Document 6R0MKqnryEJaonyeY3rqEzvD4

/#!$r On the Diagnosis and Treatment of Lead Poisoning ROBERT A. KEHOE, M. D. CINCINNATI, OHIO From the Eichbcrg Laboratory of Physiology in the University of Cincinnati, Cincinnati, Ohio N36951 DUP050315119 Reprinted front THE JOURNAL OF MEDICINE, Cincinnati, 0March, 1930 On the Diagnosis and Treatment of Lead Poisoning* Ro b e r t A. Ke h o e , M. D., Cin c in n a t i, Oh io ' From the Eichberg Laboratory of Physiology in the University of Cincinnati, Cincinnati, Ohio The essential nature of lead poisoning, as well as that of the other heavy metal intoxications, remains a matter of specu lation and hypothesis. Despite the large amount of valuable clinical and experi mental information which is available, our knowledge is scanty at certain critical points, and much of the information which has been used to explain the entire picture is at best controversial. In this situation it is well to recognize the difference be tween facts and working hypotheses. When facts, even those of the most em pirical type, are made the basis of pro cedure and practice, we cannot criticize, even when these facts are seen to be in adequate. But when hypotheses are con verted into gospels' to be passionately held or just as passionately condemned, we are in danger of using them to conjure up wish fulfilment knowledge on the one hand, and to obscure and hinder the de velopment of new facts on the other. It is with these ideas in mind that I present some new facts which are of im portance in the diagnosis and the treat ment of lead poisoning. If these facts are not discussed in relation to existing inter pretations of the character of lead poison ing, it is because adequate interpretations must come more from the future than from the present or past, and because the facts by themselves are sufficiently im portant to occupy the time at our dis posal. The diagnosis of lead poisoning rests on a proper evaluation of the following mat ters : (1) Exposure to lead compounds; (2) susceptibility to lead; (3) symp tomatology; (4) physical findings; and (5) laboratory findings specifically related to lead to a greater or lesser degree. Such experimental evidence as follows is pre sented with the purpose of clarifying somewhat the means and the limitations involved in such an evaluation. Read at a meeting of The Academy of Medi cine of Cincinnati, December 9, 1929. Ex p o s u r e . Measurements of exposure have become a matter of necessity, not only in intelli gent efforts to prevent lead poisoning but also in diagnosis. A considerable amount of information has been collected, not ably by Legge in England, and Teleky in Germany, indicating the quan tity of lead exposure which is capa ble of producing lead intoxication over a period of time. With the tremen dous increase in industrial use of lead compounds, it becomes increasingly im portant to assess the significance of the exposure to lead associated with various industries. By far the commonest and most important exposures are due to the contamination of the air with finely divided lead compounds. It is a simple matter to measure the extent of such con tamination of the air in the immediate vicinity of workers. Thus most of the occupations in a particular industry have their own hazards, qualitatively and quan titatively. The toxicity of the lead com pounds varies with their physical and cK64fical characteristics, but it may be said that any type of lead dust, regardless of its solubility or particulate size is capable of producing lead poisoning if present in suf ficient concentration in the air inhaled by animals or man. It has been established on a fairly sound basis, that the regular inhalation through the usual working day of air containing less than five miligvams of lead per ten cubic meters of air does not produce serious lead intoxication in individuals of a representative group.1 A lower figure than this should be main tained in all industrial plants where lead compounds are used. One can only be sure that this is done by means of repeated examinations of the air breathed by workers. In the non-industrial population poison ing is most frequently occasioned by the 1Legge, Thomas M., and Goadby, Kenneth W.: Lead Poisoning and Lead Absorption, London, 1912, page 207. 3 TABLE I COMPARISON OF MEAN VALUES OF GROUPS WITH VARIABLE EXPOSURE . . Subjects in Faeces Lead in Urine Number of Mgs/Cm Ash Mgs/Liter Persons .087 .088 36 Medical Students-- .080 .080 71 exposure. Thus we have a valuable meth od of determining the relative magnitude of exposure in a particular occupation, by making a study of the lead excretion of a representative group large enough to take into account the sampling error occasioned Known Exposure Same Type Workmen--- History of Previous Exp.