Jou.r1:ud ur Clh\itnJ Li4.Wr
,
~1ediduc
& Surgery
Volu1ne CJ. Nu1nl)er 6, 200 I
~lary Ann Licbc1:1. Inc.
rp. JOS- J.14
Effect of NASA Ligbt-Enlitting Diode hTadiation
on Wound Healing
HARRY T. WHELAN. M.D..1.M ROBERT l, . SMITS. J R.• M.0 .. ' ELLEN V. fl lJCHMAN, B.S .. '
NOEL T. WHELAN, B.S., •·~ SCOIT o. T lJRNER. M.S.. ' DA vrn A. MARGOLIS. M.D.,4 VITA CEVENCNl,8
HELEN STINSON. B.S..8 RON !GNATIUS,3 TODD MARTIN. B.S••l JOAN CWIKLINSKI. M.S.. '
ALAN F. PHILIPPI. M.D.,• WILLIAM R. G RAF, Ph.0 ..6 BR IAN HODGSON , D.D.S.,4 ·'
USA GOULD. M.O., Ph:D., 2 MARY KANE. B.s.,z GINA C HEN, B.S .. ' nnd JAMES CAVINESS. M.D.'
ABSTRACT
Objecri"e: The pur(lose of this study wns to ussess the effect' of hyperbaric oxygen (HllO) :lnd n ear-infrared
light therapy on wound h ealing. Backgro1111ti Datil: Light-emitting diodes (LED), orig inally d eveloped for
NASA11lant growth experiment~ in s1mceshow promise for delivering light dcetl into tissues of the body to promote wound healing a nd human !'issue growth. In this paper. we review nnd pr·cscnt our new data of' LED
lrcatJnent on cells gro" ·n in culture, on ischemic ~ind dit1betic \Younds in rat nlOdels, and on acute and chronic
\\lOUnds in hun1nus. M'uerinls anti Jl1erhod.s: 111 vitro and in vivo (animnl and hwnan) studjcs utilized a variel)'
or L·Eo '~'ave.length, J>O"'er intensily, and energy density parameters lo begin to identify conditions for each bi·
ological tissue that arc optimal for biostimulation. Res11/t<: LED produced in vitro increases of cell growth of
140-200% in mouse-derived fibroblasls, rat-der ived oskoblasts, and rat-derived skclernl muscle cells. nncl increnses in growth of 155- 17 1 % of n ormal human epitheli:l l cells. Wound siie d ecre:ised up ·to 36% in conjunc·
lion with HllO in ischemic r at models. LEO produced improveme nt of greate.r than 40% in musculoskeletal
training iu,jurics in Navy SEAL team members, and decreased womid healing time in crew members aboru·d a
U.S. Nam.I s ubmarine. LED produ ced n 47 % reduction in pain of' children suffering fro m ora.I mucositis. Conclusion: We believe that the use of NASA LED for light U1erapy :done, and in co11jw1ction. with hyperb~ric oxy·
gen, "·ill gr eatly enhan<.'c the natural " 'ound healing process, 11nd n1ore quickJy return the patient to a prein·
jury/illness h.w el of activity . This \\'Ork is SU(lported and managed llirough the NASA Marshnll Space Flig ht
Center-SBil{ Program.
INTRODUCTION
T
lhal lhc USC or Ni\ SA liglll·Cntilling dioJ os {LED) for lighl
H~
NllF.OTO CARE ror a pop11lt1ti(>11 wi£h chronic. wounds is n
g ro,ving challenge 1h(1I require..; innovative t1pprol'1chcs.
T'vo uppnliH.'hl!N thm i-p~ i fi.;(1U y nddruss 1hc idcntijiccl palho~
physiological proCe$S.t'~ in\•olveJ in woun<l b~aJing are hypcr
4
therapy alone. and in conjunction \\•ith f-U~O. \Viii _greatly en·
hanc:c the n:1turnl wound healing process. ·r his \Viii save \':tJu ~
able tinlc. and r<:$OUret:s ror both patients and hcall.h care fttclJl ..
tie~. FurLhe1·n1vre, i 1upro\led \\19und heali ng \Viii retluC".e the: risk
of infl.!(lion for 1.hc p~ttie nl. decrc"sc 1hc n1noun1 of costJy dn:b:-.·
baric o~ygen (I I BO) 1her:ipy and ltglu 1hera1>y. HllO 1hernpy is
i.ngs require.d. :Lnd a1ore quickly .retur.n the patient to a prein·
currcnlly Lhe ~tand::U'd Cl!' care for ischcn1ic1 hypo:cic, infcctt:d,
jury/illness level of neti,•ity.
and 01henvi~e slo\vly healing, 1woblen' \vouncls. \Ve believe
Laser ligh t and HBO have been 'vidcly acclniJncd to
D-Jp3nn1cr11s or •Neurology. and :111t1stic q1rgery. f\1cd ic:.I C<illepc:: (If \Visc1.1nsin. b·lilw:iukt:c-. \Visconsir1.
'.l'Q11a11111m J),n·t~ . Im:., Ban1cv~ l d. \Vi ~unsin,
1
<IChlldrc n·.~
Hui;piml of \IJisconsin.
~1filwm1kcc , \Vi ~ons-in .
.S4l11 .Qeoml Banaliou. -3tJ1 f'o.rce Service Sui)pol't Group. US~'I CR. !\1uriNtil. Ceorg.ia.
li-Nnvnl S_pci:inl \V:irf1lrc Gtu\lfl T\VO, Norfl'JU.., Virginin.
7Sub1nadnc Sc1u01dr<Jn ELEVEN. S:in Die~o. Catifur.nfo.
•N,\SA-f\ilru~hall Sp:.cc Aigh rCt:m~~r. ,\lalx1m,1.
30S
!')~d
\Vhelnn c.t al.
30li
200
g
§
• c ontrol
u
e
,g
.."'
0 4Jlcm2
100
!2i 8J/cm2
c
m
.c
u
>I?
