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SYMPOSIUM / Lead Poisoning in t'3 Children Foreword Joseph Greengard, M.D., Symposium Editor Clinical Expressions of Lead Poisoning in Childhood Joseph Greengard, M.D. Epidemiology of Lead Poisoning Harold Jacobziner, M.D. The Biochemistry of Lead Eleanor Berman, Ph.D. Neurologic Sequelae of Plumbism in Children Meyer Perlstein, M.D., and Ramzy Attala, M.D. Foreword A,.S pointed out by Jacobzincr in this sym posium, lead intoxication in children in the United States is largely a disease of the slum areas o the big cities, where housing is old and deteriorated. Residents of such areas are often largely Negro, with some Puerto Ricans and a scattering of Caucasian children. Poverty with its problems of serious crowding, high rates of unemployment, large families, broken homes, absent fathers and mothers during working hours--all contribute to lack of supervision of small children and failure to protect them from opportunity for environ mental exposure. The continuing stream of migrants to cities in the North as a consequence of social and economic pressures in the South and in Puerto Rico con tinues to flood these old neighborhoods. New. public housing, safe from the standpoint of risk of lead exposure, cannot be developed fast enough to keep pace with the demand. Since slum clearance and public housing programs are expensive, and slow at best, complete removal of sources of exposure to lead still lies in the far future. With present population situations, public health programs as described by Jacobziner re quire large sums of money and large numbers of trained people. Case finding is tedious and in large cities the case loads of social agencies are huge. Necessary laboratory facilities, particularly for quantitative lead determinations, are not widely available. Educational programs geared both to the general, public and to the medical profession are onerous in themselves. Cooperation from landlords in the correction' of housing vio lations is not everywhere obtainable. Nevertheless, every dty must make .extreme ef forts to introduce and sustain. preventive pro grams. Lead intoxication responds well to therapy if detected early, before the onset of encephalopa thy. The ecouomic cost to our communities from the brain damage of plumbism is infinitely greater than the expenditures for case finding and pro phylaxis. When this is fully realized, over the country, the same accomplishments of New York and some other cities will become more-,general. This is the most immediate approach to the eradication of lead intoxication in children. Speaking very generally, the permanent solu tions to this problem are linked closely -with the profound sociologic problems of modern living: they will fade away slowly with the reforms which affect profoundly the many ramifications of our culture.--Joseph Greengard, M.D., Director, Divi sion of Pediatrics, Cook County Hospital, Chicago, Illinois. 268 Vi. 5 No. 5 CLINICAL PEDIATRICS r t )1 f'3 i -3 GL035139 `4 Lead Poisoning in Childhood: Signs, Symptoms, Current Therapy, Clinical Expressions JOSEPH GREENGARD, M.D.* from the.Cook County Children's Hospital and the Hektoen Research Institute, Chicago, Illinois When detected early, before the onset of encephalopathy, lead intoxication subsides rapidly tinder therapy. Here for the pediatrician is an outline of -the problems inherent in- early detection, along with summaries of the therapeutic measures be ing used at one center for the early case as well as the-case with the dread com plication of lead encephalopathy. \ TJL HE number of deaths from all poisonings in United States children is approximately 1,500 per year. Nonfatal cases are estimated to be 100 to 150 times that number.* A major source of poison ing is lead, accounting for many deaths and much residual brain damage. Though largely a phenom enon of large cities, lead intoxication can and does occur in rural areas. This discussion describes the. manifestations of lead poisoning in young children, and more spe cifically, in toddlers between 16 months and five years of age. The central"'nervous system in this age group is particularly susceptible to the ef fects fef this poison and the development of en cephalopathy. Lead poisoning is linked closely with poverty and poor housing. The actual incidence in big cities seems to be increasing in spite of the fact that physicians and pubtic health officials have been aware of its presence for many years and