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MINUTES

TEXAS BOARD OF CORRECTIONS

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350th Meeting
September 13, 1976

Dallas Hilton Hotel
Dallas, Texas

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APPENDIX B

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1.

Tit!a of Jt:s~arch P~E..C?-s2.!.!. 11t~ Eff~ct of Dl~ tar)" Fat on the Fraction:ll
C:!tabol ic Clc:.L:"nncc cf Luw Dcns~ty LlpOpl'otcins in NOr.:'lill ~ubj(-cts·.

2.

oPT inc j J'a 1 .!.!1!..~ 5 t i !1i!..t..C?.!..1Uld ~'?£C?!:i£.~ ~ Pr i He 111:11 In\' cst i C::l tOl', O. 'O~v i d

'.

Taunton, '·1.0.; Associates, Oal11c1 'icshurun, N. 0 r; Ramon Sec:ura, t.I.D.;
AntOhlO 1·1. Gotto, Jr., ;·S.O.

3.

Dep&lrf.:i1~nts

4.

Clther~carch

j.

D~J>artrnent

Support:

of Hcdicine

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Lipid Research,Clinic Contract
f

s. -Dur~t~cn

,

In""l v~

r-f StudY:
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Suh:i,"ct~

,6. ·No. of

t~IH

71-21S6

8~ w~ek5

tc\ be Jfospitalii.("d:

iO

7. ·Duration of ~:.£.u'O:lncy of CCRC B~d by Each Subje~. 8~ weeks .

8.

}.;:u:ir.:·lm

~o.

.

o~tients

~

be Hospitalized at One Time:

5

• 'l3nd:~::'"ul1d 'i.:1fc·Tmat.\on:· rne fatt)" aci.d compo5i. tion c'f lipoprotcins i~ dCFC:l~­
ent l,;~-:Jn £:~C d~-;;Wi)Ci can be altcred in 10-14 dnys b)' altering the tn~e of fnt
i,~ze~'~c:d (S:11·3t2., N. rt::d Hi~):kcl, ~LA,:
J. Clint Invest. 48:78-86, lS(9).
n,,~ 1:"Jt.~· ':,rJl ic d ~~l':mce of the 1 ipoprotcins r.liiY iiI so be Dl tered by di" t sinc~
it i~.. ~!":o:.'. t';,;t cl.il3t5 h~lJh inpol>'un~ut"urated fa'tty acids cau~e a lOh·crir.g of
i-':,:i:J::!:~ c:ho :..~~ ':.~ ..... ). ;C1r.lp:L'~d to diet 5 high in sa tur.n ted fatty acids (Ahrens. E.
':., ';;:., r.:~.:~.i:';,:,;· tI:·J :'ctl:-rscn, l·LC .. L~ncet 1:943,1957). Recent stt;c!ies in
1:l:J 3 H,:::.r-:.t'l .~' ...:, .... : :·;In:.·n i.la~t an in!'usion of intralipid, i\'hich is n tat
e;:.:~! .~t). cr:::;,; :;- 'i1~ v. "")'b':":ln tr1n1)'ceri<1e, cf.Z lecithin and gl)'cCTol, C"l."~.·~:.
i:i .:i~.'1."~;:'c;~ ill i,:..
fl'r~t d."lnal catabolic clearance of LOL.
Intl'agastrlc inicsiC':1
',If r: ': :II~~'~: ;: , I'''d l:C .::ff~ct upon tho fractional catabolic clcar:mcr. of !.D~.
".n~l:.. ::;.:: ~l', t' C
;·i.ty r.ciu coml,o:;itioo of pho!>:>holipids in the 10\\' dCI:!ii~i'
lipe;; : ' j \ ·::;:s ::r·: c"':nr; -::~i" !.ntrali.:~i:i shol.=ed nn increase in .the ~a:ur:l1.c.:l =::ttl
ec,iJ '.'; _';;:',~ :'-;
~·d ~\:' ;.~'~" )..!)L t'.hosl'!~olipids prior to the injcc1:ion.
It h:tS
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" ,:.'ce'l: '. ~. ~ ·.·.1;
.:c~.
,.
' 'd composJ..tlon.o
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f tne
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1o~t c.l ens..' :;.'
t.:c:'"'
:..:'
. .ioJ t t.h
e "
1:-1\0 ~i).lO l 1.1'1
lir..'; ~·.,I·,~:::,s ilif:,~".. 1C.!i :-'hc- rate of catOlbolism of the LOL. ~Wc \dsh to c:xtc~:.l
th~~l." ~;:'~'J~cs hi i1 ~o,;,·c ~.Jh/si.Qlogjc cpr~·oOlch.
In this study \O:e 'dll inv~st~tOltc
th~ ':'Yl'c:ct of :- .. ~, .:.1::. tlH: ':omposi tlon of ph':lsphol ipids. by 'di ctaT)' mc:::.r.s a~::
dctcl"r;~:~c :hc c~ fc.',~: (·f th'::.s al teration on the rate of catacolisJ:1 0: l.OL.

I·
'10.

f~':2l·,~~~f'£::..2) (:':.t_:,

;rhc p;;11>0se of this stl:dy is 'to dctcr::li n~ the cffect.:of
dic:ta:'j' fatly ~'ici~!. on the iru~tiC\T::l1 cOlt.;.ho}ic clearance of th~ 10"" dcn~l:j'
1 ipCli'nl~ "i ns in nc.:·,,;al ~;u~ jects nnd corra l:lte this inro:·~,.:tion td. th chan~cs
in thr,; lipid clJli1:>os5tlon of t.he LDL.

.

UniCll'::1~~!O

of the

h'oi,~ct

:lnd

Prc1.;:;~ilit"

of

fi.,;'lj ':'~h:1hlc

.
i\esults:

sliO~: ~Ci:~sl1fili:;-n:'7111':'o17.,a-·. io:iTCH;'~'ui~;-rwJ;;iSi ty 1ipop:"otcin

12.

~.·hicJl \;j

11 be suitable f:.r pu1Jlicotion.

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"f Study: Ten priso:lcr vch::~tc('rs \·:ill particip:.lf:C
.::"cl.:·i·~,Ti"l--J(; ,I(:::li Ltd at a Lil:lt: •

li1 iss t:;']r
C:l t~b::..li:)!.l

in the

stt:~J"

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... ":~'" Dcscr!J,tion of Dic:.ts:~: . Isoeulcric djc:~s. eontainin~ 40!',j of enlorics 45 (4t, 40~'
· ':;' ;~":: . as c&Jl'b-Uil)'drate and 20\ ns protein to J:I.,in~61in body weicht \'.'ill be' used.: ~)ict
:' .;: '.' '. 1 will be hiL:h in sat.urntcd f.lt. nnd 'dll h&Jve, a PIS ratio of O. 2S •. Oi et. 2 \d,ll
. .,: . have a PIS ratio of4. nachof the diets \"ill contnin·.nPllrox-iT.iutel)" 400:Ji1g~'of'
· -~: :/: cbolesterol d3ily.
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\~ill

diet 1 for 14 'days, 100 mls. of blood
bo collc.:ctcd .fromeacn
. ::.' subject in fOTA. '111e red ccll swill bo rC'In!J\,cd by centrifugation. 111e' LOL
i
...;', . fraction will be isolated ·nt d 1.025 .. 1.050 by ult.l'D.ccntrifugntion.· The pUl'ity
":0£ tho 10\\f dens.ity lipopr~teins will be eV31 ua ted by imnn.inochemical tcchniGues •
.: ~. A pOl'tion of tho LOL wi 11 then be analyzed for 1 ipi.d CO:i1ll05i tion including cno, ': ....•. ' lesterol, cholesterol os.ter, tl'iglyccridcs and phospholipids.. The t"atty acid
~."
composition of the cholestcrol oster, ·tri cl)'ceridc and phospholipid frac'tions
· - ,-:-::.... will then be determined by gt\s liquid cJlromatography. A PQrtion of 'the' LOr;
.. ', .: '.,:, will' .then be labelled, wi th I ~ 25 by the iodine li1onochlol'.itlc t~chJ1ique, ~ TIle free.
'. '-f'~' iodide k'ill then be dial)"zod from the LOL. The percent iodine in the LOL epo:,,' .
prot ein ~;ill 'then be determi.ned by oxtTuctingthc lipid \o.'i th ch1oroforrn/lncth ,nol
.' , and 'dctel'minin~ ~c percentage of counts in the lipid fJ.'acrion. 2S }.:Ci of I 1 2S
.....
lab£;llc;d LOL Hill then be inj ectad thl'ough' a mi llil>orc filter and blood siU:illles .
obt2in~d at .various tim!' intervals to"determine the ..clearanco of. the lab('l~c;d
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LOL as pre\'1.ously dcscrlbed (l~ancer;~·T., Strober," 1'/. and Lcvy, R.·1. J. elln.
, .". . Invest. 51': 1528 I 1972). nlC disnppearancc of"thc I 1 ~.s WL will then be J?O'iiQ~\'ed
RI :." . for l-;'-daj's.. Urine will be, collected and tho excretion of the ! 12~ r.:oni to:-c'd. ",
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: One nra1il o~ potassium i~dide sol~tion \\'il~ be gh'en daily to l>Tcven-; th)"l"oill
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. uptake of the 1125 • 'rhe subjects .\oli11 then be 'l)laced: on .thp second di.et a.nci
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the above studies repeated..."
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.... ith thc second nroup of 5 subjects the sequence of ·the diets \':ill ·b·,:
. so' that diet 2 ,'Ii il be given fj,rst and diet 1 \d 11 folIo,,!. .

