-

)r~ltz7t IG_]?.}.i EX_PER. I E . CES lITI! ~ ~ _ > .

F'PTIC TTT.CEB '- ~ . , ~ ;._......-;;.;;.;.-~.;;.,;,;:.;;..__;B~.;;;;...........-.m--..-- • ~ ~ ~~

,,y,~·· eonidas H. Berry, V.D ., Jonas P. orri~vicius, 1. D . , T. J . ~o e, 1. D. , Robert Schoop, N •• , and tT an ta Furne_ , 'R • • , Chicaeo '

survey made a ew years af'O inr'!icates that physici~ns in the~':' ni te States see m re than 61, 000 patj en ts Hi th peptic ulcer per ~

month, and that there are approximate y four mil ion ulcer patjents at

a times. ( ) I am, therefore, brin~in~ to yo1r attention a disorder

which is by no means uncommon yet there are p~ob e~s of its patho~enes1s,

its trectment and prevention wh · ch cont nue to ba f et_ e most astute

minds of the mecic 1 cciences, an 1eave

of nan geme .t fo-r tbe clinician.

ans ·1erea imnortant que~ti on s

rr e e~r e t eric~ a · sci le of ~ntec1a t eran n the tre trient

of' peptic u cer is genera y recognize as Bertrari. T Sip. y i'lhO ive •

nd wor ea. in Ch ·. ca O'O n p .blis "en h . s cJ . ca . observations in 9 5. (2) . rowe rer' the late man Go dstein ( s ete th t ur j s

Corne1 · s Ce C! s treqte pe_ tic u cer ith nt a ci s in t e first ent ry

. D. there ore ao not hope to resent a t this t ·me an " Occas · on de

Ce ebrer" in ccJ1 · n0

to 1011-r ttent ori the u~e o'"' ant cids in the treat -

ment of ulce~ . I on y wiPh to reonen th s ~ject, consider it rPtionale

an to present some of our recent cnntro ea exper · ences 1ith n ntic

u cer, using an a~ 1 inum at prod11ct s n a t~cid.

A greFtt masc; of ev · aence c:iccun111 etea over t _e years indicates

rather convincinely that the sup ression o~ gas t r ic acidity ith antacids

is associated with re ief of ulcer s~1 ptoms an the healjng of the u cer

niche . These effects ma. be r matic and complete . However, the more

soluble alka ine antacids ~ay j_st rb the acid base balance 0 the bloc

*From The anc Provident Pospita ~, Chicaeo

- 2 -

~n producP syMntoms of a alos · s . It is a .s \el no1 m t t the e

antaci s, of •Jh · ch sooium bic":!-rbnn te : t 0 best exam e, .so ma

c~use " rebound 0 cr et · rm" of cir ~ ctri r juice. Other an ac i s, ~ uch

s c~ ci ro c rbonate n ~ ~ nesium oxide, re re ~~ive y insol1b e but

the former is constin t · n nd the tte:r ma~ be 1·_te a ~tiv n

e tra · zin , doses . othe ant~ci s, jnrlu in s th~ trin n 1osn ~tes

o~ ca c · um and m gne~iun, the exchange resins, protein 0ro ys tes an

mucins, a e in ge erA. use. et~i r-. discus~ion 0f t e erits and

emerits o~ 1 ~ t eqe p-ro~ucts will not be undert~ e this report.

