Summary of clinical section I

Slliililt~i'~

lif Clini(,lii

Sc(:lh)n

I

T I l l X'l( t h i s h a s been a fm~einatin~ sympr>si~m:3 ltlzls f<~r, :lTld c e r t a i ) d y m u c h phit+,,~,)phiziltl4 e,)tfld h+, (l~.l~* :d~)ut what we h~lv~, h e a r d . t:il:-~l. ~)f ill|, w h i h . th¢,r¢. ~tre Iltalt2v ) h i s l ~ s w h i c h hav+~ |~.elt s:aid a n d o l h e ~ w h i c h e , ~ t l d ha,c~, | n , c n ~;tid, lhr: first l|li¢lg l h l t t ~tt¢)ilbl t¢- .~:iid is: .~t|C11-2~3 is all i n i | ~ , r t a i i t ¢lrtig. 5"¢,it itl;ty :lsk, if it'~ i m p , ) r l a i l I , w h y i¢4 iI iliq~.gtr'talit? I thir)k t|i,: first o | , v i c m s :~)t.-wer i~ t h a l it n n l s ) (]¢) ~ t ~ n i e t h i n ~ w o r l h w h i h , c l i t t i e a l i y fi)r t),>op|e o r we, w u u t d ri,)t l)e. h e r e t a t k i r ~ at~,+ft it. Nevoll, t, ii {'antie~l k~. v e r y t,)xic. T h i r d , it mu~si 1,¢- li.~abl,, , ) v e r 1<,11¢ l>eri,)ds (ff t i m e if it( is I¢) |u? u.~,d ill a l o r l ~ - t e r m ,ti~T h e ))m" t>ifz ,{llt'Ylit)ll ~'}ii~'|i ~,'~'t' }t~'trt' tt¢1t ad:lr¢~se~l ollr.~(qV~'S re) al all, (.x,-ep) l,v i,)iplie;~ti,)i) i<: 11,-'.-, ih,: d r ) , ~ | , a v e - a t ~ y vllI/l,, fi)r I)i'~'V('lltili~ ;l|h¢'r¢)~eler,)tiv ¢li.-,-:i.,,,- :l,~ w,'II .:i., i)) n.Ii,'vii)~ il ? "l'he~¢, ~i~l(.~ii())i~ ,)¢'e)~Ir I*) (.)ii(' p}lil,)~,~i))li,'ail> ° wh,-)~ lle ;lII(,))+l~ :lily i)le~,li)ig Ilk), )l)i.~. < ) t i l e r ))l)Jl,),-,)F, h i z i l ) ~ t)mt I h'~','¢- <|~,~,' ~ hi~ m~)r))i)i~ wa:,~ le, (.,)mpllre th(, hi.-.l,,r:.()i thi,'< ttrtll~',- fzl)iill.E tl~,lii lit), clJiiiei:tlt t,) l h , , l:tt~(~rttl,,ry" ¢.-xt~,,r't alibi t):i(,l-: tr) )h(, <+liilli.i;lll :li,f,:lJil..+~+~ I t ) i t kllilt'.', l l i + i l t y +ti'ii~.'- tiaV¢" thi.'- +'Xll, t't"j+'lii't;' i i l i ( t +,+,rt;lil+f.v :+ll-]lt+7~,) lu+-, l:ik+*i+ lhi,,, e/iltl'm + i/i <);it f-(iiif(+l'i~iic) + fr+)lil I;i.-t l l i ~ t i I +.~ :i|llliJ.~il )',~-()tt'ri<" {,;l:-+.

Irt++(liltl'ltl

l+x+lil(" +;lt+t,I'/tl4+l°y ~'7-;~l)f'rt. ~+ 1(. l l i l ~

lll+)riiJllt~':-

ililri~ltlf'ff)Pv

rt.lll:trk5

to,"

