Lead poisoning and lead absorption

by Sir Thomas Morison Legge; Kenneth Weldon Goadby

REFERENCES.

[ [1] Gautier: Meillère’s Le Saturnisme, p. 74.

[ [2] Marsden and Abram: The Lancet, vol. i., p. 164, 1897.

[ [3] Shufflebotham and Mellor: Ibid., vol. ii., p. 746, 1903.

[ [4] Hebert: Comptes Rendus, tome cxxxvi., p. 1205, 1903.

[ [5] Fresenius and von Babo: Liebig’s Annalen, vol. xlix., p. 287, 1884.

[ [6] Glaister: Medical Jurisprudence and Toxicology. 1910.

[ [7] Dixon Mann: Forensic Medicine and Toxicology, p. 496.

[ [8] Vernon Harcourt, A.: A Method for the Approximate Estimation of Small Quantities of Lead—Transactions of the Chemical Society, vol. cxvii., 1910.

[ [9] King Alcock, S.: Brit. Med. Journ., vol. i., p. 1371, June 24, 1905.

[10] Steinberg: International Congress Industrial Hygiene. Brussels, 1910.

[11] Joulie, H.: Urologie Pratique et Thérapeutique Nouvelle.

CHAPTER XI
TREATMENT

In laying down the general lines of treatment for both lead poisoning and lead absorption, it is essential in the first place to distinguish carefully between the two states; for although lead absorption may gradually drift into definite lead intoxication and lead poisoning, with all the classical symptoms associated with the saturnine cachexia, a large number of cases, particularly those in industrial processes, do not and should not progress beyond the early symptoms of lead absorption. The treatment, therefore, will depend in the first place on whether the case be one so constantly met with in industrial processes, where generalized symptoms of lead absorption are manifest without any definite and disabling symptoms traceable and sufficiently pronounced to enable a diagnosis of lead poisoning to be made.

The facts given in the chapter on [Pathology], on the methods of entrance of lead, on the toxic manifestations, and the blood-changes, and, above all, the facts relating to microscopical hæmorrhages and other profound changes in the bloodvessels, point clearly to the lines along which the general treatment for amelioration, prevention, or cure of poisoning should be undertaken.

The treatment of the so-called “presaturnine state,” or what is preferably termed the “state of lead absorption,” is one that the appointed surgeon or certifying surgeon in lead factories or other processes in which lead is manufactured or used, is constantly called upon to treat. Lead poisoning is a definite entity as a disabling disease, whereas lead absorption, although the prodromal stage of such disease, cannot be defined as actual lead poisoning, as in many instances persons may show signs of continued lead absorption, but their powers of elimination can be maintained at such a level that the ratio of absorption to elimination remains in equilibrium.

With the preventive treatment of lead poisoning we have dealt in another place (see [p. 199]). What is particularly required here is the medicinal treatment, which may be helpful in preventing lead absorption passing on to definite lead poisoning.

For many years it has been customary in the treatment of men employed in lead works to give occasional purgatives, and it is, moreover, a common and proper precaution to keep a stock of some simple aperient medicine, preferably saline composed of sodium sulphate and magnesium sulphate, at the works in charge of the foreman, so that any man who so desires may obtain a dose of an ordinary aperient mixture. We have seen from the pathological evidence that the largest proportion of lead is excreted by the bowel, and that, therefore, the sweeping away of the bowel contents—particularly where constipation is set up—will naturally tend to remove from the body a good deal of the lead which has been already excreted into the intestine and which may presumably become reabsorbed unless it be swept away. In a large electric accumulator factory Epsom salts in the form of the granular effervescing preparation is much appreciated. In winter 50 per cent., and in summer 90 per cent. of the men are said to take a daily dose. In an important white-lead works chocolate tablets containing hypo-(thio-)sulphite of sodium are supplied to the workers.

