Document kmMnyawV2jxJGoNkYjdjeMm5J

Kill REPORT ON THE INSTIGATION OF LEAD POISONING* , - t '! jj An Investigation f load, poisoning which has boon ijjfc pres- ' ' { A, gross for the last three years at th Harvard Medical School ;I&, now :J \ boing terminated. The funds for the investigation wore donated \>y tho national. Load Institute. It is very gratifying that this organ- *\ ization has not at any tim offered suggestions as to any policy oi* i\ point of view* bat has allowed tho'work to run its course and to don\<* onstrat tho truth without regard for a possible economic effect up- \ > on the lead industries* Tho staff engaged in studying tho various problem has boon as follows:- Dr* Joseph 0. hub* Dr* tawronco t* Fairhall, Dr. Anne S. Minot* Dr* Paul Rosnlkoff* Dr. J. Albert Hoy* aided by Dr. John Brady, Dr. Herman Blmgart, Mias Dorothea E. Smith* hiss Charlotte Shan, Hiss Mary Morrison, and Mrs. Marion Frankfurter. Much bone- fit has also boon obtained by consultations with many members of tho facility of tho Harvard Med^|^||SjjhOGl^ > 41# During these three the problem,of load poisoning has bon studied neither ue cul industrial ma&rd' hor in tho light of pro- voniivo nodioino* but with the desire to understand more felly the chemistry* physiology* end clinical aspects of tho disease itself. This point of view was taken because the other types of Investigation have boon carried out frequently in recent years, and do not permit careful soiontiilo work. Any measures for preventing tho dolotori-. ous effects of load must bo fundamentally dependent upon an undor- t-- standing of Its action in tho organism if they aro to bto effective. V'o have, therefore, undertaken. on i?/oaiigation of the ,problms. of / tli absorption, rotontica* and excretion Of load toy ihjb bedyi and i\ vo have boors able in this vay to obtain a far clearor/ concoction of how arid vhy load produces the oXirdcal signs oharactdlristia of load' } i- poisoning and also of the conditions rhioh control its excretion. ! She following is a tori of .stat^?ient of the;' conclusions draw fren this n-ork;~ Load la absorbed fros the gastrointestinal tract* the lungs* i tho nacous acabrono of the nose and mouth, and the eujboui&rvooua tis \ sues. Absorption, iron, tho respiratory tract is the nest dangerous toe- cause most rapid and because it pomits direct entrance of load into tho general circulation. Absorption by tho gastro-dnttostlnal tract is r,adoy||^p|f^rigb8^i*i^y-J%rf^%'f-ihary passage of load through tho po*w tal circulatliO^btto `the .which eatcho much of the load and oo**' crotos it in tho olio, fho rate of absorption from tho alissontary can*. unatosorbod sX is also reduced because cf excretion oi^Iead corpounds in. the fdcos* in tho blood s&rvsa ` Load is transported^aa a. highly dieparsed lead phosphato* and ia deposited in the tissues largely by adsorption of colloidal particles. This load phosphate is aost insoluble at th normal hy drogen ion coneontrailon of tho body,--* pH 7.4. ?'ben a solution is tsoro acid or alkaline than this* tho Iced is dissolved to a. greater amount During active absorption load is present in many of the tissues of the body, for the most part in the bones, liver, kid neys, snd gnstro-intestinal tract, but after absorption ceases it becomes localised until nearly all is stored in the bones as a harm- ftUviJyCrMX . loss deposit of tri-lead. If load would stay permanently in the bones it would probably exorcise no toxic action except that which occurred during absorption. It is not perfectly stable in the bones, however, because for a long time after exposure has coascd it nay appear in the excreta. Occasionally certain abnormal conditions develop which apparently cause a sudden liberation and flood the organics with soluble load. This may cause an acute attack of lead poisoning. Such late acute attacks are usually associated with acute infections, heavy drinking or unusual activities. It is therefore important to know just what are the mechanisms which liberate lead, in order to establish a logical treatment and prevent development of the active manifestations of the disoe.se. In making chemical and physiological studies it became evi dent that if the reaction (pli) of the body becomes more acid or al kaline than normal, the triple phosphate of load becomes more soluble, 'fo havo theroforo studied tho effect of changing tho hydrogen ion concentration of tho body by the administration of a diet low in cal cium with acids or acid.-forming fj&fttt&P?0?. such as phosphoric acid or ammonium chloride* This causes .,IJissT,,'i./ioC fh I b\'di-Ciun from'the bones* Ivhon tried on animals it was found to^ndi^hSe t}|-,ie&& excretion. Ingested soda `bicarbonate also inoro&sod the lead excretion,--prob ably by asking the body so alkaline that tho triple phosphate of lead is rendered soluble. Those experiments illustrate how a change in tho general metabolism of tho body may suddenly liberate lead iVcn the bones and have thus suggested a now treatment of plumb!sn which has boon used on patients -with success. This may bo briefly outlines as follows:- Vhcri load is causing acute symptoms, inoothor words, when too much is circulating in tho body, largo quantities of cal cium arc given in order to favor deposition and prevent release of load from the bones* This nay bo done by giving adequate