•
50
0
20ays
3 Days
4 Days
FIG. t. Oro\Vlh phase spccifici1y or 3TJ fi b(Oblasts: cornbint:d \Vt)vtlenglhs: 4 J/cm2 \'Cl'8US ~ .l/c1112: 50 n1\V/cn1l,
.synthe.~ is
\VOi.ind healing of i.schcrnic, h ypoxic. ;\nd infected \VOtUtJs. I
at1Jcl11net11 and
l..:1scrs provide lo\v~cncrgy stimulation of tissues tJ1:H results in
increased i:cilulnr ncdvhy duiing wound hcaling.?.J
1
1 hese aclivitie.s ioc.ludc ooll~1gen production nnd anglogene-
facto r productio n (jncluding kerathlocyre gro,vth racU)r I KGF),
transfol'1nlng g1'i)\Vth facto!' JTGl•I. nnd plntele1-dcrived grO\vlh
sis." HBO 1hem1>y. \Vliich is ...:urr~n1 ty s1nn<lar<l 1hcrupy in tl1c
1rc.at1nent oi diabe1jc ulcers. graft f3ilures, radhuion nocrosis-.
and other ische1nie \\1ounct'i, h rt~ nlso het:n shown ro bc11elici\1lly
nffc<:1 1h..:se procc:-.s.sc..., Ho,vevcr. there arc n variCLy of instances
in which ::i p~ll:icnJ \Vho may bl!ncfit from HBO is unnble or uu\Villing lo be a-cmed in a high-pressure cnvironr11ent. TI1eS;e. siturnions indudc lack or nc.ccss to -a faciJit)' equipped \\•ill1 MBO.
claustrophobia. and cenain cun:enc or thro.nic n1edical co1Hlitjons 1hat would tnake HBO 1her:1py con1r.tindicaled. 111 1hcsc
instances. ligbt Lhc.~rapy proviJe.s an a hcrnaLlvc (1Jr the palienL
\Vound healing has Lbree phase.~: first, a subsc1·a1G is l;lid
do\vn. second. cells 1wolifem1e. "nd lhir<l. 1hcn:. is rc11)0deUng or
tissue. The. da1a. published so Jar suggests 1hat La.~r bio:;:thnula·
tion produces it~ pritUM)' eff~t during Lhe ce.11 1>i·olifem1ion
ph.ttse of 1he \V0111uJ healing ptoeC$$., It Ju.is been de1no11~ 1nHt.-d
that n1itochcu1tlria ore rcceptl,•e to 1nonochro1natic ue~lr-inf~irt:d
liglu and lh11t IH.scr ligJu likely increases rcspiralory n1c1abillis1n
of ccrtuin cclls.2.J.s Procc~~scs .such n:; Obroblast pnJlifcrntion.
of i.:ollngen ::ind proc:ollogcn, gro\Vlh
faclQI' IPDGF'I), nlacn,phage s~i nrol a1ion. lyn'lphocy1e ~tin1ula1ion.6 and greater rnlc of extracellular mnuix production have
been re1>0ned \Vith laser li_glu 1rca1nlent_,_,.., Aninnd stu di~::- on
the enhanced 'vound lu::•llng cftC:ct of laser light of lo\\'-PCl''' er
dcnsily have been pcrfom1cd in tqad~. 1uicc, rats, guinea pigs,
and s'vine_t~.1r. 1-luinan .-:tut.lies \vir..h laser ti.gh1 have dc1no11s1rnrt"ld gre:ltel' filllt)UUIS Of dpithclializutiOn ror W01111d
001 be efricie.nlly produced~ th!.!- Size Of \\'Onncl'i th:ll Ola}' be
1ren1ed is lin1i1.c d (due 10
l~ r
pr()cJuc1inn of u bcanl of light-n
fi.1ct incon~ is1c:.nt \\lith tre;Hiog. lnt,ge areo:ll), hcuc production
fro1n the lnser light i1solf can
~1ctu:Uly
damngc cissuc. and the
pi npoin1 be~11n of laser light c:u1 d::unnge !he eye. NASA devel-
~
0
•Control
e
,g
0670nm
0
.."'
~726nm
..
u
c
.c
lll!880nm
"#
2Days
FIG. 2-.
CIO$Ul'C
and sti1nulaLiurt of skin grafl he::i l i n_g_1.~ An cxccllcn1. revic\\· of
recent hu111a11 cxpe.riencc with near-iil frarcd Jighc Lhcrupy for
wound bc~1 l i ng \\'US publ ished by Conlan C! al . in 1996.'
l:,scrs. ho,vever, hllve $0111e inhel'e111 chartiClerisLics 1ha1
1nake their use: i1l a clinical !ieUing problc1nali1;, including liruiIUli01\~ in wavel1Jngth capabilities and be::un width. T he combined \V:J\•eleng1hs <>f 1.h e l igJu for OJ}fin1al \\10111;<.1 J1etil111g can-
3 Days
4Days
GtO\Vlh ph:L~e spcciilcity 111" osr..:ohla~a~; individual \Vi1velengihs:
RJ/c1nZ; 50 1nW/c111i,
307
NASA LED lrradintion nnd \Vound Healing
:g
c:
•
Q
u 100
E
c ontrol
0 670nm
,g
75
.."'""'
~ 728nm
c:
50
li&l BBOnm
<.>
#
25
0
4 Hours
Fl(t '.:\.
24 Mours
48 Hours
( ir'Q\Vlh 1>hase spcc.ifichy ,,f L·6 skeletal muscle cells tl'e:ued wich indh•ldunl \V:lvelcng1hs at 8 J/crnl; 50 n1W/crn2.
oped LEDs 10 offer 3u el'l"ecLive ahern:uh•e LO la~ers. 1l1ese Oat.a collection :ind C~llafog_ing 10 elucid:1ie 1he absorption coet"·
diCtde.c; ca.n. be cooligu1-ed LO ptoduce inuldple \Vaveleoglli.s, cai1 licieot~ <>f lhe vat ious hu1na11 lissues are currently unden\'ay by
1)1! amu\gcd .in J1tr'gt:. llm {UT>l)'S (::illO\Viilf! ll't:a-Unc:nt of hu'gt!
lhe printipli: invcs1igator-.
\\IO\u1d$), ;111d Jll'Odu~c nO heat It is also of i1nptJ1'UllltC tO 1101C
llmL LED lighl tht rnpy bas bccll dcc111cd ;1 no11signific3nLrisk
LED TN VITRO STUDIES
by the r'DA: 1hus. FDA approval fo r 1he "*'of LISDs in humans
rOr ligh1 therapy hns bc.-cn t1b1:1int."(].