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Ten pri scnor voluntccl's "'ho agree'. ·tn

ti 0:1 of Pi tients:

·:"e-i-i...:d ierr:-'-TIlfdr plasma lipi.ds· and lipoproteins will be
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n~1T.i~11

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before studies are

carried.~ut..

P~l"t! c;

clOcur.~l'TitE;d.

rl~vc;"~';-:
pr::.. c p.t: ..
be

',:4)

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?;.s::?~f:o'rt ~~-Subject..:~- The orrt'y discor.ltort

· l.~.m~:~!rc h'hi·ch is' Dccessary to
· JDL, .

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ob~ain

to'subjects \\'ill b~
the 1?lood and to inj ect tho
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Pot~nti~l H<l!.a,:,ds· t~ Subjects' and S.arc,3uards for Same: _There \d 11 be
5::0'111 • .
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r&ldia,tion:-eX l'05Ure associated ""itJ~ the ii;-jcctioll of the SO ~Ci of P .~;I LI>L •.
. ··.0
. The •esti:;t<l
ted total exposure: from 50\JCi 9£
I 12~ to a 70 kg subjec~ is O.u92 =ad.
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}·~et hod

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of O~'taininr. Informed Conscnt of Iluman S~lb j oct sand Cnp)' of Ccm~cnt Fo~:
Appl'oval fOl' the. study \\'ill be obt::lin~d1'rol:l the Ccmr,lft tee en Resc,ach Im.';i-:::-ir.gHur:.an Eoinr.s at the t.lcthodist Hospital :md naylor College of Nedic~nc as "'~ll
4JS the R:\(~io.i sotopc COJ;'olni ttce of The l-Iethcdist Hospi tOll,
A copy of the conscm:
fOl"m is at t~ched.·
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Possible r;xcc~si\'e E),1,cnsc ·'!'s'\ociatr.d \':1-.:1\ ~t\ldy:

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'DAYLO'it COLJ,~:Ci: 01" ~ItDICINl~ ,

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1.JI:IJU:.• L Cr.sTtn·
1101.::..0:\. 'J'a;XA:; 7;025

J11~C: Iltr"'''tIU~l or SIo"JICUY

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'May 1, 197·i

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O. 'D~\'i'" .Ta unt~'n, ~·1. D•
. Dc:pal·tirJ::nl; of 1\1cdicine
Ba)'lol' College of Medicine
.Rous ton, Tc>:a 5 7702.5

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'Th.e Baylor Committee on Research Involving Human Dein&~, is plensed
.... to info::;", you ib"t' your :-es.(:a:-ch pi'opor.al The E{{cc-t of Dis!J1.r..):....E'.a.t.Q."l..Hl.e... ;Fra c .YE.!!::~{,:dJO li r. Cl en T illlts- or L "'W Q,t:J:U:jj',~fJ,J:lp:n'cj n 'i i~'.o'" ..... ;) 1 c: U 1·}.C~
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(G~RC)

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wac apr.l,(),,(~tl, on.
April 30, 1974
Ole-cording to institution:ll &uidelh1es .~nd .
pro\'idc:d it receives the l.mailcred D-plJroval of th.e jnslilution~l coo1n1iUce in
which it is involved.
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..... ) •• Continued, rcvi C\V w~n b~ )~t?c;\li1".~d
, ( , ·a.· Arter e:ach .5ub J(·cl;l ~ '~~':PC: :iU'I'C'
( ) b.
Quarterly
,
( ) c. 'Semi-annually

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():) d.
(>:) c.
(x)!.
( ) C·

P

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Annually
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Changc ill Prol;o('.()l
D~vcl()p~n~r:,t of \.;~c,'Pt:':1.:'cl prc.blcms' or unusl:"l .
'COml)] iCi~ Liens
Olhen- "

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2.

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Iv1:cU10d of Revic""

(x)
( ,
.( )
( )

....

~nc~o::;cu)

a.
b.

Quc:Hionnaire (r:Xtllnp:'.c

c.
d.

lntcl'vic\~ wiLh. inoindpal invesi.ic ator

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Chai~n,')n,

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E. St.:\ri1 \)' Cravdo£:d, M. D. ,
CC'J111n'littcc on

Involving lIul-nan J)Ci:1CS

ESC:ib

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l~(,~;c:ll'ch

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g.

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Taunton, "'.0.
Principal Invcstig;ator

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Henry D. McIntosh, r·t. D., C,hairman
Dcpartmen t of l-~cdiciTlc
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. DETEre·UI\A'I'10N 01: INFl,UlmCfi OJ: DIFFERENT TypnS OF
DIE,.Any FAr ON J.Ol~ nr:~SITY I,JPOPR01'cINC"1"ABOLISH

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I understand that phY:'iician~ at' Da),ior Collcue of %'Jedicine and The ~fethodist
Hospital ilre cng:lt;cd in research and the stud)' of the nature of disease and of
new Iilethods of diagnos i:; am! tTeatrnent. I understand thot· Federal Lab' re,quires
. ~hat a potlent to/ho is given un investi&ationnl c.1rug should signify his Idllintness
~o receive it, after being told' its nature and purpose.
1 understand that this
j,nvestiCiltion entails' the radioactive labellint= of one of the lipid-carrying pro_. teins in l.1y blood, \,'hich h'ill then be sterilized and re-il~jected lutoay circu.;.
lation (os 112S_10,~ density lipoprotein). I hove been info:-med thtlt the total
dose of radioactivity. involvc:d (50-]CO micro'curies o~ 1 125 ) is not thought to
, lie harm~u 1 in the Ji!:h t of presl,;nt sci.c:ntific kOOh'l ~dge ~nd I sarco' to undergo
. t.his. pro~(;dure, ",'hosc ob jec:tive ~ s to. detc::mi:1e ,the illi'luc:ncc of di ffcrent types
of'dietary fat on the l'ate of clearance of 10\'1 densi tr lipoproteins from ray p12sj,ul.
I under~t>:;1J th:!.t the purpo!ie. of these procedures is to· develop icproved under. st2ndin~ knLl better methods of diagnosis and treatment of' lipid transport disoi'dcrs,
but thnt :1t the present time no representation can be made thot;ily pATt"icipation
~ili be directly beneficial to me.
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There are no .convenient al ternati ve prncp.chtres, other than t}lO ones described
to me, by \oihich this study could' be carried cut',
'I have been offerec.1 the opportunity

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and have been given the opportunity'to u:.k

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(1"'. ·:.cnssion \':i th I.'Y· ph)'sida..71
::0\" or at a future tir.ie

fk
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.01,:,

.concerning .the procedures to be. carrico ('ut.

I

I understand that I am free towithc1T<:J.\' L·IJ,' 1!dr. :.. t lti)' at''1n)'time. I
,. voluntaril)' consent to participaticJn in 1 hi! ~ :.1:01)' I" 11· n,l u:~derstan~ing of the
I'.no\m"'efiects that occur in the course thC'l';'C',f, ;.;,:1 jli:l'1';',,: T uud~rstand that not
". all effects of ~hese procedur~s are ncce~,!.'~.;:)>' LIl.·.·,1 ~. j 1.hr.' tlrcsent tiiliC.

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Patient Signature

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'IN ).1.:Iu" Dr.l'''''''I:~'' or SIIac:UT
O&u~a

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"""''''''''''''' "'.
'J'I;xAS MrJnC:.L Ct~lt:R
HOUSTON, Tl:~AS ';025

UA 1 ~u.\

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An..,51

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September'13, 19'72

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Rober·t B. Couch, M. D.
Depa rtmcnt of Microbiolc:>-gy
1I 2aylor College of Medicine '
':Hquston, Texas 77025

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I Dear ·Dr.·
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The Baylor Committee on Resea'rch .Involving Human Beings is plea.sed
I to in!orm you your research'
_C.-;.o.;.u...;;c_h

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proposal Devclor.llnent of a Raprorlucible nnrl
EIfectivc Challen~e System for Mycoplasma pneumoriiac, USPHS General 'Clinical
I:Rc:scarch Center. RB. 00350, . USPHS Contract i!P~'I-oo!-3-68-963, The l\1-ethodist
tv .. "
':r"Spltill Clinical Research Center, l<.amsey Wnit oi thc r.L'exas D(:palotment of Co~rccti~~
that

o

II wa.s approved on Seotembc:r 120 1q72
II with the following provisions: .

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iit~r~IYy~urs.