have devoted much attention to its management. Progress has been made in treatment, and, un doubtedly, many cases of acute encephalopathy Director, Division of Pediatrics, Cook County Hos pital, Clinical Professor of Pediatrics, University of Illinois, College of Medicine, Senior Attending Pedi atrician. Michael Reese Hospital, Chicago, Illinois. Address: 700 South Wood Street, Chicago, Illinois <10012. have been avoided by early recognition; there is still, however, no therapy which is truly ef fective. Early symptoms of ibis syndrome are so vague and nonspecific that the patient often fails to seek medical aid early, and the physician, when he is finally consulted, sometimes fails to consider lead poisoning as a possibility. Etiology of Lead Poisoning Pica. The usual portal of entry is by ingestion. This involves a consideration of pica, defined as an abnormal craving for non-nutritious or even harmful substances such as clay, plaster, ashes, charcoal and the like. Perhaps the most enlight ening description of this interesting condition is that of Marcia Cooper,* based on a study of 784 Baltimore children, 21.9 per cent of whom had pica. A predominance of children with the habit were Negro children, and in most cases the habit was established in die second year of life and disappeared by the fourth or fifth year. The most common form of pica was the eating of dirt, although plaster, ashes, and paint were also consumed. Cooper stresses that this is not merely random mouthing to satisfy oral curiosity among her study children; it is a persistent and purposeful pursuit of the substance. With respect to plaster, she states that those with a craving for it dug it from die walls with great determination. This description certainty fits those children in my experience with lead intoxication whose source of lead was wall plaster. There is still no good explanation for the insatiable appetite some indi viduals have for the substances concerned in pica, though die association with anemia and the conjecture that pica may represent iron hun ger has been suggested. Source of lj;ad. An important contributory fac tor is poor slum housing with buildings 30 to 50 years old. Here the walls and ceilings are often in serious disrepair with cracked plaster and peel- CLINICAL PEDIATRICS Way 1966 269 !! ' j GLD35140 gr eekgar o In other months one encounters scattered cases whose symptoms are brought on by ituercurrent infection. Just why (his is predominantly a sum mer disease is not well understood, though there is some animal experimental evidence to incrim inate the role of increased heat and humidity i and of ultraviolet rays in summer sunlight.5* Fj c . 1. X-ray of the abdomen in a child who has recently ingested large amounts of lead paint-contain ing plaster. Paint chips are clearly seen in the large bowel. trig paint. These give ready access to the prying fingers of the child. In addition, repealed coats of high lead-containing paint have soaked into the plaster over the long years. Chrome green, chrome yellow, and white lead paints are common sources; Chisolm8 estimates that small chips of such dried paint may contain 100 mg. or mote of lead. KehoeIS has calculated that 8 to 12 per cent of ingested lead is absorbed. The continued in gestion over many months results in lead intoxi cation. In the past the role of inhalation was important due to the popular use of old storage battery casings as fuel in heaters; this has been recently well controlled by city ordinances, though sporadic outbreaks still occur such as we experi enced in December of 1959.10 Summer vs. Winter. Seasonal factors are of great importance in the overt manifestations of lead intoxication. Children with high increments of lead may be symptom-free during the winter and develop serious difficulty with the advent of sunny warm weather. Most patients are seen between May and October. Symptoms and Signs Lead intoxication usually has an insidious on set with vague complaints. Parents often note a change in their child's disposition. Instead of being active and happy, he becomes listless. As sociated with this are gastrointestinal symptoms-- loss of appetite, intermittent vomiting, abdominal pain and frequent constipation.