGodLMoEWBGA1x0QO+KAxmsNwgZgQIJA1KnccjL1djGbNwAXB
eoV4TjAz8tUvQYmzLoGV8SqASQ16W+iwYbJEiZSMM1YWxEKcnv7aexz72ofbRNgSPLQSZmxV7aeHkMw9S7W
rw/Orj0L9+4tv4OvIn78avNnyqOHpn69MPfj28NfIn9+rvr2j+DP/2o//yH+/ZeKgLQQyFqABvaAYP+ChSz
IYA4OPnhLCQMwBAACppnwUCIWPmUWTiVMJeEKEY7ohysVioAhiCHiUkBkCAxQwDckiGgiCiXeuAeKFq6IWQ
AFIGfjQQtU8+IIBDyAIUIHbOhRWgvQKGGO9Ghi5ZVYWlIOhT2aNlU1CYwFgIjFVMPAAD1FJkKKKmIzZJQyd
TjljVSOwR2PwCkzpEdjftIAnwZ4dKQISSoQWgAN2FgWIpSZWOc5j4ZxZwkOFLARAx7ZuECjZKqWAJpHxugR
A8eEk+g8AsA5wqdzggdBBDJECsakJFiEUDVTIYTTkLf2ZNYyBiTzUANyAQkAXJERYECr3UEQwAUbwCDrF7S
qYGP/EQ+gyax2EkxwiAUQSNDCtAW+xMK1OgJoHgeJTEABrCqUuChy1G6ZrhTkEhIBIxlUUFgJixbggJQvgD
XVWNOIOYRxolVn771Q5EvIBY1YoIG4JbiSFEMx0kvDNDwh8ZkN1dLA5rjLvnByC+ji0HIOKwMQQMo6xCyEx
INUAAkFGJDgyjUDDCxCUiXxdEBaBWRjKCKOEWBbkQL9iVCthyqzMUdeHX1I0gMVRABcDhQzVkgCrXOR0xk/
vGaGoLGNQoozsxD3CM0ZoyYJNlvriiLSGvByjWyf2QLcKc891KEMECyC4aDJqS6OWUYu+eSUT9IBBIuX4BA
iCyBwdT8GuIOh/6BoEzrOTg3VZoziRmF9wNXJKCA6kE4ROo/Y8ewEFmM+q902T0uyaELeONIsU8gCNIq34y
u0jGgNf48wFU6Cs0D44sY39rUIBnQ+OPNB8FL5+OSXj+XlmRvmwEUCXO1OQYgIZbpkPImNugmAIbWZV/DHt
ahAn7FfAHgyjSjtI2FpMxfe8PK6i2wESsuAC0PilpZxOKkajFuAtkagEEOVhDIIKNqFROi8u/0vMjJyzkMI
sJGZiagAFUmS9AKHpkAdIjInbNz/MFSSu4WFTySo3pEoSBHJACkoJVEYhNCjs0fwrHckSICFytKAjTXJK5A
hAVToZRn6pS4B21BcZ1yXFP+exC6L4NCIRr6YuwGCBYFQjBWFzkSQpSAgVctYgAAEYKnGycwAfBReT3jCOA
UsagBBMdwAamiaMOEmdGMJjt/2VkQRkAo0aFrKsmD4RxH9aSBA7FMi0ESAyDwgJmQ5xvVkxhA+BlFbiECAE
CMzs0A2LjjVcIAUM8MDnAmCYoywGMbiKAIBVJAhSSlIZLQmkoYcqmleFBsop+aWh+BFGcS5pgKYKQ7ltPIQ
YYtaQSjzxoalT454Y8BSEjC9/02GAY0iHDwb8z/KMC6IC/jkCFK0okEN4E9q+mcJOVgQj6TIRoQTkWO658P
pWfIkirhjQf04t7jps5hAXNEs/zjPxi3/BRGWukY+e2mefS2iX/9SwdVENo8mlAw0lFHW9PDIwRk1aYKA7O
NA5rGpP5JgpGRBpCI51shIzsyRxZhkxtSEoWxUyo8IxembUNkn6pHybk2VjUEn+A6LhhIBBBjAMopxx0yV8
o98PMBNcWkCV+7Al4BgFyLcBa+UpmClRxgZE146AOU5FFnF6ghO2yaOEG7NnsabjTE20kF+msawAxwhOPu0
1H1ubauUpahSARAOxzk0qGNyEmELgNlFYWhZFwUO4g5AnAWcdWaB5aRCGKAQH+ZjPN36VrjGFYqXhiJYipu
Qq54VrRfAFQu+BcUCQgaL8bwKnZ1ILsSUcNxZVHcX/76bLn3o1NvsKuEBQZJB9E5AvIxl7w2peiudzMfe9v
pWIQnYSDiAeCiG9LVNgDwEZciGyBJwbSqcmozewrLBFKxsRfscLA+mobwaCKDACV4T+Mg7YehqFxgaC2+Ml
pUqZa2JMl+674Xi9mDOYoOzCfBhA7iRq2WUpcEmGO/w5IRg8/ZgkXn5QXlTAN56XJgZrpChf5MXz0aVUsSn
JbCJJ8yAkE2lQo7pqQ2fN+VPlHjKyUMECmnsNrj1sHEyymGFZMRJx1hlxA6JTN0SYKt9BEsckcFyiU/4UUS
liEgY/LKJPeaaHwdjb8KbilTycl87Vo3E2mpAaBKHNzVN5U/Ju//vWU/JEYaIqMTLMcElD9zlCbZyHAPw3g
g27b1PpjYsCUFTernX0kp3zTEdKvGoVWmhCpUJtExxa0/Oq0A/6yLItnUnCrUMU/wquVbLbTSriWMoBiwpl
hm6NERBJICJchpE15sem6q9NT9yVllA9VAs32I32RikxqZxW4m5bSw2VUifgfLpRQvAawv72rqUoveFBnDK
d6RXxB829pX7Kxc5NXnZJZa0DzMdECVnesROxaxbOu3Tpzo24t5GNVUFvSbm6pqsDI/KwwmcVYuHzNaeQpN
XSRMdkt3715pmFEEm3ux04vcgzoaLEgfC4i6DWLQf7YeS37yQ0JA24yNGxCL/J7i1Zbn7shnvLMAURpDa5k
rAbz4r0feIJqN75KOK/qYxMIhaPvV4iS+3hS+5dgbgfmHH0kq72qEAXj6LIdleWDXa5d4fvkfD730H/OMEP
yDCh8/whR91Ik6F+F43vrlBbLCMH3+C61J+Cq7oqAicBNmdX34Elv98xAC2eBuxSvQ4Qv0gMi/5UQxK9QmE
/R9YD7gIQlj2oZc9dUmv5WJZKom6l1nwTzR8xxcfD7kfUfKPP3jm89b5yIf+VqTvCerLzfp1WP6DtI99H3c