In order to understand the effects of LEDs on cell g ro,vth and
NASA LEDs sti1nuhuc Lhc basic energy processes in tl1c n1i·
tod1ondl'ia (energy co1npart1nenL~> of each cell. particularly pn1liferati\'Jn, \Ve hil\'e 1neasured rndiofo.beled thyntidine incorwhen Jle,1r-i11fra1'Cd light is used IQ :1c1i\•1ue the \Vt1ve.le11gd1 sen·
poration iu ~1itro in seNer:tJ cell l in e.~ 11-earcd \\•ith LED liglu ac
si1i\•e c-0nmi1ue11Ls i nside (c.-hro1uophores. cy,oc l1ro 1 ne ,.~ysLe1 ns). v:irious '"'~1ve leug1hs :111d ener",gy levels. As _ptevioui;ly 1•tponed,
Op1in1nl light '":1veleng1hs (proven in J)rior studies or lnser nud 31·3 fibrobla.s1s (rnouse-derived skill cells) fes-ponded ex11·e1nely
LED light)'-'.il.1Hl,17.IS to speed wound healing i nrl11dc 680, \VCJI to Jnser nnd LED Jight cxposurc.s.10--i1 .?0.2l.2! Cell growlh
730, :u1d SSO 1\1n. 'T'hese wave.length.I\ can be produced accu- incri?:nsed 1 50-200~1 over unrre~11e<l conLrots. Additionally, '-"i·
1111 ~ly by l\ lt\SA LEDs, \Vhich have n bund\vidth or 15 nu1. The
11.:obh1s1$ (nu derived) h11ve bcco reponi:d 10 hnvc i 11erea.~ed
dCJ>Lh of ne:ar·lnfrarcd Light pt:nc1ratir;n into human 1is,;uc h:i~ DNA sy n th csi~ :lnd in creci.~Cd cellular grO\VC.h rate 'vltCn <.~x·
been uu::isurcd spcctrosi.:opici.1 lly.2J.t9 Spectra taken fro1n the j)l)SCd 10 l.n.~er lighL23 \Vith LhD treauncJll, \\le have found that
\VriSt 0C;\Qr rnUSCli:~ in lhU f~H'CUnTI nnd TilUSCfC..'l. ill lhC Cf!Jf (Jr 1heKC ce l h~ dcmon~t nltcd a _gtt)\Vt l 1 -pha~c speci fi~ it y, rc~pc1nd i ng_
lh¢ leg demonSLr.lt<: lhat n10SI o f lhe pbOIOnS ::ti \\'l\\•clen,gr11s o f o nly when ci:;lls are in the g.n)\Yth phase. In these-e:<pcri1hcn1s,
630-800 n1n lr.1vc.I ;:i pproxi 1ntH~ly 23 c1l1 through 1he skin Sur- fi brob1aSl$ seeded 01 a concen1ra(i011- of 500 cells/,ven and osface {light inpul) and 111uscle. cxjting m lhL~ pho1011 dctc.ctor. lcobJasts. seeded tU u concenln1tioo of l >< l Ql c~Hs/\\'cll. \Vere
175
150
0
'e
Q
• control
125
<.>
E 100
0670nm
SOmW/cm>
,g
"'c:
"'
"'<.>"'
75
l?.:j 728nm
40mW/cm2
50
!l11880nm
53mW/cm2
0~
25
0
4 Hours
24 hours
48 Hours
Hours of Incubation
FIG. 4. LED l't:.Sf~)O~e :'!I 4 .llc1nl , 50 1n \V/c1n2 ushi.g individolll Wli\'eleng1hs or 670. 728, :ind 880 0111 (perecntag.e chaqge frorn
cooltol vel');USnu1nber of houl's. of1er LED 1.ren11nen1).
JOS
\\'lu:hto ct .::ii.
180
160
ec:
0
0
140
• eon1ro1
120
E 100
0670nm
80
~728nm
g
.."'
,,"'c:
..•'
50mW/cm2
40mW/cm'
60
(.)
f8}880nm
40
53mW/cm'
20
0
4 Hours
24 hours
48 Hours
Hours or lncubalion Atter LEO
Fl(;, S. LED ~ponsc at SJ/cm!; 50 m\V/c1n! u1,,ins indl\ 1dual ''>3\'elengths of 670. 728. and MW nrn (fH!t"CCntuge changt< from
contn>I ,.CfMI., nu1nber of hours aftcr LED crca1n1cn11.
12·\\Cll plate~ wilh a " 'CIJ SUrfUCC an.-;\ Q( ap(>nl.\ifU<!lCI)' ..a cm:. DNA ~~-nthesis. " 'as dctcnninctl ''" the 'c\.'ond,
1lurJ. nnd f0t1rth days in culture fnt both fibrobl:.ll\f"I (fi~. l) and
O'! l c<>hla~u1 (f<i.g. 2). E~po~ure to LED 11r..1di;1tinn nc<:c1er.11cd
1111:. ~fO\Vlh rmc of fi bl'Qblascs nnd os1eoblas11r1 in cuhurc for 2- :l
dny!\ (,;1'0\Vinp. ph:lS<"), but .sho,vc<l no sig11iflcun1 i:h:u1sc in
gro\'i'lh rUIC for celli. in culture JU 4 day~ (~l1U il1n11ry 11hm.;c ).
,ax,k,'"tl Ul
Th~'e tln111n1·~ i111por1:11u tleml')USt1"a1ions
of c:cll·lO•cCll '-'onu1c1
lnhil>i1ic111. \\'hich occu1~ ;,, vitro one-<: eelI c11hu~) fll'l'r,nlch
conflurncc:. Thi... i~ :1nu1c,gous, i11 1•;vo. 1u n hcul1hy (1r~o 1 1 is111.
'''hid1 '"ill n;~cncrutc bettling tit\:.ui:-. h1u l«IOll fu1·1hcr 1;ro"·1h
"·hen h1::d1ng i~con1ple1e. It is imponant 10 noh! 1h.u LED 1rcal·
n\Cnl J.Cctlcr.nt~ nomial he:.:llin,g and tissue re~cnerauon " 'itlt·
1Jroduc1ng. O\'Cl'J!rowt.h or neopl3.stic 1r.in,fonn:uio11.
A 't'ri~ of c:..penment") bas re....~ntly bttn ccwn1,fcte!d u''"~
an L·C• n111scuh~clccal t.""Ctl line <r:u deri\ed). Thc-.c cell*> \\ere
<JUI
~XJ'O'Cd to 1hc LED light at bulh coo1biLled ~;.t\ch.:n~1f\, iHld 111·
dn 1dudl "a''Clcngth' (670. 728. n.nd i;KO 11111). encri:> dc:n,1'1Cl
of -I and 8 J/c:rnz. anU an inh:n..,it} of j() 1n\V/c-1n!. f<ci,ulb
dcnH11t...1r1u.cd a cell ,grll\Ylh increase of nbat.11 1401ff u\cr llli·
1re;ued con1ruls. fW1icul:i.rly tu ~ J/cm? cncrt;)'. a~ $hO\\-n in
Figure 3.
