<%BANNER%>

Effects of an Eight-Week Progressive Resistance Training Program on Balance in Persons with Multiple Sclerosis

xml version 1.0 encoding UTF-8
REPORT xmlns http:www.fcla.edudlsmddaitss xmlns:xsi http:www.w3.org2001XMLSchema-instance xsi:schemaLocation http:www.fcla.edudlsmddaitssdaitssReport.xsd
INGEST IEID E20110320_AAAABU INGEST_TIME 2011-03-20T11:30:47Z PACKAGE UFE0009465_00001
AGREEMENT_INFO ACCOUNT UF PROJECT UFDC
FILES
FILE SIZE 1021 DFID F20110320_AAAXNS ORIGIN DEPOSITOR PATH gutierrez_g_Page_13.txt GLOBAL false PRESERVATION BIT MESSAGE_DIGEST ALGORITHM MD5
0925fda9914acab68905620a9c43d942
SHA-1
75d2a95942aa42916783cb92b875ef2a895ac919
1053954 F20110320_AAAXIV gutierrez_g_Page_46.tif
547ab080e3b86bd38ff3dc0379af7ad2
506b631149620f0e3a34e0515c9c29c8f6fbf68f
115431 F20110320_AAAXSP gutierrez_g_Page_48.jp2
d815f08263cbaea39116ccc94c600a9b
c855267dd513148701bee8e05cd96868e0b410bb
1956 F20110320_AAAXNT gutierrez_g_Page_15.txt
6bcb9a39cf90a3b05fe38b1601c7f54f
38f6383b37b5d9568cd252702ec2f4a42e599237
66662 F20110320_AAAXIW gutierrez_g_Page_33.jpg
3b4146e244cddd484a352ebb1c37bc06
70987796b712f5a250d4101da48078e0b8dfa301
48551 F20110320_AAAXSQ gutierrez_g_Page_50.jp2
15d805c01fed1abdaec53759d009ec77
27d808add76d34cb824bf5117217ec742dcd31f7
2047 F20110320_AAAXNU gutierrez_g_Page_16.txt
ca7359b8b4b72e1c24e6876678ab8f86
dda2353a13d8140b50929f07c116f2ba1f6973b8
847998 F20110320_AAAXSR gutierrez_g_Page_53.jp2
7c4c0d497ccffe91f8148bda359ce7e8
87fa756efc4f3afc294ef23092b9646651eb48b4
50588 F20110320_AAAXDZ gutierrez_g_Page_20.pro
871ad894d0b97d46d35629287eab8785
ccfbe35085958d0d0233fab8c52ef83ce216bc9b
1684 F20110320_AAAXIX gutierrez_g_Page_31.txt
053e991ad2c8f04d778be0be7c95025e
579d6597d69661b67d1ca46b4d66060e1e325a12
128319 F20110320_AAAXSS gutierrez_g_Page_57.jp2
719cf7217b4359dcf9aae29853ce5fce
cd8f3e003a44567bb8c90f212962720d8883e82b
1893 F20110320_AAAXNV gutierrez_g_Page_17.txt
d5fd0e3598cc5483a019f011da8999b2
204b748d4538951c1f61bd851b582bc9bfe3adbd
41483 F20110320_AAAXGA gutierrez_g_Page_25.pro
fcb5bb25f1a8c08b1b3b0d9120cdfa60
38c427a1152e73af48575669a2d49310f5a860e9
105047 F20110320_AAAXIY gutierrez_g_Page_17.jp2
7d212c8269b4b5808182a7125b06c408
64a9c4f1c80a0e37b781cea588f66315b60e5ff9
2550 F20110320_AAAXST gutierrez_g_Page_01thm.jpg
729e780f655aa6bdd8a8a3d4377c4a72
276e304b6eacebe8c2c6ab058c03b60a0d587a8c
2028 F20110320_AAAXNW gutierrez_g_Page_18.txt
d545b6e40113ccc8e33a33047bd5be76
9911b7662059ff1b42ee5327778feb00ca4e84b6
58703 F20110320_AAAXGB gutierrez_g_Page_57.pro
b8d02249560b01c56a5367b49c6b3f82
d98766b4db584e043a1c012e6212ca909ff20d63
4237 F20110320_AAAXIZ gutierrez_g_Page_04thm.jpg
d14e99eb7a168a080ab68e9c282f839c
7b13215d631fc0a025d105c2245c146006249c3a
1451 F20110320_AAAXSU gutierrez_g_Page_02thm.jpg
6f6a648bf0154aeb533cc6b836b49111
1200c3d45fb3688ff84572ffc7bb8c6c96477fe8
1967 F20110320_AAAXNX gutierrez_g_Page_19.txt
ac237996c4ae9bf08a685ce712076a81
d1a596929ae1fd17b9ef1ebfac4e28a073066a93
99243 F20110320_AAAXGC gutierrez_g_Page_46.jpg
b946abb2a406f1f709b797f3939e8355
82ded11d4654da3c58ede45acec776c9c072c650
2631 F20110320_AAAXSV gutierrez_g_Page_05thm.jpg
09fcd78a52618ae0621bd97106c88b40
c6c8e03191c9534bb94e5f68225ed7be5ada30f2
2019 F20110320_AAAXNY gutierrez_g_Page_20.txt
be1cd83da123f4e8f305a833d0288ed3
d293a890a9d56f7a6a78848e0b1eccface63bdd6
6177 F20110320_AAAXGD gutierrez_g_Page_17thm.jpg
7a2fd1ff621f251adda64ec657ab1c90
7ec49a60412eace3bdbd141ab68a0efd70320a48
3154 F20110320_AAAXSW gutierrez_g_Page_06thm.jpg
a0d6f3cf911e0ccd31590f3b55e846fe
c761816fedc169bacb3dac98a7eb3ca8ae82bf79
4954 F20110320_AAAXLA gutierrez_g_Page_51thm.jpg
d6ece5e332232bc9b053e0e7190f752f
f9a5ca3f97cb6e5764e3e58dec7331d311888c53
1955 F20110320_AAAXNZ gutierrez_g_Page_23.txt
4b72aea542d2eb93e688aba2806e19e6
e6c304d87203a232ba76164d8ad4db072f50fe98
25271604 F20110320_AAAXGE gutierrez_g_Page_53.tif
8baf7fe2a7f1eb082805676cea24c5ff
246e5abb5464f97ecaf2b130bab51cd90aa94837
5838 F20110320_AAAXSX gutierrez_g_Page_14thm.jpg
a42b7fdd4e165db11fce8430750c97fe
72b4b6dcdf3f15ca20a93c5581ee8978042ee595
50635 F20110320_AAAXLB gutierrez_g_Page_40.pro
072755ff1f582403cc82902c95ba15f8
48070e5c70741435537b7dc4a6db3038b6e81363
95986 F20110320_AAAXGF gutierrez_g_Page_10.jp2
46619ad5cc16f24ea128fdfd5c434913
fc3c7029b0bbd5d100b2bb19d192a9b3e9e32dea
6377 F20110320_AAAXSY gutierrez_g_Page_15thm.jpg
b2a4501b63b860ca2dd817dd2319379f
f51ecf829ced89cd2fcc0d2acf1e13ed725fc161
25139 F20110320_AAAXLC gutierrez_g_Page_55.QC.jpg
ddd9d5973fa8bc899a5052f5e96d9618
441a588ca947b3b20888cc88afd67ec92f1d55df
109646 F20110320_AAAXGG gutierrez_g_Page_20.jp2
c56b1e1ce1602f35f82003ea6e67f2e8
89ceb09ca2cdad4c2bf4d85c34a4f5cbf06f56d7
24071 F20110320_AAAXQA gutierrez_g_Page_16.QC.jpg
1a854cc1a8a4c4a42be208d00428959d
2f25afaab66fc86621ddbe5cd9a28658da99410e
6685 F20110320_AAAXSZ gutierrez_g_Page_16thm.jpg
97b1ae99723142efe60753b9ec1c4931
d122a32b1d1347b153c1f387d99d7c462f845159
F20110320_AAAXLD gutierrez_g_Page_37.tif
60fd3c9c65cb5197eb33e61a0e3b34db
8701bd05c15fce26d2dbdb1cf9740904608f0279
628 F20110320_AAAXGH gutierrez_g_Page_03.txt
1f42436c54e2268c4e3a6b55e79ffde2
bfd20659e99b346eda1aa67b540830aad51ad5a2
22555 F20110320_AAAXQB gutierrez_g_Page_19.QC.jpg
ff7d5a885d2d4ff8a9472c7383599301
e7b397613c2dd25859d241bab4dcf1e07d356d98
2354 F20110320_AAAXLE gutierrez_g_Page_43.txt
793891c819f81b165e696a2555405f0e
abc51ef86e86acfcb5a059180affcea5900507dc
74646 F20110320_AAAXQC gutierrez_g_Page_21.jpg
40e6d2aa1398be39c93670dccc74e7cb
7fe3c8f3df3a1ccfa9cbb6752a2be7b4582dbeb6
F20110320_AAAXLF gutierrez_g_Page_35.tif
ca38dd385eb8f2768080f65483aad9d6
e6b6ebcb260d3ecc0475de38f51487952923cc24
114131 F20110320_AAAXGI gutierrez_g_Page_39.jp2
ee30f575c1739edc8de7aab641da516e
10b2c27edbe18250f808f2b77ae7d911c683efed
22862 F20110320_AAAXQD gutierrez_g_Page_22.QC.jpg
acdbf5f852cf3c3974c0bec56e055823
4979490af47f037a59f03af56d4122685e57c4e1
119240 F20110320_AAAXLG gutierrez_g_Page_54.jp2
d95932abb80551ad33fb24f4a0039486
e9f869815b778ad4c97c2a2a293c6f4e059ad03a
103425 F20110320_AAAXGJ gutierrez_g_Page_12.jp2
8f153aaed58099d8701215b700d8e732
5a4e12f7ac62484cce5606d085a624f08c356f8b
70409 F20110320_AAAXQE gutierrez_g_Page_23.jpg
f18a9934757f703d9e578dc47b6924d1
1083a80f2fb606633e38498aa49a6c138d43dd2c
F20110320_AAAXLH gutierrez_g_Page_10.tif
0aa2e87b14c6672e5371fccd4a58315e
d5a48b96e80d953f30d022db74f271941605122b
63700 F20110320_AAAXGK gutierrez_g_Page_10.jpg
9805fe4514800171c0e3975cd2df7bd4
fc7ef69d31a2814d989188f070e450b67c3dcb6b
22710 F20110320_AAAXQF gutierrez_g_Page_23.QC.jpg
c112ed937c99610721d72a3bcbb4dfbd
c60479bf01ebfc667b6974d3ca75d8ff2d1dceae
F20110320_AAAXLI gutierrez_g_Page_29.tif
cc26ea1de1c63780045db30c6a8ec16d
e5267ba539f1517d3563c61438c1a106ac3bb988
95334 F20110320_AAAXGL gutierrez_g_Page_44.pro
6c9470e0937cef91e6606e53e4d36d60
90263bb82e439b81e9753c5cf65018ba732b40f3
31237 F20110320_AAAXQG gutierrez_g_Page_24.jpg
6900d09d26b78ce88b662cb9cd394bda
3e64cff6e9f5e26628f357009ec295ddca959965
5412 F20110320_AAAXLJ gutierrez_g_Page_08thm.jpg
0cbc0bbe44aa8a006d1e7926e0f0b8e5
a45064af3cfd8032942baa4fd9cefe20e9f5af7c
2378 F20110320_AAAXGM gutierrez_g_Page_57.txt
bf9ff87c3343725531a91825b6f21946
a7a96fdb69fb3fcb4bac6731ab2e6967b8ec9ff5
68456 F20110320_AAAXQH gutierrez_g_Page_25.jpg
8d0feb8f75416fc85b89933d4b0647db
880ef279322dfe6f4bcf1c2d07c3308758bd9346
52660 F20110320_AAAXLK gutierrez_g_Page_39.pro
6317a0ae222f97c89fdffdc4da47f8ad
5d4dc40c44704750b5414e706272aba0c5082857
24230 F20110320_AAAXGN gutierrez_g_Page_09.pro
9c7ccd9be64b46130f428ed57aead4f1
275c512611359ac140035610b3a67651490cf87b
68195 F20110320_AAAXQI gutierrez_g_Page_26.jpg
ac6bd9debab466bbdd234eb84af1a2f8
1a0723724876ba8c8900c5ad962af74fd41215ab
F20110320_AAAXLL gutierrez_g_Page_51.tif
197bdadcc3b8a174e9517c32de366845
1255a005f4b20700c9eba135a465bef5dc2890c9
41332 F20110320_AAAXGO gutierrez_g_Page_13.jpg
747f2f1ff56e0b9b8e7e7147c36c0ad1
93604b770af9df72bdf9d4e4c6bbfee94be4f198
60036 F20110320_AAAXQJ gutierrez_g_Page_27.jpg
e6965ede715e5067fa0594f83f4be929
27609441eebe332c8f9fc2b5d19983eb7e5a61e1
46107 F20110320_AAAXLM gutierrez_g_Page_26.pro
7b622c881e13300254a36649c11b525b
f3e528b24ab2e3c313aa1b2d969d0c9bf03d97bf
107518 F20110320_AAAXGP gutierrez_g_Page_11.jp2
a02b6497fa79d1487b44048d70653b98
71c90161f1def014c9cca0f69912d6e6d603d614
29463 F20110320_AAAXQK gutierrez_g_Page_28.jpg
f35e03969ea68ad16480885d726f7575
e3d0a371d9e8e01aa7ba23616ee16a093e4e6da2
23961 F20110320_AAAXLN gutierrez_g_Page_20.QC.jpg
5dff7177f94360ba7d22c692e5efa6bd
b4c27ff639e0f56d47822c465560ed0783a39fa2
8420 F20110320_AAAXGQ gutierrez_g_Page_35.QC.jpg
31b13f743aef62487d444826b9a9991d
b6202ba9b5e57841e6b2aab82348895662d082d7
70187 F20110320_AAAXQL gutierrez_g_Page_29.jpg
8d36cc101b6f8e0a90fc4d5f9c5963d8
f02cce02fbc4ed48f9a864000fad8fa61066d16e
6232 F20110320_AAAXLO gutierrez_g_Page_12thm.jpg
94c54069cccecdc75c30412dc2249231
ee6afedaa2b9082abe192e5bba91ff7be9566416
51740 F20110320_AAAXGR gutierrez_g_Page_21.pro
42aed033a95f383cbf69c9d24411b073
1905a14228db97dee95dacc095d4289bf6abbd7a
20850 F20110320_AAAXQM gutierrez_g_Page_29.QC.jpg
503f8d8f489853c0de2d027b3e1a2588
13e1beda4ff287f40cfb007b8b5ca227753cf1de
6052 F20110320_AAAXLP gutierrez_g_Page_29thm.jpg
240b5fbecada42e385c2433edea9d8d1
786d2867b3be139428c655f8bac583b1f14f93a6
F20110320_AAAXGS gutierrez_g_Page_34.tif
780240eda2624041dd2560725ccfcdb5
52486c515366f7e8c2052831aa794ba0eeb7cdf4
72532 F20110320_AAAXQN gutierrez_g_Page_30.jpg
55ae8c70c9f03fb3462d94590865c985
de70346ada71c2ec043cb06992994c2868cadf51
88422 F20110320_AAAXLQ gutierrez_g_Page_55.jpg
d0f7ab458944561927293da5dbfab604
5df11d168572c6e4cc1032c775767e47c0261ae4
40547 F20110320_AAAXGT gutierrez_g_Page_08.pro
b7b510747359f09b4f5e676c165a39de
1b0954facf8fe4800c09f1da97e768198a773621
33595 F20110320_AAAXQO gutierrez_g_Page_32.jpg
67923567cbb97ab95a8fc3990c4148a3
a602cf09b75bbac05f25747020c2b81ae8865a77
F20110320_AAAXLR gutierrez_g_Page_03.tif
a1ec76d6169da23ae08a4de8a701080b
63cecd4d8912d2e2c9da53789223a2972cbbbcb9
F20110320_AAAXGU gutierrez_g_Page_15.tif
2d9d1a2040ebad6fbc9b3ebf642ca1e3
de3b785c89e823b6f3f93ba20a9eb1eabc217628
10857 F20110320_AAAXQP gutierrez_g_Page_32.QC.jpg
786d45c93294b051d432d94dc23c9106
0ec7ef7f906a63dce1d2f6db25186974616109b2
2008 F20110320_AAAXLS gutierrez_g_Page_33.txt
67a7ae4a6763792a82b1ac99136815fe
3ce7d0a9c8b3e80c946a6ef04a46b133f5b6959d
20403 F20110320_AAAXQQ gutierrez_g_Page_33.QC.jpg
926768f288d220e5dbcc548e74175ed6
20959bc1481bbb05e6a7de27f3cee9d998aba593
46828 F20110320_AAAXLT gutierrez_g_Page_12.pro
1aed87bfa591bf8d0bdfcc59e5e7f421
5c33ac97b567c031feac1af90d276ee4b1c6b37b
836 F20110320_AAAXGV gutierrez_g_Page_07.txt
618fa47fa28040417cb6e5a3bccb3aa2
1bf62bac42f90ac62ccda3f635648d8cf8e2420b
6195 F20110320_AAAXLU gutierrez_g_Page_19thm.jpg
0f26a8c9b44bbe7196304e237addc301
54eadcc92909042cb97303663fea878a03cce83a
2636 F20110320_AAAXGW gutierrez_g_Page_35thm.jpg
800b39df36e96afb9b825d361bc9393a
eeaae46ac4e84cd006ce1783cf15864c71f5c8b1
22941 F20110320_AAAXQR gutierrez_g_Page_34.QC.jpg
a40773fc86d2ed206c3ec785b73ad5c5
6a31d9101935550577d51332aa05f6abff53f8d0
3385 F20110320_AAAXLV gutierrez_g_Page_28.pro
7a5a840cfde9945672fd957ab504d2c5
987e10ecfe09214a13db31b21005eccfcd665f63
23452 F20110320_AAAXGX gutierrez_g_Page_15.QC.jpg
a256ecadbe09746ccf0a18f15e7b6f1c
9993d4e8cdd4ac5c853fa7d111a52a01a3977b53
26135 F20110320_AAAXQS gutierrez_g_Page_35.jpg
600c15fbe8702210acce851b394619ee
8c68f49d35bef38295252cf1155730c8b5bd2290
7675 F20110320_AAAXLW gutierrez_g_Page_44thm.jpg
74a3439f7cd3492cd3d2f94d861ec84a
eb9befdb2bc75f9f191cbf72fe9042f51fe07756
3750 F20110320_AAAXEA gutierrez_g_Page_09thm.jpg
1725541c85d639b5dc1ce621962a1334
b9cba6d28182480c00843cbc20de81fe09662144
F20110320_AAAXGY gutierrez_g_Page_17.tif
fff81128059d0f7c99124f406af35b70
7606be6edc7e7a8c5ad5bc7ec058095c83998384
20769 F20110320_AAAXQT gutierrez_g_Page_36.QC.jpg
78482d9591381b01de80ed3a1306f863
e7dddb36dcfd81860e6a1534edb8c87fa79cbe2b
F20110320_AAAXLX gutierrez_g_Page_47.tif
43ceadacf6d8b64139d4eb9544dc7632
6ce3a364e3af0d8df7517fc3e4052f3f3bee36eb
F20110320_AAAXEB gutierrez_g_Page_49.tif
f9d61c0f802f1c9f208faa19ad51cb62
e0f8c4b9e0b26aa318b7f01efc296ced36c5dfdf
16778 F20110320_AAAXGZ gutierrez_g_Page_53.QC.jpg
3ca5212efc216fbdadb196db7b232143
b2304a9b1dd26b6c54da2e92e953fe5fbe4b1423
69347 F20110320_AAAXQU gutierrez_g_Page_37.jpg
95d769c43c0f7da3d1b52180d00894ec
da3c4f809f4721ca95b7adc468918d974c1a735c
6977 F20110320_AAAXLY gutierrez_g_Page_55thm.jpg
6a8358b22d800ea5666ae8bb500c3f22
7b70f537432ad805be393190d01107482d9745a9
20709 F20110320_AAAXEC gutierrez_g_Page_10.QC.jpg
ef06d8a1964cefbd0d73447259bead12
c9fd41499522e814b7e327c05daf9cf119e3465f
74769 F20110320_AAAXQV gutierrez_g_Page_39.jpg
7fe4b922aa51c570a34a0458ce770bdc
5ee423bdcc99dd83bdee2455f7b3c7d4547e6132
53004 F20110320_AAAXJA gutierrez_g_Page_51.jpg
7d6be3231a22a2010edd5f13b6430d27
a0b870b520703c843322b57cb7576b265422e9c9
2066 F20110320_AAAXLZ gutierrez_g_Page_39.txt
05c626f624a558437f4350007daf9fa3
e9d30eaaa3be4615edcb7a575d50499026f5ef53
3425 F20110320_AAAXED gutierrez_g_Page_45.txt
6a7b5c4880a1aa229af863f4f582c3ae
f010bc1c7afb5df2fb9a88e13f5c9d8ddfe8b8aa
24095 F20110320_AAAXQW gutierrez_g_Page_40.QC.jpg
e6045d243f63ba627a89a894da01c238
124996ccb7196a2239817d097dfe5f5eae8fae52
111624 F20110320_AAAXJB gutierrez_g_Page_18.jp2
46f831b571d417ad800fadc224f39038
45c49d690389148b633126ade0802e3b068ab9bc
47977 F20110320_AAAXEE gutierrez_g_Page_17.pro
f29af937595dd4f769985e0246f67fce
161911acb3876633e5973cb646391e80581b15de
35380 F20110320_AAAXQX gutierrez_g_Page_41.jpg
179bb2386fdbd4c5af68ad7dc4c0644f
d1f89007a752c5c58c52dc90a9e708db986cc45d
6593 F20110320_AAAXJC gutierrez_g_Page_38thm.jpg
0cee82d50053d478d50df2a161652119
3f792da22edb08fc373ec67146663c84439e115f
F20110320_AAAXEF gutierrez_g_Page_12.tif
bfccad3b103f92997832fe4c7b02faaf
86df9c6efac56c1c11a56714060f79c08751a7db
11372 F20110320_AAAXQY gutierrez_g_Page_41.QC.jpg
c32d6f7f245640c3acf3e50adf02aa3d
a31f9483a78dad28f4fbef5065b71d2114802226
F20110320_AAAXJD gutierrez_g_Page_55.tif
fe6a59974824a7fe1b3bcacfde0a2e73
05f7432a4a1f9c286367508613ddf5823c75237c
2036 F20110320_AAAXEG gutierrez_g_Page_21.txt
2132da1ff99124ef2767535c452e01d8
242013ae47115732fe1a7a6e0c7585edc6d070f5
724 F20110320_AAAXOA gutierrez_g_Page_24.txt
b7a1c25d5711c4cf7b40b2e6064e005b
1706071673657c7d327b42d7c51417522a7b11dd
43132 F20110320_AAAXQZ gutierrez_g_Page_42.jpg
a96c8db792c997c9b28ba1834e02f6f1
c90b93be581eaae06cfe496e26eb454e5653241c
48994 F20110320_AAAXEH gutierrez_g_Page_19.pro
de2575621c61446d9fd1d2186f3d114f
12ffbc9c1b0f2555ad1f12d1e04516b7ddbe2fbe
1177 F20110320_AAAXOB gutierrez_g_Page_29.txt
eea28f34458d4c1c879fda1afbb8bf0d
0aa8b9772f422feeaa9f2b2283c355c24188fc05
69136 F20110320_AAAXJE gutierrez_g_Page_22.jpg
118ac9feca1ba869061ea796165c828f
861e460f9f44f4a3e80f6d0a23163f1feb3946fb
6583 F20110320_AAAXTA gutierrez_g_Page_18thm.jpg
596af8bb59a005154e0e0fed58774f7d
bab0725e68a73fb6e4779ecbdf3ce7ee4de157ae
9993 F20110320_AAAXEI gutierrez_g_Page_24.QC.jpg
dd810bb77086d8254f722d3c0a2d27b8
649aadb760dfa783b115d46e946f962b71c63795
818 F20110320_AAAXOC gutierrez_g_Page_32.txt
21dad85f48501167dd92cfa16f43b4df
2fe52cff9a6129e89b55689a95b1af0d10f99c24
82765 F20110320_AAAXJF gutierrez_g_Page_43.jpg
1313b30541e0937bc7ad43f91c9faa87
017d023a4590a3286d8fef5e875b56f4901c260b
6534 F20110320_AAAXTB gutierrez_g_Page_21thm.jpg
ee942b204b726c8f656b83a24934a42d
d56d0217aca9c01e790185810a8ce74130be4e3b
71576 F20110320_AAAXEJ gutierrez_g_Page_40.jpg
d1791f93f503c16cecade5c106107a67
c6c3d28698874a7dc59c43e7979fa15ea5075922
F20110320_AAAXOD gutierrez_g_Page_38.txt
4cde91ba6f422f106cd157eef8bad6e7
33c9915aa6e15fe008ed81b83e8d827ceafe6a5a
68937 F20110320_AAAXJG gutierrez_g_Page_19.jpg
ff50fc4c93e1777f645135ef2939a867
5b27f99e87ffbfc3165fe9e0f9ce3c52f54d453b
6027 F20110320_AAAXEK gutierrez_g_Page_36thm.jpg
059bf2901da9e01f8a511bc5ebf0eceb
ef1bb900f6c4b5a698b61d3ac32e24cd0688c1d5
2062 F20110320_AAAXOE gutierrez_g_Page_40.txt
d90ae61ff87a6531f3aba4ed8f256e14
2cf8edd80fc49cb0a6fb8bf6a34af8e24adf3839
27394 F20110320_AAAXJH gutierrez_g_Page_07.jpg
c287aa692fe8246d44f57b52b3e157b9
b1bf7c5ba3f45251822f191b93e8b3760367b79a
6527 F20110320_AAAXTC gutierrez_g_Page_22thm.jpg
9ad8c626f9c88c804ca75cc39974f228
02cb69e006cf3288c6addb683eb74d6c80ee6825
51474 F20110320_AAAXEL gutierrez_g_Page_16.pro
47ca3f69a4a331b9cc411f5840ab9640
7626f9f4c82b8b854cf52271775f0feb07143609
848 F20110320_AAAXOF gutierrez_g_Page_41.txt
c84541132b529ac9990ce607a3852d82
026977c809b94135dd460526fb6a47c93e4deb43
131226 F20110320_AAAXJI gutierrez_g_Page_55.jp2
4839914b98ae130439bf050f90ba889c
9e1f686a878d73d740cc106cf40aeca37428b974
3286 F20110320_AAAXTD gutierrez_g_Page_24thm.jpg
cb0cebaea12c95b0c42c0e149297c959
8183e0b478ebc1b7378013fef7dcdbcb30f93376
1762 F20110320_AAAXEM gutierrez_g_Page_08.txt
45eb45df331e965cff11348bc1055453
cbbc196ca2f9e2fb8354a831f36b4e906c028e87
1053 F20110320_AAAXOG gutierrez_g_Page_42.txt
c2f96397c3ff467949aa73fe12d358bb
f27294098365149346d6f61f25ba8d2e79e86757
3488 F20110320_AAAXJJ gutierrez_g_Page_41thm.jpg
753fcecc949f343d5a211cd9bfbdafc5
208ad0f33b9ef71ff6ccf053ade26d6f07c2c1fc
5459 F20110320_AAAXTE gutierrez_g_Page_27thm.jpg
3b7d6bf18c17222da18b8557a5e70a6e
a0a50633675e5da606b95700a4a2b61f230a828b
F20110320_AAAXEN gutierrez_g_Page_39.tif
ff25d989019ecc796dafefca03cca44f
e99f67e884759dcf505891ff22f099a79862cafa
2924 F20110320_AAAXOH gutierrez_g_Page_46.txt
6f6532d74baf998b06d82c38f1f6476e
054725d9f6c89879805c12cefb5c0045703b46ff
125227 F20110320_AAAXJK gutierrez_g_Page_56.jp2
af6114dda6a33989a1085ca3bec41723
ce5f0612003b60be9e04931d766aa72bfae2cdd8
5389 F20110320_AAAXTF gutierrez_g_Page_31thm.jpg
2ca504ef0d9ef3baf7396c69de11f208
355c2cb37e597454643beaac1bbc2789bf2ed416
8540 F20110320_AAAXEO gutierrez_g_Page_07.QC.jpg
3e667f35b104571ecbcb65ef0bff5193
0b6cc93d08e111f02ff616c7484b1ea43ef19dc7
2233 F20110320_AAAXOI gutierrez_g_Page_48.txt
7c152b0af61ae94c8823bed9628ffb2f
bf7c47a1b6bb34312c6db920fda358024e67e2e3
31341 F20110320_AAAXJL gutierrez_g_Page_44.QC.jpg
043ce575863c0c6a4670dec74ea6d3f3
f9b5a602606706b84086cb7c1720b519e8d3d040
6248 F20110320_AAAXTG gutierrez_g_Page_37thm.jpg
e17463b4e9793de9941d45fa7746e639
8eb0848606b94ffc98ad314f7debe3e9709914a2
F20110320_AAAXEP gutierrez_g_Page_28.tif
f98f44b4ba3acf8e3cc1082a351f26db
46feb194fab19cb41ba76b096b58209621eec998
1556 F20110320_AAAXOJ gutierrez_g_Page_51.txt
52635beb22bfa485a99568f0ddcdb07f
f09206bdd798095ef24e0eac6186b163d88e2fea
5991 F20110320_AAAXJM gutierrez_g_Page_10thm.jpg
636e23441f43f42c7e4026299392a976
e3b48137b8745964668e1f940863a529914688ef
6698 F20110320_AAAXTH gutierrez_g_Page_39thm.jpg
ed10f3040c4d94547d60a31b5ba9fe75
abb658db9283d0c2de0775b421ace72903e188bc
35579 F20110320_AAAXEQ gutierrez_g_Page_51.pro
7382c0aaa0eb44e6b6368b82c4b581e4
2e5e8f5f1b63c738cd26f75d5f2503a7e243bf91
1381 F20110320_AAAXOK gutierrez_g_Page_53.txt
d96774289f1c05b83ca8eb558521a4d0
57b83b4461ca86d5dea108d510ce3df067445d6b
43214 F20110320_AAAXJN gutierrez_g_Page_14.pro
278291fa3368443f7c29f4b16405298b
6e00d0af0b49822913da47b3ce29db9d2a809499
6053 F20110320_AAAXTI gutierrez_g_Page_43thm.jpg
42ec7099ffeb786be262d1b0caa5c3e5
55d1e224ffa9f444e58dd4a717a8ee4b964410ce
F20110320_AAAXER gutierrez_g_Page_04.tif
3ae61abff2112ccfd8f5f8b50b349f0e
7f31031619e75bec522471d680cfb778f9b0915a
2390 F20110320_AAAXOL gutierrez_g_Page_55.txt
146de82dd4db113063cf906c8620d134
4d2417bb7a2fbda6678533d24295547af7a0d8bb
19509 F20110320_AAAXJO gutierrez_g_Page_32.pro
cc92c9d37811e9bae2354ba842509610
0be0aa5833522218bcf0309359b58bfd49a26b3d
6697 F20110320_AAAXTJ gutierrez_g_Page_46thm.jpg
9f48c5e48daa65919fdffaee0bac24e6
44f97256acf1ac375f29310ab14626e0927396e9
1900 F20110320_AAAXES gutierrez_g_Page_26.txt
1d8f31f79d94e244125d6549bf0eeb2b
d0c1c1a4c1ecd6ef6f2895f39e03f21805bb32ee
2306 F20110320_AAAXOM gutierrez_g_Page_56.txt
e860a381c3535a34150381e53056d0b1
3cfe3f8e3c42112be07b3617b1ded0b4fa19718c
F20110320_AAAXJP gutierrez_g_Page_07.tif
a03cad754411d61cdbab1f74fa6ac27b
45cd206dc62ed1a216724d95185a3a87ab6a3beb
6497 F20110320_AAAXTK gutierrez_g_Page_48thm.jpg
056710fb6120afb49f05160bfd64efba
d7020017091f77ce153d3bac46f6cfe8cdb9568c
727 F20110320_AAAXON gutierrez_g_Page_58.txt
928bec72ae2a02b27c92e7b4c841a296
27c62f4b83877bb79550174bd36a91abe786c360
1452 F20110320_AAAXJQ gutierrez_g_Page_49.txt
cb14d11e504fa2ac2824558f89cf2016
c3f7f66cbd73144bb3fa905afc3338bda016483f
4692 F20110320_AAAXTL gutierrez_g_Page_49thm.jpg
03bf9e5d853c16c92851729d7fc9337f
a992f7042bc1f68c2f6f64d0b112f4122ab8b507
22330 F20110320_AAAXET gutierrez_g_Page_12.QC.jpg
70ad3639e2c7687451fd2ab89b406402
ec0e52f42eba42f8882f4ff2b9aa4114f683e039
1437 F20110320_AAAXOO gutierrez_g_Page_02.pro
500f4aed13bb222983d3b72721a7298e
c23c18ed9da3beac54570b3ddef3f822ca951d42
573835 F20110320_AAAXJR gutierrez_g_Page_07.jp2
f6bca14e6ba24cb2b7e70db2cbe7dcc1
92a409d628f826022f89a3ebbdd4834becb17394
3177 F20110320_AAAXTM gutierrez_g_Page_50thm.jpg
0ae1bdcb69ca4f28356fb12e1ecb2ab9
bc530924d3295b86779af6996a895075386d97e7
22983 F20110320_AAAXEU gutierrez_g_Page_38.QC.jpg
d8398f32bf68455f1c7b8de731649150
e4b1bb329bc2d1199da959d6da1bcbf0218a864a
14564 F20110320_AAAXOP gutierrez_g_Page_03.pro
e1342d35faaf20c9aae7f1ae3bd3331f
37952b6fc9c9f741c3e47b4815930572c6b96c54
28777 F20110320_AAAXJS gutierrez_g_Page_05.pro
03a5a39877ad6b9cad5e6cad83ea44b8
5732198a7080208cde2f0ee39e62495573acdfc3
4601 F20110320_AAAXTN gutierrez_g_Page_53thm.jpg
fdd47b9730a48039eb0abba8f77daec7
e8901f22545ce1b5ce9660fc529236ecc50ab4e9
20509 F20110320_AAAXEV gutierrez_g_Page_25.QC.jpg
3bcae31d03b6ba1963815f073bcebe47
73bba0dc7a7965cc399ca70d54e85b8a1ad99f5d
72268 F20110320_AAAXOQ gutierrez_g_Page_04.pro
82d72c2c73a6b3f17e40b1b3085aec42
eb15ef18eb5a4846d714d71faadacef23a4e89db
183928 F20110320_AAAXJT gutierrez_g_Page_44.jp2
2dd152d5272f6a957bb7bbf8a2fd9cdb
3e04d437a2a8393061ab12df16275b1bcad2f885
6161 F20110320_AAAXTO gutierrez_g_Page_54thm.jpg
ce4fff48091d39d58be94339cf01b865
d6bf19df58d17080d0debf106add49c655f06940
1884 F20110320_AAAXEW gutierrez_g_Page_37.txt
208a565ee99ddf7bafcc7e1c704bed2b
153ee992a8f4391818bf031aab0c88a63ae1914c
22604 F20110320_AAAXOR gutierrez_g_Page_06.pro
020786d70b50d58419a55560384022a4
6e9a59473400bb071cbcef8038e3786168e7fab0
52701 F20110320_AAAXJU gutierrez_g_Page_49.jpg
50ba26d821f03da8c09128c3665844a9
e469305bad6d83e08606f668d70cc22c2581ccb4
6579 F20110320_AAAXTP gutierrez_g_Page_56thm.jpg
db2c26d9a1a20cf83eb482384d46cab2
8bc454e37565358435e103cf5a0454fb41c585b3
164 F20110320_AAAXEX gutierrez_g_Page_28.txt
000c4c1c68a9de9314a8ede8a233186c
1666e9b1a63680316524d5aa2d2b427a018466a4
20035 F20110320_AAAXOS gutierrez_g_Page_07.pro
15cc8512573de5539e61d3ec1f41d22f
c645a9d04c64c4887fdb67fca418d3ef15de570a
105814 F20110320_AAAXJV gutierrez_g_Page_19.jp2
3d2f12efda6d27bfb3bedd331382d53b
ca0e40d6e948236ed5c710da00af8efdc19fbfb4
6739 F20110320_AAAXTQ gutierrez_g_Page_57thm.jpg
1f0b91dce95ac0cbf902c28617881123
544cac3b708a7fc3782476172633bf1b4dcf5431
56681 F20110320_AAAXEY gutierrez_g_Page_56.pro
10db3675bbb015c3f970975a774e166c
e52c4cdb8f2c82391769aab457a14c71a9014a78
49096 F20110320_AAAXOT gutierrez_g_Page_11.pro
c7e686125175d2daeb39e3126f4c52d9
5dcab3b293d40af90d168bc8bbdd8e2c327dbbfa
1989 F20110320_AAAXJW gutierrez_g_Page_22.txt
f135b1bac83a72a9acbac337d909dd3a
a11d5a2eeaba310cbb6f7363290eea6ca14d9389
3145 F20110320_AAAXTR gutierrez_g_Page_58thm.jpg
68fde0833b054e331d4517f77638d63f
492b4c13e7128cc0c00547e5be1176159beb8ec1
32379 F20110320_AAAXEZ gutierrez_g_Page_35.jp2
284c4fe55a1a58ed05d1996421e12318
e1b560da172cd04803ce360233362f7673c697db
25545 F20110320_AAAXOU gutierrez_g_Page_13.pro
d5ff14905c5932b9d34eb18bbc281587
7dfdea5846bd9a6b868cb0fbea702828485bfe49
74399 F20110320_AAAXJX gutierrez_g_Page_49.jp2
6ee154dbdedadf600fe230505a5bae75
0a57acbd24f636b59ae656e48362f9dce2243f3d
1679287 F20110320_AAAXTS gutierrez_g.pdf
db6805a2905b3b497d9e27ac93cd3bf4
a4c1f230a0b9a7ecf628fe428df0def5532e5df9
49815 F20110320_AAAXOV gutierrez_g_Page_15.pro
48831777193d5e26fca0c82faaeec3c3
1a941b91199c0d33621358ac48c4c9a541161b8a
70288 F20110320_AAAXTT UFE0009465_00001.mets FULL
f2b4c051885a7814ed571d873a3c60f6
95818139249aa33e376518e5fca3daf23b0b906b
49665 F20110320_AAAXOW gutierrez_g_Page_23.pro
7b2704182bdc64657a35ad945b355f9c
de24fc50eb636655a4c1d4f48666ed2d33cd8f12
74879 F20110320_AAAXHA gutierrez_g_Page_34.jpg
6f5385628cd1a4e16b0fa2b61d86b4d0
3b82a437510e50a6f0a2b08627e55b8c3c72e152
2836 F20110320_AAAXJY gutierrez_g_Page_47.txt
a3d23ae0f884d6d5e2db95248a652301
859b6c115a7d4c4a9bbb3a7215b053a2e89cb622
41343 F20110320_AAAXOX gutierrez_g_Page_27.pro
2983271312a7c6fe7cf5066cc8ea6f23
6306f32525294d440def9b2e51eed9eaae9b88b5
23502 F20110320_AAAXHB gutierrez_g_Page_30.QC.jpg
0d3a50ac366a7b0f4910c3840c32bca0
09513bca3683f1cf1431971b7bd7307d473968e1
F20110320_AAAXJZ gutierrez_g_Page_36.tif
c608a59e006675a292d90873bf65c1f3
dbe5ac73b2ab049165fda8af7851928c00f5fdeb
27338 F20110320_AAAXOY gutierrez_g_Page_29.pro
a6d6ad1b7d6e188e03fd091648272a50