Another medicine made use of in lead works is the sulphuric acid lemonade, this being acidulated with sulphuric acid and flavoured with lemon. It is very questionable whether this substance has any definite effect in the special direction in which it is supposed to work—namely, that of forming an insoluble sulphate of lead in the stomach and so preventing its absorption. The use of this drug was suggested on the presumption that lead poisoning as a rule took its origin from the dust swallowed and converted into a soluble form in the stomach. As we have seen, there is very little evidence that this entrance of lead is of much importance, although it does occasionally take place. Furthermore, from the experiments of one of us [K. W. G.[1]], it has been found that the sulphate of lead is at any rate as soluble as other lead salts, such as white lead or litharge, when acted upon by normal gastric juice.

With regard to the drinks supplied to workers in lead factories, it is highly important that some form of fluid should be supplied which the men may drink without harm, particularly in the more laborious forms of employment, and, above all, in the factories where smelting, desilverizing, etc., of lead is carried on. In these factories the use of some type of lemonade containing sodium citrate is to be recommended, as it has been shown that one of the pathological effects of lead absorption is to produce an increased viscosity of the blood, and the use of such drugs tends to some extent to diminish this. A drink containing a few grains of sodium citrate to the ounce and flavoured with lemon is freely drunk by workmen engaged in the laborious processes.

Finally, as a general routine treatment, it is advisable to keep at the factory some form of mixture containing iron, which may be given to those persons who are showing signs of slight anæmia, generally associated with some degree of constipation, and it is therefore better to use a form of iron cathartic. This medicine should also be kept in the care of the foreman, who will see that it is administered to the men properly. In this way any persons who at the weekly examination exhibit signs of anæmia may be promptly treated, and what is more, the surgeon is assured that the workmen in question actually obtain the medicine prescribed regularly.

During the routine weekly or monthly examination, or at whatever intervals the medical examination takes place, particular attention should be paid to the records kept of the state of health of the various persons, and whenever possible alteration of employment should always be enjoined when early signs of anæmia make their appearance.

The surgeon should spare no pains to determine if any of the workmen are confirmed alcoholics, and such persons should be removed from work in dangerous processes, while at the same time care should also be taken to eliminate any persons suffering from those diseases which are known to be predisposing causes of lead poisoning. The card system of registration of any symptoms noted or treatment given facilitates supervision of the health of the men.

In times of stress where some particularly dangerous process is in operation, as, for instance, where portions of a building which has become thoroughly impregnated with lead dust is being pulled down, or where machines are being altered, removed, or rebuilt, especial care should be exercised with the workmen so employed, and it is advisable in such cases to adopt preventive measures on the supposition—generally correct—that such persons are absorbing a larger quantity of lead owing to their peculiarly dusty employment than they were under normal circumstances. At such times, also, it may be advisable to administer some form of mild iron cathartic to all persons employed in the factory for, say, a week at a time. It must not be supposed, however, that these methods of treatment in any way supersede the precautions for the prevention of lead poisoning by mechanical and hygienic means; they are merely additional precautions which may be put in force under special circumstances.

The Treatment of Lead Poisoning.

—The treatment of definite lead poisoning, as the treatment of lead absorption, is directed towards the elimination of the poison, the promotion of repair to the damaged tissues, and special treatment directed towards those special organs which suffer mostly in lead poisoning. At the same time, special treatment of urgent symptoms may be called for; but in the treatment of the urgent symptoms the fact of the general elimination of the poison must not be lost sight of.

We have already seen that the channel through which the poison leaves the body is mainly the fæces. Treatment must therefore be directed, as in the former instance (lead absorption), towards eliminating the poison by this means as much as possible, both by the use of enemata, and later the use of sulphate of magnesia, which may be added to the ordinary fluid enema; and it is far better in obstinate cases of constipation and colic to give enemata than to continue with the huge doses of salines or other aperients, such as croton-oil, elaterinum, or castor-oil.

Colic.