In at.ldiLion. c.:xpcrinle n1~ nrt no\\ co1nrtc1c wing a normul
hun1an epithelial cell line seeded in 12·wcll plate~ 111 :a concen1ru1ion nf 500 cell s/,~ ell in t)« lcr tt-1 PL'S~ihly explain 1bc con1inucd. dr:un:uic res-uh;; of LEO lighl 1hcrupy in prcvcn1ing on1l
111ucoi::ilis in l'anccr pn1ieo1s. Cell g1\.1wtl1 incrcn..,cd 155% over
1Hll1\!~1t1Jd C(lUCr ol;; :1t 670 1un nnd ·I J/c1n1 cni..:rgy dcn~i1y (50
111\V/c111l pvwcr dcn~ ity), ns ~ ho\\11111 f'figu1'C 4. An incn:asc of
l 7 1'l- over un1rc.n1ed cnntn)IS \\a;; ob1:.incd \\lid1 {I \\''l\·elenglh
of 880 nm and 8 J/cn1: cne.rJ)' dcni-11y (!i'.\ n1W/cn1: p<>"cr den·
si1y). all: shQ\\•n in figure S.
Colla~en symhesi> of 1hc lfaC/\T cp11h<lml cclb wos dctcrn1incd by measuring tri1ia1cd prnl111e 1ncorpor.nKHJ using. ;i
nl(Kfified method described h) Pc1crl.of,Jr.)· und D.egithnann..1.:
HaCA"r epithelial c;clf, " 'C:rt: ~c."<k!d in '"o 12·v.·~ll tissuc cullure plo1C5 "ilb 600 µL DMEM c"n1.1i11111!' JO'l FBS. I<; pcni·
c1U1n/1m:p<omycin. and 6 µL L-pmhnc (Z.3-' H (. The mcdi•
\\'"33 free of ooncsscnti:1I :uni no 11Cid~. One plJt( \YJ.S ~ ru, the
con1rol. ond the other\\'~ ue;tted \\•ith chc 1.7()..nin NASA LED
250
0
~
200
0
0
E 150
..
.,"'
0
.::
,,c:
100
"'
50
0
0
Conlrol
LED
Fl(;, ft. HnCAT epilhcJi:1J cell coll:igtn 1»y 11l l 1 c~i11 rtl ~ .l/c1n2, .~O 111\V/1:.1111. 670 n1n. Shown ill 2.1... h •1 1 pn1li11c. incorporation.
309
NASA LEf) lrr:uliat ion :and \ Vouncl Healing
140
"'
..,vs
""
120
100
~
80
..5""
60
.5
OJ
40
*
- - Conltol
- - - HBO&LED
- ··• ···· LED Only
20
0
0
FIG. 7.
2
6
4
Ch:1ng~ in v.·ound size in
10
Time (days)
8
aliquo1 wa:o: used 10 quruui1:ne 1otaJ pro1ein by lrichhJroacetic
~1cicl (TCA) prc~ipi l:uion . 'fhc 11recipi 1H11!.(I r>roteins 'vere collected by suction 0 1110 a glass fiber fiJter and nllo\\•ed 10 dry
overnight nt roool ten1per~uure. ·n ie secQnd :lliquo1 wn,!I i nl.'.: 11bated for 90 min :tl 37°C \Vilh highly puri fied btic1t: ri~1 t colk1gcnasc t.ba~ dC!~nldcd ~he cnll.tgcn in the s:unplc. Tiu• rc1naining
n<nlcollagcn prowin nlso uiltlcrwent TCA 1>reci1)iw1ion. The
folJO\\rif1£ d:l)', StintiJh:tljon nuitf \\IIL't ::lddcd Otld the ~u1nple-S
\VCre counted i 11 :1 ~cint i l b11 i on to1in1cr. Co1la~e11 cr>nltjlll \VllS
dclcnninc<l by suh1ruc1i11g 1hc nonco11agen prol¢in from 1he 10w.l proteju. f igure(> sho\Y!-l that Lhe li:JCA'r epitheliaJ cells Lhat
were NASA LED lTC~ttcd synLhesh~ed fnore l hHn t\vice the
:unounl or col111gcn th:.111 1J1:J1 or lbc oonlrol cells.
LED WOUND HEALi.NG IN RATS
An ischcn1ic "'Ollnd is a wound in \Vhic.:h there is: ii lnck or
oxygen 10 the \Vounll beJ due tn au obstru.;Lion of ::in.:rial blooJ
C>.
"'
.§
flow. '!'issue ischl!n1h1 is a sig,11ilican1 cause of i mpai~d \Vound
heaJing. 'vhich renders the \\'Ound 0101-e susceptible- 10 inrecLion.
lcr1ding 10 chronic, nonheaHng \VOW1ds. Despite progrc.'is in
"'ound healing l'ese~1r<:h . 1here is s till ve1·y linle \111de(s1:111di1lg
of \vhnt cons1j1utcs a chronic \vound, p1111icul:.irly tll the moJccufar le~·el, Consequcnlly. 1here-is 1ninhnal scientific ratio11alefor
1rca1n1e111.
In order to Mttdy the cffccL< of NASA LBD tcchnolo_gy :mJ
liBO ther~py. we developed :i. 1nodcl Of an ische1nie \vound in
nor1nal SJ>rague-D:.iwley r.11s. T\vO 1x1raJlel. I l-c1n incisions
were 1nadc 2.5 cn1 apart on Lite dorsu1n of the rats. leaving the
crunial nnd caudnl ends iraacr. l 'hc skill was elevulcd along 1tielcngll1 of the 03p. and t\VO punch biopsies created the: \vounds
in 1he cen1er of 1he flnp. A shl!et of ~ilicone \Va~·placed bel\veen
th.: skin and 1hc unc1erJying 1nu~~Je 10 :.ict as a barrier t<> \•ascul:ir growth, thus incrc:lsing the i~chcm ic insuh tQ the \vounds.
The four grOUJ>.S, each cons.isling or 15 rat.;, in 1hi$ srudy include
the cont1•ol (oo LED or HBOJ. H.BO only, LEIJ (880 run) \lnly,
oud LED and MB() i n ccunbinarion. The·HBO \vas supplied aJ
2.4 mn·1ft)r90 nlin, and rhe LED w:i~ deliver~d 111 a nuence of4
J/cru2 and 50 1n\V/c1u:? for J4 con~"ccufrvc days. 1\ future .sludy
- - c ontrol
_..,___HBO Only
_ .,._ _ HBO& LED
····•···· LEO Only
0.0020
,.,.
tr>
.....
~
...
i
0.0010
§
() 0.0005
~
16
0.0025
-2' 0.0015
LL
(!)
14
nu ischCJnic \Vt>uncl n10clt!J versus tin1e (days).
at 8 J/c1nt. After 2..J. h of incutxu.iou in 5% CC>1 nl 37.:.c. t\VO
200-/J..I,. :1liquols of nlt..'dia \Vere ren1ovcd fn11u each well. One
I£
12
/./·
f
./
'}/;
,'
,/
,
, ,_.,..,
.....
.,...
/
....,,,,,.,.....••.•....•..•......-..:;;:;;·······
,_···
...:::
0.0000 .,,-c.:-~---':.---~--~--~--~---l
2
4
10
12
14
0
6
8
Time (<fays)
FIG. R.