f2102334fe06a423ddb97fbb12c625654f3c2cb4
F20110320_AAAXHC gutierrez_g_Page_21.tif
e973b25048f4db6abc30dc8e8ff9d53e
d4ad22a666b86f17b586c0906d03330d69c0039c
50660 F20110320_AAAXOZ gutierrez_g_Page_30.pro
5120ad9541773e9bf1ef870c4ed00e7c
7c9d077b42e1083ff0d8a8b2325e07302e80ae57
66388 F20110320_AAAXHD gutierrez_g_Page_53.jpg
dbe5b642c34aa7739c9e38768be96764
dd68c0bbf5674487632bc188693f9c7a3f51ad94
24408 F20110320_AAAXMA gutierrez_g_Page_39.QC.jpg
818918d15459c691d0590a2f352149eb
f9d987a0cc0358b1fea15405d8bd41f25236f59b
7880 F20110320_AAAXHE gutierrez_g_Page_45thm.jpg
f34c0461482c00807e4fd0548ec0c381
b5ee88dbdc2c33ab4861e9a06dc5b199916a99a6
1862 F20110320_AAAXMB gutierrez_g_Page_36.txt
7340bbe59e5a034f38653964431f13b1
75628a8516d98a4f1abd513b2fcc76833fab8412
26635 F20110320_AAAXHF gutierrez_g_Page_46.QC.jpg
5c6282e03d10e98db93e3ee542864544
addd463bfbd31e813055093fe15c9d59c17a6afa
F20110320_AAAXMC gutierrez_g_Page_16.tif
6dbb2eafcc52b111ee2891a3ebf07be3
47e8cf1cbeb60b4d56fb5d6bd07363af6159c7e6
21554 F20110320_AAAXHG gutierrez_g_Page_26.QC.jpg
3f3115c857b8dc3ff8bc7d0e97d239b5
65f882648623bbeb19e9bdca650b418af62741d3
12969 F20110320_AAAXRA gutierrez_g_Page_42.QC.jpg
76ad19e5234c72c0e87d137700d32fb2
feb2f69a3fede9301881766319f4c450c32d56e1
24118 F20110320_AAAXMD gutierrez_g_Page_18.QC.jpg
c9087cd23723a21e3a03cea63aeae90d
710b381447b42eaba2c771e5d9fba8ae7f722e2d
22967 F20110320_AAAXHH gutierrez_g_Page_54.QC.jpg
ec330d904e5468d93cf9aaa0563adbbd
690ee6e8156904b263450aa56aebf639a8eb7128
121452 F20110320_AAAXRB gutierrez_g_Page_44.jpg
308d7e1b98c627dc9aa33a0e7fd85fe0
c667809bddd8167a788dd0af13e0670c33d8d7b7
40782 F20110320_AAAXME gutierrez_g_Page_58.jp2
ae268d7679a8f16b95507b10244fce82
8b551ab4de8e08017181a6c200dae522f2d3327d
23536 F20110320_AAAXHI gutierrez_g_Page_56.QC.jpg
070c2ed8e1d3c01e804aea28000a2017
1b68c3350d7b7f052426362d7a24acf4094c6005
130952 F20110320_AAAXRC gutierrez_g_Page_45.jpg
bfd68c0c695e781901ca6ccd93bff9ad
2a5c8c84bcb067eb964cc76b4eab05d740bf0c29
3658 F20110320_AAAXMF gutierrez_g_Page_02.QC.jpg
94e0f17a0fdc150fcb4642ebe3601444
9ff25dd432046f2fef40c61187b0caaf90cf3035
55798 F20110320_AAAXHJ gutierrez_g_Page_48.pro
4726011b2e1debce53b3358f942a4863
31c4efa0dbc9c0b6683b895a894c97fa670bd0f8
31967 F20110320_AAAXRD gutierrez_g_Page_45.QC.jpg
c1a090e05e74529f24f66906ac605815
91f778f11c20da05a4c1aa978817ff6053289e49
2831 F20110320_AAAXMG gutierrez_g_Page_03thm.jpg
e347670e0adf909aff73f36b5f9c4f50
cd6e007163146c75ce4d65319d058b43dfb16d47
F20110320_AAAXHK gutierrez_g_Page_13.tif
dfb747345f334c14112e080e14dfdaaa
f56535e26414baf99b707520e7ada0da022931d1
96933 F20110320_AAAXRE gutierrez_g_Page_47.jpg
81a4ce0398bdf2310c706e9007c91836
92c0449ca296af4353b5368d36aa37db8a14c309
1942 F20110320_AAAXMH gutierrez_g_Page_11.txt
3bd703ef202e8d97247b48cc5cc3c254
52f8fab9c909dbb23433867eae26d4d028228789
624 F20110320_AAAXHL gutierrez_g_Page_35.txt
1572d28726182644b9a9580a5fa160e9
aef4b05e72bad79a5f84cd2769f19e4a124d10fc
76234 F20110320_AAAXRF gutierrez_g_Page_48.jpg
cafb31b6a5f5c389642eb1e2179cca83
4c40ec941a2358d3d8533dcb8d8f6ad2aa4832d7
F20110320_AAAXMI gutierrez_g_Page_54.tif
3da9dce7c0872b02bb315861c8e2e8cb
82cf15d4183f1431efbfd7e65a953c4d016de587
31144 F20110320_AAAXHM gutierrez_g_Page_58.jpg
c3fb0a949f9f7118b4e06ac79724a0ee
208f944005c4050eab3d404a523bf4eba650ef39
22591 F20110320_AAAXRG gutierrez_g_Page_48.QC.jpg
d041cd849f4f871107e209c0f931b80e
5aed0a34a790c243ff2e0cbeb9c1dbb2eef5feb7
49652 F20110320_AAAXMJ gutierrez_g_Page_22.pro
bea6cc815539e81cebf938c807a6e484
08eab2e879a8912c5238858e64f1fc252938a3af
20284 F20110320_AAAXHN gutierrez_g_Page_14.QC.jpg
e578ee02defdbe7c41dfc8c7270a867a
9df063e138fd50d857353cabd597475cbe2be9ed
15737 F20110320_AAAXRH gutierrez_g_Page_49.QC.jpg
052e8276f1977d384a6cb7dfb395ecdf
aac1d299e82d7a4075ed34dc4a116f819305b560
76989 F20110320_AAAXMK gutierrez_g_Page_51.jp2
6066733972d86e3ce9d0f20a7fda56c0
681fcea3d8d276b38697ba726e5bb621a8998797
5419 F20110320_AAAXHO gutierrez_g_Page_52thm.jpg
fa8b7335612cdf2e82f3c9b7b8c217f1
0744eb4a0ff77156ca062c1d96c54300b3a029f6
10298 F20110320_AAAXRI gutierrez_g_Page_50.QC.jpg
bea9df073b5f48493336be1ee1f1f9be
1b76dd1021f01bef60dcea7ad8a46b1e61da7605
6110 F20110320_AAAXML gutierrez_g_Page_34thm.jpg
b8502d521c508e8b11bd77a53f2d55df
39cdcd66c6641cd5e46c1ff48ca78cc3615c6844
F20110320_AAAXHP gutierrez_g_Page_52.tif
9d189e2d00bb7adf4009376ea3726f76
c27438872bfac1dc965502c9ec69fe837769b170
68237 F20110320_AAAXRJ gutierrez_g_Page_52.jpg
1ec42dd5426c23bf14cf9c761cd23bf1
d03446cf8532db437e18e9c37fea50067b254968
43773 F20110320_AAAXMM gutierrez_g_Page_10.pro
91d6896c099c04fd05a7d489acbc70ec
0e8b6388919a85c24cc90b576a9c86819f1bd968
72285 F20110320_AAAXHQ gutierrez_g_Page_20.jpg
d434a712b8a67e784b8cc4c49d465b02
107a52abd66bb2512fc2f65b1e846fe2abbbac9b
20031 F20110320_AAAXRK gutierrez_g_Page_52.QC.jpg
db3b07d7d0ef39d58f560af890472116
2594fefffcaaab51eb8cea0b7d71db93fc7ba7d3
1799 F20110320_AAAXMN gutierrez_g_Page_10.txt
092c7759bf5326058ef5bd0c25fa20a0
0a722cbf17e96b5e69edcf56f1ab68b765c3ea88
2742 F20110320_AAAXHR gutierrez_g_Page_07thm.jpg
ce26fbadfbf513c9a78fecce954af497
ce3244982e2da0492056a231bd7f5a50b0c48968
79514 F20110320_AAAXRL gutierrez_g_Page_54.jpg
4d62d1da1c4e14f3a7f9ad31f0019e23
9d8f02d81532c378072057ee7cdb801e128075f2
23053 F20110320_AAAXMO gutierrez_g_Page_43.QC.jpg
12f0a24ae7b93e8fc91756855cecb11f
1ec5f91b66f9b74ac5a78bb18442420c8847c43f
71556 F20110320_AAAXHS gutierrez_g_Page_15.jpg
e649c496cdb348dbe21f9de78342fba3
85b9d48e5a904a92001bba43874ce1409c6f6a13
78366 F20110320_AAAXRM gutierrez_g_Page_56.jpg
4f246428a69a088ea0f445ede8d5b81d
1851d38822e4d218b2c8a5c1d63fa7c4e35c5429
22642 F20110320_AAAXMP gutierrez_g_Page_17.QC.jpg
bea66cc077d65c6dcac4fa16b3f10e0e
2c53fa87f76f801bfa9075bc30e97731fdd7323c
F20110320_AAAXHT gutierrez_g_Page_05.tif
cc2d5f2f0b859fc3851122e3c5e5c78b
5847490e435f441dda8f5b8ec746d8c431a85dda
88758 F20110320_AAAXRN gutierrez_g_Page_57.jpg
d0061126088b03fd8aafa24432de44f8
a89f8b5c2025dd9cc7528fa99f4cf97086cf1062
1813 F20110320_AAAXMQ gutierrez_g_Page_14.txt
4c0810a2b05d8d6ce3066aa990128c27
92d30b5b219fa2a01a057920656e9bbd07c93275
22337 F20110320_AAAXHU gutierrez_g_Page_37.QC.jpg
4c58cf0c14ffd129374777f6754559f6
c81e61863d812eb8bd29852dece138b3d6de6b8c
26426 F20110320_AAAXRO gutierrez_g_Page_01.jp2
586a67d17982873981c947126ed5af5c
b21bfdc9addfc7712f0fea3dfd6edd59d404f2fc
9268 F20110320_AAAXMR gutierrez_g_Page_28.QC.jpg
139bb8ef84eff91d2fb374ced858a4c2
cebbf482fc9440725bc2a67ce1fbe52dadb4be99
89232 F20110320_AAAXHV gutierrez_g_Page_27.jp2
899bec1debf8141a9e819c3992071ec6
e7af338cfb050aa48e94d232181652a0da65146b
6981 F20110320_AAAXRP gutierrez_g_Page_02.jp2
536a55713f96b6c943c4502e6d8b8910
f1af61bf9c7c1f1b2b95ae997106a7e0e2f8a9f8
96915 F20110320_AAAXMS UFE0009465_00001.xml
c23cda6b59a0286c7a66f48416e2a6f9
42bdc595c7a02a20c54814e2646e7f3a61e5c391
1051985 F20110320_AAAXRQ gutierrez_g_Page_04.jp2
e99c1ed25b36e75ce6f70d2c1c18495b
a7215f3e089a10c2cd50ec1a8c3bfdb4ae0df64f
102751 F20110320_AAAXHW gutierrez_g_Page_34.jp2
9707b83ad2a2ba0e304cec5b67a82a3b
ba403dfe68408d258facb63ab69c0b711c8d1195
708209 F20110320_AAAXRR gutierrez_g_Page_05.jp2
39663196da79cfbee25ea522388d2aa4
2daaac311117c66cc16363103c3b1de9da2b01b2
6517 F20110320_AAAXHX gutierrez_g_Page_23thm.jpg
921a124a068e01c90e24faa00ac21727
a92330121e8323d64095854a800e862781771bcf
848625 F20110320_AAAXRS gutierrez_g_Page_06.jp2
cf538231294b1ed0c72e4726d62fcfff
5b07fbb8c32825e9eb88363f4e62cc29e9078ba8
F20110320_AAAXMV gutierrez_g_Page_09.tif
e8ba7495325265c836da6123a67de906
fe4c757aec9065ccf52ab9419f866a8f79fb363e
F20110320_AAAXHY gutierrez_g_Page_11.tif
f659563157df26b7dea4027a10d70a1a
e6f7cc936545c2e5314ed649c8b15336ac2d2503
55160 F20110320_AAAXRT gutierrez_g_Page_09.jp2
5f039940f0114ec4d16af12e189eaaff
8a355d5e96ca94012133cb3d944b9c1d09bff902
F20110320_AAAXMW gutierrez_g_Page_14.tif
0e0a7d55e1a45829397ab1593d19f805
646f44ce7b6fa87ddd764c42cdc59e38247f4fb2
34872 F20110320_AAAXFA gutierrez_g_Page_31.pro
b03989f25bc036064fcd8252ef96b12b
60133a794a75ae1cf9a4c2a339d47505ae37e4d3
1164 F20110320_AAAXHZ gutierrez_g_Page_05.txt
c5578e785eff62dd906b34691411b20e
29281dadda1d941d220846fb1187ddd97321cb3c
57896 F20110320_AAAXRU gutierrez_g_Page_13.jp2
dac870d905c0beb388aa2e324748d66c
77ce3069b44a6dd83e9885da136d9193d9906952
F20110320_AAAXMX gutierrez_g_Page_19.tif
91ade33f0748877cdfaee20a3e7716b7
36a1fc21fbfe33048a00d786cdd9da3b94ecd843
18791 F20110320_AAAXFB gutierrez_g_Page_31.QC.jpg
e064951ff404ecf5be7d3e40c269314c
bb2a47efe38832ed3e5c9398fd023316ff38f429
94805 F20110320_AAAXRV gutierrez_g_Page_14.jp2
0e8d0d9ebb8560c400ca3e7ff533cfc7
e6b346c9adda9d99e9dcc64a7ec4e113b734f497
F20110320_AAAXMY gutierrez_g_Page_20.tif
bed812f978245906f961e78df8f9f835
42ab7b77f9047f567b004f69f675b11b556ac9f6
F20110320_AAAXFC gutierrez_g_Page_06.tif
41ff0082fd10fa5d80652deb64a56324
3109a776a3d972b3c34e6658860842e2bb592974
110562 F20110320_AAAXRW gutierrez_g_Page_15.jp2
383ed18f8961be17be94c04b03b54dd7
08c028831f839b5fe65d3e0f459cfa697ed03664
31344 F20110320_AAAXKA gutierrez_g_Page_05.jpg
023cbfd485219b708618ed33c3be4444
485c721cee1040140464a83c491c35be46bdda2e
F20110320_AAAXMZ gutierrez_g_Page_23.tif
e4328b63d2dbc0b7d0a9fb37add6b16c
9aad37d9107034dd8ce754ad3a04cbd4156a8617
58256 F20110320_AAAXFD gutierrez_g_Page_42.jp2
28c19f755966ec0492f3b7a95a8d87cb
08db4b7c9b89f0bb2049ecc1db75ae39d8623028
113239 F20110320_AAAXRX gutierrez_g_Page_16.jp2
a3c492bcca96c5eeebea257deb01498d
7697e94b59fb7ed84a31763762da546d27003a94
1680 F20110320_AAAXKB gutierrez_g_Page_27.txt
cbcb657b051c3dacaf741b81833ed5ba
3ea77ec6529b5d69781359457946b43154de3d3f
F20110320_AAAXFE gutierrez_g_Page_50.tif
e50812591c5c3859af18d13a67833ef0
62a281c99f3c3d65a5ad6e9e09559df362d8120a
112182 F20110320_AAAXRY gutierrez_g_Page_21.jp2
8d4a149b04acaac22c98429161a3e7ee
d7c12937339d6c06551d4df43e1953b36bf3a786
61429 F20110320_AAAXKC gutierrez_g_Page_31.jpg
164594ed0956ec91763f4642cc574b74
7f69e088160908391bdc780db7ab2aa16e0c9e4f
19338 F20110320_AAAXFF gutierrez_g_Page_27.QC.jpg
cbec1dace9e3b5899cb878ca1c856fa7
6be9dd605d5aed67522c5480bed2d42aaef359ce
106402 F20110320_AAAXRZ gutierrez_g_Page_22.jp2
566f1eda86aca559a16b3b4339cb8500
c94432fb27bfcac57de37e6e335f03595dcef9c9
1786 F20110320_AAAXKD gutierrez_g_Page_25.txt
bd8fa86654c1393ce27b65e659aa2776
f2b04d6e949bdfaab5f4e93663999a628bab0dbd
64384 F20110320_AAAXFG gutierrez_g_Page_36.jpg
80c0941ae65288b1eec1d33cebc4a8c5
8d7ce0b8862fc172f48d7e2599648cd139c94d0d
43676 F20110320_AAAXPA gutierrez_g_Page_33.pro
a2bf880eb31dc8410f7dd0b21f6d2a19
09aedb0b2714e885fa0ab57c918f898e236eda23
F20110320_AAAXKE gutierrez_g_Page_58.tif
49317058b73387d029864acb41f87493
fb12530850cf224417d0e449ea503bcb419b800d
108131 F20110320_AAAXFH gutierrez_g_Page_38.jp2
9f918224e5026f2c481b8f17d32cc624
5819fe8d079819630606736c80d646af224a2844
49414 F20110320_AAAXPB gutierrez_g_Page_34.pro
2e072e0c60637df53dbfd4fb33622ae0
4c98dba38141767070f19dd7657b9da21675e268
59087 F20110320_AAAXKF gutierrez_g_Page_04.jpg
662f029dae5cdbec28b1d94c013e4fc4
b51bde95042695e7b60053c5c48e3102429e003d
F20110320_AAAXFI gutierrez_g_Page_22.tif
4b0ea04cf7db0682a65b7efe914862fa
62adb8c522e34440e0442ddd0b55e809c774f4b7
44071 F20110320_AAAXPC gutierrez_g_Page_36.pro
fcd7e9901d94c1e70f8fd62d69b5a135
f20780f37c42c7118714f82b1bd3a914489a86ce
F20110320_AAAXKG gutierrez_g_Page_34.txt
7338ced4cfd8d680ac724649167955d4
6246b8cf9d533efdc04911decb87d2e33933d3af
49163 F20110320_AAAXFJ gutierrez_g_Page_41.jp2
d20091c7192664de1bc503cd9d3898cc
bbeefe4eac26c47e6ef8c18d392d866a74b15669
47733 F20110320_AAAXPD gutierrez_g_Page_37.pro
d20df87e80b3dc6f159a80796cac21d2
1574ab4c55f5f0a7b2fdfd731477a9d73c72e0de
6521 F20110320_AAAXKH gutierrez_g_Page_20thm.jpg
09986b955d3fa58e3f282faa4a85ffb3
2e7ec8001632c3b632b014786d112bab74730e95
26556 F20110320_AAAXFK gutierrez_g_Page_47.QC.jpg
2c0c6880315a7a502eeb172553ad7c79
b2ca6931d315a09c9b45a0f01ccbc27c50251367
50578 F20110320_AAAXPE gutierrez_g_Page_38.pro
24163c801434205c3d3c4eed307a50a6
5d7f65176d062ef8ed9fd24a74acfce4f3be4cd1
6402 F20110320_AAAXKI gutierrez_g_Page_26thm.jpg
51f04bb1091de1157c2ba815a79c8626
d8778c1898aec6120514c6d9637b874885216767
36096 F20110320_AAAXFL gutierrez_g_Page_49.pro
730c5defa33ada59191e7abbf3d238fc
4b1e253b5828acb94b9e4311585d9d19bcf50e15
21329 F20110320_AAAXPF gutierrez_g_Page_41.pro
3a0672af8536289d80aa263ee53de9a1
80b3886a9761fec80f5ef37aed2d45ac3a1f8c25
F20110320_AAAXKJ gutierrez_g_Page_42.tif
8ea113f3eb92dd5950359aa6ba48a408
6f15c1165f25c46fd12f6f2a1a261288c237d23c
936540 F20110320_AAAXFM gutierrez_g_Page_52.jp2
d3edbb98cf3b68af1002125a77c0fd19
123810616d798366db1b873a26bb061d6e419da8
25894 F20110320_AAAXPG gutierrez_g_Page_42.pro
f29caf506a9e9da1b53220333feafe95
aaa9659b81531859f6451fcfaffb93e871f9b9a2
F20110320_AAAXKK gutierrez_g_Page_33.tif
759b693dd5b5154f105c3620dc9b78e7
de16e8e9773cdb3be17a9f65bf58feea60e1af07
F20110320_AAAXFN gutierrez_g_Page_18.tif
274085a49d12e5709b0c6f396f3e51b0
c12d7e5a1349d1e6899830641fcd091d6d1b58d3
59663 F20110320_AAAXPH gutierrez_g_Page_43.pro
ab932e573e3700990ae50a6dbc275afc
e611ecdb82510d648c77658677e105d1312cb7c6
3862 F20110320_AAAXKL gutierrez_g_Page_13thm.jpg
42162e357c903b6f71f8aaf6a9343487
73a3e08208a83bd1e0b700f7e59ba284a39ec6c0
5626 F20110320_AAAXFO gutierrez_g_Page_33thm.jpg
513da55ef8d32d20a1fc88226198ddd7
bfee288d9f819cdae2221907c327cd580441dee0
88659 F20110320_AAAXPI gutierrez_g_Page_45.pro
3b2eccd13e75b666400b6374ef9c5879
c45c9703939bc888edaf93a03531bfce97e8a0a1
34237 F20110320_AAAXKM gutierrez_g_Page_50.jpg
49c9eb06e15346c99c8195db9968476e
c817fb61ad7096e6f02e7c2149aa0937a86e522b
21733 F20110320_AAAXFP gutierrez_g_Page_50.pro
37b4bbc96275890f506923862a061d62
3fb25d0865c3d0feacae99513e396f249b8c9045
75316 F20110320_AAAXPJ gutierrez_g_Page_46.pro
2dfa31d89ef4e96058c45ea3f6777659
ea26b0a513b22035a3ac84c3d650dced8867405d
6624 F20110320_AAAXKN gutierrez_g_Page_30thm.jpg
ea37807da726af33c79f243cd5340e01
2b69e2d7245da1627978543f02714769e68c74b9
24972 F20110320_AAAXFQ gutierrez_g_Page_57.QC.jpg
d1fbc7a82b147a00f4fd12e055a28a24
bf65fcc25718bb1f5d58b99ccc92ea728668dc6f
72263 F20110320_AAAXPK gutierrez_g_Page_47.pro
2a5b93119075f97118cb3dc2b1a0d8e2
826983895021c269abe69e14682931bcc756ee77
8996 F20110320_AAAXKO gutierrez_g_Page_01.pro
ad45aa63b382cb312f0e28b69e462864
4c6ce1ebeff9b87780dc60192d0c0700ed062d4a
3662 F20110320_AAAXFR gutierrez_g_Page_44.txt
37e5e9a6ee765c98abf9148b168fef72
e423b04cc9df7dddb47dacd183ac65badb1c2467
39085 F20110320_AAAXPL gutierrez_g_Page_52.pro
88a69c8461eae43adb58c8b4fdf2ff11
614aac32ba8b6e0e91ef4c7036e3649cd9713542
69761 F20110320_AAAXKP gutierrez_g_Page_17.jpg
71907db1d55b19ed734eb30384953ac2
15992dfeb7c0b1ab3b3a3f50f0bb33b7addf9666
10181 F20110320_AAAXFS gutierrez_g_Page_58.QC.jpg
216fab15fb17ca525d687505e717d5fd
3473ee3cd742bf3a829012c4b29251cbdf0c2d3e
53836 F20110320_AAAXPM gutierrez_g_Page_54.pro
c473ec2176d5142c84ceab76685b80e2
1f4a23a006bb320b324c1d1d9e31973c3a8894f1
1998 F20110320_AAAXKQ gutierrez_g_Page_30.txt
b0aa22ea59bbbb6d7064342f03478536
2c5df7ea62de1262f1fcd26c05d299473810d737
6726 F20110320_AAAXFT gutierrez_g_Page_40thm.jpg
19f668939d78ad26f975059d9d1f5744
fc1ba6729d5266d080b11dd42df7c614cd9f49ca
17049 F20110320_AAAXPN gutierrez_g_Page_58.pro
bab92f4c7e580e87328383496024d3da
c12dbc1b84b0a2e6272b05aaf713c76809e3506b
F20110320_AAAXKR gutierrez_g_Page_30.tif
8d0196025a7745f3e7006e7ff716f834
6f85d6e5e00810062c26873264b99e67668c53ab
26124 F20110320_AAAXPO gutierrez_g_Page_01.jpg
32e46f5d7af7cc69522781a8a0409a4c
27cd48876fd2d46fcd3d8f1f80514450060f14f9
F20110320_AAAXKS gutierrez_g_Page_57.tif
9b50a663f59e2641b6bb8ad35a866349
6b1d88888813b428784ed5a037277f1c71a061c6
19552 F20110320_AAAXFU gutierrez_g_Page_08.QC.jpg
811be2f66940c84ceb4ed68c24c0401d
f81464c850751b076c36b6a9e05214a9ba10f2ba
7955 F20110320_AAAXPP gutierrez_g_Page_01.QC.jpg
1a6749185fad89061b597be3f75ac64a
4e4e13026ef2cf3002a863e75695e746c1d6cf32
13621 F20110320_AAAXKT gutierrez_g_Page_35.pro
c1ed0accfacad7a35ca8350b4bc368a4
47340bb03c4b98afa58a805db63e7e0d4ee888a2
70593 F20110320_AAAXFV gutierrez_g_Page_38.jpg
fe6a94cd0b469c0641e3617e3cb6836c
b7189b45022db999a56af0c0f15f8d858f9c005d
11231 F20110320_AAAXPQ gutierrez_g_Page_02.jpg
2d753a0018dae06bff21d68668377165
409718ae5ccbdcbc1c241b079f628814af098578
16100 F20110320_AAAXKU gutierrez_g_Page_51.QC.jpg
f0529f33e2926ee0ef2526f576ca70c9
293d9d48abe8c0c1566257a75e37b0ad32fd8117
22581 F20110320_AAAXFW gutierrez_g_Page_11.QC.jpg
7695beb1c533fba9e501c59a9733ae70
2ca998c1cf666afc2b96a429c4de2443dad43eb7
27487 F20110320_AAAXPR gutierrez_g_Page_03.jpg
9dc0651ee13a81b3133bdf457a36faae
898413e4069df8a00e41ad8613cc0bf679b1bb25
2193 F20110320_AAAXKV gutierrez_g_Page_54.txt
141bd2173fc0071fb47378a8bde7ea74
9ae78930032e7f6e85105b1406d1f85e6a67e823
50717 F20110320_AAAXFX gutierrez_g_Page_18.pro
dbe394c0299d9d11da1ba055f36ca858
1eb26257b2f19781aa4a7294a72c14d33a79b1a0
9105 F20110320_AAAXPS gutierrez_g_Page_03.QC.jpg
11f2768b42675c29a5a45b866ad93c82
07692613d2e0957a066daef56c085fe1e59758ac
39507 F20110320_AAAXKW gutierrez_g_Page_09.jpg
8e8e0c4534c66ed6019c3d69e3a1e48b
6187427f2142c2c70bb946bcd47013281ce993d8
58921 F20110320_AAAXFY gutierrez_g_Page_55.pro
609b1a2425d73199d77423838726951a
8798299b8e66a24780cb52b93598e6655d4a119a
15451 F20110320_AAAXPT gutierrez_g_Page_04.QC.jpg
d4618575ec533c97d299dd382abb0754
36e068be034064e61505c059df8e79b34aef5228
18011 F20110320_AAAXKX gutierrez_g_Page_24.pro
76dc76051bc9f29722864d6c943aa1bb
f5174cb6b74bb3fb170162e865e32b449816aa62
3436 F20110320_AAAXFZ gutierrez_g_Page_28thm.jpg
6d6b8d97f64c6b57121d37b9ab01c1a4
05d12cfecddbcb2efb75a3652391357bf844e77e
9016 F20110320_AAAXPU gutierrez_g_Page_05.QC.jpg
90fcf953ee0656975eee7dd85d0da6b4
b3ed7188dd10ae34c1917dcb56cf295b5040839e
72980 F20110320_AAAXKY gutierrez_g_Page_18.jpg
adc7d9cd7832f77d93bececda1e0dfc3
7aa01180cef3e68e12e1fb5fd01c1f6dc6058acd
13006 F20110320_AAAXPV gutierrez_g_Page_09.QC.jpg
a522902a1945321ffad83b4b9f2aad01
488444a647cf4425227440227276cf69de1dd0ac
68228 F20110320_AAAXPW gutierrez_g_Page_12.jpg
9713b1bcde98a44055fc15c7cc81b19d
1d9efb440b556b3e1c548dd4ddd568686ab4d6ae
23912 F20110320_AAAXIA gutierrez_g_Page_21.QC.jpg
a285a272ce0431d639f635e3367d82bc
5a5d6d544749935277f50e8a20910006962ba4f1
13628 F20110320_AAAXPX gutierrez_g_Page_13.QC.jpg
f7e90b7767082f9a67d9e2034ae33b2e
d33e6c8a4210f6e8f5ebb786c8e348717f67a56f
62231 F20110320_AAAXIB gutierrez_g_Page_08.jpg
c890883b8a76a3e4f9973e036aff7c3c
45412bc8b8e32502a3cf5ae359287249a43f906b
3944 F20110320_AAAXKZ gutierrez_g_Page_42thm.jpg
1f5ea1b55217b1cc7f8e9aff93a692ac
8d914aeb893245074a9612e1dedab82cbc5faf1a
64113 F20110320_AAAXPY gutierrez_g_Page_14.jpg
4ed12a8bebfb7b718f2974df7f643b91
c2c27cd4a5b2fce2b1382593bd7e2b7dd4946dda
F20110320_AAAXIC gutierrez_g_Page_38.tif
979e5a73fff09f12cb9bf3b284746573
7297a26fc55935605ef43fc816aa855241db66dc
F20110320_AAAXNA gutierrez_g_Page_24.tif
9b56bcb1532ecdde97968b038fb77f81
90420e2f3e4fd8952da28d92e4be12d5aaef2851
74530 F20110320_AAAXPZ gutierrez_g_Page_16.jpg
fa89b43c0bf9218f04d2919497624e72
f7eaa71b78267d5fa20b2f9522b123ab3aa86251
899 F20110320_AAAXID gutierrez_g_Page_50.txt
d883ea682b13d7a10d8921ec224b948e
8b23884e58b61ba79e26e751531f070287726162
F20110320_AAAXNB gutierrez_g_Page_25.tif
4565c415ea9dc044c83b71f8f60135e6
b88de98d5f9f23168ced78d85dd53af50e38c56c
34104 F20110320_AAAXIE gutierrez_g_Page_53.pro
685e7c1fb582ed2c68585bd23267be7d
5639ee2775610370613a158096834bf40b0550ed
F20110320_AAAXNC gutierrez_g_Page_26.tif
ea9ce0def768d6a1c9b14d087711c088
e640e1de826bd56db1836b366e11dbfd2773b056
1640 F20110320_AAAXIF gutierrez_g_Page_52.txt
6111d0c41b642176a979059e1d9a6ac4
b4067dbd2235556bc85b2a6830b9b3659287e8d8
107600 F20110320_AAAXSA gutierrez_g_Page_23.jp2
4c4461e5fde511dbdba45961e1e95402
93693064a9e875e4a05a5787ef472bc660ae60b2
F20110320_AAAXND gutierrez_g_Page_27.tif
105549a5890609bd5747b9b2fe27af6d
5763f88bc2680f5593fd50fe54c0b63021f97934
41739 F20110320_AAAXIG gutierrez_g_Page_24.jp2
1fa6dd5183baef8a6bbc917f639c9d4b
fa8b04c5979b3ad9a98c9090019b551ab4a6a469
F20110320_AAAXNE gutierrez_g_Page_31.tif
8181f11a9d72a3362b46dd56c38fe3e2
d036f8166fcb6c21d3ec96561ec4ec96fb6ad801
90767 F20110320_AAAXIH gutierrez_g_Page_08.jp2
17e128e82c46738fcc9c3ee32d3e014c
081661b34e746c358582bfe481d0f9c9c440c393
916031 F20110320_AAAXSB gutierrez_g_Page_25.jp2
af0bc241d65a6e4ccefea964fae2a687
0fe9dd27831bd9335d4c058ac6112ce537c413db
F20110320_AAAXNF gutierrez_g_Page_32.tif
ce4cfbc9ed2c42efe61dba575d3547ed
4d6949c81db3f9420abdd3f5a7cfd0b323dba39d
3301 F20110320_AAAXII gutierrez_g_Page_32thm.jpg
56cf5cb5a3f1c0d68a32efc693cd3e6e
f17ac448b6fae226feea2a4595c48b51fc4b6982
101308 F20110320_AAAXSC gutierrez_g_Page_26.jp2
a0bb57ee33ca5ba881c21228fe657645
484d243435e7c183e121ef9ac52e5814ad4bfe8c
F20110320_AAAXNG gutierrez_g_Page_41.tif
7a260fcc2c605bae0e3049dcd1d93ebd
1bc52cd36b53e90649b81a6c814197e87097e342
6389 F20110320_AAAXIJ gutierrez_g_Page_11thm.jpg
42b11be3b58e28150ee0178bed547221
63b087bb7a386c9cd4c655e98e4dc74c8e253257
F20110320_AAAXSD gutierrez_g_Page_29.jp2
e23a1a897a569402a527150254c1573a
f2a0fb57b1a0f724501fc72142f11a4dfc5436c6
F20110320_AAAXNH gutierrez_g_Page_43.tif
c2902f866045ff97ba14483e2560efe5
b48e4195ed68118b619b5c0b9cefca51682d5f69
6041 F20110320_AAAXIK gutierrez_g_Page_25thm.jpg
5756ddb01cfa4ba4011c8ef68cff27a9
59bb18eab174601e8760908607ac6cce87b5c8d4
110399 F20110320_AAAXSE gutierrez_g_Page_30.jp2
653ad40df855c3b88047d5b85b98b016
78301ad8cd6945ef3afbffbb4d1a5de828f62245
F20110320_AAAXNI gutierrez_g_Page_44.tif
460e10ce5a7fb8c1ef45a556d59891fc
ecea9a6e6314f561ecb632a2851be105091cf19c
34336 F20110320_AAAXIL gutierrez_g_Page_03.jp2
6c53f236751d9add247e2dd8c558badb
eceea7f4ecdedb013e858a09246a5edc577ad215
843257 F20110320_AAAXSF gutierrez_g_Page_31.jp2
f488148a3ed7644391d7cb31225c1921
b899b64e223018896b0454313ca2fe70c856314f
F20110320_AAAXNJ gutierrez_g_Page_45.tif
69c562ccde40613cf475a2c27d33b865
60385cd500638fca1de04c6d6084c3d56ed26123
F20110320_AAAXIM gutierrez_g_Page_08.tif
2880919f01a21a2e5070f02aae7955e3
052aff9716efe01c9c509b94fbcc2728e45a6f56
45942 F20110320_AAAXSG gutierrez_g_Page_32.jp2
38b7f6b5f5004bf6e7c3c99acd33cb20
852a51d46f48dfce3e411a965291a052066e0f49
F20110320_AAAXNK gutierrez_g_Page_48.tif
d50530ab4defda9f4d58a3491af8e973
c1e023c81d636ed90bce30f2d1f89e2c882e035d
F20110320_AAAXIN gutierrez_g_Page_02.tif
c9c2b6dd64edd5829199f750fb60e477
9caa79bb1897d81deddb6f64ed93f20ed704516c
92485 F20110320_AAAXSH gutierrez_g_Page_33.jp2
51e57c8c5fe71cc814a5d4c743c1518f
5d45a85e52209e21097aaee9e1e2edebb7dcc6d8
F20110320_AAAXNL gutierrez_g_Page_56.tif
e86de8728945be88fe7e578744ad107d
1172445121d7aa55da024cf97808da856d321039
10779 F20110320_AAAXIO gutierrez_g_Page_06.QC.jpg
f2ea547aa9bfbb16233f0c0f2a0994e7
94915a78ec1a32d82667837b63fc9c614493e979
96962 F20110320_AAAXSI gutierrez_g_Page_36.jp2
c1b6a9dbcd5bf98008c697b9d2a3256a
62d56ceb2a4f39695b4def0154cc87776f4a9c2c
477 F20110320_AAAXNM gutierrez_g_Page_01.txt
91549474027a3776ef4a26cbf63058d1
ee02991b046545e65b299c374fc73fff0af57284
F20110320_AAAXIP gutierrez_g_Page_40.tif
d97c4920083a3f0ce205ea8cc59173e5
2ba378e8f4f46ffaff311d524e0d68dedee81756
104246 F20110320_AAAXSJ gutierrez_g_Page_37.jp2
036540bd8510c99194e78b9f2acb448b
3b26044231d64b70a1d50918a6ec0a3a62589cfa
134 F20110320_AAAXNN gutierrez_g_Page_02.txt
9c4fd9f86668ea9a0e63dea3c22725b9
f0a6b9c2ad5bc137952dc1fa5c505d8efa50ab81
7081 F20110320_AAAXIQ gutierrez_g_Page_47thm.jpg
e72d853ede91a5c4d2a97b8ee2ff5c9b
fbd2f02d5851e996c645dfacb7ff63d69eb34501
109772 F20110320_AAAXSK gutierrez_g_Page_40.jp2
b7d0b8ea99a48645c6332dd4f557b3d0
bfa9018daeb89e4d248ffdfe84c8a8bd57c6f458
2960 F20110320_AAAXNO gutierrez_g_Page_04.txt
0ae0fb72d03bd12e61ba11ef04bcb500
258384eef7bffe6310451796248c24aa994092fa
69755 F20110320_AAAXIR gutierrez_g_Page_11.jpg
0bd7bda995d25bad87ad7bd11053280b
c16a8fa913f6ce321d95b58bdd1fef9fef46bd2e
121924 F20110320_AAAXSL gutierrez_g_Page_43.jp2
0e814837bf3cf93c26dd5b015eb969d3
4e5b409745b0f4f4d1c6f25932a2149d65c6d33f
950 F20110320_AAAXNP gutierrez_g_Page_06.txt
aefeb2e55d314343216db2b50e2bc296
88ce8dbad4d30efd98b9b1b7c5f3684dfe0348cf
F20110320_AAAXIS gutierrez_g_Page_01.tif
49203a6febd2a6af15c554892c28bb0e
fae7b440b7fe549b99ada6cbfd16688e04fa6837
1051907 F20110320_AAAXSM gutierrez_g_Page_45.jp2
38316fa5bfca79cc0704ff860adff81c
de0017b99f5cf2807e4cc647bc4f5ceabe577998
962 F20110320_AAAXNQ gutierrez_g_Page_09.txt
ea7fe0c807a108bafaf7fe6cf7f14a4f
79133d30fa7e8eb6fbcb55c050916068b0d298a1
35133 F20110320_AAAXIT gutierrez_g_Page_06.jpg
04106a5ae6e5e37f5f32232a5ce07c08
e5e14ebb7aff697f79c28fecccd0b32adf1b310b
150447 F20110320_AAAXSN gutierrez_g_Page_46.jp2
6519d9107aa27e4dcb498da18243cc0b
e2396d38cb504c0011e4bf692bbd9b7d0740a149
1856 F20110320_AAAXNR gutierrez_g_Page_12.txt
df3233b3f578e5696d660eadedc446ba
3fbd22872d9714d1a3aa75e8176ca93be4bd5833
1051903 F20110320_AAAXIU gutierrez_g_Page_28.jp2
111947a83d5adc9da61101cb75b2358d
5510c00a5e8d7e82cd9b3179af958e8f45e005a9
144343 F20110320_AAAXSO gutierrez_g_Page_47.jp2
4cf231886e7b0a2e66e6190bc5587ac2
e99dd489e4f64e407cd4c12067c01740a1c4af76