—Lead colic may be simple, acute, recurrent, or chronic and continued. In whatever form colic appears pain is invariably referred to the lower part of the abdomen, frequently into the groins, and occasionally to the umbilicus. The pain has to be distinguished particularly from acute gastritis, and occasionally from appendicitis, and sometimes from that of typhoid fever. Acute colitis—not common in this country—and dysentery, may, to some extent, simulate the pain of lead colic, but John Hunter’s[2] original definition of “dry bellyache” conveys very vividly the type of pain. Occasionally diarrhœa may be met with, but as a rule obstinate constipation is present. In continued colic, or chronic colic, sometimes lasting for several months, obstinate constipation is the rule. In the simple acute colic the pain passes off in the course of five or six days, generally disappearing about four days after the lower intestine has been thoroughly cleared.

The pain of lead colic is relieved by pressure upon the abdomen, whereas that of gastritis and most other forms of abdominal pain may be generally elicited along the descending colon and splenic flexure; mucus is commonly found in the stools, especially the first evacuation, after obstinate constipation occasionally of several days’ duration associated with an ordinary attack of lead colic. Blood may be passed, but this symptom is not common. The pain in the acute form is paroxysmal; it is rarely persistent, being typically intermittent. During the paroxysm distinct slowing of the pulse-rate with an increased blood-pressure takes place, and the administration of vaso-dilators—such, for instance, as amyl nitrite—during a paroxysm rapidly relieves the pain and lowers the blood-pressure, and in this way distinguishes acute colic of lead poisoning from, say, subacute appendicitis.

Vomiting may or may not be present, though the patient usually complains of feeling sick, but there may be at times vomiting of a frothy mucus.

It is unusual for a patient to die from acute colic, but acute paroxysms have been recorded in which yielding of the blood-vessels of the brain has occurred.

Recurrent colic is as a rule less severe than the simple acute form, but may last for several weeks, clearing up for three or four days at a time and then recurring with little diminution in violence from the first attack. Such cases are probably due to the gradual excretion of lead by the intestine, and should be treated on this supposition.

In the continued or chronic colic the pain may persist for as long as two months, during the whole of which time the patient complains of uneasiness and even constant pain in the lower part of the abdomen, which becomes considerably worse after each evacuation, and almost invariably is associated with exceedingly obstinate constipation. It is this type of case that olive-oil or liquid paraffin relieves, while in the acuter forms drastic purgatives such as castor-oil, croton-oil, or pulv. jalapæ comp. may be administered.

For the treatment of pain in colic one of the various vaso-dilators should be used, as, in addition to the spasm of the intestine, a very considerable vaso-constriction of the whole of the vessels in the mesenteric area occurs. Amyl nitrite gives immediate relief, but the effect passes off somewhat rapidly, whilst scopolamine, although taking somewhat longer to act, is better for continuous use, as its action is longer maintained. Sodium nitrite, liquor trinitrini, and antipyrin are also of use. Atropin may be used, but it is perhaps better given in conjunction with magnesium sulphate.

Whatever form of purgative is given, some form of anodyne should be combined. Drissole and Tanquerel[3] are said to have obtained excellent results with croton-oil; one drop is given, followed seven or eight hours later by another, and then by an enema of 2 pints of normal saline. After two or three days the croton-oil may be again given, one drop at a time each day. In addition, Tanquerel made use of belladonna and opium together, finding that their combined action was better than that of opium alone, as the physiological effect of belladonna probably assists in preventing the intestinal cramp.

Hoffmann[4] recommends the use of olive-oil and opium, giving 3 to 4 ounces of olive-oil. He says that this relieves the spasm of the pylorus, and is of particular use where severe vomiting is associated with the colic. This use of olive-oil, first suggested by Hoffmann in 1760, and revived by Weill and Duplant[5] in 1902, is somewhat interesting, in view of the modern tendency to administer paraffinum liquidum in the treatment of chronic constipation.