/9d+Pg3vHT/7ym/9K4U+/+tfP/va7//3wj7/850//+tv//vjPv/73z//+
+///ABiAAjiA/wRYgAZ4gAiYgAq4gAzYgA74gBAYgRI4gRRYgRZ4gRiYgRq4gRz4Vuf3gSAYgh/YgSTlftz
nfydoICnIfysoIC2ofy/IHzGIfzNoHzVof+QiP/dyg/UnDdRgDScGD79xAgikEvnBg/T3GjNghCmggyrAhP
OBhPOnhClBE6cjTiKhELpxCMyxQkPYZgshQFOjEBXWGlIof1SICGshGWxWWKtyYqjjE0Chg0mhPNKkE5HlE
+ZxhvGXhl9RE2PxP2dxYnBxCGuog5vTTXdIiIpwZtrBh/DnhyYWFbzzbY30PAHRYJYhFUM4AnW4iJGRifAB
ie8nieZGG2CECJkWHBGhEP9e0Rv9wEtwcRLSxIpbeAh2Rx2kaIKlSILqxYu+uHfst4vtR4zXYYzrh4zToYz
px4wHEozCmIzQeFvAOI19Vo3WaHzq54zft3yyRiDc2H0owjYO9GzGsiH+sBE1JjOHcEeiwUnoaBr1dWzgmI
3XaFnA047rmCb7NiP7SGKWERnw6EP39SXf6IL26Ds41kCP5Tb8SChK4pAkBkNRMZA2xxENUGKctCJkU4bP6
CgiGJKSoJB0VEoNCVIP2Tj/yGEzQgCYwhDxGCP7ZRoaSVQxwlzoEY5voJPe9Xz7pE7+MD37+HpJspI/ZEQw
SZDEVpMjhgDdYxK5qIvcBQp8FVOThAD/QwkjMtKUPsOSm8cUr1dsHNR1lBEQIJIAMPaIzlVXxtVdxgdwQpk
IgvIrSeccseRWSwGTiSCTJHBlCCGPWxOVy+hcxBV3VNmT3Yhb3hIA4DJM8eKW9raN69Iu70IiRDAvkoKY4l
hS/OIv4BdEWyM0MmAwAgFHCzMPpmmYkdmM6AFMiyBMJqAxTNExNwAySaBXmvmYN9AyB2lEKLMt3dFEjvBEo
FcCQCOaRDNZzMQ1SxMXlvE00iQ1X1g1r7M/24Q02UA2X4MI4TQ2BTEWZtNNsecwF5lkzWNl2nKQ4eB0HnlP
KnAQIzeYkCOS9FmfAYA+wicR6Ng5n3NU2DA6PVE6/3qBOrizOibQOvpzFFj0n7TjhrYzVqqjGwMDiOOpmgE
3YvUGOMd2kMVgXBlKKWK1bzj5kZVnnyYqgvhZCwzZPkzxPoqgg11EoP5wPyWQP1Zjnf2jDILoOl+EOgVUTj
tXlcYGQc8WJdPDKHz0EFGyIWcyQV8GWUS0Og9mlqQBUbgYovI5HsLZCMR5TjkxRYhiRUCBRpsnoDEaWQWqK
nhzYvpjRgtqW5YIVhmSpvQDpBXalmuaCIAEJ3o0cQ8gbRiFAI7BeBTVSk8CS3uaR3ukb9IjAEtyEo4qlebh
mooAmxVqTFlobsqEYqroTExzpvUTNRvCS9k0HNYUO9zkNKoodv/d2TX6NYkAkJr5aW9INjPuxADNiSiAemw
vElXyJihqYquJQFsQZhE/4RAWEVxZwZNaYFKKgFKfeVdMwVLK+ndv2SinRVOWVCq6amXcIGu9OgrX80lIVU
tq2puy8RzdM6KEwaxZIFeHQFeWuQJ4ZQS4uXvXOqRa9mbDQibJQKybR6jj6hGbAzrHomXoakTxaYaKqVuOa
VcNkpvW565X4CzQYqERq42s6SpsOX2HqbHhR7FqILJ4upohO5XRJbFo4J4vMHlvsDLjRbIre6InqpCzGTdP
OXae+DxHuXkVhos7JQOnJF+cJAr1xm5sdgK7CgMMFgRw91nVswLZJj4J+Zb/PnFaYBVPM/Jti4RRT/GzR7c
USzgWDsBLlcdr0wAjC+B5mTUDCwkET0tD3+NTMVu1tHomELWnlZGdLJQhusZJU5E9C7EcYgtZlNGnq4KTjp
EU1RAaYhW4iAJbaxtFzFUMi0FaqwOoofaqhlsCGJJmmlETuDhlkaFYCtCRI1BnGdkrM2RVoXVDewG7FXJCv
iGgXmq3PvlhUxEQBhC1/Bg0fuSKTBG4SxUQDYeWF+I0ulRstrtThqpWerS7i/MAiPu1E1dWglpKmstIbwFC
tpte66ZTSYUkpjQOQQga7OpHt+a7V+ccGBmrqLRpg0W8AHe7uDuvP3mw5rq35ugRf/uz/8SyIb6iZaeUkQt
AabG5LB2VPNciDmZ7LJWrDODKeAlnk/HoQzGpeRdljjT5EInzlP0VYfAWSlBrpXdpbfM7Cppnv/cLsfe1JA
aAIVq7GNxgZv/bJ4IbGR91LDBmGRLFthOpVjDUwCsGYUuhtmMxwZprk8gbYy0VNLaUOjRzViZAxTyMN6EKJ
gVWwu/bJhgHN9mgKDAms8WHIo1SFsuSs0XSEx3CAFIERIB7Tzz7EJLVjseCJqZytmtjEpwIegYgF2oaFt+5
DEqMnn60IlAKIm6cuqDWTB00ZS3JJEbnMWCHZ4DjupA8WqV1Qyo8xi3sscX4ybkrjaKMv8NYyqZMyv+oHK2
qvMqxyXs35LKoR8bDR3szJH20HHy2/JVA0nm67MqsLGymd3uwl8u6t8uZFZbHDMyVBzCtZ3vHZ8y4B8uI4n
u+vMzMfKcbm83FiY3cLM1/xs3E1Mrf3IvizMIne86zesrqTLPu/M41q87yPM/0XM/2fM/4nM/6vM/83M/
+/M8AHdACPdAEXdAGfdAIndAKvdAM3dAO/dAQHdESPdEUXdEWfdEY3R3wXJ90sNH0OQceLZIq6wsdDZlwAM
7NDLLCJQco/cosbdIYSwgv+FzkmbJeQNMxvXojvSNgYLHFBcqQ1wU+ndOCIF0r3QW5xZi7dX0fi9SL2ZijL
NM7XQP/mDkrYQCvASCvuvld5oRdX4DVWg2xVgCF+pFdASOaMUCaCNPVQMAwbMvUX+CsiQCtKb0CMeIcHukC