-- <Jarage Mechanics Moderately Ex posed workmen Severely Exposed Workmen........... .074 .100 .130 .192 .730 .096 84 by individual variation. On the other hand, with these data, we are able to clas .130 114 sify future subjects as to the significance .120 70 of their exposure to lead, by merely study .181 10S ing their excreta. .210 122 In the individual case in which the diag nosis is at stake the examination of a sin gle sample of faeces or urine or both does ingestion of lead with drinking water and not yield adequate information. This is wines and food, and in the case of chil especially true if the exposure has been dren especially, by chewing or sucking discontinued for some days or weeks prior toys, furniture, or other objects painted to examination. In the latter situation we with lead paints. That cases of the latter must study the individual's excretion long type occur is sufficient reason for abolish enough to determine the average rate of ing the use of lead paints on toys, beds, his excretion, and whether it is on the playpens, and furniture commonly used decrease. by children. Table II shows the continuous lead ex In the latter instances there is no sim cretion in the faeces and urine of one ple way of determining the extent of ex subject, J. F., whose lead exposure has posure, and even under industrial condi been moderate. The initial drop in excre tions the ordinary methods of measuring tion is most significant. It is a character exposure are inadequate in that they do istic feature of the excretion of all lead not indicate the extent of absorption of workers in a dusty atmosphere if observed lead which results from carelessness or immediately after removal from exposure. the improper use or inadequacies of res The first figure in the curve of faecal ex pirators and bathing and washing facili cretion represents largely lead inhaled ties. A better measure of the total pic during the previous day while at work, and ture may be obtained by a study of the subsequently carried from the upper res excretion of lead occurring among per piratory passages with mucus, etc., to sons who are experiencing lead exposure. the intestinal tract, where most of it is Table 1 illustrates the variation in the excreted without having been absorbed. extent of lead excretion shown by repre With the clearing of the nose and throat sentative groups selected because of ob and alimentary tract, the excretion falls served variations in degree of lead ex to the level occasioned by the magnitude posure. It is clear that the exposure to of lead which is actually absorbed into the lead on the part of most non-industrialized persons, is small. Nevertheless the con ditions of life on an earth consisting part TABLE II Lead Excretion JF ly of lead and in an environment in which lead is used for many purposes, presup pose some degree of lead absorption on the part of everyone. That such a small ab sorption produces a regular excretion of lead, militates against our ancient concept of an almost quantitative accumulation of lead in the tissues, and equally strongly against the notion that lead may exist in an immobile state in the body. It demon strates also that the toxicity of lead has a quantitative aspect. The table shows that lead excretion increases with . increased DUP050315121 TABLE US Urinwi) Cnnl<on of Lc<uj. severe. None of these men was ill at the time of study but all of them except the first, showed such signs of lead absorption, as lead line, considerable stippling of the erythrocytes and high faecal and urinary lead excretion. It would appear that even under conditions of severe exposure, measurable Quantities of lead in the circu lating blood are inconstantly found. The variation in this respect probably repre sents both sampling error and variation in the quantity of lead in the tissues. That is to say, a single subject may show lead in his blood at certain times and not at others, while one with a large lead content is likely to show a blood lead higher than tissues. Now as excretion continues, the one with a small lead content. This point amount ol lead in the body diminishes, will be referred to later. and the rate of excretion drops. Table III shows the resuits of similar observa tions on the urinary excretion on this sub ject and another, R. S., whose exposure was more severe--in fact enough to pro duce actual intoxication in a short time. The height and slope of the curves tell the story of the relative magnitude of the pre vious lead exposure. One cannot ignore the fact that the lungs probably contain lead in these cases, and that this lead is being continually absorbed into the blood and distributed in the tissues. Thus ab sorption is not entirely complete, and un til it is complete we cannot obtain the true picture of the relationship of excretion to the lead content of the body. It would appear, however, that this factor is not of sufficient importance to seriously