PAGE 1

EFFECTS OF AN EIGHT-WEEK PROGRESSIVE RESISTANCE TRAINING PROGRAM ON BALANCE IN PERSONS WITH MULTIPLE SCLEROSIS By GREGORY MICHAEL GUTIERREZ A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE UNIVERSITY OF FLORIDA 2005

PAGE 2

Copyright 2005 by GREGORY MICHAEL GUTIERREZ

PAGE 3

ACKNOWLEDGMENTS I would like to thank Dr. Mark Tillman, Dr. John Chow, and Dr. Lesley White for their support and guidance in the completion of this work. I would also like to extend my deepest gratitude to my family and friends for their encouragement and moral support throughout this thesis project. I especially need to thank my parents; without them I would not be the person I am today. Special thanks are extended to Dr. Mark Tillman for his personal and professional advice throughout the years, for which I feel forever indebted to him. iii

PAGE 4

TABLE OF CONTENTS page ACKNOWLEDGMENTS.................................................................................................iii LIST OF TABLES.............................................................................................................vi LIST OF FIGURES..........................................................................................................vii ABSTRACT......................................................................................................................vii CHAPTER 1 INTRODUCTION........................................................................................................1 2 LITERATURE REVIEW.............................................................................................5 Multiple Sclerosis.........................................................................................................5 Expanded Disability Status Score (EDSS)...................................................................7 Symptoms.....................................................................................................................9 Risk of Falls................................................................................................................10 MS, Exercise and Remyelination...............................................................................11 Balance.......................................................................................................................13 3 METHODOLOGY.....................................................................................................16 Subjects.......................................................................................................................16 Instrumentation...........................................................................................................17 Force Platform.....................................................................................................17 Isokinetic Dynamometer.....................................................................................17 Experimental Setup.....................................................................................................17 Postural Sway......................................................................................................18 Strength Testing...................................................................................................20 Functional Tests...................................................................................................21 Resistance Training.............................................................................................21 Data Reduction...........................................................................................................22 Design/Analysis..........................................................................................................23 4 RESULTS...................................................................................................................24 Strength.......................................................................................................................24 iv

PAGE 5

Balance.......................................................................................................................25 Functional Tests..........................................................................................................26 5 DISCUSSION.............................................................................................................27 Strength.......................................................................................................................27 Balance.......................................................................................................................29 Limitations..................................................................................................................31 Summary and Conclusions.........................................................................................31 APPENDIX A INFORMED CONSENT............................................................................................33 B EXPANDED DISABILITY STATUS SCALE..........................................................43 LIST OF REFERENCES...................................................................................................45 BIOGRAPHICAL SKETCH.............................................................................................49 v

PAGE 6

LIST OF TABLES Table page 1 Muscle groups being tested, the movement they produce, and the corresponding joint angles...........................................................................................................................20 2 Strength measures for the MS training group (mean SD). All strength (torque) measures in Nm. denotes p<0.05.............................................................................24 3 Strength measures in the non MS control training group (mean SD). All strength (torque) measures in Nm..............................................................................................24 4 Mean balance measures for the MS training group. All balance measures in m. denotes p<0.05.............................................................................................................25 5 Mean balance measures for the control training group. All balance measures in m..25 vi

PAGE 7

LIST OF FIGURES Figure page 1 The self-selected (E) stance.........................................................................................19 2 The feet apart (F) stance..............................................................................................19 3 The foam pad (P) stance..............................................................................................19 4 The semitandem (S) seen from a A) frontal view and B) sagittal view.......................20 5 The tandem (T) stance seen from a A) frontal view and B) sagittal view...................20 6 Diagram depicting the movement of the COP throughout a balance trial...................22 vii

PAGE 8

Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Master of Science EFFECTS OF AN EIGHT-WEEK PROGRESSIVE RESISTANCE TRAINING PROGRAM ON BALANCE IN PERSONS WITH MULTIPLE SCLEROSIS By Gregory M. Gutierrez May 2005 Chair: Mark Tillman Major Department: Department of Exercise and Sports Sciences Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system, which leads to degeneration of the myelin sheaths that protect the neural axons. MS can affect any part of the central nervous system, so persons with MS experience a wider variety of symptoms than most neurological disorders, including problems with balance and strength loss. The aim of this study was to determine if a strength training program, designed to increase muscle strength, could improve postural sway measures in persons with MS. Nine MS subjects and four non-MS controls participated in an eight-week strength-training program. They were tested for isometric strength for their knee extensors, knee flexors, plantar flexors, and dorsiflexors prior to and following the strength-training program. Postural sway was also evaluated before and after training in 5 different stance conditions: 1) self-selected, 2) feet 6 inches apart, 3) feet 6 inches apart on a foam pad, 4) semitandem, and 5) tandem. Four dependent variables were calculated from the tests of postural sway: path length (PL), average speed (AS), antero-posterior viii

PAGE 9

amplitude (AP), and medio-lateral amplitude (ML) of the COP movement. Wilcoxon signed rank tests were performed on all strength and balance variables to determine if changes occurred due to the strength-training program with a conventional significance level of 0.05. For the MS training group, the Wilcoxon signed rank tests revealed a significant increase in PL and AS for the self-selected stance and an increase in isometric strength in the knee flexors. The non-MS control training group had no significant differences in strength or balance after training. The results indicate that strength training is safe for persons with MS and may lead to an increase in muscular strength. However, it does not appear to have a significant effect on standing balance in the stance positions studied. A training program more specific to balance may demonstrate more significant improvement in balance for persons with MS. ix