-The child may also seem pale. These symptoms and signs are not striking and, in the age group involved, may not arouse much concern. If cite mother consults a physician, he too finds little on physical examination to indi cate serious illness. He will frequently not pursue any special .laboratory procedures unless he is by past experiehce alerted to the problem of plumbism. As a result, the complaints are passed off as "flu" or some digestive disorder; not infre quently, an antibiotic is given along with instruc tions to return if there h no improvement. With the advent of.central nervous system in volvement, there may be drowsiness and the child may evidence clumsiness or definite ataxia; the latter is a common sign of lead encephalopathy. Not infrequently the seriousness of the brain in volvement is not appreciated until the onset of dramatic symptoms such'as severe and repeated convulsive seizures, coma, or even respiratory ar rest. These last will, of course, bring the child to die hospital, but all too. often with a fatal out come. With brain involvement there may also be focal neurologic signs, though these. are usually not striking. Fever is sometimes also present along with changes in.cardiac rate and rhythm. Approaches to Diagnosis Clinical Expressions. Greenberg et al.* have de scribed the vaiue of a history of pica in a case finding program by the New York City Health Department. It is certainly an important clue to the diagnosis, but parents rarely volunteer dm history. When in cross examination pica is un covered. most parents seem surprised that the doctor deems it unusual. Pallor due to anemta of die iron deficiency type is an almost constant accompaniment of lead in* 270 Vo!. 5 No. 5 CLINICAL PEDIATRICS GL035141 LEAD POISONING: SIGNS, SYMPTOMS, THERAPY toxicatton in this age group. It should be given equal weigh? by the examining physician with pica. Its mechanism of production is still to some extent controversial. Recent experimental data seem to support its being due to two factors: l) interference by lead with the enzymatic in corporation of iron into protoporphyrin: anti .'2) diminished survival time of red blood cor puscles. Basophilic stippling of erythrocytes has long been described as a characteristic of lead poison ing. In actual practice, the percentage of children revealing this finding on ordinary blood exam ination with light microscopy is a relatively low SO to 40 per cent. Experimental studies utilizing electron microscopy have revealed enlightening data on this aspect'. Bessis and Breton-Gorlus * showed that basopliilic-stippled cells contain mitochondria which are not present in normal mature mammalian erythrocytes. Pirrie 11 and McFadzean and Davis * showed that basophflic-stippled cells are removed from the circulation at an accelerated rate by the reu'culo-cndothelia! system; this was demonstrated by finding that erythrocyte counts remained high i the guinea pig poisoned by lead, but pre viously splencctomircd or subjected to 'reticulo endothelial blockade by trypan blue. . - - As noted below, the sulfhydryl enzyme, delta aminolevulinic acid dehydrase, is partially inhib ited by lead, and its substrate appears in large amounts in the urine. As a consequence the syn thesis of heme from iron and protoporphyrin is interfered with to a significant degree. The pres ence of increased amounts of coproporphyria Ifl in the urine of children with lead poisoning is based on this interference with heme synthesis, and, while not specific, is an extremely important diagnostic finding and a* guide to therapy as well. Parents and physicians`are obviously impressed by catastrophic symptoms such as repeated con vulsions, coma, and respiratory arrest. Early symp toms of intoxication are another matter, however; the recognition of early lead encephalopathy is a challenge of great significance, since it is only in the early stages that good results may be achieved. A high index of suspicion by tire physician is essential component. This involves an aware ness of the etiologic factors noted above. Thus, any child aged one to three years living in a deprived area where deteriorated housing is prev alent, and who presents during the summer months with vague symptoms should be under Fig . 