inter fere with the drop in excretory rate. It may be possible to take this factor into account by a study of the lead in the blood, Another means of obtaining informa tion as to the extent of lead exposure and absorption is found in the various methods of recognizing the histological changes in the blood. I have not found any great superiority displayed by any one of these over the other. Variations in the reticu lated and basophilic erythrocytes are ap parently indicative of the same general type of change in the blood, as is shown by variation in the number of erythrocytes showing punctate basophilic stippling. Examination of the blood smears for stip pling is somewhat easier than any other method. Its sensitivity for the purpose for which it is used is entirely satisfactory. As a matter of fact all the microscopical blood changes used to estimate the extent of lead absorption show a significant change prior to the development of symp toms of intoxication, except in instances references to which will be made further on in our discussion. TABLE IV The lead content of the blood, has not, LEAD IN CIRCULATING BLOOD to my knowledge, been used as a means of clinical interpretation. In the present state of our information, one must be cau tious in arriving at conclusions as to its usefulness. It is entirely safe to say that Present Subject Exposure W.B.M.... Slight E.B___ J.W............ None i.p...... L.McD. Haemo - Sympgldbitx toms Stip/50 F 80 None 80 None None 80 None 95 None 1 6 0 6 %. Nil Nil Trace lead in any considerable amount found in TABLE V the circulating blood, furnishes evidence LEAD IN CIRCULATING BLOOD of significant lead exposure at some time. Table IV shows the result of .analysis of the blood in a number of subjects with lit tle or no exposure to lead. Table V represents a number of similar observa tions on a group of subjects whose ex posure to lead at the time of sampling' was Present Subject Exposure O.O. F..... Moderate M.M....... Heavy fc Heavy Heavy J.S------- Heavy W.D....... Heavy F.JJ..... Heavy E.M.___ Heavy J.F------- Moderate Haemo- Svmt>- Pb /Mgs globin toms Stip/50 F % 82 None 26 Nil 74 None 151 75 None 71 0.10 Trace 79 None 85 70 None 75 None 70 None --89 -- 0.19 0.42 74- None . .45 0.15 6? None 40 0.15 of sudden absorption of overwhelming amounts. Therefore it is merely a matter of convenience and experience as to which is used in following a group of workmen, or in arriving at a diagnosis. The only necessity in the use of these methods is that they be applied uniformly and quanti tatively, in relationship to known stand ards. Table VI shows a comparison of stippling counts, made by a standard meth od, for several groups of men under ob served variation of exposure. The sig nificance of the figures shown is unques tionable. In ascribing significance to microscopic blood changes, however, it is necessary to recognize that none of them is specifically due to lead-absorption. One must rule out other anemias and leukemias as well as the effects of the continued in halation of benzol, gasoline, and perhaps certain other volatile solvents. Even vari ations in exposure to sunlight involve his tological changes in the formed elements of the blood, and the limits of normal variation must be known more accurately than they are now, before we attempt to make refined conclusions on such findings. The foregoing evidences of exposure to lead, and consequent absorption, may not be used as a means of recognizing the presence or the likelihood of lead intoxi cation. All that can be. established by the study of lead excretion, lead content of the blood, and histological variations on the blood is the extent of the individual's ex posure. Obviously if his exposure can be shown to be of a type associated with the occurrence of lead poisoning, one may ex plain readily, perhaps too readily, the background of characteristic symptoms and physical findings. In industrial practice, however, it is not possible to anticipate the development of TABLE VI COMPARISON OF MEAN VALUES OF STIPPLING OF ERYTHROCYTES OF GROUPS WITH VARIABLE EXPOSURE , Subject Stippled Erythrocytes per 50 fields Medical Students..--.....-- 0.95 Workmen--No Known Exposure .................... .. 1,35 9iite Type Workmen-- History of Previous Exposure .............. 1.68 Auto Mechanics --........... 