PAGE 10

CHAPTER 1 INTRODUCTION Multiple sclerosis (MS) is the most common cause of nontraumatic neurological disability affecting young adults in the northern hemisphere (Goodkin, 2000). MS is an autoimmune disorder of the central nervous system that leads to widespread degeneration of the myelin sheaths that encase axons in the central nervous system. The loss of the protective myelin layer causes lesions to form on the axons, which can eventually develop into hardened scleroses that inhibit the normal conduction of nerve impulses down the axons (Herndon, 2000). The extent of axonal loss is variable, but usually substantial, with some axonal loss occurring in every lesion (Trapp et al., 1998). Symptoms from axonal loss cannot be alleviated. However, experimental efforts to improve conduction in neurons without axonal loss have been promising (Herndon, 2000). The four accepted patterns of pathology in MS as defined in 1996 are: 1) relapsing-remitting, 2) secondary progressive, 3) chronic progressive and 4) progressive relapsing MS (Goodkin, 2000). However, specific lines separating these disease patterns are not completely clear thus making specific diagnoses challenging. Furthermore, the variable nature of the disease leads to a difficulty in creating an ideal outcome assessment measure for patients with MS. In all patterns of MS, the level of disability in patients is typically categorized using the Expanded Disability Status Score (EDSS). The EDSS scale was designed by John F. Kurtzke and is based on the maximum function of a patient as limited by their neurological deficits (Kurtzke, 1955). Aside from a few 1

PAGE 11

2 shortcomings, it serves as a familiar and quantifiable method of communication amongst healthcare professionals concerning individuals with MS. MS lesions occur in different areas of the central nervous system and due to this variable distribution of demyelination, people with MS may experience a wider variety of symptoms than any other neurological disease including balance, coordination, strength and sensation disorders (Cattaneo et al., 2002). Furthermore, individuals with MS have been found to have a reduced amount of skeletal muscle and a tendency to supply energy through anaerobic pathways (Kent-Braun et al, 1997), which implies a decrease in the number of slow-twitch muscle fibers. Along with a decrease in skeletal muscle fiber size, persons with MS also face a reduced ability to activate muscle (Lambert et al., 2001), which is associated with the demyelination of nerves (Kent-Braun et al., 1997). This reduced muscle size and compromised motor unit activation cause the muscle weakness associated with MS, which coupled with spasticity, further compromises the ability to balance by affecting the sequencing and force of muscle contraction (Frzovic et al., 2000). Inability to maintain standing balance impacts a patients ability to perform activities of daily living (ADLs) and puts them at an increased risk of falling and subsequent injury, which contributes to the development of a fear of falling that may lead to a change in quality of life (Cattaneo et al., 2002). Therefore, balance assessment and implementation of rehabilitation strategies to improve balance is important in attempting to maintain a favorable quality of life for persons with MS. Patients with MS demonstrate reduced physical activity when compared to non-MS individuals (Ng & Kent-Braun, 1997), which is usually attributed to muscle weakness

PAGE 12

3 and fatigue, but could also be due to a patients fear of falling (Cattaneo et al., 2002). When balance is compromised, even simple ADLs such as dressing, walking, and standing become challenging, which may contribute to the anxiety and depression that affects about 65% of patients with MS (Joffe et al., 1987). The muscle weakness and fatigue demonstrated in persons with MS is consistent with human models of disuse and provides a rationale for therapeutic intervention in the form of exercise training as a means of reversing some of the reduced sensory and motor functions in individuals with MS (Kent-Braun et al., 1997). Individuals with MS experience muscle weakness and more symptomatic fatigue with exercise, however Kent-Braun and colleagues found that they were not weaker compared to healthy individuals when the amount of fat-free mass was taken into account. Therefore, an exercise-training program designed to enhance muscle strength and endurance is a reasonable therapeutic intervention in persons with MS and may be helpful in improving the functional capacity of individuals with MS and offsetting the deleterious effects of their disease. Furthermore, the demyelination associated with MS is not always permanent; remyelination has been documented in MS (Chang et al., 2002). However, these remyelinated nerves often fail to return to baseline functioning because of the decline in activity following an acute MS attack (Herndon, 2000). Strength training may assist in both promoting strength that may have been lost because of physical inactivity and returning proper neural function to the remyelinated tissue. In addition, physical activity has an important benefit in reducing the risk of secondary diseases and improving overall health.

PAGE 13

4 As stated earlier, persons with MS often face a reduced ability to balance, meaning they are frequently unable to maintain the bodys position over its base of support (Rogers et al., 2001). Quantifying a patients level of balance impairment is important, therefore many different techniques have been proposed to measure a persons ability to maintain static or dynamic balance. In research settings, postural sway analysis is widely accepted as a reliable way to quantify the complex and multidimensional nature of a persons standing balance (Tillman & Chow, 2002); however little research has been conducted using postural sway in persons with MS. In addition, the influence of strength training in MS patients has not been evaluated. Thus, the primary aim of this study is to determine whether an eight-week program of progressive resistance training is tolerable for persons with MS and if it could enhance standing balance in ambulatory individuals with MS.

PAGE 14

CHAPTER 2 LITERATURE REVIEW A review of the literature revealed a significant shortage of relevant information concerning strength training and balance in persons with MS. This work is intended to fill that void. More specifically, it aims to provide more data regarding the effects of resistance training on balance in individuals with MS. Multiple Sclerosis Multiple sclerosis (MS) is the most common progressive neurological disease in young adults (Kraft & Wessman, 1974), usually diagnosed in individuals between the ages of 20 and 40. MS is a degenerative inflammatory autoimmune disorder of the central nervous system that destroys the myelin sheaths that encase and insulate the neural axons (Chang et al., 2002; Kidd, 2001). The etiology of MS is not known, however the most widely accepted hypothesis is that it is a virus-induced autoimmune disorder (Herndon, 2000). The myelin in the central nervous system and the cells that form that myelin, the oligodendrocytes, are the primary targets of attack (Herndon, 2000). Lesions form on the myelin sheaths and can eventually develop into hardened scleroses that inhibit the normal conduction of nerve impulses down the axons (Herndon, 2000). MS lesions occur in different areas of the central nervous system and can range from acute plaques with active macrophages containing lipid and myelin degenerating products to chronic, inactive glial scars. The plaques appear to begin with the macrophages and lymphocytes forming perivascular cuffs about the capillaries and venules (Herndon, 2000). This is followed by diffuse infiltration by inflammatory cells, 5

PAGE 15

6 edema, astrocytic hyperplasia, and macrophages consuming the myelin off the axons causing an increasing number of lipid-filled macrophages and demyelinated axons (Prineas, 1975). The extent of axonal loss is variable, but usually substantial (Trapp et al., 1998), with some axonal loss occurring in every lesion. Experimental efforts to improve conduction in neurons without axonal loss may produce dramatic improvements in many symptoms that result from conduction failure in unaffected axons, however the symptoms that result from axonal loss cannot be alleviated by these interventions (Herndon, 2000). There are four accepted patterns of pathology in MS that were defined in 1996, which include: 1) relapsing-remitting, 2) secondary progressive, 3) chronic progressive and 4) progressive relapsing MS. The relapsing-remitting form of MS is the best understood and is more common in younger patients. Approximately 85% of MS patients experience an exacerbation at disease onset (Goodkin, 2000). Multifocal discrete inflammatory demyelinating lesions in both the gray and white matter of the CNS are characteristic of this pattern (Herndon, 2000) and patients are usually stable between exacerbations (Goodkin, 2000). Secondary progressive MS has characteristics consisting of a combination of both relapsing-remitting and chronic progressive MS (Herndon, 2000). In these individuals, old, inactive, multifocal lesions coexist with progressive diffuse demyelination (Herndon, 2000). Chronic progressive MS (also known as primary progressive MS) is more typical in older patients and is less dramatic than relapsing-remitting MS. The demyelination is diffusely scattered involving individual fibers or small groups of fibers interspersed with normal appearing myelinated fibers. The inflammatory infiltrates and macrophages are much more limited and diffuse than in

PAGE 16

7 relapsing-remitting MS (Herndon, 2000). Chronic progressive MS involves a gradual progression of disability without superimposed relapses (Goodkin, 2000). The fourth pattern is termed progressive relapsing MS in which patients experience gradual disability progression accompanied by one or more relapses (Goodkin, 2000). However, specific lines separating these disease patterns are not completely clear which makes specific diagnoses challenging. During the process of demyelination, some conduction failure is unavoidable in the affected fibers. Some lesions are known as clinically silent lesions, which occur when a minority of fibers in a conduction path become demyelinated at any one time, leaving intact conduction in the unaffected fibers in the path (Herndon, 2000). The causes of conduction failure associated with demyelination are not completely understood, but it is hypothesized that it may be due to 1) damage to the nodal sodium channels (Kaschow et al., 1986a & 1986b), 2) a virtual absence of these sodium channels (Ritchie et al., 1977), and/or 3) increased membrane capacitance in the demyelinated region (Waxman, 1995). There is substantial evidence that the nodal membranes are damaged by various enzymes released by the inflammatory cells that appear to produce extensive damage to the myelin. Furthermore, an increased membrane capacitance causes the amount of current required to depolarize the axon to be higher and therefore make impulse conduction slower or in some cases blocked. These characteristics of demyelinated fibers help explain some of the features of the motor fatigability and activity related failure of neurological processes that affect individuals with MS (Herndon, 2000). Expanded Disability Status Score (EDSS) The very nature of the disease leads to a difficulty in creating an ideal outcome assessment measure for patients with MS. In all patterns of MS, level of disability in

PAGE 17

8 patients is typically categorized using the Expanded Disability Status Score (EDSS). The Disability Status Score (DSS) was designed in 1955 by John F. Kurtzke and measures the maximum function of a patient as limited by their neurological deficits (Kurtzke, 1955). The DSS was expanded in 1983 to include more extensive criteria and is now known as the Expanded Disability Status Score. The EDSS scale is based on any lack of function in eight functional systems: 1) Pyramidal (degree of paralysis), 2) Cerebellar (coordination of movement), 3) Brain Stem (cranial nerve functioning), 4) Sensory, 5) Bowel and Bladder, 6) Visual (optic), 7) Cerebral (mental), and 8) Other neurological deficits attributed to MS. The scale ranges form 0 to 10, where 0 is normal functioning and 10 is death due to MS (Kurtzke, 1983). The scale is primarily based on the patients ability to ambulate and deficiencies in any of the eight functional systems make the score more specific to the patients actual disability level. The most favorable aspects of the EDSS scale lie in the coverage of four of the eight functional systems: the pyramidal, cerebellar, visual, and mental systems (Coulthard-Morris, 2000). The pyramidal scale measures disability in the appendages (i.e. paralysis in a limb). Cerebellar function is measured by the ability to coordinate movements, which can be affected by the ataxia suffered by MS patients. Visual impairments are characterized by a loss of visual acuity and/or temporal pallor. Finally, mental functioning is measured by decreases in mentation leading to dementia. Although we will not be directly testing disability level in any of the eight functional systems, the ones that are most important for maintaining balance include the pyramidal, cerebellar, sensory and visual systems.

PAGE 18

9 Even though the EDSS scale is the most widely accepted MS impairment measure and provides a familiar and quantifiable method of communication among health care professionals, it lacks the sensitivity needed to detect the small changes in disease status experienced by people with MS over short time periods. Furthermore, low interrater reliability makes reproducible assessments more challenging. The EDSS scale predominantly measures ambulation and many clinicians feel it does not adequately assess impairment and disability in persons with MS (Coulthard-Morris, 2000). Aside from its few shortcomings, the EDSS scale is the best measure available for quantifying disability in persons with MS to date. However, more comprehensive scales for balance deficits in MS would be beneficial. (See Appendix B for the complete breakdown of the EDSS scale). Symptoms Without proper neural functioning, individuals with MS may suffer from a variety of symptoms, including sensory loss in the appendages, slowly progressive motor deficit, acute motor deficit, optic neuritis, and/or a variety of other ailments (Paty, 2000). Due to the variable distribution of demyelination throughout the central nervous system (Cattaneo et al., 2002), people with MS may experience a wider variety of symptoms than any other neurological disease. These symptoms can lead to problems with balance, coordination, walking mechanics (gait), and postural control. Much of the disability associated with MS results from axonal destruction in very long pathways, such as the pyramidal tract, which supplies the legs and dorsal column with efferent and afferent signals. The imbalance and coordination issues encountered by individuals with MS are due to the slowed conduction in these tracts of proprioceptive impulses and the inability to monitor motor processes that pass through the demyelinated areas (Herndon, 2000). In

PAGE 19

10 many of these individuals, symptoms are exacerbated by an increase in core body temperature of as little as 0.5 C (Paty, 2000). The combination of factors causes individuals with MS to have reduced skeletal muscle fiber size, lower oxidative capacity per unit volume, and a greater tendency for the muscle to supply energy via anaerobic pathways (Kent-Braun et al., 1997). The variability in muscle strength in MS patients appears to be the result of reduced ability to activate muscle (Lambert et al., 2001), in part, because of poor motor unit activation associated with demyelination of nerves (Kent-Braun et al., 1997). Also, MS often results in muscle atrophy and high fatigueability associated with reduced physical function during MS relapses. Following an acute MS attack, intact motor units may not function fully because of disuse, and coupled with spasticity, further compromise the patients ability to balance themselves, affecting both the sequencing and force of muscle contraction (Frzovic et al., 2000). Risk of Falls Balance assessment in conjunction with the implementation of rehabilitation strategies is important in a clinical setting to improve mobility and reduce the risk of falls and subsequent injury in persons with MS. Patients with MS, even those only mildly affected, demonstrate reduced physical activity patterns compared to healthy individuals (Ng & Kent-Braun, 1997). This reduced physical activity is usually attributed to muscle weakness and fatigue, but could also be due to poor balance, frequent falling, fear of falling, thermoregulatory issues and a global decline in functional capacity (Cattaneo et al., 2002). Recreational and social activities may also be reduced, especially when considering that leisure activities are the first lost when an illness is present (Petajan et al., 1999).

PAGE 20

11 In patients with compromised neurological function, falling has a multifactorial origin and consequently there are many reasons why these individuals face an increase risk of falling (Cattaneo et al., 2002). The role of improved balance in decreasing the risk of falls has important implications in reducing injury and long-term disability. Unfortunately, little research has been performed on falling behavior in persons with MS, however the risk of falls in MS is comparable to that of the elderly (Cattaneo et al., 2002). Gryfe and colleagues (1977) reported that 45% of adults age 65 and older experience on average one fall per year. Furthermore, falling is the leading cause of injury related deaths in older adults with 27.2% of injury related deaths in persons age 70-79 being attributed to falling behavior (National Safety Council, 2000). Most published studies have found that balance impairment is an important risk factor in predicting falling behavior (Cattaneo et al., 2002). MS has a global impact on patients and impairs their ability to perform even the simplest ADLs. When balance is compromised, many common activities such as standing, dressing, and walking become challenging. Inability to maintain balance when performing ADLs can lead to anxiety and depression, which already affects about 65% of patients with MS (Joffe et al., 1987). MS, Exercise and Remyelination The muscle weakness and fatigue demonstrated in persons with MS is consistent with human models of atrophy, which provide the rationale for exercise as a therapeutic intervention to reverse reductions in functional capacity in individuals with MS (Kent-Braun et al., 1997). Kent-Braun also found that even though individuals with MS experience more symptomatic fatigue with exercise, they were not weaker when compared to control subjects when differences in fat-free mass were taken into account.

PAGE 21

12 The finding that MS patients are in fact not weaker than control subjects also supports the idea that strength training to increase the quantity and quality of skeletal muscle is a viable means of improving the function and quality of life in individuals with MS. Improvements in muscle strength, endurance, range of motion, and coordination may improve balance in individuals with MS (Armstrong et al., 1983). An exercise-training program designed to enhance these variables may improve the functional capacity of individuals with MS and offset the deleterious effects of their disease. Unfortunately, little research is available on resistance training in MS, however there is information available concerning MS and exercise, specifically aerobic exercise. Several studies have found that even a short term aerobic exercise program can improve aerobic fitness and fatigue, and may lead to an increased level of physical activity and an improved perception of health status in persons with MS (Mostert & Kesselring, 2002; Petajan et al., 1996; Gehlsen et al., 1984). This strengthens the rationale that an exercise-training program may improve quality of life in persons with MS. Furthermore, the demyelination associated with MS is not always permanent; remyelination has been documented in MS (Chang et al., 2002). Bunge and colleagues (1961) demonstrated that central nervous tissue could be remyelinated in a cat and this was later proven to be true in other species including the tadpole, rat, mouse, rabbit and dog (Hommes, 1980). Remyelinated areas in experimental animals show 1) an increased number of oligodendrocytes, which contrary to traditional beliefs can proliferate (Ludwin, 1984), 2) thin myelin sheaths of uniform thickness, and 3) short internodes (Herndon, 2000). Demyelinated areas that become remyelinated are often unused after an MS attack and thus do not reestablish baseline function. Furthermore, demyelination

PAGE 22

13 of newly remyelinated areas may result in scarring that prohibits further remyelination, creating a glial scar. The progressive accumulation of demyelination, axonal damage, and increasing disability provides a rationale for early implementation of therapeutic interventions (Herndon, 2000). Following an acute MS attack, intact motor units may not function fully because of disuse, thus neural recruitment through activity may contribute to positive neural adaptations. Exercise training may facilitate positive neural adaptations and help regain strength that may have been lost because of physical inactivity. Although remyelination has been documented in MS, it will not be evaluated in this study. However, if resistance training contributes to remyelination or improves conduction and recruitment in remyelinated fibers, improvements in strength and function could be significant. Moreover, improving the function of unaffected skeletal muscle may also improve overall physical function and help attenuate disability. Furthermore, physical activity has an important benefit in reducing the risk of heart disease and improving insulin sensitivity. Balance As stated previously, maintaining balance is a major concern for persons with MS. Balance is the ability to maintain the bodys position over its base of support (Rogers et al., 2001). The study of human standing balance has provided insight into the basic mechanisms of neurological integration and into biomechanics in both health and disease (Kirby et al., 1987). For this reason, many different techniques have been proposed to quantify a persons ability to maintain static or dynamic balance. In clinical settings, balance tests must be reliable and valid, use readily available equipment, and be easy to administer and master (Smithson et al., 1998). However, in a research laboratory,

PAGE 23

14 postural sway analysis has been widely accepted as a reliable way to quantify the complex nature of a persons standing balance in both healthy individuals and in special populations (Tillman & Chow, 2002). The center of gravity (COG) of the body shifts continuously even during quiet standing. Postural sway is the corrective actions made by the body in an attempt to control body position and is measured by observing the vertical projection of the COG onto their base of support using force platform technology (Rogers et al., 2001). This vertical projection of the COG onto the force platform is commonly referred to as the center of pressure (COP). Increased sway as measured by the path length, speed of sway, and the amplitudes in the sagittal and coronal planes indicates greater effort to maintain upright position and therefore poorer balance (Rogers et al., 2003). Individuals who have sustained multiple falls demonstrate greater postural sway than age-matched peers (Era, 1985). Analysis of postural sway is a valid measure of standing balance control in many populations, but little research has been conducted using postural sway in persons with MS. Postural control is dependent on complex, integrative processing from a variety of sensory and motor inputs (Teasdale et al., 1991) and it is therefore difficult to quantify the origin of poor balance. There is no single global clinical test that can reflect the complexity and multidimensional nature of balance (Horak, 1987). Instead, balance measurements should test a patients ability to maintain steady standing in a variety of different stance conditions and their ability to remain stable during and after self-generated perturbations (Frzovic et al., 2000). Sway velocity has been found to be higher when the feet are positioned close together resulting in a functionally small base of

PAGE 24

15 support (i.e., semitandem, tandem, or unilateral stances), which indicates that in these conditions there is a higher likelihood of falling and subsequent injury (Rogers et al., 2001). The effect of a strength-training program on balance has not been evaluated in MS patients. However, none of the training in this study is designed to be balance specific. The goal of this study was to evaluate the efficacy of a resistance training program on improving balance in persons with MS without specifically concentrating on balance training so as to provide a rehabilitative intervention available to all individuals with MS without the need for special balance training equipment.

PAGE 25

CHAPTER 3 METHODOLOGY This experiment investigated the effects of resistance training on balance control in persons with MS. Postural stability in a series of different stance positions and altered support surface and isometric strength was measured before and after an 8-week resistance-training program. Subjects Nine MS subjects (7 female and 2 male, mean SD, age: 43.3 12.1 yrs; weight: 69.6 10.3 kg; height: 1.69 0.08 m; EDSS: 4.44 1.67) and four non-MS controls (3 female and 1 male; age: 46.8 11.4 yrs; weight: 82.0 9.1 kg; height: 1.71 0.07 m) were recruited from the local Gainesville population. The subjects were examined by a neurologist for disability status and cleared for participation prior to the outset of the experiment. For participation in this study, the subjects were required to meet the following criteria: Subjects must have been able to walk a distance of at least one city block (100m) Subjects could not have any coexisting orthopedic disorders, visual impairments (blindness, diplopia, blurred vision, severe nystagmus, etc.) or tremor that would adversely affect their ability to balance. Each subject was asked to sign an informed consent agreement approved by the Institutional Review Board of the University of Florida prior to participation. The subjects were asked to fill out a Physical Activity Readiness Questionnaire (PAR-Q), a RISKO: Heart Health Appraisal, and a Health Risk Questionnaire to assure that they were healthy enough to participate in a resistance-training program. 16

PAGE 26

17 Instrumentation Force Platform A Bertec 4060-10 Force Platform System (Bertec Corporation, Columbus, OH), Peak Motus 2000 Motion Analysis System (Peak Performance Technologies, Englewood, CO), and a Motion Analysis Hawk Realtime system (Motion Analysis Corp., Santa Rosa, CA) were utilized to measure postural stability of each subject prior to and after an 8-week progressive resistance-training program. The force platform is capable of measuring forces and moments in the x, y, and z directions, which allows for the center of pressure to be tracked in the frontal and sagittal planes. The analog data were sampled at 40 Hz with the amplifier set at a gain of 5. Isokinetic Dynamometer A Kincom isokinetic dynamometer (Model AP125, Chattecx Corp., Chattanooga, TN) was used to perform all isometric strength testing. Isokinetic dynamometers can be used to measure isometric force production at a preset joint angle for each exercise. The dynamometer sampled data at 100 Hz. Even though subjects trained isotonically, isometric testing was preferred because it has been found to be more reliable (Todd et al., 2004) and data are readily available in the literature for comparison purposes (Chetlin et al., 2004). Subjects were seated and restrained using shoulder and lap belts and the axis of the joint being studied was aligned with the axis of the dynamometer. Seat position and orientation on the dynamometer were stored in the computer database as well as on data sheets to ensure reproducibility of body position for all testing. Experimental Setup Subjects performed the tests of standing balance and muscular strength in the Biomechanics Laboratory in the Center for Exercise Science in the Florida Gym at the

PAGE 27

18 University of Florida prior to and following an eight-week resistance-training program. They were advised to wear comfortable clothing and footwear, although the balance testing was performed with the subjects barefoot. Prior to data collection, the purpose of the study and procedures were explained to the subjects and all questions were answered. Sex, age, height, weight, and lower limb dominance (as ascertained by asking Which foot would you kick a ball with?) was recorded. Postural Sway For the tests of static balance, the subjects were asked to stand on a force platform for two trials lasting 20 seconds each in five different stance positions. The subjects were asked to stand quietly with their hands at their sides in a neutral position for each 20-second trial. All five conditions were administered in a randomized testing order and subjects were allowed to rest as much as needed between trials. The five different stance conditions were: The self-selected (E) stance feet apart at a self selected distance (See Figure 1). Distance between the toes and heels were measured. The feet apart (F) stance feet 15.2 cm (6 in.) apart (See Figure 2) The foam pad (P) stance feet 15.2 cm (6 in.) apart on a foam balance pad; to simulate altered support (See Figure 3). The semitandem (S) stance feet 15.2 cm (6 in.) apart and the heel of their dominant leg in line with the toe of their non-dominant leg (See Figure 4a and 4b) The tandem (T) stance feet inline heel-to-toe and the dominant limb in front. (See Figure 5a and 5b)

PAGE 28

19 Figure 1 The self-selected (E) stance. Figure 2 The feet apart (F) stance. Figure 3 The foam pad (P) stance.

PAGE 29

20 A B Figure 4 The semitandem (S) seen from a A) frontal view and B) sagittal view. A B Figure 5 The tandem (T) stance seen from a A) frontal view and B) sagittal view. Strength Testing The subjects were tested for isometric strength prior to and following an 8-week study period. The muscle groups and corresponding joint angles are depicted in Table 1. The subjects were asked to contract their muscles to attempt to produce maximal force. Muscle Group Tested Exercise Joint Angle Quadriceps Knee Extension Knee Angle = 90 Hamstrings Knee Flexion Knee Angle = 90 Ankle Plantarflexors Plantarflexion Ankle Angle = 0 (neutral) Ankle Dorsiflexors Dorsiflexion Ankle Angle = 0 (neutral) Table 1 Muscle groups being tested, the movement they produce, and the corresponding joint angles. To normalize the force measurement to leg length, the highest force (F) reading was multiplied by the moment arm (r) to determine the maximum torque (T) produced. T = F r

PAGE 30

21 Functional Tests Functional tests were also performed prior to and following the strength-training program. These tests included a 100 ft. walk test and a 3-min step test. For the walk test, subjects were asked to walk a distance of 100 ft as quickly and as safely as possible. The time taken to complete the walk was recorded. For the step test, subjects were asked to step up onto a platform 15.2 cm (6 in.) above the ground with both legs as many times as possible in a 3-min period and total number of steps were recorded. Subjects were allowed any assistance necessary to complete the step test. Resistance Training During the next eight weeks of the study period, MS and non-MS control subjects were asked to visit the Center for Exercise Science or Living Well Fitness and Wellness Center twice a week, either Monday/Thursday or Tuesday/Friday sessions to perform resistance training exercises. Exercises were performed under the supervision of staff trained in cardiopulmonary resuscitation, emergency procedures, and proper exercise safety for individuals with disabilities. A training protocol was established using recognized criteria for load assignment in older/disabled persons (ACSM, 2000). During the first training session, subjects were asked to lift a submaximal load until they could no longer complete a full repetition for each exercise (2-20 repetitions). A predicted 1-repitition maximum (1-RM) was determined using the Kuramoto and Payne (1996) prediction equation for older women. During the second training session, subjects performed one set of 6-10 repetitions at 50% of the predicted 1-RM. In subsequent sessions, subjects completed one warm-up set and one training set for each exercise. Their warm-up consisted of five repetitions at 40% of the predicted 1-RM on each of the weight-machines. The training set consisted of 10-15 repetitions at 70% of predicted 1

PAGE 31

22 RM for lower limb exercises (using one leg at a time leg) including knee flexion and extension, plantar flexion, trunk flexion and trunk extension; in that order every time. Exercises were performed at a self-selected, comfortable pace with at least one minute of rest between exercises. Each training session did not exceed 60 minutes. When subjects were able to complete 25 repetitions for any exercise in consecutive sessions, the resistance was increased by 2-5%. All training sessions were supervised. Data Reduction The COP was tracked for all trials and the average COP path length (PL) the sum of the displacement vectors, average path speed (AS) the PL divided by the total time, and the amplitudes in the medio-lateral (ML) frontal plane, and antero-posterior (AP) sagittal plane directions were calculated for each of the five conditions. A representative diagram of COP movement throughout a trial is depicted in Figure 6. Figure 6 Diagram depicting the movement of the COP throughout a balance trial.

PAGE 32

23 Design/Analysis This study was a pretest-posttest control group design. Descriptive statistics (means and standard deviations) were calculated for each of the four dependent variables (total sway path length, average sway speed, and sway amplitude in the AP and ML directions) in each of the five stance conditions. Due to the small sample size, nonparametric Wilcoxon signed ranks tests were performed to determine if any changes occurred in any balance and/or strength measures following eight weeks of strength training. Descriptive statistics were calculated for the functional tests, however no statistical tests were performed on the data. All statistical tests were conducted with the conventional level of significance, =.05.