snoDhxGNWyDXiEDXLh0DM3EIb/2ekbUCZF2jXkGj1GhvV0ObNmCb1HoDM0ipiWCp44wCgJEtObDXVBCDmI0
Imt3NM1CvMODYKLDYJ6DaLmd8x/kNyRlZy6k0z/ScnBOdo0o1iVCdCnqdW8O3IgE20fmdk3g2fDaDW8oIXb
rOKfCvHVLbWGPYsWoMC3CLDlBAsSglzXkS2m2g8BlZXVSFTCHdcO0Fy70Izf0dK5UUCUAADgA7WVNfvd3dl
yIS5+uq+3ANtqEM/9J52KlcssCxn57DFKAzO6TDRVcYqqkYyJqhoL6NNbLDoDPioDxKp7pDoZsNeiH9CCna
AnVmEgcbkaH0EAbQG8ZQidPQddNapgewFAyw4m0jAHbhRePtQvtN4VHN4R3OCB9OA+3NnfKtAHXIQYkNFS8
+GYzBhLVzsAogo8dARSod4Jy1PgvhPtiQozC64D2a2IxNFzf62zl6ADsaQDMaWT96QF0tPj3eCD/eAkRu4m
OuWNgAR0yIQHjV38aA5wvBGKhz49u0D2N+3hnT5ovw5jIQ5BYy5InoNDKaCMvVovm9o/yNOsKbvoQu4McCp
lW0EFc04RhsplyepmLEpjfqpv+gbhhqNKcRWqdqHqRikN6KsN4sYBFq0g/kdjcBgSbuAEcqLhD1ChUgwucC
gBk2Pg5zARZkuuNaIOuJQOtAPq1Bjuo7S1sCFqDUFlljlEaX+OQC5oQmS+iYehvJBLup6qnOOeqiSk0qcqr
Y5O7ALRLeZEStSjbk9OravAWj/S0XM9gqFRoHzKkiEVj98ACmqRDZDewtju7+QOyn2A9mhOxZsw/nnun6Xj
H9nu8toOjtbhJnpHSCWhIHkKtjcTYFTzer6uTF4t/omNd1XdPS6vI8cK9JEIOAfQiCrfFvx7Ml6AU3HwA5v
+FFLbGoTQQ0bwhXTZkd6+9hMBOYbtlgANb/lbnVQQ3zGesFSQ3VFj/0WP/US03lXB/ugDDThanpUn3TZQ/U
V2/1Z3/TS7/1R70FOG32Oj3ls1fSTX3SME33YS9+e98GLa3z8WLo59fRhG9+IH345ZfRjD8LP934frYvbw/
596IBAaABlO9n3jIBmX9hznIImNP5EJMBgS3694IBitAzpn8jFDDrq28iEgD0zgIBpP+wr08gEaD6o4ABk3
/79ej76RL4wG/Vw4+yxQ+cx58gwp/8W7D8zO8dz7990c8gzj/95GH9BoL52L/93N/93k+AIvj9f18E1f/95
FL+3n/+4p/3SL/+Vd/
+7t/2CvKh6N/9sZCrjBYr9B///2sPAsBBJABgLIi5sm0bGC4byLV947m+873/A4PCIbFoPCKTyuWPxhIUXI
hFIOAwDaqDAyBRDQgAsG51wV05meo1u+1+w+PyOX2YNjEGpi8iUVIQGEAdHCwICBCoDITBCJgBGM7UTVJWW
l5iZmrG3QFArSAEIBQ0YDUwMJgIoKYCLIoZMHwFtO5t3uLm6u7y9ja1IBBsASiI+hE3FhAWHCofMMM6nr34
VltfY2drC3USZ1UxHExVXblqEVIFQI95VZWibcfLz9PXU3YPPb/j4Nv7/wMMKNCWkS96dPQbqHAhw4aYEra
B6HAixYoW7UySeHEjx44XNbZ4VQSkx5ImT//S67Sg3KCQYUaijClzZrxOxRQEe+BCJBGSNH8CDQqnm6Njst
y5Stfq2zCm01z4FCp1KlVuMgoQeMpggSs9BkQNKtQM3UsZUauiTatWkgsBBxFVifIqFAJUqljdtXF2Ld+
+QPG5BRBKpwO5YeiGZZa4LFS/jh+nBXzwWwHDgkWZC9D0nF7Inj//3HtENOjSpv2Rhnl6NeuGqXu2ji3732
uMs2/jzlbbau7evnV1+volzNclu38jT656xVcViNYcVy59+o7gmB2UKA6lQIBH7cD4iE59PHm2zGeF014Aw
YgGiBQxRlh+Pn3e51U8c6D9ICm7ruLnIF59A/pmHX7M7Gd6AimLhUeggw82xoJwVSRwQIIAkFJIXADyA6GH
D+6mT4Mfkkjfawb9UqKK4wnYQ4srwqjWi9XFWONvM8pno4634Rjgjj/G1mOHQBJp2ixHIpmkkksmWaSTT0I
ZpZRTUlmllVdimaWWW3LZpZdfghmmmGOSWaaZZ6IJZQgAOw==);\">",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_430=[""].join("\n");
var outline_f0_26_430=null;
var title_f0_26_431="AU fibrin glue";
var content_f0_26_431=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=SURG
%2F54580&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=SURG
%2F54580&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Injection of fibrin glue into the anal fistula",
" </div>",
" <div class=\"cntnt\" style=\"width: 288px; height: 166px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCACmAS
ADASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwDysptyDTlGMEirl7AUbdjiq6npWhyPuQXMII8xP+BD1Fc3e6UiSedF/q
27ehrq+hqpcQiF/MHMTfeX0qrcysCfKYdtaA4wh4q/FbAHGytSKCJgCvA9KlWEfX0rFprc0Xvaol8MRGPWL
cqDjdXpt5FOq5AypHFcT4Zg36pbbR827pXq7PFDbzmeMnyV8xgB2Fa0anIrsVal7RJGPpmi3F/CsqvGu3kq
