Prontosil Ionization

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b e in g A

THESIS

f o r th e degree o f M.D»

o f the U n iv e r s it y o f Glasgow, by James S tew arts M«B.« Ch.B.

ProQuest N um ber: 13849806

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CONTENTS

I d tr o d u ct i o n .................... Page

1

I o n i z a t i o n . . . .............

0.

page

Chemotherapy....................... Page

20

E x p erim e n ts......................... Page

41

C ases,

Page

62

D is c u s s io n

page 149

Summary

Page 172

R e fe re n c e s ........................... Page 177

IN TBO'DUCTIO'H

INTRODUCTION

An e x t r a c t from a le a d in g a r t i c l e in th e B r i t i s h M edical J o u r n a l o f 22nd F e b ru a ry 1941 i s o f i n t e r e s t . I t s a i d , "Some e n t e r p r i s i n g c l i n i c i a n s

had

a p p lie d su lp h a n ila m id e l o c a l l y w ith good r e s u l t s , b e f o r e th e work o f F i l d e s and Woods f i n a l l y gave sy ste m ic and l o c a l su lp h a n ila m id e chem otherapy a co m p letely r a t i o n a l b a s i s ............. L o cal a p p l i c a t i o n i s th e r e f o r e r e a s o n a b le ; w hether i t succeeds may depend on v a r io u s l o c a l c o n d i t i o n s , and can b e s t be decided by p r a c t i c a l t r i a l . * 1 The f i r s t t r i a l made by me was commenced on 1 2 /4 /4 0 and u n t i l Ju n e 1940, I was one o f th e afo rem e n tio n ed group who was unaware t h a t s u lp h a n ila m id e had been a p p lie d l o c a l l y by o t h e r s , b e f o r e th e tr e a tm e n ts to be d e t a i l e d h e r e in had been i n s t i t u t e d .

As r e p o r te d in th e

B r i t i s h M edical J o u r n a l 6 /7 /1 9 4 0 . 29. i t was an a r t i c l e by J , A. Smith 2 2 /6 /4 0 in th e same J o u r n a l which made me r e a l i s e t h a t su lp h a n ila m id e had been a p p lie d l o c a l l y as a method o f tr e a tm e n t by a t l e a s t e i g h t p e o p le , a c c o rd in g to Smithes r e f e r e n c e . I t was in th e l a t t e r p a r t o f 1939, a f t e r o b s e rv in g how q u ic k ly t o n s i l l i t i s was cured when p a t i e n t s f i r s t g a r g le d and then drank a m ix tu re c o n ta in in g s u lp h a n ila m id e ,

and the remark made by a drug salesm an t h a t su lp h a n ila m id e was e x c re te d f o r th e most p a r t unchanged, t h a t th e th o u g h t o cc u rred t h a t , i f t h i s were so , th en i o n i z a t i o n w ith su lp h a n ila m id e might be e f f e c t i v e in t r e a t i n g l o c a l s t r e p t o c o c c a l and s ta p h y lo c o c c a l l e s i o n s .

Since i t

was e x c re te d unchanged, t h i s to me, as a g e n e r a l p r a c t i t i o n e r , r u l e d o u t any chem ical change in th e stomach and bowel, b u t in d i c a t e d t h a t t h e r e must be a p h y s i c a l com bination o f some k in d in th e body t i s s u e s . Should t h i s be th e c a s e , th e n , ran my th o u g h ts , i f su lp h a n ila m id e could be io n is e d i n t o th e t i s s u e s f o r some l i t t l e d is t a n c e around a l e s i o n , t h i s com bination w ith th e body f l u i d s would b e s e c u r e d .

The n e c e s s i t y o f

ta k in g i t by th e mouth, and th e t o x i c e f f e c t s o f which we were a t t h a t time warned, and r a t h e r tim orous o f m eetin g, would be av o id ed . S ix y e a rs ago, 1 was a p p o in te d h o n o rary o f f i c e r in charge o f the P h y sio th e ra p y Department o f th e Royal L a n c a s te r I n fir m a ry .

I t was th e o p p o r t u n i t i e s

h e re o f f e r e d which made me d e c id e to u nd ertak e an i n v e s t i g a t i o n on c l i n i c a l l i n e s to f i n d o u t : 1.

I f P r o n t o s i l i s s u i t a b l e to a c t as an e l e c t r o l y t e 2.

2.

I f so , i s l o c a l a p p l i c a t i o n o f P r o n t o s i l e f f e c t i v e by i o n i z a t i o n in tb e tr e a tm e n t o f l e s i o n s con tam inated by germ s, th e growth o f which i s n o rm ally i n h i b i t e d by, o r may r e a s o n a b ly b e ex pected to be s u s c e p t i b l e t o , th e sulphonam ide drugs?

3.

Which type o f l e s i o n i s a . E s p e c i a l l y b e n e f i t e d , and where such tr e a tm e n t sh o uld be i n s t i t u t e d , w ith good hopes o f s u c c e s s , as th e method o f e l e c t i o n . b . Which ty p e i s h e lp e d in a u s e f u l d eg ree in th e m a jo r ity o f c a s e s and th e tr e a tm e n t r a n k as one w orthy o f t r i a l , w ith f a i r hopes o f s u c c e s s . c . Which type i s n o t h e lp e d a t a l l , o r i f s o , o n ly on r a r e o c c a s io n s , and th e tr e a tm e n t o n ly worthy o f t r i a l when o t h e r methods f a i l .

4.

I f th e number o f c a s e s was too s m a ll to f o rm u la te any c o n c lu s io n s , co uld th e s e c a s e s b e s i f t e d o u t, and a p o i n t e r g a in e d , g iv in g a d i r e c t i o n in which to c a r r y o u t f u r t h e r i nve s t i g a t io n • 3.

.

L a t e r when X le a r n e d t h a t su lp h a n ila m id e was b e in g a p p lie d l o c a l l y 5.

I s su lp h a n ila m id e e f f e c t i v e by i o n i z a t i o n

when l o c a l o r o r a l a p p l i c a t i o n f a i l ? An a c u te i n f e c t i o n may h e a i sp o n ta n e o u sly o r be cured by sim p le methods o f tr e a tm e n t.

I t would, t h e r e f o r e ,

be no u s e f u l t e s t o f th e id e a o f i o n i s i n g s u lp h a n ila m id e , t o apply i t in any b u t a c h ro n ic and sim ple ca se , where no p o s s i b l e harm could r e s u l t from such an exp erim ent. In March 1940, such a case p r e s e n te d i t s e l f a t th e P h y s io - th e r a p y Departm ent, a case which was sim ple Ca p a ro n y c h ia ), had been in e x is te n c e f o r f o u r months, and which th e u su a l methods o f tr e a tm e n t had so f a r f a i l e d to c u re .

!0ais case i s r e p o r te d l a t e r and was

a ls o mentioned in the a r t i c l e in th e B.M .J. 6 /7 /4 0 . The method was p e rs e v e re d w ith , and having g iv en h o p e fu l r e s u l t s in a few c a s e s , se a rc h was then made i n t o th e l i t e r a t u r e on l o c a l tr e a tm e n t with th e drug. A ccess to the l i t e r a t u r e has n o t been easy. F a c i l i t i e s in L a n c a s te r are n o n - e x i s t e n t and were se cu red by correspondence w ith th e B.M.A. and o t h e r medical l i b r a r i e s - n o t a very s a t i s f a c t o r y method o f t r a c i n g 4.

r e f e r e n c e s and c ro s s r e f e r e n c e s .

With th e e x c ep tio n o f

O to la ry n g o lo g ic a l j o u r n a l s , which co uld n o t be o b ta in e d , a l l r e p o r t s , so f a r as can be t r a c e d , up to A p r i l 1941, on l o c a l tr e a tm e n t w ith the sulphanamide d ru g s, a r e in c lu d e d in t h i s essay . By the time th e f i r s t case h e r e in r e p o r te d was t r e a t e d , abo ut f i f t e e n r e p o r t s have been tr a c e d in B r i t i s h , American, French and German j o u r n a l s as h aving been p u b lis h e d b e f o r e t h a t d a t e .

Kb r e p o r t s have been found

on i o n i a a t i o n w ith any o f th e sulphonam ide group o f drugs. io n i z a t i o n se cu res a p e n e t r a t i o n i n t o th e t i s s u e s much s u p e r i o r to t h a t o b ta in a b l e by e x t e r n a l l y a p p lie d powder, l o t i o n o r o in tm e n t.

ihe p r i n c i p l e in v o lv ed

in u sin g an e l e c t r o l y t e in i o n i z a t i o n which i s s e l e c t i v e i n a c tio n a g a i n s t c e r t a i n germs o n ly , i s e n t i r e l y new. P r e v io u s ly th e e l e c t r o l y t e was used as an a n t i s e p t i c i s used - in a g e n e r a l way a s d i s t i n c t from a s p e c i f i c p u rp o se.

Dr. A. R. F r i e l , a p u p il o f Leduc, and a u th o r

o f s e v e r a l books and a r t i c l e s on i o n i z a t i o n , in a p e r s o n a l communication, gave i t as h i s o p in io n t h a t t h i s new id e a may be very im p o rta n t. 5.

The q u e s tio n has been a s k e d , why d id I use F r o n t o s i l ? The s o l e reaso n was t h a t in th e d is p e n s a r y t h e r e was a l a r g e su p p ly in s to c k which was n o t b e in g u se d 9 having been p assed by in f a v o u r o f p r e p a r a t i o n s n o t c o n ta in in g d ye.

Also i t was em inen tly s u i t a b l e - in aqueous s o l u t i o n ,

in s t e r i l e ampoules, and o f a handy c o n c e n t r a t i o n . There seems no reaso n why a B r i t i s h p r e p a r a t io n sh o u ld n o t be used.

Having commenced th e i n v e s t i g a t i o n w ith

P r o n t o s i l i t was d ecided to c o n tin u e u sin g t h i s drug, and l a t e r compare th e e f f e c t i v e n e s s o f t h i s one p r e p a r a t i o n w ith t h a t o f o th e r m a n u fa c tu re rs. Many o th e r s have w r i t t e n to me w ith th e i n t e n t i o n o f t r y i n g t h i s method o f tr e a tm e n t .

S ix months l a t e r ,

a f t e r c i r c u l a r i s i n g th e s e e n q u i r e r s , th e m a jo r i ty , on a c c o u n t o f th e w ar, have been unable to g iv e i t a t r i a l , o t h e r s have n o t been t r a c e d and o n ly one has r e p o r te d a case.

The r e p o r t from t h i s surgeon i s inclu ded in th e

s e c t i o n g iv in g d e t a i l s o f th e c a s e s t r e a t e d . In t h i s t h e s i s , t h a t which fo llo w s I s a rran g ed a f t e r th is p la n .

F i r s t a resume o f th e h i s t o r y , p r i n c i p l e s ,

i n v e s t i g a t i o n s , and r e s u l t s secu red by i n v e s t i g a t o r s o f i o n i z a t i o n i s g iv e n - Next th e s u b j e c t o f sulphonam ide 6.

drugs i s t r e a t e d on s i m i l a r l i n e s .

The e l e c t r i c and

chem ical s u b j e c t s a r e then combined, f i r s t in ex p e rim en ts th e n as ex e m p lifie d by a c t u a l c a s e s . The experim ents and c a s e s a r e d is c u s s e d i n a f u r t h e r s e c t i o n and l a s t l y fo llo w s a summary. The p l a n , t h e r e f o r e , may be i l l u s t r a t e d as f o llo w s .

In tro d u c tio n Io n iz a tio n

Sulphom&mides

Experiments

-

Cases

D ise u ssio Summary

R eferen ces

I O N I Z A T I O N

IONIZATION I t would be im p o s sib le f o r me to a tte m p t a com prehensive review o f what has been w r i t t e n on such a lo n g and w e ll e s t a b l i s h e d method o f tr e a tm e n t as Io n iz a tio n .

A r e p r e s e n t a t i v e sample o f th e i n v e s t i g a t o r s

and o f the d is e a s e s th e y t r e a t e d , s u f f i c i e n t to prove th e r a t i o n a l n e s s and e f f e c t i v e n e s s o f th e method, i s a l l t h a t w i l l be atte m p te d in the fo llo w in g n o te s . H. Lewis Jo nes Cl) d e f in e s I o n i z a t i o n as "a method o f tr e a tm e n t whereby e l e c t r i c c u r r e n t s a r e used to s e t i n motion in a d e f i n i t e d i r e c t i o n th e c o n s t i t u e n t s o f an e l e c t r o l y t e . ”

F r i e l (2) d e f in e s i t a s ”th e

i n t r o d u c t i o n i n t o th e t i s s u e s o f p a r t i c l e s c a l l e d io n s by e l e c t r i c c u r r e n t , and th e exchange o f io n s w ith in th e t i s s u e s . ”

A com bination o f th e two d e f i n i t i o n s

would p ro b a b ly d e s c r ib e th e p ro c e s s more e f f e c t i v e l y . In b r i e f , i t i s a means o f d r iv in g some drug i n t o th e t i s s u e s o f th e body by a c o n s ta n t o r g a lv a n ic c u r r e n t , th e b a s ic r a d i c l e e n t e r in g th e body under th e p o s i t i v e p o le and th e a c id r a d i c l e under the n e g a tiv e p o le

To a p p ly t h e p r i n c i p l e o f i o n i z a t i o n to th e body, th e commonest method i s to m oisten a pad o f l i n t w ith t h e e l e c t r o l y t e and a p p ly t h i s pad (which i s j u s t l a r g e enough to cov er th e a r e a to be t r e a t e d ) to the r e q u ir e d p a r t o f th e body.

A nother pad m oistened w ith a

co n d u c tin g s o l u t i o n , such as sodium c h l o r i d e , i s a p p l ie d to any o th e r s u i t a b l e p a r t o f th e p a t i e n t . As th e s e pads a r e f ix e d to e l e c t r o d e s , th e chosen e l e c t r o l y t e undergoes d i s s o c i a t i o n when th e c u r r e n t o f a few m illeam peres i s g r a d u a l l y sw itch ed on, and so th e d e s ir e d p a r t o f the e l e c t r o l y t e i s conducted i n t o th e body.

This c o n tin u e s as lon g as the c u r r e n t i s

ru n ning and th e lo n g e r t h i s i s c a r r i e d o u t , th e d eep er i n t o th e t i s s u e s i s the drug d r iv e n . I n s t e a d , t h e r e f o r e , o f s c a t t e r i n g a drug th ro u g h o u t th e whole body by o r a l a d m in s tr a tio n t o t r e a t one l o c a l i s e d a r e a , a p u r e ly l o c a l a c tio n ta k e s p l a c e . Drugs can th e r e f o r e be in tro d u c e d i n t o l o c a l a r e a s t o which th e y could n o t n o rm ally g a in a c c e s s , o r , i f s o , o nly in extrem ely minute i n e f f e c t i v e d i l u t i o n s Cthe sulphonamide drugs a r e in a c a te g o ry by them selves and t h i s p o i n t i s d is c u s s e d l a t e r ) . 9.

Wounds can be

t r e a t e d to a depth n o t o th e rw ise o b ta in a b l e , and in g r e a t e r c o n c e n tr a tio n than th e blood cou ld c a r r y to such a s i t e .

t o x i c a c t i o n i s t h e r e f o r e av oided , a

c o n d itio n always d e s i r e d , b u t e s p e c i a l l y i s t h i s so in a weak, d e b i l i t a t e d p a t i e n t or c h ro n ic c a s e .