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E. 'St:l 11 Y Cr:lw{o, d, M. D. ,
Ch:lir ·I:1., COl1uniUe,c 01' RC!icarch

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Jnvol('~n~ HU:11:ln

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Method o{ Review
(x) a.
QuesHonnair? (e:-:ar'lple ( 11C10:" cc:.)
( ) b.
New ProLocol
( ) ,c.
Intervicw with prir.cipal illvcsl"iCD.tor
( ) d.
Other

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Continued Teview will be rcqlliJ"':cl
( ) a.
After ca.c:h subject! s t::=.... ,~~: ·'.f': c·
( ) b.
Quarterlv
(. ) c.
Senli -annualJy ..
(JC) d •
Annually
(,X)
Chanr;c
in ProlCic; !
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Devcloprrlcnt 0" u".: C': ,,'"..........
compli caHons
Other
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accoloding Lo ins titu tiC?nal guido:lines

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... Title: Development of a Reproducible and Erfcclivc Ch"lIenge Syslcm for
Mycopla~ma pnc\lmo~iae
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. ' :Princir,al In'vestfgator'and Associates: Robert B.' Couch, M. D.
, .. ,
Vernon I(night, M.D.
;
, •..Stephen Grcellb~rg, M.D.
.~
, Julius A. I<asel, Ph.D:
Dep:lrtmenl Involved:. Microbiology

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Granting Anency: USPHS General Clinical Research Center RR 00350
.USPHS Contract itPt:!-43-68 ... 9 63
Duriltion of Support: 10/1/6,6 to 10/1/76'
. 1~/~9/7~ to 12/19/72
Location: The Methodist Hospital Ciinica'i Resea't'ch Center
Ramsey
Unit of the Texas Department
.
. 'of..Corrections
Oultin(::
Bacl{9!'ound Information: COllsi.dcrable cxperi"ncp. is available (a sub..
stanUcd . proportion by us) with challenr.e o~ nerma I adu.lt volunteers wiLh
.
.Mycoplasma
pnetl~oliia~, This organism is an imps!'Ulllteau~~oFt".t'$p;:'ator}' disease in all
age group~ and p~rliclliarly of pneumort\:J , '; ! 1,-,.,. cnl1~r~r. ilnc! young ~dults (see
.. prolucol enlill~d "Evaluation
'of lnat;livatp.d· Vaceinr- far M• r.!leuil1Qr.i~l\~ Infection").
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In challenge of v~luntee~s~ 3· va:'iable5 of lhe. cf7allange agent 41rc
involved;' these are sou~c-e and method of:·21rc....th of ti~c: lnocl'lum, inuculalion
method, and dose. InClcula used for challe.nge d v 11unteers have v~ried in '
propagation
history; these' inclu'de 'no pro~,ag,1lioft. (natural
throat secretions),
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tissue .cl;Jlture grown organism.s., an~ variclus passage' levels of organisms
propagated on. artificial media. Methods IJsed for ii1~c'ulat!ons h:lve included
na'sopharyngea! spray, naS'l1 drop~, and inhalation of small parlicle,",crosol.
Pneumonia has resulted from each inoculation method and with each source
and method of growth of orgunisins.

T~c studies with vilrying ievels of passa9c or orgnnis~s on ::I'tificial
media S1I9CJcslcd lh~l propilgaliol1 in artificial If,,;di::l resulted in loss of infectivity

I
I

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I

I
\.

I·:
~-

~

I
I
I

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-.
.Despite this experience, no defiried,
reproducible
challenge
s)'st"em
. . . ., is
..

I

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I
I
I
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I

. .
available (or ~neumon(ae. 'If the resu1ts ~f studies in volunteers are to
.
' . '. .
conlinue to be an important determining
factor in new vaccine and therapeutic
,
.
developmenllhen belter defined methods for eyalJation are needed. New
vaccines are being developed
whichooWiU requir~, 'indications
of effecl,iveness
.
.
.
before proceeding 10 field-trials ... W. believe befQre they are evalu.ated .
in volunteers the challenge' ~y.ste,p,"shoufd b~ beiter defined and an aLlernpt
·.a

.'

.

.

.

should be made to more. -closely
approximate. patterns of naturally occLl!"rir.~
..'

illness. To·obtain this ~nformation '!ie plan b use varying doses of or0ar ..;:' .
for inoculalionof l~e' upper. (nasal drops) and the lower (small parlicl~' •

a~.roso~) r~sPir.ator~ tradt in, o"re.;.~tp:.d~termine ~e minim'll dose tha.t \', m

..

..

•

. pr~duce inrection and.an illness
resf)Onse..$fmllar to natural disease. M, ~c'
.'
."ycr, only tissue culture grown Qrga'l'Jisms will·be used for this pUI'Jlo~e. T'.:
desired p~ttern of illness response is.int~rmcdiate betwcen Ulat report~d f·)(
families and that reported for military personnel. In families abol.t aoi'o
illness, about two-UJirds
are lower'respiralory, and 20 to :30~o
. exhibit
..
.
. exhibit abnormal chest x-rays. In the .military.only about ~O to 30/,0 exhibil
•

.

•

•

•

. °

•

•

•

•

II,

•

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o· Illness and:3 to·.IO}'.
•

hav.e.p~eumoni~~_.
: . .• . '

• • 10

.: .
••

0°

,

•

or ,

t

•

In addition. to d~.finjng ~·.ch~.lIell~e

•

system, detailed e.xa~linali~n
the immune 'rc·sponsc· (humora~ ~ncfccUular) wHI be performed in or~cr lo bel.ter
• •

•

t

erucidille the desired vaccine response.

•

.

., •

.'

,

f

•

~

.

Selection of Subjects: Recruitment of volunleers will
. be pel'formed accordin n~
lo~melhod5,d-escrib~d (SQa--~m-G-e-sc.ri.ptjo.o). Volunteers who iU'C hospiUil ized
at ~he Methodist Hospil~l will. receive $5 per day (or the durali "n of their
hospi~1iziltion (a rate set by the Department of Corrections). Th: tlnClncial

{
[

_.to •

~t~

reward a,lid lI,le opportunity to,be Free from w'ork, guards, and to !
i1nl
environment, free lime and good food available is iln inducemenlto volunlcc'r.
~o\Yevcr, it is significunlly negated by the fact lhal volunleers who pnl'ticipalc
in studies at The·Methodist
Hospital must
remain in prison for one ncldilionat
.
.
day for 'each tv/o days in the ,hospital. Since the study will be Clppro>:imately
.

"

4 weeks in duration, the volunteer will be rcquil'ed to stay ali u~ldilionnl 2 weeks
.
. .....
in prison beyond his specifi
ed retea se date. .Volunteers who parliciilille
,
at.HI~ Ramsey Unit of the Texas Department of Correclions will receive $:35
. for U,e study. This isconsidercd by the T~xa5 Department'of Corrections
.. (\fficials to be an acceptable Clnd not excessive incentive.,'
"

,

,

Discomfort to Subjec'ts: '0 iscomfol"t nssociated with 'obta inina

fii;CC

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11.

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:mr '15

t.

fr.:r. isola lion tests and b.lood and secretions fa ,~ntibody assay and IYI,;ph:~~~ ,'~
~ludies is minfmal. Other discomforts will be those which will be as!"ocirtteJ
wilh any illness that occ~rs. 'Illness may be of varyin~:j severity ;'l1d iacludc' m:'I'in~iliC;/C
~febrile am! febrile pharyngitis, tracheobronchitis and pneumonia. H~:l~::cl:,
.
rnalaise, and myalgias are common symptoms. Cough is the most ch:l:'ac~~~r;~L:;,
syrnptom of M. pneulTIoniae infection. Illnesses may las~ for 5 Lo 7 da~'s but
not longer since specific treatment is availJble and will be given. t\nalDesics
and other symptomatic medications will also be administered as indiciiled •
pneumonia and that seen previously in volunteers was
.. Naturally occurring
,
•
\
usually limited to a single sCDmenl of one lobe and required 7 to 10 days
!
for clearing. If pneumonia occurs, chest discomfort and significnnl cough
,I
rna v occur but the overa II illness is rarely sev(';I'e enough to require hed rest.
Based 011 prior experiences in v~lunleers a,'ld descriptions of naturally occllrring

I

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.

.

disease it is L:lllikcly l!lilt morc severe'i1lness will be sccn.

.

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, Purpose of Project: To' develop il reproducilJlc chnllc~lge system for
volunteers which can be used for cVilluation of experimenUlI vaccines'nnd
ch~mother;]peulic agents.
Description of Study: Volunteers will be obta ined .according to procedures
desc,ribed 'lInder ProgriJlll Description 'and brolJght to' Methodi'st HospiliJl. .,.'.'
.
..
. '
Antibody-free individuals (growth inhibiting initially I mOie sensitivc methods ..
later) \'Iii.
r receive
and x-ray e>:amin~tiolis
.
.thoro,ugh hi slory I physical,. laboratQry
.
.' ..
to insurc uood
lo Lhcm in
. health. They will lhen have the study explnincd
.
delail and will be asked to sign the enclosed consent form. In the e\'ent that
an insufficient . number
of antibod}I-free individunls
are available for
the
.
.
.
.
Methodist Hospital studies, the study may be completed at the Rnlll~::y Unit of
. the' Texas Dep3rtmenl of Con'ection5\- but no studies will be done at U::ll site
until after initial aerosol inoculCltions. are pc'rformed' al The Methodist Hospitnl.
'

rhe planncd number of men is as follows:
Dose
1000 cru

100 cfu
10 cfu
1 cfu
0.1 cfu

B

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3
3
3
'3

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......
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3

.