TzS+RDBcbHIULyzGtC5ngWKC8tZ2AlTCqOD+Irz74la02k+FZizn7bcsY4sd/X8qyrYhz0iXSoqC1K/j/wA
eG5ul8P8AhRDcX0vyST/wpnsP8aztD+GNlpkD3niGZb26bkRofl3H3710vwu8E2Wk+GI9U1VidRuE86Qkco
p6Ln1pNemmu5ke2BEER+Ve5pU7uVh1ZKKuc5q/g7w/Pp8sssX2UqMmRGJK15payalpBkubJJZ9OifCysvGP
X2r2Sf7VLbbbuaG0hY8iRRlh6YNWE1bSEh+xQWc1wrDayQwblb8q7p0oyXvaHFTryjtqcboHxTa3RBfEzRD
G4N95fpijx78SpxPAPDdxCICuWbGXz6Gnal8G9f12+mvfDelpBYkbvLllwwPsMfpXntz4c1S1159DMWLsnB
RgByPeuL2/LeCkdywylaXKemeCviXaXaJb+ImMU4J/fAfKwPrX0f4Dl0ieGNrMq7yKCsoPDe1fCOqWL6fey
20hy8Zw+Ox9K67wh491jQ4I1t7p0it3DuOu5cgYqZp1YctyZKVGpzxXqfbev6dbyyW0vnNC1s27av8Q9DXI
y+JfBul6pdkavZRXk5Hmp5nORT5dcW48LJeTsSWgDFvqM18XSXButdurooWQyMcnnGTxXkwoyquUZO1j0/a
wilOKu3qfQ/xa1/TtQS1k0a7iuZFJD7GzgYrzSyvlMw3SKJAa561S4s5B5Jy8uCe+BXVQ2kE8fmiMrc7cEh
eDXdTo8keVHJVq80rs1bQC+G1iAw7jvXQadZR2/UEsfWuIt7K7ju0khSUIrAng816WZrIWELruEzYBzx9au
dNozjUT0OU8SvNDOsMUn3xn2+lUHupoYlaSMA9yOldzPZQXJyyqw6VVk0ZJIzEqAqezda9KhOMYJNHn11Nz
bTOW06aa4cyuR5a9q1Yta+z4MOAfanXmktpltIUQ+Xjn2rj2dvN4PHWurkhPVIx55rdnp+keLTvEd4AVP8A
EO1dXBdQ3Cb42yCK8OWZhjmtjSPE8lncCPJKCpcWthp30Z6RrUmLUqDkk1lQBXQq4z60q6xaX9r5jNt2jJp
Lfy5U8yFgyt0INXzJk2sYev8AhxLiFpbEKsq87c8GvJtRtrqLU9l1E6yBu4r3hCUcAkiqmr6VZapAVuYwH7
OOCK5a+Xwq6w0Z2UMxlB8tXVHj0eRcqIziQ8KKuazG9tp8EEv+taUytj3FddB4Uj0/zZSRO+Dtc8beK5bxG
3najaW68ssAB+teH7OdGbjLdHtzcalNTg9Gbt425QtZhUrx79auTPzg/U1CRuHPavUk9bnjQV42IQuGJ9Kd
IqyRlXAwRTmXH40wc8d6E76haxRjDQSiJzwD8p9auxttk59aZcwebHheHXkVFC5k6/eXrVyXMrkRfIzr/Dz
SwXH2i1jWSVOUU9DXZ+GBcnWrm+1CfzFli8s2/YVxuhBXtoyW2jIJrpxfGC6edgiQk8Hpk1yuO6R181teh0
d9ZRGNJliCyKcrhgAB6YrxPx8s3iDx5puml41gt2DkZ6E4NdLqfj3S7TUhBqNzlGP3kPC/WvPtZ1XT5Piba
ajZzedYqFJdPpSjSatcn2vM9Ee33U00kYgkUC3Tg7RwayNY1rQrO1aOaYK+OPLOSD+Fcj8SvGX2nRorXQZj
YkNmWZmx5i46DFeV6d4llsoifs8c1wf+WsnP6Vak43USPZKprI9l8Oa3pJ1qN9V064uNNzh5riUYUeuDX0r
puhaBHb211p0ESwyIHj8vgMCMg1+e2pa1qGosftVy7Kf4AcL+Ve3Wvx6bSfCOjaXotnPcX1tapDIZyPL3AY
OAOTXJi/bSXu63OyhGnDTY+qJbuKGPACRADpkLn8a+Sv2ldb08+NdOutCuYv7RgjYXBhIIVs8ZI4J61xPij
xp4y8SCQajeXEFo/It0zHGB9OtcKytvIwSc1lh8HKMlOb+RtPFRScYI1tc1EXbxpAQysBJI+PmdzycnuAel
dZ8NPDVzqniSS7vIY20+BiLjPKn2/QVx+k6Ld6hcKqwuI8jcxGOK9S0DRbiyZ4LG6ubWGYfvBGcZNejCHLa
x4uPzGnTTUnqyb4geLtWsmNrprBrZPl2hMjHpXnti6XdzvuIPs+85bYMKT6kV3914eu9OH2iSaS8tVOZI5e
Titqy0TSNStUuLWFcH+72pxppdDh/tmjBJpNruchH9jt5g6ym4YjAVVIras7jVxtNlpReI/wB4g10ll4eso
ZgSGUHjmussdJltIleJUngPRoxV/CdlDEUsWrwlc4lNQ1uBQZtIYr3xSnxVbRf8fti8YHXch4r0iF4T8uNj
ejimXdlZXsTQ3cEciNwVYdaqNRdTSVFrZnDReN/D0ce6WdYlHrzWvaa7o+qoDY30LOenzAGs/Wvhf4dv1Oy
3a3bsYj/9euE1H4R3dlOZdJvyVByA3DVajzPQhWS1ep6szh4mguNro4wTXnviTQJrGdpYBvt2547Vq+GI9T
tLdbbVN42fxua2ZLlJWa3jUzPjoOwpyrxwvvVGkiadGeKfLTi2zzdW4OazhIfPdh611euaJcRrJJDCVzztr
lJLeaHIlidPqK78PisNiFenNP5mNfCYmg7VINfI0rPUWhI5+XuD0NWdK8Tf2bq5h3ZtpeQuehrn0jeU4HAH
euZ165EWoIID/q+pHrVTgoptk0b1ZcqPom1v4b2IMjAN9asN/q8t1FeQ+GtZlktkKOQy+9dafEUrwrGyYbH
JqoqxlN2djozLEWKu3yE8iuB1WzWy8TPqF2yi0Q5QZ6j0qxcai8kuFJ5rn9S06+1W6JmdvIThQehrjxcaHx