The l o c a l

t i s s u e s and th e b o d y 's d e fe n s iv e mechanism a r e s t i m u l a t e d . I n c r e a s e d v a s c u l a r i t y a t th e d is e a s e d p a r t , c o n c e n tr a tio n o f l o c a l a c tio n and, w ith P r o n t o s i l a b a c t e r i o s t a t i c e f f e c t , a r e a l l g a in e d .

A lso, t h e r e i s a b re a k through

th e a t t a c k i n g ran ks o f d is e a s e and a p r o t e c t i v e b a r r i e r o f P r o n t o s i l and s tr e n g th e n e d , s t i m u l a t e d , defen ding t i s s u e s formed ahead o f th e a t t a c k e r s , as i t w ere. The io n s o f a drug a r e s u b s t i t u t e d f o r th e io n s o f th e t i s s u e s , and become f ix e d in th e t i s s u e s .

By sim ple

l o c a l a p p l i c a t i o n , a drug does n o t become so f ix e d , b u t i s carx'ied o f f by the blood and lymph stre a m s .

The

d rin k in g o f w ell w a te rs , says L u f f (3 ), would n o t have s u r v iv e d c e n t u r i e s , i f n o t e f f i c a c i o u s and i s c e r t a i n l y n o t due to th e chem ical com position p e r s e , f o r th e s e can be m anufactured c h e m ic a lly .

The e f f i c a c y ©f

n a t u r a l m in e ra ls depends upon th e d i s s o c i a t e d io n s o f th e c o n s t i t u e n t s .

So to o , w ith i o n i z a t i o n as compared 10.

w ith

d i r e c t l o c a l m e d ic a tio n . The f a c t t h a t th e human body i s an e l e c t r o l y t e and

t h a t drugs could be in tro d u c e d through th e unbroken s k in was, a p p a r e n tly , f i r s t re c o g n ise d by P i r v a l i , o f Venice in 1747.

N ea rly one hundred y e a rs e la p se d

b e f o r e s i m i l a r experim ents were c a r r i e d o u t by F a b re P a l a p r a t who a tte m p te d m ed icatio n by io n i z a t i o n w ith io d in e in 1833.

Faraday had been i n v e s t i g a t i n g th e

phenomena o f e l e c t r o - c h e m i s t r y a b o u t t h i s tim e and in Ja n u a ry 1834 p u b lis h e d f o r d e s c r ib in g i t .

th e te rm in o lo g y he had d ev ised

I t was then t h a t e l e c t r o l y t e ,

e l e c t r o l y z e , e l e c t r o d e , c a th o d e , anode, ion e t c . were used f o r th e f i r s t tim e. In a Navy Medical R epo rt from H.M.S. Modeste In 1853 T. Spencer Wells ( 4 ), th e famous su rg eo n , gave d e t a i l s o f tre a tm e n ts he had c a r r i e d o u t a s a s h i p 's surgeon s in c e 1847, on u lc e r s and g r a n u l a t i n g s u r f a c e s u sin g a g a lv a n ic c u r r e n t .

rtThe r e s u l t s have been most

rem arkably b e n e f i c i a l 1* he q u o te s .

*1 have o f te n been

a s to n is h e d a t the change e f f e c t e d in tw e n ty -fo u r ho urs in th e c o n d itio n o f u l c e r s .

At one d r e s s in g th ey a r e

seen to b e deep, c u p - l i k e e x c a v a tio n s . 11

At th e n e x t

th e g r a n u l a t i o n s have n e a r l y reach ed th e s u r f a c e . fl A nother remark i s w orthy o f b e in g quoted - *X have made numerous t r i a l s o f th e method o f Bays tow and S c o t t , o f w a te r and dry d r e s s i n g s , o f e l a s t i c bandages and v a rio u s o th e r ac ce p te d modes o f t r e a t i n g u l c e r s , and have found no means so ca p ab le o f u n ifo rm ly p ro d u cin g a r a p i d growth o f h e a l t h y g r a n u l a t i o n as g alv an ism . n In 1853 a l s o , H e s s e n s te in , and i n 1859 R ic h a rd so n , fo llo w ed in

F a b r e - P a la p r a ts f o o t s t e p s , b u t un sy m p ath etic

c r i t i c i s m , i n c r e d u l i t y and marked o p p o s itio n l e d to th e abandonment o f th e method.

Even Edison (5 ),

renowned i n v e s t i g a t o r as he was, aro u sed no en thu siasm i n 1890 when he p u b lis h e d a most i n t e r e s t i n g r e p o r t . Not a p h y s ic ia n , he was s t r u c k by th e f a c t t h a t l i t h i u m s a l t s were taken i n t e r n a l l y to d is s o lv e g o u ty c o n c r e tio n s and s e c u r e t h e i r e x c r e tio n .

The d i f f i c u l t y

o f s e c u r in g th e a b s o rp tio n i n t o th e system o f l i t h i u m m ight p erh ap s have "more r a p id s u c c e s s i f th e a p p l i c a t i o n were made e x t e r n a l l y , employing th e w e ll known p r i n c i p l e o f e l e c t r i c a l endosmose to c a r r y th e l i t h i u m i n t o th e tissu e s" .

This method he hoped would b r in g th e

l i t h i u m more d i r e c t l y i n t o th e neighbourhood o f t h e 12.

c o n c r e tio n s .

A f t e r ex p e rim en ts, he used 2% l i t h i u m

c h l o r id e a t 4 m ille a m p e re s , under th e p o s i t i v e p o le , f o r two hours d a i l y , f o r one week.

In th e u rin e

2 .4 3 gms. o f u r ic a c id were e x c re te d and 3 c c s . o f c o n c re tio n removed from one f i n g e r o f an o ld man o f 73 y e a r s . a m e lio ra te d

The man*s g e n e r a l c o n d itio n was e v e n tu a l ly and he was a b le to walk a b o u t. (So f a r I

have n o t t r i e d t h i s method.

Cases o f g o u t , in my own

p r a c t i c e , have, so f a r , responded to tr e a tm e n t a t home and no o th e r cases have appeared a t th e P h y s io th e ra p y D epartm ent.) Prom th e band o f w orkers, M arg aret A. Cleaves (6) must n o t be o m itte d .

She in v e n ted a s p e c i a l speculum

to f i t t i g h t l y a g a i n s t th e v ulvae and pumped in copper s u lp h a te s o lu t io n to b a llo o n up th e v a g in a l p assag e and so s e c u re good c o n t a c t th ro u g h o u t.

By

means o f the c o n s ta n t c u r r e n t she secured e f f e c t i v e tr e a tm e n t in cases o f u t e r i n e c a t a r r h , g on orrh oea, o v a r i t i s , v a g i n i t i s , p r u r i t u s vulvae e t c . ( P r u r i t u s I have t r e a t e d , and t h a t s u c c e s s f u l l y , b u t s u b j e c t to r e l a p s e s .

The same a p p l ie s to v a g i n i t i s b u t

t h i s i s now only t r e a t e d by io n i z a t i o n when S to v a r s o l 13.

o r Devegan s h o r t wave o r u l t r a - v i o l e t r a y tr e a tm e n t fa lls .

O v a r i t i s I have n ev e r t r e a t e d by i o n i z a t i o n

n o r gonorrho ea) The fo re g o in g were among t h e p r i n c i p a l p r o s p e c to r s in th e f i e l d o f i o n i z a t i o n .

They walked a lo n e t r a i l .

The work o f Spencer W ells i n th e s u r g i c a l f i e l d i s to d a y h e ld in r e v e r e n c e .

His work in p h y s ic a l m edicine

i n th e cu re o f u l c e r s , and about which he was e u l o g i s t i c , a s th e q u o ta tio n o f h i s a c t u a l words shows, i s f o r g o t t e n and unheard o f by th e g r e a t m a jo r i ty . The s p o ra d ic i n t e r e s t in i o n i z a t i o n was co m p letely a l t e r e d a t th e b e g in n in g o f th e p r e s e n t c e n tu ry by l e w is Jo nes in t h i s c o u n try , and S tephane Leduc in P ra n c e .

They p la ced i t upon a sound s c i e n t i f i c b a s i s ,

and f ir m ly e s ta b li s h e d i o n i z a t i o n as an e s t a b l i s h e d method in th e tr e a tm e n t o f many d i s e a s e s .

The a b s o rp tio n

o f drugs by e l e c t r o l y s i s was b e lie v e d to be i n s i g n i f i c a n t , and due to sk in a b s o rp tio n o n ly .

Leduc (7) a p p lie d a

pad moistened w ith s tr y c h n in e s u lp h a te to a

ra b b it

w ith o u t a f f e c t i n g i t a t a l l , even when l e f t i n d e f i n i t e l y . When th e g a lv a n ic c u r r e n t was a p p l ie d , however, th e r a b b i t dropped dead.

Io d in e can be found in s a l i v a and

u r in e a b o u t a q u a r t e r o f an h ou r a f t e r i o n i z a t i o n w ith t h a t s u b s ta n c e .

A p a rt from co n v in cin g th e world t h a t

io n s e n te r e d th e body in an a p p r e c ia b l e d eg ree , much im p o rta n t work in th e e x p e rim e n ta l and p r a c t i c a l f i e l d s was c a r r i e d o u t by th e s e two o u ts ta n d in g men th e v e l o c i t y o f p e n e t r a t i o n , depth o f p e n e t r a t i o n , q u a n t i t y d e p o s ite d , the methods o f a p p l i c a t i o n o f d ru g s, th e d is e a s e s b e n e f i t e d , th e p o le s to use, s tr e n g t h o f c u r r e n t , d u r a tio n o f tr e a tm e n t, in b r i e f th e pharm acopoeia, as i t were o f i o n i z a t i o n .

S uccessful

r e s u l t s were o b ta in e d by Leduc (7) in th e tr e a tm e n t o f ankylosed j o i n t s , g la n d s , a b s c e s s e s , n e u r a l g i a , w a r ts , f i b r o s i t i s , a l o p e c i a e t c . (Since Leduc*s tim e th e armamentarium o f the p h y s i o t h e r a p i s t has been g r e a t l y implemented w ith very more e f f i c i e n t m achines.

Thus

f o r ankylosed j o i n t s 1 have found sho rt-w av e o r i n f r a ­ r e d ra y tr e a tm e n t more e f f e c t i v e in some ca se s than io n iz a tio n .

For a d e n i t i s , i o n i z a t i o n i s r a r e l y used,

u l t r a v i o l e t r a y tr e a tm e n t b ein g most e f f i c a c i o u s and i s a lm o st s p e c i f i c .

A bscesses did respond to zin c

i o n i z a t i o n , b u t P r o n t o s i l , in my opinion r e p la c e s zin c as th e e l e c t r o l y t e o f cho ice and t h a t , in a very

decided manner.

N eu ralg ias respond to i o n i z a t i o n b u t

e q u a lly good r e s u l t s a r e o b ta in e d now from i n f r a - r e d r a y and sometimes sho rt-w av e th e ra p y , as does f i b r o s i t i s . i o n i z a t i o n i s s t i l l u s e f u l in w a rt e r a d i c a t i o n ) . Jo n es (8) covered th e same f i e l d a s Leduc b u t had happy r e s u l t s in th e tr e a tm e n t o f r o d e n t u l c e r s w ith z i n c , and was i n t e r e s t e d in experim ents on lu p u s .

U n til

combined w ith radium th e ra p y , by Doyle ( 9 ) , r o d e n t u lc e r s r e c u r r e d w ith in s i x months in 25% o f c a s e s , perm anent cure was a t t a i n e d in a l l c a s e s by the combined method.

( I have n ever t r e a t e d a ro d e n t u l c e r . )

P r i e l A.R. (10) s p e c i a l i s e d in the tr e a tm e n t o f e a r s and noses w ith o u ts ta n d in g s u c c e s s . (E a rs, I have found d i f f i c u l t to cure w ith zinc i o n i z a t i o n .

They

e i t h e r were cured in th r e e o r fo u r tr e a tm e n ts o r n o t a t a l l , more o f te n , n o t .

P ro n to s il io n iz a tio n is

somewhat more e f f e c t i v e in o t i t i s media.

25inc i o n i z a t i o n

in Hay F ever i s very e f f e c t i v e b u t P r o n t o s i l i s b e t t e r than zinc in n a s a l c a t a r r h tr e a tm e n t ) . A case o f c o l i t i s s e n t to him by A rth b u th n o t Lane was cured by Webb (1 1), who io n is e d th e colon w ith 0.1% s i l v e r n i t r a t e , th u s g a in in g th e a b s o rp tio n o f the 16.

s i l v e r i n to the p ro to p la sm o f th e c e l l s . T a y le r, H .P. (12) had good r e s u l t s in cases o f r o d e n t u l c e r s , lu p u s , d i p h t h e r i a and n e u r i t i s .

(Lupus has always

been t r e a t e d by me w ith u l t r a - v i o l e t r a y tr e a tm e n t, th e Kromayar lamp b e in g e s p e c i a l l y e f f e c t i v e .

I have had no

f a i l u r e s w ith a f a i r l y l a r g e number o f ca ses a lth o u g h t r e a t m e n t has had to be p ro lo n g e d .

The r e s u l t s have been

a e s t h e t i c a l l y so good, I have seen no reaso n t o change in view o f the r e p o r t s o f o th e r tr e a t m e n t s .

Only one c a se o f

d i p h t h e r i a has been t r e a t e d by me and t h a t was e x p e rim e n ta lly cured w ith P r o n t o s i l .

Normally D ip h th e ria c a s e s a r e

b e t t e r k e p t o u ts id e a g e n e r a l h o s p i t a l . ) F i n z i , N.S. (13) cured many c a se s o f ch ro n ic v a r ic o s e and s y p h i l i t i c u lc e r s w ith z in c . ( S y p h i l i t i c u l c e r s I have n e v e r t r e a t e d b u t w ith v a r ic o s e u l c e r s I have had good r e s u l t s w ith zin c as w ith P r o n t o s i l i o n i z a t i o n ) . Bokenham, T . J . (14) r e p o r te d 21 ca ses o f haem orrhoids cu red a f t e r o n ly a few tre a tm e n ts by z in c i o n i z a t i o n ( I have n o t been so s u c c e s s f u l .

R e s u lts have v a r i e d ) .

F o r t h r e e y e a rs R id d e ll (15) had no f a i l u r e s in th e tr e a tm e n t o f f i f t y - t h r e e cases o f ringworm, u sin g a 1% s o l u t i o n o f m ercuric c h l o r i d e , o r 1% w a te ry s o lu t io n o f io d in e . 17.

T ay lor and MacKenna (16) cured lu p u s , when X -ray and u l t r a - v i o l e t r a y tr e a tm e n t f a i l e d *

They improved on

o r d in a r y zin c i o n i z a t i o n , by b r i s k l y ru b b in g th e i l l developed e p ith e liu m w ith l i q u o r p o t a s s a e , and then a p p ly in g th e u su a l i o n i z a t i o n tr e a tm e n t w ith z i n c .

This method

allow ed tr e a tm e n t o f a c t i v e f o c i in th e d e p th s, and gave a much s u p e r i o r s c a r . Most o f th e d is e a s e s b e n e f i t e d by i o n i z a t i o n have been mentioned above.

The r e p o r t s quoted, however, a re only

r e p r e s e n t a t i v e o f a v a s t number

in th e l i t e r a t u r e .

The names

s e l e c t e d have been th o se who have f i r s t i n v e s t i g a t e d a p a r t i c u l a r d is e a s e , o r developed a new method in tr e a tm e n t . S u f f i c i e n t d a ta has been mentioned to prove th e e f f i c a c y o f io n iz a tio n .