l))ir( " ,'|iliic):li)> +)i, t h l , ti>,' ~+i ttl+" (tt')i~ i)t l):li i~'i)l:-+ :iil+l lh~'i+ tv~+ h:tvt" l~'+,i) l+r~))l~h+ |,~,+ l ) r . ~ti+lllt)i.r~',~ ci)li('til~.tilig i ' i ' l l / i l i ' k ~ tt:l(+k i l l t h l . + lr.itxirlill,l'y f i i l l i i l i ~ > ;i:~ tt) ~vh;li lhi. ~ 1,, r c a l f y ,t~,t,'i7 t~:l>ic:ttly t,) th(" ..-ier(~t pr~)tih', if )-t~)ll ~ll'itl. l h i , > i t , r i l l li/',,lll~ ' ,,f lht' t)l,),,tl, .~tl)+,tti~'/" llttllll,~ | tli~+ttl~ltl +if ,dt Iti<)i'ilill~ i- t i l l ' irillti+,lti.(- t)l" ;t t n l ' i l l : i t :w,.~ lit lh+* titvi"-¢i~:tl,)i" "~tl(')i h+" l;l+'kh',~ :~ I~r,)t)h'lll l i k e l h i - . t) h'~5 1,(,(,n i x , r h , ( , i t v ~ltt.¢i(,il~, lh;il t.:l(-lt i)( ih~)-.,- ~tl,, h:i- >lti(li(.fl l h b , ;i~i,iii |i;i> ,tl,ii(- >() ~vilh ;l l>i:i.~. "l't)~'r," i< ltitl|iili~ t t i ' i t l l 7 ; i t ~ I ) l t .~i l)i:i< I l l i l t ' - < %1"t" t'i~*l l)lllP:-t*|t't'~ t l i t i l Wt" l i l ) l i ' l illi%'~' i)ll~'- A l l +,f !t... illt ), i" I~i~'ii'ti ;t t'~l'rtiitlI " l ; l l ' ~ "~. i J~F. ! i V r i ~ | i l ~tlll| h t - ~l'+)ll t) tt;illll~:i|i%" l~,<)kc~f :tl 111t~ f l ( ) I t i t ill" l+~l;il~lfl;itll~li t)~)illt ~)f vi~'/~, 1 it, t%flUli| A t t t l d ffi> a-<--~,i-i:!ti" t+.,k~',t ill ii fl'i)lil

t i i i ' ~'tiiiiC;)|

l)liiill

iif % lt'%V.

.~,)tv, ! ~,~,*ilhl -it~7~'~,t ltt:tl ~lt" iic~'~t li~ ~t't ~)lll-i(t(' t)f t)ilF ~V¢ii l>i.'i~, ~lit.~hlt ~ t,f ( ) t t r ttl*lll l l l * ' l l t l t l '.-l'l. )l!t't ' I':Itt .'it'i'('|)l IPtt;II ] I '"l)l',ll "-~:')~i tilt~'~ iiil]tlt'lil't' ..,l(+r~)l -)'flih~'.--i5 lit tllll"ytlttlt'~i~, lilitl lliill if Ill)t)'- l i l t .~,ll~lllli" f~itl)l'~il~li" t } l i i l ~ 5 t'liltic;l|l)'. ~.1 l | i i t l k ' ")"~ ."-~ tFiilh)'r t(*v:l~l al ili~ -l('p ~v("lt t l : l l t " l(i ;li't'l'lil lli~" l a l t ) ' f , ili .~l)ii)" ))f | ) r . lili.,-<-< ti'.',i it:it:i, t~-)':l)t>)" cli)li)-i:tli- h:l~(, l~,~-it lilitl~,.-,,..it~i l h ; i t t h i > ~h'ii~ i t ) ~ , - t i ( , l p : i l i ~ i l i i i Ill lt,ll~t. "~ t l i t i tti, -li~)iilfl ,'i'-k i)tlr>.i,lvl-;, tt() llie,,--i, lt%tl l t l i l t ~ < rl-:llt)" ti:i%'t, : i t i y l i i i l i t ~ t~) (t~) ~ i l l l t,;tll-|i - t h o r ? ()i* ~iri, l h ( ' F j t l - I i,(i),\i,,,li,lit l)ht,iitiliii,ii:t7 )','()i|till7 i- i>:l>t,,r i~) ",til) Jill,i, ill tlrll)~ ~t+~)l'k, l h : t l i 1,) ~ ' 1 ~l ~ll'li~ fr~)ill lh*' [:li)~)l':ili,l'y t)t" ( ' v i , l l f¥1~lli £))til l()rt' lti,.~tiCili), Wtlich h;l,', ()Ill- wi,ll-i'('('i)l~lii~.('lt :l('li~)li ;llill li) l~rtili,cl £fl)iil t h : t i ),v(,li.rt,t,t~ltil,,~l l,ti:~-.,,i,)l~)~it,;tl ))i i-litllc:ll :i(+tiltii l i l : i l .,ill It--- ,)th),r l,ffl,~'l- illFl" ,ill il)e ~lill)i' t)ll>i- %tI-+- ha~), ~,i*ii i h i - h;itilX'lt. ()f t'(ill!'--i% il) i h c l'~'~(.'l'liiit~' ht'l~l, il) lfi~" .',~'l'))ll)llifi ;tilt| l i l i l i "-I'l'i>tt)liiti .--~|il:it)l)l+', ;lii~t ~--,) )~lt. I! i- -l ill (ftii'+-.tl~ili~lt)tt" ;ilil+~l)~ l i l i i l i V t)f il+~ t t i i ( - t h i * i lhi" I ' l l ' a l l y l l l ' ( ~ t ' l i c h e l l i i ( ' a l (it" litiv:-i~)lt)t~ic;tl li/'lil~li', i l l ;l

