Document KzvbgY8qkjnGZ9nLOoNqB2Jr0

D r . Th eodore L. Br y an - (2) - A p r il 4, 1955 d iffe r e n t d e gr e e s of su b d iv isio n in th e e r y t h r o cy t e s: 1. O n e can u se th e M cC o r d t ech n iq u e - th e so - c a lle d Ba so p h ilic A ggr e gat io n T e st , w h ich in v o lves a ll of th e e r y t h r o cy t e s w h ich con tain b asop h ilic m at e r ial - stip p led c e lls, b asop h ilic er y th r ocy tes, an d som e, at le a st , of th e r e t icu lo cy t e s. M cCord h as d e scr ib e d th e tech n ique an d h as given th e lim it s c it s sign ific a n c e on a q u an t itativ e b a sis. 2. One can u se an y of the m eth ods th at h ave been d escrib ed for stain in g the er y th r o cy tes, an d an y of th e p r o ced u r es ad vised by v ar io u s o b se r v e r s fo r obtain in g qu an titative o r sem i-q u an titative estim ate s of the n u m b ers. v, Th e m o st im p o r t an t th in g is to d evelop d ata in o n e 's own h an d s, fr o m h is own u se of th e m eth od se le cte d , an d to put the p r o ced u r e on a s u n iform an d qu an titative a b a sis a s h is sk ill an d fac ilit ie s w ill p erm it. In coun tin g th e n u m b ers of stip p led er y th r o cy te s on e m u st fir st h ave excellen t m icr o sco p ic equipm en t, m u st develop a very good an d u n iform m eth od of m akin g an d stain in g the film s,an d m u st spen d en ough tim e on e ach film to d e t e r m in e th e n u m b e r s of "st ip p le d " e r y t h r o c y t e s (n ot t h o se th at a r e b aso p h ilic but th ose th at h ave d istin ct gr an u le s, w h eth er c o ar se o r fin e ) in r e la t io n to..th e t o t a l n u m b e r s o f e r y t h r o c y t e s se e n . Th e b e st m e a n s o f e x p r e ssio n i s th at o f n u m b e r s of "st ip p le d V e r y t h r o c y t e s p e r m illio n ar y fh r p sy :tes-. In a r r i v i n g a t t h is e St im h t e , w e f in d i t n e c e ss.a r y to coun t not l e ss th an fifty fie ld s in w h ich th e e r y t h r o cy t es a r e d istr ib u t ed even ly w ith out o v e r lap p in g. . I attach h erew ith a d e scr ip t io n of the p r o ced u r e w h ich we u su ally u se . We som etim es u se W righ t's stain in stead of that d e scr ib e d , an d it w orks sat isfact o r ily if one ch ecks the stain carefu lly , from tim e to tim e (certain ly e v e r y n ew b at ch ), w ith a film (o r film s) o f known c h a r a c t e r , w ith r e fe r e n c e to the n u m bers of stippled eryth rocytes th ereon . A s I h ave in d icated ,th e en tire p roced u re is a p oor one fo r the p u rp ose. Som eth in g lik e h alf o f th e film s ob tain ed (on e -per m an ) fr o m an y gr ou p o f exp osed m en - u n le ss th eir exp osu re is of th e g r o ssly d an gerou s type th at r e su lt s in frequ en t c a se s of le ad poison in g - w ill give n orm al r e su lt s at an y tim e you ch oose to look at th em . Th e h igh r e su lt s a r e n ot n e c e ssa r ily in d icative of d an ger, an d th e low r e su lt s give no r e a l a ssu r a n c e of safe t y . Th e b e st th at on e can say is th at th e av e r age valu e of a ll of th e fin din gs fr o m a sp e cific grou p of m en w ill give som e club to the se v e r ity of the e xp o su r e of th e gr o u p a s a w h ole, a s co m p ar ed w ith th e fin d in gs fr o