F u r th e r q u o ta tio n s would seem to be

re d u n d a n t, f o r I o n i z a t i o n w i l l be used d a i l y in ev ery h o s p i t a l p o s s e s s in g a p h y s io - th e r a p y d ep a rtm en t.

As L.D .

B a ile y (17) most s u c c i n t l y says nA few p io n e e r s have n o t o n ly a tte m p te d b u t have succeeded in p la c in g t h i s s c ie n c e on a r e p u ta b le b a s i s , i f n o t on a se c u re f o u n d a tio n .

T hat

th e fo u n d a tio n i s in s e c u r e i s n o t th e f a u l t o f th e p io n e e r s th e m selv es, b u t due to th e f a c t t h a t th e p eo p les o f th e c o u n t r i e s which th e y have invaded ( i f such a term i s 18

a p p l ic a b le ) have been slow to a p p r e c i a t e th e b e n e f i t s o f th e methods w ith which, u n t i l r e c e n t l y , th e y have been u n ac q u ain ted , though th e m a jo r ity make use o f th e m .rtTimeo Danaos e t dona f e r e n t e s , ”

C H E M O T H E R A P Y .

CaBMDTHEBAPX

S ulp h an ilam id e was f i r s t mentioned in 1908 by Gelmo (18) a German c h e m ist s tu d y in g azo d y es.

E ise n b e rg (19)

f i v e y e a r s l a t e r , su g g e sted th e use o f su lp h a n ila m id e i n M edicine, when he d is c o v e re d th e b a c t e r i c d a l powers i t p o sse sse d in v i t r o .

Two o t h e r German c h e m ists,

M ietsch and K la r e r (20) s y n th e s iz e d sulphonamide - c h r y s o d in e , p a te n te d i t , c a l l i n g i t " P r o n t o s i l . "

Domagk (21)

working w ith th e two l a s t named c h e m is ts , d isc o v e re d th e s p e c i f i c power o f P r o n t o s i l to overcome s t r e p t o c o c c a l s e p tic a e m ia in mice. Becker (2 2), a f f ir m s B ayer, was th e f i r s t to use P r o n t o s i l as an e x t e r n a l a p p l i c a t i o n .

He used i t in

a v a r i e t y o f c a s e s , c a r b u n c le s , a b s c e s s e s , tr a u m a tic u l c e r a t i o n and in sk in d i s e a s e s , claim in g good r e s u l t s . P u rd ie and Fry (23) in th e same y e a r , 1937, were th e f i r s t in t h i s c o u n try to ap p ly sulpham ilam ide l o c a l l y to a wound.

This was a c h ro n ic wound i n f e c t e d by

s tr e p to c o c c u s Baem olyticus fo llo w in g p u e r p e r a l s e p s is t h r e e y e a rs p r e v io u s l y .

By a d m in is te r in g p-am inobenztne-

sulphonamide o r a l l y and i r r i g a t i n g th e wound w ith a 1% 20

s o l u t i o n o f th e drug, th e wounds were s t e r i l i s e d in t h r e e weeks, and complete h e a lin g r e s u l t e d in s i x .

V arious

o p e r a t iv e p ro ced u res and u l t r a - v i o l e t ra y tr e a tm e n t had f a i l e d to g iv e any r e l i e f .

They b e lie v e d th e r e s u l t

was n o t a spontaneous c u re b u t to be due to th e su lp h a n ila m id e powder in s o l u t i o n . About th e same tim e, i t was su g g e sted by S i g e l (24) t h a t P r o n t o s i l might be u s e f u l as a p r o p h y la c tic in th e tr e a tm e n t o f i n f e c t e d , o r d i r t y wounds, and o b ta in e d p rim ary h e a lin g when he gave i t from th e s t a r t i n some h e a v ily contam inated c a s e s . J a e g e r (25) cured c e r t a i n sk in d is e a s e s u sin g P r o n t o s i l l o c a l l y , and T i l i n g (26) t r e a t e d c a se s o f s t r e p t o c o c c a l empyema w ith i n t r a - p l e u r a l i n j e c t i o n s o f th e same drug. Colebrook and &enny (27) i n j e c t e d P r o n t o s i l in to th e p erito n eu m of mice and fo u r days l a t e r , a c u l t u r e o f stre p to c o c c i.

There was no to x ic e f f e c t , and o u t o f

tw elve anim als so t r e a t e d , two died w ith in t h r e e days. In u n tr e a te d c o n t r o l s , however, n in e d ie d . A ccording to B u t t l e , Gray and Stephenson (28) when t e s t i n g v a r i a t i o n s o f sulphonamide, the drug was a c t i v e 21.

a g a i n s t s t r e p t o c o c c i , gave some p r o t e c t i o n a g a i n s t m eningococci, b u t n o t a g a i n s t s ta p h y lo c o c c i, o r pneumococci.

Je n sen (35) and M ilian (6 3 ), to mention

b u t two names, found t h a t su lp h a n ila m id e was e f f e c t i v e a g a i n s t s ta p h y lo c o c c i.

(In my ex p erim en ts P r o n t o s i l d id

on every occasion i n h i b i t th e growth o f sta p h y lo co c cu s a u re u s and f iv e ca se s o u t o f s i x were cured when s ta p h y lo c o c c i alone were found and the s i x t h was g r e a t l y improved.

Many c a se s o f mixed i n f e c t i o n - s t r e p t o c o c c i ,

s ta p h y lo c o c c i and pneumococci - r e a c te d f a v o u r a b ly and were c u re d .

S ulph an ilam id e t h e r e f o r e , in my o p in io n ,

does i n h i b i t th e s e germs.

In my s e r i e s no m eningococcal

c a se s were m et). Good r e s u l t s a g a i n s t s t r e p t o c o c c i , b o th in experim ents on mice and again in man, were r e p o r te d by Long and B l i s s (29) S in c la ir

(30), a Canadian d e n t i s t , t r i e d th e e f f e c t

o f su lp h a n ila m id e l o c a l l y in r o o t s o c k e ts o f i n f e c t e d t e e t h and in compound f r a c t u r e s o f th e jaw , s e c u r in g more prompt h e a lin g a s a r e s u l t . An o in tm en t c o n ta in in g P r o n t o s i l and a p p lie d l o c a l l y i n f u r u n c u lo s is and im petigo c le a r e d th e s e c o n d itio n s 22.

up - Merz (31)* In 1937, Bohlman (32) su g g e ste d o r a l a d m i n i s t r a t i o n f o r c ru s h in g i n j u r i e s and compound f r a c t u r e s , and l a t e r t r i e d l o c a l a p p l i c a t i o n s w ith s u c c e s s .

He c i t e s

Mellon and Co-Workers (33) as r e p o r t i n g t h a t su lp h a n ila m id e does n o t n e u t r a l i z e t o x i n s , b u t t h a t i t in c r e a s e s th e m o b il iz a tio n s o f p h a g o c y tic c e l i s a t th e s i t e o f a

i n f e c t i o n , and h a s Ab a c t e r i o s t a t i c e f f e c t .

(With r e g a rd

to th e s ta te m e n t t h a t s u lp h a n ila m id e does n o t n e u t r a l i z e t o x i n s , my p a t i e n t s , a f t e r tr e a tm e n t , c o n s i s t e n t l y s t a t e d th e y f e l t much b e t t e r th e fo llo w in g day.

This could

n o t have been e n t i r e l y due to th e c le a n s in g o f th e wound and co nsequ en t re d u c tio n in a b s o rp tio n o f t o x i n s . to o r a p i d .

I t was

I t may have been p s y c h o lo g ic a l to some

e x t e n t , b u t t h i s would n o t occu r in every c a s e .

Case 35

(See Case R eports) died o f toxaem ia, a f t e r tr e a tm e n t was sto p p e d , b u t h i s to x ic c o n d itio n improved so much w ith p r o n t o s i l i o n i z a t i o n t h a t i t was v i s i b l e , even to h is re la tiv e s.

O ral a d m in is t r a tio n may n o t , v i s i b l y n o r

o b j e c t i v e l y , appear to n e u t r a l i z e to x in s on ac co u n t o f i t s own d e p re s s in g e f f e c t , b u t by i o n i z a t i o n , I am o f o p in io n t h a t i t does, to some e x t e n t , n e u t r a l i s e to x i n s . The r e p o r t o f my experim ents show th e b a c t e r i o s t a t i c 23

e f f e c t to be most d e f i n i t e and p ow erfu l) S in ce w r i t i n g t b i s , th e p a p e r by Osgood and Brownlee (34) bas been p e ru s e d .

In t b i s p a p e r i t i s s t a t e d t b a t

t h e major a c t i o n o f su lp h a n ila m id e on th e b ae m o ly tic s tr e p to c o c c u s seems to be n e u t r a l i z a t i o n o f th e t o x i n s . I t d e c re a s e s th e r a t e o f c e l l d i v i s i o n , and does n o t k i l l th e s e organism s d i r e c t l y .

I t allo w s th e b a c t e r i c i d a l

p r o p e r t i e s o f th e human serum and p h a g o c y to s is o f le u c o c y te s to k i l l the germs.

There i s no d i r e c t e f f e c t on

p h a g o c y to s is , th e y b e l i e v e .

A case i s quoted by M ellon,

i n which c u l t u r e s r e v e a le d a p u re growth o f s tr e p to c o c c u s h a e m o ly tic u s, b u t a f t e r tr e a tm e n t y ie ld e d a growth o f d ip h th e r o id s and comment i s made on th e r e v e r s i b i l i t y o f d ip h e ro id s to s t r e p t o c o c c i (Did t h i s o cc u r in Case No. 12 h e r e in r e p o r te d ? ) The i n t e r e s t in su lp h a n ila m id e and th e r e s e a r c h ta k in g p la c e from 1938 onwards, may be lik e n e d to a sp earh ead - b ro ad enin g w id e ly , th e f u r t h e r we go from th e p o i n t o f a t t a c k .

I t becomes i n c r e a s i n g l y d i f f i c u l t

to p la c e each worker in c h ro n o lo g ic a l o r d e r a c c o rd in g to h i s due, and a t th e same time n o t be l e f t w ith a jumble o f c h e m istry and p r a c t i c a l ex p e rim e n ts. 24.

As th e p a p e r

d e a ls w ith l o c a l a p p l i c a t i o n , th e r e s e a r c h d e a lin g w ith o r a l a d m i n i s t r a t i o n o f the drug has been o m itte d , e x c e p t so f a r as i t may a f f e c t l o c a l l e s i o n s v i a th e g e n e r a l sy stem ic r o u t e . In *Becent Advances in Chemotherapy*1 (1939), F in d la y (35)

s t a t e s t h a t su lp h a n ila m id e , when g iv e n o r a l l y o r

s u b c u ta n e o u sly , becomes w id ely and u n ifo rm ly d i s t r i b u t e d i n th e body, e x c e p t in bone and f a t , which have a s m a lle r c o n c e n tr a t io n , and l e s s in t h e plasm a, than in whole b lo o d .

I t i s found in s a l i v a , sw ea t, b i l e , p a n c r e a t i c

j u i c e , plasma e t c .

I t p a s s e s to o , in to th e amnio t i c

f l u i d and th e f o e t u s , when g iv en to p r e g n a n t r a b b i t s . In man, i t p a s s e s slo w ly in to th e c e r e b r o - s p i n a l f l u i d . (Experiments 4 and 10 w ith P r o n t o s i l gave a v i s i b l e c o n firm a tio n o f th e w idespread d i s t r i b u t i o n a f t e r i o n i z a t i o n , b u t t h i s i s f u l l y re p o r te d on l a t e r i n th e l i s t o f experim ents c a r r i e d ou t by me.) Given by mouth or in tr a m u s c u l a r l y , a c o n c e n tr a tio n o f 10 - 20 mgm p e r c e n t in the blood may be s e c u r e d . A s i n g l e dose reach es i t s maximum c o n c e n tr a tio n in th e b loo d in a few hours and i s soon b e in g e x c re te d .

The

maximum c o n c e n tr a tio n , however, can be m ain tain ed by 25.

s m a lle r c o n tin u ed o r a l a d m i n i s t r a t i o n s .

Here, however,

th e danger o f to x ic symptoms looms up, so t h a t where p o s s i b l e e x t e r n a l a p p l i c a t i o n would be the i d e a l , e s p e c i a l l y s o , in weak o r d e b i l i t a t e d p a t i e n t s .

Again, by l o c a l

a p p l i c a t i o n , th e wounds can be s a t u r a t e d w ith s u lp h a n ila m id e . A c o n c e n tr a t io n , around th e wound, approaching 800 mgm. p e r c e n t f o r some c o n s id e r a b le tim e i s secu red a s a g a i n s t th e 10-20 mgm. p e r c e n t o b ta in e d by sy ste m ic m ed icatio n — J e n s e n , Johnsrud and Nelson (36).

S tu c k , Maxwell and

Monsalvo (37) quote s i m i l a r f i g u r e s .

Jen sen a f t e r

im p la n tin g 10 gms. o f s u lp h a n ila m id e in a wound, found th e blood c o n c e n tr a tio n v a r ie d as fo llo w s 12 10 6 6

4

2 30

36

60

Hours On th e o th e r hand, the c o n c e n tr a tio n in the serum o f th e is wound i t s e l f shown in t h i s i n t e r e s t i n g t a b l e Amount p la c e d Hours s in c e L ocal c o n c e n tr a tio n Blood c o n c e n tr a tio n in wound c lo s u re in mgm. % in mgm.% 5 gm. 10 « 8 t!

24 hours 26 M 30 ff

666.5 509.0 250

2 .7 _

5 .9

Most a n t i s e p t i c s a re used in c o n c e n tr a tio n s which d e s tr o y th e le u c o c y te s b e f o r e d e s tr o y in g the b a c t e r i a Fleming (3 8 ).

S u lp h a n ila m id e , he s t a t e s , o n ly a f f e c t s

le u c o c y t i c f u n c tio n in c o n c e n tr a tio n some tw e n ty -f iv e tim es g r e a t e r than can be a t t a i n e d in th e human body, w h ile i t i n h i b i t s th e growth o f s tr e p to c o c c u s pyogenes in c o n c e n tr a tio n o n e - f i f t i e t h o f such th e r a p e u t i c c o n te n tra tio n . 1.

He summarised i t s p r o p e r t i e s as f o l l o w s :-

S ulp han ilam id e i s s p e c i f i c in a c t i o n . (With f o u r e x c e p tio n s , a l l th e cases t r e a t e d i n my i n v e s t i g a t i o n were ty p e s known to be s u s c e p t i b l e to s u lp h a n ila m id e .

No comment can

t h e r e f o r e , be made on t h i s p o in t) 2*

S u lp han ilam ide has l i t t l e a n t i b a c t e r i a l a c tio n when l a r g e numbers o f b a c t e r i a a re p r e s e n t . (This i s d e f i n i t e l y so in many o f th e c a se s r e p o r te d which f a i l e d to r e a c t to i o n i z a t i o n , e s p e c i a l l y th o se w ith e a r t r o u b l e s .

Mention

i s made o f t h i s in th e d is c u s s io n l a t e r ) . 3 . S ulphanilam ide i s i n h i b i t e d in a c t i o n in e x t r a c t s o f b a c t e r i a and in p epto ne. 27

4.