PAGE 33

CHAPTER 4 RESULTS All subjects completed the eight-week resistance-training program (16 sessions) with no MS-related exacerbations reported. The protocol was occasionally adjusted when subjects missed days between workouts for personal reasons, although adherence remained at 100%. Strength Eight of the nine MS subjects were tested for strength prior to and following the strength-training program. One subject was unable to produce muscular force from several lower extremity muscle groups at the time of the day the pre-testing took place, therefore he was excluded from the isometric strength analysis. The MS training group significantly increased strength in the knee flexors (p<0.05). Although not statistically significant, all other muscle groups also increased isometric strength (Table 2). Stance Pre Post % Change p-value Knee Extension 66.8 29.5 81.6 38.7 + 22.17 % 0.069 Knee Flexion 34.9 17.2 42.7 14.4 + 22.02 % 0.012* Plantar Flexion 45.6 28.9 68.2 33.5 + 49.54 % 0.069 Dorsiflexion 25.7 10.8 28.2 9.5 + 9.89 % 0.484 Table 2 Strength measures for the MS training group (mean SD). All strength (torque) measures in Nm. denotes p<0.05. Stance Pre Post % Change p-value Knee Extension 94.4 24.5 112.5 30.3 + 19.15 % 0.068 Knee Flexion 43.5 9.8 50.7 18.3 + 16.54 % 0.144 Plantar Flexion 71.1 24.7 92.5 47.6 + 30.13 % 0.144 Dorsiflexion 42.7 9.7 45.1 10.7 + 5.45 % 0.144 Table 3 Strength measures in the non MS control training group (mean SD). All strength (torque) measures in Nm. 24

PAGE 34

25 The non-MS control training subjects displayed increases in isometric muscle strength similar to those seen in the MS group, although again not statistically significant (Table 3). Balance Several of the MS subjects could not complete certain stances for the entire 20 seconds, primarily the more difficult stances, such as the T and P stances. However, subjects that did require assistance required a similar amount of assistance in the pre-test and post-test. In the MS subjects, a significant increase was noted in the path length and average speed for the E stance (p=0.028), however none of the other dependent variables for any of the other stances changed significantly (Table 4). Furthermore, the control subjects did not significantly change any of the dependent balance variables evaluated (Table 5). Stance PL pre PL post p AP pre AP post p ML pre ML post p E 0.780 1.068 0.028* 0.041 0.046 0.139 0.026 0.032 0.214 F 0.841 1.001 0.066 0.051 0.050 0.767 0.033 0.036 0.374 P 1.109 1.297 0.374 0.084 0.071 0.859 0.062 0.057 0.859 S 1.100 1.234 0.441 0.054 0.044 0.374 0.067 0.045 0.767 T 1.305 1.329 0.953 0.062 0.069 0.260 0.047 0.038 0.314 Table 4 Mean balance measures for the MS training group. All balance measures in m. denotes p<0.05. Stance PL pre PL post p AP pre AP post p ML pre ML post p E 0.395 0.681 0.068 0.018 0.019 0.715 0.009 0.008 0.715 F 0.416 0.663 0.144 0.020 0.016 0.144 0.009 0.012 1.000 P 0.608 0.813 0.144 0.046 0.042 0.144 0.030 0.025 0.273 S 0.545 0.766 0.144 0.028 0.022 0.144 0.029 0.025 0.144 T 0.829 0.911 0.465 0.044 0.025 0.144 0.038 0.034 0.715 Table 5 Mean balance measures for the Control training group. All balance measures in m.

PAGE 35

26 Functional Tests Prior to strength training the MS group was able to complete the 100 ft walk in an average time of 33.9 s and following training that time decreased to 31.5 s. The control group was able to complete the walk in 14.3 s, which decreased to 13.8 s after training. The MS group completed 58.1 steps in the 3-min period prior to training, which increased to 68.2 following training. The control group began the training able to step an average of 111.6, which increased to 127.3 after training.

PAGE 36

CHAPTER 5 DISCUSSION The aim of this study was to evaluate the effects of an eight-week progressive resistance-training program on postural sway in persons with MS. More specifically, the efficacy of a training program that is not balance specific in improving the balance of persons with MS was evaluated. Furthermore, little research is available concerning lower extremity muscle strength training in persons with MS, therefore the study was also designed to determine whether persons with MS could adhere to and endure a resistance training program. The results indicate that persons with MS can complete an eight-week resistance-training program, with no MS exacerbations, and increase lower extremity muscle strength. However, it remains unclear whether a strength training program, not designed to be balance specific, can positively influence balance in individuals with MS. Strength A statistically significant increase was noted in only one of the muscle groups tested in this experiment. Although not statistically significant, strength increased in all muscle groups for both the MS subjects and the controls. In fact, the plantar flexor isometric muscle strength increased 45% in the MS training group. Increases in muscle strength were expected from the training program, in that it was designed to increase lower extremity muscle strength. The lack of statistical significance may be due to the limited sample sizes in both the MS and control groups and high variability. Debolt and McCubbin (2004) found that a home-based resistance-training program was well tolerated by persons with MS, and improved their lower extremity muscle 27

PAGE 37

28 power. Furthermore, Kraft et al. (1996a & 1996b) resistance trained arms and legs in MS subjects for eight weeks and also found improvements in strength, along with improved function and psychosocial well-being. Most recently, White et al. (2004) found increased strength and function, along with a decrease in daily fatigue after eight weeks of lower extremity strength training. These studies, along with the findings of this research support the practicality of a strength-training program as a viable means to increase strength in individuals with MS. Increased strength is desirable in this population because they are often faced with an increased level of fatigue, which decreases their daily activity levels, and eventually causes muscle atrophy. An increase in strength due to strength training may help to counteract the atrophic changes noted in the musculature of individuals with MS, and perhaps increase their daily activity levels. Furthermore, it is known that the first neuromuscular adaptations to strength training are more neural than muscular. Positive neural changes are especially important in a population afflicted with a neurological disorder. Neural recruitment gained through physical activity may have a favorable functional outcome, although this may be limited by the severity the MS lesions already present. This suggests that resistance training may be an early intervention strategy in persons with MS that may help to maintain function and hopefully, limits exacerbation of MS symptoms. In fact, in all research previously mentioned concerning strength training in individuals with MS, no MS related exacerbations were reported and there were no reports of increased MS-related symptoms (Kraft et al., 1996a & 1996b; Debolt and McCubbin, 2004; White et al. 2004).

PAGE 38

29 Strength training is known to have many benefits, including, but not limited to, increasing bone mineral density (Asikainen et al., 2004). Since most individuals who suffer from MS are female, and females are at a higher risk of osteoporosis, strength training to increase bone mineral density may have profound effects on the quality of life of these individuals as the age. Furthermore, the performance of the subjects in the functional tests also lends itself to supporting strength training in this population. All subjects were able to walk faster and step more following training. This should be expected from a strength-training program designed to enhance muscle strength and endurance. Balance Decreased ability to maintain balance is a concern in individuals with MS, which may lead to an increased susceptibility to falls. For this reason, an intervention strategy to improve balance is desirable for individuals with MS. This study was intended to determine if static balance could be improved with a training program that is not balance specific. As stated earlier, the training protocol in this study was designed to increase lower extremity muscle strength. A significant increase was noted in the strength of knee flexors after strength training, and the knee extensors and plantar flexors also tended to be stronger after the strength training, however only two measures of postural sway were significantly different following training, and that change represented a decrease in postural stability. The results suggest that strength training has little effect on postural sway in persons with MS or control subjects. The MS subjects who participated in this study represented a broad spectrum of disability levels, which is common for a condition like MS. Some subjects had little or no visible or obvious disability, while others required assistance to complete the tests of

PAGE 39

30 standing balance. For those who did require assistance to complete the tests of standing balance, the amount of assistance required did not change for between the pre and post-tests. Furthermore, the data indicate that the strength training did not improve postural sway characteristics in these subjects. This could be due to a couple of different possible explanations: 1) the subjects were perhaps too disabled, more specifically, their loss of function was already too extensive, to have dramatic improvements in just eight weeks, or more likely 2) the training was not specific enough to the stances studied to cause positive alterations in postural sway. Even though strength did increase in these subjects, that increase did not result in improvements in static balance. The finding that increased strength does not significantly influence balance is supported by the work of Katayama et al. (2004), who found that knee and toe muscle power does not appear to be a dominant factor in maintaining balance. This corroborates the assertion that lower extremity muscle strength training may not have a significant influence on postural sway. On the other hand, Judge and colleagues (1993) found that an exercise program emphasizing postural control, moderate resistance training and walking improved single leg static balance in neurologically intact elderly individuals, however double leg static balance measures did not improve. Two important conclusions can be dawn from this work: 1) a training intervention intended to improve balance should be focused on training for balance, and 2) double leg static stances may not be sufficiently challenging to unimpaired individuals to show significant changes after any training program. Although most subjects in this study were impaired in some way, some of the MS subjects had no obvious disability and may not have been challenged enough with the stances tested to change postural sway characteristics significantly. This

PAGE 40

31 assertion is supported by the performance of the control group, who showed no significant changes in any of the balance measures tested. Limitations There are limitations in the experimental design that may account for the lack of significant changes in postural sway characteristics. As stated earlier, eight weeks may not have been a sufficient amount of time to significantly influence balance. Therefore, a more elongated and extensive strength-training program may have elicited more significant responses. Furthermore, a larger subject pool may help eliminate some of the variability, which could account for the lack of statistically significant differences. With such a small sample size, even a small amount of variability would eliminate statistical significance. The strength gains should be interpreted cautiously because the training was isotonic and the testing was isometric, so strength gains noted in this work may not be clinically applicable. Another possible origin of variability is the change in motion analysis systems used to collect the postural sway data midway through the study protocol. Unfortunately, several subjects were pre and post-tested on different motion analysis systems, therefore some inherent variability between the two systems may have changed the final data enough to account for the lack of statistical significance. Additional work with larger sample sizes, longer training protocol, more intense training, and more balance specific training is desirable and could lead to promising intervention strategies to improve balance and reduce the risk of falls in individuals with MS. Summary and Conclusions This study was designed to determine the efficacy of a progressive resistance-training program on postural sway in persons with MS. The training program was not intended to be balance specific. It was designed to focus on increasing general lower

PAGE 41

32 extremity muscle strength. Only two out of 20 postural sway characteristics evaluated significantly changed following strength training in the MS group. Strength increased significantly in the knee flexors and tended to increase for the knee extensors and plantar flexors. It appears that the increased strength in the lower extremity may not influence static balance in individuals with MS. Additional research with larger sample sizes for both groups, and increased duration and/or intensity of training is recommended. A training program designed to focus specifically on balance would potentially demonstrate more significant changes in balance and could present a promising intervention strategy to improve balance and reduce the risk of falls in persons with MS, or any other neurological disorder.

PAGE 42

APPENDIX A INFORMED CONSENT IRB# 340-2002 Informed Consent to Participate in Research You are being asked to take part in a research study. This form provides you with information about the study. The Principal Investigator (the person in charge of this research) or a representative of the Principal Investigator will also describe this study to you and answer all of your questions. Before you decide whether or not to take part, read the information below and ask questions about anything you do not understand. Your participation is entirely voluntary. 1. Name of Participant ("Study Subject") _____________________________________________________________________ 2. Title of Research Study Resistance Training Effects on Muscle Function in Multiple Sclerosis 3. Principal Investigator and Telephone Number(s) Lesley J. White, Ph.D., Assistant Professor Department of Exercise and Sport Sciences College of Health and Human Performance University of Florida (352) 392-9575 ext. 1338 Email: lwhite@hhp.ufl.edu 33

PAGE 43

34 John Chow, Ph.D., Associate Professor Department of Exercise and Sport Sciences College of Health and Human Performance University of Florida (352) 392-0584 ext. 1263 Anne L. Rottmann, M.D., Neurologist 4410 West Newberry Rd. Suite A3 Gainesville, FL 32607 After Hours/Emergency Telephone Number: (352) 374-2222 4. Source of Funding or Other Material Support National Multiple Sclerosis Society What is the purpose of this research study? The primary purpose of this study is to determine whether a sixteen-week progressive resistance training exercise program influences measures of your muscles performance and your ability to walk and balance more effectively. This study is part of a project to learn more about your muscles ability to become more effective in producing energy during activities after you exercise train. We plan to measure your walking mechanics and your balance before and after you exercise train. We will also get pictures of your leg muscles using a technique called magnetic resonance imaging (MRI). Then we can get information about the chemistry of your muscle using a technique called magnetic resonance spectroscopy (MRS). 6. What will be done if you take part in this research study? If you volunteer for this study you will be asked to participate in a 21 week experimental period that consists of evaluation of several functional measures such as muscle strength balance, and walking mechanics, followed by a sixteen week exercise program. Midpoint evaluation will occur after 8 weeks of resistance training. Follow-up evaluation will occur after sixteen weeks of exercise training program. Listed below are descriptions of each visit should you choose to participate in this study. Visit #1 On the first visit of week one of the study, you will be familiarized with the experimental protocol and be examined by a neurologist. Your disability status and physical readiness to participate in an exercise protocol will be assessed. If you are cleared to participate in this study, you will be asked to read and sign an informed consent, which will inform you of all the risks/benefits of participation in the experiment. The approximate time required for this visit will be 60 minutes. Visit #2

PAGE 44

35 On the second visit of week 1, you will have an MRI/MRS performed on your legs. During the MRI/MRS you will lie on a bed, which rolls in the opening of a large magnet. A flat coil of wire (a radiofrequency coil) will be placed on your thigh and calf. A computer will look at the radio waves passing through your leg and constructs pictures and chemical information of your muscles. The total procedure will last approximately 45 minutes. An MRI/MRS is used routinely to detect structures or gain chemical information about the muscles of healthy subjects or hospital patients. Just prior to and following the MRI, we will draw 20ml of blood (about 4 teaspoons) by venipuncture to test levels of blood sugar, triglycerides, and cholesterol. This will take an additional fifteen minutes. The total time of this visit, including MRI/MRS and blood sampling, will take approximately 60 minutes. Visit #3 During the third visit in week 2 of the experimental period, you will have your body composition assessed using a three-site skinfold technique, and measurements of the waist and hip circumference will be taken. You will then be asked to perform muscular strength and endurance tests on a Kin-Com isokinetic dynamometer for the following exercises: abdominals, back, leg extensions, leg curls, and ankle flexion exercises. The Kin-Com is a muscle testing machine commonly used for evaluating muscle function in healthcare settings. During the testing, you will be asked to be seated on the machine and you will be asked to perform a muscle contraction at a constant, predetermined speed. The discomfort associated with this procedure is minimal, but will require you to put forth a strong effort. In conjunction with the muscle testing, two self-adhesive electrodes (2 x 4) will be placed on your thigh close to your knee and hip. During your knee extension strength evaluation an electrical pulse will be delivered to your thigh muscle. The level of stimulation should not be painful, though it may cause a prickly sensation on your skin and will make your muscle feel like it is being squeezed. The feeling will be very similar to what you experience when you climb stairs or ride a bicycle for an extended period of time. The procedure is used to evaluate the ability of your muscle to generate force during the strength testing. The strength testing will be used to determine your 10-repetition maximum, which will be used in the training aspect of the study. Testing is expected to take 60 minutes. Visit #4 During the fourth visit in week 2 of the experimental period, you will be asked to perform tests of balance, and gait (walking mechanics). For the balance test, you will be asked to stand on a force plate without support for 20 seconds. You will be asked to repeat this test 3 times. Balance tests will be completed with your eyes open and closed. A test of your functional reach will be completed after a brief rest period following the balance test. During the functional reach test you will reach forward as far as you can until your heels come off the floor. A safety harness will be used to ensure your safety during functional tests. The harness may cause minor skin irritation. For the gait analysis you will be asked to walk on an 8-meter walkway twice. The gait testing will require you to have special sensors and reflective markers placed on your lower back and legs. The special sensors will measure your muscle activity during walking. Your skin preparation will include shaving areas displaying body hair with an electric razor that causes no skin

PAGE 45

36 irritation. Your skin will then be sanitized with an alcohol swab. There is not any expected irritation or discomfort associated with the shaving or alcohol swabbing. Testing will also consist of a timed 25-foot walk test where you will be asked to walk as fast as possible within your comfort. Lastly, you will be asked to perform a three-minute step test where you will be asked to step up onto a platform as many times as possible in the allotted three minutes. During this visit we will ask you to wear shorts and exercise shoes. These tests will be conducted in the Biomechanics Laboratory in the Center for Exercise Science and will take will take approximately 60 minutes to complete. Visits #5 and #6 During the fifth and sixth visits, in week 3 of the experimental period you will be asked to repeat all the testing performed in week 2. This is designed to more accurately quantify baseline measures. These visits will each take approximately 60 minutes to complete. Visits #7 through #22 During the next eight weeks of the study period (weeks 4-11) you will be asked to visit the Center for Exercise Science or Living Well Fitness and Wellness Center, or North Florida Regional YMCA twice a week, either Monday/Thursday or Tuesday/Friday sessions to perform resistance training exercises. Twenty milliliters (4 teaspoons) of blood will be drawn before and after exercise to determine the effect of training on glucose, triglycerides, and cholesterol. Subjects will be required to attend strength training sessions requiring blood draws at the Center for Exercise Science. All training will occur in a supervised exercise environment with staff trained in cardiopulmonary resuscitation and emergency procedures. The staff will also be trained in proper exercise safety for individuals with disabilities. During each exercise session you will be asked to perform one set of 15-20 repetitions at 70% of your 10-repetition maximum (RM) for each of the following exercises: leg extensions, leg curls, ankle plantarflexion, and an abdominal/lower back regimen using free-weight machines or a Kin-com isokinetic dynamometer. This is not a maximal exercise protocol and is not designed to be exhaustive. When you are able to complete 15 repetitions with proper technique, for two consecutive sessions, the resistance will be increased by 10% of your 10-RM. To assess your level of fatigue you will be asked to rate your level of effort (perceived exertion) at the end of each exercise. Because of the functional variability of MS individuals, the protocol may be adjusted on an individual basis to maintain your comfort and safety. A Certified Strength and Conditioning Specialist (CSCS) or exercise physiology research assistant will supervise all training sessions. Each training session will last 30-45 minutes. You will be asked to perform a self-reported dietary recall at weeks 2, 4, 8, 12, and 16 of the experimental period when you come to the laboratory for exercise training. You will be asked to follow the dietary guideline established by the American Heart Association for the duration of the study to ensure that the appropriate amounts of nutrients are being consumed to meet the nutritional needs associated with a strength-training program. These guidelines are similar to those suggested for the MS population.

PAGE 46

37 You will also be asked to complete a functional independence measure at weeks 1, 5, 7, 9, 11, 16, and 20. We will also randomly ask you to wear an accelerometer throughout one day during weeks 2, 12, and 20 to assess your level of activity. The accelerometer is a small device that will be worn around the waist to measure your activity throughout the day. Visit #23 (Midpoint evaluation) On the first visit of week 12 of the study period, following first phase of the exercise training period, you will be asked to perform all testing measures as performed at the beginning of the study. Again, you will be asked to perform self-reported questionnaires examining functional independence and fatigue impact. The completion of these questionnaires will take approximately 10 minutes. Following questionnaire completion, your body composition will be reassessed via the three-site skinfold technique, and measurements of the waist and hip will be taken. Twenty milliliters (about four teaspoons) of blood will be taken before and after exercise to determine if any changes in your resting levels of blood glucose, triglycerides, and cholesterol occurred. Again, these factors will be examined for experimental use and for your own personal information. This portion of the study will take 45 minutes. The total time for this visit will be approximately 90 minutes. Visit #24 During the second visit of week 12 of the study period, you will be asked to perform tests of muscle strength and endurance on a Kin-com isokinetic dynamometer with electrical stimulation. This testing will follow the same procedure and include the same exercises as was performed in weeks 2 and 3 of the study. Testing will take approximately 60 minutes. Visit #25 During the first, and only, visit of week 13 of the study, you will be asked to perform follow-up tests of balance, and gait. Testing will also consist of a timed 25-foot walk and the three-minute step test. These tests will again be conducted in the Center for Exercise Science Biomechanics Laboratory and will take approximately 60 minutes to complete. Visit #26-42 During the next eight weeks of the study period (weeks 13-21) you will be asked to continue twice weekly exercise training sessions until you have completed 16 consecutive weeks of training. Twenty milliliters (4 teaspoons) of blood will be drawn before and after exercise at week 20 to determine the effect of training on glucose, triglycerides, and cholesterol. Any special needs that you require will be accommodated throughout the duration of the study. All data collected in the post-testing phase will be compared to the information gathered in the pre-testing to determine if any improvements were made in any of the factors that were studied in this experiment. 7. What are the possible discomforts and risks?

PAGE 47

38 The risks of drawing blood from a vein include discomfort at the site of puncture; possible bruising and swelling around the puncture site; rarely an infection; and, uncommonly, faintness from the procedure. The risk from having a catheter inserted into an arm vein for time needed in this study is possible infection of the vein, but the risk is very low because we will have a trained phlebotomist collecting the blood samples. The amount of blood we will take should have no negative effects. You will be closely watched for any possible ill effects. There is also a risk of mild muscle soreness associated with the initiation of any strength-training program, however this risk is minimal. Potential soreness may last for three days but is not expected to limit any activities. There is also a slight risk of skin irritation associated with electrode and reflective marker placement for the electromyographic analysis. Balance and gait testing with the safety harness may cause some mild skin irritation. There is also a risk of skin irritation associated with the electrical pulses to your thigh, however, the equipment used is highly reliable with safety features to minimize pulse strength. The short duration pulses may contribute to mild muscle soreness, however the risk is minimal. The risks of MRI/MRS are: the MRI/MRS scanner contains a very strong magnet. Therefore, you may not be able to have the MRI/MRS if you have any type of metal implanted in your body, for example, any pacing device (such as a heart pacer), any metal in your eyes, or certain types of heart valves or brain aneurysm clips. Someone will ask you questions about this before you have the MRI/MRS. There is not much room inside the MRI/MRS scanner. You may be uncomfortable if you do not like to be in close spaces ("claustrophobia"). During this procedure, you will be able to talk with the MRI/MRS staff through a speaker system, and in the event of an emergency, you can tell them to stop the scan. The MRI/MRS scanner produces a loud hammering noise, which has produced hearing loss in a very small number of patients. You will be given earplugs to reduce this risk. If you are a woman of childbearing potential, there may be unknown risks to the fetus. Therefore, before you can have the MRI/MRS, you must have a pregnancy test. This test will be done at no charge. 8a. What are the possible benefits to you? It is possible that you may experience improvements in gait, balance, muscular strength, and endurance. You will also receive eight weeks of personal exercise training. Blood cholesterol, nutritional profile and analysis, will be provided for your own personal records. 8b. What are the possible benefits to others?

PAGE 48

39 Research findings from this study may help in the design and use of therapeutic exercises designed to help other individuals with MS. 9. If you choose to take part in this research study, will it cost you anything? All costs associated with the assessment of your percent body fat, gait analysis, and quality of your diet will be paid for by the Center for Exercise and Sport Sciences. Additional measurements of blood cholesterol, glucose, and insulin levels will be absorbed by funding supporting the principal investigators of the study. The principal investigator will also pay for the MRI/MRS and any required pregnancy test. 10. Will you receive compensation for taking part in this research study? At the completion of the study, subjects with multiple sclerosis will receive $200.00. Subjects who do not have multiple sclerosis will not receive monetary compensation for study participation. 11. What if you are injured because of the study? If you experience any injury that is directly caused by this study, only professional consultative care that you receive at the University of Florida Health Science Center will be provided without charge. However, hospital expenses will have to be paid by you or your insurance provider. No other compensation will be offered. 12. What other options or treatments are available if you do not want to be in this study? The exercise training and dietary counseling are in addition to standard therapy for your condition. You may choose to continue with your current therapy. 13a. Can you withdraw from this research study? You are free to withdraw your consent and to stop participating in this research study at any time. If you do withdraw your consent, there will be no penalty, and you will not lose any benefits you are entitled to. If you decide to withdraw your consent to participate in this research study for any reason, you should contact Dr. Lesley White at (352) 392-9575 ext 1338. If you have any questions regarding your rights as a research subject, you may phone the Institutional Review Board (IRB) office at (352) 846-1494.

PAGE 49

40 13b. If you withdraw, can information about you still be used and/or collected? If you withdraw from the study, information about you will not be used or collected any further. 13c. Can the Principal Investigator withdraw you from this research study? You may be withdrawn from the study without your consent for the following reasons: failure to make scheduled training visits and cardiovascular risk factors contraindicating your participation in a strength training program. 14. How will your privacy and the confidentiality of your research records be protected? Authorized persons from the University of Florida, the hospital or clinic (if any) involved in this research, and the Institutional Review Board have the legal right to review your research records and will protect the confidentiality of them to the extent permitted by law. Otherwise, your research records will not be released without your consent unless required by law or a court order. If the results of this research are published or presented at scientific meetings, your identity will not be disclosed. 15. How will the researcher(s) benefit from your being in this study? In general, presenting research results helps the career of a scientist. Therefore, the Principal Investigators may benefit if the results of this study are presented at scientific meetings or in scientific journals.