m a gr o u p th at is n ot su b je ct e d to an y e xp o su r e to le a d , o r w ith t h o se fr o m gr o u p s w h ose e xp o su r e to le a d is c le a r ly m u ch g r e a t e r o r m u ch l e s s se v e r e . Th at is to sa y , the m eth od w ill d iffer en tiate gr o u p s, to som e KE 0019986 D r . T h e o d o r e L. Br y an - (3) - A p r il 4 , I9SS e xt e n t , in a c c o r d a n c e -with t h e se v e r i t y of t h e ir e x p o su r e , bu t it s a p p lic a t io n to the in d ivid u al.m an is v e r y u n tru stw orth y. T h e r e is on e fe a t u r e of th e ph en om en on th at i s of Som e sign ific a n c e . If a m an who h as b een givin g low r e su lt s b egin s su dden ly to d evelop an in c r e a se of a p r o g r e ssiv e c h a r a c t e r in th e n u m b e r s, on e h ad b e t t e r lo ok ou t. Even th is, h ow ever, is not sp ecific eviden ce of in cr eased lead ab sorp tion , sin ce n o r m al in d iv id u als, fo r no r e a so n w h ich on e can fin d , h ave sh ow er s of st ip p le d e r y t h r o cy t e s in t h e ir p e r ip h e r a l blood fr o m t im e to t im e . P e o p le v ar y in th is r e sp e c t , som e ten din g to be v e r y st ab ile an d o th er s la b ile , w ith r e fe r e n c e to t h e ir h e m at o p o ie t ic r e sp o n se to n o n - sp e c ific st im u li. In deed th e m o r e on e st u d ies th is ph en om en on , tile m or e u n r eliab le it is foun d to be in r e latio n to le ad ab so r p t io n . I m u st say an ad dition al w ord of cau tion on a m atter of m ed ical tech n iqu e. If I h ad to a c c e p t th e m e d ic a l r e sp o n sib ilit y fo r a grou p of m en w h ose occu p ation in volved d an ge r o u s e xp o su r e to le a d , w ith out h avin g th e fa c ilit ie s th at w ould en ab le m e to b e a r th at r e sp o n sib ilit y in ac c o r d an c e w ith sou n d m od ern m ed ical kn ow ledge an d tech n ique, - an d th an k God o r good fortu n e t h at I 'm n ot in t h at p o sit io n , alt h o u gh I d `d h av e su c h s e r i o u s r e sp o n si b i l i t i e s b e fo r e iw e in v e st ig a t e d an d d e v e lo p e d r e a l l y s a t i s f a c t o r y m e t h o d s an d p r in cip le s - I w ould depen d l e s s upon th e n o n - sp e cific lab o r at o r y fin d in gs b a se d on h e m ato lo gical ch an ges,' an a m o r e upon w hat I cou ld fin d of p r o d r o m al an d in cipien t sign s of lead in toxication , in m y h an dlin g of the situ atio n . I w ould u se th e lab o r at o r y fin d in gs, sin ce th ey w ould h elp, but I w ould n e v e r allo w th em to a lt e r m y c lin ic a l ju d gm en t in an y in st an ce in w h ich I su sp e c t e d th at in t o xicat io n m s im p en d in g o r in w h ich I fou n d it in an e a r ly st a ge . In m y opin ion , th e d epen d en ce of a w ell tr ain ed an d cap ab le p h y sician , in su ch a situ ation , upon th e fin d in gs of a tech n ician in a h e m a t o lo gic al la b o r a t o r y ,b o r d e r s on c r im in al n egligen ce o r m a lp r a c t ic e , in t h e se d a y s o f k n o w le d ge on t h e se m a t t e r s . So m e c lin ic ia n s, lik e JElst on Belk n ap , sa y th ey depen d on "st ip p lin g" to gu ide th em . Do n ot be d eceived ; th ey do n oth in g of th e kin d. Th ey know th at th e exp o su r e in t h e ir p lan ts is u n der