S u lp h an ilam id e i s e s s e n t i a l l y b a c t e r i o s t a t i c in a c t i o n and th e defen c es o f th e body com plete th e d e s t r u c t i o n o f th e b a c t e r i a . (A ll my ca ses confirm ed t h i s p o i n t as d id my experim ents 6, 7, 8, & 9, so f a r as the a c t i o n o f P ro n to s il Io n iz a tio n is

b a c te rio sta tic ).

On a n o th e r o c c a s io n , Fleming (39) showed t h a t serum and su lp h a n ila m id e i n h i b i t s th e growth o f s t r e p t o c o c c i , b u t b lo od and s u lp h a n ila m id e did n o t do s o .

L o cal a p p l i c a t i o n

sh o u ld th e r e f o r e on t h i s acco u n t be more e f f e c t i v e .

A g a in s t

t h i s i s th e f a c t t h a t in c o n t a c t w ith p u s, w ith a l a r g e number o f b a c t e r i a , o r w ith p e p to n e , th e a c t i o n o f s u lp h a n ila m id e was h in d e re d , o r no a c t i o n a t a l l took p la c e .

T h e o re tic a lly ,

s t a t e s P r o f . Fleming 11. . . . .s u lp h a n ila m id e sh o u ld n o t be a v ery good a n t i s e p t i c f o r wounds t h a t a re r e a l l y s e p t i c . " " I t m ight, however, be argued t h a t i t would be q u ite easy to wash o u t the pus from th e c a v i t y o f the wound, and t h a t su lp h a n ila m id e then a p p lie d l o c a l l y would su c c e e d .

We have now to c o n s id e r th e slo u g h s which

ca n n o t be washed away.

These, l i k e the p u s, e o n ta in

m u ltitu d e s o f b a c t e r i a and many broken down c e l l s which, in t h e i r b re a k in g down, have l i b e r a t e d p r o t e o l y t i c f e rm e n ts , and th e se in t h e i r tu rn have broken down

p r o t e i n s i n to p e p to n e s.

The p o s i t i o n in the sloughs i s ,

th e n , e x a c t l y as i t was in th e pus and th e r e could be no r e a s o n a b le hope o f l o c a l a p p l i c a t i o n o f su lp h a n ila m id e i n f l u e n c i n g the i n f e c t i o n . ' 1 ( I t i s most d e f i n i t e l y t r u e t h a t su lp h a n ila m id e i s n o t e f f e c t i v e in the p re s e n c e o f much p u s.

This i s ex e m p lifie d in some o f th e c a se s

o f o t i t i s media e t c . , where the c l e a n s in g by H202 was n o t s a tisfa c to ry .

On th e o t h e r hand, p a t i e n t s have been

cu red where sloughs were p r e s e n t .

My o p in io n i s t h a t

t h i s was e f f e c t e d by the P r o n t o s i l b ein g fo rc e d in behind th e slough by th e c u r r e n t , as a p i n c e r movement.

L o ca l

a p p l i c a t i o n o f a powder had proved to be u s e l e s s .

The

s u c c e s s , o r o th e rw is e , o f the i o n i z a t i o n method depends on t h e slough n o t b ein g too “j u i c y ' 1 and on th e c le a n s e d p a r t o f th e wound b ein g f re e d from l i q u i d pus a f t e r tr e a tm e n t , and a l s o to a good blood su p p ly to th e p a r t . When once t h i s fo o th o ld has been g a in e d , th e p i n c e r movement by i o n i z a t i o n i s extended by each su b se q u en t treatm ent,) • B u t t l e (40) found t h a t a g a i n s t b a c t e r i a in a p o o r medium f o r s u p p o rtin g grow th, e . g . u rin e or b lo o d , sy ste m ic tr e a tm e n t by su lp h a n ila m id e i s very e f f e c t i v e , b u t , i f in a good medium e . g . a c o l l e c t i o n o f pus o r o th e r 29

p r o d u c ts o f t i s s u e b re a k down, drugs have l i t t l e e f f e c t . S ulphanilam ide should be more e f f e c t i v e in p ro p h y lax is than in c u re .

L o c a lly su lp h a n ila m id e h as n o t y e t been used

e x te n s iv e ly . In th e e x p e rim e n ta l f i e l d Je n se n C36) f r a c t u r e d r i b s in mice and co ntam inated th e f r a c t u r e s w ith s ta p h y lo co c cu s a u r e u s .

The r e s u l t o f tr e a tm e n t was -

in c id e n c e o f i n f e c t i o n in c o n t r o l s 71%?when su lp h a n ila m id e was given s y s t e m ic a l ly 80%5and when given l o c a l l y only 20%

A few months a f t e r the p u b l i c a t i o n o f t h i s p a p e r

H i t t i 141J p r e s e n te d h i s r e p o r t on l o c a l a p p l i c a t i o n o f su lp h a n ila m id e to a r t i f i c i a l l y produced wounds.

There

was no sig n o f l o c a l i r r i t a t i o n in doses o f 1 - 2 gms. p e r k i l o and even up to 5 - 6 gms p e r k i l o , l i t t l e t o x i c i t y was shown.

The e f f e c t was much more p rolo ng ed than by

t h e mouth, though th e c o n c e n tr a tio n in the blood i t s e l f was n o t so g r e a t .

The anim als, a r t i f i c i a l l y wounded,

th e wounds in f e c te d w ith s t r e p t o c o c c i , then packed w ith su lp h a n ila m id e , su rv iv e d f o r 8 - 1 0 days, i f n o t in d e fin ite ly .

He envisaged w ith c o n fid e n c e , th e p r e v e n t a t i v e

and c u r a t i v e tr e a tm e n t o f s e p t i c co m p lic a tio n s o f war wounds, and o f l o c a l tr e a tm e n t a s a p r e c io u s a d ju n c t to o r a l ad m in istra tio n s. 30

At th e P a s t e u r I n s t i t u t e , Legroux (42) re p ro d u c e d a c o n d itio n e q u i v a l e n t in m icro b ic s t a t e to a war wound o f 12 - 30 ho urs d u r a tio n , by c ru s h in g th e A dductor Magnus Muscle in g u in e a - p ig s , im p la n tin g a sm a ll sq u are o f c l o t h i n f e c t e d w ith a c u l t u r e o f s t r e p t o c o c c i and then s u t u r i n g up th e wound.

The anim als d ied in 18 - 48 h o u rs .

When however, su lp h a n ila m id e was placed in th e wound as w e ll , d eath was d elayed th r e e days and f o r a f u r t h e r th r e e days i f the wound was opened and more powder i n s u f f l a t e d . I f , i n s t e a d o f t h i s i n s u f f l a t i o n , su lp h a n ila m id e was now g iv e n p e r o s , l i f e was prolonged f o r twelve d ays, and by removing th e fragm ent o f c l o t h and pus on th e tw e l f th day and r e p u l v e r i s i n g , th e anim al l i v e d i n d e f i n i t e l y # I n f e c t i o n once e s t a b l i s h e d was n o t stop ped by th e i n s u f f l a t i o n o f th e wound, n o r by o r a l tr e a tm e n t.

These e x p e rim e n ta l

f in d in g s were confirm ed in the French .Army, when i t was found t h a t to have su lp h a n ila m id e in wounds im m ediately was much more e f f e c t i v e than to w a it f o r debridem ent. (X have g iv en none o f my ca ses su lp h a n ila m id e by th e mouth. To have done so would o n ly have in tro d u c e d doubt as to which tr e a tm e n t was g iv in g r e s u l t .

Again, Legroux s t a t e s , t h a t

when i n f e c t i o n was e s t a b l i s h e d , i n s u f f l a t i o n o f th e wound 31.

o r o r a l tr e a tm e n t by su lp h a n ila m id e d id n o t e f f e c t th e wound. This i s tr u e o f s e v e r a l o f th e c a se s r e p o r te d l a t e r , b u t th e i n f e c t i o n was overcome by i o n i z a t i o n , even when i t had been e s t a b l i s h e d f o r some c o n s id e r a b le tim e ) . Experim enting on r a b b i t s ' b r a i n s w ith l o c a l a p p l i c a t i o n o f su lp h a n ila m id e , R u s s e ll and F a lc o n e r (43) found no a p p r e c ia b le damage to th e t i s s u e s b u t e x c e s s iv e q u a n t i t i e s gave r i s e to f o re ig n body r e a c t i o n . In experim ents c a r r i e d o u t by Hawking (44) on g u in e a p i g s , l o c a l tr e a tm e n t was more e f f e c t i v e in p r e v e n tin g i n f e c t i o n o f wounds by gas gangrene organism s than sy stem ic tr e a tm e n t . h o u rs .

The u n tr e a te d anim als died in tw e n ty -fo u r

T reated a n im a ls, f o r th e most p a r t , were saved.

R eports o f a c t u a l l o c a l tr e a tm e n ts o f human l e s i o n s a r e f a i r l y numerous and show g r e a t d i v e r s i t y o f d is e a s e s t r e a t e d , alth o u g h th e numbers o f c a se s quoted a r e n o t la rg e . G lover (45) s u c c e s s f u l l y t r e a t e d Gonococcal O phthalmia Neonatorum. In the tr e a tm e n t o f b o i l s , c a rb u n c le s , c e l l u l i t i s , i n f e c t e d wounds, ab scess c a v i t i e s , v a r ic o s e u l c e r s , b u rns and t o n s i l l i t i s , Bosse and Bosse and S c h irp (46) 32

employed s u lp h a n ila m id e in l o t i o n , powder and o in tm e n t. Some c a s e s , which responded p o o r ly to o r a l tr e a tm e n t, were cu red by l o c a l a p p l i c a t i o n .

(With th e e x c e p tio n o f

t o n s i l l i t i s , s i m i l a r typ es o f c a s e s , which f a i l e d to r e a c t to o r a l o r l o c a l tr e a tm e n t a re quoted in t h i s t h e s i s and were cured by th e i o n i z a t i o n m ethod.) Chandler (47) had good r e s u l t in th e tr e a tm e n t o f c h ro n ic o s t e o - m y e l i t i s . Sezary (4S) r e p o r t s e x c e l l e n t r e s u l t s by u sin g powdered su lp h a n ila m id e l o c a l l y in th e tr e a tm e n t o f s o f t chancre and in sk in l e s i o n s , and quo tes H anchell and Lepinay a s having had l i k e c u r e s .

Gate and C u i l l e r e t ,

he s t a t e s , found powdered su lp h a n ila m id e p e r se was more e f f i c a c i o u s than when used in th e form o f an o in tm e n t. (In d e r m a t i t i s , I found P r o n t o s i l i o n i z a t i o n d id n o t prove o f any u se.

The germs were c o n t r o l l e d , b u t th e

sk in was n o t s tim u la te d to new grow th.

i t was e f f e c t i v e

in f u r u n c u lo s is , b o i l s and im p etigo c o n t a g i o s a . ) . In an o u ts ta n d in g r e p o r t J e n s e n , Jo h n sru d and Nelson (36) gave d e t a i l s o f a method th e y evolved by i n s e r t i n g 5 - 1 5 grms. o f s u l p h a n i l a m i d e , a f t e r c le a n in g up th e wound, i n t o compound f r a c t u r e s and compound d i s l o c a t i o n s . 33.

F o rty -o n e

ea ses were t r e a t e d and a l l h ea led by f i r s t i n t e n t i o n e x c e p t two, which were re-compounded and l a t e r h e a le d p e rfe c tly . 27$.

T h e ir r a t e o f i n f e c t i o n had p r e v io u s l y been

This p a p e r, a f t e r i t s p u b l i c a t i o n in J u l y 1939,

a p p a r e n tly aro u sed the i n t e r e s t o f surgeons in th e use o f s u lp h a n ila m id e .

In the fo llo w in g y e a r many r e p o r t s a p p e ared .

B r i t t a i n and L a t t e r (49) and Hodgson and McKee (50) found t h a t wounds t r e a t e d a f t e r the manner o f J e n s e n , showed b e n e f i c i a l r e s u l t s , p o s t - o p e r a t i v e i n f e c t i o n and p y r e x ia were e x c e p tio n a l and t h a t even C l. W elchii i n f e c t i o n remained co n fin e d to th e wound. L e v a d i t i , G erra rd -M o isso n n ie r, B re c h o t and Tournay (51) secu red very s a t i s f a c to ry r e s u l t s i n th e l o c a l tr e a tm e n t o f twelve o ld wounds.

A ll markedly

im proved. The c u r a t i v e p r o p e r t i e s o f su lp h a n ila m id e a g a i n s t human i n f e c t i o n by haem olytic s t r e p t o c o c c i , and by some o f the gas gangrene organism s, s t a t e F u l l e r and James (52 ), make t h i s drug o f g r e a t im portance in th e tr e a tm e n t o f war wounds.

Most d eath s from i n f e c t i o n s in th e G re a t War

were due to th e se two groups o f organism s.

The

h ae m o ly tic s t r e p t o c o c c i were a l s o r e s p o n s ib le f o r th e 34

g r e a t m a jo r i ty o f c o m p lic a tio n s (Douglas, Fleming and Colebrook, 1930) 90% p rim ary h e a lin g in compound f r a c t u r e s was se c u re d a f t e r l o c a l l y im p la n tin g su lp h a n ila m id e by Watson Jo n e s (5 3 ).

Nor, he s t a t e s , can th e r e be any doubt as to th e

v a lu e o f

th e s e p r e p a r a t i o n s (su lp h a n ila m id e ) i n such c a s e s .

H e a lin g w ith drunks and p a t i e n t s in poor p h y s i c a l c o n d i tio n , S tu ck , Maxwell and Monsalvo (37) t r e a t e d tw enty-one f r e s h compound f r a c t u r e s and f iv e compound f r a c t u r e s which had p r e v io u s l y had o s t e o - m y e l i t i s o f some months d u r a tio n . w ith o u t d r a i n s .

These c a s e s were a l l p l a t e d and c lo se d Twenty-two h e a le d by p rim ary union, th e

o t h e r s , a t th e time o f the r e p o r t had n o t then h e a le d . (54) The War O f f i c e Arecommended th e im p la n ta tio n o f su lp h a n ila m id e i n t o th e depths o f wounds a t th e time o f d ebridem en t.

Owing to the outcome o f th e campaign in

F ra n c e , and th e c h a o tic c o n d itio n s p r e v a i l i n g , few c a s e s o f l o c a l tr e a tm e n t were a b le to be follow ed up and r e p o r te d on - Page (5 5 ).

His im p ressio n was, t h a t th e in c id e n c e o f

se co n d ary i n f e c t i o n in wounds t r e a t e d w ith s u lp h a n ila m id e was low er than he expected from h is e x p e rie n c e o f th e l a s t War.

Colebrook (56) spoke i n much th e same s t r a i n and 35

quoted one s e r i e s o f seven o r e i g h t c a s e s , a c q u ir e d a s t r e p t o c o c c a l i n f e c t i o n ; f i r s t in te n tio n .

two had

th e o th e r s h e a le d by

A t two C . C . S . te n c a s e s t r e a t e d by

packs remained f r e e from i n f e c t i o n up to f iv e days a f t e r tre a tm e n t.

Handley 157), O g ilv ie 158), Page (59) and

King (60) a l l r e p o r te d t h e i r im p re s sio n s as b e in g fa v o u r a b le in th e war wounded th e y had t r e a t e d .

O g ilv ie based h i s op in io n

on t h r e e hundred c a s e s from Dunkirk.

King was th e f i r s t

to quote a c t u a l ca se s and th e se were from memory.

iie

cle a n se d th e wounds w ith P ero xide a f t e r s u r g i c a l tr e a tm e n t, and then packed w ith s u lp h a n ila m id e .