PAGE 50

41 16. Signatures As a representative of this study, I have explained to the participant the purpose, the procedures, the possible benefits, and the risks of this research study, the alternatives to being in the study, and how privacy will be protected: ___________________________________________ _____________________ Signature of Person Obtaining Consent Date You have been informed about this studys purpose, procedures, possible benefits, and risks; the alternatives to being in the study; and how your privacy will be protected. You have received a copy of this Form. You have been given the opportunity to ask questions before you sign, and you have been told that you can ask other questions at any time. You voluntarily agree to participate in this study. By signing this form, you are not waiving any of your legal rights. ____________________________________________ _____________________ Signature of Person Consenting Date

PAGE 51

42 Consent to be Videotaped and to Different Uses of the Videotape(s) With your permission, you will be videotaped during this research. Your name or personal information will not be recorded on the videotape, and confidentiality will be strictly maintained. When these videotapes are shown, however, others may be able to recognize you. The Co-Principal Investigator of this study, John Chow, Ph.D will keep the videotape(s) in a locked cabinet. These videotapes will be shown under his direction to students, researchers, doctors, or other professionals and persons. Please sign one of the following statements that indicates under what conditions Dr. John Chow, Ph.D has your permission to use the videotape. I give my permission to be videotaped solely for this research project under the conditions described. ______________________________Signature ____________________________Date I give my permission to be videotaped for this research project, as described in the Informed Consent Form, and for the purposes of education at the University of Florida Health Science Center ______________________________Signature ____________________________Date I give my permission to be videotaped for this research project, as described in the Informed Consent Form; for the purposes of education at the University of Florida Health Science Center; and for presentations at scientific meetings outside the University. ______________________________Signature _____________________________Date

PAGE 52

APPENDIX B EXPANDED DISABILITY STATUS SCALE The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a Functional System Score (FSS) in each of these systems: pyramidal cerebellar brainstem sensory bowel and bladder visual cerebral other EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory, while steps 5.0 to 9.5 are defined by the impairment to ambulation. Kurtzke Expanded Disability Status Scale 0.0 Normal neurological examination 1.0 No disability, minimal signs in one FS 1.5 No disability, minimal signs in more than one FS 2.0 Minimal disability in one FS 2.5 Mild disability in one FS or minimal disability in two FS 3.0 Moderate disability in one FS, or mild disability in three or four FS. Fully ambulatory 3.5 Fully ambulatory but with moderate disability in one FS and more than minimal disability in several others 4.0 Fully ambulatory without aid, self-sufficient, up and about some 12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Fully ambulatory without aid, up and about much of the day, able to work a full day, may otherwise have some limitation of full activity or require minimal assistance; characterized by relatively severe disability; able to walk without aid or rest some 300 meters. 5.0 Ambulator y without aid or rest for about 200 meters ; disabilit y severe enou g h to 43

PAGE 53

44 impair full daily activities (work a full day without special provisions) 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to preclude full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Constant bilateral assistance (canes, crutches, braces) required to walk about 20 meters without resting 7.0 Unable to walk beyond approximately five meters even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; May require motorized wheelchair 8.0 Essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms retains some self care functions 9.0 Confined to bed; can still communicate and eat. 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS

PAGE 54

LIST OF REFERENCES Armstrong LE, Winant DM, Swasey PR, Seidle ME, Carter AL, Gehlsen G. Using Isokinetic Dynamometry to Test Ambulatory Patients with Multiple Sclerosis. Physical Therapy. Aug 1983, 63(8): 1274-9. Asikainen TM, Kukkonen-Harjula K, Miilunpalo S. Exercise for Health for Early Postmenopausal Women: a Systematic Review of Randomised Controlled Trials. Sports Medicine. Nov 2004, 34(11): 753-78. American College of Sports Medicine (ACSM). ACSM's Guidelines for Exercise Testing and Prescription. 6th Edition. Philadelphia (PA): Lippincott, Williams & Wilkins, 2000. Bunge MB, Bunge RP, Ris H. Ultrastructural Study of Remyelination in an Experimental Lesion in Adult Cat Spinal Cord. Journal of Biophysical and Biochemical Cytology. 1961, 10: 67-94. Cattaneo D, DeNuzzo C, Fascia T, Macalli M, Pisoni I, Cardini R. Risk of Falls in Subjects with Multiple Sclerosis. Archives of Physical Medicine and Rehabilitation. Jun 2002, 83(6): 864-7. Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating Oligodendrocytes in Chronic Lesions of Multiple Sclerosis. New England Journal of Medicine. Jan 2002, 346(3), 165-73. Chetlin RD, Gutmann L, Tarnopolsky M, Ullrich IH, Yeater RA. Resistance Training Effectiveness in Patients with Charcot-Marie-Tooth Disease: Recommendations for Exercise Prescription. Archives of Physical Medicine and Rehabilitation. Aug 2004; 85(8): 1217-23. Coulthard-Morris L. Clinical and Rehabilitation Outcome Measures. In Burks JS and Johnson KP (Eds.), Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. (221-290). New York: Demos Medical Publishing, 2000. Debolt LS, McCubbin JA. The Effects of Home-Based Resistance Exercise on Balance, Power, and Mobility in Adults with Multiple Sclerosis. Archives of Physical Medicine and Rehabilitation. Feb 2004; 85(2): 290-7. Era P, Heikkinen E. Postural Sway During Standing and Unexpected Disturbance of Balance in Random Samples of Men of Different Ages. Journal of Gerontology. May 1985; 40(3): 287-95. 45

PAGE 55

46 Frzovic D, Morris ME, Vowels L. Clinical Tests of Standing Balance: Performance of Persons with Multiple Sclerosis. Archives of Physical Medicine and Rehabilitation. Feb 2000, 81: 215-21. Gehlsen GM, Grigsby SA, Winant DM. Effects of an Aquatic Fitness Program on the Muscle Strength and Endurance of Patients with Multiple Sclerosis. Physical Therapy. 1984, 64: 653-7. Goodkin DE. Treatment of Progressive Forms of Multiple Sclerosis. In Burks JS and Johnson KP (Eds.), Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. (177-200). New York: Demos Medical Publishing, 2000. Gryfe CI, Amies A, Ashley MJ. A Longitudinal Study of Falls in an Elderly Population: I. Incidence and Morbidity. Age and Ageing. 1977, 6: 201-10. Herndon, RM. Pathology and Pathophysiology. In Burks JS and Johnson KP (Eds.), Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. (35-45). New York: Demos Medical Publishing, 2000. Hommes OR. Remyelination in Human CNS Lesions. Progressive Brain Research. 1980, 53: 39-63. Horak FB. Clinical measurement of postural control in adults. Physical Therapy. Dec 1987; 67(12): 1881-5. Joffe RT, Lippert GP, Gray TA, Sawa G, Horvath Z. Mood Disorder and Multiple Sclerosis. Archives of Neurology. Apr 1987, 44(4): 376-8. Judge JO, Lindsey C, Underwood M, Winsemius D, Keshner EA. Balance Improvements in Older Women: effects of exercise training. Physical Therapy. 1993, 73 (4); 254-66. Kasckow J, Abood LG, Hoss W, Herndon RM. Mechanism of Phospholipase A2-Induced Conduction Block in Bullfrog Sciatic Nerve I: Electrophysiology and Morphology. Brain Research. 1986a, 373: 384-91. Kasckow J, Abood LG, Hoss W, Herndon RM. Mechanism of Phospholipase A2-Induced Conduction Block in Bullfrog Sciatic Nerve II: Biochemistry. Brain Research. 1986b, 373: 392-8. Katayama Y, Senda M, Hamada M, Kataoka M, Shintani M, Inoue H. Relationship Between Postural Balance and Knee and Toe Muscle Power in Young Women. Acta Medica Okayama. (2004), 58 (4); 189-95. Kent-Braun JA, Ng AV, Castro M, Weiner MW, Gelinas D, Dudley GA, Miller RG. Strength, Skeletal Muscle Composition, and Enzyme Activity in Multiple Sclerosis. Journal of Applied Physiology. Dec 1997, 83(6).

PAGE 56

47 Kidd PM. Multiple Sclerosis, an Autoimmune Inflammatory Disease: Prospects for its Integrative Management. Alternative Medicine Review. Dec 2001; 6(6): 540-66. Review. Kirby RL, Price NA, Macleod DA. The Influence of Foot Position on Standing Balance. Journal of Biomechanics. 1987, 20(4): 423-7. Kraft AM, Wessman HC. Pathology and Etiology in Multiple Sclerosis. Physical Therapy. 1974, 54: 716-20. Kraft GH, Alquist AD, de Lateur BJ. Effect of Resistive Exercise on Function in Multiple Sclerosis (MS). Archives of Physical Medicine and Rehabilitation. 1996a; 77: 984. Kraft GH, Alquist AD, de Lateur BJ. Effect of Resistive Exercise on Strength in Multiple Sclerosis (MS). Archives of Physical Medicine and Rehabilitation. 1996b; 77: 984. Kuramoto AK, Payne VG. Predicting Muscular Strength in Women: a Preliminary Study. Research Quarterly for Exercise and Sport Sciences. 1995; 66: 168-72. Kurtzke JF. A New Scale for Evaluating Disability in Multiple Sclerosis. Neurology. Aug 1955; 5(8): 580-3. Kurtzke JF. Rating Neurologic Impairment in Multiple Sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. Nov 1983; 33(11): 1444-52. Lambert CP, Archer RL, Evans WJ. Muscle Strength and Fatigue During Isokinetic Exercise in Individuals with Multiple Sclerosis. Medicine and Science in Sports and Exercise. Oct 2001, 33(10): 1613-9. Ludwin SK. Proliferation of Mature Oligodendrocytes After Trauma to the Central Nervous System. Nature. 1984, 308: 274-6. Mostert S, Kesselring J. Effects of a Short-term Exercise Training Program on Aerobic Fitness, Fatigue, Health Perception, and Activity Level of Subjects with Multiple Sclerosis. Multiple Sclerosis. 2002, 8: 161-8. National Safety Council. Injury Facts, 2000 edition. Itasca, IL: National Safety Council, 2000. Ng AV, Kent-Braun JA. Quantitation of Lower Physical Activity in persons with Multiple Sclerosis. Medicine and Science in Sports and Exercise. Apr 1997, 29(4): 517-23. Paty DW. Initial Symptoms. In Burks JS and Johnson KP (Ed.), Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. (75-9). New York: Demos Medical Publishing, 2000.

PAGE 57

48 Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of Aerobic Training on Fitness and Quality of Life in Multiple Sclerosis. Annals of Neurology. Apr 1996, 39(4): 432-41. Petajan JH, White AT. Recommendations for Physical Activity in Patients with Multiple Sclerosis. Sports Medicine. Mar 1999, 27(3): 179-91. Prineas JW. Pathology of the Early Lesions of Multiple Sclerosis. Human Pathology. 1975, 6: 531-5. Ritchie JM, Rogart RB. Density of Sodium Channels in Mammalian Myelinated Nerve Fibers and Nature of the Axonal Membrane Under the Myelin Sheath. Proceedings of the National Academic Society. 1977, 74: 211-5. Rogers ME, Fernandez JE, Bohlken RM. Training to Reduce Postural Sway and Increase Functional Reach in the Elderly. Journal of Occupational Rehabilitation. Dec 2001, 11(4): 291-8. Rogers ME, Rogers NL, Takeshima N, Islam MM. Methods to Assess and Improve the Physical Parameters Associated with Fall Risk in Older Adults. Preventive Medicine. 2003, 36: 255-64. Smithson F, Morris ME, Iansek R. Performance on Clinical Tests of Balance in Parkinson's Disease. Physical Therapy. Jun 1998; 78(6): 577-92. Teasdale N, Stelmach GE, Breunig A. Postural Sway Characteristics of the Elderly under Normal and Altered Visual and Support Surface Conditions. Journal of Gerontology. Nov 1991; 46(6): 238-44. Tillman MD, Chow JW. Applications of Force-Plate Technology. Athletic Therapy Today. Nov 2002, 7(5): 60-1. Todd G, Gorman RB, Gandevia SC. Measurement and reproducibility of strength and voluntary activation of lower-limb muscles. Muscle Nerve. Jun 2004; 29(6):834-42. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. New England Journal of Medicine. Jan 1998; 338(5): 278-85. Waxman SG. Voltage-gated Ion Channels in Axons: Localization, Function, and Development. In Waxman SG, Kocsis JD, Stys PK (Eds.), The Axon. (218-43). New York: Oxford University Press, 1995. White LJ, McCoy SC, Castellano V, Gutierrez GM, Stevens J, Walter GA, Vandenborne K. Resistance Training Improves Strength and Functional Capacity in Persons with Multiple Sclerosis. Multiple Sclerosis. Dec 2004; 10(6): 668-74.

PAGE 58

BIOGRAPHICAL SKETCH Gregory M. Gutierrez has an innate drive that has allowed him to succeed in many aspects of his life. His competitive nature has helped him succeed on the field of play, and in the classroom. He received his bachelors degree in exercise and sports sciences in December of 2002 from the University of Florida. He immediately began his masters degree in biomechanics in the same department. Under exceptional guidance, he has matured in many ways and is ready to pursue a Ph.D. in biomechanics. Gregorys long-term goal is to one day become an orthopedic surgeon, while still contributing to research as a biomechanist. 49


Permanent Link: http://ufdc.ufl.edu/UFE0009465/00001

Material Information

Title: Effects of an Eight-Week Progressive Resistance Training Program on Balance in Persons with Multiple Sclerosis
Physical Description: Mixed Material
Copyright Date: 2008

Record Information

Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
System ID: UFE0009465:00001

Permanent Link: http://ufdc.ufl.edu/UFE0009465/00001

Material Information

Title: Effects of an Eight-Week Progressive Resistance Training Program on Balance in Persons with Multiple Sclerosis
Physical Description: Mixed Material
Copyright Date: 2008

Record Information

Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
System ID: UFE0009465:00001


This item has the following downloads:


Full Text












EFFECTS OF AN EIGHT-WEEK PROGRESSIVE RESISTANCE TRAINING
PROGRAM ON BALANCE IN PERSONS WITH MULTIPLE SCLEROSIS
















By

GREGORY MICHAEL GUTIERREZ


A THESIS PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE

UNIVERSITY OF FLORIDA


2005

































Copyright 2005

by

GREGORY MICHAEL GUTIERREZ















ACKNOWLEDGMENTS

I would like to thank Dr. Mark Tillman, Dr. John Chow, and Dr. Lesley White for

their support and guidance in the completion of this work. I would also like to extend my

deepest gratitude to my family and friends for their encouragement and moral support

throughout this thesis project. I especially need to thank my parents; without them I

would not be the person I am today. Special thanks are extended to Dr. Mark Tillman for

his personal and professional advice throughout the years, for which I feel forever

indebted to him.
















TABLE OF CONTENTS

page

A C K N O W L E D G M E N T S ......... .................................................................................... iii

LIST OF TABLES ........... .................. ....................... .... vi

LIST OF FIGURE S ......... ....................... ............. ........... vii

ABSTRACT ........ ........................... .. ...... .......... .......... vii

CHAPTER

1 IN TRODU CTION ................................................. ...... .................

2 LITER A TU R E R EV IEW .............................................................. ....................... 5

M u ltiple Sclero sis ................... ................................................................. 5
Expanded Disability Status Score (ED SS) ....................................... ............... 7
Sym ptom s .................................................................9
Risk of Falls ............................................................ ....... .... ........ 10
M S, Exercise and Remyelination .............................. ........... ........ ......... 11
B a la n c e ...............................................................................1 3

3 M ETH OD OLO GY ........................ ................................... ..................... 16

Subjects ......... ......... ................................. ............... 16
Instrumentation ............... ......... .......................17
Force Platform ................. ......... ...................17
Isokinetic Dynamometer ................. ................................17
E x p erim en tal S etu p .....................................................................................................17
P o stu ral Sw ay ...............................................................18
S tre n g th T e stin g ............................................................................................. 2 0
F u n ctio n al T e sts............................................................................................. 2 1
R e sistan ce T rain in g ....................................................................................... 2 1
D ata R e d u ctio n ..................................................................................................... 2 2
Design/Analysis ................................................... 23

4 R E S U L T S .............................................................................2 4

S tre n g th ........................................... .. .................................................................. 2 4









B a la n c e ...............................................................................2 5
Functional T ests .................. ................................... ...... ............... .. 26

5 DISCUSSION ............ .................................. .....................27

Strength ............... .....................................................27
B a la n c e ...............................................................................2 9
L im stations ......... ............................................................ 3 1
Summary and Conclusions .............. ...... ........ ...............31

APPENDIX

A IN F O R M E D C O N SE N T ....................................................................................... 33

B EXPANDED DISABILITY STATUS SCALE .............................. 43

L IST O F R E F E R E N C E S .............................................................................................. 45

B IO G R A PH IC A L SK E T C H ........................................................................................ 49
















LIST OF TABLES

Tablege

1 Muscle groups being tested, the movement they produce, and the corresponding joint
angles .................................................................................20

2 Strength measures for the MS training group (mean SD). All strength (torque)
measures in Nm denotes p<0.05. ..........................................................................24

3 Strength measures in the non -MS control training group (mean SD). All strength
(torque) m measures in N m ..........................................................................24

4 Mean balance measures for the MS training group. All balance measures in m. *
denotes p<0.05. .........................................................................25

5 Mean balance measures for the control training group. All balance measures in m..25
















LIST OF FIGURES


Figure page

1 The self-selected (E ) stance. ........................................ .......................................... 19

2 The feet apart (F) stance. .................................................................... ...................19

3 T he foam pad (P) stance. .................................................................... ...................19

4 The semitandem (S) seen from a A) frontal view and B) sagittal view.....................20

5 The tandem (T) stance seen from a A) frontal view and B) sagittal view...................20

6 Diagram depicting the movement of the COP throughout a balance trial .................22















Abstract of Thesis Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Master of Science

EFFECTS OF AN EIGHT-WEEK PROGRESSIVE RESISTANCE TRAINING
PROGRAM ON BALANCE IN PERSONS WITH MULTIPLE SCLEROSIS

By

Gregory M. Gutierrez

May 2005

Chair: Mark Tillman
Major Department: Department of Exercise and Sports Sciences

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system,

which leads to degeneration of the myelin sheaths that protect the neural axons. MS can

affect any part of the central nervous system, so persons with MS experience a wider

variety of symptoms than most neurological disorders, including problems with balance

and strength loss. The aim of this study was to determine if a strength training program,

designed to increase muscle strength, could improve postural sway measures in persons

with MS. Nine MS subjects and four non-MS controls participated in an eight-week

strength-training program. They were tested for isometric strength for their knee

extensors, knee flexors, plantar flexors, and dorsiflexors prior to and following the

strength-training program. Postural sway was also evaluated before and after training in

5 different stance conditions: 1) self-selected, 2) feet 6 inches apart, 3) feet 6 inches apart

on a foam pad, 4) semitandem, and 5) tandem. Four dependent variables were calculated

from the tests of postural sway: path length (PL), average speed (AS), antero-posterior









amplitude (AP), and medio-lateral amplitude (ML) of the COP movement. Wilcoxon

signed rank tests were performed on all strength and balance variables to determine if

changes occurred due to the strength-training program with a conventional significance

level of 0.05. For the MS training group, the Wilcoxon signed rank tests revealed a

significant increase in PL and AS for the self-selected stance and an increase in isometric

strength in the knee flexors. The non-MS control training group had no significant

differences in strength or balance after training. The results indicate that strength training

is safe for persons with MS and may lead to an increase in muscular strength. However,

it does not appear to have a significant effect on standing balance in the stance positions

studied. A training program more specific to balance may demonstrate more significant

improvement in balance for persons with MS.














CHAPTER 1
INTRODUCTION

Multiple sclerosis (MS) is the most common cause of nontraumatic neurological

disability affecting young adults in the northern hemisphere (Goodkin, 2000). MS is an

autoimmune disorder of the central nervous system that leads to widespread degeneration

of the myelin sheaths that encase axons in the central nervous system. The loss of the

protective myelin layer causes lesions to form on the axons, which can eventually

develop into hardened scleroses that inhibit the normal conduction of nerve impulses

down the axons (Herndon, 2000). The extent of axonal loss is variable, but usually

substantial, with some axonal loss occurring in every lesion (Trapp et al., 1998).

Symptoms from axonal loss cannot be alleviated. However, experimental efforts to

improve conduction in neurons without axonal loss have been promising (Herndon,

2000).

The four accepted patterns of pathology in MS as defined in 1996 are: 1) relapsing-

remitting, 2) secondary progressive, 3) chronic progressive and 4) progressive relapsing

MS (Goodkin, 2000). However, specific lines separating these disease patterns are not

completely clear thus making specific diagnoses challenging. Furthermore, the variable

nature of the disease leads to a difficulty in creating an ideal outcome assessment

measure for patients with MS. In all patterns of MS, the level of disability in patients is

typically categorized using the Expanded Disability Status Score (EDSS). The EDSS

scale was designed by John F. Kurtzke and is based on the maximum function of a

patient as limited by their neurological deficits (Kurtzke, 1955). Aside from a few









shortcomings, it serves as a familiar and quantifiable method of communication amongst

healthcare professionals concerning individuals with MS.

MS lesions occur in different areas of the central nervous system and due to this

variable distribution of demyelination, people with MS may experience a wider variety of

symptoms than any other neurological disease including balance, coordination, strength

and sensation disorders (Cattaneo et al., 2002). Furthermore, individuals with MS have

been found to have a reduced amount of skeletal muscle and a tendency to supply energy

through anaerobic pathways (Kent-Braun et al, 1997), which implies a decrease in the

number of slow-twitch muscle fibers. Along with a decrease in skeletal muscle fiber size,

persons with MS also face a reduced ability to activate muscle (Lambert et al., 2001),

which is associated with the demyelination of nerves (Kent-Braun et al., 1997). This

reduced muscle size and compromised motor unit activation cause the muscle weakness

associated with MS, which coupled with spasticity, further compromises the ability to

balance by affecting the sequencing and force of muscle contraction (Frzovic et al.,

2000).

Inability to maintain standing balance impacts a patient's ability to perform

activities of daily living (ADLs) and puts them at an increased risk of falling and

subsequent injury, which contributes to the development of a fear of falling that may lead

to a change in quality of life (Cattaneo et al., 2002). Therefore, balance assessment and

implementation of rehabilitation strategies to improve balance is important in attempting

to maintain a favorable quality of life for persons with MS.

Patients with MS demonstrate reduced physical activity when compared to non-MS

individuals (Ng & Kent-Braun, 1997), which is usually attributed to muscle weakness









and fatigue, but could also be due to a patient's fear of falling (Cattaneo et al., 2002).

When balance is compromised, even simple ADLs such as dressing, walking, and

standing become challenging, which may contribute to the anxiety and depression that

affects about 65% of patient's with MS (Joffe et al., 1987).

The muscle weakness and fatigue demonstrated in persons with MS is consistent

with human models of disuse and provides a rationale for therapeutic intervention in the

form of exercise training as a means of reversing some of the reduced sensory and motor

functions in individuals with MS (Kent-Braun et al., 1997). Individuals with MS

experience muscle weakness and more symptomatic fatigue with exercise, however Kent-

Braun and colleagues found that they were not weaker compared to healthy individuals

when the amount of fat-free mass was taken into account. Therefore, an exercise-training

program designed to enhance muscle strength and endurance is a reasonable therapeutic

intervention in persons with MS and may be helpful in improving the functional capacity

of individuals with MS and offsetting the deleterious effects of their disease.

Furthermore, the demyelination associated with MS is not always permanent;

remyelination has been documented in MS (Chang et al., 2002). However, these

remyelinated nerves often fail to return to baseline functioning because of the decline in

activity following an acute MS attack (Herndon, 2000). Strength training may assist in

both promoting strength that may have been lost because of physical inactivity and

returning proper neural function to the remyelinated tissue. In addition, physical activity

has an important benefit in reducing the risk of secondary diseases and improving overall

health.









As stated earlier, persons with MS often face a reduced ability to balance, meaning

they are frequently unable to maintain the body's position over its base of support

(Rogers et al., 2001). Quantifying a patient's level of balance impairment is important,

therefore many different techniques have been proposed to measure a person's ability to

maintain static or dynamic balance. In research settings, postural sway analysis is widely

accepted as a reliable way to quantify the complex and multidimensional nature of a

person's standing balance (Tillman & Chow, 2002); however little research has been

conducted using postural sway in persons with MS. In addition, the influence of strength

training in MS patients has not been evaluated. Thus, the primary aim of this study is to

determine whether an eight-week program of progressive resistance training is tolerable

for persons with MS and if it could enhance standing balance in ambulatory individuals

with MS.














CHAPTER 2
LITERATURE REVIEW

A review of the literature revealed a significant shortage of relevant information

concerning strength training and balance in persons with MS. This work is intended to

fill that void. More specifically, it aims to provide more data regarding the effects of

resistance training on balance in individuals with MS.

Multiple Sclerosis

Multiple sclerosis (MS) is the most common progressive neurological disease in

young adults (Kraft & Wessman, 1974), usually diagnosed in individuals between the

ages of 20 and 40. MS is a degenerative inflammatory autoimmune disorder of the

central nervous system that destroys the myelin sheaths that encase and insulate the

neural axons (Chang et al., 2002; Kidd, 2001). The etiology of MS is not known,

however the most widely accepted hypothesis is that it is a virus-induced autoimmune

disorder (Herndon, 2000). The myelin in the central nervous system and the cells that

form that myelin, the oligodendrocytes, are the primary targets of attack (Herndon, 2000).

Lesions form on the myelin sheaths and can eventually develop into hardened scleroses

that inhibit the normal conduction of nerve impulses down the axons (Herndon, 2000).

MS lesions occur in different areas of the central nervous system and can range

from acute plaques with active macrophages containing lipid and myelin degenerating

products to chronic, inactive glial scars. The plaques appear to begin with the

macrophages and lymphocytes forming perivascular cuffs about the capillaries and

venules (Herndon, 2000). This is followed by diffuse infiltration by inflammatory cells,









edema, astrocytic hyperplasia, and macrophages consuming the myelin off the axons

causing an increasing number of lipid-filled macrophages and demyelinated axons

(Prineas, 1975). The extent of axonal loss is variable, but usually substantial (Trapp et

al., 1998), with some axonal loss occurring in every lesion. Experimental efforts to

improve conduction in neurons without axonal loss may produce dramatic improvements

in many symptoms that result from conduction failure in unaffected axons, however the

symptoms that result from axonal loss cannot be alleviated by these interventions

(Herndon, 2000).

There are four accepted patterns of pathology in MS that were defined in 1996,

which include: 1) relapsing-remitting, 2) secondary progressive, 3) chronic progressive

and 4) progressive relapsing MS. The relapsing-remitting form of MS is the best

understood and is more common in younger patients. Approximately 85% of MS

patients experience an exacerbation at disease onset (Goodkin, 2000). Multifocal discrete

inflammatory demyelinating lesions in both the gray and white matter of the CNS are

characteristic of this pattern (Herndon, 2000) and patients are usually stable between

exacerbations (Goodkin, 2000). Secondary progressive MS has characteristics consisting

of a combination of both relapsing-remitting and chronic progressive MS (Herndon,

2000). In these individuals, old, inactive, multifocal lesions coexist with progressive

diffuse demyelination (Herndon, 2000). Chronic progressive MS (also known as primary

progressive MS) is more typical in older patients and is less dramatic than relapsing-

remitting MS. The demyelination is diffusely scattered involving individual fibers or

small groups of fibers interspersed with normal appearing myelinated fibers. The

inflammatory infiltrates and macrophages are much more limited and diffuse than in









relapsing-remitting MS (Herndon, 2000). Chronic progressive MS involves a gradual

progression of disability without superimposed relapses (Goodkin, 2000). The fourth

pattern is termed progressive relapsing MS in which patients experience gradual

disability progression accompanied by one or more relapses (Goodkin, 2000). However,

specific lines separating these disease patterns are not completely clear which makes

specific diagnoses challenging.

During the process of demyelination, some conduction failure is unavoidable in the

affected fibers. Some lesions are known as clinically silent lesions, which occur when a

minority of fibers in a conduction path become demyelinated at any one time, leaving

intact conduction in the unaffected fibers in the path (Herndon, 2000). The causes of

conduction failure associated with demyelination are not completely understood, but it is

hypothesized that it may be due to 1) damage to the nodal sodium channels (Kaschow et

al., 1986a & 1986b), 2) a virtual absence of these sodium channels (Ritchie et al., 1977),

and/or 3) increased membrane capacitance in the demyelinated region (Waxman, 1995).

There is substantial evidence that the nodal membranes are damaged by various enzymes

released by the inflammatory cells that appear to produce extensive damage to the

myelin. Furthermore, an increased membrane capacitance causes the amount of current

required to depolarize the axon to be higher and therefore make impulse conduction

slower or in some cases blocked. These characteristics of demyelinated fibers help

explain some of the features of the motor fatigability and activity related failure of

neurological processes that affect individuals with MS (Herndon, 2000).

Expanded Disability Status Score (EDSS)

The very nature of the disease leads to a difficulty in creating an ideal outcome

assessment measure for patients with MS. In all patterns of MS, level of disability in









patients is typically categorized using the Expanded Disability Status Score (EDSS). The

Disability Status Score (DSS) was designed in 1955 by John F. Kurtzke and measures the

maximum function of a patient as limited by their neurological deficits (Kurtzke, 1955).

The DSS was expanded in 1983 to include more extensive criteria and is now known as

the Expanded Disability Status Score. The EDSS scale is based on any lack of function

in eight functional systems: 1) Pyramidal (degree of paralysis), 2) Cerebellar

(coordination of movement), 3) Brain Stem (cranial nerve functioning), 4) Sensory, 5)

Bowel and Bladder, 6) Visual (optic), 7) Cerebral (mental), and 8) Other neurological

deficits attributed to MS. The scale ranges form 0 to 10, where 0 is normal functioning

and 10 is death due to MS (Kurtzke, 1983). The scale is primarily based on the patient's

ability to ambulate and deficiencies in any of the eight functional systems make the score

more specific to the patient's actual disability level.

The most favorable aspects of the EDSS scale lie in the coverage of four of the

eight functional systems: the pyramidal, cerebellar, visual, and mental systems

(Coulthard-Morris, 2000). The pyramidal scale measures disability in the appendages

(i.e. paralysis in a limb). Cerebellar function is measured by the ability to coordinate

movements, which can be affected by the ataxia suffered by MS patients. Visual

impairments are characterized by a loss of visual acuity and/or temporal pallor. Finally,

mental functioning is measured by decreases in mentation leading to dementia. Although

we will not be directly testing disability level in any of the eight functional systems, the

ones that are most important for maintaining balance include the pyramidal, cerebellar,

sensory and visual systems.









Even though the EDSS scale is the most widely accepted MS impairment measure

and provides a familiar and quantifiable method of communication among health care

professionals, it lacks the sensitivity needed to detect the small changes in disease status

experienced by people with MS over short time periods. Furthermore, low interrater

reliability makes reproducible assessments more challenging. The EDSS scale

predominantly measures ambulation and many clinicians feel it does not adequately

assess impairment and disability in persons with MS (Coulthard-Morris, 2000). Aside

from its few shortcomings, the EDSS scale is the best measure available for quantifying

disability in persons with MS to date. However, more comprehensive scales for balance

deficits in MS would be beneficial. (See Appendix B for the complete breakdown of the

EDSS scale).

