Document b5k8ZnzK5Dmq32zQr8v98awkZ

COPY March 10, 1955 The Jo u rn al of the American Medical A ssociation 535 Hoijth Dearborn S tre e t Chicago 10, I llin o is TO-'THE' F.DIT0H: ; Hie January 22 issu e of th e Jo u rn al contains a re p o rt authorized -by the Council on I n d u s tr ia l Health and the Council on Pharmacy and /Chem istry, e n title d "Misuse of .dathamil Ca le ium-Di s odium f o r Prophylaxis o f Lead Poisoning." Some of th e view points expressed th e re in are more c o n tro v e rsia l than may be apparent to the casu al re a d e r. Inasmuch as there a re divergent opinions supported by su b stan tial evidence, these deserve to be recorded in the Journal. ' Since the re p o rt cen ters around "prophylaxis*`of lead poisoning, a d e fin itio n of prophylaxis is required. In th is p a rtic u la r connection, prophylaxis may mean the prevention of lead accum ulation, or i t may mean prevention of tis s u e damage secondary to lead accum ulation. There i s no questio n th a t the lo g ic a l means of preventing lead accumul atio n is to prevent exposure to lead in absorbable fo ra , lienee, in the present s ta te of our knowledge, adm inistration of any chemical agent fo r th is purpose would tr u ly be a m isuse. ' On the o th e r hand, in a d d itio n to the la rg e number o f in d iv id u a ls mentioned in the re p o rt who have lead poisoning, there are many more who have la b o ra to ry evidence of s u b s ta n tia l lead accumulation b u t may o r may no t have minor c l i n i c a l evidence of lead poisoning, such as m ild anem ia,occasional mild c o n stip a tio n , e tc . The prevention of overt symptoms of lead poisoning such as lead encephalopathy, p e rip h e ra l neuropathy, severe anemia, o r lead cramps by reducing e x is tin g lead accumulation in th ese in d iv id u a ls i s a lso prophylaxis. Use of edathamil calcium-disodium ("Calcium Disodium Versenate*) fo r t h is purpose is not, in my opinion, a misuse of th e m a te ria l. On the c o n tra ry , when the in d u stria l physician has been unable to achieve h is f i r s t objective-- namely, the prevention of lead accumulation -- h is second objective must be the recognition and treatm ent of the disease as early as possible, p re fe ra b ly before demonstrable tis s u e damage has occurred. The re p o rt im plies th a t th e re i s no j u s t i f i c a t i o n f o r the ex isten ce of in d u s tr ia l lead poisoning. Though th is may w ell be tr u e , the p rac tic al fa c t is th a t lead poisoning continues to e x ist despite many years of in te n siv e e f f o r t to elim inate i t on the p a r t cf dedicated persons in the medical profession. N 9764 TO THE EDITOR 2 March 10, 195$ This f a c t i s c le a r ly in d ic a te d by th e fig u re s quoted w ith in th e re p o rt. Since lead poisoning does e x is t, the re a lis tic a ttitu d e fo r a physician must he th a t i t i3 hi3 re s p o n s ib ility , having done what he can to prevent the condition, to tre a t i t or to prevent i ts exacerbation. As the re p o rt in d ic a te s , th e re i s a s u b s ta n tia l evidence o f the value of Calcium Disodium Versenate* a s a th e ra p e u tic agent when given p aren terally in the presence of ex istin g lead poisoning. This fa c t i s a tte s te d by w ell over 20 p u b lic a tio n s in the m edical l i t e r a t u r e . However, the re p o rt questions th e e ffic a c y o f `Calcium Pisodium Versenate ` when given by mouth* The bases fo r t h is pessimism seen to .lie f i r s t in the established fa c t th a t the m aterial is poorly absorbed from the g a s tr o - in te s tin a l t r a c t , and second, th a t even though u rin a ry e x cretio n o f lead may be increased by the o r a l use o f th is m a te ria l, fe c a l e x cretio n of lead may be correspondingly decreased. That such a diversion might occur is suggested by a b rie f a b stra c t report of stu d ies performed in ra b b its aciitely poisoned by lead a c e ta te . I t i s apparent th a t th ere are major biochemical d ifferen ces between lead poisoning in ra b b its and humans, and a lso between acute lead poisoning and chronic. That these d ifferen c e s are of c r i t i c a l importance is ind icated by th e f a c t th a t d ata from 3 d iffe re n t la b o ra to rie s have now e sta b lis h e d th a t th ere i s an o v e ra ll in crease in t o t a l lead e x cretio n follow ing the o ra l a d m in istratio n of 'Calcium Disodium. V ersenate' to humans w ith lead poisoning. Moreover, th ere i s now ample c li n i c a l evidence o f both o b jec tiv e and sub jectiv e improvement in in d iv id u als w ith mild lead poisoning when tre a te d w ith o ra l 'Calcium.Bisodium V ersenate' . Such d a ta are found in 3 published a r t i c l e s , '^ ) (3) (h) in 3 more papers which are c u rre n tly in p re ss, and in unpublished d a ta from over 20 individual in v e stig a to rs throughout the country. These rep o rts describe su b ject ive improvement which was not d u p licated w ith placebos, and o b jectiv e improvement as measured by in crease in the hemoglobin and red c e l l count, decrease in stippled c e lls , increase in urinary, lead output, and decrease in blood lead} a l l of fa r g re a te r magnitude than th a t seen in control p a tie n ts during comparable periods of tim e. The re p o rt s ta te s th a t "Even i f th e re should be some o v e ra ll in crease in the rate of elim ination of lead, the quantities of lead involved in rela tio n to the to ta l q u an tities absorbed or retained in the body under the conditions of p o ten tially hazardous exposure to lead probably would be too sm all to be of p ra c tic a l sig n ific a n c e ." l l ) h ie d e rs, I-.: E ffe ct of O ral NajjCa Ethylenediarainc T e traa ce tate on U rinary and F ecal E xcretion o f Lead in R abbits, Fed. Proceed. 