Ch!lnge in vascul:u· e11tlo1helial gro,vth f[!Ctt)r <VEGF) coucentralioo (µ2f1ng p1·01cin) ver!ius Li:n1e (days}.
Whelan et al.
3'10
c
ea.
0.12
j
"'
.E
"'
0.08
.,
0.06
2;
c:
0
e
c
Q)
"0
c:
0
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......~·"
/
....."
../ ' , ,
,
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...'
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0 .04
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.
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• ........ .., •.&!:
I
0.02 ..... ,
(!)
u.
- + - Control
-.t.- · HBO Only
--e-· HBO&LEO
····•···· LEO Only
0.10
0.00
0
2
4
6
8
Tlme(days)
10
12
14
flG. 9. Chung<: in b:tsic fR>n 1bl;1$Lg.r0\\11h racto'l' (J':CP-2) eoncentr::1tion (µgllng protein) versus lime fday~).
\Viii inCOfj:>Ol'i.lle the cv1nbin:tti(l11
o(
three \Vavcle_ngths (670.
728, ood 880 11111) i111..he 1reaunen1 groups.
The wounds \vcr..: 'roc;etl rnanually<>n days 4. 7. 10. and 14.
1"hese tracings \Vere subsequently scanned inh,1 11
cornpu 1 ~r.
und 1he !>ize of 1he '''Ouuds \Vas lracked using Sign)aSc;.:.111 Pro
soft\Yare. Figure 7 depicts the churtgc in \ V(}und ~it,e ovc1· Lhe
course of tbc 14·day experiment. The cornbinHlion of HBO
und L.EO (880 1101) proved to have t.he grea1esl effect in wound
hc.alin.&in tt>nns o f Lhis qualiH:tLi ve asses~n1e1n or \\'OWld area.
A 1 day 7. \\'f'unds. 1.1r tl1e H B O and L ED (880 11111) grou1>" 'ere
36% .s1nullcr than lhosc or the con1rol g.l'o up. Thnt :\ize dis~
crepancy remained by da)' I 0. T he LED (880 nm) alone :ilso
speeds wound closure. On day 7, 1he LED (880 nm) trca1cd
'vounds wns 20% s:nH1rlcr thnn 1he t1)11trol wounds. By day I0.
the diffe re nce bcl\vcc:n tJ1ese 1\\l() groups d ropped to 12 1»>. This
'''as due 10 the fact Lhat there is n point 'vhc.n 1he \Voundi> fro 111
:'a.I I of 1hi.: grOIJ()S \viii be closed. Hence. the early differences
aru the n1os1·ialportanl iu terniS of dc1cnnining 1he Qp1i1naJ efl'CcLS ora given Lteatme.nt. Tbis ..:an he seen 01day 14 (Fig, 7},
\Vhcn 1he po inL~ ureeonvcrging due LO the fact lhat lhe \vounds
arc he;lJi:ng.
Analysis-of the biocbcrnicol makeup <1f lhe wounds at doy.o; 0.
4, 7. :)nd 14 was pcrfO mlcd. TI1e day 0 lime 1~ i 1u \VilS dctcrn1i.ned by evaluating the punch biopsy snmpJcs fro1n rhe c)rigi-
nnl surgery. 111e levels of b.a$ic fibroblast gro\vth (actor (FGF..
2) and \'Uscuhtr 1;.ndOLheUal gn}\\flh (act.01· (VE(lFj were
ELT
I0
MEAN (SartAreal
I • MEAN tWound area cm>\
Conlrol
'1.0 121
i.0244
ELT
0 .8548
0 .7307
FLG.10. Typc. l dial>Ctic n1jcc with excj sioJ1nl skin \vound$ tre::ited \Vith co1nbined LED '"aveltJngtbs. 4 J/cn12. 50 n1W/cm2. The
t>qutu\: root of \V011nd ~lrCa i'> 11~d in 1he dcpende111 variable in lheanalysis. This tr.lnsfom1:nion W'.L't needed 10 correct for noncon~
s1an1 error in 1hc. guncnll lineiir n•0<.1el. SqrtA rea could be jnrerpreted as being propc;irtian<ll 10 the radi us of n circular "'<'Ju1u.I.
311
NASA LED l rntd.h11io n nnd \Voood Flealing
140
.,
120
.5'
Qi
""'
ID
E
• Baseline
100
0ROM
80
0
"'"'
c:
"'
"'u
~
(2J Pain
60
llSJ Girth
40
•:,!? 20
0
FJG. LJ . Ct10\t1lt11ive results or dala fro1n 11 pa1ien1~ iSEALS) sho\vin,g in1provernen1 In range of motion. pain. and s irth reported
as pt:irccn1:1gech•inge fro1n chronic. uoi1nproving injured baseline afler LED treallnenl at 4 J/c1nl , 10 m\ V/cn12,
de1cnnj ocd usiug ELL..'iA (e.nz.yn1e linked U1ununosorbenl as·
S:ty). n u.::. ch~1 n ges Jn 1he VUGF conccn1.nuion 1hrougbou1 the
J.i-·duy cxpcrimcnl can bcJ>Ccn in Pigur1: 8. The LED t880 urn)
1ucnt. \Vhcrcas 1he 1cvcl would normally dr<lp offby d:ly 1 for a
LEO.only tre;ued \\'Ound, Lhe HBO effecl seizes control, causing 1he cooce1nrotion of .FOEt-2 co plate.:iu. Hence, an elev:ned
FGF·2 concei1ll'ilti(>tl i~ achieve-d 1broug.hou1 the greater pan or
1he 14-day 1.re111nu:1n \Vith botl1 loLBO and LED (880 11111) therapic.s. Further unalysil't 1:ir 1he excised \Vt;1unds \Viii include 1n111rix
ntc1t1Uoprotci-n:asc 2 and 9 <MMP-2 anti MJvlP·9) dctcnnimnion
by El .IS1\. hisl.(llO£it.al exn1nilu1tio11, :ind RNA extri.H.'tion.