1.70 Large Group Persons in Dusty Lead Industry__ 17.0 Selected Persona with Heavy Exposure.........98.00 Number of Subjects 71 84 114 70 122 11 lead intoxication in an individual case, by means of these or any other known meth ods of observation. It can be said only that under a certain set of conditions of exposure, cases of intoxication are certain to occur in time. Armed with this infor mation the industrial physician can dem onstrate the need of limiting the exposure of the men under his care. This brings us to consider a question that has been at issue many times. When does lead absorption develop into lead in toxication? What are the earliest evi dences of intoxication ? In my experience the earliest signs of lead intoxication usu ally appear in the form of blood changes, except in those instances in which a sud den and large increase in exposure or a complicating illness bring about the sud den development of gastro intestinal ot nervous system symptoms. If the ex posure is comparatively regular and quan titatively constant, the first signs are like ly to be a drop in the haemoglobin con tent of the blood. This is usually preced ed by a progressive rise in the number of stippled erythrocytes, and followed by a diminution in the erythrocyte count. These occur very frequently without any subjective symptoms, or any other phys ical signs. On this basis, a steady rise in the number of stippled erythrocytes in any lead worker is to be regarded as a sug gestive sign of impending intoxication, while a progressive diminution of the haemoglobin content of the blood is to be regarded as an actual evidence of intoxi cation, with or without associated sub jective symptoms, except in those instances in which the blood changes are due to other causes. Su s c e p t ib il it y . Very little can be said about the under lying nature of susceptibility to lead com pounds as it is so dramatically observed in the case of certain individuals. With out attempting any explanation of the facts, it should be pointed out that there are certain conditions which are known to influence susceptibility. The most im portant of these are, (1) general vascular disease, (2) general hepatic disease, (3) tuberculosis, (4) active chronic infections in general, (5) starvation, and (6) fa tigue. In addition to these, immaturity in both animals and men is an important 6 i i i DUP050315123 factor. Any explanation of the mechan TABLE VIII ism concerned with lead poisoning must THE FIXATION OF LEAD IN THE CENTRAL account for these facts. I mention them NERVOUS SYSTEM at this time only to point out the neces sity for care in the exclusion from lead occupations, of persons in whom any of these factors are at work. In connection with vascular disease I cannot but state my tentative conclusion that lead intoxi cation is only doubtfully to be regarded as a cause of vascular disease. It rather appears that the incidence of arterio Rabbit No. 86 16 38 47 60 74 75 40 78 Ratio of Cone, in Brain to Lead in Brain Cone, in Entire Time in Days Mgs/% Carcass After Treatment 1.62 0.72 ' 1.15 1.45 1.31 2.08 1.86 1.69 1.27 2.0 0.6 6.0 16.0 18.0 52.0 23.0 42.0 53.0 1 3 150 330 270 420 240 300 510 sclerosis among lead workers is little if any higher than it is in a corresponding age group of the general population. On the other hand, the occurrence of lead intoxication in persons with arterio sclerosis is high indeed. I suspect that it is only because so many lead cases have arterio-sclerosis that the orthodox cause and effect relationship has been said to exist. Sy mp t o ma t o l o g y . It has been stated by many persons that the symptoms in lead poisoning are due to lead in the circulating blood. Up to the present there has been no direct evidence that such is the case. In fact, previous attempts to discover lead in the blood have failed because of a lack of analytical methods of sufficient sensitiv ity. If the symptoms are due to lead in the blood it should be possible to find lead present. Furthermore, the continual excretion of lead in the urine presup poses some quantity of lead in the blood. Accordingly we have attempted to find what quantity of lead is present in the blood. The previous tables (IV and V) have shown that it may be found. Table VII further illustrates the point and shows that in all the cases of acute ill ness studied by us to the present, lead is uniformly found in the blood in measur able quantities. It may well be that a range of concentration may be found con stantly associated with the presence of symptoms. At present it* may only be said that more than traces of lead in the blood indicate the strong probability of recent exposure of a significant type. The seriousness of nervous system symptoms as a result of lead absorption justifies some special consideration. Lead encephalopathy is the most dangerous manifestation of lead intoxication, and the most unsatisfactory from the point of view of treatment. Furthermore lead palsy, while usually not serious as to life, presents a gloomy prognosis as to the return of normal function. It is prob able that this is due to a quality of ner vous tissue, which is apparently not shared by any other tissue of the body. Nervous tissue has a striking ability of fixing such lead as reaches it. This is shown in Table VIII, in which a series of rabbits treated in various ways, but with considerable quantities