Document 09g4qepOr9ndyXy8Z90mXRpV

THIRD REPORT OH THE IWE3IXGAT1GH OF LEAD POX SOHO. An Investigation of lead poisoning which has boon m pro gress for the last thro yours at the Harvard Medical School:id, now being terminated* Th funds for th investigation wen donated the Rational Load Xnatltat. It is very gratifying that this or i isstion has not at any ta effored suggestions as to my policy point of view, tut has allowed th work to run its ours and to castrate the truth without regard for a possible economic effect up on th lead industries* 1h@ staff engaged in studying the various problems ha beezx as follows?- Dr* Joseph 0* Aub> Dr. Lawrence T* Fsdrhall, Dr. Anne S. Minot, Dr* Paul Reznikoff, Dr* J. Albert oy, aided by Dr* John Brady, Dr. Herman Bltaag&ri, Miss Dorothea E. Smith, Miss Charlotte Shaw, Miss Mary Morrison, and Mrs. Marion Frankfurter. Mush bene fit has also boon obtained by consultations with mny misabora of the faculty of th Harvard Medical School. During those thro years th problem of load poisoning has been studied neither as an industrial hazard nor in the light of pre ventive medicine, but with the desire to understand more fully the chemistry, physiology, and clinical aspects of the disease itself* This point of view was taken because the other typos of Investigation have been carried out ;j^uwu careful scientific work. for preventing th deleteri- ?0y ous effects of lead must be fundamentally dependent upon an under- --1-- N41776 standing of its action in tfe organism if they arc is bj effective, w hero, therefore, underinfcon an Investigation of th isf ' i' ili absorption, retention, and excretion of load % this body! and /, we haw boon able in this way to obtain a far olearer/ conception of f how and why lead produces tit clinical sign charaOtdr&stio' of load i i` poisoning and also of the cwcn&litons which control |ia oxorotloa* 531 following is a brief statement .of the; oonolasiono drawn frora this worlc;- tend is absorbed ttm tbs gastrointestinal tract* the lungs, i th mucous aaobran of tbs nose and mouth, and the fuj^ubsnoottf tit* \ sues. Absorption fro the respiratory tract is the most dangerous be cause most rapid and because It points diroot entrance of load into tlie general circulation. Absorption by the goatro-1nteetinal tract is mad less dangerous by the primary passage of lend through the por- tal circulation to the liwr --- which oatohos much' of the load and * crotos it In the bile* fho rate of absorption from tho disaontary om unabsorbod al ls also reduced because cf excretion oi^l&ad compound in the fccoa. in the blood mrm load is transported^* a highly dieporsod lend phosphate, and is deposited in the tissues largely by adsorption of colloidal p; this load phosphate is most insoluble at th normal hy drogen ion concentration of tho body,-- pH 7.4. v?hn a solution la raoro acid o?' alkaline than this, tho load io <E a solved to a. greater amount. <w t . Daring active absorption load is present in many of the tissue* of the body, for the moat part in the bones, liver, kidnays, and gastro-intestinal tract, but after absorption aeasea it becomes localised until nearly all is stored in the bones as a harm* pUvtfyCtfi less deposit of tri-lead. If lead would stay permanently In the bones it would probably exercise no toxio action except that which occurred during absorption. It is not perfectly stable in the bones, however, because for a long time after exposure has ceased it may appear in the excreta. Occasionally certain abnormal conditions develop which apparently cause a sudden liberation and flood th organism with soluble load, This may cause an acute attack of load poisoning. Such lat acute attacks are usually associated with acute infections, heavy drinking or unusual activities. It is therefor important to know just what are the mechanism which liberato lead, in order to establish a logical treatment and prevent development of th active manifestations of the disease. In making chemioal and physiological studies it became evi dent that if the reaction (pa) of the body becomes more acid or al kaline than normal, the triple phosphate of lead becomes more soluble. We have thi^f^re^stu^fd ;|^,sffect of changing the hydrogen ion concentratioW^l^tlio body by the administration of a diet low in oal* cium with acids or acid-forming substances such as phosphoric acid or ammonium chloride. This causes 10ss of calcium from th bones. Ihen tried on animals it was found to increase the lead excretion. - S- Ingested soda bicarbonate also increased the lead excretion#--prob ably by making the body so alkaline that til triple phosphate of lead is rendered soluble. Those experiments illustrate how a change in the general metabolism of the body may suddenly liberate lead from the bones and have thus suggested a new treatment of plumb! a which has been used on patients with success. This may be briefly outlines as follows*- When lead is causing acute symptoms, inoother words, when too much is circulating in the body, large quantities of cal cium arc given in order to favor deposition and prevent release of lead from the bones. This may be done by giving adequate quantities of milk. For lead colic active catharsis and atropine should also