Briquet[6] recommends 4 grammes of alum and 4 grammes of dilute sulphuric acid three times daily, with the addition of 0·05 gramme of pulv. opii at night. Briquet says that although the purgative method rapidly diminishes the colic, the elimination of the poison does not take place as rapidly as by means of the treatment he recommends, though it is open to doubt whether the use of either of these two drugs is likely to produce any further neutralization or excretion of absorbed lead than sulphate of magnesia. It is quite certain that the magnesium sulphate does not act as a neutralizer of the poison, as in a factory where sulphate of lead is manufactured some cases of definite lead poisoning occurred, in which at least half must have been due to the inhalation of lead sulphate dust. Under these circumstances it seems hardly worth while to attempt to form a sulphate of lead in the body. The action of magnesium sulphate and other salines, however, in promoting the flow of fluid towards the intestines, and rapidly diluting and washing out the contents, tend to eliminate such lead as has already been excreted into the bowel.

A number of other drugs have been given from time to time for the purpose of forming an insoluble compound with the metal in the intestine, such, for instance, as sulphur in many forms, which is still much used in French hospitals. Peyrow[7] advises sulphide of soda, whilst Meillère prefers potassium sulphide as being less irritating. He considers sulphuretted hydrogen a proper prophylactic against reabsorption. Both experimental work and clinical observation show that a change to sulphide does take place in the lower bowel, and that staining of this part of the intestine is due to lead sulphide; but as the figure on [Plate II.] shows, the lead may exist in the form of granules of a dark nature, deeply embedded in the intestinal wall, besides being situated in the exterior.

Stevens[8] suggests the use of ¹⁄₂-grain doses of calcium permanganate thrice daily to relieve pain.

A certain number of other drugs may be also made use of from the point of view of diminishing the pain, and one French observer advocates the hypodermic injection of cocaine, but it is doubtful whether any good would follow from such a procedure. Hypodermic injections of morphia should be given whenever the pain is great, and diaphoretics as well as diuretics should also be given, such, for instance, as ammonium acetate, citrate of potash, or soda. Chloroform water and chloral and bromine water may be also used, and when no other drug is at hand, the inhalation of chloroform will rapidly relieve the acute vaso-motor spasms associated with colic.

During the attack of colic, and for at least a day subsequent to its disappearance, the patient should be kept on a fluid diet; milk is best, and 10 grains of sodium citrate should be added to each glass of milk. After the colic has subsided, a light farinaceous diet should be given, and it is better not to give meat until at least a week has elapsed. Alcohol is to be avoided.

The Anæmia of Lead Poisoning.

—As has been pointed out in Chapter VIII ([p. 135]), the anæmia of lead poisoning is one due to the destruction of the red blood-cells. This is evidenced not only by the curious sallow complexion, by the occasional presence of hæmatoporphyrin in the fæces and urine, and often by the curious yellow of the sclerotics, but also by an increase in the viscosity of the blood itself. Moreover, the urine of persons suffering from lead poisoning is invariably highly coloured, and may even show the presence of methæmoglobin. As the anæmia is generally a symptom of continued lead absorption for a long period, and does not necessarily occur with every case of colic—in fact, acute colic may often supervene without any symptoms of continued anæmia—the persons suffering from lead anæmia should be removed from their direct contact with the dangerous processes, and should be given, if possible, work in the open air. Iron and arsenic may be used, preferably in combination, whilst the iodide of iron often gives good results. Whatever preparation of iron is given, care should always be exercised in avoiding any constipating effect, and the free action of the bowel should be maintained, together with a liberal supply of milk. Potassium iodide may be also given.