No such ca ses d ie d ,

and even wounds 48 - 72 hours old showed improvement in t h e i r c o n d itio n .

When the powder ran s h o r t , and f l a v i n e

packs were employed, some p a t i e n t s died and most had toxaem ia in some d eg ree.

( I t i s o f i n t e r e s t t h a t in

F eb ru ary , 1941, King should remark th e b e n e f i c i a l e f f e c t o f BgC^combined w ith s u lp h a n ila m id e .

This h a s been t h e

r o u tin e tr e a tm e n t given in my c a s e s s in c e A p r i l 1940) Biches (61) and Buxton (62) t r e a t e d a i r r a i d c a s u a l t i e s w ith powdered su lp h a n ila m id e and found the method s a t i s f a c t o r y . 56

In S i r H arold G i l l i e s * p l a s t i c s u r g e r y u n i t , Colebrook (63) e lim in a te d i n f e c t i o n from s u p e r f i c i a l g r a n u l a t i n g wounds.

He bad been a s to n is h e d a t th e r e s u l t s i n old

burns and in f e c te d road a c c i d e n t c a s e s . In a c u te i n f e c t i o n s o f s t r e p t o c o c c i and s ta p h y lo c o c c i such as im p e tig o , M ilian (64) found an a l c o h o li c s o l u t i o n o f su lp h a n ila m id e e f f e c t i v e as a l o c a l a p p l i c a t i o n . S e p tic s in u s e s c le a r e d up a f t e r i r r i g a t i o n w ith P r o n t o s i l s o lu b le - C h ild re y (6 5 ;. By i n j e c t i n g P r o n t o s i l i n t o th e p l e u r a l c a v i t y , Smith (66) cured an empyema in a rem arkably s h o r t c o u rse o f tr e a tm e n t s .

O th er c a ses which responded w e ll were

a b s c e s s e s , where gauze soaked w ith the su lp h a n ila m id e p r e p a r a t i o n was used as a p ackin g, o r by th e use o f an o in tm e n t. Two n u rse s having been found to be n a s a l c a r r i e r s o f d i p h t h e r i a , Payne and A uchinleck (67) i n s t i t u t e d f r e q u e n t use o f a sulphathiozoje s n u f f .

The swabs were

n e g a tiv e on th e second day and remained so f o r 7 - 12 d ays. (

Case No. 12 was a n a s a l d i p h t h e r i a which was

cured by i o n i z a t i o n w ith P r o n t o s i l .

I t i s o n ly su g g e sted

t h a t i o n i z a t i o n might prove o f use in r e f r a c t o r y ca ses o f n asal d ip h th e ria .)

In th e p o s t - o p e r a t i v e tr e a tm e n t o f r e s e c t i o n o f

th e

rectum , Mayo and M i l l e r (68) a f t e r c le a n s in g w ith Hydrogen

P e ro x id e , used i r r i g a t i o n s o f su lp h a n ila m id e In

normal s a l i n e .

A y e a r* s work on th e s e l i n e s had proved

v e ry s a t i s f a c t o r y .

They b e l ie v e d t h a t t h i s use of

p e ro x id e o f hydrogen had enhanced th e a c t i o n o f th e su lp h a n ila m id e in acco rdance w ith S h a f f e r ’s th e o ry t h a t th e mode o f a c tio n o f su lp h a n ila m id e i s due to i t s o x id a tio n p r o d u c ts .

( I have p r e v io u s l y mentioned the r o u t i n e tr e a tm e n t

ado pted in my c a s e s .

I have been hoping to meet a

p a t i e n t w ith two f a i r l y s i m i l a r l e s i o n s to t r e a t one l e s i o n with HgOg and then a p p ly P r o n t o s i l and th e o t h e r d is e a s e d p a r t t r e a t w ith H2 O2 and i o n is e w ith P r o n t o s i l . No such case h as y e t ap p eared . a t p re se n t la c k in g .

This p a r t i c u l a r c o n t r o l i s

I t must be no ted t h a t a good number

o f my ca se s had been t r e a t e d l o c a l l y w ith s u lp h a n ila m id e powder and then cured w ith i o n i z a t i o n ) . At th e Mayo C l i n i c , H e r r e l l and Brown (69)

u sin g a

s o l u t i o n o f s u lp h a n ila m id e in normal s a l i n e , t r e a t e d tw enty-one cases o f o p e r a tiv e and tra u m a tic wounds o f th e s c a l p , th o ra x and p e ric a rd iu m as w e ll a s f r a c t u r e s and sin u se s.

The r e s u l t s , though n o t uniform , were so

s a t i s f a c t o r y as to j u s t i f y c o n t i n u a t i o n .

They b e l i e v e d

th e b e n e f i c i a l e f f e c t o f l o c a l a p p l i c a t i o n can be e x p la in e d to some e x t e n t by a b s o r p ti o n .

On the o t h e r hand th e

a b s o r p tio n , where th e wound a r e a was sm a ll, was so s l i g h t as to be i n d e t e c t a b l e .

The r e s u l t s were o u t o f p r o p o r ti o n

to th e re sp o n se expected from th e c o n c e n tr a tio n p r e s e n t , judged by o th e r methods o f a d m i n i s t r a t i o n .

(This may be

e x p la in e d by the amount o f serum p r e s e n t .

X have n o tic e d

w ith i o n i z a t i o n , t h a t a f t e r s e v e r a l tr e a tm e n ts a wound te n d s to become tanned by th e P r o n t o s i l . d ry .

I t becomes

The a s t o n i s h i n g l y r a p id growth o f sk in o r h e a lin g

t i s s u e now slows down a t t h i s s t a g e .

The io n s o f th e

t i s s u e s have been r e p la c e d e n t i r e l y by P r o n t o s i l io n s . The c o n c e n tr a tio n can be too g r e a t .

The body f l u i d s can

n o t then p la y t h e i r im p o rta n t p a r t ) Unusual i l l - e f f e c t s were r e p o r te d by F rankland (70) and F l e t c h e r (71).

The form er quoted s i x c a se s o f

f o o t- d r o p , g l u t e a l p a r e s i s and u l c e r a t i o n o f th e sk in w ith p e r s i s t e n t s in u s , fo llo w in g i n j e c t i o n s o f s u lp h a n ila m id e .

F l e t c h e r quoted a case o f complete a n u r ia

w ith f a t a l te rm in a tio n fo llo w in g s u lp h a p y rid in e tr e a tm e n t by th e mouth in a case o f pneumonia.

The more common

t o x ic e f f e c t s o f o r a l a d m i n i s t r a t i o n need n o t be d is c u s s e d a t le n g th - n au sea, v o m itin g , abdominal p a in , d ia r r h o e a , a n o r e x ia , m a la is e , weakness, v e r t i g o , t i n g l i n g , d i s o r i e n t a t i o n , r a s h e s , a c i d o s i s , c y a n o s is , h y p e rp y re x ia , shock, ja u n d ic e , sulphaem oglobinaeraia, anaem ia, le u c o p e n ia , a g r a n u l o c y to s i s , o p t i c n e u r i t i s and p s y c h o s is - B i g i e r and Haralambie (72) These c o m p lic a tio n s , i f uncommon, are n e v e r t h e le s s e n t i r e l y avoided when l o c a l tr e a tm e n t i s u t i l i s e d .

F or

l o c a l l e s i o n s , l o c a l tr e a tm e n t is ^ a c c o r d in g to the r e p o r t s p r e v io u s l y quoted in t h i s s e c t i o n , o f undoubted and in e s tim a b le v a lu e .

As a l o c a l p r o p h y la c tic th e sulphonam ides

a r e alm o st a d e f i n i t e g u a r a n te e o f a smooth, uncom plicated, h e a lin g by f i r s t i n t e n t i o n .

When i n f e c t i o n has taken

p l a c e , l o c a l tr e a tm e n t i s n o t so u n f a i l i n g b u t n e v e r t h e le s s i s o f paramount im po rtan ce.

B X P E B I U E H

I 8

EXPERIMENT No. I .

B

A f

\

>****
» O | V .

D ia m e tr ic a lly o p p o s ite , a l i t t l e p i l e o f pads m oistened w ith 2-£/6 P r o n t o s i l was a p p lie d to a raw s u r f a c e r e p r e s e n t i n g a wound.

This c o l l e c t i o n was a t ta c h e d to th e p o s i t i v e p o le .

The pads were k e p t in p o s i t i o n by e l a s t i c ban ds, and to keep the P r o n t o s i l pads m oist th ro u g h o u t th e ex perim ent, th e y r e s te d in a su pp ly o f t h i s s o l u t i o n in a sm a ll b a s in . 57.

T h i s a r r a n g e m e n t was made a s t h e P r o n t o s i l was n o t m a r k e d l y o p aq u e t o t h e X - r a y s , v i s i b l e X -ray p i c t u r e , f o r some t i m e .

and t h e r e f o r e ,

to have a

t h e c u r r e n t w ould have to p a s s

Thus t h e p a d s w e r e p r e v e n t e d f r o m

becom ing dry d u r in g th e e x p e r im e n t. were p a s se d f o r f o u r h o u r s .

100 m i l l e a m p e r e s

An X - r a y f i l m was t h e n

taken. RESULTS

M

(a) X -ray

Pronjtosiui££^ Muscle,

uscle:

UNAFFECTED P R O N T O S IL

T

The p r i n t ,

e n d o n

IN

i- ia r r o W .

.

f r o m t h e X - r a y p l a t e shows t h a t t h e

P r o n t o s i l has been f o r c e d i n t o th e s u b s ta n c e o f t h e m u scle. The m u s c l e u n d e r t h e n e g a t i v e p o l e was u n e f f e c t e d .

The

sh ad ow i n t h e b one i t s e l f was due t o a d e n s e i n f i l t r a t i o n 58.

o f P ron tosil.

No information was gained from the X-ray

f ilm which was n o t found on d i s s e c t i o n .

I t i s , however,

a v i s u a l c o n f ir m a tio n . Cb)

V is u a l.

On d i s s e c t i n g th e meat, th e muscle

was v ery d eep ly dyed w ith th e P r o n t o s i l on th e p o s ti v e p o le s i d e o f th e bone.

The f a s c i a l l a y e r s were s t a i n e d

on th e s id e a d j a c e n t to the muscle b u t the P r o n t o s i l had n o t been fo rc e d th ro u g h . u n a f f e c te d .

The f i b r o u s tendons were

Through th e s e s u r f a c e s , however, r i n g s o f

s t a i n i n g were r e a d i l y seen around blood v e s s e l s .

The

a r t i c u l a r s u r f a c e o f th e bone, which was p e a r l y w h ite b e f o r e tr e a tm e n t, was now glow ing w ith a f a i n t p in k is h hue. The d ia p h y s is was u n a f f e c te d .

The spongy bone and th e

m edulla ossium were unifo rm ly s t a in e d a l i g h t shade o f red .

In the m ed u llary c a v i t y th e deeply s t a i n e d a r e a ,

seen in th e X -ray, was found to have sp read from a blood v e s s e l thus a c c o u n tin g f o r i t s o r i g i n .

In the spongy

bone a few deeply s t a i n e d s p o ts burrowed i n t o th e bone P r o n t o s i l p a s s in g alo ng blood v e s s e ls b e fo re d is s e m in a tio n .

59

M ttS c l £ ^

unaffected

MARROW,

BLOOP

S LI GHT LY

YgSSEl

STAINED.

WITH

STO N IN G

UNAFFECTED

FASCtft,

MUSCLE, DEEPLY

RAW

STAINED.

A

T E N D O N . UNft FPECTEja

DEEPLY AflTfCULflfl

CONCLUSION.

STAINED

S URF AC E

STAINED S PO T S

STAINED

ftREfl

IN

IN

SPONGY

PRINT

PlN K .

MARgOW. gQiNE.

From a raw s u r f a c e , P r o n t o s i l i s i o n i s i b l e

d eep ly in to th e su b stan ce o f mammalian muscle. p a s s e s alo n g sid e blood v e s s e ls through f a s c i a .

It In t h i s

manner to o , i t p a s s e s i n t o bone where i t d i f f u s e s in th e marrow.

C onfirm ation o f most o f th e s e s ta te m e n ts

i s shown in the X -ray p r i n t .

60

.

S U R FA C E , REPRESENTING

n+ve

DEEPLY

.

WOUND.

AROUND.

EXPERIMENT 11

A ttem pts were made to X -ray th e r a t e o f p e n e t r a t i o n o f P r o n t o s i l i n t o mammatian m uscle.

The o p a c ity o f

P r o n t o s i l was n o t s u f f i c i e n t l y dense to g a in t h i s o b j e c t . C onfirm ation o f th e p r e v io u s experim ent was a l l t h a t was secured.

C A S K S.

CASES. In th e

S e c tio n on I o n i z a t i o n i t has been shown t h a t

drugs a r e f o r c e d i n t o th e t i s s u e s , and confirm ed in th e E x perim ental S e c tio n t h a t t h i s holds good in th e case of P ro n to s il.

A gain, in th e chemotherapy s e c tio n numerous

r e p o r t s show t h a t s u lp h a n ila m id e , used l o c a l l y , i s l ik e w is e a pow erful weapon in mastering many p a t h o l o g i c a l c o n d i tio n s . Combined use o f two such e f f e c t i v e methods sh o u ld , i t i s re a s o n a b le to ex p ect b e more e f f e c t i v e than e i t h e r used se p a ra te ly . Ever y case which was g iv en tr e a tm e n t i s in clu d ed in th e fo llo w in g r e p o r t s .

The ca se s have been grouped a c c o rd in g

to th e type o f l e s i o n t r e a t e d .

The group c l a s s i f i c a t i o n

o f each ca se i s in d ic a t e d a t th e top r i g h t hand co rn e r o f each pag e.

The number quoted i s the c h r o n o lo g ic a l number,

o r o r d e r o f app earan ce a t th e P h y sio th e ra p y Departm ent. To save r e p e t i t i o n in th e r e p o r t s , each l e s i o n was c le a n se d and i r r i g a t e d w ith Hydrogen P ero x id e 1 in 4*

The i o n i z a t i o n s

were g iv e n tw ic e o r t h r i c e weekly.

This r o u t i n e tr e a tm e n t

was commenced on I 2 th A p r i l , 1940.

With r e g a rd to t h e use o f

i

P ero x id e o f Hydrogen, Mayo and M i l l e r (68) on 25th September 1940, r e p o r te d t h a t , in th e Mayo C l i n i c , they found th e 62

! i

p re v io u s use o f t h i s l o t i o n , b e fo re th e a p p l i c a t i o n o f s u lp h a n ila m id e was more e f f i c a c i o u s than th e a p p l i c a t i o n o f su lp h a n ila m id e alone* For s u p e r f i c i a l wounds, a pad moistened w ith P r o n t o s i l was used as th e anode.

Deep a b s c e s s e s , a f t e r thorough

i r r i g a t i o n w ith hydrogen p e ro x id e , had th e c a v i t y f i l l e d w ith P r o n t o s i l and m oistened rib bo n g au ze packed in around th e p o s itiv e electro d e .

A v u lc a n it e speculum was used to t r e a t

e a r cases and t h i s in s tru m e n t was k e p t f i l l e d w ith P r o n t o s i l . With nose c a s e s , m oistened rib b o n gauze was packed up th e n a s a l p assag es and, when the a n t r a l c a v i t y was b e in g t r e a t e d , a c a n n u la was l e f t in s i t u and k e p t f i l l e d .