bo given. After the acute symptoms have subsided elimination of the more easily mobilized lead may be accomplished in several ways,-- )' r v the mBl^gatisfactory of which is to give a diet containing little oeiXci1^,>p.lu%qhi%?forming substances. The diet consists of moat, potatoesi^rigd,-maoaroj^,ftpplS> bananas, sugar, salt butter, and bread made without milk. Milk, green vegetables or other fruits may not be included ithxthis T^g$ to ten grama of ammonium chlo ride is given daily in water. By this treatment lead excretion is increased more than three times. Other methods fhieh are not so ef fective but which do increase elimination of lead involve administra tion of large doses of soda bicarbonate or potassium iodide. Thus, by varying the diet and the medication control of load metabolism is now possible. A study of the mechanism underlying wrist drop is not'com pleted, but the experiments so far all suggest that wrist drop Is - 4- produced by muscular fatigue and that the action of the lead la on muscle and not nerve. ' i?e have also $ lead la the hones of individuals who had* a far as they knee* not boon ex posed to lead in industry. It was present In only three of twen ty-two cases, This indicates that the average Individual does riot rotfcih lead under present conditions of life. The knowledge of distribution is important .fra* tbs raodfbo-legjal point of view in regard to deaths-ascribed to load poisoning. If lead,has boon an important factor in causing death it should be distributed in many organs. If, however, it is present only in the bones, it sig- only tlmt '>'*<> *M USan place, loa(J Sf^tl^p^^ced4%^iw intoxication or death. *" '' A p ?0Studi'ea^of the mechanism by which1 lead affects the body cells wore made with red blood corpuscles and muscle. Its action on blood colls was oarefblly investigated, and the roaults partly checked by its action on muscle cells. The effect on red colls is to make them, hard, brittle, and inelastio. They break up more rapidly than normal cella- This is th explanation of tho high peripheral blood destruction in lead poisoning -- with the result ing anaemia. This is due to a reaction of the lead with tho inor ganic phosphate of th cell surface, which produces a change In per meability and elasticity with a resultant definite strain. In iso lated muscles, this is demonstrated by an increased permeability - 6- to inorganic phosphates and "by more rapid fatigue* The following detailed reports of these investigations hare in the medical literature been published, and they give a complete outline of the work done*- Thirhall, L. T.: lead Studies, I, The Estimation of Minute Mounts of lead in Biological Material, J. Indust. Hyg. . 4s 9-20 (May) 1922. Minot, A. S.s lead Studios, II, A Critical Bote on the Electrolytic Determination of lead in Biological Ma terial, J. Biol. Chem. 55s 1-8 (Jan.) 1925. Aub, J* C.j Reznikoff, Paul; and Smith, D. E.s lead Stud ios, III, The Effects of lead on Red Blood Cells, J, Exper. Med. 55 s 151-208, 1924. Key, J. A.s lead Studios, IV, Blood Changes in Acute Load Poisoning in Rabbits, to. J. Physiol., to be published. Minot, A. 3.s Lead Studies, V, The Distribution of load in the organism in Acute and Chronio Lead Poisoning, J. Indust. Hyg. S: 125-186, 157-143, 149-168 (Aug) 1924. Biumgart, H. L.t Lead Studies, VI, The Absorption of Lead from the nasopharynx, J. Induat. Hyg. 5i 155-158 (Sept*) 1925. Fairhall, L. T-: Lead Studios, VII, The Phosphates of Lead Equilibrium in the System Load Oxide-Phosphoric AnhydrideWater at 25 deg., J. to* Cheia. Soc. 46t 1593-1598 (July) 024. Fairhall, L. T.s Lead Studies, VI11, The Mioroehemic&l Detection of Lead, J. Biol. Chem. 57: 455-461 (Sept.) 1923. Fairhall, L. f.s Load Studies, IX, The Solubility of Va rious Lead Salts in Blood Serum, J. Biol. Chem. 60* 481-484 (July) 1924. Tair5talL3b,.. L. T., and Shaw, Charlotte; Lead Studies, X, The ' " ' Bbp'dsitiorf d^/Lead Salts in Bone Tissue, J. Indust. Hyg. 6* r. ,, 159-168 (tog) 024. Fairheili, L. T. j Lead Studies, XI, A Rapid Method of Anal yzing Urine for Load, J. Biol. Chem. 60s 485-488 (July) 1924, 6 u Minot, A. S,, and Aub* 4* Ch|i t Load Studies* XII, Th Mesh,* ardsms for Storage and| Excretion of toad, to be pub lished. A Mb, J. C. , and Minot, A. S. | /'.'|ioad Studies, XITI, Th Treat ment of L&ad Poisonia^l':be published* Koenlkoff, Paul; and Aub, J. |,C. | Lead Studies, XIV, Experimen tal Studios in Lead Ps|sy| to bo published. Aub, J. C.; Minot, A. S. } L^trhall, 1. T.; and Rsznikoff, Fault Load Studies, XV, Reoejdt investigations of Absorption and Excretion of Lead in |heJOrganiam, J. of th A. a,. A., '63/:BS8ASaE,(Aug.2$')|i9Z4. : it' t t \u.\ ' f{ In addition to these idieijp is still one report to be published, a monograph, -which is njim nearing completion. It is to appear in the medical journal entitled nM0dioina" in the near future, and also as a monograph published by Williams and Wilkins of Baltimore. Th? * fitud.v hns tfe-.v This study has throrrn light on several nm aspects of the action of lead on th body which should be of importance not only in understanding the Action of load itself but also that of other toxic substances* ru -j a fW-fijAi A\ VAWT^bGbOn,*yjGGiGAi * $"} VfUc*A'rf'eti! i 7