VWdmE9s/dpbGrMx83PQVMQUCt2NR3CbXwexqcrvteOgrjexvHR3GZ59RSFFJ6YpqcD2qZAD3FTa5aYwIBzV
a5t/KkEyfdPDCrrL6GnInmxNH/eGBVLQTVzsvh2q/Y5VcK2XOCecCm/Ebw5qVzp/wBp0eTeYhlos449RVLw
FK0SGInBVytehWl6C/lt9Oa8ivOVKs5QPShBVaSUkfI2ova+bIbqSWa5GQQv3QfrVaTVJfKWO3RIEA52Dk/
ia96+J3wsttXSTUvD6JBf/ekhHCyepHoa8j1XTUk1zT9Es7M28sap57OuGLEZY59K66VaNVXe5hOn7N2S0I
tD8F634gieeBFCgZBmfaW+lX7D4Z69cN+
+SGBAcEs4J/KvVrS8ttNtUhjYhVAAxzVO7177YTFDKV7U3VcnaKM23H4mcvZfD/SNOkVtUuXujjmNflwfwr
e+z21lpskmg6TBCo+XzWXLA/iK1bLRiwEsu4s3frXY6dpaf2bNbNEoDLnPvT+r8799g8VKMGqe9jzfTtDN/
Mbi/YNIevAH6VMPCMcd2wiij2dRlRXS6fD+98vHzA4roUsiNrAcEc1tCMI6WPga+KrTk5Sd2cjZ6CYQNqoD
7AVsw6RlR8pLV0cNhlc7TmrtnZEnGOa1bS2OF1W9ZHODSBLEVkTORhhXOzaSPCt0lzaxONPlOJl67Seh+le
u2liqSJv5J4rQfR7aeN45Yg8bcFSMg1m5uRpSlulszgLXTVvYFmgKvG4yGHermk2txpd0G+ZrSTiRD29xW3
pGijw7qZt4iW065JMYPPlt3/Cujl08MDheahqUtGbYapVw1X2tHdGLe6QGUMUDxsMqRWLPpUsRJgbP+y1eh
Wdn5umNAxIKfdrn9ahazgLt94dPeuWVX2Ls9j9Fw6WNoqtDRvp5nGyTtE5i2HzuyHpVSa2vXBNxLsB5wK6S
z04Ir318eSM5PYelOg0p9WYSnIgHKgelfJ5jnVWtU5aLtFdup9bl2XYbDQ5q6Un1b6eSOGubB7793GGPPLV
dstKXTgG2g/3jXUa3JZ6HaPJIUjVBnniuI1TxtpctiZEmTdtPAPfFea51q6s7s9yi6V+anFRRt3NrDcQg4B
U9DXOajpkYJDIv5Uzw34iS7hiBYbX966SeNZ4snHtShKph58r0Na1GNRdzzy90e3YMFjC57jiuPn8AWj3hk
NxKsZOSn/169P1CDYxzWLcNgk17mHx9dRtGbPBr5dRcruKOMXww2jXifZp2e2fsw6GtNLc4YlsGrmr3A+yg
sfunNc//AGgoViz4HpmvWp4/FVafLz7Hj1svw1KpzcmrNbdDGuTjPrUIvQFY+/Fc3fa0gwE5xWRNqjkH94R
k0KjKesncTrQpq0Uegz/M5OOvQ0+26lSOtSCN3O1QCT3qYWjgq392vfZ82nZWM6VfLkKnoOn0qRRgDHerV/
GvyybgT0qC25YrUDT0HffOcVctYG4bbxVWNCZ1T1PFdPEES2WPArKpPlOilDm3Kuixm2upHU5UfOR9a6W1v
Y3Ynd9OaxYlEbDBwG4qhqNwdPdSM+Wx6jsa5K9Ln99G8J8j5T0HTL8O7KT93jNGpaRpOolp7m3iW4K7TcKM
P+dcjoWpLFa+ZK2GkOcGtyxml1KZByI89B3ricXF6HQpqSszN/4QmKOEGCR5tzZOT/D/AI0+30DTTcYitXA
XjJ4r0mxhgs4kaX5nPQetYnivSbqQG9t3G0nHkiroY+MqnJL7xVsFJQ54/cRzaVa29vD9jmEmeq5zg0+CFk
l2upDY6VF4ethLa7VQC7TkqT1rp7a08+KOKUD7bnIHfFeqqrjpLY4Y0lLVbnAzW/2bVZwVADHcD7Vqw+cIm
eNT5aDJ4zWp4j0hoZ0kYZx8pIq54SlgmLRDGzoVPWuetV5IuUdWfG4rBWxroy0i2rvyZlaX4u0CW7jsprjZ
dN0DIVB/EjFdlBYxuvmRAHPTByK5y+8L2d/cPBJbI6k9cVYtfDuueHVSTRbk3NmvWzlOQB/s968DB8SKUrV
4fcfWY/gjDpJ4Wtr2l+jX6nR/Yj8vHIrTggxGMjmuNuPFupGbyLXQLoXA4LTLhP0q5FD4l1GMSTSraL3SL/
69epiOIcHSX7u8n2SOPBcJYinLmq2gvNr8lc2tZFu2nyieVEC4Oc8g1JY3kTWkLN95lya5+40eP7I8k26SU
EZLHrzUxkZQufugdKMlzV5nOV48qRycRYaGTKFSlLmcrrbtY6vT5I5JGC4IIrJ8XQpJNawgAFz0+lR6JLI1
3GEOB3qLxdcLDqsMkjbViUnJ+la581Rws2j2OEMS8Yk7bX/IxvEbLcXNrpMAAJwXx2Fa+s3dr4Y8Ny3ExAE
cefrXJ/D+5/trXNRvJd0uJCiEjoB6V2etaINctZLa6hZrfG3ae9fA4XCTr1eVL/gH2uMlGhKNGb0jq/Ns+W
fHOr6trl79tlYtpzZCQ9vxrz3UNMfz98DMgbgrgkCvrux+D1oqhLm7YwhtyxgdParVx8KdLgJltbWB39CvJ
r7HC1quEoODotpbWt/w55+PVDFYmNSlW5dNd/w6HzH4IstYjvVikgcQDkSYwMV7RYbhaJ5h5xzV3W9OOlIU
mtzCo4Hy4rlrrWoYLdwXC4PrXy+NxEsXVbULeR9dgqKpUF7/ADeZLrMibW55Fcbf3iqxGah17xJGEY+YOPe
uDvvEglf5CSfavSwOCqyWxw4zE0qW7NbxdqyxWqRqfmY5riJdQZu5Oa1U03UfEF0MoYogPvvwKt3HgK7Rcx
XETcZwa+swmAlGnsfGY7Mqc6zSkcmbhi+c8UySVnNamp+G9T01Q15btGrfdJB5rP8AsVxjIjJHtXR7GS6HL
7VPqe1RSuOmBjirBkZh15qsAQcqvBp3zLyxwa6Oh5yepDLbtJL8z5Jp9tCVc7x7VIrZbPf1pJGfaSOveoNb
