Document jyqVO2d13KvkGqJmg5qXLJNLO

American Journal of Disc DEBORAH JACKSON. B.S ANIi l.ASl.O KAJDI. M l). ItAl.TIMOHF. l*i tty-six ytai> ago (1 8 7 4 ) W egner1 showed that inorganic phos phorus administered in small doses; as was formerly the practice in the treatment lor rickets, causes the freshly.forming traliecttlae at the ends of the shafts of the long hones to multiply and Become closely packed together. To this dense, thicket-like formation of tralieculac at the end of the shaft induced by phosphorus W egner gave the name "osteo sclerosis.'* Years later (1918) Phemister* discovered that dense shadows appear in the x-ray photographs of the long bones of children after the administration of minute doses of elementary phosphorus for five weeks or more. These shadows appeared in the parts o f the shaft that were in process o f growth during the administration of phosphorus and continued to form, so Phemister thought, for a time after the phosphorus Had been stopped. Since the long bones grow in length at their ends because of the growth activity in the proliierative zone of the epiphyseal cartilage, the dense shadows made their appearance at the ends o f the shafts immediately under the cartilage. Old bone remained unaffected, and new bone, formed some time after the administration of Submitted for publication, Aug. 16, 1930. From the Department of Pediatrics, Johns Hopkins University, School of Medicine and the Harriet Lane Home, Johns Hopkins Hospital. The fact that lead produces these shadows in the x-ray pictures of long growing hones was observed at the same time by Dr. John Caffcy of the Depart ment of Pediatrics, Columbia University (personal communication). A report of this phenomenon induced by lead was made by one of us (E. A. P.) in the dis cussion of a paper by Stafford McLean, "The Bone Lesions of Congcnitat Syphilis: The Correlation of the Roentgen and Pathologic Observations." and delivered l>efore the Pediatric Section of the New York Academy of Medicine on Nov. 14, 1929. The discussion was published in the American Journai. or t h e Diseases or CiitLDRrx 66:899 (April) 19.10; the article will be published in full in a later issue. 1 Wegner. G.: Ueber das normale und pathologische Wachstum der Roelircuknialien, Virchows Arch. f. path. Anat. 61:44, 1874; Der Eiutluss drs Phos phors aid den Organismus, Ibid. M :ll, 1872. 2 Phemister, D. B.: The Effect of Phosphorus on Growing, Normal and Diseased Bones. J. A M A 76:17.17 (June 8) 1918. 4 phosphorus had been stopped,seemed normal in structure. It the admin istration of the phosphorus had been stopped long enough, the shadow took the fortn o f a band which in the x-ray picture had the ap|>earance o f having sunk back toward the middle o f the shaft. In reality, o f course, it remained where it had developed, but new normal bone had formed beyond it. I'hentister attributed these dense shadows, which lie noted in the x-ray photographs of the long Imnes after the phospliorus administration, to the osteosclerotic formations of Wegner. FigT- t-*-- X-ray photographs of the knees o f * white boy, aged 6`1 years, who had been receiving cod" liver oil and elementary phosphorus for nineteen months. The action of elementary phosphorus in the production of such shadows in bones was first described by Phemistcr. Not only the ends of the shafts which grew rapidly but also the nuclei of ossification show the effect of phosphorus. The photograph is exhibited for purposes of comparison with the somewhat simitar though less dense shadows produced by lead. In the course o f study o f the x-ray pictures o f tnanv (tone* removed after death from the Ixxlies o f children, w e observed that the ingestion o f lead may cause shadows to appear at the growing ends o f the long *1 am permitted .to include this X-ray photograph through the courtesy of Dr. Helen J. Zillmer oC Milwaukee. (See Am. J. !)i*. Ciui.i*. S8:1.U4 ipearance if the long courtesy of -1344 IDec.l r.u<K i.i .ii..--sii.u u m \s I'K n ix cr.n n v l i .a u Ihiiics similar to those seen after continued administration of phos phorus, though the hands induced by lead in our four cases were not so broad or so striking as those obtained by means o f phosphorus. Altogether, we have now seen the phenomenon well develop'd in three cases o f chronic lead |x)isoning and moderately develojied in one. In two o f the cases we had the opjiortunity to study the condition at autopsy. REPORT OK CASES C a s k 1.-- History.