594

llOtll;llT W. "~VILKIXS

drug really are responsible for all its cli~ieaI effects. Let's keep this in mind with r e s p e c t t o MER-29+ ~ V h a t e v e r else w c c a n s a y a b < m t t h i s d n l g , a s o f t o d a y , l t h i n k w e will all ngrr.e w h e n w e c o n c l u d e t h i s c o n f e r e n c e that, MI~II+29 is ~ . r v i n g t o o p e n u p act ivo i+z~ - e s t i g a t i o n ill a n a r e a w h e r e l o n g ag~+ it M m u l d h'~ve b e e n d o n e ; n a m e l y , o n w h a t a r e t i l e h o n ~ : ~ s t a t i c r n e e t / z m i s m s b a s e d w h i c h c o l l t r o l ehote+.~tcrol l e v e l s in p e o p h L w h e t h e r o r n o t t h i s ha.s a n y t h i n g t o d o , ,+~s. I Stll~|)-ost~++ We .+Ill b e i i e v e t h a t it do~+s, w i t h a t h e r o s e t e r o s i s , a n d w h a t a r e t i l e p a l h w a y s t)f s t e r o l s y n t l l e s i s , l i n d w h e r e s h o u l d t h e y and can t h e y b e b l o c k e d ? I a m ~ : r £ a i n t h a t m u c h o f t h e i t f f o r m a t i o n t h a i w e will t a k e a w a y w i t h n s will trot c o n t r i b u t e s u b s t a n t i a l l y t o t h e p r o f i t ~ ~ f T h e *Win. S. 5 I e r r e | t ( j e m ~ p a n y from, t h e i r s a t e o f t i l l s d r u g . B e t h a t a s it m a y . w h a t h~ive w e h e a r d t h i s I n o r n i i l ~ a l m u t c l i n i c M e x p e r i e n c e s ? W e ' v e h e a r d l)r+ I < o u n t z and :~overal +~ther~ a t t e s t {Ira+ t h i s d r u g s e e m s t o lesse|~ a+tginal a t t a c k s in c e r t a i n p a t | e l l i s + Yet w e h a v e h+n~r~t : d : ~ t h a t it d o e s n o t h~--+~t+ a n g i m d a t t a c k s in +~lher p a t i e n t ; < ; ~ n d if w e aer+,pt I)r+ Ru~k's rel>O~, it d t + ~ not te+~+~,n l h e eridcq+ec.s o f a n g i + m +.cI~wis w i t h s t a b l e eo++lr,A ~t~+p I ~,~t data. N o w , w e h a v e n o cti~tic.'d i+ff,~rmation, e x c e p t a hilll fr,+m l')r+ |'~++uldz+'lh:,I t h i s d r u g m a y a ! . ~ t:,e e f f e c t i v e b+ h:<~.t~i++g t h e sympt++mat~+h,g~ + o f l+~mti~+++t~ wit h i n t e r m i t t e n t e l a u d i e a t i o u + A s f a r a s I w a s ahh+ t<+ ~ a t h e r , w e h a d +m >uggr.-ti,,n t h a t it h+~- alt+-r(~3 t h e +'o++rm+ +ff c e r e b r a l va~+~+lar di+..++a+~o, at l++a.~+tf n , m th++ .t:u++l+ p o i n t tlllto~Iarl, ilt m y I h i n k i t i g , o r d i l l y [t vl-ry r~.mt+t+. o r l i l l y rt+lati+mM~ip }~+qwt++*n t h e +'+lilt|eel imtir++vpn+t+nt t h : d th+. d+++'l~+r i+~ int+.r+,-t++d itl al+d y-~)rnl.+ of tilt.+ l~Ir+L'+tlr++mt+llt:-+ thief h a v t . |m+<+ll r+-l~,rt+,,|? +l'akt+ th+. prim+. ,m+.. t|l~+ el;+J|+mt+.+rol Ie,,+ r e l a t i + m a h i p b<+tw+++i+.n c|i:~ieal impr++v++mtqd, wl+on h t4++=s r+q~r)~'d+ a n t i | h r fall it+ t h e bl+~.~d el++A+++ster++|+ N o w . t h i s is a .imp|+, thi+lg. ~+ l++tN +.+.+t+tbli+++h it ++r l~+l"+ t||r¢+W it OUt+ S+?r++mdly. w a s l}+e ilI|l++rov+~+II|++Ii|, whi,+h wa.~ u+,,lmlly s|++t<.d I++ o+-e+:r +tithh~ t h r e e t++ ~+ix w+++ks, p r o g r i ~ i v + + +it did it +.+cur iIl+Irt+ ++r h++~+q u i e M y +~llll| +tat+i||++? M y impr++.x-d+n+ fr<+m w h a t w+~;. +~aid w a s t h a l it ++ee++~rr++d +lui+++kly a+l+l s|M+iliz+-l. T h i r d l y . +l+a,+. it o c c u r ,lui++k|y +t+++l th++l+ st+tl,ilim+ f,+r++v++r, <,r ++an il +fill +.++'ur d i l l y a f t t . r m + m l h s t+f e+mt i+m+.| +r++aI m++t+t wh++++ ++t++.trly ++r i++i|ial il++l+r++v++llll.t+t oe++,+Lrr+Pd? T|+c++~+- art++ ++.+.r~,. i/++p++rl;i++t +lit+roll+m++ "l'|++'r++ w+~+ +m++lh++r su~,.+~li,m