pjiwF0v+zWkszOMVhjhlY9c1oRSbZVHODWM43N6baVjZ5+zE4yR0NWL2yW9szE4ySOKhgbdHsHT1rc0+INb
RN1OKx5uXRm/Lzo4q1Ekl2tqqfOnB9q7/AMMOluzPNj5OBiud1+NdLuBcRr88/BPYUaTebxu3HaD+ZrysRJ
3cYnXQglaTPTbS4Ekvmvyx+6PQVopMCQz4PoK43T747Rk/MelbdvOSo3HmvN9kkej7ToaS2UDXf2pV2S+oO
K1dOf7IWeJAZG+9IeTj0rHt5unOa1LZxwK19vVgrX0FGjTm721NKS1E8BZRvydxU1TtdE8idpbaMKrnLHpi
pku2WT9y2MfrWra3alQsi9epFdNPHQkrT0PEzTJJVpqrH/gnMz6kZ9Sks7VvLEZzJIBnNOsNVe41GS2iv/J
iQcMw61zNz4b1yHxFqot9z2lwPNt5lb7p6lSK5bW7h9KsUe8ZkuJJdjxnqp4/OvAjSnTlz2uj7KjDD1oqnF
62XS/zPoa0CtbRs21zj72OtVxqUEk4t4Dvmzjb6CmaC5fw9aPjBMII/KvLrLxDc/8ACVXsFtC/mRE/ORgD8
a7MTKdBU246Na6anj4TBfWZVNfhPT9WEU1lMkeN6n5sdsVy8zDnB61L4WluLmO+89xJLKTgL2rQ07QJpcPe
kRj+4OTXqZFWinNqOh8lxdlNeu6dGlrZu/zSKegrM93G8S5AbB9MV111ZW92ALiFJPqKbBDFblYYFCqOT61
ar2Iy9pzc2xWU4B5bRVNSu92yva2VtaLi2gjiH+woFWKKQHOa0jFR2R6MpOTuxaKKM0xFXUtPtdStZLa9hS
WFxgqwrxPx38C1vnkuPDt+8RJz9mkPyj6GvdqKzlRpyfNJamsK9SC5YyaR8L+MPh1qGixSpqENxHInIYghW
+hrF8G3NrA5t5oIsk4yyg4Nffd5aW17EY7uCOaM/wALqDXjXjf4O+D4r7+1VhuIZpWx9nilIDt7DtXTRqwp
e7Y469OdXVyPOfC/hTUPE98IdKjUQA/vJDwqD/GvYfDvw203S9QhEqG8kQZeV+x+lS2tvL4N0W0s9JCIjkb
ywySfUmsi78W3kN+6STgLjJK8UVq9WorXsh0MNTpatXZ6tcaZp9zCYZ7K3kjxja0YIxXnviX4J+EtZDvBan
T52OTJB/geKveFNak1STYkztjqc9K2tRmu4Z8K0hjx61jCc47M3cYy3PlNpSABnmljG4HLZqHCBSWNQvN2Q
8e1dV9DzHozSUIBkHml4wV9ayfNdDwDzTzdsGxg/Siw+YuGNTnGantj8u1sbh0qi8/IKg5I7U6C6aOYMefW
s3E1jPU6XTGLtsIrpIJ1t0CH14FcvpsoNxGwzsc4zWlrrG3vIVPRlyK5Kqu7HfQbS5kXPH4jk8JyShgrI6n
PtXEeHr8TFMHCDoKvfEu/e28DSPk5aZFx6ivPfDGq8JhunauadDmTaNZVvfWh7Xp02WDA8V0VpPlQSa4XQL
oTopzXRGbYowa8yorOx3wldXOstZ13danm1NQ3lRnnua4qXU2toyCfnbpUdjqRJ+Y7ieprCUL7nRS0dz0Ww
uQxAzzXRWUoOM815/pd4jqpVuRXVabdZA5rkmrHa4+0gdvYhCu5Tg9xWdr/AIV0fXVX+0bNHZTkMOCDTtLu
MEc8VsggjIr3MvnTrR5ZJHz2IU6NS8Wc9qVjqVpYPHpc26JI9qRn7/0BrzNJb68v762kjktJIwNyEcux6c1
7d25rjfHOojS5bd7WNJrt2X9zjmQd6xzbAw5PauTVvmvkelk+NmpukoKTls9vvNHwPpQ03Ro/NANw/Lt/St
DXtasdEsnudQuY4I1Gcsah0ibUrpy91BHbWzRjaoPzg9+K5zxF4CTUjLMLqSadgcLMflrrwyf1aMKK07/rY
8nMqtRTnVa5pXvZP9fI5LwN8W7HX/iVLokMcvlyoxjmboxHoK9or5EuLm3+HXxi0+91u28iKM7HIHGG/iHt
X1raXMV5aw3Ns4khlQOjDoQeQa1wUVSTpp/f+JhHEyxUFVnDlezRNTF4Yg0+o5CEdWPc7a7JS5Vdha489KA
MVHcSiJAzdNwFSZGM549aXtI8zjfYfK7XAHgE0ksixRs7HAHNUNTuRb6bI+77nBNZmiXcms28zrJtGdmPQe
v1rneJvUVKPVGyovk9o9jVsbk3jNMDtgXp2zXJabcnxP4xuZwVfTNO+SI9mk/ipfijrv8AwjvhkWlhgXt2R
bwgdctxmtPwNoy+H/Ctvan/AI+GTfM3cueprpp0fY09XdsxlPnnZKyRR8TRpPZzsAcoCVrw/XrtorgEjnnN
e8arGPsjgjrXinjazKTFlGMGtY2aIndalnwH4nGm6kwkfakmOTXtVprUF5CjBlbIr5VeVo8kE5FdFoXi6ay
QIzsQPU1EqbeqHGqjjCjOdp3AZq5b2MSY5J+ta0CQseduafKkWeB09O1dVjz3sUFskJAJ4NSvbWkGCylm9K
eWAHyEYoSLzFbc3v15oego6mbcOCz/AGZM1RkEwO4px9a32tkSLOVUD361Vfa4xwD65qfMp9hmlX/lSANkD
0rrdbZbq1sJgc/KBkVyJiU5GRn1rW0e7Chba55j3ZUnsayq0+b3lujehW5XyS2ZhfG+T7PoWnWwPEx34+le
T6JO0N2MZwetenfHuUNJosQ/hjY8fWvK9POLpc9DWdFe7qdFZ72PX/DN8VVChruBdDyQ7HgDmvF9M1X7EwA
ORXX6NrDaoMZxGvG31rzMVh3B36HZg66mlE2dQvHlkZwevCj0p9pO0aZzmojFuJbr2FOm2Wto8shwqjJrk0
aseilY1bPVWjkVQ3NdtoWqFyuSc188DxlAl8RGWbL4zjrXpnhTXUuFUocMOorPE4VqN2jbC4pN8qZ7vpl5u