-- T. L.. a lioy, aged 13 months, was admitted to the Harriet Lime Home on March 14, 1929, with the complaint of convulsions. For three weeks before admission the patient had had a cold, and eight days before admission a treatment of three injections daily of "cold vaccine" was started. Five days before admission, on the third day of treatment, two generalized convulsions occurred, each of which lasted for several minutes. The temperature rose to 39 C. (102.2 F.), and all night the baby remained in a convulsive state. On the following day, he seemed dull, had a stiff neck and the arms kept twitching, and again a severe generalized convulsion developed. During the three days before admission, the child had no fever, but seemed more and more sick, and on the day lieforc admission he ceased taking fluids. On the day of admission he was regarded as dying, but his condition improved slightly after a lumbar puncture which was said to have yielded a normal fluid. Throughout the illness the patient was constipated. "A feature of the child's story," the history relates, "is that he has lieen in the habit of gnawing paint from his pen, from his crib and from hfs walker. This lias been going on for about four months and was such an obstinate habit that his mother had recently taped these objects so that he could not satisfy himself." A blood smear examined on the day before admission by Dr. Margaret Handy of Wilmington, Del., showed stippling of the red blood cells. l:xaminatiou.-- On admission we found a well nourished and developed pale baby, apparently conscious but unresponsive even when painful stimuli were applied, flaccid between convulsions and sweating profusely. The fontanelle was depressed. The musculature wa,s hypotonic, but there was no paralysis. The neck was not stiff. The tendon and abdominal reflexes were considered normal. The Ilahinski sign was negative. The examination of the heart, lungs and abdomen yielded negative results. The spleen was not felt. There was no lead line on the gums. The temperature was .Vi.6C. (97.3 F.). The urine was normal. The cere brospinal fluid was clear, under normal pressure, with 6 cells per cubic mil limeter, and there was no globulin. Kxamination of the blood showed: hemoglo bin, SO per cent: red cells, 4,000,1(XX); white cells, 10,000; polymorpliomictcars. 488 A M l i K l C . t X J O U R X A L O F P tS F . t S F S (>! < U l l . O K I . S (104.7 F.> and from that time remained continuou>ly elevated. The baby lay; with eyes open and seemed, conscious, but responded poorly to stimuli and took food poorly. The evegrounds were found normal on two examinations. Another spinal puncture yielded normal fluid (2 cells anil no globulin). Though stippled red blood cells were seen before admission, as already mentioned,^tliey could not be found on the five days succeeding admission, but on the sixth day (the day ntthe commencement of fever) stippled cells suddenly appeared in numbers amounting to from 2 to 3 per high power field. On the ninth day they were absent, but on the eleventh and eighteenth days they were again noted "in some fields but not in all." The blood calcium was 10 mg., and the phosphorus, 4. mg. The urine remained normal. The Wassermann test of the blood and the spinal fluid gave negative results. An intradermal tuberculin test gave a negative reaction. Xu attempts were made to identify lead in the urine or stools. , The f>aby was treated, according to.the suggestions of Aub,a with a milk diet and calcium lactate in large doses and also irradiated ergosterol, with the idea, 'which was probably erroneous, that the latter might favor the deposition of lead in the (tones. On discharge the child was improved to the extent that death no longer appeared imminent, but he remained critically sick. ' After five days at home the baby was again admitted, because generalized con vulsions had once more set in, and he now seemed in an almost hopeless condition. The eptire body was spastic, except for the right arm, which, as befo-e. was in ceaseless motion. Similarly, the head was rolled continually from side to side and the mouth continuously performed a chewing movement. On admission the temperaturd was 38.2 C. (100.8 F.), but it rose in the next thirty-six hours to 42 C (107.6 F.). Still no lead line was dcmojristrated, and the eyegrouuds were normal. The spinat fluid contained 10 celts, and the Pandy test now gave positive results^ The red blood cells on this admission showed no stippling. Death occurred. A utopsy.-- At autopsy nothing of great importance came to light, except that ott chemical analysis lead was found in the brain. Dr. W. G.MacCallum's note states: "There are defects in the convolutions on both sides of the median fissure just above theoccipital lobe. On one sectionwith the knife through this part there is no gross abnormality ta be seen. The microscopic sections of the brain are said to show distinct degenerative changes in the ganglion cells with reduction in their number. There is not inflammatory reaction. There is a definite thrombus in the superior sagittal sinus; it is quite fresh."' No edema of the brain was -thought to be present. Slight pneumonia was found. The organs otherwise appeared normal In regard to the ribs, which were the only parts of the skeleton examined, the examiner's note states: "The line of