Document wgm2QR81qy6nV7jMKVvVzKppQ

January 12, 1943* Dr* K a rl ieunbaoh., Dept# b io lo g ic a l Chords t r y , College of -iedicine, d iv e r s ity of C incinnati, C in c in n a ti, Ohio* Dear Dr* basabachs I have road w ith in t e r o a t your paper w ith Kehoe and logan in th e l a t e s t Jo u rn al o f Pharmacology and Ixporirasat& l horapexitics and should bo g ra te fu l for a reprint* I t is unfortunate th a t you were led to s ta te th a t your d a ta c a s t doubt upon my c o n c lu s io n s , when as- a -flatter o f f a c t th e d a ta you r e p o rte d a r e r a t h e r irrS'5&*Snt t o th o s e c o n c lu s io n s S in ce I r.n.y have f a i l e d to some e x te n t in leaking m ysolf p e r f e c t l y c l e a r i a my paper on th e le a d c i t r a t e com plex, p erhaps I may ta k e t i l l s o p p o rtu n ity o f c l a r i f y i n g th e i s s u e . by studying p o to n tio m s tric a lly c e r ta in s o lu tio n s o f sodium c i t r a t e and lo a d n i t r a t e I -was a b le t o a r r i v e a t a fo rm u la and a d is s o c ia tio n c o n s ta n t ( a t th e io n ic s tr e n g th end pH o f p l a s m ) f o r a le a d c i t r a t e complex w hich I " had p re v io u s ly shown to e x is t* From th e v a lu e f o r t h i s c o n s ta n t and th e norm al c i t r a t e c o n c e n tra tio n in human b lo o d i t was p o s s ib le to a r r iv e a t a v alu e o f about 20 fo r th e r a tio s (lo a d c i t r a t e complex)/ ( lead io n )* To s t a t e i t sim ply th o se d a ta in d ic a te t h a t 20 tim es as much load e x is te d as a so lu b le lead c i t r a t e io n th a n as sim ple lead ion* Mince w ith o u t knowledge o f th e presence o f so lu b le complexes o f lead in th e blood a l l th e so lu b le le a d m ust be in th e f o r a o f th e sim p le le a d *on, I Tree a b le t o s t a t e t h a t 11t h e norm al b lo o d c i t r a t e i s c a p a b le o f k eep in g i n so lu tio n . sn amount o f load 20 tim es as g reat as th a t which tho s o lu b ility o f the in so lu b le lead compounds o f th o body would o th e rw is e p e rm it* I do n o t ace how your fin d in g s o f lo s s th a n 10.5 o f th o blood le a d in th o sensei ( a f a c t w hich I had alw ays assumed as so on p u re ly th e o r e tic a l groundc) in any way c a s ts doubt on o r i s even p e r t i n e n t to my co n clu sio n * b o te t h a t I d id n o t say t h a t c i t r a t e o f norm al blood keeps 20 tim e s a s much le a d i n s o lu tio n ns i n in s o lu b le form* i-ote a ls o th a t you have no reason fo r assuming th a t blood in plasma is in ' s o lu tio n ,a s a m a tte r o f f a c t th e re is good re a so n t o f e e l th a t m ost o f th e plasm a lo a d i s n o n - d if f u s ib le * bven w ith 1,5 o f th o le a d o f th e b lo o d p r e s e n t in th e p la s m th e re could s t i l l be 20 tim es a s much le a d w e s e n t as th e c i t r a t e complex than as sim ple load ion* In o n ly one o &bq do y o u r r e s u l t s ap p ro ach p e rtin e n c e t o my c o n clu sio n s* N13982 This i s your experim ent w ith c i t r a t e a s an a n t i~o ongule n t * From p u re ly th e o re tic a l co n sid eratio n s I should expect c itr a te to cause mi in crease in plasma lead a t th e expense o f e ry th ro c y te lead* b u t oven here a f a ilu r e to observe such a r e d is tr ib u tio n would n o t r e f l e c t upon th e v a lid ity of njr co n clu sio n s sin c e c i t r a t e co u ld cau se an in c re a s e in d if f u s ib le over n o n -aiffu sib le lead e n tire ly w ithin th e p lasm lead frac tio n w ithout causing a change in t o t a l lead in th e p lasm * In your experim ent , however th e o i t r a t o wae in c o n ta c t w ith th e whole blood o n ly m om entarily b efo re c e n trifu g a tio n - ijardly a f a i r lortfith of tim e in which to d e te c t changes in so complex a system o f e q u ilib ria N e v e rth e le ss, th o you fin d no s ig n if i c a n t change in plasm a lead a f t e r th e a d d itio n of c i t r a t e , 1 f in d on exam ining your own f ig u r e s a s i g n i f i c a n t in c r e a s e i n p la s m le a d where c i t r a t e was used over t h a t w ith no a n tic o a g u la n t* t T i* o'-io ig n o re s th o ''le s s th a n " s ig n i n th o e x p erim en t on an im a l 7 on f in d s a mean in c r e a s e in plasm a le a d w ith o i t r a t o o f 45/ w ith a s ta n d a rd e r r o r o f 15*4, a t v a lu e o f 2*S2 and a p v a lu e o f 0*05 o r le s s -which i s c e r t a i n l y s ig n if ic a n t* I f on le a n s ov er backwards and c a l l s th e in c re a s e in anim al V n i l , one fin d s a mean in c re a s e o f 40$ w ith a sta n d a rd e r r o r o f 1 7 ,1 , a t o f 2*54 and a p value s lig h tly g re a te r than 0 ,0 5 , which c e rta in ly approaches s t a t i s t i c a l s i g n i f i c a n c e ) Ih u s we f in d t h a t f a r from c a s tin g do u b t on my c o n c lu s io n s , th o one p e r t i n e n t sxperitror v i.n y o u r p ap er a c t u a l l y eon* firm s my t h e o r e t i c a l p re d ic tio n s * \ i As a m a tte r o f f a c t f o r th o p a s t s i x months 1 have boon w orking in a s s o c ia ti o n w ith Nr* Aubifea an e f f o r t , among o th e r t h i n g s , to t o s t my th e o re tic a l conclusions as th ey apply to tho lead p a r titio n in blood in v itro and in vivo, i t req u ires ra re than an understanding of the p a rtitio n o f lead between plasma and c o lls to oonfirm o r r e je c t th e sig n ific a n c e of th e lead c i t r a t e complex in th e s ta te o f lead in th e blood* A d ir e c t approach would be by a study o f lead ion c o n ce n tra tio n in blood, b u t cinoe th a t is m a n ife stly im possible w ith p re se n t te c h n iq u e s, an approach can be made by stu d y in g th e d i f f u s i b l e f r a c tio n o f p la s m load and th o e f f e c t o f o itr a to thereon* Perhaps 1 , i n t u r n hove m isu n d ersto o d your c r i t i c i s m o f my c o n c lu s io n s * I f so above explanation m y have boon unnecessary* Aside from tlia t one reg etao $ l k fco o n etru ctio n I f e e l th a t your paper was most in te r o p tin g and has answered a problem o f fundam ental im portance in th e physiology of lead eoinoning* "legp o e t f u l l y , X E 0012267 Coymour f* f e t y