Symptoms

Without proper neural functioning, individuals with MS may suffer from a variety

of symptoms, including sensory loss in the appendages, slowly progressive motor deficit,

acute motor deficit, optic neuritis, and/or a variety of other ailments (Paty, 2000). Due to

the variable distribution of demyelination throughout the central nervous system

(Cattaneo et al., 2002), people with MS may experience a wider variety of symptoms

than any other neurological disease. These symptoms can lead to problems with balance,

coordination, walking mechanics (gait), and postural control. Much of the disability

associated with MS results from axonal destruction in very long pathways, such as the

pyramidal tract, which supplies the legs and dorsal column with efferent and afferent

signals. The imbalance and coordination issues encountered by individuals with MS are

due to the slowed conduction in these tracts of proprioceptive impulses and the inability

to monitor motor processes that pass through the demyelinated areas (Herndon, 2000). In









many of these individuals, symptoms are exacerbated by an increase in core body

temperature of as little as 0.50 C (Paty, 2000).

The combination of factors causes individuals with MS to have reduced skeletal

muscle fiber size, lower oxidative capacity per unit volume, and a greater tendency for

the muscle to supply energy via anaerobic pathways (Kent-Braun et al., 1997). The

variability in muscle strength in MS patients appears to be the result of reduced ability to

activate muscle (Lambert et al., 2001), in part, because of poor motor unit activation

associated with demyelination of nerves (Kent-Braun et al., 1997). Also, MS often

results in muscle atrophy and high fatigueability associated with reduced physical

function during MS relapses. Following an acute MS attack, intact motor units may not

function fully because of disuse, and coupled with spasticity, further compromise the

patient's ability to balance themselves, affecting both the sequencing and force of muscle

contraction (Frzovic et al., 2000).

Risk of Falls

Balance assessment in conjunction with the implementation of rehabilitation

strategies is important in a clinical setting to improve mobility and reduce the risk of falls

and subsequent injury in persons with MS. Patients with MS, even those only mildly

affected, demonstrate reduced physical activity patterns compared to healthy individuals

(Ng & Kent-Braun, 1997). This reduced physical activity is usually attributed to muscle

weakness and fatigue, but could also be due to poor balance, frequent falling, fear of

falling, thermoregulatory issues and a global decline in functional capacity (Cattaneo et

al., 2002). Recreational and social activities may also be reduced, especially when

considering that leisure activities are the first lost when an illness is present (Petajan et

al., 1999).









In patients with compromised neurological function, falling has a multifactorial

origin and consequently there are many reasons why these individuals face an increase

risk of falling (Cattaneo et al., 2002). The role of improved balance in decreasing the risk

of falls has important implications in reducing injury and long-term disability.

Unfortunately, little research has been performed on falling behavior in persons with MS,

however the risk of falls in MS is comparable to that of the elderly (Cattaneo et al.,

2002). Gryfe and colleagues (1977) reported that 45% of adults age 65 and older

experience on average one fall per year. Furthermore, falling is the leading cause of

injury related deaths in older adults with 27.2% of injury related deaths in persons age

70-79 being attributed to falling behavior (National Safety Council, 2000). Most

published studies have found that balance impairment is an important risk factor in

predicting falling behavior (Cattaneo et al., 2002).

MS has a global impact on patients and impairs their ability to perform even the

simplest ADLs. When balance is compromised, many common activities such as

standing, dressing, and walking become challenging. Inability to maintain balance when

performing ADLs can lead to anxiety and depression, which already affects about 65% of

patient's with MS (Joffe et al., 1987).

MS, Exercise and Remyelination

The muscle weakness and fatigue demonstrated in persons with MS is consistent

with human models of atrophy, which provide the rationale for exercise as a therapeutic

intervention to reverse reductions in functional capacity in individuals with MS (Kent-

Braun et al., 1997). Kent-Braun also found that even though individuals with MS

experience more symptomatic fatigue with exercise, they were not weaker when

compared to control subjects when differences in fat-free mass were taken into account.









The finding that MS patients are in fact not weaker than control subjects also supports the

idea that strength training to increase the quantity and quality of skeletal muscle is a

viable means of improving the function and quality of life in individuals with MS.

Improvements in muscle strength, endurance, range of motion, and coordination may

improve balance in individuals with MS (Armstrong et al., 1983).

An exercise-training program designed to enhance these variables may improve the

functional capacity of individuals with MS and offset the deleterious effects of their

disease. Unfortunately, little research is available on resistance training in MS, however

there is information available concerning MS and exercise, specifically aerobic exercise.

Several studies have found that even a short term aerobic exercise program can improve

aerobic fitness and fatigue, and may lead to an increased level of physical activity and an

improved perception of health status in persons with MS (Mostert & Kesselring, 2002;

Petajan et al., 1996; Gehlsen et al., 1984). This strengthens the rationale that an exercise-

training program may improve quality of life in persons with MS.

Furthermore, the demyelination associated with MS is not always permanent;

remyelination has been documented in MS (Chang et al., 2002). Bunge and colleagues

(1961) demonstrated that central nervous tissue could be remyelinated in a cat and this

was later proven to be true in other species including the tadpole, rat, mouse, rabbit and

dog (Hommes, 1980). Remyelinated areas in experimental animals show 1) an increased

number of oligodendrocytes, which contrary to traditional beliefs can proliferate

(Ludwin, 1984), 2) thin myelin sheaths of uniform thickness, and 3) short internodes

(Herndon, 2000). Demyelinated areas that become remyelinated are often unused after

an MS attack and thus do not reestablish baseline function. Furthermore, demyelination









of newly remyelinated areas may result in scarring that prohibits further remyelination,

creating a glial scar. The progressive accumulation of demyelination, axonal damage,

and increasing disability provides a rationale for early implementation of therapeutic

interventions (Herndon, 2000).

Following an acute MS attack, intact motor units may not function fully because of

disuse, thus neural recruitment through activity may contribute to positive neural

adaptations. Exercise training may facilitate positive neural adaptations and help regain

strength that may have been lost because of physical inactivity. Although remyelination

has been documented in MS, it will not be evaluated in this study. However, if resistance

training contributes to remyelination or improves conduction and recruitment in

remyelinated fibers, improvements in strength and function could be significant.

Moreover, improving the function of unaffected skeletal muscle may also improve

overall physical function and help attenuate disability. Furthermore, physical activity has

an important benefit in reducing the risk of heart disease and improving insulin

sensitivity.

Balance

As stated previously, maintaining balance is a major concern for persons with MS.

Balance is the ability to maintain the body's position over its base of support (Rogers et

al., 2001). The study of human standing balance has provided insight into the basic

mechanisms of neurological integration and into biomechanics in both health and disease

(Kirby et al., 1987). For this reason, many different techniques have been proposed to

quantify a person's ability to maintain static or dynamic balance. In clinical settings,

balance tests must be reliable and valid, use readily available equipment, and be easy to

administer and master (Smithson et al., 1998). However, in a research laboratory,









postural sway analysis has been widely accepted as a reliable way to quantify the

complex nature of a person's standing balance in both healthy individuals and in special

populations (Tillman & Chow, 2002).

The center of gravity (COG) of the body shifts continuously even during quiet

standing. Postural sway is the corrective actions made by the body in an attempt to

control body position and is measured by observing the vertical projection of the COG

onto their base of support using force platform technology (Rogers et al., 2001). This

vertical projection of the COG onto the force platform is commonly referred to as the

center of pressure (COP). Increased sway as measured by the path length, speed of sway,

and the amplitudes in the sagittal and coronal planes indicates greater effort to maintain

upright position and therefore poorer balance (Rogers et al., 2003). Individuals who have

sustained multiple falls demonstrate greater postural sway than age-matched peers (Era,

1985). Analysis of postural sway is a valid measure of standing balance control in many

populations, but little research has been conducted using postural sway in persons with

MS.

Postural control is dependent on complex, integrative processing from a variety of

sensory and motor inputs (Teasdale et al., 1991) and it is therefore difficult to quantify

the origin of poor balance. There is no single global clinical test that can reflect the

complexity and multidimensional nature of balance (Horak, 1987). Instead, balance

measurements should test a patient's ability to maintain steady standing in a variety of

different stance conditions and their ability to remain stable during and after self-

generated perturbations (Frzovic et al., 2000). Sway velocity has been found to be higher

when the feet are positioned close together resulting in a functionally small base of









support (i.e., semitandem, tandem, or unilateral stances), which indicates that in these

conditions there is a higher likelihood of falling and subsequent injury (Rogers et al.,

2001).

The effect of a strength-training program on balance has not been evaluated in MS

patients. However, none of the training in this study is designed to be balance specific.

The goal of this study was to evaluate the efficacy of a resistance training program on

improving balance in persons with MS without specifically concentrating on balance

training so as to provide a rehabilitative intervention available to all individuals with MS

without the need for special balance training equipment.














CHAPTER 3
METHODOLOGY

This experiment investigated the effects of resistance training on balance control in

persons with MS. Postural stability in a series of different stance positions and altered

support surface and isometric strength was measured before and after an 8-week

resistance-training program.

Subjects

Nine MS subjects (7 female and 2 male, mean SD, age: 43.3 12.1 yrs; weight:

69.6 10.3 kg; height: 1.69 0.08 m; EDSS: 4.44 1.67) and four non-MS controls (3

female and 1 male; age: 46.8 + 11.4 yrs; weight: 82.0 9.1 kg; height: 1.71 0.07 m)

were recruited from the local Gainesville population. The subjects were examined by a

neurologist for disability status and cleared for participation prior to the outset of the

experiment. For participation in this study, the subjects were required to meet the

following criteria:

* Subjects must have been able to walk a distance of at least one city block (100m)

* Subjects could not have any coexisting orthopedic disorders, visual impairments
(blindness, diplopia, blurred vision, severe nystagmus, etc.) or tremor that would
adversely affect their ability to balance.

Each subject was asked to sign an informed consent agreement approved by the

Institutional Review Board of the University of Florida prior to participation. The

subjects were asked to fill out a Physical Activity Readiness Questionnaire (PAR-Q), a

RISKO: Heart Health Appraisal, and a Health Risk Questionnaire to assure that they were

healthy enough to participate in a resistance-training program.









Instrumentation

Force Platform

A Bertec 4060-10 Force Platform System (Bertec Corporation, Columbus, OH),

Peak Motus 2000 Motion Analysis System (Peak Performance Technologies,

Englewood, CO), and a Motion Analysis Hawk Realtime system (Motion Analysis

Corp., Santa Rosa, CA) were utilized to measure postural stability of each subject prior to

and after an 8-week progressive resistance-training program. The force platform is

capable of measuring forces and moments in the x, y, and z directions, which allows for

the center of pressure to be tracked in the frontal and sagittal planes. The analog data

were sampled at 40 Hz with the amplifier set at a gain of 5.

Isokinetic Dynamometer

A Kincom isokinetic dynamometer (Model AP125, Chattecx Corp., Chattanooga,

TN) was used to perform all isometric strength testing. Isokinetic dynamometers can be

used to measure isometric force production at a preset joint angle for each exercise. The

dynamometer sampled data at 100 Hz. Even though subjects trained isotonically,

isometric testing was preferred because it has been found to be more reliable (Todd et al.,

2004) and data are readily available in the literature for comparison purposes (Chetlin et

al., 2004). Subjects were seated and restrained using shoulder and lap belts and the axis

of the joint being studied was aligned with the axis of the dynamometer. Seat position

and orientation on the dynamometer were stored in the computer database as well as on

data sheets to ensure reproducibility of body position for all testing.

Experimental Setup

Subjects performed the tests of standing balance and muscular strength in the

Biomechanics Laboratory in the Center for Exercise Science in the Florida Gym at the









University of Florida prior to and following an eight-week resistance-training program.

They were advised to wear comfortable clothing and footwear, although the balance

testing was performed with the subjects barefoot. Prior to data collection, the purpose of

the study and procedures were explained to the subjects and all questions were answered.

Sex, age, height, weight, and lower limb dominance (as ascertained by asking "Which

foot would you kick a ball with?") was recorded.

Postural Sway

For the tests of static balance, the subjects were asked to stand on a force platform

for two trials lasting 20 seconds each in five different stance positions. The subjects were

asked to stand quietly with their hands at their sides in a neutral position for each 20-

second trial. All five conditions were administered in a randomized testing order and

subjects were allowed to rest as much as needed between trials. The five different stance

conditions were:

* The self-selected (E) stance feet apart at a self selected distance (See Figure 1).
Distance between the toes and heels were measured.

* The feet apart (F) stance feet 15.2 cm (6 in.) apart (See Figure 2)

* The foam pad (P) stance feet 15.2 cm (6 in.) apart on a foam balance pad; to
simulate altered support (See Figure 3).

* The semitandem (S) stance feet 15.2 cm (6 in.) apart and the heel of their
dominant leg in line with the toe of their non-dominant leg (See Figure 4a and 4b)

* The tandem (T) stance feet inline heel-to-toe and the dominant limb in front. (See
Figure 5a and 5b)





















Figure 1 The self-selected (E) stance.


Figure 2 The feet apart (F) stance.


Sigure j ne toam paa (t) stance.





















Figure 4 The semitandem (S) seen from a A) frontal view and B) sagittal view.


Figure 5 The tandem (T) stance seen from a A) frontal view and B) sagittal view.

Strength Testing

The subjects were tested for isometric strength prior to and following an 8-week

study period. The muscle groups and corresponding joint angles are depicted in Table 1.

The subjects were asked to contract their muscles to attempt to produce maximal force.

Muscle Group Tested Exercise Joint Angle
Quadriceps Knee Extension Knee Angle = 90
Hamstrings Knee Flexion Knee Angle = 90
Ankle Plantarflexors Plantarflexion Ankle Angle = 0 (neutral)
Ankle Dorsiflexors Dorsiflexion Ankle Angle = 0 (neutral)
Table 1 Muscle groups being tested, the movement they produce, and the
corresponding joint angles.

To normalize the force measurement to leg length, the highest force (F) reading

was multiplied by the moment arm (r) to determine the maximum torque (T) produced.

T=F*r









Functional Tests

Functional tests were also performed prior to and following the strength-training

program. These tests included a 100 ft. walk test and a 3-min step test. For the walk test,

subjects were asked to walk a distance of 100 ft as quickly and as safely as possible. The

time taken to complete the walk was recorded. For the step test, subjects were asked to

step up onto a platform 15.2 cm (6 in.) above the ground with both legs as many times as

possible in a 3-min period and total number of steps were recorded. Subjects were

allowed any assistance necessary to complete the step test.

Resistance Training

During the next eight weeks of the study period, MS and non-MS control subjects

were asked to visit the Center for Exercise Science or Living Well Fitness and Wellness

Center twice a week, either Monday/Thursday or Tuesday/Friday sessions to perform

resistance training exercises. Exercises were performed under the supervision of staff

trained in cardiopulmonary resuscitation, emergency procedures, and proper exercise

safety for individuals with disabilities. A training protocol was established using

recognized criteria for load assignment in older/disabled persons (ACSM, 2000).

During the first training session, subjects were asked to lift a submaximal load until

they could no longer complete a full repetition for each exercise (2-20 repetitions). A

predicted 1-repitition maximum (1-RM) was determined using the Kuramoto and Payne

(1996) prediction equation for older women. During the second training session, subjects

performed one set of 6-10 repetitions at 50% of the predicted 1-RM. In subsequent

sessions, subjects completed one warm-up set and one training set for each exercise.

Their warm-up consisted of five repetitions at 40% of the predicted 1-RM on each of the

weight-machines. The training set consisted of 10-15 repetitions at 70% of predicted 1-











RM for lower limb exercises (using one leg at a time leg) including knee flexion and

extension, plantar flexion, trunk flexion and trunk extension; in that order every time.

Exercises were performed at a self-selected, comfortable pace with at least one minute of

rest between exercises. Each training session did not exceed 60 minutes. When subjects

were able to complete 25 repetitions for any exercise in consecutive sessions, the

resistance was increased by 2-5%. All training sessions were supervised.

Data Reduction

The COP was tracked for all trials and the average COP path length (PL) the sum

of the displacement vectors, average path speed (AS) the PL divided by the total time,

and the amplitudes in the medio-lateral (ML) frontal plane, and antero-posterior (AP) -

sagittal plane directions were calculated for each of the five conditions. A representative

diagram of COP movement throughout a trial is depicted in Figure 6.

0.275



0250 I
z _
O J "-.' --1 '- .- oLL
-ILI

S0.20025

I~--
O o







MEDIO-LATERAL AMPLITUDE (m)-
0.1725 I -


0.150





0.250 0275 0.300 0325 0350 0375 0.400
MEDIO-LATERAL LOCATION (m)
Figure 6 Diagram depicting the movement of the COP throughout a balance trial.









Design/Analysis

This study was a pretest-posttest control group design. Descriptive statistics

(means and standard deviations) were calculated for each of the four dependent variables

(total sway path length, average sway speed, and sway amplitude in the AP and ML

directions) in each of the five stance conditions. Due to the small sample size,

nonparametric Wilcoxon signed ranks tests were performed to determine if any changes

occurred in any balance and/or strength measures following eight weeks of strength

training. Descriptive statistics were calculated for the functional tests, however no

statistical tests were performed on the data. All statistical tests were conducted with the

conventional level of significance, a=.05.














CHAPTER 4
RESULTS

All subjects completed the eight-week resistance-training program (16 sessions)

with no MS-related exacerbations reported. The protocol was occasionally adjusted when

subjects missed days between workouts for personal reasons, although adherence

remained at 100%.

Strength

Eight of the nine MS subjects were tested for strength prior to and following the

strength-training program. One subject was unable to produce muscular force from

several lower extremity muscle groups at the time of the day the pre-testing took place,

therefore he was excluded from the isometric strength analysis. The MS training group

significantly increased strength in the knee flexors (p<0.05). Although not statistically

significant, all other muscle groups also increased isometric strength (Table 2).

Stance Pre Post % Change p-value
Knee Extension 66.8 29.5 81.6 38.7 +22.17 % 0.069
Knee Flexion 34.9 17.2 42.7 14.4 +22.02 % 0.012*
Plantar Flexion 45.6 + 28.9 68.2 + 33.5 + 49.54 % 0.069
Dorsiflexion 25.7 10.8 28.2 + 9.5 + 9.89% 0.484
Table 2 Strength measures for the MS training group (mean SD). All strength
(torque) measures in Nm. denotes p<0.05.

Stance Pre Post % Change p-value
Knee Extension 94.4 + 24.5 112.5 30.3 + 19.15 % 0.068
Knee Flexion 43.5 + 9.8 50.7 + 18.3 + 16.54 % 0.144
Plantar Flexion 71.1 24.7 92.5 + 47.6 +30.13 % 0.144
Dorsiflexion 42.7 9.7 45.1 10.7 + 5.45 % 0.144
Table 3 Strength measures in the non -MS control training group (mean SD). All
strength (torque) measures in Nm.









The non-MS control training subjects displayed increases in isometric muscle

strength similar to those seen in the MS group, although again not statistically significant

(Table 3).

Balance

Several of the MS subjects could not complete certain stances for the entire 20

seconds, primarily the more difficult stances, such as the T and P stances. However,

subjects that did require assistance required a similar amount of assistance in the pre-test

and post-test. In the MS subjects, a significant increase was noted in the path length and

average speed for the E stance (p=0.028), however none of the other dependent variables

for any of the other stances changed significantly (Table 4). Furthermore, the control

subjects did not significantly change any of the dependent balance variables evaluated

(Table 5).

Stance PL PL p AP AP p ML ML p
pre post pre post pre post
E 0.780 1.068 0.028* 0.041 0.046 0.139 0.026 0.032 0.214
F 0.841 1.001 0.066 0.051 0.050 0.767 0.033 0.036 0.374
P 1.109 1.297 0.374 0.084 0.071 0.859 0.062 0.057 0.859
S 1.100 1.234 0.441 0.054 0.044 0.374 0.067 0.045 0.767
T 1.305 1.329 0.953 0.062 0.069 0.260 0.047 0.038 0.314
Table 4 Mean balance measures for the MS training group. All balance measures in m.
denotes p<0.05.

Stance PL PL p AP AP p ML ML p
pre post pre post pre post
E 0.395 0.681 0.068 0.018 0.019 0.715 0.009 0.008 0.715
F 0.416 0.663 0.144 0.020 0.016 0.144 0.009 0.012 1.000
P 0.608 0.813 0.144 0.046 0.042 0.144 0.030 0.025 0.273
S 0.545 0.766 0.144 0.028 0.022 0.144 0.029 0.025 0.144
T 0.829 0.911 0.465 0.044 0.025 0.144 0.038 0.034 0.715
Table 5 Mean balance measures for the Control training group. All balance measures
in m.






26


Functional Tests

Prior to strength training the MS group was able to complete the 100 ft walk in an

average time of 33.9 s and following training that time decreased to 31.5 s. The control

group was able to complete the walk in 14.3 s, which decreased to 13.8 s after training.

The MS group completed 58.1 steps in the 3-min period prior to training, which increased

to 68.2 following training. The control group began the training able to step an average

of 111.6, which increased to 127.3 after training.














CHAPTER 5
DISCUSSION

The aim of this study was to evaluate the effects of an eight-week progressive

resistance-training program on postural sway in persons with MS. More specifically, the

efficacy of a training program that is not balance specific in improving the balance of

persons with MS was evaluated. Furthermore, little research is available concerning

lower extremity muscle strength training in persons with MS, therefore the study was also

designed to determine whether persons with MS could adhere to and endure a resistance

training program. The results indicate that persons with MS can complete an eight-week

resistance-training program, with no MS exacerbations, and increase lower extremity

muscle strength. However, it remains unclear whether a strength training program, not

designed to be balance specific, can positively influence balance in individuals with MS.

Strength

A statistically significant increase was noted in only one of the muscle groups

tested in this experiment. Although not statistically significant, strength increased in all

muscle groups for both the MS subjects and the controls. In fact, the plantar flexor

isometric muscle strength increased 45% in the MS training group. Increases in muscle

strength were expected from the training program, in that it was designed to increase

lower extremity muscle strength. The lack of statistical significance may be due to the

limited sample sizes in both the MS and control groups and high variability.

Debolt and McCubbin (2004) found that a home-based resistance-training program

was well tolerated by persons with MS, and improved their lower extremity muscle









power. Furthermore, Kraft et al. (1996a & 1996b) resistance trained arms and legs in MS

subjects for eight weeks and also found improvements in strength, along with improved

function and psychosocial well-being. Most recently, White et al. (2004) found increased

strength and function, along with a decrease in daily fatigue after eight weeks of lower

extremity strength training. These studies, along with the findings of this research

support the practicality of a strength-training program as a viable means to increase

strength in individuals with MS.

Increased strength is desirable in this population because they are often faced with

an increased level of fatigue, which decreases their daily activity levels, and eventually

causes muscle atrophy. An increase in strength due to strength training may help to

counteract the atrophic changes noted in the musculature of individuals with MS, and

perhaps increase their daily activity levels. Furthermore, it is known that the first

neuromuscular adaptations to strength training are more neural than muscular. Positive

neural changes are especially important in a population afflicted with a neurological

disorder. Neural recruitment gained through physical activity may have a favorable

functional outcome, although this may be limited by the severity the MS lesions already

present. This suggests that resistance training may be an early intervention strategy in

persons with MS that may help to maintain function and hopefully, limits exacerbation of

MS symptoms. In fact, in all research previously mentioned concerning strength training

in individuals with MS, no MS related exacerbations were reported and there were no

reports of increased MS-related symptoms (Kraft et al., 1996a & 1996b; Debolt and

McCubbin, 2004; White et al. 2004).









Strength training is known to have many benefits, including, but not limited to,

increasing bone mineral density (Asikainen et al., 2004). Since most individuals who

suffer from MS are female, and females are at a higher risk of osteoporosis, strength

training to increase bone mineral density may have profound effects on the quality of life

of these individuals as the age. Furthermore, the performance of the subjects in the

functional tests also lends itself to supporting strength training in this population. All

subjects were able to walk faster and step more following training. This should be

expected from a strength-training program designed to enhance muscle strength and

endurance.

Balance

Decreased ability to maintain balance is a concern in individuals with MS, which

may lead to an increased susceptibility to falls. For this reason, an intervention strategy

to improve balance is desirable for individuals with MS. This study was intended to

determine if static balance could be improved with a training program that is not balance

specific. As stated earlier, the training protocol in this study was designed to increase

lower extremity muscle strength. A significant increase was noted in the strength of knee

flexors after strength training, and the knee extensors and plantar flexors also tended to

be stronger after the strength training, however only two measures of postural sway were

significantly different following training, and that change represented a decrease in

postural stability. The results suggest that strength training has little effect on postural

sway in persons with MS or control subjects.

The MS subjects who participated in this study represented a broad spectrum of

disability levels, which is common for a condition like MS. Some subjects had little or

no visible or obvious disability, while others required assistance to complete the tests of









standing balance. For those who did require assistance to complete the tests of standing

balance, the amount of assistance required did not change for between the pre and post-

tests. Furthermore, the data indicate that the strength training did not improve postural

sway characteristics in these subjects. This could be due to a couple of different possible

explanations: 1) the subjects were perhaps too disabled, more specifically, their loss of

function was already too extensive, to have dramatic improvements in just eight weeks,

or more likely 2) the training was not specific enough to the stances studied to cause

positive alterations in postural sway. Even though strength did increase in these subjects,

that increase did not result in improvements in static balance.

The finding that increased strength does not significantly influence balance is

supported by the work of Katayama et al. (2004), who found that knee and toe muscle

power does not appear to be a dominant factor in maintaining balance. This corroborates

the assertion that lower extremity muscle strength training may not have a significant

influence on postural sway. On the other hand, Judge and colleagues (1993) found that

an exercise program emphasizing postural control, moderate resistance training and

walking improved single leg static balance in neurologically intact elderly individuals,

however double leg static balance measures did not improve. Two important conclusions

can be dawn from this work: 1) a training intervention intended to improve balance

should be focused on training for balance, and 2) double leg static stances may not be

sufficiently challenging to unimpaired individuals to show significant changes after any

training program. Although most subjects in this study were impaired in some way, some

of the MS subjects had no obvious disability and may not have been challenged enough

with the stances tested to change postural sway characteristics significantly. This









assertion is supported by the performance of the control group, who showed no

significant changes in any of the balance measures tested.

Limitations

There are limitations in the experimental design that may account for the lack of

significant changes in postural sway characteristics. As stated earlier, eight weeks may

not have been a sufficient amount of time to significantly influence balance. Therefore, a

more elongated and extensive strength-training program may have elicited more

significant responses. Furthermore, a larger subject pool may help eliminate some of the

variability, which could account for the lack of statistically significant differences. With

such a small sample size, even a small amount of variability would eliminate statistical

significance. The strength gains should be interpreted cautiously because the training

was isotonic and the testing was isometric, so strength gains noted in this work may not

be clinically applicable. Another possible origin of variability is the change in motion

analysis systems used to collect the postural sway data midway through the study

protocol. Unfortunately, several subjects were pre and post-tested on different motion

analysis systems, therefore some inherent variability between the two systems may have

changed the final data enough to account for the lack of statistical significance.

Additional work with larger sample sizes, longer training protocol, more intense training,

and more balance specific training is desirable and could lead to promising intervention

strategies to improve balance and reduce the risk of falls in individuals with MS.

Summary and Conclusions

This study was designed to determine the efficacy of a progressive resistance-

training program on postural sway in persons with MS. The training program was not

intended to be balance specific. It was designed to focus on increasing general lower









extremity muscle strength. Only two out of 20 postural sway characteristics evaluated

significantly changed following strength training in the MS group. Strength increased

significantly in the knee flexors and tended to increase for the knee extensors and plantar

flexors. It appears that the increased strength in the lower extremity may not influence

static balance in individuals with MS. Additional research with larger sample sizes for

both groups, and increased duration and/or intensity of training is recommended. A

training program designed to focus specifically on balance would potentially demonstrate

more significant changes in balance and could present a promising intervention strategy

to improve balance and reduce the risk of falls in persons with MS, or any other

neurological disorder.














APPENDIX A
INFORMED CONSENT


IRB# 340-2002


Informed Consent to Participate in Research


You are being asked to take part in a research study. This form provides you with
information about the study. The Principal Investigator (the person in charge of this
research) or a representative of the Principal Investigator will also describe this study to
you and answer all of your questions. Before you decide whether or not to take part, read
the information below and ask questions about anything you do not understand. Your
participation is entirely voluntary.