/\ 'vound healing i1n 1>airtd type '2 tliabclic n101.1SC n1odeJ hM
also been studied. /\s previously rcponcd. genetically dinbciic
group cxpcrii:nccs J VEGF peak n l day 4 nu1ch J i k~ du: C<)ntrol
group. Ln eon1ras1. 1hc. f:typcroxic effect of 1hc 1-113() .'t-up11rcs~e.i:
tlie doy 4 peak, and instc:1J, 1bc HBO groups peak ni clay 7. The
•y11ersislic effect of 1he HllO >11d LED (880 nm) can be $<en m
day 4. l 'hc VEGP Jc\lc.I for 1hc gr oup rc<:ci\1ing b<>th tren.1 1nt:n1.s
is markedly higher ot dny 4 than the HBO only group. T he HBO
hod Lf.D ( 880 n1n) 1reat~d group also t:xp..:orience..~ the day 7
peak cha.racJcrizc:d by 1hc I IBO 1ren1n\et1L I lence. lhi!-l'C is .a ruice 1rea1ed '"ith IO\\' leve1 la~er i1·radialion den1onstr;i1cd sign1on: unifom1 rise and f:ill t<> the VEGF level in 1he eo1nbined nificnntly enhanced 'vound cJosure gl'ossly. ond hnproved
u-catn1cnl group as opp(•scd 10 lhc sudd(!n i n c.:re~t:~ -seen in 1he \VOund epilhelinJii:1tion, cellular COtlleJH., £ 1':1JlUl:tliOll tissue (l)t•
wntrol. LED only. and HBO only groups. Byd"y 14. the ~mo­ mulion. C\11J;1gen dl:poii1jon, iJnd <Xll!J~ sjve 11tov1isculari1;tliOn
u-e:11M groups hn\1e dropped clo~er to the normaJ level than the on hisrologic:il evalu~nion.11 Jn our s1udy. lypc 2 <li:1bctic nticc
LED (8~.0 nm) only Ur control l!rou11s.
\Vilh l!)CCisionnl skin \VOUUds \verl! 1re.i1:ed \Vilh LEDs i1l intli v i d~
·n1c syncr~istk cffocis of HBO 1md LED (880 nm) can nlso ual wavelengths or MO. 7"0. tmd 880 nm m 4 Jlcm' and 50
be Sf..'1!11 easily in Fi_gure 9. 1·11c paHen1 of LJ1c t:hange." in basic n1\V/c1u.!. LED ueallncnt produced incre-ascd heal ing nucs.
fibroblrtst gro,\11h ractor (FGF-2) com.:en1rn1ion is ::1ir11ilar 11) 1hn1 co1npar¢d 1() surgic:::il ccuutol:->. as seen in Figure 10.
.,r the VEGF dotn. Lt is clear lbOL the LED (880 m•I) dny 4 peak
A repe:ued 111ens11rcs an11lysis \\1:1$ Cl)1\duc:1cc.I using n .sc11ernl
is higher thun the cJny 4 pe~lk of chc conlr-OI group. 11lcse peaks linear model \vj1h S11rtArea as 1hc. dcpen1lent vnriable and Treat
can be ouributcd 10 the hypoxic cJfccl or the tissue ischcrnia as the indcpendcn1vnrittble. The intcrac1i<)n elTect Dayt-Trea1is
c:rea1ed in 1he surgery. 111e hypero:<ia of 1he HBO therapy has a ;~ igniJicaot (p \1alue = 0.0095). indicnling that 1.hcre is a signifi·
greater effect on suppressing lhe FGF·2 c.:oncernnuioo HI d~1y 4 cruu diJTeren~e bel\Veen uenunenrs on !-Ofll e clays. l 'his test is or
than the VEGF' conccntr.ilion at the same fjmc point The syn· primary interest in this si1u~Hi on. bcc:luse it shc)ws that 1bc t:rCal·
crgy rJf the l\Vt) l1'eilll1\eo1s. js l!Vide111 \\then looking at the HBO n1ent.s nro effecLive for son1e pan of the rreat.n11:nL period {Fi g.
:ind LED (880 am) trc;ncd group. The cunccntrntion o f PGF-2 lO). This an1dysi!'O \VU$ carried 0111using 1hc SAS s1~11is-1ic(ll.:,:ofl.
:11 day ~ is signifirnnlly enhanced tiy 1hc LED (880 nm) treal·
ware"package. puhJjsltcd by 1110 SAS"lns1i1u1c. lnc.
'fAULE I. PAIN l'N1·£.~s 1·rv IN Nl ucos111s PA1'11l.'4TS ls Rsuucell UY L ED T HERAf' \' J'N Cue1~K.s CoMtARED TO
T HROAT (CO~'l"ROL = 1()0%)
Control (thro31)
Righi c h cc~
Left cheek
ConlrOI SEM
Rizht SEM
Left SEM
Da)' I
Day 2
Day 3
Day4
Dny 5
D"y 6
IJa,\' 7
/Jay ,y
Day 9
100
98.56
104. J
JOO
67.8 1
71.2 1
100
JOO
100
86"1 6
86.82
17.8
24.5
24.3
lOO
63.79
60.93
18.9
24.1
25.9
100
51.73
53.27
JOO
5S"<i5
100
5i.48
6 1.48
58.65
21.7
12.6
22.8
17.9
17.7
11
18
15.8
:l3.2
22.9
3'1.78
81.4S
20.7
34.2
33.8
25.2
20A
24
20.6
79.78
82.32
IS. I
23.5
24.1
l I.I
312
•control
(throat)
0Right
cheek
~ Left
cheek
2
3
4
5
6
7
9
8
Observation Day
FJ(;. 12. De<:n:•tSc: in pain inh:nl):ily over Lime after daily treaunen.l with N1\SA LED Jiglil ti.t ()70
nff1, 4 J /<,:1n 2,
50 n1\V/ccn1..
LED WOUND HEALING lN HUMAN SUBJECTS
rne11ts i n cen1i1nerers. percc111 chan£eS over tin1e i 1t nJI of the
nfore1nentionecl ptu:~11ne1ers, anti nu1nbc:r of LED·Lrc<11.n1~~111s rc-
Clinical LED \vound he1:lll1tg studies have bci;;.n reported pre·
viously;11-u add ii ion;il llata on human Lrials arc su1nn1arized
below,
?vlilitt'lry Special OpCrmiuns ;ire ch;.-irac1erizcd by ligbtly
equipped, highly 1uobitc troops c.ntcdag siLuaLi(')n.~ requiring
optiinaJ physical conditioning 3t ull ti1nes. \Vounds are tin obvi-
qulrt:-d f"or the subje~t 1u be lit·for-full·<luly (FFD}. TI1~se in~
juries \vcre su:,tuincd I month. to I year prior to LED Lr~atn1 e n1
and h~1 d been c.hro1iic nod u1Linlproving in na1ure. See sununnry
of d:1ttt in Figure 11.
ln collnhoration \\lith U.S. Novy Subtnariue. Squ:1Jrnn
ELEVW~. data have ah:o been rocei\'ed rrun11hl!' USS Sall Luke
City' (subn'K1ri ne SSN 716 nr 1he U.S. N11vnl Pacific Flcc1). Sub~
mnrine 11 1n1 t1sph~reto< arc lc.>\V i n oxygen und high in carbon dioA·
ide. whioh cur11pounds th.: nbs~n,·c of crc'v exposure 10 sun·
OU$ phy,s.iC'nl risk during co111ba1 op..:nuj oo~ • •<\.ny simple nnd
lighl\\'Cig.ht i.:.Quipmcol that prornOll$ wound he.ding ;u1d mus.