ossification in the ribs is not irregular but it forms a broad band sharply outlined against the rest of the bone, evidently con taining laminae of the bone, and this band is marked out by its paler color and by an especially pale line along its border toward the bone. The other border, toward the cartilage, is also pale yellowish, but not jagged." The x-ray photographs (fig. 2) of the anterior ends of three of the middle ribs obtained at autopsy revealed narrow bands of intense shadow extending trans versely across the terminal 3 mm. There were three of these bauds; the one lying farthest hack front tile cartilage junction, a rihlxm-like stripe of dense shadow i '. i k k n r . t i . t u . m o i i ' s n u > r c n n k y u .m > alxuit 1.5 mm. wide, crossed the shaft 1.5 tnm. from the end; the second, a mere line of intense shadow at the extreme end of the bone, corresponded to the /one of provisional calcification of the cartilage and subjacent trabeculae, and the third was situated between the other two, appearing; as a line of shadow of much less intensity and clearly visible only in the middle one of the three ribs. The riblion-likc stripe first mentioned is the unusual one, and is thought to have been formed under the influence of the lead. The two lines of shadow may or may not have been produced by the lead. They resemble the growth lines in bones described by one of us * as the result of a variety of factors which suddenly alter the growth of the cartilage. Microscopic examination of the ends of the ribs showed that the trabeculae at the ends were normally formed but unusually numerous and thickly placed, and seemed thickest at the levels at which the transverse stripe and lines lay in the x-ray photographs. The examination indicated that the cause for the shadows in the x-ray photographs was the abnormally dense formation of trabeculae which Fig. 2 (case 1).-- X-ray photograph of three of the middle ribs of T. L., taken after their removal at autopsy. The ends of the ribs are marked by a band about 1.5 mm. wide and two lines. The band is thought to have been produced under the influence of the lead. The most distal line, L e., the one at the extreme end of the rib, marks the provisional zone of calcification of the cartilage and adjacent trabeculae. The other line, lying between the band and the line just mentioned, is not distinct and can be dearly seen only in the middle one of the three ribs. The two lines may or may not have been produced by the lead. must have obstructed the x-rays by supcrinipositimi. Of course the trabeculae ma$ have contained lead, and the lead may have been a factor in the production of the dense shadows. Cask 2.-- H istory.-- U. R,, a boy, aged 22 mouths, was the youngest of three children. The parents described a decrease in activity and drowsiness beginning three weeks before admission, then constipation, projectile vomiting, occurring in attacks, and, finally, a generalized convulsion. The convulsion was the immediate cause of entry into the hospital.4 4. Flint, M. M .; Souther, S. IV, and Park, !*.. A. Trai Plates of the Fong Hones of Children, Hull. Johns Hopkins *4<H A . U E K l C . t X J O C N X A l . O F D I S E A S E S O F L H I I . D K l i X At 16 mouths the baby had begun to walk, and since thcn4 that is, for six months, had gnawed paint off the furniture and porch railing. Examination.-- On admission examination showed a well nourished, pale clllhf, thought to have slight rickets, in a state of recurring convulsion^, each limited to the right side, including the face, and lasting for about ten minutes. Between' the convulsions the body was completely flaccid, with tendon reflexes absent. The fontanelle, which was small, bulged a little. The eyes'-were staring and crossed; the dilated pupils reacted sluggishly to light. Both disks were choked, but there were no hemorrhages in the fundi. No lead line was demonstrtited in the gums. Examination of the heart, lungs ami atidnmcn gave negative results. The spleen was not felt. The temperature was .17C. (99.2 1\). The spinal fluid showed greatly increased pressure, 9 cells per cubic millimeter; the results of the Bandy test were positive; ` Examination ofjthe blood revealed; white cells. 16,000; polymorphonuclear neutron Fig. 3 (case 2).-- X-ray photographs of two of the middle tier of ribs of H. R , removed after death. The terminal Z S mm. of the ribs are covered by a dense s--h-a--d..o.w.. ,r w...h..i.c..h. --can be explained by unusually rg>r-eat den--sivty o--f the t--r-a-b--e--c-u- lar formation in the corresponding part of the bone, as revealed by microscopic study (see figures 4- and 5). phils, 58 per cent; lymphocytes, 40 per cent, and monocytes, Z per cent. The hemoglobin was not determined. The red Mood cells showed coarse and tine stippling, from 3 to 5 stippled cells per oil immersion field. Many ring forms were seen. The results of the Wassermann test of the blood were negative. Treatment.