of lead, have been killed for analysis after various per iods of time. Even after seventeen months, during which. practically all the other lead of the body has been lost, the brain of Rabbit No. 78 still retains an amount which is almost as great as that found in the brain of any animal of the series. It is interesting to note that the skeleton of this animal contained no de tectable quantity of blood. The imuortance of this lies in .the fact that if one has absorbed lead into the brain, he may presumably develop en cephalopathy at any time afterward. Thus may be explained the occasional develop ment of central nervous signs of lead in TABLE Vil toxication years after lead exposure has LEAD IN CIRCULATING BLOOD been discontinued. Subject Present Haemo- Sytnp- Ph/Mgs Exposure globin toras Stip/50 F % R.R____ Heavy J.L.B-- SI. Prolonged C.G.H..... Heavy C.G.H.... Heavy C.G.H.--. Heavy R.S------- Heavy 56 Slight 247 75 Slight 0 -- Encephalopathy -- -- Encephalopathy -- -- Colic -- 70 Colic 149 0.19 0.12 0.21 0.13 0.04 0.87 Just what occurs to enable lead in the brain to produce symptoms may not he stated with any certainty, but that symp toms are associated with lead in the brain tissue is shown by the following table 7 TABLE IX DISTRIBUTION OF LEAD {CLINICAL ENCEPHALOPATHY) CASE J. G. Tissue Lead Lead Mgs Mgs%* Weight Found per 100 gms Mgb %~ in Grams Milligrams tissue in carcass Rib Bone....... 15.00 Long Bone__ 12.25 Bone Marrow 6.60 Cartilage ..... 5.00 Suprarenal .. 5.00 Fat ........... . 20.00 Pancreas ...... 50.00 Spleen ........ . 150.00 Heart ........... 423.00 Kidneys ....... 300.00 Liver ........... 1300.00 Lung (rt)..... 650.00 Lung (It)..... 800.00 Brain ........... 1250.00 Spinal Fluid.. 13.75 Blood ........... 75.30 1.95 0.98 0.18 0.23 Nil Nil 0.18 1.29 0.58 0.65 9.20 0,68 0.44 4.85 Nil 0.10 18.000 S.000 2.769 4.600 Nil Nil 0.360 0.860 0.137 0.217 0.708 0.106 0.055 0.348 Nil 0.133 31.71 19.51 6.75 11.22 Nil Nil 0.88 2.10 0.83 0.53 1.73 0.26 0.13 0.85 Nil 0.32 5077.S0 20.81 0.410 1.00 This ratio between- the concentration in a particular tissue and that in the carcass as a whole represents a selective affinity for lead, which we have called an "index of selective absorption". (Table IX) illustrative of the distribu tion of lead in the tissues of a typical fatal case. It should be noted that the small amount of spinal fluid contained no lead, or at most an amount too small to detect. A terminal lobar pneumonia in the necropsy findings in this instance, does not exclude lead intoxication as a primary cause, though it may be supposed that the pneumonia contributed to the pic ture. In fact there is quite commonly a contributing factor in the development of lead encephalopathy. I have seen lead encephalopathy develop after prolonged anaesthesia, and again what appeared to be lead encephalopathy followed an illness resembling epidemic influenza. Here the differential diagnosis is a matter of some doubt, but the cerebral symptoms were distinctly more characteristic of lead than of a post influenzal encephalitis. That such conditions as produce cerebral anox emia are effective in influencing the de velopment of acute brain symptoms due to lead is strongly suggested by these facts. It is not my purpose to discuss the symptomatology of lead intoxication, ex cept to the extent that it is possible to in troduce new experimental evidence relat ing to it. The clinical picture in lead poisoning is too well known, and too read ily available to justify further discussion. Accordingly I pass over the protean man ifestations of lead intoxication to touch briefly on certain considerations as to the treatment. Tr e a t me n t . It has been my observation that in most instances of early lead intoxication, re covery occurs spontaneously when ex posure to lead compounds is discontinued. Most cases which do not respond thus are either complicated by ailments which need medical attention, or are the result of repeated or prolonged injury from ex posure over a considerable period of time. The first requirement of good therapy, then, is to avoid doing anything which may interfere with the normal processes of recovery. To accomplish even this re quires some understanding of the nature of these processes. One of the important factors in recovery has to do with the elimination of lead from the body. Atten tion has been called to the fact that lead is steadily eliminated in both the faeces and urine, and that the rate of excretion bears a relationship to exposure, or pre sumably, to the amount of lead in the body. Thus the patient, left alone, will tend to eliminate from his body the of fending agent. In time he will excrete all of the lead except that portion which is firmly bound in bis tissues. At present, there is no evidence that lead is fixed in any tissue of the body, with the exception of the central nervous system. Therefore there is no need for the use of therapeutic measures which will aid in the elimination of lead from the tissues, except in the case of the brain. Here unfortunately, no such measures are known, though it is likely that experimentation will discover them. However, it is possible to remove unab sorbed lead froni the alimentary tract, TABLE X Foeceil ExcreKon of Lead J.F DUP050315125 TABLE XI TABLE XII DISTRIBUTION OF LEAD Rabbit No. 242 Tissue Lead Lead Mgs Mgs % Wt. of tissue Found per 100 gms Mgs % in Grams Milligrams tissue in carcass Kidneys ........ . 13.0 Liver .............. . 102.0 Spleen ............ . 1.5 Fat .................. . 29.0 C. N. S........... , 14.0 Skin and Hair. . 283.5 Blood .......... . .. 92.0 Muscle ............ .. 794.0 Remainder .... .. 425.0 Bboe ............ . 227.0 Int. Tract....... .. 255.0 Contents of Int. Tract.... .. 397.0 Nil Nil Nil 0.25 0.246 1.09 Nil Nil Nil Lost in Preparation 0.13 0.930 4.13 0.60 0.17 0.210 0.185 0.93 0.S2 0.35 0.71 3.35 0.044 0.167 L475 0.20 0.74 6.55 0.14 0.055 0.25 0.21 0.053 0.24 2633.0 5.91 Total lead excreted___.. 5.16 0.225 1.00 Total lead recovered...... 11.07 and also to maintain rapid evacuation of such lead as is excreted into the intestinal tract so as to avoid its re-absorption. Magnesium sulphate has long been used orally in cathartic doses for this purpose. Table X shows its effectiveness for this purpose. The use of the generally recommended measures for increasing lead elimination from the tissues during the period of lead intoxication, is dangerous and unneces sary. There is one means which may be employed effectively and without risk, which has not received attention. Table XI shows the extent to which lead excre tion by the kidneys depends upon water excretion. The diminution of the symptoms of lead intoxication which usually follows on removal from exposure is not due solely to the excretion of lead. On the contrary, much of the effect is due to factors which work to some extent in the opposite di rection. Under normal conditions lead disappears out of the circulating blood very rapidly. There is evidence that this occurs initially through the influence of the liver. However, whatever be the mechanism, a large amount of absorbed lead appears shortly in the bones, with smaller amounts in the liver, muscles, con nective tissue and fat. The normal type of distribution is illustrated in Table XII. The speed with which the lead is re moved from the blood--this being done almost quantitatively, when lead is ab sorbed by way of the alimentary tract--' saves the other tissues from the effects of high concentration over long periods of time. This is shown by Table XIII, Total lead injected..... .. 12.00 which compares the distribution of lead in a series of animals treated intraven ously with lead and killed at variable pe riods after treatment. The eventual dis tribution is the same as if the lead had been administered orally except that cer tain tissues, notably the brain, have ab sorbed lead brought to it by blood which had not passed through the liver. Under conditions which permit of the carrying out of this normal type of distribution of lead in the tissues, symptoms of intoxica tion are likely to disappear rapidly. In fact it is doubtful if symptoms occur so long as lead is distributed in this normal fashion, It would be of the utmost im portance, therefore, to understand fully the factors necessary for this normal dis tribution. The existing data are inade quate to define these factors. We must TABLE XIII RELATIVE DISTRIBUTION OF LEAD*-- TIME EFFECT <r> CMOOd d.S ad.sS CO S3 tc<M-o e> C--D( gi u S'j3 Ptfej wSS S 2cH S3 o: *1 PSt H LKiivdenrey Spleen .-- ___ 20.75 . 4.N28il FC.atN...S......... 9.47 02..4638 0.20 Bone ..... . 0.96 Int. Tract 0.43 trace 6.24 74.07 trace 1.23 3.70 0.27 3.26 2.19 3.22 1.64 2.95 4.V3 13.83 0 0.36 0 6.45 trace 12.40 trace 0.33 0.12 1.46 3.66 1.47 1.78 0 3.00 -- -- 0 -- -- 3.00 -- 00 1.09 1.68 0 trace -- 4.13 00 0.K2 0 0.20 0,40 6.55 5.22 0.25 0.34 The figures above represent the ratio between the concentration in any one organ and that in the total carcass, in each instance. Thus one can see the shift ing- which occurs with time. Thus the lead is out of the blood after 16 -hours. It has reached practically the normal distribution after 65 hours. & DUP050315126 TABLE XIV Lod n Stood. TABLE XVI t.cnllon ,,f Lead Jr content ourselves, for the moment, with the recognition of certain things which modify the normal processes. In general it may be said that an in crease in the lead content of the blood, and in the excretion of lead, indicates the existence of conditions which operate against the normal distribution of lead in the tissues. Table XIV shows a number of factors which influence the lead con centration of the blood. The broken line shows the drop in the blood