With regard to the action of potassium iodide, there is division of opinion amongst various physicians as to the efficacy of the drug in the elimination of lead from the body. At the same time a very large number of persons hold that the administration of fairly large doses of potassium iodide in the case of a person suffering from chronic lead absorption may at times be associated with sudden exacerbation of the disease, and that the drug apparently may determine the production of acute symptoms, such as encephalopathy or paralysis, when these have not been previous features of the case. Our experience supports this statement, and on more than one occasion one of us (K. W. G.) has seen a distinct increase of symptoms follow the administration of large doses of potassium iodide. From a comparison with other cases it seems that these symptoms would have been unlikely to make their appearance without some secondary cause. Against this point of view must be quoted further experiments already referred to by Zinn[9], who found that when lead iodide was administered to experimental animals iodine alone was found in the urine; but it must be pointed out that no estimations were made of the fæces, and it is possible that a certain amount of lead was eliminated in this way. What exactly is the action of iodide on the solubility of lead in the body it is difficult to say; yet the use of iodine compounds has been followed with considerable success in a number of chronic inflammatory diseases, and it is possible that it may have the action of splitting off the particular lead compound from its organic association with the tissues, especially as it is well known that iodine plays a very important rôle in the process of cell metabolism. Another point which tends to support the use of iodine is the fact that the other two halogens, bromide and chloride, both of which enter largely into cell metabolism, also have a slightly beneficial effect on the excretion of lead. The dose of the iodine given should not be large to commence with, 3 grains three times a day is sufficient, the dose being run up to some 30 or 40 grains per diem, the symptoms meanwhile being carefully watched.

Other symptoms often associated with the anæmia of lead poisoning are—

Rheumatic Pains.

—These pains are suggestive of muscular affection, and are possibly due to minute hæmorrhages occurring in the muscle tissue, which have been discovered in the muscles of experimentally poisoned animals. For the rheumatic pains diaphoretics and citrates of soda and potassium may be given.

Lumbago.

—The lumbago constantly complained of in chronic lead poisoning and even in the early stage of lead absorption, is very generally related to chronic constipation rather than to a definite affection of the lumbo-sacral joints.

Nephritis.

—Affections of the kidney associated with lead poisoning are almost entirely confined to sclerosis. The presence of albumin in the urine is not a very common symptom. As has been pointed out already, the presence of lead in the urine is by no means a regular feature of lead poisoning, though it may at times be present, and the urine should always be examined for changes in the kidneys; but as a number of cases of chronic lead poisoning are associated with alcohol poisoning, the changes in the kidney cell are almost certain to be present. On [p. 95] the illustration showing the disease in the kidney produced by experimental dosage with lead, and the kidney of a fatal case of lead poisoning in a man who at the same time had a strong alcoholic history, shows fairly definitely the difference between these two points.

Acute nephritis occurs so rarely in the course of industrial lead poisoning that it cannot be considered to be a disease due to lead.

In chronic nephritis treatment should be along the ordinary lines and the same remark applies to enlargement of the liver.

Heart.

—Symptoms due directly to disease of the heart are rarely caused by lead alone. The heart muscle may suffer in the same way as the other muscles of the body, and in lead poisoning in animals distinct hæmorrhages are found between the muscular fibres in the heart muscle, and it is therefore probable that a form of myocarditis may exist in lead poisoning. This, together with the increased arterial tension, may cause dilatation, but the symptoms are those related more to the general condition of arterio-sclerosis than to any direct heart lesion, and as a rule these symptoms do not call for any special treatment.

Treatment of Nervous Manifestations in Lead Poisoning.

—With one or two exceptions, the diseases of the nervous system associated with lead intoxication only appear when actual lead poisoning is established. Certain evidences of affection of the nervous system are occasionally seen in the prodromal stage, or stage of lead absorption. These may be merely temporary and disappear often under treatment, by change of employment and reduction in the quantity of lead absorbed. Thus, dilatation of the pupils—the reaction to light being extremely sluggish or absent—is often a feature of the later stages of the condition of lead absorption. Tremor may also be a symptom, the outstretched hands exhibiting a fine undulatory movement, often increased on attempting to perform some act such as touching the nose, or touching the two fingers together, and when these symptoms occur they must always be regarded as of somewhat grave import. But it must be remembered that tremor may occur as a common complication of alcoholic cases, and further, follows excessively hard manual work, though there is usually little difficulty in distinguishing between the various forms.

The symptomology of nervous diseases associated with lead poisoning has already been carefully set out in [Chapter IX.], and the pathological changes underlying these symptoms in [Chapter V.]