-- The patient was treated, according to the method recommended by Aub,3 with intravenous injection of calcium chloride, but without demonstrable favorable effect. The convulsions continued, moderate fever appeared, ami death took place about forty-eight hours after admission. Autopsy.-- At autopsy the brain was found to be edematous. "The convolu tions were so swollen that the sulci were not visible." On examination with the microscope no changes in the nerve cells nr evidences of inllaumiatiou were found. In other respects the autopsy showed little that was abnormal. In the Mme- m rinir O in n lfit O ill* w tu * ( u u iiJ *uiJ, O f - -- m m ^ p ;# i '5 p || -y '. : . v'- - , ..''$'$*/&*'*;*'i?.-v-*,-_ /'.fA'K /:/ .// .%//.> ir\ r i c n n n u> in u t t > ` tm hi gross examination o f'the ribs am) femur, nothing l-trn-Jv almorni.il was noted. Till' nit surface nt llii upper -lt<.l of the friniir Wii* de'i ribed as timirlv" I iiormal. amt that of tin* till as suggestive of "a lato stage of healing rickets," i without reason being-1g' iven. 'T' he "line of ossification" was descri,bed as bring ' "slightly irregular." Doubtless. the gross appearance at the costochondral junction p g g l was abnormal, owing to the /one of thieklv placed interlacing tralieculae so clearly seen on examination with the microscope, but its nature was not recognized. '-., J s5-* m $M W Bm J'"i'-'.I^vmf'*'m'^j*0 ere negative. [demonstrable i. Mt$3i ry^&NiwS Fiir. (case 2).-- The cartilage shaft junction of one of the ribs of If. R.. shown in figure 3. Decalcification in formic acid staining with hematoxylin. The* dense formation of trabeculae in the terminal part of the bone (a-ti) is clearly shown. The somewhat similar condition sometimes seen itv congenital syphilis teaches that these thickly studded tralieculae may lie the cause of dense homo* Keneous shadows at the ends of lames in x ray photographs. Magnification, x Id The x-ray picturrs dig. .1) of the anterior portions of two of the middle tier of ribs, taken after autopsy, showed a densr homogeneous shadow which coveted tile terminal 2.5 mm of tile lames and completely hid their finer structure Jf w fe f i v. . - . m&wmmw l 3$s|g .. * -n.-i /. ; 3SS1 i -311 I <mz ^$$$ f~e-Vt\ <;/rM$-,:-, .- I ^ X '\ - DARK ET .11..--SHADOWS PRODUCED HV LEAD 4< > .) Wlu'ii tlic ends of the two ribs were examined under the microscope (figs. 4and 5), in order t learn the cause of the dense shadows, it was found that the trabeculae fora depth of several millimeters from the extreme ends were unusually numerous. They did not seem abnormal individually, but were packed close together. In the aggregate they must have formed a much denser mass than exists ordinarily at the end of the bone. A cause sufficient to explain the dense shadows at the ends of the ribs ini this case would seem to be the unusually thick, mass of parallel branching trabeculae; though a factor which cannot be excluded is the lead itself. The lead may have Ix-en deposited in these trabeculae and may have contributed to the density of the sliadows. Case 3.-- History.-- F. S., a Negress. aged 7*/i years, was first admitted to the hospital in June, 1929. in what appeared at the time to be an attack o f catarrhal jaundice, but afterward was regarded as the beginning of the lead poisoning. Examination.-- In addition to the jaundice, the child showed a moderate anemia, with a hemoglobin of 60 per cent. The gums, were not examined for a leadline. The patient recovered from this illness without event. Second Admission.-- The patient was admitted to the hospitat a second time, in August, because of convulsions. On this occasion a definite tead line was found, atid the spinal fluid contained 14 cells per cubic millimeter and gave a positive Pandy reaction. Course.-- The patient was treated with sedative, the convulsions stopped within twelve hours, and complete recovery seemed to take place. T h ird Admission.--O n September 22, the patient was. admitted for the third time. In the interval she was well, except for attacks of abdominal pain and occasional vomiting. She row had generalized convulsions. There was a marked lead line in the gums. The spinal fluid gave an unusually marked Pandy reaction with 9 cells per cubic millimeter.. There was a moderate anemia-- hemoglobin of 60 per cent-- with marked stippling of the red blood cells. The convulsions kept on recurring, largely in the form of twitching?, for more than one month. When the convulsions ceased, the child entered into a state of motionless conus which lasted one week. Then voluntary movements returned. Later, she began to take notice of her surroundings, but at first could recognize only large objects very dose to her. Finally, she sat up and mumbled words. A t present, almost a year after the" first admission, the child is healthy, but has almost no intelligence. The intradermaf tuberculin and Wassermann tests of the blood were both negative. The treatment during the last admission consisted of magnesium sulphate given intravenously when convulsions developed. No satisfactory history of the ingestion of lead was ever obtained, but the greatest shiftlcssness and ignorance in the household (Negro) made the search, unsatisfactory. X -R a y Examination.