2. Dense "lead lines" are seen in these x-rays of the upper and lower tibia! and fibular metaphyses of a child with lead intoxication. suspicion for lead poisoning. If the mother vol unteers a story of pica or should such a history be elicited on questioning, the possibility is even stronger. A urine specimen should be obtained as soon as possible and analyzed for coproporphyrin III. A strongly positive reaction is a high presumption of lead intoxication; the child must be hospital ized and the diagnosis pursued further. Radiography. The x-ray is a valuable aid to presumptive diagnosis. The abdomen may show flecks of radiopaque material in the intestinal tract, occasionally in large amounts as seen in Figure 1 when lead-containing plaster has been recently ingested. The bones may reveal a dense line at the metaphysis as seen in Figures 2 and 3, the knee being a particularly good area to dem onstrate this. "Lead lines" are frequently also striking at the iliac crests as in Figure 4 and the tips of the scapulae. In Figure 5 the lumbar spine is demonstrated in a three and one-half-year-old child who had lead intoxication. Lead lines arc seen in the ver tebral bodies (this film was kindly supplied by Dr. Harvey White of Children's Memorial Hos pital, Chicago, and is unique in our experience). CLINICAL PEDIATRICS May 1966 271 GLD35142 * GREENGARD Fig . S. Wrist and hand o{ the same child in Figure 2. Note the dense metaphyseal lines in the radius and ulna, in the metacarpals and phalanges, and the con centric rings on the carpal bones. disproportionately low because of impairment of renal function in this disease. Treatment Encephalopathy. Within die past six years we have treated 182 cases of lead encephalopathy at the Cook County Hospital in Chicago.1**1* Our programs of management are based upon clinical studies of these patients. We Erst classify the individual case as mod erate or severe. Frequently ibis is difficult, be cause a child who is conscious and seemingly not too severely involved on admission may unpredictably develop convulsions and lapse into coma eight to 12 hours later. The definitive clinical diagnosis of encephalopa thy is based upon spinal fluid Endings, yet the lumbar puncture itself may precipitate grave or even fatal complications, unless carried out with great precaution. This hazard is the sudden re lease of fluid under increased pressure with re sultant herniation of the cerebellar tonsils through the foramen magnum or of the temporal lobes through die'tentorium. When the diagnosis of encephalopathy is sus pected, the needle must be introduced with great care, using a three way stop cock connected with a manometer. The fluid is never allowed to spurt When encephalopathy is advanced, with marked cerebral edema and increased intracranial pressure, splitting of the sutures, particularly the sagittal and coronal, may also be seen. Tests for Lead. When clinical and radiologic findings are presumptive, a blood sample should be drawn in a lead-free syringe, placed in a leadfree tube with a hard rubber stopper, and sub mitted to the appropriate laboratory for lead analysis. This is the one specific diagnostic End ing in lead intoxication. Values up to 0.06 mg. (60 meg.) per 100 ml. of whole blood are con sidered within the normal range, whereas 0.08 mg. (80 meg.) and higher are found in true lead intoxication. In the child with lead encephalopa thy very high values are obtained; we have seen levels as high as 825 meg. per 100 ml. Kehoe10 states that the rapid rate of lead ab sorption in young children is responsible for their high rate of encephalopathy. Unfortunately, most hospitals are unable to perform lead analyses and blood and urine specimens must be sent out--a time-consuming process. Urinary lead determinations are much less re liable. Methods of collection without contamina tion are difficult; urine lead levels may also be IV.. 4. Lead lines are seen here in the able of the ilium due to repeated lead intoxication. 272 Vol. 5 No. S CLINICAL PEDIATRICS 6 LP 35143 A LEAD POISONING: SIGNS, SYMPTOMS. THERAPY out. but is diverted into the manometer so that ihe pressure may be read directly. If the child is i'tng hard, a feu* moments are allowed to pass until die often falsely high pressure reading stabi lizes. \ About one or two milliliters of fluid are carc- tully collected; the needle is then withdrawn, the puncture site being compressed with a sterile -|>onge for a few moments and then scaled so that fluid will not -seep externally or into the livtues. Even with the greatest precautions, catas trophes do occasionally occur. In suspected cases the lumbar puncture is a necessity to rule out intracranial infections requiring specific treatment. Severe encephalopathy, characterized by convul sions. coma and at times respiratory arrest, always .hallcnges the therapeutic ingenuity of the at tending physician. Convulsions are unusually pro- uacted, repeated, and very difficult to control. Hie barbiturates