1. Name of Participant ("Study Subject")




2. Title of Research Study

Resistance Training Effects on Muscle Function in Multiple Sclerosis


3. Principal Investigator and Telephone Number(s)

Lesley J. White, Ph.D., Assistant Professor
Department of Exercise and Sport Sciences
College of Health and Human Performance
University of Florida
(352) 392-9575 ext. 1338
Email: lwhite@hhp.ufl.edu









John Chow, Ph.D., Associate Professor
Department of Exercise and Sport Sciences
College of Health and Human Performance
University of Florida
(352) 392-0584 ext. 1263

Anne L. Rottmann, M.D., Neurologist
4410 West Newberry Rd. Suite A3
Gainesville, FL 32607
After Hours/Emergency Telephone Number: (352) 374-2222

4. Source of Funding or Other Material Support

National Multiple Sclerosis Society

What is the purpose of this research study?

The primary purpose of this study is to determine whether a sixteen-week
progressive resistance training exercise program influences measures of your muscle's
performance and your ability to walk and balance more effectively. This study is part of a
project to learn more about your muscles ability to become more effective in producing
energy during activities after you exercise train. We plan to measure your walking
mechanics and your balance before and after you exercise train. We will also get pictures
of your leg muscles using a technique called magnetic resonance imaging (MRI). Then
we can get information about the chemistry of your muscle using a technique called
magnetic resonance spectroscopy (MRS).

6. What will be done if you take part in this research study?

If you volunteer for this study you will be asked to participate in a 21 week
experimental period that consists of evaluation of several functional measures such as
muscle strengthbalance, and walking mechanics, followed by a sixteen week exercise
program. Midpoint evaluation will occur after 8 weeks of resistance training. Follow-up
evaluation will occur after sixteen weeks of exercise training program. Listed below are
descriptions of each visit should you choose to participate in this study.

Visit #1
On the first visit of week one of the study, you will be familiarized with the
experimental protocol and be examined by a neurologist. Your disability status and
physical readiness to participate in an exercise protocol will be assessed. If you are
cleared to participate in this study, you will be asked to read and sign an informed
consent, which will inform you of all the risks/benefits of participation in the experiment.
The approximate time required for this visit will be 60 minutes.


Visit #2









On the second visit of week 1, you will have an MRI/MRS performed on your
legs. During the MRI/MRS you will lie on a bed, which rolls in the opening of a large
magnet. A flat coil of wire (a radiofrequency coil) will be placed on your thigh and calf.
A computer will look at the radio waves passing through your leg and constructs pictures
and chemical information of your muscles. The total procedure will last approximately 45
minutes. An MRI/MRS is used routinely to detect structures or gain chemical information
about the muscles of healthy subjects or hospital patients. Just prior to and following the
MRI, we will draw 20ml of blood (about 4 teaspoons) by venipuncture to test levels of
blood sugar, triglycerides, and cholesterol. This will take an additional fifteen minutes.
The total time of this visit, including MRI/MRS and blood sampling, will take
approximately 60 minutes.

Visit #3
During the third visit in week 2 of the experimental period, you will have your
body composition assessed using a three-site skinfold technique, and measurements of
the waist and hip circumference will be taken. You will then be asked to perform
muscular strength and endurance tests on a Kin-Com isokinetic dynamometer for the
following exercises: abdominals, back, leg extensions, leg curls, and ankle flexion
exercises. The Kin-Com is a muscle testing machine commonly used for evaluating
muscle function in healthcare settings. During the testing, you will be asked to be seated
on the machine and you will be asked to perform a muscle contraction at a constant,
predetermined speed. The discomfort associated with this procedure is minimal, but will
require you to put forth a strong effort. In conjunction with the muscle testing, two self-
adhesive electrodes (2" x 4") will be placed on your thigh close to your knee and hip.
During your knee extension strength evaluation an electrical pulse will be delivered to
your thigh muscle. The level of stimulation should not be painful, though it may cause a
prickly sensation on your skin and will make your muscle feel like it is being squeezed.
The feeling will be very similar to what you experience when you climb stairs or ride a
bicycle for an extended period of time. The procedure is used to evaluate the ability of
your muscle to generate force during the strength testing. The strength testing will be
used to determine your 10-repetition maximum, which will be used in the training aspect
of the study. Testing is expected to take 60 minutes.

Visit #4
During the fourth visit, in week 2 of the experimental period, you will be asked to
perform tests of balance, and gait (walking mechanics). For the balance test, you will be
asked to stand on a force plate without support for 20 seconds. You will be asked to
repeat this test 3 times. Balance tests will be completed with your eyes open and closed.
A test of your functional reach will be completed after a brief rest period following the
balance test. During the functional reach test you will reach forward as far as you can
until your heels come off the floor. A safety harness will be used to ensure your safety
during functional tests. The harness may cause minor skin irritation. For the gait analysis
you will be asked to walk on an 8-meter walkway twice. The gait testing will require you
to have special sensors and reflective markers placed on your lower back and legs. The
special sensors will measure your muscle activity during walking. Your skin preparation
will include shaving areas displaying body hair with an electric razor that causes no skin









irritation. Your skin will then be sanitized with an alcohol swab. There is not any
expected irritation or discomfort associated with the shaving or alcohol swabbing.
Testing will also consist of a timed 25-foot walk test where you will be asked to walk as
fast as possible within your comfort. Lastly, you will be asked to perform a three-minute
step test where you will be asked to step up onto a platform as many times as possible in
the allotted three minutes. During this visit we will ask you to wear shorts and exercise
shoes. These tests will be conducted in the Biomechanics Laboratory in the Center for
Exercise Science and will take will take approximately 60 minutes to complete.

Visits #5 and #6
During the fifth and sixth visits, in week 3 of the experimental period you will be
asked to repeat all the testing performed in week 2. This is designed to more accurately
quantify baseline measures. These visits will each take approximately 60 minutes to
complete.

Visits #7 through #22
During the next eight weeks of the study period (weeks 4-11) you will be asked to
visit the Center for Exercise Science or Living Well Fitness and Wellness Center, or
North Florida Regional YMCA twice a week, either Monday/Thursday or
Tuesday/Friday sessions to perform resistance training exercises. Twenty milliliters (4
teaspoons) of blood will be drawn before and after exercise to determine the effect of
training on glucose, triglycerides, and cholesterol. Subjects will be required to attend
strength training sessions requiring blood draws at the Center for Exercise Science. All
training will occur in a supervised exercise environment with staff trained in
cardiopulmonary resuscitation and emergency procedures. The staff will also be trained
in proper exercise safety for individuals with disabilities.

During each exercise session you will be asked to perform one set of 15-20
repetitions at 70% of your 10-repetition maximum (RM) for each of the following
exercises: leg extensions, leg curls, ankle plantarflexion, and an abdominal/lower back
regimen using free-weight machines or a Kin-com isokinetic dynamometer. This is not a
maximal exercise protocol and is not designed to be exhaustive. When you are able to
complete 15 repetitions with proper technique, for two consecutive sessions, the
resistance will be increased by 10% of your 10-RM. To assess your level of fatigue you
will be asked to rate your level of effort (perceived exertion) at the end of each exercise.
Because of the functional variability of MS individuals, the protocol may be adjusted on
an individual basis to maintain your comfort and safety. A Certified Strength and
Conditioning Specialist (CSCS) or exercise physiology research assistant will supervise
all training sessions. Each training session will last 30-45 minutes.

You will be asked to perform a self-reported dietary recall at weeks 2, 4, 8, 12,
and 16 of the experimental period when you come to the laboratory for exercise training.
You will be asked to follow the dietary guideline established by the American Heart
Association for the duration of the study to ensure that the appropriate amounts of
nutrients are being consumed to meet the nutritional needs associated with a strength-
training program. These guidelines are similar to those suggested for the MS population.









You will also be asked to complete a functional independence measure at weeks 1, 5, 7,
9, 11, 16, and 20. We will also randomly ask you to wear an accelerometer throughout
one day during weeks 2, 12, and 20 to assess your level of activity. The accelerometer is
a small device that will be worn around the waist to measure your activity throughout the
day.

Visit #23 (Midpoint evaluation)
On the first visit of week 12 of the study period, following first phase ofthe
exercise training period, you will be asked to perform all testing measures as performed
at the beginning of the study. Again, you will be asked to perform self-reported
questionnaires examining functional independence and fatigue impact. The completion
of these questionnaires will take approximately 10 minutes. Following questionnaire
completion, your body composition will be reassessed via the three-site skinfold
technique, and measurements of the waist and hip will be taken. Twenty milliliters (about
four teaspoons) of blood will be taken before and after exercise_to determine if any
changes in your resting levels of blood glucose, triglycerides, and cholesterol occurred.
Again, these factors will be examined for experimental use and for your own personal
information. This portion of the study will take 45 minutes. The total time for this visit
will be approximately 90 minutes.

Visit #24
During the second visit of week 12 of the study period, you will be asked to
perform tests of muscle strength and endurance on a Kin-com isokinetic dynamometer
with electrical stimulation. This testing will follow the same procedure and include the
same exercises as was performed in weeks 2 and 3 of the study. Testing will take
approximately 60 minutes.

Visit #25
During the first, and only, visit of week 13 of the study, you will be asked to
perform follow-up tests of balance, and gait. Testing will also consist of a timed 25-foot
walk and the three-minute step test. These tests will again be conducted in the Center for
Exercise Science Biomechanics Laboratory and will take approximately 60 minutes to
complete.

Visit #26-42
During the next eight weeks of the study period (weeks 13-21) you will be asked
to continue twice weekly exercise training sessions until you have completed 16
consecutive weeks of training. Twenty milliliters (4 teaspoons) of blood will be drawn
before and after exercise at week 20 to determine the effect of training on glucose,
triglycerides, and cholesterol.
Any special needs that you require will be accommodated throughout the duration of the
study. All data collected in the post-testing phase will be compared to the information
gathered in the pre-testing to determine if any improvements were made in any of the
factors that were studied in this experiment.


7. What are the possible discomforts and risks?










The risks of drawing blood from a vein include discomfort at the site of puncture;
possible bruising and swelling around the puncture site; rarely an infection; and,
uncommonly, faintness from the procedure. The risk from having a catheter inserted into
an arm vein for time needed in this study is possible infection of the vein, but the risk is
very low because we will have a trained phlebotomist collecting the blood samples. The
amount of blood we will take should have no negative effects. You will be closely
watched for any possible ill effects.

There is also a risk of mild muscle soreness associated with the initiation of any
strength-training program, however this risk is minimal. Potential soreness may last for
three days but is not expected to limit any activities. There is also a slight risk of skin
irritation associated with electrode and reflective marker placement for the
electromyographic analysis. Balance and gait testing with the safety harness may cause
some mild skin irritation. There is also a risk of skin irritation associated with the
electrical pulses to your thigh, however, the equipment used is highly reliable with safety
features to minimize pulse strength. The short duration pulses may contribute to mild
muscle soreness, however the risk is minimal.

The risks of MRI/MRS are: the MRI/MRS scanner contains a very strong magnet.
Therefore, you may not be able to have the MRI/MRS if you have any type of metal
implanted in your body, for example, any pacing device (such as a heart pacer), any metal
in your eyes, or certain types of heart valves or brain aneurysm clips. Someone will ask
you questions about this before you have the MRI/MRS. There is not much room inside
the MRI/MRS scanner. You may be uncomfortable if you do not like to be in close
spaces ("claustrophobia"). During this procedure, you will be able to talk with the
MRI/MRS staff through a speaker system, and in the event of an emergency, you can tell
them to stop the scan.

The MRI/MRS scanner produces a loud hammering noise, which has produced
hearing loss in a very small number of patients. You will be given earplugs to reduce this
risk.

If you are a woman of childbearing potential, there may be unknown risks to the
fetus. Therefore, before you can have the MRI/MRS, you must have a pregnancy test.
This test will be done at no charge.


8a. What are the possible benefits to you?

It is possible that you may experience improvements in gait, balance, muscular
strength, and endurance. You will also receive eight weeks of personal exercise training.
Blood cholesterol, nutritional profile and analysis, will be provided for your own personal
records.


8b. What are the possible benefits to others?










Research findings from this study may help in the design and use of therapeutic
exercises designed to help other individuals with MS.

9. If you choose to take part in this research study, will it cost you anything?

All costs associated with the assessment of your percent body fat, gait analysis,
and quality of your diet will be paid for by the Center for Exercise and Sport Sciences.
Additional measurements of blood cholesterol, glucose, and insulin levels will be
absorbed by funding supporting the principal investigators of the study. The principal
investigator will also pay for the MRI/MRS and any required pregnancy test.

10. Will you receive compensation for taking part in this research study?

At the completion of the study, subjects with multiple sclerosis will receive
$200.00.
Subjects who do not have multiple sclerosis will not receive monetary compensation for
study participation.

11. What if you are injured because of the study?

If you experience any injury that is directly caused by this study, only professional
consultative care that you receive at the University of Florida Health Science Center will
be provided without charge. However, hospital expenses will have to be paid by you or
your insurance provider. No other compensation will be offered.

12. What other options or treatments are available if you do not want to be in
this study?

The exercise training and dietary counseling are in addition to standard therapy
for your condition. You may choose to continue with your current therapy.

13a. Can you withdraw from this research study?

You are free to withdraw your consent and to stop participating in this research
study at any time. If you do withdraw your consent, there will be no penalty, and you will
not lose any benefits you are entitled to.

If you decide to withdraw your consent to participate in this research study for any
reason, you should contact Dr. Lesley White at (352) 392-9575 ext 1338.

If you have any questions regarding your rights as a research subject, you may
phone the Institutional Review Board (IRB) office at (352) 846-1494.









13b. If you withdraw, can information about you still be used and/or collected?

If you withdraw from the study, information about you will not be used or
collected any further.


13c. Can the Principal Investigator withdraw you from this research study?

You may be withdrawn from the study without your consent for the following
reasons: failure to make scheduled training visits and cardiovascular risk factors
contraindicating your participation in a strength training program.

14. How will your privacy and the confidentiality of your research records be
protected?

Authorized persons from the University of Florida, the hospital or clinic (if any)
involved in this research, and the Institutional Review Board have the legal right to review
your research records and will protect the confidentiality of them to the extent permitted by
law. Otherwise, your research records will not be released without your consent unless
required by law or a court order. If the results of this research are published or presented at
scientific meetings, your identity will not be disclosed.

15. How will the researchers) benefit from your being in this study?

In general, presenting research results helps the career of a scientist. Therefore, the
Principal Investigators may benefit if the results of this study are presented at scientific
meetings or in scientific journals.









16. Signatures

As a representative of this study, I have explained to the participant the purpose, the
procedures, the possible benefits, and the risks of this research study, the alternatives to
being in the study, and how privacy will be protected:



Signature of Person Obtaining Consent Date

You have been informed about this study's purpose, procedures, possible benefits,
and risks; the alternatives to being in the study; and how your privacy will be protected.
You have received a copy of this Form. You have been given the opportunity to ask
questions before you sign, and you have been told that you can ask other questions at any
time.

You voluntarily agree to participate in this study. By signing this form, you are not
waiving any of your legal rights.


Signature of Person Consenting


Date









Consent to be Videotaped and to Different Uses of the Videotape(s)

With your permission, you will be videotaped during this research. Your name or
personal information will not be recorded on the videotape, and confidentiality will be
strictly maintained. When these videotapes are shown, however, others may be able to
recognize you.

The Co-Principal Investigator of this study, John Chow, Ph.D, will keep the
videotapes) in a locked cabinet. These videotapes will be shown under his direction to
students, researchers, doctors, or other professionals and persons.

Please sign one of the following statements that indicates under what conditions
Dr. John Chow, Ph.D has your permission to use the videotape.


I give my permission to be videotaped solely for this research project under the
conditions described.


Signature Date


I give my permission to be videotaped for this research project, as described in the
Informed Consent Form, and for the purposes of education at the University of Florida
Health Science Center


Signature Date


I give my permission to be videotaped for this research project, as described in the
Informed Consent Form; for the purposes of education at the University of Florida Health
Science Center; and for presentations at scientific meetings outside the University.


Signature


Date














APPENDIX B
EXPANDED DISABILITY STATUS SCALE

The EDSS quantifies disability in eight Functional Systems (FS) and allows

neurologists to assign a Functional System Score (FSS) in each of these systems:


pyramidal
cerebellar
brainstem
sensory
bowel and bladder
visual
cerebral
other

EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory, while

steps 5.0 to 9.5 are defined by the impairment to ambulation.

Kurtzke Expanded Disability Status Scale
0.0 Normal neurological examination
1.0 No disability, minimal signs in one FS
1.5 No disability, minimal signs in more than one FS
2.0 Minimal disability in one FS
2.5 Mild disability in one FS or minimal disability in two FS
3.0 Moderate disability in one FS, or mild disability in three or four FS. Fully
ambulatory
3.5 Fully ambulatory but with moderate disability in one FS and more than minimal
disability in several others
4.0 Fully ambulatory without aid, self-sufficient, up and about some 12 hours a day
despite relatively severe disability; able to walk without aid or rest some 500 meters
4.5 Fully ambulatory without aid, up and about much of the day, able to work a full day,
may otherwise have some limitation of full activity or require minimal assistance;
characterized by relatively severe disability; able to walk without aid or rest some
300 meters.
5.0 Ambulatory without aid or rest for about 200 meters: disability severe enough to









impair full daily activities (work a full day without special provisions)
5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to
preclude full daily activities
6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk
about 100 meters with or without resting
6.5 Constant bilateral assistance (canes, crutches, braces) required to walk about 20
meters without resting
7.0 Unable to walk beyond approximately five meters even with aid, essentially
restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up
and about in wheelchair some 12 hours a day
7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in
transfer; wheels self but cannot carry on in standard wheelchair a full day; May
require motorized wheelchair
8.0 Essentially restricted to bed or chair or perambulated in wheelchair, but may be out
of bed itself much of the day; retains many self-care functions; generally has
effective use of arms
8.5 Essentially restricted to bed much of day; has some effective use of arms retains
some self care functions
9.0 Confined to bed; can still communicate and eat.
9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow
10.0 IDeath due to MS















LIST OF REFERENCES


Armstrong LE, Winant DM, Swasey PR, Seidle ME, Carter AL, Gehlsen G. Using
Isokinetic Dynamometry to Test Ambulatory Patients with Multiple Sclerosis.
Physical Therapy. Aug 1983, 63(8): 1274-9.

Asikainen TM, Kukkonen-Harjula K, Miilunpalo S. Exercise for Health for Early
Postmenopausal Women: a Systematic Review of Randomised Controlled Trials.
Sports Medicine. Nov 2004, 34(11): 753-78.

American College of Sports Medicine (ACSM). ACSM's Guidelinesfor Exercise Testing
and Prescription. 6th Edition. Philadelphia (PA): Lippincott, Williams & Wilkins,
2000.

Bunge MB, Bunge RP, Ris H. Ultrastructural Study of Remyelination in an Experimental
Lesion in Adult Cat Spinal Cord. Journal of Biophysical and Biochemical
Cytology. 1961, 10: 67-94.

Cattaneo D, DeNuzzo C, Fascia T, Macalli M, Pisoni I, Cardini R. Risk of Falls in
Subjects with Multiple Sclerosis. Archives ofPhysical Medicine and
Rehabilitation. Jun 2002, 83(6): 864-7.

Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating Oligodendrocytes in
Chronic Lesions of Multiple Sclerosis. New England Journal of Medicine. Jan
2002, 346(3), 165-73.

Chetlin RD, Gutmann L, Tarnopolsky M, Ullrich IH, Yeater RA. Resistance Training
Effectiveness in Patients with Charcot-Marie-Tooth Disease: Recommendations for
Exercise Prescription. Archives ofPhysical Medicine and Rehabilitation. Aug
2004; 85(8): 1217-23.

Coulthard-Morris L. Clinical and Rehabilitation Outcome Measures. In Burks JS and
Johnson KP (Eds.), Multiple Sclerosis: Diagnosis, Medical Management, and
Rehabilitation. (221-290). New York: Demos Medical Publishing, 2000.

Debolt LS, McCubbin JA. The Effects of Home-Based Resistance Exercise on Balance,
Power, and Mobility in Adults with Multiple Sclerosis. Archives of Physical
Medicine and Rehabilitation. Feb 2004; 85(2): 290-7.

Era P, Heikkinen E. Postural Sway During Standing and Unexpected Disturbance of
Balance in Random Samples of Men of Different Ages. Journal of Gerontology.
May 1985; 40(3): 287-95.









Frzovic D, Morris ME, Vowels L. Clinical Tests of Standing Balance: Performance of
Persons with Multiple Sclerosis. Archives ofPhysical Medicine and Rehabilitation.
Feb 2000, 81: 215-21.

Gehlsen GM, Grigsby SA, Winant DM. Effects of an Aquatic Fitness Program on the
Muscle Strength and Endurance of Patients with Multiple Sclerosis. Physical
Therapy. 1984, 64: 653-7.

Goodkin DE. Treatment of Progressive Forms of Multiple Sclerosis. In Burks JS and
Johnson KP (Eds.), Multiple Sclerosis: Diagnosis, Medical Management, and
Rehabilitation. (177-200). New York: Demos Medical Publishing, 2000.

Gryfe CI, Amies A, Ashley MJ. A Longitudinal Study of Falls in an Elderly Population:
I. Incidence and Morbidity. Age and Ageing. 1977, 6: 201-10.

Herndon, RM. Pathology and Pathophysiology. In Burks JS and Johnson KP (Eds.),
Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. (35-45).
New York: Demos Medical Publishing, 2000.

Hommes OR. Remyelination in Human CNS Lesions. Progressive Brain Research. 1980,
53: 39-63.

Horak FB. Clinical measurement of postural control in adults. Physical Therapy. Dec
1987; 67(12): 1881-5.

Joffe RT, Lippert GP, Gray TA, Sawa G, Horvath Z. Mood Disorder and Multiple
Sclerosis. Archives ofNeurology. Apr 1987, 44(4): 376-8.

Judge JO, Lindsey C, Underwood M, Winsemius D, Keshner EA. Balance Improvements
in Older Women: effects of exercise training. Physical Therapy. 1993, 73 (4); 254-
66.

Kasckow J, Abood LG, Hoss W, Herndon RM. Mechanism of Phospholipase A2-Induced
Conduction Block in Bullfrog Sciatic Nerve I: Electrophysiology and Morphology.
Brain Research. 1986a, 373: 384-91.

Kasckow J, Abood LG, Hoss W, Herndon RM. Mechanism of Phospholipase A2-Induced
Conduction Block in Bullfrog Sciatic Nerve II: Biochemistry. Brain Research.
1986b, 373: 392-8.

Katayama Y, Senda M, Hamada M, Kataoka M, Shintani M, Inoue H. Relationship
Between Postural Balance and Knee and Toe Muscle Power in Young Women.
ActaMedica Okayama. (2004), 58 (4); 189-95.

Kent-Braun JA, Ng AV, Castro M, Weiner MW, Gelinas D, Dudley GA, Miller RG.
Strength, Skeletal Muscle Composition, and Enzyme Activity in Multiple Sclerosis.
Journal ofAppliedPhysiology. Dec 1997, 83(6).









Kidd PM. Multiple Sclerosis, an Autoimmune Inflammatory Disease: Prospects for its
Integrative Management. Alternative Medicine Review. Dec 2001; 6(6): 540-66.
Review.

Kirby RL, Price NA, Macleod DA. The Influence of Foot Position on Standing Balance.
Journal ofBiomechanics. 1987, 20(4): 423-7.

Kraft AM, Wessman HC. Pathology and Etiology in Multiple Sclerosis. Physical
Therapy. 1974, 54: 716-20.

Kraft GH, Alquist AD, de Lateur BJ. Effect of Resistive Exercise on Function in Multiple
Sclerosis (MS). Archives ofPhysical Medicine and Rehabilitation. 1996a; 77: 984.

Kraft GH, Alquist AD, de Lateur BJ. Effect of Resistive Exercise on Strength in Multiple
Sclerosis (MS). Archives ofPhysical Medicine and Rehabilitation. 1996b; 77: 984.

Kuramoto AK, Payne VG. Predicting Muscular Strength in Women: a Preliminary Study.
Research Quarterly for Exercise and Sport Sciences. 1995; 66: 168-72.

Kurtzke JF. A New Scale for Evaluating Disability in Multiple Sclerosis. Neurology. Aug
1955; 5(8): 580-3.

Kurtzke JF. Rating Neurologic Impairment in Multiple Sclerosis: an Expanded Disability
Status Scale (EDSS). Neurology. Nov 1983; 33(11): 1444-52.

Lambert CP, Archer RL, Evans WJ. Muscle Strength and Fatigue During Isokinetic
Exercise in Individuals with Multiple Sclerosis. Medicine and Science in Sports
and Exercise. Oct 2001, 33(10): 1613-9.

Ludwin SK. Proliferation of Mature Oligodendrocytes After Trauma to the Central
Nervous System. Nature. 1984, 308: 274-6.

Mostert S, Kesselring J. Effects of a Short-term Exercise Training Program on Aerobic
Fitness, Fatigue, Health Perception, and Activity Level of Subjects with Multiple
Sclerosis. Multiple Sclerosis. 2002, 8: 161-8.

National Safety Council. Injury FactsTM, 2000 edition. Itasca, IL: National Safety
Council, 2000.

Ng AV, Kent-Braun JA. Quantitation of Lower Physical Activity in persons with
Multiple Sclerosis. Medicine and Science in Sports and Exercise. Apr 1997, 29(4):
517-23.

Paty DW. Initial Symptoms. In Burks JS and Johnson KP (Ed.), Multiple Sclerosis:
Diagnosis, Medical Management, and Rehabilitation. (75-9). New York: Demos
Medical Publishing, 2000.









Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of
Aerobic Training on Fitness and Quality of Life in Multiple Sclerosis. Annals of
Neurology. Apr 1996, 39(4): 432-41.

Petajan JH, White AT. Recommendations for Physical Activity in Patients with Multiple
Sclerosis. Sports Medicine. Mar 1999, 27(3): 179-91.

Prineas JW. Pathology of the Early Lesions of Multiple Sclerosis. Human Pathology.
1975, 6: 531-5.

Ritchie JM, Rogart RB. Density of Sodium Channels in Mammalian Myelinated Nerve
Fibers and Nature of the Axonal Membrane Under the Myelin Sheath. Proceedings
of the National Academic Society. 1977, 74: 211-5.

Rogers ME, Fernandez JE, Bohlken RM. Training to Reduce Postural Sway and Increase
Functional Reach in the Elderly. Journal of Occupational Rehabilitation. Dec
2001, 11(4): 291-8.

Rogers ME, Rogers NL, Takeshima N, Islam MM. Methods to Assess and Improve the
Physical Parameters Associated with Fall Risk in Older Adults. Preventive
Medicine. 2003, 36: 255-64.

Smithson F, Morris ME, lansek R. Performance on Clinical Tests of Balance in
Parkinson's Disease. Physical Therapy. Jun 1998; 78(6): 577-92.

Teasdale N, Stelmach GE, Breunig A. Postural Sway Characteristics of the Elderly under
Normal and Altered Visual and Support Surface Conditions. Journal of
Gerontology. Nov 1991; 46(6): 238-44.

Tillman MD, Chow JW. Applications of Force-Plate Technology. Athletic Therapy
Today. Nov 2002, 7(5): 60-1.

Todd G, Gorman RB, Gandevia SC. Measurement and reproducibility of strength and
voluntary activation of lower-limb muscles. Muscle Nerve. Jun 2004; 29(6):834-42.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transaction in
the lesions of multiple sclerosis. New England Journal of Medicine. Jan 1998;
338(5): 278-85.

Waxman SG. Voltage-gated Ion Channels in Axons: Localization, Function, and
Development. In Waxman SG, Kocsis JD, Stys PK (Eds.), The Axon. (218-43).
New York: Oxford University Press, 1995.

White LJ, McCoy SC, Castellano V, Gutierrez GM, Stevens J, Walter GA, Vandenborne
K. Resistance Training Improves Strength and Functional Capacity in Persons with
Multiple Sclerosis. Multiple Sclerosis. Dec 2004; 10(6): 668-74.















BIOGRAPHICAL SKETCH

Gregory M. Gutierrez has an innate drive that has allowed him to succeed in many

aspects of his life. His competitive nature has helped him succeed on the field of play,

and in the classroom. He received his bachelor's degree in exercise and sports sciences

in December of 2002 from the University of Florida. He immediately began his master's

degree in biomechanics in the same department. Under exceptional guidance, he has

matured in many ways and is ready to pursue a Ph.D. in biomechanics. Gregory's long-

term goal is to one day become an orthopedic surgeon, while still contributing to research

as a biomechanist.