--On examination of the x-ray pictures of the extremities characteristic shadows were seen at the upper and lower ends of the tibia and fibula (fig. 6). the lower end of the radius, ulna and femur and the upper end of the humerus. The shadows could not be picked out at the slow-growing ends of these hones or in the compact bones of the tarsus or carpus, in the metacarpal or metatarsal bones or phalanges, in the cortices of the long hones or their centers of ossification in the epiphyses. The breadth of the shadows varied. At the lower ends of the tihiae and fibulae the shadow was approximately 1 cm. hnud. hut at the tipper ends it was aliout 1.5 cm. broad. It was almut I t cm, broad at the lower etui of the radius and ulna. The shadow was not clearly defined at its upper border hr the x-ray picture of the lower end of.the femur, hut seemed to measure 2.5 cm. The upper end of the humerus- was- not shown clearly it* the x-ray pictures. These measurements- are interesting, because? they indicate the relative' rates of growth at the various ends of the different Imncs mentioned. When the x-ray pictures were held far away from the eye, the impression was gained that the affected ends of the Ixmes mentioned were clouded. When they were held close, it became apparent that the clouding effect depended on an inten sification of the shadows cast by the trabeculae in the partsaffected. The individual trabeculae stood out more plainly in the affected than ire the nonaffectcd parts. The trabeculae in the parts that cast the dense shadows seemed more numerous. Fig. 6 (case 3).-- X-ray photograph o f the ankle of F. S., aged 7J6, showing a shadow t cm. broad marking the lower ends of the tibia and fibula. The shadow is obviously formed by a summation of the shadows of the trabeculae which are thought to he more numerous and perhaps larger in the affected than in the adjacent normal parts. The width of the shadow in a child, aged 7, indi cates that the factor responsible for the shallow, lead, has been in operation a long time and perhaps individual trabeculae seemed thicker. Out in regard to these last two points it is most difficult to be certain. The line of demarcation between < affected and unaffected bone was sharp, except in the lower end of the femur and the upper end of the humerus. But the x-ray photographs of the humerus and the femur were poor. The shadow at the lower end of the femur was the most dense and homogeneous--in the x-ray picture it had a snowy appearance-- probably because of the greater thickness of the bone. X-ray pictures taken a year later showed the shadows as distinctly as before. Very little growth in the defined at its but seemed to clearly in the r indicate the entioned. mpression was L When they d on an intenThe individual affected parts, ore numerous. | 7 & showing 1 fibula. The the trabeculae e affected than I, aged 7, indi in operation a of the femur I the humerus emur was the j appearance-- r.lK K HI .11..-SHADOWS PRODUCED 11Y LEAD 495 length of the bones liad occurred in that time, not more than from 1 to 2 mm., for example, at'the lower end of the radius or the upper end of the fibula, and no normal lionc had made its appearance immediately adjacent to the epiphyseal cartilage; so the shadows still seemed to reach to the extreme ends ofjthe shafts. C ask A.--History.- 15. C.,.a white girl, aged 2J4 years, was known to have eaten paint for one and a quarter years. For the six months prior to admission frequent vomiting .and obstinate constipation had been present. During pertussis, six months before admission, nine long, severe, generalized convulsions had taken place. Since then there had been gradual mental deterioration. Examination, On examination the defective mental development was obvious. A state o f anemia was found, with a hemoglobin of 50 per cent; the red blood cells showed marked stippling, from 3 to 4 cells per high power field. Three weeks later the stippling could not be-found. No lead line was demonstrated. The spinal fluid was normal,' except for a positive Pandy reaction. The eye- yr.ui'.ds were not examined. __ _ j Course.