By t h i s means

th e antrum was io n is e d th ro u g h o u t. I n s te a d o f w r i t i n g m ille-am p ere each tim e , th e a b b r e v i a tio n M*A* i s used.

63.

(Abscess)

Case No. 1 . Name

Mrs, B.

Age

H is to r y o f L esio n

21.

O ccupation

Shop A s s i s t a n t ,

A p a ro n y c h ia developed in December 1939,

The n a i l was removed and th e u su a l d r e s s i n g s a p p lie d ,

A new n a i l grew one t h i r d o f th e normal

l e n g t h , b u t was s o f t and oozed p u s,

d e a n sin g s

w ith hydrogen p e ro x id e , mag, su ip h . com presses, Kromayer lamp tr e a tm e n t and z in c io n i z a t i o n were a l l trie d . C ondition - 1 s t a t te n d a n c e . 1 2 /4 A 940.

The n a i l was s o f t and

pus was r e a d i l y e x p r e s s i b l e . Fus

No exam ination was made.

This was th e f i r s t

t r i a l o f the method o f t r e a t m e n t . I o n i z a t i o n 3$ P r o n t o s i l was used a t 3 m ille-am p eres (3 M.A.) f o r 10 minutes under th e p o s i t i v e p o l e . R e s u lt

19/4/1940

There was no pu s;

th e n a i l was h e a lth y

and f irm T reatm ents g iven Pollow -up

Two.

One month l a t e r the n a i l was s t i l l growing and was s t i l l h e a lth y .

64

She could n o t be t r a c e d In 1941,

(Abscess)

Case No. 2.

Name

Mrs. H.

Age

H is to r y o f L e s i o n .

47

Occ u p atio n

H ousewife.

This p a t i e n t had a s e p t i c elbow f o r

four or fiv e y e a rs.

I t seemed to be h e a lin g b u t

would then b re a k down a g a in . P re v io u s tr e a tm e n t.

Foments, p o u l t i c e s and s u lp h a n ila m id e

o r a l l y had a l l been t r i e d . C ondition - 1 s t a t te n d a n c e .

On 9/5/1940 t h e r e was a l a r g e

f l u c t u a n t a r e a over th e r a d iu s f o r 5* below th e elbow, 3 ’1 wide, and deep in th e t i s s u e s . oozed from th r e e s in u s e s , each

Pus

o r more in

d ia m e te r. X-ra.v

No d is e a s e o f th e bone was seen .

Pus

A mixed i n f e c t i o n was p r e s e n t .

I o n iz a tio n R e s u lt.

3% P r o n t o s i l a t 4 M.A. f o r 10 minutes was used. A f t e r f i v e tr e a tm e n ts , th e t i s s u e s were f irm and th e s in u s e s were h e a lin g .

F ifte e n f u r th e r

tr e a tm e n ts r e s u l t e d in p e r f e c t h e a lin g ex c ep t f o r one s in u s which was over th e acromian p r o c e s s and was only sk in deep.

The arm was p la c e d in a s l i n g

to p r e v e n t ex cessiv e movement.

I t l a t e r h e a le d .

Follow -up The arm was in s p e c te d a t f r e q u e n t i n t e r v a l s . 6 5 /? - 5 M*A. T reatm ents giv en R e s u lt

Four.

One tr e a tm e n t r e s u l t e d in a t h i n d isc h a rg e o nly b e in g p r e s e n t.

A f t e r th r e e tr e a tm e n ts

th e r e was no d isc h a rg e , b u t a f u r t h e r tr e a tm e n t was n e v e r th e le s s g iv e n . P o lio w - up

10 /1 1 /4 1 ,fI have remained f r e e from c a t a r r h

f o r 12 months11 w rote t h i s woman.

103

(Nose)

Case No. 16,

Name Mr. L.

Age 55

H is to r y o f L esio n

O ccupation

Works Manager.

Xn J a n u a ry , 1940 a sudden i n t e n s e

c a t a r r h o f h i s nose d eveloped.

X -ray showed

d u lln e s s o f b o th a n t r a . P re v io u s Treatm ent

A n tr a l w ashouts.

A to m iser u sin g

e p h e d rin e , f l a v i n e e t c . calcium i n j e c t i o n s , Vitamin “D1, a l l had been t r i e d as w e ll as v a c c in e s . He was s e n t f o r zin c i o n i z a t i o n . C o nd ition - 1 s t A tte n d a n c e . 1 /1 1 /4 0

Yellow, p u s - l i k e

c a t a r r h a l d isc h a rg e in both n o s t r i l s . Pus

Mixed i n f e c t i o n .

Io n iz a tio n

One n o s t r i l was t r e a t e d w ith 5% P r o n t o s i l a t

3^ M.A. f o r f i v e m inutes.

The o th e r n o s t r i l was

t r e a t e d w ith Z in c. R e s u lt

P r o n t o s i l gave the g r e a t e r r e l i e f , th e d is c h a r g e

was c o n s id e ra b ly reduced.

Zinc showed some, b u t

n o t so marked an improvement.

He r e f u s e d f u r t h e r

P r o n t o s i l tr e a tm e n t as i t d is f ig u r e d h is l i p and s t a i n e d h is h a n d k e rc h ie fs .1 Remarks

Even th e p a t i e n t agreed t h a t th e P r o n t o s i l

i o n i z a t i o n was the b e t t e r o f the two. 104

This was

d e f i n i t e l y n o t p s y c h o lo g ic a l, as th e o p p o s ite o p in io n would have been e x p e cte d .

N othing d e f i n i t e

can f u r t h e r be deduced from t h i s ca se ex cep t t h a t P r o n t o s i l had r e s u l t e d in a l i t t l e improvement. I t may be mentioned t h a t th e z in c tr e a tm e n t d id n o t cure h i s c o n d itio n in th e end.

(Ear)

Case No. 17.

Name

T.O.H,

Age 19

H is to r y o f L esio n

O ccupation

E n g in e e r.

F eb ru ary 1937 - O t i t i s Media w ith

m astoid a b sc e ss 10 days l a t e r . P re v io u s tr e a tm e n t

m astoid o p e r a tio n 8 /7 /3 7 .

H ealed

by 1 8 /9 /3 7 1 2 A 0 /3 7

Pus oozed from the old m astoid i n c i s i o n .

1 4 /7 /3 8

S ulphanilm ide was t r i e d p e r Os and ag a in on 2 7 /2 /3 9

4 /1 1 /4 0

M astoid o p e r a tio n again p erform ed .

C o n d itio n - 1 s t A tte n d a n c e . 7 /11/40

The I n c i s i o n was

n o t f u l l y c lo s e d , so a f t e r r o u tin e i r r i g a t i o n w ith d ilu te d Pus

P ero x id e o f Hydrogen, i o n i z a t i o n was g iv e n .

S ta p h y lo c o c c i, s t r e p t o c o c c i and pneumococci.

Io n iz a tio n

5% P r o n t o s i l a t 3 M.A. f o r 4 minutes was

used. R e s u lt

One tre a tm e n t made th e p a t i e n t c o m fo rta b le , d e-o d o rise d th e wound.

The pus became th in and th e

wound h e a le d a f t e r two tr e a tm e n t s . w atery pus oozed from th e e a r .

A week l a t e r ,

N ineteen f u r t h e r

tr e a tm e n ts were u n s a t i s f a c t o r i l y given to t h e e a r th e a p e r tu r e in th e drum was s m a ll. 106

On 3A / 4 1

(ear)

pus commenced to ooze from th e m astoid i n c i s i o n . T reatm ent was sto p p ed and he underwent a f u r t h e r o p e ra tio n . Treatm ents given Follow -up

Twenty-two

On 1 1 /8 /1 94 1 pus again began to i s s u e from

th e e a r and from th e m astoid a r e a through th e o p e r a tio n s c a r .

A polypus was now seen to be

p r e s e n t behind th e drum Remarks

No i o n i z a t i o n w ith P r o n t o s i l could cure a

p o ly p u s.

107

(Hose)

Name

Mias J*.

Age

H is to r y o f L esion

53

O ccupation

Housewife

For s e v e r a l y e a rs t h i s p a t i e n t

had r e c u r r i n g a t t a c k s o f P h a r y n g itis and T r a c h e i t i s . Both A n tra were blocked (Xray) P re v io u s Treatm ent

M edicinal tr e a tm e n t;

C o nd itio n - 1 s t A tte n d a n c e .

On 2/1 /4 1

A n tr a l w ashouts. th is p a tie n t

was s e n t from the t h e a t r e a f t e r a w ash -ou t. Pus

No swab was taken under the c irc u m s ta n c e s .

Io n iz a tio n R e s u lt

b% P r o n t o s i l a t 4 M.A. f o r 5 minutes was used.

One n o s t r i l was p e r f e c t l y c l e a r t h e fo llo w in g day, th e o th e r did no t show very much c a t a r r h .

Follow -up

Two veeks l a t e r she r e p o r te d no c a t a r r h worth

m entioning and on 8 /4 /4 1 r e p o r te d q u ite c l e a r . Remarks.

One tr e a tm e n t only was a b le to be g iv e n .

This a p p a r e n tly r e s u l t e d in a c u re .

As t h i s

may have been a c a t a r r h o f nervous o r i g i n . t h e r e may have been a p s y c h o lo g ic a l e f f e c t behind the re su lt.

I t i s r e g r e t t e d t h a t no swab could h e re

be ta k e n .

108

(Nose)

Case No. 27

Name S h i r l e y D

Age 7

H is to r y o f L esion

Occupation

S c h o o lg ir l

For f o u r y e a rs sh e had s u f f e r e d from

c o n s ta n t n a s a l c a t a r r h , mouth b r e a th in g and cough. P re v io u s T reatm ent

Her t o n s i l s and adnenoids had been

removed when t h r e e y e a rs old and a g a in , two y e a rs la te r.

V accines, calcium o r a l l y and

p a re n ta lly ,

U l t r a V i o l e t Ray tr e a tm e n t (g e n e ra l and by

Kromayer

lamp l o c a l l y ) had a l l been t r i e d . C o nd itio n - 1 s t A tte n d a n c e . 1 3 /1 /4 1

The t u r b i n a l s were

e n la rg e d and th e r e was much c a t a r r h in both n o s t r i l s . Pus

Mixed i n f e c t i o n .

Io n iz a tio n

The nose was packed w ith gauze soaked in

5% P r o n t o s i l and a c u r r e n t of 4 - 10 M.A. was p a sse d f o r 5 - 1 0 m inutes. Treatm ents given

Five

R e s u lt S l i g h t c a t a r r h was p r e s e n t b u t she b reath ed , b e t t e r and now s l e p t w ith h e r mouth c lo s e d . were no lo n g e r e n la rg e d .

The t u r b i n a l s

Her mother s a id tfI f she

s ta y s l i k e t h i s , we s h a l l no t g ru m b le .11 Follow-up

Ju n e , 1941.

the s t r e e t .

This p a t i e n t was enco un tered in

Her mouth was c lo s e d .

c a t a r r h s in c e h e r l a s t tre a tm e n t. Remarks.

Cure. 109

She had had no

(Nose)

Case No. 48

Name Miss H.

Age

H is to r y of L esion

25

Occupation

N urse.

N asal and p o s t - n a s a l c a t a r r h and

headache had tr o u b le d t h i s young woman s i n c e she was a g i r l . P re v io u s Treatm ent

T onsilectom y was performed

in

1925, 1938, 1941 and sub-mucous r e s e c t i o n and a n t r a l w ashouts in 1941.

I n h a l a t i o n s , sp ra y s and

s u lp h a n ila m id e had been t r i e d . C o n d itio n - 1 s t A tte n d a n c e .

30/9/41

Her t h r o a t was

in flam ed, h e r t e e t h were good, a t h i n d is c h a rg e was p r e s e n t in h e r nose. Pus

Staphylococcus a u re u s .

Io n iz a tio n

22% P r o n t o s i l was used on gauze to pack th e

nose, and f o r 10 minutes 3 M.A. were p a s se d . T reatm ents R e s u lt

Four tre a tm e n ts were given to th e nose.

The c a ta r r h ceased.

The t h r o a t was n o t t r e a t e d

and rem ained somewhat inflam ed b u t l e s s than b e fo re tr e a tm e n t. F o llo w - u p

1 4 /1 1 /4 1

in th e n o se .

No f u r t h e r tr o u b le has o c c u rre d I t has been f r e e from c a t a r r h .

t h r o a t was improving t o o . 110.

The

(Nos e)

Remarks.

The p a r t t r e a t e d was cu red and has rem ained

so f o r two months, a f t e r h av in g had d a i l y c a t a r r h f o r a t l e a s t 16 y e a r s .

(Hose)

Case No. 51

Name Mrs. M.

Age 35

H is to r y o f L esion

Occupation Housewife.

N asal C a ta rrh f o r 10 y e a rs was th e

c o m p la in t. P re v io u s T reatm ent

T o n sillecto m y 10 y e a rs ago Double A n tr a l o p e r a tio n 5 y e a rs ago A n tr a l Washout O ctober 1941 N asal douches i n h a l a t i o n s , v a c c in e s

C o n dition - 1 s t a tte n d a n c e

Mucous c a ta r r h was p r e s e n t .

The l e f t n o s t r i l showed the mucous membrane to be sw ollen and in flam ed . Pus

The t u r b i n a l s were e n la r g e d .

S ta p h y lo c o c c i Aureus and Alb us and D ip h th e ro id b a c i l l i (No K .L.B.)

Io n iz a tio n

2^% P r o n t o s i l was used a t 4 M.A. f o r f i v e

m in u tes. T reatm ents given R e s u lt

Treatm ent was giv en once a week. Two

Follow ing the f i r s t tr e a tm e n t she was f r e e from c a t a r r h f o r th r e e days, then s l i g h t c a t a r r h fo llo w ed .

A f t e r th e second tre a tm e n t she had a v ery co m fo rtab le week w ith h a rd ly any c a t a r r h a t a l l Follow -up

She i s s t i l l under tr e a tm e n t .

112,

V.i'J u o c ;

Case No. 53

Name

Miss C.

Age 39

H is to r y o f L esio n

Occupation Home d u t i e s .

Follow ing s o r e t h r o a t s and n a s a l

c a t a r r h seven y e a rs ago, to n s ille c to m y was perform ed b u t b r o n c h i e c t a s i s supervened. c u re d .

The c a t a r r h was n o t

Pain developed in th e a n t r a l re g io n s a

few

months ago. P re v io u s tr e a tm e n t

A n tr a l w ashouts.

C ondition - 1 s t A ttendance

She a tte n d e d on 2 /1 2 / 1 941 a f t e r

an a n t r a l i r r i g a t i o n . X -ray This showed d u lln e s s of b o th a n t r a , hence th e o p e ra tio n . Pus

Mixed i n f e c tio n

Io n iz a tio n

2%>% P r o n t o s i l was used a t 3 M.A. f o r th r e e

m in u tes. Treatm ents g iv e n H e su lt

Two 5/12/1941

Some improvement b u t, o f c o u rse , i t i s too e a r l y to claim t h i s as d e f i n i t e .

Follow-up

She i s s t i l l under tre a tm e n t.

113*

(Skin)

Case Ho. 8

Name

Mrs* S*

Age 42

H i s t o r y o f L esion

Occupation

1938 Phelgm asia

Housewife Alba Dolens

Three l a r g e V arico se D icers developed P re v io u s Treatm ent

ifeny e l a s t o p l a s t bandages 19-Kromayer Lamp tre a tm e n ts Various ointm ents in c lu d in g s ulphan ila m id e .