are notoriously ineffective in die patient with lead encephalopathy; in our 'opinion, they actually carry a definite hazard of precipitating respiratory arrest, since the dosage may be pushed to the point of medullary paraly se in an attempt to control the seizures. It is extremely important to exert every means to I control convulsions, however, since the' accomI p;nying and ensuing anoxia contributes to resulti .mi brain damage. Paraldehyde is a safe drug; it is usually given icttaily in a dosage of 0.6 cc. per kilogram tip ro 10 cc. It may be given intramuscularly, or, tardy, even intravenously when more rapid action is desired. If paraldehyde proves ineffective, an in- halation anesthetic, such as ether, may be used, this will often stop a convulsion promptly, but may recur after a brief period of time. Chloral hydrate, another useful drug, is admin istered per fectum in dosage of 0.05 Cm. per kilogram body weight; no more than 1 Cm. per day should be given. Chlorpromazine may be Helpful in potcutiating other anticonvulsants. Di lantin has proved to be of little value in con trolling the convulsions of lead encephalopathy. When otherwise intractable, it may be neces sary to administer a barbiturate, but only with k'-cat caution. This is best -done using amobarbiul or pentobarbital intravenously. A syringe is filled with a solution containing a dose calculated it 0.1 grain per kilogram of body weight. The needle is introduced into the vein and the bar biturate injected slowly until the convulsion * vases. This will usually occur when about 5/4 n> 1 grain of the drug has been injected; at this |">int, the injection is stopped. We do not give Ftc. 5. Lead lines are seen in this x-ray of the ver tebral bodies. (Courtesy of Dr. Harvey White, Chil dren's Memorial Hospital, Chicago.) barbiturates intramuscularly, orally, or rectally in divided doses for this condition. Morphine, of course, is absolutely contraindicated. Since the brain dysfunction seems based prin cipally on severe cerebral edema, symptomatic therapy to overcome this edema is essential. In our hands intravenous urea has been useful.11 A concentrated solution (50%) may be used if the need is felt to be urgent, but we prefer a 4 per cent solution, because there is less likelihood o! throm bosing veins, or of producing sloughs if some of the solution should leak into the surrounding tissues. Urea is administered by fairly rapid intra venous drip, about 60 drops per minute, through a polyvinyl catheter threaded several inches into the vein. The dosage is 1 Gm. per kilogram of body weight. This amount will produce sustained diuresis up to 12 hours. Because of the likelihood of rebound of the cerebral edema after this pe riod, the doses are repeated regularly every eight hours for two to three days. The serum levels of electrolytes, blood urea nitrogen, and creatinine are checked daily. Moderate hyjxjdicrmia by application of the water mattress and air cooling seems also to be useful in reducing brain volume and in decreas ing the demand for oxygen by ganglion cells.54 CLINICAL PEDIATRICS Moy 196$ 273 61035144 GREENGARD We recommend its use in the severe encephalopa thy, exercising care not to reduce the body tem perature below 96 K. Myocardiopathtes have been described in severe lead intoxication,** and dis turbances in cardiac rhythm arc common in our experience. Excessive cooling may bring about cir culatory collapse.. In the hope of further reducing cerebral edema and brain volume, we supplement the hypo thermia by giving a corticosteroid, methyl pred nisolone sodium succinate, parenteral)}' in rela tively large doses over three or four days. We have treated 83 patients with severe lead en cephalopathy in this manner, but have been unable to demonstrate a statistically significant change in survival rates.** Extensive craniectomy has been recommended for severe encephalopathy with marked brain swelling.8 We have used this operation in 25 severe, sometimes moribund, children with lead encephalopathy.** Though in an occasional se lected case the method may be life saving, we have found its routine use unrewarding and have abandoned it for our patients. Chelating Agents. Chelating agents are of con siderable importance in the management of lead intoxication, particularly in the early case. Severe encephalopathy can undoubtedly be prevented by early diagnosis. Unfortunately, this is often not possible for reasons noted above. Calcium disodium edetate is the agent which has been used over the longest period of time.