Of the general treatment, little needs to be added to what has already been stated for the treatment of lead anæmia and general lead intoxication. Iron and arsenic (not strychnine, especially in presence of colic), and other similar drugs, should be employed together with iodides either as potassium iodide or as an injection in the form of an organic compound, of which there are several varieties on the market.

The injection of normal serum has been advised, as well as saline injections, and in some instances venesection has been practised, but it is doubtful whether anything is to be gained by this form of treatment.

Further, it has been stated that some lead is excreted through the skin, and for this reason sulphur baths, bathing in sulphuretted hydrogen water, etc., have been recommended to neutralize any lead that has gained access to the skin. Serafini[10] has claimed that by means of electrolytic baths a certain amount of lead can be found present in the water after continuous passing of a current, and it has been supposed by these observers that the lead has been actually driven out of the body under the action of the electric current. It is, of course, possible that such lead as is discoverable in the water was merely that which had already become incorporated with the patient’s skin through mechanical contact.

Whatever form of treatment be adopted of a general type, the patient must certainly be removed from the chance of any further lead absorption; a person who is suffering from wrist-drop or other form of paresis should not be employed in any portion of a lead works where he may come into contact with any form of lead or its compounds for at least a year after the paresis has disappeared, and even then it is inadvisable for such a person to return to any form of dangerous lead work.

The electrical treatment of the injured nerves and muscles should be undertaken energetically; both the galvanic or faradic currents may be used. Probably the best form is the galvanic. A small medicinal battery may be utilized, the method of application being as follows: One pole of the battery should be placed over the affected muscle, and the other pole placed in a basin of water into which the patient’s hand is dipped. The current should then be passed. It is better not to use a current of too great intensity, particularly at the start, although it is found in practice that a much greater current can be borne in the early stages of the treatment than when the muscles and nerves commence to recover. As a rule the patient experiences no inconvenience whatever from a considerable current during the first week of his affection, but at the end of a fortnight or three weeks less than one-third of the initial current can be borne. The current should not be passed continuously, but should be used for a short time and then shut off, being again switched on for five or six minutes, and then again shut off. The applications may also be modified by placing one hand in the vessel of water and stroking the affected muscle and nerve with the free electrode. The application of the current should be for not more than half an hour at a time, and may be applied twice in the twenty-four hours. It is quite easy to instruct the patient to perform the electrical treatment for himself in this manner when the paresis is affecting either the upper or lower extremity.

With the faradic current the circuit should be closed while the current is at a minimum, and then the quantity of current raised to some 15 to 20 milliampères.

For affections of the lower extremity the application may be made by means of one of the usual baths in which the foot is immersed, the other electrode being placed on the back or other suitable position. If both the lower extremities are involved, then both feet should be placed in a bath into each of which the source of electricity is connected.

Ionization by means of the faradic current may also be made use of. For this purpose one of the halogens, preferably iodine or chlorine, should be used, it being remembered that chlorine and iodine ions enter from the negative pole, so that in such a case the bath in which the affected limb is placed must be connected with the negative pole of the battery.

Subsequently, with either form of electrical treatment, the part should be well rubbed, and passive movements as well as massage are an advantage in promoting the return of normal function. As the muscles gradually return towards their normal state, graduated muscular exercises should be used.

When treated in the first week or two of the onset, lead paresis frequently recovers, and in a person suffering from lead palsy for the first time, confined only to the hands or to a group of muscles in the shoulder, prognosis is good. The prognosis of palsy of the lower limbs is not so good.

Paralysis of the facial nerve is occasionally seen in lead poisoning, and where this occurs it should be treated as previously recommended, by means of iodides in association with localized electrical treatment. One pole of the battery should be placed below the external auditory meatus, and the other one passed over the face on the affected side.