cuJ1.\S~e te·1:d rch~1 hi l i 1r11ioo :ind condi1ioning has potc.otial Ineri1.
r\n LED :trruy \Vilh tllrcc \Vavclcngths co111bi.necl in a single unit
(670, 720. ond 880 rnn) was delivered IQ N" val Spe<:iol Worfare
Group-2 (SEAJ..S) in Norfolk1 Virginiil. Trcatn1cn1 'vas 'vitJ1 4
J/~012. A d3t:1 calJecLion ~ystem ha.ii- been implen1en1e<l for tllUS·
culoskcletal training j njul'ie..~ 11·~ated \Vith LJms. Data ct,llcc:tio11
i r1s 1 ru 1nc n l.~ no\v include injury J iagnusis, day from injury,
range of 1110Lion n1c:1surcd \Vilh goniometer. pain iiuensi1.y
scnles -r<:poncd un scnlc 1- 10, g.inb·t ircumfcrcn ti:al n1casu1-e·
light. making \VOund healing .slower than on the surfitce.
Repo1ts indic:ue n 50% t"nster healing of ln<:erntions in c:-rcw
rnernber; cn.:aLe:d \Vilh it LED ~UTU)' \vilb three '''avclengths
con1hincd in a single uni1 (670. 720. 88() nn1) com1x1red to lllt·
Lre:.lled con1rol henlin_g (7 Jny~ t:Onlplrcd to npproxi1Tt(Hely 14
days. rcspcc1ivcly). Co1nple1c analysis or data is still undcl'\\lay.
R ~cc i p1 of c<'.>nCrQI dflHl fr()m .subn1mincs \Vithout J..ED ;:uniys:ou
board continues. rind nnotht'l' $ub111arinc reccnLl.y tJcplQycd rroJn
o, "-~~~~~~~~~~~~~~~~~~~
1
2
3
4
5
6
Time (days)
7
8
9
FIG. ·13, The difference bet\vcc-n LEO.rre;.11ed (1nou1h} and u111rcn1cd control ((hro3t) bc<.'011icS n1orc dnun:11jc over ti.Jue. \YiLh
daiJy 1re:.1tmen1 using NASJ"\ LED ligh1ac (>70 nnl, 4 J/c1112, 50 111\V/c1ol
NASA Ll!O lrr:.Hli:uion ::ind \Vound Jleulin~
U.S. N;;,·al Stati(\n-S'3.D Diego <Hl 3 6-month m1,~ion i\
cqu1~ -.1th a LED <nap-light array oo boonl.
In 3ddi1ion. \\C ha'c recent!~ begun u..i~ing NASA LF.Ds 10
pru11101c hc~1hng of acute oral lcsioo.i;- in ~JiMric lculcm1;1 pacien1 .... ""'~'final life-saving effon._ lt'ukc1n1:i p;1t1<nt'\ arc ii\·cn
healthy l:k>nc rnarro"'· from an HU-\-nt:Hchcd donor. Prior to chc
1n:1nS(>l:uu, che p:nlent is given u lcthol do~e of ~he11101hc:rupy In
orJ..:r lu dc111r(1y his or her O\\'n canc~rous. l>onc nuuTO\v, 8\:c1111c:.c rn;u)y chcmother.tpL'Ucic dn1g~. ui.; \vcll n,s r:tJintion thcr·
.11>y. )..iJI nll r11pidly dividing cc.Us indiscrin1inately, 1hu 1n11cosul
linin~l'> of lhe gu~trointcstin:tl trac1 ate of1c11 d11n1t141ccl during lhc
1run1n1t.•1u. A~ 11 re.stilt tJJ' 1..hese gns1t<1in1\.•.;1innl cffcl'I-,., g1•catcr
lh:1n l)Ot·lhird l)UtiC!Rl.S tre:ucd \Vilh C}'IOIU~iC dftl};\ llevclop
Ulcers in !heir lllOUlhS (or.11 t11UCO~itis) anJ/Or SUf(cr fronl llOll·
or
..c.a :uul diorrheu. Oral 1nucositis. Y.'hich cau:o.e, :o...:\c1'C p,1in.
blecdinJ. an Increased ri.5.k for infec1ion. anJ con1pron1i-,.cd obll~
ily 1ochc" and ~wallow. is 3 $ignifican1 risk for 1hii J>Opuhuion.
Cum:nt lrca1n1cn1 for mucos1us aJdre<">"lf!..' pain n1an:t.1!'c.:rncn1
and 1nft..--ction prc,-ention. The use o( or.al agcnc~ 10 pron1C>te
ck:anor.1nl!. d..:bnJc1nenL !lOd con1fo11 urc l"t'\iommcndt.."<I. nnd
ptTiph)'lx1ic or.al ru1Liviml .and :tnlifung:1I :1gcnt<. hJ\c been u'ied
1n minhn1zc infection.\. B-ec:i~ l~cr.t ha\ c bc~n "hO\\ n hl
\peed hca.lin1; of oral 1nuco~i1i.;,'2S~ we h.a\'C receruly expanded
1hc wound·hcolini ubilitios of LED ligJ11 thcmpy 10 include
1h c~c
on1I l e~ions.
A .i J/c1n l, SO rll\V/c1nZdosc of670·n1n Jlglu fro1n LIJD~ \VO;;:
np1>lied dolly 10 the c•utsidc or each pr11ie111'-,: lcfc check bi;giu.