.

A(:rosol illoculations are performed with a special aerosol inoculating a:'/p~:i:tL.S
fabricated for us which provides good cerUrol on dose. Follo,....ing inuculat1:.n

.

,

,

. volunteers will be placed in isolation and examined once ~r twice d:lily.for
illncss. Spec imens will be obtZli ncd iJccording to the enclos~d protocol (sec
,

,

Attachmcnt 1) and i flness wi /I be qUZlntitated and recorded on the endosed
form (scc Auachmcnt 2>.. Shedding of the
,

illncss

rcspol1~·e

or9~nism

I

will be compared according Lo dose

of l!J~ in(",cliIlU JgcnL.

the immune rcsponse, Zll]d
~nd

mcthod of i:loculilliol1

.

.

.

"

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'.
.

~

wiUlthis study is the occu)'rence of pl1c~monia and, as stated, it ismild~

~

\

Polciltini Hazards and Safeguards: The major pos~ible hazard associatcd
,

Cold ag~lutinills

will

~.;.

probably-develop, but'lhe'likelihood of. a Uter occurring ,

[

.' whiph is severe enough to wal'rant concern aboul hemolysis is eXlJ'cmely

•

,

,

remote and has never been seen in previous volunteer studies. Pneumonia may

P

be of varying severity and the moment illness is considered of significant
,

.

severity (clinical
judgment) or pneumol~ia clearly has occurred, the individual
,
.
.

t

will be given telracycline or erytlll'omycin th~rap)'. This therap)1 ha~ been,
•
shown to produce an afebrile state within 48 hours in nCllurafly occurring cases

I

and Lo hasten the resolution,of x-ray'and abnormal,signs in a laroe ,number of
• ' fndividuals. We believe that with this therapy and the
which
. cOl1dltions'undei
.
,
.
the study r/il! be conducted that there i~ little hazard to the volunteer of either

-

U

prolonged discomfort or occurrence of injury. Volun~eers within the Methodist

[

Hospital \',ill have physicians amI' exten~jve m(:dicnl c,tr~~ i\vaibblc in the ~
.

.. ' .

.-

.

.

.

[

event of unexpected campi ications. Volllnt(cj'~ ~t ~d::n!if:Y v'; II have im mediat~
acccss to physicians anct in the event thi:t rr:edir.:ci
"

Ciii(; rilciliti~s arc

.

considcr'cd

-

inad~qllute, arrangeme;~l~:'ha~~'been rmHb fu lo"Ii~.;Jr.:i.in:; U.e \'olunteer fo The Methcdist Hospital for morc definitive (,ar;'.

t

.

. Benefits: Benefit to an in,dividui11 vol~!Iltcer cc.ii,~i~.' ... ~r cxp~i'i(":tcing ~n
.

infeclion, which he has

,

Cl

high likelihood of acrj:Jirin(l il~tul'(dl}', u~dcj' the

L

supervision of a physici~n. In addition, he wii! ~c contributinn toward

..

,..

acquisition of new in,formation on an importr.nt calls~ of human disaasc thnt

f."

maya id in development of n.ew approach~s to prevention nnd lrcaLncnt.

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Method of Obtai "ing Informed Consent: A detailed description o'f the
study Lo be performed will be given to volunteers verbally and Uley will be

.

.

asked to sign the enclosed consent forro. They will be given an opportunity
to as~ any questions they desire and it will b~ 'm~de clear that they may rcrnpve . ,
themselves from the study at.,any tim~.

•

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IJousroN. 'r':XAS 7702:;

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VOLUNTE'ER 5 CON,~,~NT. FORM
1

..

u';dcrst~nd that I am consenting 't:o CI~~e;;l nas~1 drops ~'i to fJrchthe.

•

, ':

I' , .. '

. I understand that frequent nasal washings, throat sVlnb and cOll~h ~pecimC'ns,
. and blood 'dra\'li ngs wil r be performed and us~d for tests. X-r~ys and other
. : tests \',ill be performed as indicated:.·
"
. ' .

,',
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I, ' .

.

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r:hi~)

.'

proposed study has been clearly explained to me and 1 undc:-st:~nc
" ;m,J accept the hazards involved. I have heen given ~n OPPol'lunit~' to z~.~: (i'.'}
(~uesli')r.s 1 might desire and I understand thatl have the: right to \'Iilhcl:~\':
. " .' from'lhe study at any Li!Jle 1 may choose.
~

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study will be lIsed for developing, nc\', metr1cds (01' control of the L:fc .Ut, L.
FtlrUl~rl1lorc, 1 undel'sland th~t 1 will reccive.S5 pcr day for the dll,.::thr: )f
my time in the hospital. (Alternative for the RC\:t1sey Unit: I unde:·~~~lld,h(~.
1. 'NiH I'eccive, $35 for my pZlrticipation
at U1C completion of the stud)'.
.
.

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I understand that lhe information obtaincd from my pal'Ucipaticn in

~..

.,

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-------------.
----...------------

Signature-

.

Date

.,

---------------

Witness

1 have careJully

explaincd the m:lure, demands, and foreseeable risks of
',. ' the Cl:iove study, to the norm~ I voluntcer.
" •
:

. ..

.

~.

,

Sign"turc

'

..

,

_

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a mist which contCl ins an infectiolls aocnt ,..., hich I mayor mily not "c~tch .1.'
::. to·
•••. 'If 1 "cCltch it," it mayor may not make me ill.
If I dcvelop ail illncss it
, .. may, include eClrachc, nasal obslruc~ion, and discharge, sore throot, hcarsenes,s,
' , .' . cough, alid chest pa in. '1 understand th,at fever m~y occur and I OlDy develop
head~che, vicakness, muscle aches and loss of appetite. I have been lold
',.,. :: that pneLiinoniil may also develop but lh~t it is usuully mild. Fever m:ly last
',. " ,.. 2 to 4 days and symptoms for 7 to 10 days. I ,understund th~t ,other ~)'mjJloms
'.. ' . . .: might occur and th~t it is possible, but unlikely, thut jUnes·s will las~
IOIlDc:r U.1an 10 days. . .
'. ' . " :
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nllrJill' .1' M.IC'RO,'IOLO'"

Ol~ i\1j~0lC:INE

Cou.r.c:r.

---------------

.... , ..

.'. ...

'.

RESPlRATORY'DISEASE STUDY - 111

.,

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'.

Ity .Report of Illness

••

'

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re all findings negative? XA@
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Site
Find;nq
N ~ Obstruction'

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Findinq
Photophobia

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Coniunct. erythema

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Anorexia
Nausea
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Pain or tenderne~s
Diarrhea
!Ipablc ~i\'er
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Cervical adenitis

Time

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Pneumonia

Other OA@

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Patient's opinion: Does patient feel he is
well? (Y or N)
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., ADDITIONAL INFORMATION FOR NtH'

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: 'Title of Research Project: Development of a Reproduc'ible .and Effective

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Challenge System for Mycpplasma pneumoniae '

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o O"ration of Study: ~ months

: 'Subjects:' '3D adult (age 21-45) male prisoner volunteers
See Program Description for other qualifications and exclusions.

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'.- Additional Narrative Infcrmation:
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. '... 2 b•. Chal(en~eagent:,Mycoplasma pneumoniae'.

S~urce: i.

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Strain 10433: throat swab'collected from a '
• I

Grc":p

HE.': 1t1 qnopi!ralive.