reason ab ly good con trol, an d th at se r io u s d isab ility is not to be expected am on g the m en un der th eir su p ervision , if they keep th eir clin ical ey es open . If th e "st ip p lin g" w arn s th em th at a m an n eeds sp e cial atten tion , th ey give it, an d a c t acco r d in gly . If it fa ils to w arn th em , a s u n fortu n ately it so m e t im e s d o e s, th ey h ave a r e lat iv e ly m ild c a se o f le ad poison in g to d eal w ith . Fu n d am en tally , Belk n ap , who is a b e t t e r clin ician th an m an y, d ep en d s upon h is clin ical ju d gm en t. If it co in cid e s w ith th e la b o r a t o r y fin d in gs, a ll is w ell an d e asy ; but if the two do not agr e e , h e ac t s on h is clin ical ju d gm en t. H e d en ies t h is, but I am qu ite cu re it is t r u e , n ev er - th ele ss. ^ E 0019987 D r . Th eod or e L . Bryan . - (4) - A p r il 4 , 1955' In g e n e r a l, t h e fi g u r e o f 8 t o 12 st ip p le d e r y t h r o c y t e s p e r fift y m ic r o sc o p i c fie ld s- {b y o u r t e ch n iq u e t h is i s ab o u t 6 0 0 to 1000 st ip p le d e r y t h r o c y t e s p e r m illion ery th r ocy tes) is com m on ly r e gar d e d a s th e poin t of d ifferen tiation betw een sa fe an d d an ger o u s ab so r p t io n . It is a s good a r u le o f th um b a s an y , bu t a s I sa id b e fo r e , if y ou ap p ly t h is r ig id ly , you t ak e m en emt of w ork who a r c in no d an ge r at a ll, an d you le a v e m en at w ork w h ose d an ge r , h ow ever sligh t it m ay be, is im m in en t. I h ave tak en m u ch m o r e t im e th an I can affo r d to sa y th e se th in gs in a l e t t e r , w h ich I hat-re said , in t h e l i t e r a t u r e , n o t a b ly in t h e r e p o r t o f th e Com m ittee on h e ad P oison in g of th e A P H A, an d a lso in the w ork ed ited by J ran k P atty , In d u strial H ygien e an d Toxicology, pu blish ed by In ter scien ce P u b lish e r s, I n c ., w h ich , in cid en tally , vn ll corn s out in a n ew edition b efo r e m an y m on th s. H ow ever, I h ave spen t so m uch o f m y life in an effo r t to get d ecen t m eth od s of m e d ic a l con tr ol in to th e Ibad t r a d e s, th at it se e m s a-'bit late to econ om ise. I t r u st t h at v o u r - q u e st io n s h a 1/ a b e e n a n sw e r e d in su ffic ie n t d e t a il to b e o f assist an ce to you. ' Cord ially y ou rs, Robert , Keh oe, M. D. ei 0019388 T H E O D O R E L . BR YAN , M . D . 3 12 0 Stp.te,v S t r e e t E a s t St . Lo u i s , I l l i n o i s M arch 9, 1955 D r. R ob ert Kehoe Ketterin g Lab oratory College of M edicin e Eden & Beth esd a A ves. C in cin n ati 17, Ohio D ear D r , Kehoe: In ch eckin g of blood sm e ar s of m en th at w ork ar ou n d le ad fu m e s in th e sm e lt in g, e t c . , th e p r o b le m h a s b een r a ise d a s to the n um ber of field s and the ap p roxim ate n um ber of c e lls th at sh ou ld be ch ecked to d eter m in e th e p r e ce n t age of stipplin g. An oth er p rob lem is w h eth er or not b asip h illic red c e lls ar e coun ted. Th e la st qu estion is w hat do you con sid er th e upper lim it s of n or m al of stipplin g and b asip h illic r e d c e l l s ?I I w ould ap p r e ciate you r tim e an d co n sid er atio n in t h is m a t t e r . T LB:gm K& 0018989 0 Th eodore L . Bryan , M .D .