**** There are, however, two important shortcomings to its use in encephalopathy: (1) dosages within tire range of safety remove only a small fraction of the body burden of lead over a period of sev eral days, and this is not sufficiently rapid with a convulsing or comatose child; (2) in addition, the institution of EDTA therapy not infrequently produces an exacerbation of the symptoms for the first 48 to 72 hours. Chisolm* has stated that experimental studies in animals have shown the lead-EDTA chelate to be significantly dissociable in body fluids. Further more, the inhibition of heme synthesis by lead is intensified by the administration of EDTA in the experimentally poisoned animal. Since the inhibi tion of sulfhydryl enzymes by lead can be reversed by 2,3 dimercaptopropanal (BAL), he investigated lire effect of alternate and simultaneous doses of EDTA and BAL in lead poisoned children by measuring the levels of delta aminolevulinic acid (AALA) in the blood, urine, and plasma. This substance, a precursor of heme, is the sub strate of a ALA dehydrase. a sulfhydryl etuyme which is inhibited by lead. Delta aminolevulinic arid was found to be increased four to 25 fold in the child with lead intoxication; and each injec tion of EDTA was followed by a further 10 to J50 per cent increase in the plasma concentration. This rise was sharply reversed by each dose of BAL when these two drugs, were given alternately. On this basis, Chisolm has recommended a new therapeutic approach to lead encephalopathy, em ploying EDTA and BAL in combination. In our patients during the summer of 1964, 11 children with acute encephalopathy were treated by his technic, six recovered and five died. The method should be pursued further--it would' seem to be a rational approach. BAL alone has been aban doned in most centers as an unsatisfactory chelat ing agent in lead. We have also been employing penicillamiije on an experimental basis. Our results have been con flicting, but sufficiently interesting to pursue the investigation further. Complications of Lead Intoxication Respiratory Arrest. Complications in lead en cephalopathy may be severe. Coma with accom panying respiratory arrest is perhaps the most ominous. Attention to details of management are of extreme importance here,-A convulsing, uncon-' scious child must be kept under constant nursing and medical supervision. .To prevent further in jury, a soft mouth gag is employed to protect the tongue from being bitten, and the eyes are pro tected by lubricant and dressings. A laryngoscope, suction, endotracheal tubes and mechanical respirator-must be kept readily avail able for an emergency. If apnea occurs, the child will require resusciution and assisted respiration, and in most instances, via tracheostomy. This complication is of extremely . grave import. Though children may be maintained by the Ben nett, Byrd or Mordi artificial respirator for man} days, the ultimate outcome is almost invariably fatal. In our series, however, five of 20 patients have recovered after. varying periods, with the respirator. Methyl prednisolone succinate had been given to all of these, and is one reason why we are inclined to administer a steroid for severe encephalopathy. Anemia, live anemia of lead intoxication may be an important factor in the shock seen in the severe lead encephalopathy. Blood transfusions arcused in such cases, and are also necessary when surgical procedures under general anesthesia arc contemplated in these children whose hemoglobin levels may be as low as 5 to 7 grams per cent. 274 Vol. $ No. 5 CLINICAL PEDIATRICS 6103 5145 LEAD POISONING: SIGNS, SYMPTOMS, THERAPY All of these children require iron therapy which , ;m usually be administered in the form of oral ferrous sulfate. In those instances where the hemo globin level is quite low, or if for social as well as medical reasons the physician wishes to be certain iliat sufficient iron is quickly administered, it may he given intramuscularly as an iron dextran prepa ration while the patient is still hospitnlired. Gastrointestinal Tract. In all children whose x-ray films show large collections of lead-contain ing material in the gastrointestinal tract, repeated xaline enemas, dulcolax suppositories, or cathartics should be given as the first phase of therapy. The chelating agent is hot employed until after the radiopaque'material has been removed completely. All ocher medications such as calcium disodium edetate is