quanta ties of milk. For lead colic active catharsis and atropine should also be given. After tho acute symptoms have subsided elimination of the more easily mobilized load may bo accomplished in several ways,-- the most satisfactory of which is to give a diet containing litt!. calcium plus acid-forming substances. The diet consists of noat, potatoes, rice, macaroni, .apples, bananas, sugar, salt butter, and bread mad without milk. Milk, green vegetables or other fruits may not bo included .wl Mthvthis eight to ton grams of ammonium chlo ride is given daily in water. By this treatment load excretion is increased mere than three times. Other methods which are not so f- but which do increase elimination of lead involve administra tion of largo doses of soda bicarbonate, or potassium iodide. Thus, by varying tho diet and the medication control pf load metabolism is now possible. A study of the- mechanism underlying wrist drop is not' com pleted, but tho experiments so far all suggest that wrist drop is produced by muscular fatigue and that the action of the lead is on muscle and not nerve. Te have also s`vs;"a' r'.'o.'h"' e'd"0--r- of load in the bones of individuals who had, so far- as thoy knew, not boon ex posed to lead" in industry. It was present in only three of twen ty-two caoosi' This indicates that tho average individual doos not retain load under present conditions of life. Tho knowledge of distribution, is important from. the medico-legal point of view in regard to deaths ascribed to load poisoning. If load has been an important factor in causing death it should be. distributed in many organs. If, however. It 1.s present only in tho bones, it sig nifies only-that absorption has taken place, but n0* recently.produced active intoxication or death. Studios of tho mechanism by which lead affoots tho body colls wore made with rod blood corpuscles' and ran solo* Its action on blood colls was carefully investigated, and the results partly chocked by its action on muscle colls. The effect on rod colls is to aako then hard, brittle, and inelastic. Thoy break up more rapidly than normal colls. This is tho explanation of tho high peripheral blood destruction in load poisoning -- with tho result ing anaemia. This is duo to a reaction of tho lead with tho inor ganic phosphate of surfap^ vjh^ip^^roduoos a ohango In por- '<, .< y ij meabiilty and ciasticity^with^ a rpispltant^dofiirito strain. In iso- latod muscles, this is doxnonstratod'by'hh increased permeability to inorganic phosphatos and by more rapid fatigue. Tho follovring detailed reports of these investigations have in the medical literature boon published, and they give a complete outline of the -work donos- Fairhall, L. T.: Load Studies, X, The Estimation of Minute Amounts of Load in Biological Material, J. Indust. Hyg. . 4: 9-20 (May) 1922. Minot, A. S.f Lead Studios, II, A Critical Lot on the Electrolytic Deierrain'ation of Lead in Biological Ma terial, J. Biol. Chera. 55: 1-8 (Jan. ) 1922. Aub, J. C*j Roznikoff, Paul; and Salih, D. E.: Load Stud.ios. III, The Effects of Lead on Red Blood Cells, J. Expor. Mod. .55: 151-208, 1824. Key, J. A.: Load Studios, I?, Blood Changes in Acute Load Poisoning in Rabbits, Am. J. Physiol., to be published. Minot, A. 3.: Lead Studios, V, The Distribution of Load in tho organism in Acute and Chronic Lead Poisoning, J. Xndust. Hyg. 8: 125-136, 157-148, 149-158 (Aug) 1924. BXungari, H. L.i Load Studies, 71, She Absorption of Load froat)n^.,|ps.opharyi', J. Indust. Ht:g. 5: 155-158 (Sept*) Fairhaili L. T.: Lead Studies, YII, Tho Phosphates of Load jss K` `Equilibrium in tho System Loud Cxida-Phosphoric Anhydride-- bator at 25 dog., J. Am. Chen. Soc. 4G,:,-1593~1598. (July) 1924, . Fairhall, L. I.; Lead Studies, VIII,. Tho Mici'ochemical Detection of Load, J. Biol. Chom. 57; 455-461 (Sopt.) 1923. Fairhall, L. T.: Load Studios,'IX, Tho Solubility of Va rious Lead Saits in Blood Scrum, J* -Biol. Chen. 60; 481--484 (July) 1924. Fairhall, L. T., and Shavr, Charlotte: Lead Studies, X, Tho Deposition of Load Salts in Bone Tissue, J. Indust. Hyg. 6: 159-168 (Aug) 3324. Fairhall, L. T.; Load Studiea, XI, A Rapid Method of Anal yzing Urino for Load, J. Biol. Choau GO: 485-488 (July) 1324. H 14 ? \\ liinot, A- S., and Attb, J. C.'j \ toad Studios, XII, The Xoch ardssaa Tor Storage and'. Ekcrcilon of Load, to "bo pub lished- ; . 1S Aub, J. 0., and Minot, A. S. : f ' ^oad Studios, XIII, Tho Treat ment of Lead Poisoning| to be published* Kcsrdkcff, Paxil] and Aub, J. ?G-f Lead Studios, XIT, Ibcperlsontel Studios in Lead PsJsy; bo published. Aub, J. C. j III not, A. S.j LJ&irhall, L. T. j and Seznikoff, Pauls Lead Studies, XV, liecqhtinvestigations of Absorption and. Ibcoretion of Lead in i|ho ;<3rganisa J- of the A. U. A., 83/ SSS-SSr , (Aug. 23),as 2dX In addition to these tioi is still one report to be published, a monograph, -which id nbw nearing completion. It is to appear in tho nodical ^ournajL entitled *,Eodlcin*` in tho near future, and also as a monograph.published by Lillians and Alikins ! '/ of Baltimore. Ti5 - fa- Ann h `Dhis study has thrown light on several new aspects of the action of load on tho body which should bo of. importance riot only in understanding tho action of lead itself but also that of ;:i1N vh!mmm rothor toxciic suubbestances. v*V.-nu?;v) A rMjMAAX :Vr. .\ 3 . ini a .; 7- *