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r' ;:'.. '/.;' I'\,~j':::' 1: la;'.d, ;'Jc:,th Carolina, with naturally occurring M. pneumoniae'

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. ' Slrain 1428: throat-swab
. ., collected
.... from a Marine

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,', ~l:l(urall~J uccurring uncomplic~ted case of M. pneumoniae pneumonia in t~e

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.1._ Sf:'ain 10433: harvest from third passage in

to

!, ('. ·~!,III(::\' l"i:'-~,lJe r.!"ture~

maintained i~l MEM with

51. c~io~en

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~C. Strain
_".H~~,r~ le!: -C ;':,:'."'ck .p~':J.G br~lh
'cc:m;:;ir;~oL:£J i:;'.

r '··:!.:nt

1428: initially passaged

;tno used for

t\'li~e in

volunt~er inoculations

wi thout

'nt..:ulum is harve!:t from two additional passages in

hUinc1n (:11I~ryon;c kidn£:}' (issue cultures main.tained in MEM 'with 5~. chicken

. .

serum and penici Ilin.
'Purity: Purit~ of Loth pools was insured by the accompanying safety
test procedure and by specific identification with Research Reference antiserum
~ M. pncumoniac. The lalter .idc:nt!ficaUor~ was by growth inhibition WiUl a

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Impregnat~d disc on agar and growth Inhibition as measured by
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,2 c. Blood: antecubital v.ein. Total volume within a 3 month period"
'~', ,.,; :' not exc'eed 500 mi.
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,Nasal secretions: nasal rinse Viith 10 ml Lactated Ringer's'Solution
Nasal wash: nasal rinse with 10 ml veal infusion broth
' :
Throat swab, 'anal swab: standard proc~ure$ . '~ :... , '.
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2' d'. Included ,in pro,tocol.·
,

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:':,. ,:,.' ~"" .,; :. : , ,.~: 1. Strain 10433 HEK 3 : ?5 loglO/ml
• " " : '" 0:, .:',:',; " .
.:'
2. Strain'1428 BR2 HEK 2 : 8.,0 loglO/ml
',' .. ' ':..,".. :... :.'.' ',:" . : . Challenge diluent: MEM with 21. human serum albumin

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BAYLOR COLLEC;!:: 0'" 1\1EOICINF.

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1'I:XAS Mr.DICA" CClfTL'R '
HOUSTU!'f. ~t:XAS '17025'

.

1Iol\l~SOI.OUY

VOLUNTEER'S CONSENT FORM
I understand that 1 am consenting to accept spray and nasal dr·.. ·~c: which'
contain an infectious agent, Mycoplasma pneumoniae, which 1 rna:
. Y hot
"catch." If I"catch it,ll it mayor may not make me ill. If I devt~ i .
illness it may include earache, nasal obstruc,tion and discharge, sora tllll.l.::t,
hoarseness, cough, and ,chest pain. 1 understand that fever may occur and
I may develop headache, weakness, !'11uscle aches and loss of appetite. 1
have been told that pneumonia may also develop but that it is USUc1lly mild ~
·Fever may last 2 to 4 days and' symptoms for 7 to 10 days. I understand
that other symptoms might occur and that it is possible, but unlikely, that
illness will last longer than 10 days. At the compl etion of the study, 1
\'Jill be gi ven an antibiotic to aid in riddi.ng me of the organism.
:
0

1 underst~nd that frequent nasal washings, throat swab and cough specimens,

anti blood drawings wi II be performed and used for tests. X-rays and other
lp.sts \'Jill be performed as .indicated.'
.. ,
.
.' I understand that the: information'obtained from my participation in this
~tudy will ,be used for developing new methods for control of the,infection.
I'~.ll'thermore, 1 understand that I will receive' $50 for my participat:oli .:.t ::K'
c(\mpietion of the study.

.

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Signature

--------------Witness
------------Date

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The proposed study has been clearly expla inea to me and 1 understand
the hazards involved. 1 have been given an opportunity to ask any qu£:stir.·n!
1 miqht
. desire and 1 understand that 1 have the right to withdraw from the: f,iu,,··'.
':' 'lI~y·time t may choose without prejudice to me.

I have carefully explained the nature, demands, and foreseeable risks of
the above study to the normal, volunteer •

.

------------

Signature

----_._--------

Date

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~i;le:

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'Development'of G' reproducible and
for ~. pneumontae
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A crucial cOD\po~antln this pr.oJect is' thl: certaic clefinitlon '.

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For

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of the p.:l:ticipants as antlbody-po:1tive or ant1body-nesative.
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'the ~olCl'Dittee .was .• dy1s~ci.
. by: tbe:1DB

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challenge assays shc.uld start. "'ith

th~

..

lowest do=te of

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the o·;';'°t;•. l1.a.=;Q

pUle

pa):ag~aph
.

that persistant infections

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Consent fortnS shovld
At .the end of

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ih5.s latter ass8)' could be done :It F'lo\l Labs.

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'l':ycopl~:;tIla and proceed in an i::.Ci 1~:1lr'.lti, 1 l.:r..r.n~;:-·•

otudy.

.-'

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for Austra 1ian antigell and examina tion of the vacclue

, .for rc"o':-t"se trtlnscr·iptase.
.
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4.

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grown in

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Oth~r safeguards included assay of tbe antis~n prepftratio~~

2.

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this r~ar.on the Committee .felt that the 1nv~stigators'shou~d e~plo1.·· .'
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the most senslt:Lve assay available for ,H. pneumonia autibo~U.es~.... ::' .... :,

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Principal Investigator:' R.~ B. Couch

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effe~t1Y.· ~.~~~~~. ':~:Li~i .:/\.>;'1

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IUAtD 'CRe Octob,x: "16, :,·19:.7% .:.•:~":~~:.

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the cli,s~ase under

.ftw.\

:·houl<i also sea te

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therapy.

5. Recomncndatians

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BAYLOi, COL~CE. OF r.1RDICtNE

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Mr.olCA" Cc::ta:n •

Hovsr "='. ~.\S '7025

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Department of Medicine ~
aayJor ~ollege' M'edicine '
'Houston, Texas' 770ZS

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Dt-. Greenberg
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fitcpbdri B~ Greenberg,' M. D.

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review,will be

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Sincerely yours,

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iodethod o! Review
" (x) a.
Qucstionnair~ (exampl~ ~nc:oted)
. ( ) b.
New Protocol
( ) c.
Interview with principal invcsti£ator
d.
Other
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Continued
rC'l';~rc:d
( ) a. After each subjc ctt!:i ':":~~: on~:tf~,'
( ) b. Quarterly
(. ) c.
Semi-annually
(x) d.
Annually
•
(x) c.
Change in Protocol
.
,(x) i. . Development of une~ .jectec J":-o°,J1c; :1',::
complications
'
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.-:..._Tract Infection on Pulmonary Function

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The Baylor C:ommittce on Research Involving.Human Beings is pleased
"111 yuu tha.t your ~csc:.rch prop::sal Effect of Viral and My£?pbcma1

·

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....

197~,

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Cr"," r
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" Ch~irll:\l " C01~'ullillce on Research
Involvins Hun1an Dcinss

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Benefits:
' ..
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The information 9.aine.d fro.m sequential study is unlikely ~o. be of dire~t bqnefit
. to this vo.lunteer. However,' since the majo~ity of 'volunteers are ~mokers the ..
.
.
Ir:aformation gained from hi 5 initial study mayindi~ate. the need·tO cease smoking for
.
..
his future health. Othenvise, information gained will relate to the influence of the
'common r~spiratory infections on pulmonary fUllction acutely and will elucidate the
." severity. and rate 'of recov~ry. The nature
of any defect 'wql. indicate the need for
.
. . ·"symp.tomatic 'therapy during ·the cornmon·.r~spiratory infections as :well'~s ·the pO$sible
need for prophylactic measure.s.
'

..

Method of Obtaining Informed Cpnsent:
. A detailed description of the study to be perfonned wi II· be
. ..given to yolunleers
• verbally and Lhey wi II be asked to sign the cnc losed consent form.. Thi 5 explanation
will include all known hi.zal·ds associated with live agenl challe~ge and the pulmonary
funcUon stL:·~i e~. He! · i II be Diven ~n ~pportunily to asr~ ~ny questio.ns he desires,
and it will, /..\: j"li&1c!·. cl~ ~.' t';.!; h~ can remove himself from the study at any lime.

..

"Robel't 8. Couch, r~. 0 _, Investigator

.~;;2Z;;'~l"galOr :
R.

• Wi fi'ims I Ph. 0_, cting ChJirman

Deparlmenl of Microbiology

r.,

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-.....-...:a .... ...... :..

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.........-,
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.. Henry U. MC'llitosh, M.D. I Chairman

OeparlmellL of Medicine

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~ b~ eXP'erienct~g',:
Analgesic~ and oUler s~mPlomauc medic~lions "w'ill

pneulmnia and Lo all otlu!rs"with" this infection who are.jucig'eet

m
~

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Illnesses of moderate .severity.

.

be administered as indicated:

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Discomfort associated with pulmonary functio,n stud~es include'those associated

with dra\'li~g' of blood gases and swallowing of the esopha'geal balloon' (or com- ' .

.

.

.

plianc~ measurements. Spirometry measurements cause minimal discomfort. ''The
..
.
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v~lunteer ~iII be aske~ to'coope~~~ for a.boul' two hours each time these studies are

obtained.

.

"

Potential Hazards to Subjects and Safeguards for Same:

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.In the event that p~eumo~ia or an'y other severe. illness is noted from

!!: pneumoniae inoculation,.antfbio~iCS

wi.1I

'

~e i~mediately ad~inistered •. The

-above d..:scribed illness responses for influenza constitute those seen by us- among
apprOXimately' 300

artjfi~ia!ly induced

infectionsj' specifically, pneumonia has

never occL:r(~d. There seems little likelihood of a m~r(' sever~ illness occurring
among these men lh~n that described. Ne\'~rt:;ehs!: .. Pi:r.r \.0 :noculatiofl, yol.~nt~er~
,

.