I sli.o ilo i e to point out, ho ,rever, that there are genera .y accep e

stan ards ari0 i te ie rhi ch r re ''T e s cr.:.aracteristics of an i ea

antaci~ in e treat en~ o~ neptic u1rer . heoret·c 1 r i ~ n tacid

s~ou d be (1 n6htoxic, (?, rel t ·ve y iDsol ~bln or 1na or ble

therefore sh0l11n not (Hst rb he aci b c:-e ba ance o the bloo ., (3)

s 1 0 not c " acid reb0 1 .d" or seconfi9t' rise in P'2Str:tc acinity,

( shou n e~ 0 t prolon 00 neutr~liz · ~ ef~nct in s a1 ~ es, b t

sho 1fi not st ress gast~ic ciaitv b0von p of b it 3 . ~ to 5, (~

• t sho l a be ~'"17t!:!b1e .n rrl t~_vel 1 · nexnpnc::dve, ,... n (6) cha 1.1r1 not

_a ve an C"ess i ve v con o-r ax ive e feet. _To ~mt. c; as as

yet been eViSP Tfiich ets a 0t nest o t - ores

Il·. 1 ed hc:Ve tfieir roo0 poi.nts. frToc:;t rlinicB} inves i~atOTC::: tod ~1 gree

t a +hp 1 .r'linu n :rrorJ t s rriore ne y meet t_ - :i teri~ set f'n ~ f0-r

t:be ir r~l a.nt~~in. (Pe •

Tn rerPn mont w .have t ri. · e n":::stri.c c: r e tion in re t · on to

n , f pe · ~ 11 l rer on o

i:.ros~i t~ s. le have been interest A in pro :r;tne . and comul Ptcness o?

ea:!.jnr· ·Ti th X-ra.1 n P',.. stroscopic c ntrol. SeconClly, ,, e tterrnter to

assess cJ inic_:J __ evide,;nces o+- roript encl ~nnn1ete calin a judged b

tota a ri rro o.1.P'ed re j ef o ui 0 r S""7mrto"Tis anc. our 01m experiences in

- 3-

va a ting adherance t o medica a iscipline . Third1y, ~e st died the

ncidence of recurrence in these groups 0 patien ove 2 pe::r i o of

R rlonths . n all of t PS8 eva atio s we emphas ze the i rort ce of

recognizine; and sep .ratin to e i ect ' to cer 8'11 ot!i.er

associate g strointesti.nal s:m to _ . DI ~JO TJr~ IES

~ e i ~nost · c cri er a were s rict an ccns · ste o~ aboTeto r

nd clinical evi~ence. t 1-1 f not e'l1 to ~erP l 1 ave X- y def'ormities.

Each p~tjent hed a u er +o~J "ndicetive of act "vit • any patients

ha repeat , -ray an g ~s troscopic e a inations before tre~tmen 1 s

storte . • It is or custom to h re the patient keep diary of' sv ptoms \

dur ·ng the uor __ up pe o in or( er to con irri or deny the oriP'inaJ story.

OccPsiona.l io~ena. defo it was rP ·arde . as a hea e scar or inactive

u cer becatse a u cer s narome r s not nresent . he gastro intestjnal

symptoms ·n s ch c ses were often indicative o f nctiona re distrE:-ss,

associate cbolecvst · · other - trointes ine ; ora rs.

rhart I

IT TD~

'11he f'}r>st s e sb..o •Ts d · nos i c and treatment st J. · cs involving

99 ulcerative esions consisting of 77 duoden ~ ulcers, 11 benign astric

u cers, 1 gastrojejuna u lcer ,

hvnertro~hic gastritis.

ma ign nt gastTic leer an 9 cases of

Indicted are the number of ~ -r y examinatio~s be ore ana after

treatment. In 99 ulcerative esions before treatment, 77 duo ena

patients had 86 e aminations, gastric u cer p tients 5 examinations,

w i e gastrojejunal an. aliEnant e~stric ulcer 1a one ex~rination

each . ThP X-ra fo low- up du ·ng a d afte treat~ent consi~tea al o of

~ulti~le examinati ~s .

