Document X4YEjLmXyX5b53ergmBKbaqy

Ba l t im o r e Cit y H o s p it a l s F r e d e r ic G. H u bba r d d ir e c t o r 4 9 4 0 EASTERN AVENUE BALTIMORE, MARYLAND 21224 January 10, 1966 fN REPLY REFE R TO: Dr. Robert A. Kehoe The K e tte rin g 'Laboratory C ollege o f M edicine Eden Avenue C in c in n a ti 19, O h io . ' Dear Dr. Kehoe: " I am indebted to you fo r yo ur le tte r o f December 23 fo r i t makes me take a more c ritic a l look a t the questions w hich you raise. 1 do b elieve tha t chronic: or recurrent acute infections may have a deleterious e ffe c t in the grow ing c h ild upon the ultim ate outcome o f chronic lead in to x ic a tio n , p a rtic u la rly i f there are repeated or chronic in fection s during the firs t year fo llo w in g the c h ild 's recovery from acute lead encepha lo p ath y and his rem oval from abnorm al lead exposure. The data w h ich I person a lly have to support this are scanty. They are mentioned in my paper e n title d "Q u a n tita tiv e U rinary C oproporphyrin Excretion and its R elation to Edathamil C alcium Disodium A d m in is tra tio n in C h ild re n w ith A c u te Lead In to x ic a tio n " a re p rin t o f w h ich I am enclosing. The p e rtin e n t paragraph is found on page 1134 and 1135 w h ich I have marked. I have looked up the data upon w hich the statements in this paragraph are based and can g ive you some more d e ta il. The e vid e n ce is based upon studies in fiv e c h ild re n d u rin g acute b a c te ria l in fe c tio n s (pneum occocal p ne u m o nia-2, stre p to co cca l tons i 1i tis --3) w h ich occurred two to tw e lve months fo llo w in g recovery from acute lead encephalopathy. A ll had been removed from abnorm al lead exposure. S erial blood lead determ inations showed continuous decrease in blood lead concentration and no rise at the time p f the acute in fe c tio n . Two o f the three patients who showed a s ig n ific a n t increase ijn u rin a ry co p rop o rp hyrin e x c re tio n re ce ive d EDTA as w e ll as tre atm e n t fo r th e ir in fe c tio n . In response fjo EDTA a d m in is tra tio n , th e ir u rin a ry lead e x c re tio n increased to q u a n titie s comparable to the outputs shown in figure 2 o f the enclosed reprint. In other words, the y resppnded just as w e ll as those c h ild re n w ith o u t acute in te rc u rre n t in fe c tio n . Two o f thpse patients had a number o f other studies. The o n ly a bn o rm a lity found was an increase in cerebrospinal flu id protein co nte nt a t the tim e the urinary coporporphyrin was e le va te d . One o f the two patients who had acute b a c te ria l in fe c tio n and showed no rise in u rin a ry co prop o rp hyrin o u tp u t also showed no s ig n ific a n t increase in urine lead excre tion when EDTA was adm inistered: Sub sequent random observations in grow ing c h ild re n have shown th a t the urinary copro porph yrin fa lls when the in fe c tio n is brought under c o n tro l w ith a ppropriate a n tib io tic s . I f one w aits u n til the urinary coproporphyrin decreases and gives EDTA at that point, 2. January 10, 1966 there w ill be no s ig n ific a n t increase in urine lead e xcre tio n . G ra nte d , these represent observations on a ve ry few patients^ b ut I b e lie v e th e y are v a lid and 1 m ight say we use them in the c lin ic now in the sense th a t any c h ild re co verin g from lead in to x ic a tio n who has acute in fe c tio n always g et a u rin a ry co prop o rp hyrin d e te rm in a tio n and receives treatm ent i f the o u tp u t is s ig n ific a n tly increased. I have concluded from these data th a t acute in fe ctio n s, p a rtic u la rly during the early re co very phase, can cause an increase in the "c h e ia ta b le " lead. The source o f this lead is, o f course,, a m a tter o f sp e cu la tio n . I t may sim ply be th a t thefe is a re d istrib u tio n o f lejad w ith in in d iv id u a l so ft tissue ce lls in the presence o f in fe c tio n cjnd th a t the lead is m erely removed to another com partm ent w ith in the c e ll o r bound to <jj d iffe re n t p ro te in where i t is more accessible to EDTA. M y assumption th a t some o f the lead w h ic h is e x crp te d may comp from bone is c e rta in ly based upon in d ire c t in fo rm a tio n , but it should be noted thd t growth arrest lines re g ularly occur w ith each in fe c tio n in the young g ro w in g c h ild . The lines seen by x^-ray represent the fa c t th a t new bone is not being la id down in the presence o f in fe c tio n , This, in tu rn , may in te rfe re w iith the normal d e p o sitio n and redejposition o f lead pn the bone crysta l. A t this tim e, t seems lik e ly th a t sjuch lead m ight be released in to the c irc u la tio n and taken up by tlje so ft tissues; howeVer, I have n p 'd ire c t evidence on this point. - ; I o rig in a lly becjame interested in the re la tio n s h ip between in fe c tio n la n d chronic lead in to xica tio n because o f the observation in a few patients that the permanent brain damage suffered by them seemed opt o f proportion to both the length o f the in i t i a l abnorm al leajd ingestion and the se v e rity o f the in it ia l acute illness. I noted in th e ir records thatj they suffered repeated acute respiratory infections during the first ye ar fo llo w in g th e ir rem oval from abnormal lead ingestion. I have also seen four ch ild re n who have djemonstrated peripheral neuropathy o f the type reported in chronic lead in to x ic a tio n . The neuropathy in these ch ild re n occurred in association w ith infections during the w in te r fo llo w in g th e ir recovery from acute lead encephalopathy. A t the times these episodes o f neuropathy o ccurre d, we could fin d no e vidence o f renewed abnorm al le|ad ingestion. , Thus, I do b e lie y e th a t repeated in fe ctio n s d urin g the firs t six to tw e lv e months fo llo w in g rem oval frpm abnorm al lead sources can have a d elete rio u s e ffe c t in terms o f causing an exacerbation o f lead in to x ic a tio n . Repeated m inor insults may be c u m u la tiv e and thus Worsen the u ltim a te outcom e. I w o u ld agree w ith yo u ,, however, th a t this problem should be more c a re fu lly worked out. I hope during the coming year to begin a study on the ch ro n ic phase o f lead in to x ic a tio n in c h ild re n andj this is c e rta in ly one o f the points on w hich we shall try to obtain better.data. | 1 hope I have answered the questions in your le tte r o f December 23 c lia r ly . I f n o t, I do hope you w ill! w rite me. A g a in , many thanks fo r yo u r le tte r. ; S incerely yours, ; / A ssociate Professor o f Pediatrics Johns Hopkins U n iv e rs ity Scjhoo! o f M e d icin e a9