In long-standing cases where no attempt has been made at treatment in the early stages of the disease, and where considerable muscle degeneration has already taken place, the prognosis as a rule is very bad. Efforts should always be made in an early case by passive movements and massage of the affected muscles to improve their nutrition as far as possible. The diet should be light, and alcohol should not be given at any time.

Affections of the Central Nervous System.

—The typical form of affection of the central cerebral nervous system caused by lead, is lead encephalopathy. The disease may be insidious in its onset, and may be preceded by a long stage of chronic headache with slight or total remissions. Headaches may last for several months before the actual acute stage of the disease is reached. In the examination of several brains of persons who have died from lead encephalitis, microscopic sections of the brain have shown signs of hæmorrhages which must have taken place some considerable time prior to death, and were no doubt associated with the headache that had been complained of for some time previously, before the onset of the fatal illness. (See [Plate III.]) Persistent headache occurring in a lead-worker should always be regarded with grave suspicion, and such a case should be treated on the assumption that it is an early case of lead encephalitis. Bromides and iodides should be given, and the patient placed in quiet surroundings, and fed on light, nutritious diet, and every attempt made to produce elimination of the poison.

In the acute attacks vaso-motor spasm is no doubt partially accountable for the symptoms, and various dilators, previously noted in discussing colic, may be made use of, such, for instance, as amyl nitrite, scopolamine, etc., whilst pyramidon, antipyrin, phenacetin, and other similar drugs may be given between the attacks. Under no circumstances should any person who has suffered from encephalitis or other cerebral symptom of lead poisoning be allowed to resume work in a lead industry.

The treatment of eye affections in lead poisoning requires little comment, as the essential treatment must be the same as in other cases, mainly devoted towards the elimination of the poison. Attempts may be made to treat paresis of the ocular muscles by means of mild electric currents, but of this we have had no experience. About 50 per cent. of cases of lead amaurosis and amblyopia recover, but a number progress to total and permanent blindness, and prognosis in such cases must always be guarded.

Prognosis.

—The prognosis of the first attacks of lead poisoning of simple colic or even slight unilateral paresis is good; practically all cases recover under proper treatment. It is unusual for a person to succumb to a first attack of simple colic, or paresis.

In most cases the serious forms of poisoning only make their appearance after three or four previous attacks of colic, but a single attack of paresis is much more frequently followed by a severe form of poisoning, such as encephalitis.

A limited number of persons are highly susceptible to lead poisoning, and these persons rapidly show their susceptibility when working in a dangerous lead process. Lead poisoning occurring in an alcoholic subject is more likely to result in paretic and mental symptoms than in a person who is not addicted to alcohol, and the prognosis of lead poisoning in an alcoholic is much less favourable than in the case of a normal person.

Mental symptoms very rarely follow from a single attack of lead colic, and as a rule do not become established under three or four attacks at least.

A small number of persons exposed to excessive doses of lead absorption through the lungs develop mental symptoms, such as acute encephalitis, without any prodromal stage. The prognosis in such cases is always exceedingly grave.

Sudden generalized forms of paralysis are not common in the early stages, but are invariably of grave import. A few cases of paresis, particularly those of the peroneal type, and affecting the lower limbs, become progressive, and eventually develop into a condition resembling progressive muscular atrophy with spinal cord degeneration.

The prognosis of simple colic in women is about as good as for males, but if an attack of abortion is associated with lead poisoning, eclampsia often supervenes and permanent mental derangement may follow. In the dementia associated with lead poisoning the prognosis is not so grave as in other forms of dementia, especially alcoholic, but depression is an unfavourable symptom. The mania of lead poisoning is not so noisy as that of alcoholic mania, but where there is suspicion of alcoholic as well as lead poisoning the prognosis is exceedingly grave.

As a rule the prognosis of cases of lead poisoning occurring in industrial conditions is more favourable when colic is a marked feature than when it is absent, and there is no doubt that the prognosis in cases of industrial lead poisoning at the present time is more favourable than it was before the introduction of exhaust ventilation and general medical supervision—a fact no doubt to be explained by the relative decrease in the amount of lead absorbed.