.

are told that· pneumonia sometimes o(.ca.:rs ·.../ith th;$

\'1(1.":'

be by r.asal drops (as cj)po~ed to a~ros,I>.I:.'hi:'h

~ C.l ••:;,: ~:: nificantly reduces

w::

ideedon. Inoculation wi II

the hazard of pneumonia. RhinOvirus and Con,ackic J.:.1 rc;. C'~mmol1 cold vi,rus)
infections have been produced in approxiri7atEly ~.9c.::) \o!untt:erf, and there seems
, little reason to p,~'pecl an untoward rcactio:i.
. Physicians will see all volunteers claily Zo:td ~','J;"e c:!aily if indicated. They
will be on call 24 hours
therapy when indicated.
" .

.

a day during the period. of i ~olaljon Clnd wi II administer
..

Arterial .blood gases have been associated with :ocal h~ma.tolT'.a &1Jld dameage

J.

to th~ peripheral artery in rare j·nstances. A trained t~chnician who performs this

1J

service in the hospital every day will obtain·the blood gases. There is minimal

,

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discomfc:ot from passing of the ~sophageal balloon. Vasal responses have been'
.

-

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repor~~d with this procedure. All pulmonary function studies including the passing cf lhe
esoj):-:z.;cal

1

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f

he wi!:

b~lloon

wiij be done by ~ physician

cr: in ~~~cr:clance

t:ain~d

dudn; the entire procedure.

in

pUlm~n3ry diseases; and

0°

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" physlcia~ will be ira attendance v,hiJe allpulmona;y ~unctio~ stUdies ate being

perr~r~,~d •.
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Selection of Subjects:
.... ' Recruitment of volunteers will be
performed
according
to methods
described
'..
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(see

earliea: submitted Program·Description). Volunteers who are hospitalized at

.

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The Melhodist.)iOsPital will rec~ive $S p~r day for the duration' of· their hospi"tali, zaUon ,(a rate' set by the Department of Corrections). This financial reward and the
opportunity to be free from work, guards, ana to have pleasant environmen~i free time
and good food 'available is an inducement to volunteer • However, it is significantly
'
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negated by the fact that volunteers who participate in studies at The Methodist '
,

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Hospital must remain in prison for o,ne additional day for each two days i~ the,
.hospital. Since the study will be approximately 4. weeks in duration, the volunteer
will be required to stay an additional 2 weeks in prison beyond the spe~ifjed release

.

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." dale. This is considered by the Texas Department of Corrections official s to be an
.
,(~ceptabIQ and not excessive incentive.
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fJ isca~mfort to Subjects:
:---_
.._---~-

. ()iscomfort asso:iated with obtaining specimens for isolation tests t;iC

~1L.c:!

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ilile·:tioll
will be a common cold, sometimes with fever. Illness from M. .pr:;"wnr::
.
. - - ..... _.
may be of varying severity and include myringitis, afebrile and febrile phar~'nil:s,
r

'tracheobronchitis and pneumonia. Headache, malaise, myalgias are common
~ssociated symptoms and cough is the most characteristic sym~lom, ~f!:!: ~:IOI.;~C

I

infection. lliness may last for 5 to 7 days but rarely longer. The range of illnesses
to .influenza fnclude' no illness, mild to severe afebrile upper
. resp·iratory" illness with
cough, and febrile upper r.espiratory
illness with cough. Fever is of varying' ,degree and
,
.
may last frem.l to 5 days; respiratory symptoms occasionally last longer. During the
febrile period, individuals may experience significant' headach~, myalgias, malaise, and
,

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I

secretions for antibody assay is minimal. ,Other discomforts will be thcSQ \.. hich
\'Iill be associated with Urness that occurs. inness 'from rhinovirus crCtixs;:t;!{;~ ,:.::.::

::llld

-

t

t

.

, anorexia. ' S;lecific treatment is ava'Hable for M.... p'neumoniae and will be 9i~en to

ail ;:ldividuals wi'lo

c~ve:o'p

...._-

0

"

=_=..=.....

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pathoge~e.lic

factor in the

~ev~Jc~!l1ent of small airway obsLru~t!on. Certai~':~i~~·~:. :....:,"~:·-:~:-~o.c<:':~t

and mycoplasrr.al infections may ~e more inlportanllhan others in causingpulmonar.y..

J
J

idenlify~,
..
patients with early airway obstruction should allow us to determine lh~e precise role
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of resPitat.6ryviral and

nycopias~1 infections in the pathogenesis of airway obstructio~.

Purpose or-Project:

]

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To'determine if measurable alterations in pulmonJry iunction occur..during

.'

.

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acute viral and mycoplasmal respiratory infections in n.ormal volunteers.

, '

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Unit:lueness of the Project and Pro.babilily'of Publishable Resu.lts:
rViinimal information is pcesently in the published literature on this subject. The opporlunfty to study volunteers in a sequential fashion and for defined infections

V·.• i.t.···.~:. .=:. "'il: ::;:' C!,;;&i,',~c according to procedures described under the
.

pr.;.. i~ 0.5!:'

! .. ~:. :',

M... ~I;~(.::

t!J~:'.

ph 'S;·. ·~i. i i . ';"

for Norma! Volunteers. and brought to The

. .. ;~('d~··'~i·C(; individuals will receive a thorough history,
.
.
,I ' \ ' " ,;'J:.: t·~ar:Jir.ations to insure good 'health. Approximataly

,; :::_;.('l \'.;~··:i.·., ; J,:i~: ':e .~iven a rhinovirus (see ren'ewal approval, June 20,

6:'"

l!. 7;·

_

,

"~c~'lrr.:,;,: D.:sc:ripti~n

':: ;:ye"\'): :';.. '1;

~,

~tL!dh~,

• •_

• • • • 0.- • •

Ill~I.'&.:i;I~I';: .. ~ .. (s,~c

• • • •_

.~

•••

_ ~

eRe protocol approval, 9/13/72). Later
•

: .. :: in:' ~'~~:.' !nflll£'n;·..:;. ~;',d ~o;.:sackie A21 (previously approvecl.agents). Blocd

;lnc! n: !:c"

S : •. :

vaccimtU .. ~

."

\'.·il! h~ obtaip~d beFore 'inoculation and at. 2 and 4 weeks following

'.;;". :e:;'~ ..~: : b.,; examined daily ar.dtwice daily if incicated,by ~

phys ician. Vc,:~nt~er~ v. :I "emJin in i~olalion for a variable period depending upon
the ag:mt under study

1

.]

publi51~3t.fe.

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0

.

Routine pulmonar:l fun~lion Sludies plus stalic and frequency dependent.
.

compliance, closing volume and arterial blo,cd gases will be obtained in these

j

,': .~' {

dysfunction
acutely and possibly
permanenLly. ' The. fact that Vie can now
.
.

. "should provide pre~ise frequency and severity d~ta thal will unquestionably be

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...·...~I

,~":~I :.;,.···.~

volunteers. ' The puimonary func tion lests wi 11 be performed before inoculation, d~ring
aCL'le illness and·~t ap~:,oximately weekly intervals lhereafter as needed. A

I
I
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.'

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title: Effect of Viral and 'Mycoplasmal ,Respiratory Tract Infeclion on' Pul~onary
•
Function"
,Princip311nvestigator and Associates:

Depart~nts Involved:

Microbiology and' Medicine

Other Research Support:

~

Stephen B. Greenberg, M. D. , Robert B.
Couch, M. 0 .,Paul Stevens, M.D., and
John Pettigrove'" M.D.

I
I

..

None

I

"

Dural-ion of Study:

Indefintte

f

'Number of .subjects:' Approximalfly 6 per agent wil~ an estir:r.ated .lotal of 25

[

Duration of Occupation of GCRC;Sed: . 3..1/2 weeks
Maximum number of patients to be hospitnlized:

!

·6

...

,

Backgro:,md Inforr.'?ticn:
Recf;nl

sludif.~

"f

., .

have shown that

aCl:~(: (;':~t'(.r;.~.,J;,i;~:

c.;

.,hr( (',ie. airwaj' disease. ,
'

. may be due to upfler respiratory vir~1 if!fc~llvn.,
.

,infections, pulmonary f.unction

:)1';; .::

.:;-'.:c,,.

I·c.~,;;;r~

dete(i~rat.es fl!!'~~·lc. ;" r .•':':. nt .;:c~:..

. the role of upper respirator)' viral infcctlcm. ir. ~:',. ; ... i.:.'"
.. dise3s~ has-n~t been clearly defined.
Recent develofJments in measuring

. ~::. :'

:Ci'Y ',Iiral ir.f~tior.s .