13*397 ( March)19Siu (2) Sidbury, J.B . J r .} Bynum, J.C . and F e ta , L.L.} E ffe c t of C helating Agent on U rinary Lead E xcretion. Comparison of Oral and Intravenous A dm inistration, Proc. 3oc. Exper. B io l, and Med. 82:226-228 (Feb.) 1953. (3) Bradley, J .E . and Powell, A .iC 'J r . j O ral Calcium EDTA in Lead In to x icatio n of Children, J . P e d ia tric s b5*297-301 (September) 195b. (b) C o tte r, L .II.: Treatment o f Lead Fclsoning by C helation, JAMA 1$$:906-908 (Ju ly 3) 195b. ----- Ke 0 008614 / ' V b TO TTF. EDITOR March 10, 1955 I t i s tru e th a t, a t the present tim e, there i s no p ra c tic a l sh o rt term method to fre e th e body of i t s t o t a l burden o f le a d . However, th e symptoms and sign3 of lead poisoning a re produced by a r e la tiv e ly sm all fra c tio n of the to ta l body lea d . I t i s , th ere fo re , not necessary to render the p a tie n t le a d -fre e in order to improve a l l indices of lead poisoning and to reduce the danger of serious sequelae. I t i s only necessary to render h is s o f t tis s u e s r e l a ti v e ly f r e e from le a d . That s ig n if ic a n t amounts of s o f t tis s u e lead can be removed in a reasonably sh o rt period of time by means of o r a l 'Calcium Disodium Versenate' therapy is w ell established by the extensive experience mentioned above. I f t h is enables th e workman to re tu rn to h is job . more q uickly and shortens th e prolonged absence from work which i s commonly required f o r e x cretio n of s o f t tis s u e le a d , the r e s u lt i s certainly "of practical significance." The re p o rt a lso s ta te s " C e rta in ly , i f a s ig n if ic a n t in crease in elim ination were to be achieved, v ir tu a lly continuous use of the p ro p h y lactic agent would be re q u ire d ." I know of no evidence in support of t h is statem en t. Furtherm ore, so f a r as I know, no respons ib le person has recommended the continuous use of 'Calcium Disodium Versenate' except as a research procedure under carefully controlled circum stances. On the c o n tra ry , th e lo g ic a l approach would be to use th is m a te ria l in courses a t in te r v a ls to remove accumulated le a d . The re p o rt s ta te s "When th e p hysician in in d u stry undertakes by m edical means to p a l l i a t e th e e f f e c ts of ab so rp tio n o f dem onstrably dangerous q u a n titie s of lead by in d u s tria l employees, he must look a t h is reasons f o r doing so and in a l l h u m ility and p ro fessio n al in te g r ity ask him self where the w elfare o f h is in d u s tr ia l wards may l i e . " In f u l l agreement w ith t h i s statem en t, I submit th a t th e "w elfare o f h is in d u s tria l wards re sid e s in removing "the demonstrably dangerous q u a n titie s of lead" as rap id ly and sa fe ly as p o ssib le. I submit f u rth e r th a t the removal of lead from the body by means of a ch elatin g agent i s in no sense of the word " p a llia tio n " . On the co n tra ry , the treatm ent of lead poisoning in i ts e a rlie s t recognizable fora,'w hich i s fe a s ib le by a d m in istratio n of o r a l Calcium Disodium V ersenate", i s in my opinion, c o n s is te n t w ith the h ig h e st id e a ls o f the m edical profession. In summary then, i t i s my opinion t h a t s u b s ta n tia l published and unpublished evidence dem onstrates the e ffic a c y of Calcium Disodium V ersenate' when given by mouth to remove le a d . Second, th a t any safe and e ffe c tiv e means o f removing lead from th e body i s a d ir e c t and lo g ic al approach to the treatm ent of lead poisoning, whether diagnosed by symptoms o r by lab o ra to ry evidence o f lead accum ulation. T hird, th a t th e use of Calcium Disodium Versenate to remove lead from an in d iv id u a l who has been shown to have absorbed "demonstrably dangerous q u a n titie s of lead" should no t be condemned as "misuse" simply because previous methods have fa ile d . He 0003315 TO T ir EDITOR 4i- March 1 0 , 195$ And fo u rth , to condemn the use of a chemical agent to remove lead on the basis th a t th is might encourage la x ity in the prevention of lead accumulation seems to me to be analagous to arguing t h a t p e n ic illin should never have been made a v a ila b le because i t makes the cure of v en eral d ise ases too easy, and thus encourages prom iscuity. Both concepts may be tru e b u t a re sc a rc e ly proper d e cisio n s f o r the p h y sician who i s c a lle d upon to care fo r th e i l l or p o te n tia lly i l l . S incerely Yours, Nn'K -m d Norman Y>. X arr, M.D., Ph.D. D irecto r, C lin ic al Research Riker Laboratories, Inc.