QYNdVptyJEwTzXmGg3u5Rz1rs9OuMEHPFefQqyw9RSReNw6qRujqqgms7eadJpIUaVPusRyKfbyiSINmoNR
u1tY9x796+kq4mjPDupU1R8/CE1PlhuYuoeMdK0qSaLUpvJdDwMZ3Vlw+OI9WtpZNGK5jOGDDJHv9K8U+Km
rRy+KPKnk
VfM/1WT1rH0XVbjR72O5tWLDpJGP4h6V5eBzGrFQ9p8P6H1+O4OWNyucsDUar2utdLrW3zLPx1Mvi6D7Zcq
kc9t8nlKOUP175r1P9nDxTHqPg+HR7ucG/sRt2seSvbH0rx74iXc11NZ6hbR/6LPw5HQn3+lYHhmx1q41ZN
R8LrNHNA4HmpwpOehPTmvQcZUqnuu63XzPhMqxjxeG/wBoVqkdJLs1ofcNVr9RLbSR7grEcE8V5bYeLvHMd
hs1PQUa6AwJImAU/UVwPjLW/iRexSfZoPIX0TqKuvUq1E4RjozupezTUpSset3fi+1jt7nTNSkEd7GvysvI
b0rF8JfERLuO40+
+Uxzwn5Gb+MZr578OavqVlfvH4hMzXDE/PNyf1ra1rUlLCSGTawHDA1jTy2o9ZVHe1i6mY007Rh7t7nuviP
xBFJazRJKDFOvmBs/pWl8KL+C50i7VXBeCTD/TGc18zab4kkiLwXLl4W6Z7V3HgPxUmlnUJo2wHiOVz1pYf
DVKFZc2pvVxFKtRfJpbodaZT4z+MEYbLadpqlvYOOletXk6gnng9q8n+EBj/s291RWHnXkxJ9gDXY3l84Lf
MK9ivO82lstDz6EUocz3ZPq1yNm3PGK8t8ZuGViOQDW5rmrTKTgcD3rgtav5ZlbKHminF3JqySOXul3O23N
Z0sbAknNaEhlJOIz+BqpOLgryuK6Ucoxr7ykLAnNZ02vSB+CR2qu8pBx+dM8mKUEkc0no7nOtSUa2xGMket
TDV5dhEbZbtWbLZjaRVdoniAZM5FPmQcrRPd3+oMCVL4FUTrmoQMA/K1o299JwHjDCrU8NvMNoUbiORRqNW
2sUbTxIWOJCVPrWza6yshBLcdq4/U9Oa2YuASlVYbhoTuVsD0ppobh2PRdesE8V20GJh9sgUqgY8OPT615z
eadLp955U8bIytg57Vu6ZqjjDIxVhXRy/ZPE1strelYrz/lnPjHPoamdJx96OxcKl/dlucFLaSqd65Ke1aG
iakbK5GWIUnn2rcudIudLc297Hgjow5Vh6g1z+oaYwnM0Y+TuK5KjU1ZnTSThK/Y9S0W5S6iV1OR/OqfxMm
W18MGNJMNIcNg8iuN8O6/JpDhSvnDqEPSpbnSvEHjnVk24WBm+Vc/LGteS8PyVOaTtFHtQxHtadoq72M74c
6PBd3rX2oJutIeAPVq6PW/EOn6RrEX2GN4yThwOmKn8V+DbnwpaW72cjNEABIf9r1rh9Yje/QysAJFHzH1r
pjyYn96ndbGDc8PL2LjrufRvhTXILu1jkVwQeetejaXqKOgwa+RPAepapo+rQWrljayDdgngfSvcbHxGkKL
IH/CvDxuG9lPRnvYWsq9O0j2i31ZbRAztway/GOsyzWP+jqeB8o9TXP8Ah65j12AuJsSIeIyea1r7wneXni
GwuhemLTVGJoBzurnw9lK1R+72PPzWjKnSvhnao+vY+V/ihBqN3eG5nDmeNsqcHj6V6J8ALa28YPI9/gvag
LLGf4j619OHRNKeLa1haupXad0YPFcFofw/0zwx4w1DUtBAhhvhmSJfuoc9FHpXsY1RVFXS8rHFkWIxeCU6
caj95O7/AK6k918KdHurC7tRI6Qz8oq9Iz7VzXw/0xvB2pTeF9ZRXsLp90LkdGGNp+teqR36DKJIGZeoB5F
YOvwW2q3FvPKjrNbNlXxjOazjioqKi+hnDLr1pVUrOW77+bOpiskMIjuPndeN3qPWs+
+0pFBIAIPqKz9Di1G/Mh1Gd4Lq3mJh2j5Wi7Z9a6K+l8tDvx7V6FCuq0U0rJmOKoKk2r6njHxK8NWdzZySP
CokTkMByK+etSaaCRkZjheBX1f4wkjltJAccivmzxbYql27AfLmvQpaHm1Hc5aORmIO7it7RZt4niDYJjP4
1g4CPgVo2Egt7iOUjaM8+4raXcmDtodNo/iy/wDD9navbuWtgzCWPt9a72Dxil9apKkgO4eteSXAw08JOUb
51H1rN0rU20u4McxY2xPbtWrpRmubqUq0oPlZ7Jdaj9o6nPesi6O8k5yKo6XLHfxq1rOjqecZ5+lba6dIqA
nv61nZLYbcpHPyxEZxVOeFvm5OK6iS16hV5qpPZZTJHIp8wJHnTp17+tIoKnjpSnvzTd+c8UdTFovLH5gyM
H2qFrck8gE1HA7RnIJxWnbuki54yaHYRQTS3kHyDBp91p7xssiZzjBrbjlEK5Xj3pouhcSBCBimBz8kfmIU
mGQeK5nVLA28w28oa7+WyBJyOazdXsA9q2V5WpKTscWhMTAjpWrZ3JBBU81kyfKSD64qW2cqODXVFkTjdHp
mga3Fd2wsdWAki6K5+8v0NP8AEPhi5sUW6iUT2b8iReePcdq4ixmOc55r0/wRrx+zNY3R8y3cbSp9K5cVh7
+9A2w9Sz5ZnjeqJ5N4WjBXnpXrnwz1dGs0RFCMODzXO+PPDRsLxyEzBL80TgcfSuZ8H6jLpusLCcje2AD0r
x8RTVek12PXwlX2NZN9T6G8VWg1Tw9MoAZitfO2o2zRPIi+6kV9GaS7z6M/mgZ29vpXhGqwN/aVyMceYf51
52U/FOmz085laMKkdyv4aivDYxwyQPI0LM6yAEkg9vwr0r4exRX2qxCZN6q3K9ia5/wjqJs47iHO1WjYZ9O