- DiaP'nostic - ::....i.;

--·~B. __ e_-~ore anp_ After P~

nastrosco ic eYaminations bPf re tTeatnent an. in fo~lov-tD stuoies

-4-

were a so m ltii e. n a~dit1on rrct · on~ e~str · ~ enal s · , b ood,

urine, an stoo examin~ ions, liS ve

colon ~er ~0ne on all patient •

~EC11ETORY

Y-r~v nf gall bl~dder nd

Jn order to study the neutr~Jizin~ effPct o~ se ecte . ant cifi

upon the stric jnic0C! of' 01r C' SP o u ntiC' nlrerative esions, our

:met o0s rere as fo o·rs: (C' ide . DA.A form ar) !in a umjnum _ronuct,

Dihydroxy A umi m inoacetate, was chos_ It i~ a sa t of ~n amjno

acia, amino~cetic acid and al uninum hydroxide, a indic~ted n the

diagram. Slide 4 .. - secretory data) The princiiJ)al P.;rou for secretory

studies consisted of 79 patients with eptic ulcerative lesions. 30

pat · ents raven to have negative GI tracts by :-ray exam ·nation ·were

used as controls. 109 secretory e periments were run or t wo hours

or more on 79 ~atients with pe tic ulcerative ]P~ion ana 30 p~tients

wjth negative GI tracts. Aliquot nort "ons of gastric juice were removed

per "odica y, easured nd retirnP.0 to the stom ch excPpt for minjmal

quantities from which to Qet. rmine eJectromet~ica 1y the pH, f'ree and

tota aci ities. (S idP 4 ) Af'ter a control rm of' l hoLr, ? gms and

in a sw~1ler ~roJr of' cases ~ms of' Dihydroxy tl 1minum inoFcctr:ite

Trere cru~hed in t 02' o+> "l·Tater aDCl washe thro "f: - a evi e tube in.i..o the

tom;icb ·rith n a<10 "t iona ~ounce of w'")+Pr. In th ase of 4 ~ms 2

Qlm('t='.'S of ·r .te~ ·were 1 C'G • P lio mt n"'f>tio-ns 1•P=~rP removcr1 Pr r 15

m · nutPC' fo!' at 1 en st another h0Pr fo-r vo 111metri c me surements, rlT_, free

~na tota acia ~ete-rmin~tions.

Slide 5A ( Jeg. n • • ) The next sli_<1r shows a P"raft of' Mean o:r comnos · te

secretory c rves of pH and free aci - 30 cese ·rith norma GI tracts.

Adequate . prPssion of' frPe acid · in ic~~P<1 af'ter · ntrod ctio~ 6f

Di_hydroxy Aluminum AminoarPtate .

S ice 5B show~ a si jar ~raft of 20 d1nden 1 nJcer C""'Ses indic!'.lting

-5-

adeqriate supprrssion of free acid to a H of 3. 5 or above (or clinical

units of anproximately O for 45 r1inutes in most cases, aft er intro uction

of DLA .

S ide 5C shows the act a sprear of pH in 10 cases of duodena ulcer

before and after DAP_ .

t is obvious from these grafts that the drug selected , ihydroxy

Aluminum Aminoacetate , is capable of suppressing gastric aci jty to points

within the range of the socaJ ed i ea pH rar.ee of 3. 5 to 5. for an

average of 5 minutes in most cases . As gastric acidity is reduced the

digestive act.iv;ty of uepsin is suppressed, and therei n lies the effacacy

of antacid therapy . The acid neutrPlizinJ ower of the rug was j ist as

effective in the stoFach with ulcerative lesions as it was in the 30

normal stomachs used as cnntrols. Other experiMents not detai ed here

invo ved secretory studi.es after Histamine stimu c.t inn as well as in

fasting basal secretjons, ~ith no essentia ri fere~ce in neutral . zing

ef ect~ .