NI:MNIAI~Y

OF

[:l,|NitJAt+ ~ECTION

I

+~95

re|ati+~g t o e h o l e s I ( w o | |ev+~] h+ L h e . ~ e l i n i e a l | y ob~.~rved p a t i e n t s : t h a t it m a y I),I[, th(m it m a y r i ~ cm eo+,ti+luation o f the ~ame d r u g t h ( ~ a p y i a n d t h e n , in ~t ; n a l u e { y , th:tt y,++} ¢+:{nn++t toll w}mt a d n { g w i | | d o a f l e r f o u r o r |iv,. y,'ar.¢ +~l"tr+,:~t mvt=t ",vithcmt wa}ti n g h , u r o r five y e a r s , T h , . q,~++sti+m +ff .,'m,e |,~,rm~m;d, h, m m r z d o r en+|~,rrinolugical c h a n g e wm~

l:¢~nl'-~ sttuli,+~ t+, li~M ~-ml+" melh+~| ,,( e v : d , m t i n ~ ;~ther+,~++nh+ a n d a n t i - a + h c r o { D ' i l i r p r , , o , ' , i , | r , ' ~ +,r l r,-;+ll}l,'lll,~ t l l r ~ n l g h t h e i r effo+.t.~ in M m u l a t , < ! ~tre~.~ M t n a ti+,+*~. 1 tbi++k +}mr h e {~'r-,l:ld+xl ,I~ Ih+tt +his m ; i y }*. a u.-eful m,.th+~{ o f a t | l i c k , m ~h+o wiml,+ pr,,i,|,+m+ t h i t ins,* ",vh:tt it nl+,zins t,, thi¢ qtlt'.:;tic~lz, t+Xc++pf f o r t h e ~ o n M r | m m t imt i~ i-.,',,mpt+-++'ly +*|++:+rI,+ h i m . A~ai~,. thi~ is a Ida.- i,1 w h i c h h++ is l,:~rlh+,darly i,+I++r,*:.t++t :rod ,+,wtamly
t,,r,d+ N + , t . . l y

! h~+v++ h,=~r,t ha+.- }w+l ,,.iv~+,~ :~ {u'n:+'n~:~e tigur,: th:~t is "'Mg-niti-

:malv-.l.+ t~nl w~+ 1~ +.,| It+ kn+.t~ t h r I~'r++t+ttl;~g,+- ill ras,,~ in w h i c h w e g e t :! l++weriHg

t++rily l,, th+- M+-a tlm{ ~,, +,u~ht t~+ t h i n k re, m+ :d,~,ut tlw-~- ca.-.cs t h a |

h-rr~Id++ .,,d,j+,-l+ ,+f a|~i++h { h~w+ l~+,+l+ ~ m l l y

dt~n't

-*+ ma~+y linu-~. ~,f ++,,oml,inati~+n

a,+~,t+ ~|.++h ~ ,.a.t t+, ",,~+,,k m -,m~," pat~.,~ts+ :rod M I':tl+:2:+ w l n , ' h is s d d z,+ ~ r k itl ~ I I I I I + |i;ttl~'lll', It!i~|ll i~+--ih|y ~ , , r k In-I t~+r Io~,qh~+r l | m t t ..ith+,rom+ d~'.-, ahme+ T h a i +++.rt+,i,,ly ,,,',+d~ ~+'D" m~l+4+ m+,n. -lu, iy a m | i~, t++ m,-+ :~ v~.ry intt.r,,Ming id,+;++ I t h i n k Ill:+t | ) r T , ~ h t +lid ,-l:~rify f+~r ,l-. tirol nl l,,a.t a . | a t :~s ".|U" ha:< ~om" il~ h,+r .~I,Mi,+-..-|,++ +. +++,l e, m v h w , n{ + ha'. I hi~ d r u ~