C o nd itio n - 1 s t A ttendance

1 2 /8 /4 0 .

Three deep

v a r ic o s e u lc e r s were p r e s e n t on one l e g , no corium was p r e s e n t .

Two o f th e u lc e r s measured

2 square inches and one, one sq u a re inch in a r e a . Pus h a l f f i l l e d th e se c r a t e r s . Pus Io n iz a tio n

2-^3 P r o n t o s i l a t 10 M.A. f o r 15 minutes was

g iv e n weekly. R e su lt

A f t e r n in e t r e a tm e n t s , the u lc e r s were c le a n , g r a n u la tio n s were showing and the a r e a had been reduced by one t h i r d . Slow p ro g re ss was k e p t up and by 5/1/1941 th e s m a lle r u l c e r had h e a le d .

One o f th e l a r g e

u lc e r s was the s i z e o f a pea, the o t h e r was l e s s than h a l f the o r i g i n a l a re a , and l e v e l w ith th e normal s k in . 114

(Skin)

H ea lin g slowed down and tr e a tm e n t was sto p p ed on 3 A A 9 4 1 .

She re tu r n e d on 17A ^1941 a s th e

u l c e r s had grown r a p i d l y and pus seeped through th e b an d a g es. T reatm ents g iv en Follow -up

T reatm ent was recommenced Twenty

O ctober 1941.

The u lc e r s had been h e a le d f o r

th r e e o r f o u r months. Remarks.

There was no d ram a tic h e a l i n g .

In t h i s

p a r t i c u l a r c a s e , compared w ith t h e lo n g t r i a l s b y o t h e r methods o v er two y e a rs , i o n i z a t i o n was e f f e c t i v e and s o o th in g .

When th e tr e a tm e n t was

sto p p e d th e u lc e r s v ery q u ic k ly broke down.

115

(Skin)

Case No. 18 Name

Raymond H.

Age

H is to r y o f L esion

7

O ccupation

Schoolboy

This boy had a se v e re im petigo

c o n ta g io s a and f o r f iv e months had been t r e a t e d a t th e C hild W elfare C l i n i c . P re v io u s Treatm ent been used.

E L a s to p la s t s t r i p s and o in tm e n ts had He was given G eneral U ltr a V i o l e t Ray

tr e a tm e n t as asked f o r . C o n dition - 1 s t A tten d an ce.

21/10/40

Two u l c e r a t e d a r e a s ,

one 2" in d ia m e te r, the o th e r l ^ ' 1 x h e a l. Pus

would n o t

P r o n t o s i l i o n iz a t io n was used.

S ta p h y lo c o c c i Aureus

Io n iz a tio n

P r o n t o s i l a t 4 M.A. f o r f i v e minutes was

used. T reatm ents g iv e n R e s u lt

Three

A f te r one tr e a tm e n t, the u lc e r s had n e a r ly h e a le d , b u t were s c ra tc h e d to p ie c e s a f t e r th e secodd tr e a tm e n t .

Two f u r t h e r tre a tm e n ts r e s u l t e d

in a good h e a lth y s k in . Follow up Remarks.

24 /2 /4 1

F i t and h e a lth y , no blem ishes on s k in .

The sk in cases so f a r co n sid e re d would i n d i c a t e

t h a t , when u lc e r s are n o t denuded o f the e n t i r e s k in , P r o n t o s i l i o n iz a t io n s tim u la te s growth, and k i l l s i n f e c t i o n very q u ic k ly .

(Skin)

Case No. 25

Name

Mrs* W.

Age

H i s t o r y o f L esion

47

O ccupation

Housewife.

Mrs. W. had a v a r ic o s e u l c e r on h e r

r i g h t l e g , f o r 10 y e a r s . P re v io u s T reatm ent

She had had many v ein s i n j e c t e d

and f o r many months on end wore ELas top l a s t b andages.

Ointments and v ita m in i n j e c t i o n s were

a l l trie d . C o n d itio n - 1 s t A ttendance

8 A /4 1

A deep, c o r iu m - le s s

in d o le n t u l c e r 3 M x 4 H was p r e s e n t on h e r r i g h t l e g . Wassermann R eaction Io n iz a tio n

N e g a tiv e .

I o n iz a tio n w ith 5% P r o n t o s i l a t 5 M.A. f o r

6 - 1 0 minutes was g iv e n , tw ice weekly. R e s u lt

Four tre a tm e n ts were r e q u ir e d b e fo re the b a s e looked h e a lth y .

Improvement was g r a d u a l.

By 2 8/2 /4 1 th e u lc e r measured lk " x 2 ”, a f t e r 10 tre a tm e n ts had been g i v e n .

A f u r t h e r 15

tr e a tm e n ts r e s u l t e d in a re d u c tio n in s iz e to a q u a r t e r o f th e o r i g i n a l .

1 2 /8 /4 1 .

A f t e r two weeks

r e s t h e r u l c e r was s t i l l q u i e t , alm ost l e v e l w ith s k in , b u t l i f e l e s s in ap p earan ce.

Slow growth

fo llo w e d . T reatm ents g iv en

Twenty f i v e .

Follow-up This p a t i e n t was seen in November 1941. 117

A sm all

(Skin*

c r a t e r th e s iz e of a l e n t i l was a l l t h a t remained unhealed and t h i s was d ry . Remarks

The p r o g re s s in t h i s c a se resem bles th e

p re c e d in g one, slow to s t a r t up from r e s t , g a in e d a f a i r l y r a p id movement, then the motive power seemed to become t i r e d and growth became alm o st sta tio n a ry .

118

(Skin)

Case No. 26

flame Mr. F .

22

Age

H is to r y o f L esion

* Occupation

E n g in ee r.

For 5 y e a rs t h i s man had v a r ic o s e u lc e r s

on h i s l e g s . P re v io u s T reatm ent

Some v e in s had been i n j e c t e d , p a r t

o f th e Femoral vein had been e x c is e d , i n j e c t i o n s o f a r s e n i c , ointm ents in c lu d in g su lp h a n ila m id e , E L a s to p la s t bandage and U l t r a - v i o l e t Ray tr e a tm e n t had a l l been t r i e d . C ondition - 1 s t a tte n d a n c e .

On 1 6 /1 /4 1 th e r e was p r e s e n t

on th e l e f t le g an u lc e r th e s i z e o f h a lf-a -c ro w n and on th e r i g h t l e g one the s i z e o f a f l o r i n were p re se n t. I o n iz a tio n

The W.R. was n e g a tiv e .

5>i P r o n t o s i l a t 5 M.A. f o r 10 minutes was

us ed. T reatm ents given R e s u lt

F iv e .

Both u lc e r s were h ea led except f o r a minute a r e a , th e s i z e o f a p in -h ea d on one u l c e r .

Follow-up

I t has n o t been p o s s ib le to t r a c e t h i s man.

Ho r e p l y has been re c e iv e d to s e v e r a l e n q u i r ie s . Remarks.

The growth here was q u ite d ra m a tic .

The

u lc e r s were n o t e n t i r e l y devoid o f p o in ts o f g r a n u la tio n t i s s u e .

For u l c e r s , which had been

c o n s t a n t l y p r e s e n t f o r f i v e y e a r s , to h e a l in two weekswas more than s a t i s f y i n g

119.

(Skin)

Case No. 29

Name Mrs. W.

Age

H is to r y o f L esion

39

O ccupation

Housewife.

This woman had onychiafc o f h e r

f i n g e r n a i l s f o r fo u r y e a rs . P re v io u s Treatm ent

Ointments and l o t i o n s had been used;

X -ray tr e a tm e n t f o r s ix months had been g iv e n . C on dition - 1 s t A tte n d a n c e .

1 0 /4 /4 1 .

Her r i g h t thumb

n a i l was v ery b a d ly a f f e c t e d , n e x t in s e v e r i t y h e r f i f t h r i g h t f i n g e r n a i l and l e a s t a f f e c t e d was h e r l e f t thumb n a i l . Pus

Ho fungus was found m ic ro s c o p ic a lly and a c u l t u r e c ou ld not be made.

Io n iz a tio n

This case was only undertaken as an experim ent.

The n a i l s were t r e a t e d as fo llo w s:

R e s u lt

Follow

Most a f f e c t e d n a i l

Badly a f f e c t e d n a i l

L east a ffe c te d n a il

2*2'% P r o n t o s i l

' 1% Copper s u lp h a te

I t Z inc s u lp h a te

a t 10 M.A. f o r 15 mins.

i ,

a t 10 M.A. f o r 15 mins.

a t 10 M.A« f o r 15 mins.

Improved !g r e a t l y improved No change a f t e r s i x treatm en ts! a f t e r s i x tre a tm e n ts a f t e r s i x tr e a tm e n ts up

A f t e r one monthfs r e s t from tr e a tm e n t, th e

n a i l which had been t r e a t e d w ith copper was 120

(Skin)

d e c id e d ly b e t t e r , th e P r o n t o s i l had n o t p re v e n te d r e t r o g r e s s i o n w h i l s t th e n a i l t r e a t e d w ith Zinc was much worse* Remarks.

The a c tio n o f a sulphonamide on a fdngus b e in g

unknown t h i s tre a tm e n t was, as s t a t e d , c a r r i e d o u t p u r e l y as an ex p e rim en t. marked.

121

The improvement was n o t

(Skin)

Cas e Ho . 32.

Hame

Mrs. C.

H is to r y o f L esion

Age

36

Occupation

Housewife

For a t l e a s t te n y e a r s , h e r f i n g e r s

and hands had been raw and b le e d in g .

Her f e e t

too were sometimes a f f e d te d . P re v io u s tr e a tm e n t

Various ointm ents

C o nd itio n - 1 s t a tte n d a n c e . A ll f in g e r s and both hands and s c a t t e r e d a re a s on both f e e t were more or l e s s raw, e n c ru s te d w ith pus and dead e p ith e liu m . Pus

Mainly stap h y lo co ccu s a u re u s .

Io n iz a tio n

The r i g h t hand was t r e a t e d w ith 2^% P r o n t o s i l

f o r 6 - 2 0 minutes a t 6 - 30 M.A. The l e f t hand (the l e a s t a f f e c t e d ) was g iv en u l t r a - v i o l e t ra y tr e a tm e n t. The f e e t were t r e a t e d with 1% Zinc c h l o r id e . Treatments, given R e s u lt

F if t e e n

A f te r n in e tr e a tm e n ts , th e P r o n t o s i l had

g r e a t l y improved th e c o n d itio n , th e r e was no change w ith th e u l t r a - v i o l e t Ray t r e a te d hand, th e f e e t had n o t improved as much as the P r o n t o s i l - t r e a t e d hand. A l l were changed to P r o n t o s i l , s ix f u r t h e r tre a tm e n ts were given to 20/6/41 when a l l the so re s had h e a le d . 122

(Skin)

As th e s k in was very dry O live O il and i n f r a - r e d ra y s were a p p lie d . Follow up

1 2 /8 /4 1 .

No so re s anywhere could he found

h u t th e s k in was s t i l l v ery dry.

128

(Skin)

Case Bo. 34

Name

Mrs. N.

Age

H is to r y o f L esio n

55

Occupation

Housewife

H y p e rk e ra to sis and u l c e r a t i o n o f

b o th hands f o r over one y e a r. P re v io u s T reatm ent

X-ray tre a tm e n t had been g iven f o r

many months;

i n f r a - r e d ra y tr e a tm e n t p lu s o liv e

o i l and ointm ents o f v a rio u s kinds had been a p p lied . C o nd itio n - 1 s t A ttendance t h i c k , rough

The sk in o f h e r f i n g e r s was

and deep raw f i s s u r e s were p r e s e n t

on h e r k n u c k le s. Io n iz a tio n

She was s e n t from th e X-ray departm ent w ith

th e r e q u e s t rlto g iv e h e r something" du rin g the absence o f some o f th e s t a f f , b u t n o t to g iv e h e r u l t r a - v i o l e t ra y tr e a tm e n t. 2|-% P r o n t o s i l a t 5 M.A. f o r 10 minutes was u t i l i s e d R e s u lt

The raw a re a s showed no sig n s o f h e a lin g a f t e r t h r e e tr e a tm e n t s .

The h y p e r k e r a to s is was n o t

affected . Remarks

No change in

her

c o n d itio n was o b serv ed .

124

(Skin)

Case Uo» 37 Age 27

Name. Mr. B.

H is to r y o f L esio n

Qccupation

B agineer.

A day or two b e fo re C hristm as 1940,

t h i s mat^s r i g h t f o o t s lip p e d down a manhole, b r u i s i n g th e s k i n . P re v io u s tr e a tm e n t Pus

D e rm a titis fo llo w ed .

O intm ents.

Mixed i n f e c t i o n

C o nd itio n - 1 s t A ttendance

1 4 /5 /4 1 From

th e knee, h is whole r i g h t le g

t h e ankle

was covered

to w ith

a c r u s te d p u s t u l a r d e r m a t i t i s . Io n iz a tio n

He was given tre a tm e n t

w ith

- 20 minute*

P r o n t o s i l a t 15-40 M.A.

T reatm ents given R e s u lt

f o r 15

F o u rte en .

A few tre a tm e n ts showed improvement, then a t h i s n e x t a tte n d a n c e , th e le g was as bad as ev e r.

Subsequent tre a tm e n ts r e s u l t e d in no

change f o r th e b e t t e r . Remarks .As a l l p re v io u s sk in l e s i o n s had r e a c te d so w e ll, i t was hoped t h a t a s im i l a r r e s u l t would have been o b ta in e d .

There i s no doubt t h a t he s c ra tc h e d

some a re a s which showed a l i t t l e improvement and a l s o he was determ ined to have compensation. 125

(Skin)

n e v e r t h e l e s s , I do n o t t h i n k he d e s tro y e d e n t i r e l y th e growth which should have shown I f P r o n t o s i l was g oing to have been su c c e s sfu l*

126

(Skin)

Case Ho, 38

Mame

Miss P.

Age

H i s t o r y o f Lesion

25

O ccupation

Household d u t i e s

This young woman s c r a tc h e d h e r

fin g e rs w h ils t c u ttin g ro ses, a f o rtn ig h t before a t t e n d i n g a t th e Department.

P u s tu le s formed

then the pus spread under th e ep id erm is. P re v io u s tr e a tm e n t

B oracic l i n t d r e s s in g s ;

b a th s in

D e tt o l. Pus

S taphylococcus A ureus.

C o n d itio n - 1 s t A tte n d an ce.

22 /7 /4 1

The second and

t h i r d f in g e r s o f l e f t hand up to th e hand were sw ollen and e n t i r e l y denuded o f normal s k in . Raw sh in in g weeping a re a s were i n t e r s p e r s e d w ith a r e a s o f p us, scabs and e p i t h e l i a l d e b r i s . Io n iz a tio n

Fpr l o m inutes, 2-%% P r o n t o s i l was used

a t 15 M.A. T reatm ents given R e s u lt

Three

A f te r th r e e tr e a tm e n ts , the f in g e r s on 2 9 /7 /4 1 were normal in s i z e , new s k in had begun to form except a t th e k n u ck les, where i t was s t i l l a l i t t l e raw. were g iv e n .

Ho f u r t h e r tr e a tm e n ts

On 8 /8/41 th e f in g e r s were norm al. 127

(Skin)

Follow up

Again seen in September, when h e r f i n g e r s

were s t i l l normal*

128

(Skin)

Case Ho. 45

Hame

Mr. P.

Age 71

H i s t o r y o f L esio n

O ccupation

R e tir e d .