As mentioned previously, our experienc e, as we 1 as reports of ot er

o"b~ervers, indicates t _at t_ e aluminurri prod.nets are probably the most

satisfactory anta.c:ids in use tonay . They are nontoxic, re ".l_tive y un­

ahsnrbab e, do not a · st1rb ~ci _base be ence, c~rah l P jn smR11 qiantities

of depr sin~ ~rge emo1 s of e bP l o r a nF of 3.5 to 5. Besi e a.bsorbat ·ve

mulcPnt action . An important short co~ · r of he

not

8 umin mi yiror1. 11cts hes been he cirkec1 tP 1n.ency to r-rm st · te es!.1ecia ly

when frequent administrations are nesired. h ' o~cur at times ·n snite

of concurrent usp of mjJd lRXativ s . n o,, · t"r"e tr11 nt tt d · PS .. Di hvnrrrv 1

r. 1 inini1m A j oacetat 1 s a.~a n 1 ~ a n :!JrPferPn~P to tli_p lumj_ m

hvnrox nes, honi·"'r' to avojn or r0duce t e ai,,Do~1ai1ce of constip tiori.

ncl second y to detern Le whet her in other r~::)C•pects this ~ u:r.iinum

-6-

rt of n ~mine aci~ ~hn1 d be regardPd ~an effectjve a~tac· , c1 "nic ly.

T · s U.S .P. pro 1ct contaj1ls 55~ less oft ~ constjn t:lnC' Aluminum ele1 ent

tha~ the hydro · es. (Bef •

.1_ BLE SLJ_DF 61 C_l_inicf1 Rx _§ tug ies

99 patients witb u cerative lesions and clinical symptoms of activity

were treated ·with a bland diet ancl Dihydroxy 1\.J n.minum Aminoacetate s an

antaci • The n'ltientq ·were instructed to chew t~·ro tab Pts (1 grn, two

hours c=ifter meals and at bed t " e. ome )aticnts with very active

symptoms rere given gram every 2 hours for 8 or 9 doses a aay . This

was especially true in cases of uo enal ulcer wjth partial ~loric

obstruction an. in the c ses of astrjc ulcer. No anticholinergic or

antispasmodic or other drug was given except an occasional dose of

phenobarbita as a sedative in c few ca !:e • ':1hese patients were on

treatment from three weeks to lt years. They were seen regularly by one

of us . A few of thera _a i y while hosni tali zed, riost of them once a week

untiJ comp etely relieverl and then every two or three weeks . A _i igent

attempt was made to determine whether the· specific ulcer symptorrs were

relieved . Certain svm~toris,such as o~er abdominal istres?, bloatine,

areopha y, might persist while the typica1 rythmic epie~stric burning

or gnawing after --:ea ls ·muld b~ effectively relieved . (Lj P'hts)

SLIDE 6B Clin · _c_a-=-Re~sults o Rx

Table

The next slide s~o1s that 2bout 90% of the cases ~ere completely

rel eve of symptoms in less than three wee_ .. s . In some instances milder

s.,rmptoms returned occasiona ly ·or longer periods . On y about ?c;' req ired

periods longer than 3 weeks for co!Yl.l:") ete relief and only 2 p tients rnre

in the category of not being compJete y re1ievea e.nd one of these was a

malignant gastr "c ulcer. The bre""' down uith reference to duodena_ ulcer,

eastric ulcer, 5Ses trojej .na l u cer, h~1 pertrophic gastritis and malL_,nant

ulcer is incicated.

-7-

ST.iI:QE

Table

Cl ini.,c2 Result~

The next s i o e sho,· s c ini ca results in s rrrnary . Inc _ dea. is the

interestins f act tha.t only 3% complained of' constipatj.on not previously

noticed . Onn patient comp a nea o~ nausea attrjbutea to the peppermint

f Pvorinc: of the drug . It was of es_ecial interest to us because we

have obsPrved stm · ar instances before t the c~se of m..,lignant P~stric

u ~er w not co. n etely r P i evf'd of symntnr s ·with V8ry r ig i d mana e. ent

· ncl11<1ing inall thr:. ddj jnn o anticho :inere;ics. It is our feeling in

spite of' the reports in the literat re th t ~ost cancero~ astric u cers

couJa be iagnose by a c~reful an Jsj~ of t A c inicq course w _ich

und r r • gid medical a apPrie t over a perior of 4 to 5 reel s . 1' i le I

wo1 a not rev upon this ~lone •tis an irnno,...tant aaiuvant oft times ~

equal tot P 1~bo,...atory m ~on · n the ..:..r er nti 1 a. · afnos · of' ma l ianrnt

~er .

rn~ 6n Bvioen~e of'

Tab__g

Evi .ence of' hea ing was fro~ _ Pd in o clinicPl, X- ray, nd stroscopic

eviaence. It is o~vio1 ~ro t ~next t~b e that the results were excel ent .