iml~wlau+ly

i+dhl,-z+r~+~ t h," cl+,t +

li,l~ tn,'+'i+:+++i+,,,l+~+ N++v,+rth+q,.+++-+- h - ~+,,+d+l ++er+ai+dy 1~- t h e fir-t t++ ~+y +hat f,l,ltr • a t , ' l+,,+ I'+,~+ Ira! i,.,,t.. ++,; ~+Im+|, +,, ,l,+:+u a,+v ..x++,++{,l,{~ c,,tlchl-.h,tt-. ¢ '+,,,+i,,m {+++,,+kl,, +*,,~{+,+-ri,,,,l,m w a l -+d,' +'fl,'r+.+ lm+~+il,ly | ) r lll,,h,,, ,+h'ar,',l u p f+,r +1++++,1, :+{+l~nr+'+,l r++l,lli,q lh:{{ {)r+ +{',+r,+ I+t+'nli,+l+,~|+ +~alII,'ly. l|l:lt +++It|+" ,.hl,w|y

59t~

R()IJY~~gT

W+ WLhKINg

f(,male patients do bleod sliglltiy fl'om flu: vagim+ as if there were +mu, e.~tr~+go~fie+ effect of this drug. |~'+'17miT~tir~gou| that evel~ in animals ~he +h'ug muy pote~ttiute the amounts of existing e~trogcu: am], of cOtlrSe. W(++klv+)w {hlit il~ |l|l~l+l+rl I+ei.~.~ estrogel]8 don't all +.+()me fl'om lhe ovaries. Dr. Corcomlt ~s dinical o!)~+,rvations aud thole of Dr. t,eel+;crt showing +:tr<~bu+++ l,iott in ehol+tero] levels it+ l l or 15 and .1 of 9 <+,fl,wt) differem gro:qr~ of p+'il+ient.~ w+.¢c s++mewlmt al+ variance with the obu+.,rv+iti+ms tim+ Dr. ~qteili|mr~ shoWe+]i l)r+ Stei~fl~erg was strewing a particular type of study+ A+ut yet. I th ~k thrmiRh + old all of this ~x+ have haJ'~ the >uggcstlon hat we are+/'| regitly Itl|('~tSlltJlI~+ whirl w(; Otlght to |+e me~L+~tlri+lgev(m i~l mlr sterot ll'+(*,It:qlr(;tll+~tit,~.. I +tllt s|!r++,+ We will +. . t the (~ther chemi(+.:d (,xtwrts wh{+ will ' vhmfy ' Jill be i~(i(+,l~l~++(]to ])r+ A v ~g.m +t+,( fi~r us the way i. whid+ we sh+mld m¢~sure the~++thiug+ eliuie:diy+ (k+riainly+ if | know the stalistics, 20 per Pent is .+1 fairly 0+)llllilOtl fit~ura ft,r fig{WIlCO ++,+Wi+lqll~ ++f the blo+M cho|esten,l as Illoasilr(~|, till(] if thi+~ is indeed ae(+++mi+++i for |W l|w appcarml+'e of :i new stert+t, 2.t-<]ehydro+:hoh+,st+er
e+mstructb:e and qu++ti+mi++g +~um+narT. I! ++mph:i+[ze+~th++ +tail+in+mr ,+f the +at++ Dr. E~r+me I)uf+i+, that th+, ev,'thmlitm ++f a
diffietflt

prtjr+<~++,

iJ~tla]Jy l'ntWh me+r+++ +Ji||+m+[l+ t]ta+~ th+ + ++x[M+ri+++¢+~+t+

that +Phe ph,,+siol<,~i+~t+ and chemi+|+.+ el+Pry +m! ii~ tl,i.ir ]:d,<,mt,r++++.+. +l+h++ fiuu; d+eisi()++ +++ff involve hut;dr<.+ds o+ th+m~a+id+
therefor(+, i1 is a major res|~msibi|ity ;m+J va+m+)t I~+ tak+,+i light[y+ In order to m+.ditate a+~,iit this, we ++'ill now :[dj