withheld for at least 24 hours because of Its effect in aggravating symptoms, arid they are never given orally. . Gastrointestinal bleeding occurs with a fair de gree of frequency. It was encountered in six of our SS children with severe encephalopathy. This may be due to acute peptic ulceration of the duo denum. since such lesions are found at autopsy not Infrequently. When bleeding occurs with a stress uker, it is apt to be severe and uncontrollable; surgical inter vention may be necessary. The stool -should be followed carefully with daily tests for blood in these cases. We give calcium carbonate and aluminum gel preparations along with anticholinergic drugs prophylactically in alt patients with severe lead en cephalopathy. Shock. This occurs frequently in these children, and is an ominous complication. In oiir series of eight children, it resulted fatally in seven. Blood pressure must be taken at regular intervals with these patients, and may .have to be kept up by means of pla&ma expanders and vasopressor drugs. Steroids are of value here, also, as potentiating agents. Low molecular dextran solution intra venously seems to be of value in overcoming sludging of blood in the peripheral circulation. Serum electrolytes must be followed carefully in these cases, particularly when diuretics are em ployed, in order to correct any specific losses quickly. Nephritis. The kidney is a target organ of lead intoxication and EDTA is also a nephrotoxic substance. We have seen instances of acute urinary suppression, an extremely grave complication and usually fatal. Chisolm7 has pointed out the fre quency of aminoaciduria, often severe, in children with lead intoxication, and has concluded that its association with hypophosphatemia and 'gly cosuria is significant of a renal tubular dysfunc tion as seen in the Fanconi syndrome. This triad has occurred most frequently in those children with severe intoxication, but was reversible, al though long term follow up would be necessary to determine whether or not permanent impair ment had occurred. In this connection, Henderson14 reported fol low up studies on children in Queensland, Aus tralia who had acquired lead intoxication from powdered white lead paint many years previously. Many of these had died of chronic nephritis. In 187 who could be located, he found hypertension and proteinuria in 17. We have no personal data on this subject. Prevention The prime consideration in therapy of lead intoxication is removal of the child from the source of lead. While this is axiomatic, it is ex tremely difficult to accomplish this practically. In a city like Chicago, with thousands of dilapidated old dwellings in the poorer neighborhoods and several hundred patients suffering from appre ciable lead intoxication each year, the task of removing such children from further contact with lead containing paint and plaster is enormous.In spite of good cooperation by the Health De partment, a dozen or more repeaters are seen each year at Cook County Hospital. Sometimes this second attack is fatal. The best one can do is to try to correct the environmental factor in each individual case. To re-emphasize, we must stress once more that the only truly satisfactory approach to the man agement of lead intoxication remains its pre vention. This is a difficult problem; it involves a cooperative effort by practicing physicians, pub lic health agencies, welfare clinics, housing au thorities, building commissioners, avenues of com munication, school teachers, and the general electorate who supply the funds through govern mental agencies to deal with the problem of slums. Bibliography 1. Baetzer, A. M. et al.: Arch. Environ. Health 1: 465, I960. 2. Bcssis, M. and Breton-Gorius, Etude au micro scope electronique des granulations ferrugineuses des erythrocytes normaux et pathologique--Anemies hemolytique, hemoglobinopathies, saturnisme. Rev. d'Hemat. 12: 45, 1967. Quoted by Chisolm, J. J.: Disturbances in the biosynthesis of heme in lead intoxication. J. Pediat, 64: 174, Feb. 1964. 3. Bucy, P. C. and Buchanan. D. N.: Simulation of intracranial tumor by lead encephalopathy in CLINICAL PEDIATRICS Moy 1966 275 GREENGARD children, with remarks concerning surgical treat* went of the latter. J. A. M. A. 105: 244, 1935. 4. Byers, R. K.: Lead poisoning, review of the litera ture and report on 45 cases. Pediatrics 23: 585, 1959. 