concentra tion following cessation of exposure, in an untreated subject. The solid line shows the variations coincident with sev eral types of treatment of another subject. Table II shows the variation in the faecal and urinary excretion of lead under these same influences. Tables XV and XVI show the influence of activity on lead excretion. The heavy lines in the horizontal axis on Table XV indicate night, the thin lines daytime. It is plain from the combination of blood and excretory findings following the effect of exercise, that a condition of rest is favorable to the distribution of lead in the tissues, while exercise promotes ex cretion. Some interesting speculations are prompted by these observations. The most characteristic physiological responses in exercise are an increased utilization of oxygen and an increased production of lactic acid. One can scarcely refrain from relating the increased output of lead to one or the other of these factors. It is espe cially significant that lead compounds are peculiarly soluble in lactic acid. It seems likely that the increased lactic acid in the tissues brings about an increased solubil ity of lead, which escapes into the blood, to be subsequently removed by the liver and excreted after some delay into the alimentary tract. Whatever be the explanation, we cannot but conclude that exercise is bad for the patient suffering from lead intoxication. On the other hand the activities of the lead worker promote elimination and combat accumulation. In the same terms, fatigue doubtless contributes to the production of symptoms. The foregoing facts, although present ed very briefly, permit the laying down of a few general principles for the treatment of lead poisoning. The patient should be removed from all exposure to lead com pounds, and he should be put in a condi tion of rest.' The alimentary tract should be freed of its unabsorbed lead through the use of such a cathartic as Epsom Salts. The free emptying of the alimen tary tract should be mantained throughout ( DUP050315127 the duration of the symptoms, to prevent reabsorption of lead excreted into it. Water should be given in large quantities to promote excretion of lead, and a suffi cient amount of calcium, potassium, and sodium salts should be given to maintain a proper salt balance in the tissues, during the high water intake. Large quantities of citrus fruit juices are particularly ad vantageous in obtaining both increased water and salt intake. A full mixed diet should be provided so as to promote and maintain as nearly normal physiological state of the body as possible. AH agents which are believed or known to promote a quick release of lead from the tissues should be strictly avoided. In the case of cerebral involvement, the above regime is not likely to prove success ful. Here, one must resort to procedures which are to some degree empirical. I have regarded this condition as due in part to edema of the brain, and, in one or two cases, I have had encouraging results from intravenous injections of hypertonic salt solutions. Two percent Magnesium Sul phate was especially effective in one case, in that it suppressed a delirium and re stored normal consciousness each time it was used. That edema is usually present in these cases is not to be doubted, and al though combatting the edema does not constitute an entirely adequate treatment, it is the best I can recommend on present information. When the acute symptoms subside, the most important measure is to eliminate any chronic disease which may be present. Especially important is the cleaning up of the badly infected mouth that is so com monly seen. Chronic infections in gen eral are serious obstacles to complete re covery and should be treated as completely as is possible. 'Even at this time, attempts to eliminate lead rapidly from the tissues are unneces sary. If the patient is let alone the lead will be eliminated, and without the neces sity of constant medical care. The latter is often impossible, while without it, rapid lead elimination is unsafe. There is usu ally no advantage in sacrificing safety for speed in these cases. The patient should be cautioned against excesses in effort, and in his use of alcohol. He should be ad vised as to the danger of recurrence of his symptoms as a result of undue fatigue, or the occurrence of acute infections within the succeeding few months. Thus he should avoid exposure to cold and unclement weather conditions, and in every re spect he should live as carefully as is pos sible. He should understand that it is in advisable for him to resume his exposure to lead compounds. With the above attention, the typical case of lead poisoning without involve ment of the central nervous system, will recover uneventfully, and in most in stances will show little or no residual ef fects from his experience. 11 DUP050315128