F or more than a y e a r h i s l e f t le g

had been u lc e r a te d . P re v io u s tr e a tm e n t

Ointments and E l a s t o p l a s t bandage had

been t r i e d . C o n d itio n - 1 s t a tte n d a n c e .

21/10/41

The low er h a l f of

h i s l e f t l e g was p r a c t i c a l l y a l l fcczematous. S e v e r a l v a r ic o s e u lc e r s were p r e s e n t in t h i s a r e a . Two were th e s i z e o f a f l o r i n , one t h a t o f a s h i l l i n g and numerous o th e rs which were sm all b u t deep. Pus

Ho germs were found.

Io n iz a tio n

2-J% P r o n t o s i l was used a t 30 M.A. f o r 20

m in u tes. T reatm ents given R e s u lt

Fourteen

cu red.

F ollow -

up

Ho r e l a p s e has occurred w ith in th e month

which has elap sed s in c e h is d is c h a rg e .

129

(Skin)

Case No. 46 Name

Mr. W.

Age

H is to r y o f L esion

72

O ccupation

R e tir e d

F or over two months an u l c e r on h i s

g r e a t to e had g r a d u a l l y become b ig g e r . P re v io u s tr e a tm e n t

o in tm en ts and d r e s s i n g s .

C o n dition - 1 s t A ttendance

A f t e r adm ission t o th e Wards

i t was found t h a t he was a d i a b e t i c .

A lthough

l a r g e doses o f i n s u l i n were g iven h i s blood su g ar n ev e r became s a t i s f a c t o r y w h i l s t th e r e was no g l y c o s u r i a On 1 0 /9 /4 1 th e u lc e r was l^*1 x

n and was f a i r l y

deep. Pus X -rav

Staphylococcus Aureus No bony d is e a s e

I o n iz a tio n

10 M.A. f o r 20 minutes was u se d 9

2

P r o n t o s i l b ein g the e l e c t r o l y t e . Treatm ents

T w enty-eight

R e s u lt By 7 /1 1 /4 1

the u lc e r was one t h i r d the o r i g i n a l

s i z e and a b rid g e o f h e a lth y sk in had grown a c ro s s th e middle o f the u l c e r .

U n fo rtu n a te ly

on 1 8 /1 1 /4 1 he had a se v ere p ain in h i s a n k le , h i s f o o t became sw o llen , gangrene s e t in and sp rea d to th e whole f o o t. o u t b u t the p a t i e n t died . 130

Amputation was c a r r i e d

(Skin)

Case No. 47

Name

Mr. F .

Age 39

H is to r y o f L esion

O ccupation

C lerk

u l c e r on h i s 4 th r i g h t to e had been

p r e s e n t f o r 11 weeks. P re v io u s T reatm ent

O intm ents, S ulph anilam id e i n t e r n a l l y

and e x t e r n a l l y . C ondition - 1 s t a tte n d a n c e

On th e in n e r s i d e o f th e

4 th r i g h t to e an u l c e r th e s iz e o f a s h i l l i n g and deep was p r e s e n t . Wassermann R eaction Blood Sugar Pus

Pus f i l l e d th e u l c e r .

N eg ativ e.

This was w ith ih normal l i m i t s .

S taphylococcus Aureus.

Io n iz a tio n

This was g iv en a t 4 M.A. f o r 20 minutes

u sin g 2-^% P r o n t o s i l . T reatm ents g iv en R e s u lt

F o u r.

No change was se cu red .

His d o c to r asked i f he

could be ad m itte d f o r i n v e s t i g a t i o n .

E x cisio n o f

%

the u lc e r was c a r r i e d o u t on 1 2 / L l A 941.

He was

s e n t from th e Wards on 1 A 2 /4 1 f o r P r o n t o s i l io n iz a tio n .

H a lf o f the te r m in a l p h alan x had

d isa p p ea re d and the whole to e was now u l c e r a t i n g . 131

(Skin)

Follow up

He i s s t i l l under tr e a tm e n t and no a p p r e c ia b le

change has y e t been observed ex cept t h a t the pus i s c o n s id e r a b ly l e s s .

(Accident)

Case Ho« 6 * Ha me

Sapper R*

H is to r y o f L esion

Age 28

O ccupation

S o ld ie r.

This man was a c c i d e n t a l l y s h o t

th ro u g h h i s l e f t hand on 1 4 /7 /4 0 .

The b u l l e t

p assed between th e second and t h i r d m e ta c a rp a l bones. P re v io u s Treatm ent

An o p e ra tio n was perform ed in a

m i l i t a r y h o s p i t a l b u t th e wound had d isc h a rg e d pus s in c e i t s i n f l i c t i o n . C ondition - 1 s t A ttendance

On 1 8 /8 /4 0 the e x i t wound on

the palm o f the hand had been a b o u t l ^ ,f in d ia m eter and was now a d is c h a r g in g s in u s the s i z e o f a th ree p en n y p ie c e and about one inch deep. Pus

S ta p h y lo c o c c i and S tr e p to c o c c i

I o n iz a tio n

For 10 minutes the wound was io n is e d w ith

2%jt a t 6 M.A. Treatm ents given R e s u lt

Four

The wound was co m p letely h e a le d a f t e r fo u r tre a tm e n ts (He was re tu r n e d from the m i l i t a r y h o s p i t a l l a t e r f o r c o r r e c t io n o f l i m i t a t i o n o f movement).

Follow up

6 /11 /4 1

tr e a tm e n t.

The hand has remained h e a le d s in c e The f in g e r s have remained s t i f f .

Remarks A d e f i n i t e and speedy c u re , w ith no r e l a p s e .

133

(Accident)

Case No, 20 flame

Sydney B*

H is to r y o f L esio n

Age 17

O ccupation A p p re n tic e E n g in eer

In a c a r a c c id e n t

on 2 2 /4 /4 0 , t h i s

young nan s u s t a i n e d a compound comminuted f r a c t u r e o f h i s r i g h t Femur, P re v io u s T reatm ent

An open o p e ra tio n was perform ed, th e

fragm ents o f bone b e in g removed and the condyles p in n e d . On 1 3 /6 /4 0

he ran a te m p e ra tu re , pus

was found under th e p l a s t e r , which was removed. A la r g e a re a o f h is h e e l , knee and s m a lle r a re a s were found denuded o f sk in and were oozing w ith pus* Various d r e s s in g s and su lp h a n ila m id e powder were t r i e d .

Tersch g r a f t i n g was c a r r i e d

o u t on th e h e e l. C ondition - 1 s t A ttendance

4 /1 2 /4 0 .

th e h e e l was s a t i s f a c t o r y . a r e in d i c a t e d .

134

The c o n d itio n of

The unhealed wounds

(Accident)

There was no s k in ov er th e knee, th e wound was f i l l e d w ith pus and measured 6" x 4 11 (1) Wounds (2) and (3) measured l ^ ,f d ia m eter and 2

*i x

r e s p e c t i v e l y , th e form er s u rro u n d in g a

s in u s

in d ia m e te r and which s q u i r t e d pus on

p re ssu re * Pus

S h o r t ch ain s t r e p t o c o c c i wire p r e s e n t .

Io n iz a tio n

5*> P r o n t o s i l was used a t 4 M.A* f o r 5

minutes* R e s u lt

A f t e r 7 tre a tm e n ts wound (1) had h e a le d w ith

th e ex cep tio n o f 1 sq uare in c h .

Wound (2) s t i l l

oozed pus b u t only the sin u s remained and o b v io u sly a sequestrum was involved or th e p e rio ste u m , alth o u g h the X-ray r e p o r t was f a v o u r a b le .

The

to

s in u s p assed downAth e bone.

Wound (3) was h e a lin g

b u t n o t so d r a m a tic a lly r a p i d . A f t e r 20 f u r t h e r tr e a tm e n ts only the s in u s remained unhealed and he was d isc h a rg e d from the wards to a t t e n d a s an o u t - p a t i e n t , 1 4 /2 /4 1 . L ip ia d o l was i n j e c t e d in to the s in u s and X -ray showed s e v e r a l w inding tr a c k s making t h e i r way to th e s u r f a c e a t th r e e p o i n t s as w e ll as to th e p r e s e n t opening.

Fragments o f bone were a l s o observed.

135

(Accident)

He was d isc h a rg e d on 1 3 /6 /4 1 from the departm ent f o r o p e r a t io n . Treatm ents g iv en Follow up

Tw enty-four

O p eratio n perform ed 1 7 /9 /4 1 b u t t h i s has n o t

y e t h e a le d ( 6 /1 1 /4 1 ) .

The p r e - p a t e l l a r wound has

n e v e r broken down. Remarks

I f th e re had been no s e q u e s tr a * t h i s boy could

have been d isc h a rg e d from h o s p i t a l a f t e r seven tr e a tm e n t s .

The s ti m u la tio n o f growth o f sk in was

n o tew orthy , w h i l s t th e c le a n s in g a c tio n in th e i n h i b i t i o n o f pus form atio n was e v id e n t a f t e r th e f i r s t tr e a tm e n t. Ian K itc h in , F .R .C .S . th e o r th o p a e d ic su rg eo n , whose p a t i e n t t h i s was, gave u n s t i n t i n g p r a i s e , c o n s i d e r i n g the r a p i d i t y w ith which th e s k in h e a le d as most s u r p r i s i n g .

136

(Accident)

Case No. 22

Uame Miss W.

Age 58

H is to r y o f L esio n

O ccupation

House d u t i e s

In Ja n u ary 1940, she f e l l down

s t a i r s and f r a c t u r e d b o th m alleoli o f h e r l e f t le g w ith

backward d isp lace m en t o f the

astra g a lu s .

Wooden s p l i n t s were used b u t as

s o re s developed she was s e n t to the Royal L a n c a s te r I n f ir m a r y .

The whole le g was very oedematous

and l a r g e a re a s w ere.denuded o£ s k in . P re v io u s T reatm ent

S tim u la tin g d r e s s i n g s , s u l p h a n i l a -

mide powder and sk in g r a f t s were t r i e d b u t a l l fa ile d . C ondition - 1 s t A tten dan ce

2 4 /1 2 /4 0 .

ifce l e g was

v e ry w asted , the knee j o i n t and an kle were an k y lo se d .

X-ray showed g e n e r a lis e d r a r e f a c t i o n

o f th e bones o f th e a n k le and at^phy o f th e knee jo in t.

Large raw a r e a s , as in d ic a t e d were p r e s e n t,

th e f a s c i a co v erin g th e muscles showing when th e f o u l s m e llin g pus was c le a r e d away.

The sk in

between th e se a re a s was t h i n , r e d , f r a g i l e and s h in y .

137

(Accident)

Pus

S ta p h y lo c o c c i only were found.

Io n iz a tio n

P r o n t o s i l was used a t 20 M.A. f o r

10 m inutes, B e s u lt

A f t e r fo u r tr e a tm e n ts , t h e r e was no sm e ll

from th e wounds , th e p a t i e n t f e l t much e a s i e r and b e t t e r , th e wounds were cle a n and d ry , g ra n u ­ l a t i o n s were p r e s e n t and th e re was some growth inwards from the edges. F ou rteen more tr e a tm e n ts were c a r r i e d o u t. Only one sm all a r e a , the s i z e o f a six p e n c e , was n o t q u ite h e a le d though l e v e l w ith the now normal s k in aro un d. in

This was a t th e an k le (1 ).

A- l i k e c o n d itio n

A nother,

b u t s l i g h t l y l a r g e r was

p r e s e n t over the head o f th e f i b u l a ( 3 ). o t h e r wounds were com pletely h e a le d . 138

The

She was

(Accident)

d is c h a rg e d a f t e r having s p e n t ov er a y e a r in h o sp ita l.

On a c co u n t o f th e d i s t a n c e from

L a n c a s te r she was unable to a t t e n d a s an out* p a tie n t. Treatm ents given Follow-up

e ig h te e n

7 /1 1 /4 1

The l e g has remained " b e a u t i f u l l y

h e a le d up" Remarks

The h e a lin g h e re was slo w er than in th e p re v io u s case (No. 2 0 ).

This was to be expected on ac co u n t

o f (a) age (b) th e lo n g e r d u ra tio n o f i l l n e s s (c) th e d e b i l i t a t e d s t a t e o f th e p a t i e n t (d) the l a r g e r areas in v o lv e d .

N e v e rth e le s s s i x

weeks tr e a tm e n t r e s u l t e d in a cure a f t e r one y ea r o f th e u su a l methods o f tr e a tm e n t.

As in the

p re v io u s two c a s e s , th e new s k in was alm o st normal in ap pearan ce, was p l i a b l e , t h i c k and in every way s a t i s f a c t o r y .

139

(Accident)

Case 30.

Name Mr. H.

Age 18

H is to r y o f L esion

O ccupation L o rry d r i v e r . 3 /3 /4 1

His arm was caught in the

b ra k e o f a heavy t r a i l e r and r e s u l t e d i n a T shaped f r a c t u r e o f the humerus and l a c e r a t i o n s round th e whole elbow. P re v io u s Treatm ent

Routine d r e s s in g s and P r o n t o s i l

powder. C ondition - 1 s t A ttendance

24 /4 /4 1

A band 6" wide

a l l round the elbow j o i n t was devoid o f s k in ex c ep t f o r a b rid g e o f d e v i t a l i s e d s k in 3 lf wide ta p e r in g to 1" in th e A n t i c u p i t a l F o ssa . P a r t s o f th e denuded a r e a were showing f a s c i a o r muscle s u r f a c e and over a l l , pus was p r e s e n t (See p h o to g r a p h ) . Pus

m ainly s ta p h y lo c o c c i

I o n iz a tio n

2^% P r o n t o s i l a t 10 - 20 M.A. f o r 10 - 20

minutes was io n is e d on to elbow, t h r i c e weekly Treatm ents g iv en R e s u lt

e ig h te e n .

In two weeks time the sk in had grown 1 Ma l l

round th e edges, fo llo w in g s i x tr e a tm e n ts . a d d i t i o n a l twelve tre a tm e n ts h ealed

An

the elbow

e n t i r e l y ex c ep t f o r sm all p r a c t i c a l l y h ea led p o in ts ab o u t -J" in d ia m eter in a l i n e and th e s e 140

1 -4 0 .' -p a g e see

(

Case

30*

24/ 4 / / 941 .

B efore

irertm en t.

A F T E 'R ,

IR£,

3.M .J.

2 8 / 6 / 4 1 . 986 .

18,

G.elmo*

(S tuck-T esas S t a t s J , J u l y 1940 225 )'

19,

Eisemberg ,

( S t u c k - T e x a s S t a t e J . ."led J u l y 19---0. 225 )

Med.

20

,

H ie ts c h & X la re r

( S t u c k - T e x a s S t a t e J , Med J u l y 1 2 4 0 . 225 )

21

.

Domagk G ,

J i l i n M sc hr, 13. 1413 I S 57 ( S t u c k - T e x a s s t a t e J . Med. J u l y 1 2 40, 325 )’

28 ,

Beeker

I ' t s c b - M e d . Vsschr, 1 2 5 7 . 7 , 3 3 1

25*

B u r d i e , A.W. & Hey R.W L a n c e t 5 r d J u l y 1257

24 ,

(Bayer)

18.

H o r t s o h r , T h e r , 4 1 3 5 S . 222 ( B a y e r )’

S igel Jaeger

Btsch. J e d . M schr, 3 2 . 1 8 5 1 IS 56 (Bayer)

26,

T ilin g , B

Munch, n e d « J s c ih r , 8