Such results o· conrc;e ar e not dif'fic1lt to oht:.in vith caref'u . and

c onsc · entious ma arement, when one h..,~ the confidenC'e and coop.era~ion of

the patient.

The fo lowing seriR.1 vie 11 re i . lustrative of the X- ray and gastro-

scopic evinence of he~ling n 01r eroup of cases:

S IDE 7A (Case L. S . ) A middle aae ma e had a g strid ulcer on t e lesser

curvnture i'lith rather r11 · 1a S/mpto'11s, ras treated for rriorths in the clinic

before our study, w"th little f'Vidence of hea ing . He was fjnally

hos:'.:"i ta zed for better control and the 1 cer hea led almos t · comp etely in

10 days by X- ray and gastrosco~jc control. Slide 7B, Slide 7C, Slide 7D,

S ide 7E, Slide 7~ .

-8-

C as e · .D. A 38 yeer oln fema e was first seen w"th rather severe s mutoms

of partia py oric obstruction ~ue to healin~ d1 oden u ce • (8lire 8l'

8 months Rfte subta l ~nstric r ef0ction s e dP Jone a g stroiei1ma

11lcer (S ine BB .. thouzb thesP 0sio are often ver, tljff "cult to

han le, medica y, in th "s c2se hea ·.c w s rt . r corrinl.ete '1S C"hown b

~ - ay a~n P,astros~opy . ( 0 lide 8r (S ine 8n

Ca~e F . C. 4n ye r o r ma e pr~ en tea f" "rlv typic~l u cer story end

ras reported b! X- r 1 to have a benirn pr~nyloric ulcer (S ide 91 wi t h

some antral s sm . A astrosconv trP f~Jt the p tien had a neli()'nant

J 1 cer. ( R ia e 9B) urger' was a v · sed .

na~enent was inst "tut ed r a t her inten ·ve y for about three months.

Symptoms were re ieved b lt nev r comn Pte 'I; , 1·d th Blan d · et, antacid

management, nor when nticholinPrgics were aaded . (Slide 9C IText slide

i~ a ~astroscopic viffiT s~mrins some evi ence o he ·nr and rough scarring

but not the smooth epithe iazation o~ benien u cer . Surgery was finally

performed 6 Months after diaenosi anc ca.rcinonia conf · rmed . No metastc:isis

were found .

All or these cases were treated with the aluminum prod ct, Dihydr oxy

luminum Amjnoacetate and Blan diet but the a pro?ch waP tli.at of apprais­

ing an tre~ting t~e tot 1 pati0nt in addition to the oca1 1anifestation

of isP~ e. 'T1he inc ence of recurrence of c in i ('\~ 1 s~1mntoms -.:i .('lter

cessation o~ antacjd therapy ~or one fuonth or nore was observed. A of

thes e cases had origina __ _ y been on regular tea Ment or three wee1 s or

more before cessation. correlation OT history ata indicates usua 1

recurrences were associate with short perio s of theran1, or some cefinite

an speci ic erisode snch as dietary ·na · scretions, a bo .t of cocktails,

acute up 1 er rPsnirator infections , or e~otiona storns, iKe a tuE of war

rith the spouse, e(\o~om · c revercps, et0 . There was X-rny and gastros copic

ev1dence of recurrence · n one CRse of b~ni ~n "stric u cer oft the lesser

curvatu e 7 months fter cessatio~ of ther apy .