Kp+DfFUuj6hIRbPIofIZa0xlKdVy5UXgK8KcY83U97lkj0vXfOkiS3hkxhlGAfaurk8TWQsHVZ0DlcLzk5r
wfxN4uuPFFjFa+U1vGjhwxPzZFVdPnFiBNcTnjqzt0rzIYOe7Z218RRqJXV7HuFnrU7xKs05Y47cVxfxq1/
V7Twcy+H5zFcO+JmT7wT2PY1wc/xGhWTyNP/fSdC/YV13hKK48RwvFKvnFl3PnoBW3s3h2pMx541bqOh0Hw
V1KGbwBYSxzNcXj5+0M7ZfdnrXpVovzAy4ZSQea+VdT1bU/CmqzppdpLp1rDJjB6t9Pavf8AwD4jbW/D9td
yqyOw6N1NOtSlBKp0lsY80al6cd1ud1rsrQWAurcfvYvmA9R3FYWv6oZbCC/tjutpBg4/hPpU2p6kv2CTew
2hTXitx461Sxhu9K0rTJLmOTJ8x1O1fccV0YbFOVVyei0+85KuDboKLWt9PQ6TWNQadGGcivPtY077VKwZS
QfatTw3rlzqUTxX2nTRTRfekI+VvpVm9miZcKwU9K+ipVI1FeLPnqtCdJ2mjz250iK3LMVHBrndSfDkAdBX
X+JZfLDEHI74rhrq4ErEpk1so21MlPm0sTx3nmxR7v8AWx8Z9RVXU41Y5TlT0qzotqJbh2dcxqhJqxq8Ecc
UTRHKMoIralU97lCpD3VIwbC8n0+X907KmecHFdppnizUYYlMUwkT/bGcVxskWabBK9rJleUPVaucE9SYyP
UrLxxATtvbbYe7g/0rattY0q/H+j3Chj2bivJ1KTpvQ/hUfllSWXg1n7NPYt1WtyY8ng0gk5PrSuhXkmmiM
nkVBFx4Y4PvUqSOntUCjAPI4oHLfNTA047gn7x4q3CoJ3qRxzxWRGQMVchlIGM4pCOl8kvCsinINV76JfII
I5xzU+h3a/Z3jkwQDkVBrs6pZzyngIhaou0zWytc8rvHHnyAdmP86bAcniqRn8yVzngsTV63xW8ZXHOPKjU
tzgccVvaPdeVKrBu9YEBDD2qyk3lsAK6LcyOR6M9lneHXfCktvNgvGu5G7jFeNatZ/Y7+3uIwdynmu68JXb
PZTR7scYNZuvaU04AVsc8GvGrwjCo0epTqOUU2dn4e8ZW6aPmU/vNu3YOua86v5zLeyyJjMjHj8amEK2Fsz
Ftxxx9a5SXV0g1Fnk3BB+NcVPBxoycqfU76mOniUo1NkdTbRSp3Iz1xWhBAqqCAAK5weLtOSHISV5B0G3is
PUNc1HVz5cZ8i3PRFPWn7Kcnd6GntIRVo6nWat4pstL3JARcXI42r0B964+71PVNcn/fyOsPZFOAKu6N4Tv
7x1MVnNIT32HFeneF/hbqM0iNeokEP15qJ16NBaasqNKrVfvaI47wto0jyqkUbO57AZr6A+HtrPoFpI0uPO
lGNo7D0rY8NeDdP0qNVjQH1JHP5111vaWkQG2Jc+/NeLiK0qz02PVpQhRWupxF94e0zWNSF3f2qSyg5+atD
ULG8is9mh+TDKCAu/hQO/SuskjgOF2rn2rK1KM24MiNlR29K53fRt3sdNOpFt2VrmRYafJbK0mp30l3P6Pg
Kv0xRdX8cKYCID7AVla1qKbWkaTaoHNeb6n44tLY+Ws+8nnAOaqFKdZ+6jWdWnRinNnok2roWZdqknsAK4n
xTcxLMXhIU45A6CucHit7pSbRSjnqxpcm4hZpSWLdSa9rLsDVo1OeWi/M+ezbMaFak6cdX+RiaterPA6BsM
c81xtossVwwY7ua66/0yLeWDEVj3OllTvglyxPQ19E0rXPmoN/CakO220O4ufutJhVHr61gLK4XBYsvpV/x
RcG3s7WzQE+WNzDHc1zovtuBiohpqjeovs2NXeh6cE9jULxbjyKjhnR0wQM1IlwAMtzW6rW0ZhyEsIaMgqe
B29atowkHy8HuKht3jlHyHn0NO2GNsr1qlrqga6MtEArzzTSM8dqKKxAYyhSfWncEcADNFFNCH5A4AqSMFu
/WiigEX9PLCbZmq/ji8eDw/MF6yN5RPtRRUz2NKfxI8sVivSrVvcMDg0UVnBu52zSa1Nu2kIiz6c1Kk5LAA
UUV2xZ500j0PwPZ79HuJ2c7ieB6YrQnffbksBleKKK86vrUdzqp6QOO1yQ5KDjAzXG3FuLm5dGOMc5FFFZ7
RubUtWi5oegx32oRW4cAufvMM4r6H8FfD3RtOt0kliFzPjkyDI/AUUV4uPqT2ue3hIR7HoNrbQWsYWCJY1H
ZRip42y4NFFeajtkaMb4ANIZiVyaKKRSKouXFwzE8gYFLJP9oiKsODwaKKgqT6nyt8V/E2oyeJ7nSIZfJto
mxleprM0vSYUjR2JdyM5bmiivrcLFQpR5VY+Wx1SU6r5nc67TrNPLTGAPQVsxRoibQvFFFdK2OB6sxtSiUy
MR0rGtI92rRoT8gOcUUVTb5RxS5zE1K4abU53fnDEYPpVaS1huRnZtb1FFFWtrCk3cq3dkbaHzEk+XHSs0X
LUUUi4agbqROUODWhputyeYIrhPMB7jiiimpNPQtxTif//Z);\">",
" </div>",
" <div class=\"lgnd\">",
" A catheter is inserted through the external opening and is gently advanced
into the internal opening. A seal of fibrin is injected as the catheter is
withdrawn.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Bradley J Champagne, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_26_431=[""].join("\n");
var outline_f0_26_431=null;