5. Chisolm, J. J.: Childhood lead intoxication: a pre ventable summer disease. Pediatrics Digest 6: 29, July 106i. 6. Chisolm, J., Jr.: The use of edathamil calcium di* sodium fEDTA) and 2,5. dtmercaploproponal (BAL) in combination for the treatment of acute lead encephalopathy. J. Pcd. 63: 843, 1963. 7. Chisolm, J., Jr.: Aminoaciduria as a manifestation of renal tubular injury in lead intoxication and a comparison with patterns of aminoaciduria seen in other diseases. J. Ped. 62: 1, 1962. 8. Cooper, M.: Pica. Springfield, lit, Clrarles C Thomas, J957. 9. Greenberg, M., Jarobzioer, H., McLaughlin, M. C., Fuerst, H. T. and Pellitteri, O.t Pediatrics 22: 756, 1958. 10. Greengard, J. el ah: Lead encephalopathy in chil dren, Intravenous use of urea in Us management. New Eng. J. Med. 264: 1027, May 18,1961. 11. Greengard, J., Voris, 1). C. and Hayden, R.: The surgical therapy of acute lead encephalopathy. J. A. M. A. 180: 660, 1962. 12. Greengard, J., Adams, B. and Berman, E.: Acute lead encephalopathy in young children, evalua tion of therapy with corticosteroid and moderate hypothermia. J. Ped. 66: 707, 1965. IJ. Henderson, D. A.: A followup of cases of plumbism in children. Australasian Annals of Medicine 3: 219, 1954. 14. Ingraham, F. D. and Matson, L>. i>.: Neurosurgen of Infancy and Childhood. Springfield, HI*. Charles C Thomas, Publisher, 1954. 15. Kehoc, R. A.: The metabolism of lead in man in health and disease. Archives of Environmental Health and Disease 2: 418. 1961. 16. Kehoc. K. A.: The metabolism of lead in health and disease. J. Roy. Inst. Publ. Health & H\ gicne 24: 177, 1901. 17. Kline, T. $.: Myocardial changes in lead poisoning A.M.A. J. Dis. Child. 89: 48, 1960. 18. McFadzean, A. J. S. and Davis, L. S.: On tire na tuve and significance of stippling in lead poison ing with reference to the effect of splenectomy. Quart. J. Med. 18: 57, 1949. 19. McLaurin, R. L, and Nichols, J. B,, Jr.: Extensive cranial decompression in treatment of seven, lead encephalopathy. Pediatrics 20: 653, 1957. 20. Nelson, W. F..: Textbook of Pediatrics. Philadcl phia, Pa., W. B. Saunders fc Co., 1964, p. 1561. 21. Pirrte, R.: The effect of splenectomy and reticulo endothelial blockade upon the^memia of lead poisoning In guinea pigs. J. Path. Bact. 64: 2U. 1952. 22. Statement on diagnosis and treatment of lead poisoning in childhood. Pediatrics 27: 676, 1961. ,, 23. Rapaport, M. and R'ubin, M.t Amer. J. Dis. Child. 61: 245, 1941. 24. Rosomoff, H. Li and/ T. A.: A.'study ol brain volume and during hypothermia. pinal Quid pressure . J. Phyikrf. 183: 19. 1955. READER'S CHECK LIST Experimental Animals Comparative Hematology. War * r en An d r ew , M.D., Ph.D., In* diana University School of Medi cine. New York, Grune and Stratton, 1965. 188 pp. 11G figures plus J 4 full-color plates. 22.75. A summary of the major findings with respect to leukocytes, erythro cytes and analogous cells in a great array of multicellular creatures in cluding common laboratory animals. The Pharmacological Basis of Therapeutics, Ed. 3. Edited by L. S. Go o d ma n and A. Ge l n iek . New York, Macmillan, 1965. 1,784 pp. 22.50. Jam-packed with information in its nearly iwo-thousand double-col umned pages, this masterwork cor relates pharmacologic observations and principles with clinical and therapeutic phenomena. Along with discussions of the various drugs, an esthetics, hormones, vitamins and poisons, there is an excellent exposi tion of the characteristics and prin ciples of use of the antibiotics, sul fonamides and related agents. Vision Screening of the Preschool Child; Report of a Study. R. A. Sav x t z , R. B. Reed and I. Va l a d x an . For sale by Supt. of Docu ments, U. S, Govt. Printing Office, Washington, D. C. 20402. 70 pp. 45 cents. A report of a survey of 94 young slum children in Boston by assorted tests. Six probable cases of ambly opia (corrected vision of less than 2Q/40) were discovered. "These chil dren arc culturally deprived, and it is interesting to speculate about the possible role of sensory deprivati' In the etiology' of amblyopia." The Foetus and the Recent Research. Brie Med. 3>! .Vofc 22, No. I, Jan. I960. $5.'" Nineteen stimulating papers I 27 leading British investigators mu vcy a diversity of phenomena biochemistry, physiology, ma:L lisra and resuscitation. General Recent Advances in Paediatr. 3rd Ed. Do u g l as Ga ir d x er . I itor. Boston, Little, Brown ;< . Co., 1965. 360 pp. $13.50. A collection of 15 comprehem ' and well organized review's by "< known authorities in England. Si" (Continued on page 291) 276 Vol. 5 No. 5 CLINICAL PEDIATRIC GLD351A7