n1np on lhc day or l>ane n)llrr-Q\V u:anspl11111alion, The s1u1u!I of
1hclr or:tl u1uco!'J\, n1ou1h. und lhronl pain \vn-; a-;se-.st::d 1111-ce
1in1cs :1 week by l\\'O cnlibnucd dc.nutl clinlcift11', l~dl ,idc of
1he UlC'HtlJl "''" 1;ec1red ui..ing-1hc Schube.n Oml Muco,ilh Incle'(
(Oti.11 ). 1hc 111uoo!l.a \Vere pho1ogr.1phcd. and 11mu1h and Lhroat
pain \\·ere J~\C<i~ using a 1-10 Visual .An:tlog ,cnh:.:' \Ve
hJ\C Ol)W t·ornplCJcd ltcatmCOI 10 half Of OUr inlcndcd pJlicnl
popuhuiun and hilvc not.iced Sblne \"t'r)' e-ncoun1gin~ tr~nd,. bu1
51a11Mial \i~n1ficancc "ill require more patient..,. 3( 1n1c:ntk:d in
our currtnl ~tucJy do,;gn., \re have MSes.~"'tl lc:fl chc.-cl~ riaht
chccl.. and throo1 pain in each ir.iticnt. and ha\~ nocal 1h;u 1hcrc
h U() 'IOIL'tical d1ffCl'el1(."'C fil percci\•ed p:un 00 C:lfhCr ~idC or the
11101uh. cun-,.i}.t~nt with cJle e:tpected tfs.,uc pcnc1rnfio11 f2J c111)
ol' LEO hsht. 1111\):JI p:ain, however. \\':t.-t c,)1b.1"1cnll) higher
1han 111ouch pain. and hecaust.':our light doe" nol cxrcncl in10 this
region, \Ve hav~ u.;;cd 1hil\ priin as our C•lnlrul. Althou~h 111ou1h
:111d thl'<'IJI 1xd11 were initi~1ll~ sin1iJnr, tU<Julh 1>11in 1>cnkcJ ;u
~{1% nr lhro111 pnin on doy 5 afler lrllll'! J>lfln1 unll 1routi11cc1ucn1ly
313
tioo rore~paoding our ~1udy 10 i111:ludc at k:a.\l lhrcc mun: aca·
dcrnic medical ren~ in :.dJi1K>n 10 our O"'"· to be supplied
v.·ilh NASA LED :lWJ.)'\ b) Qua.n1un• l)c,·ica. Inc. A muhi ...irc:trial 15 being plannc..'tf 1hn"ltlgh th< tnccm.Jtiorutl Bone ~l3rr0\\'
Tra11>plont Regis<ry.
RESEARCH COLLAIJORATION
\\le nre nO"' invcstig;:uing ne\\I c<1llnhoru1ion~ \Villi 1hr.:- De·
Rcsc::tJ'c h Projt::Ch Agenc.y (l)ARPA) ror rur-
fl.ln~c. Ad\'UJlccd
1her 1n ilitary applications of NJ.\SA Ll~I) " '01111tJ hc:aling tech·
nology in 1niliwy 1neclicinc. Sc\'eral uniquely 111ilitruy
situ:ujon!"\ and i ndico1ions could be ttddre..,\Cd i1' the ne\l.r collal>0011ion. Tbcscjncludc bunu;, 111JUriC( fro111 chc1nical ngcnts.. r.i..
diotion. lughly infected '")"nd> (which Jr< I) pica! for the h)~
~ienic condi1ion:. o.....~urring in 0011JeOclds). in(ectioo~ di.sc;i.scs.
.ind c~lcm.aJ ,,·ounds occurring in c:nv1nM1n1cn1~ \\ ilh no solar
irr.tdi.atioo, lo\\' oxy~en. t\.00 high t:arbon d1u'.\:iJic fwbmarines
nnd ~pacccn,·ironmc.nL~). Thednunalic n:\ul1' \t.ilh useo(nearinfrarcd NAS.-\ LED tight U.> prt,ent di~,1hc n111cosnl Jesi~
(nn1cositis) and pain in cancer patient~. uftcr hiBh--Liose
chcn1olhcrapy and rudiation. suggest 1hi.: pott!ntinl lb r militory
11.':iC or OC3r.. inFr:irc:d light 10 1rea1 U.S. lroop:-. c~p()!)cd to che1nicnl and rndiOilCliVC. v.•nrfnn: nscntS in lhC ficrdlll 'f11C!>C JifC-$3\'i11,g ;ipplicu11ons require especially 11cc..:lcr:11cd \l/011nd healing.
rapid rcduc.1..ion of infections, 111uJ 1>ain 1nudul;11ion.
ACKNO\VLfmGM1£NTS
\Ve wish to thank Karen Zeqin for
o~~i:-.taJM.'.'C
in rn:muscripl
prcparnuon. llle LED ~Yt- \\CfC prov•ded b)' Quwllun1 DcviL-es.
Inc. (Barneveld. WIJ. Wcalsogrntcfully acknowledge the Depor1mc111 of Ocfc:rue.. Afr Force M:uerfal Cmnmond. Ann~UOO• L:ib-
.-orics. Davi.< Hyperlxlric Whcir.•1111}. Bniob Air~Bose.
Te:<a>. for providing the hyp1:maric ch:lmbcr "'"d 1n 1hb rese=11.
'flit: hypcrbaric OX)~n 1m.1111Cfll\ ol (JUr hurn.in 5ubjects "'ere
performed by Estelle Woodard, C.R.T.• C.11.T. Thi' \\OrL """
>Upponod by 1be Defen"' Advonctd ll•'<C;1n:h Proj<Xts Agency
gr.mt NM,()() 1-01-1-&969 und the Nmionol Acrom1utics :ind Sp:1ee
Ad1ninislrJtion. Marshall S1lni.-e Fligh1 CcuH:r SBlR g[:JnlS
NAS8·99<.> 15 and NASS-97277, Children's Hospitnl Foundmion.
the ?vtACC Fund. and Quan1u1n Dt:viocs. Inc.
l'cll 10 only 53q, of rcpone<I ~mm poin by day 7 (T11blc I. Pl~·
ure~ I .? und 13). The gremest difft".rence between 1hro1u and
1nou1h llain v.-as rcpo11ed on dny 7. 'vhcn. surprisinp:ly. oral rnu..
C(Ji!;tl ulceration I~ l,elicvcd 10 be \vorst in un1rea1cc.J p:uicnLt..
Addi1lon;.ill). \\Care dctennining e\tenl or ulccDrion. heal·
ing n11e in 1nn1!/d.ay. anJ ~liog time in day~ (Of' 11~ J>allcnt'4.
and v.e: will 001op..'U'C these values \\ilh epcdcm1olot?u.·a1 control
d.11:a. A chart n:' 1t!w ls 31,:,(1 in prog:~s 10 a.~~,\ morphine
ptunp UK' ;ind n.."qwre1nenb for intrJ\ cnous fttJ1ng .. in Ll'.0..
1rea1cd p:111c11b con1p:trcd to control~. Con1act v.ilh 1hc r:DA'~
R1ch.1rd r-.cltcn or the Gencn.tl Surgery Devices Brunch ha. . produc"'~ an avcouc for guid:utcc r-o linal d:-un coJll.-ctiun .ind f'0f\
approval t1r thi~ ccchnalogy ns ch~ stundard or 1hcrupy ror ui:acn1cn1 ol' n1ui.:o~itis. FOA fC\•ic\v of our curl'C!OI dnio and pro1ocol
dC\ll;ll 1... (\Ugoing. and hrL~ already led 10 an F'DJ\ rccon1r11enda·
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A<.Jdrt-ss reprint rcqucsiS' to:
Dr. Harl'y T. \Vltcln11
Departnuutl of Neurology
iWcJical Cotlegl: a/ \Vi.~1~011Jltr
Mi/1,.cmkee. \VJ 53226