:::t:er.ls •.However,
:~:' ':.n!c :,;"jr','la}'

~'L:ii;i:",;' :'~' .: ~>:.:- "!iIi ,);)~ :~.if;.::ai;y

in

measuring changes in resistance of small a:r",zy:i ;~l;:~ p: v;':";c .~hL: r.c~eH~ar:1. tools
for understanding the nalural history of Chrc.ilic a!r.'1~:, 0. ~~: 'cl: :;n. r:;"I?'~U(;~cy
. dependence of compliance ar.d closing
vo!l:.. . ;,~~ Clri.' ~,'~ •..•:',\/
i'Tir..·.$L:re..,er.ls. that are
.
' .
'sen~itive enough

to demonstrate early reversibi ~ o~struc d:)n of 3mall .:.irways.
.
..
. Recent evidence indicates that so;n~ atutc viral iiifec.tions. of tha upper

·.'' y obstrcction (OLlr Lo eight weeks aft~r clinical

iespiralcry tract·cause peripheral air..

recovery. The abnormalities were reversed
been observeclthat clearan:e of i:ihal ec
acute viral infection of the
Supporllo the view lr:ut

lJpp~r

rej)e?~cc

~fte(

~:r~I:

an additional six weeks. It has also

pJrtic Ics

WJS

m.;;rkcdl y prolonged during

respiratcry t::cl. Beth of lhe:e observations lend
inft:clion:- r:'.~IY be

~r. :m~c .. ~ant c~;olo9ic

and

..

.

f·

~~....

"

f'

:

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'

.

.

BAYLOa COJ.L::GI::

o:~ rvrEDICliu:

't"i:XAS ·:.;;:DICAL CENTr..' l
HOUSTON. Ta~ 77025

•

VOLUNTEER IS CON SENT FORM

I.
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~ I understand th3t I am consenting' to accept nasal drops· or tei breathe a mi st
which cOI~~ins an infectious agent which I mayor may net "catch. II If 1 "catch it,'II
it mayor rr.ay not make me ill. If 1 deveiop ~n illness it may include earache; nasal
obstruction and discharge, sore throat, hoarseness, cough, and chest pain. I understand that fever may occur and I may develop headache, weakness, muscle aches and'
loss of ajJpetite. I h~ve been told that pn~umonia may develop but that it is usua.lly ,
mild. Fever may las.t 2 to 4 days and symjJtoms from 7 to 10 days. I understand that
other symptoms ~lay occur and thai it is pdssible, ~ut unlikely., that illness will last .
longer
than ten oays.
'. , 1
. .c .
'. . ' .
.
•

..

.

I understand that frequent nasal washings, throat swab and cough specimens, and
blood drawings will be performed and used for tests. X-rays and other tests Vlill be
.

'Perform~d as ir.c!icated.

f
~
.!

.

.

I understand that 1 wi iI have several lung fur.ction tests during my hospilal
stay. These lung tests will require my breathing into a tube many times and s\·:all~·wi;:9
a thi n ru1i!le~ tube.
.
.

.

.

bf~nt;fjt

1 understar:d that the information gained from this study will be of nc di: :.'.:'
to me except that a thorough evaluation of my IUI~g function may i:;c!ici I:· .; ..... "

r.ccr,;;J treatment. The information gained may be of benefit to other people.

:

undcr!:zr.d that i Vii II receiv~ $5 per day for ~he duration of my time in th~ h~:r··a=: .
The proposad study has been cl~arly ~xplained to me and 1 unc!en~aNj ;:::.~
1 have been given an OPiJorlunity to ask allY Clue', :~:.'.i;:
11l1:gi1t desire and I understand that I have the rig~t to withdraw frum the study.: .. :','y
time I may ch~osc.
Signature

, .

~C:'(::'lt the ha;:ards involved.

------------- -

-------------------------

Date

Witness

I have carefully explained the nat;..:,=, dcmands l and foreseeable risks of Ule
above study to lr.e norr.lal volunLeer. .

.

·Signature,

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---------------

'Oale

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Ad~endum . ,to protocol entitled "Effect

.,
,

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: ....J

Qf Viral and MYc~plasmal Resp1.~~~~ry. '. :. ~ ':

Tract Infection on'PulmonartFunction"
.' .

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, ,,~'. ,t.:, :.: ' I

"

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. ... ... . -. . ~ ..: .., ."f'
......
", ~
.. : ..-.
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:. '.
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'1. 'Change in Principal I.n~estig~tor ~ to Robert B. Couch. M:' D~

,

'

2. This protocol is paired with. the protocol entitled "Effect of~Nat~ral
, , Viral and

.

~Iycoplasmal
.

.

.

. . ' 'I

.. ....

Pulmonar,y
Function and
.Respiratory Infections,on
.
.
.

.

.

1

Immunologic Function of the'Lower Respiratory
Tract."· The
.
.immunologic'
. -.
studies in that protocol involve measurement of T and B lymphocyte function,

..t
·1

,thYmidine by stimulated lymphOCytes" new methods·forasses~~ng. antibOdy,
and polymorphonuclear leukocyte function •. Altho'Jgh ,these assays are·
'.approved for other protocol s • .we w1 sh

tr, ~dd the.~l

protocol since the studies are iJail'e(! \'/. i:. ,~i:!(J:{

.~

tc the present

tlf

.
m,t.ural1y occurring,

disease.
perforil1~d

so the consent form does
•

•

~ot

.

•

•

•

un per'1:"'C';'_'1

nClt ch~!n~p..

alter"the limitation 6n,Llood tQ

bl·:~ .. ~ .:j.~: ,li'~Hll

•

(no

ffior~

,

'1

secreti.ons

F~ !'f'-~·.7, .. r.i':C c'.: thf!' 5t",.iiE:s· will
~e obta1~cd

.... ~

.....
,

All studies are

]

"

tha" 500

,

'

•

'.

"0

c~

•

0

O'

0

0'.

0

during the study).
"

.,--

,

~1~'

?'~'// h,;'
'.t!..d:~!L,_~~.~(~~',~~_ _
Robert H. ~ouch, M. D. .
'.
Principal Inv~~tigator

,,

••'

.~

~

Vernen Knight, N, O. ....)
Chairman, Department of .
Microbiology and I~munology

,.
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·."';
m'. ......
4

..

. . . . .

BAYLOR COLLEO£ OF' ~iEDICINt:

,

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TEXAS MEDlCAL CC:otTER
HOUSTON. TEX4S 71~5

..

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u ....aI&W'I or Il.TC."U MeDIC""
,

m,~)~l

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. -,

I:"

Robert B. 'Couch, M.D.
Department of Microbiology & Immunology
Baylor College or Medicine
Houston, Texas 77025

f~~,

Dear Dr.

I

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C:;:o_u:;.;:c:.;,h

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The Baylor Committee' on Research Involving'H~rnanBeings' 1:5' pleased'
to inform )..ou that your research proposal

•

I
!'
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ADDENDUM: EfFect of Viral and

MY'9plo,mal Resl?iratory Tract Infection on Pulmonary. Functton

I

•

(GCBe)'

was approved on
Jonugry Z. 1975
ac co':'ding to institutional gUidelines and
provided it receives the unaltered approval 04 t~.e i"nstitutional committee in
which it is involved.
'.
'
will be r,-~quirc:d ~
After each subj(}ctl:J cX!-'I.,\cure'
Quarterly
Serni-an.nuall.y
Annually'
Change in Protect.:
Development 01 u:)(':-~p~ctc:d proV ,'~!,'~s or unl:sual
complications
Other

1.. Continued
(

) a.

( ) b.

( ) c.

j
4

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•

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, .... ..

:

8, 1975

January

..

;

",

(x) d.
; (x) e.
. -: (x) f.

2.

.0

]

..
( ) g.

~e~iew

0

0

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Method of Review
(x) a.'
Questionnaire (exam?lC' cncl'~sc:~t)
,( ) b.
New Protocol
c. ~nterview with principal investigator
( ) d.
Other
(

)

Sincerely yours,

:

J.L" L
~ , ...... ~
I f /71. c - - «=........

•
11

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HB:ib

Harold Brown,lI.i. D••
'Chairman, Committee on
Involving Huma.n Beings

. .

R~search

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,'. :"':r

Title of Research Proposal: Lymphocyte Cytotoxicity to Influenzavirus in
• Peripheral ~Iood of Norl!1al Volunteers
'.

PrinciPal Investigator and Assoc iates: Stephen 'B. Greenberg, M. C.
. '
Robert B. Couch, M.D.
. .
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'...
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Department Involved: Microbiology and Immunology
: • •.•.
0:, .0;:
._

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Location of. Research: Baylo; College of Medicine :
Ramsey Unit of t,he Texas Department of

-

Duration of Study: 6 months to 1

.'

Nurribcr of SubjectS: 2'0 - 30

.

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...

• • tIt

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~.

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'n:":1 "un 1f:I rJf PaJent~ to be H05pita lized at One Time:
...M~:(
- -'.- _
.
'""
"r. •
I
-..... _._----,......·"
....--..-.-.-..-

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C~rrect.ions. .
, .

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None
. ..
,

.

'I ·...
, .. ·.~.',I" ' . ' .
o J ' .... ~
•

~

·I·~(·

t!l~i)
.

"C'! .' Q. :Y"

;:j'.': .. y~,(:!:

in hos t response to influenza is uncertain apart from
,

,

ii. al!~i:''':ci}'

"ormation.
A rather Iimiled body of evidenc'e currently
. ,
sur;: ~:'" , t :;{ "'~.'-i,::~di:;~ri (;:spr-ilses may contribute to host rcs'istance in viral
'"
ii1r(~ U: 15 ·A .. :,&; •,;:::,.i'" ~Ol" ~:'"1ct. Lymphocytes from the lung or from other lymphoid
tiSS~iC ~re t:ilr ab!n cj ptnd~cing mediators of cellular immunity in response to virc!'l
~ntigen=, •. AIt.;~o!gh th~:'e'is no . good'eVide~ce that'cell~ni~d'iateiimmunity
is a.
.
.
pi- ;h :;"

.1(. •

~

cl'itical dcterrninr.nt in influenza or other respiratory tract

r
~

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,

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~.

, ,
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Duration of Occupal1:Y of GCRC
Bed by Each Subject: None
._--~-----~-

-----~.

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y~r

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Ie·.. •

••

Other Research Support: NIH/NIAID Contract No. 73-250.6
'

. '.

infect~~nS" ,specific

and

, non-sp~ific, iJctivation of lymphocytes during infection must be looked fo~.as
n~E:ssary components of host resistance.
. ,
.. ' Lymphoid cells have effector functions in certai,n tissue";damaging immune
reactions. A number of.!!l vitro models have been designed' in order.to throw light
on the mechanism
of. thcs'e tissue-damaging
reactions. Lymphoid cells fjom
.
, .

1

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1~
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I·

sensitized donors
will destroy. tissue.
culture cells carrying
the antigen and this
.
.
.
has been used to develop an..!!!.~ test'of lymJ:lhocyte mediated cytotoxici~y.
.
.'.
. .
.
Chromium-51
infected tissue cultJ,lre. cells can be
.
.
,
..labelled, influenzavirus
examined for specific lysis when inoculated with,peripheral lymphocytes from
antibody posilive and negative individuals. If specific lysis does occur in
..
individuals with previous proven influenza infections, this would suggest that'
lymphocyte cytotoxicity plays a part in host res istance to this virus.

I
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Project~

, Purpose of

,

"

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.

To d~lennille if lymphocyte mediated cytotoxicity occurs in influenza
, negative and positive individuals.
'"
.'

UniQueness of the Prc;oct
The-re is presl~nfly
.

c~1ulo; ~i~ ~.'>'
!I'i

110

.

,

;\v~i,lable informCltionconcerning 'lymphocyte mediated

.,.... ~h previ ous influenza virus infectiorh The informati on
r;:i;: S.;1·::Y",'; l b SI a.a",le for publicCltion.
•

".

•

•

•

I.

•

:-,tu' ...
":
-_.:-::tiGn
.. _----

.

, '

Probability of Publishable Results:

,

Da~cri

'

:n i nd:-.'k::,~a 1"
•

obt:,i:: ,,';

a~ci

-...". - .

...

anU~ody

. .,

('Ii'

Vol~nl,~ei:)

\-::iJ ;..e :"·$k.. d I'J

!~:ve appro~;matc,ly

100 mJ

'one":"~ifth

pint) of

blct:.d chtfJjn,~ :.y ":~n;i U!·.~ l'"ar,. :Lm;:.tocrit~ will be performed and no person with
a hernaloc,rit I~~oe:; t::Z1n 4(' wi H b:l~ i;skcd to vo'lu~teer. 'The same individual will not
be

aslc~d

to con:ribuel.Hs leO ml cf blood more often than once every 2 weeks, and

J

t:he toUlI !-hall riot f!XCi::Ca 500 mi· for any :3 month periqd. The 1.0 O. ml of blood
will be collected in heparil1i7.~d plastic tubes. The lymphocyte population will be

J

separated using a ficoll-hypaque gradient. The lymphocytes will be counted and
a specified number will be added to tubes containing 51Cr labelled, influenzavirus
infeCted, tiS,sue cuiture ceJI~: At various incubation times, the amount of SI Cr
released from the virus infected cells wil: be measured.

J

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Selection of Subjects:
.

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Medi.cal C,enler personnel will be asked to volun~eer through a posted
notice.. 'Prisoners from the Ramsey Units; Texas Department of Corrections,
..will be asked to volunteer by' posted notice, also. Volunteers will received
.
'
$? .00 for. obtai ning this blood sample.
'~, .. , "

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Discomfort to Subjects:

.

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f

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.The only discomfort from the procedure is that associated with venipuncture •

..

..,

Potentia I Haza~ds to Subjects' and Safeguards for Same;

I

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" Venipuncture can be a.ssociated with ~xtra.vasationpf blood into surro'unding
tisst{e. Trained personnel
wiH draw
the blood and check ftlr proper local hemostasis.
.
.
.
.
No one- with
. a history of a bleeding disord(:!' wi II be ask.:d to volunteer.
.

.

Melhod

oF" Obtllining Informed

'

Con!!.~!~~:

I

t

A description of the study :.0 b~ F~i: .".·i,.. ··J ' -i I;

Jive;l ~o th~

volunteers
.
verbally by the principal investigator and: ,i: ~i \d~! bl' j".::.kcd l!; sinn a consent
form (see enclosed fonn). The VOIUi·,t.~~r \:~;i ..': -: -':,~I ili,~ f'~il(jrtunity tc ask any
questions that he desires, and it wi!! L: ~:'li',· " k~Ii' f·o!:l. b~ ~~:.' r~m(:vc himself
from the study at any time.
.

-f

'

;Jf,

,

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,

.

t
Ii

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n
.
e
f..,t:.,.
b
lJlAt.....:..) oJ') ~ A u:.Ch.. .f \£'-f

~
. 1

J

'1

. Stcph~n B. Greenber~, M.D.
Principal.tnvesligator

; J!{.

JI

Vernon !<ni9ht, r1l1. D. .
U
ChairmJn, Department of Microbiology
and Immunology

f).

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BA.YLOR COLLECE OF MEDICINE

,

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'TEXAS MmlcAL CENTt:a

'

HouS1'uI'I•.Tl:XAS 170~

"

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lifo. Mc...1ClI tIG't AJ'O 1aUI~ ,

n.a~l

'.

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VOLUNTEER'S CONSENT FORM

.

,

(5 tablespoons) of blood

.

d~w!l from a vein in m~' arm.

t understand that occasionally blood may leak into
surrounding tissue after such a procedure and cause some
discomfort.'
' .

.

,

.' , 1 understand that the information obtained from my
.

.'

pGirlicipation in this study )vill b~ of no direct benefit to me
but may help us to understand ho\v we are protected from the "f1U. 1I
Furthermore, 1 understand that 1 will. receive $5 for the' donation
of my blood.

.

Th~ p:-opused study has been clearly explained to me and

• 1 unc1t.:r~il(mu and

a~cept the hazards involved. 1 have been given
;m ('~.:p"l'liJnH·,y !,n ;: sit ,lOy qu~stions I might desire and I uliderstand .
lh;;. l h-. vr~ ~:1" : ;~~it to withdraw from the study at any time llmay

eh"·F.....

.....

Signature_'_.

I
I
J:

,

t understand that 1 am consenting t~ have'lOO' ~I

.'

_

-----------------------

Dale

Witness

1 h::t Vt' ca .. eh!!ly· explai ned the nalu'rc, demands, and foreseeabl'e -

risks

or the 1bcvc study to the normal volunteer.

~

_

Si9natur~

~

,

1

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,

--------------

Date

--..__..-_

_-.-. -_,. __

. ; :.;_

~~_._.=_.==.:-;_~

s;:;;=_II"':;;.=::_;;:::,::::.:_::;=;~:.;.:::.~::.:=.

.,
. '

I

lltle of

R~~ch

Proposal:

In~m.inoresponsiveness

Infection

during Influenza Virus

Principal Investigator:

Thomas R.Cate, M. O.

Collaborating Investigators:

Robert B. Couch, 11. D.
J. A. Kasel, Ph. D.
Roger D. Rossen, M. D.
HONard R. Six, Ph. D.
Vernon Knight, M. D.

.'

"

Mic..obiology & Immunology
\.

~~t'itnti 09

'er':od of

Agency:
Gr~nt:

NIH contract AI-42528
June 26, 1974 - June 25. 1379
Ramsey Units of t:l0 TC:(J~, Of.:pal'tlr·jnt i.:~
Corrections, and l3ay101" Col1~S~! ,~': :·dc!·:.;i ..:

.,

Several reports have suggested that infection \'Iit~ certuin lion-or:"'O~':11'"
..:it' u!\es can cause inununosuppr'css i on as manifes ted by decreased de i oj'<:c :lYf.·t:t'·
~ensitivity

responses, decreased

~

vitro proliferative responses of

lymphocytes to both phytohe.nagglutinin and heterologous antigens, and
impairment of both prir;lary. and secondal"Y antibody
antir;ens (1).

re~ponses

to heterologous

'.