-- A rapid improvement in the constipation and eating habits took place in the hospital, and the child was discharged. A year after discharge the following special note was made by Dr. T. Campbell Goodwin:. "Patient began ingesting lead when she was from 11 to 12 months old. This continued steadily for six months, when she became too weak to walk. But from the mother's story her restricted environment did not decrease the amount Of paint chewed, so even up to the time of admission to the hospital at 27 months she was steadily eating (taint, plaster, chewing on toys, etc. "When seen today, she was physically perfectly normal, reflexes all right, no lead line, not anemic, weight and height average for her age. Her mental retardation was not as marked as it was when she was in the hospital. She is beginning to talk, using short sentences. She recognizes all of her family, calls them by name and can play fairly well for a child of 3% years." X -R a y Examination.-- The x-ray pictures of the extremities showed shadows at all of the rapidly growing ends of the long bones. The shadows at the upper and lower ends of the tibia and fibula, the upper end of the humerus and the lower ends of the radius and ulna were about 1 cm. broad, that at the lower end of the femur was wider, measuring about 1.5 cm.' The shadows were light, giving the impression, when the x-ray picture was held at a distance, of a faint clouding. The shadows were not dense enough to hide the finer structure on close examina tion. Indeed, on close inspection of the x-ray photographs, the finer structure could tic seen in both its longitudinal and transverse arrangements more clearly than in the unaffected parts of the bones, and one gained the impres sion that it was the increased density of the finer structure that gave rise to the clouded appearance. Extending transversely through the affected etuis of the shafts were many transversely disposed lines of growth. It was difficult to say whether or not the slowly growing ends of the long bones, namely, the lower i tid of the humerus and the upper and tower ends of the radius and utna were affected. No definite evidence could be found of involvement of the centers of ossificatidn of the epiphyses or of the small bones of the hands and feet or of the cortices. TOMMKNT Win'll taken for a sufficiently long jxriod in suHicicnt dosage, lead, apparently. can produce changes in the Ifi'H1* in tp,y e y of fo^n;iti -t> which arc reflected in the x-ray photographs a s .shadow* o f increased density. Like elementary phosphorus and perhaps some other heavy metals, e. g., arsenic,* lead can cloud bones in x-ray photograph*. T he clouding is most conspicuous where growth is occurring most rapidly, namely, at the anterior etuis of the middle six ribs, the lower ends o f the femora, the upper end of the humerus, the lower en d s.of the radius and ulna and at both ends o f the fibula and tibia. In our two cases in which the banding was most marked, cases l and 2. only the ribs were studied with the x-ray, but in cases 3 and 4 , in which banding was well marked in the fast growing parts o f the skeleton, it was not noted in the slow-growing parts. That only those parts o f the skeleton in process o f growth at the tim e o f ingestion o f lead are aiTected is proved by the entirely normal structure o f the old bone proximal to the lesions, the sharp limitation o f the lesions to the growing (>arts and a degree o f involvement at any point exactly proportional to the rate o f growth at that point. Obviously growth in any Ixine takes place in many*'places, but only where growth occurs rapidly d o the changes readily reach such .magnitude.as to show in x-ray photographs. T h e fact that only the bone in process o f growth is affected must mean that the lead either enters into the chemical composition o f the' bone or influences cellular activity in such a way that the diam eter o f the bone' formed becomes altered. T he work o f H unter and Aub indi cated that lead is actually deposited in the bones, and this study, in conjunction with that o f Bauer, Aub and A!Ibright.r brings forward strong indirect evidence that the place o f deposit is the tralieculae lying in close proximity to the cartilage. The evidence just cited, that lead actually does enter the skeleton, and th e fact supplied by-our ow n x-rayphotographs, that only the growing ends o f th e shafts showed the lesion, led u s to expect that the dense shadows cast by the ends o f the shafts were actually due to the presence o f lead in them and to anticipate that the appearance under the microscope would be normal. W hen we made sections of the bones through the zones o f clouding in cases t and 2 ( figs. 2 and 3 ) , which were the only cases available fo r microscopic study, we found that a pathologic condition existed in the part o f thg Ixine corresjxinding to the clouding in th e x-ray plate, which could 5. fijes, T .: Experimcntclle Untersuchungm fiber den Einfluss ties Arsens au fen Organisum*. Arch. f. exper. Path. u. PharmaknI. 8:175. 1H77. 6. Hunter, D., and Aub, J. G : Lead Studies: XV. The Effect of the Para thyroid Hormone on the Excretion of Lead and of Calcium in Patients Suffering from Lead Poisoning. Quart. J. Med. 88:123. 1926. , 7. Hauer, W.; Aub. J. C., ami Allbright, F.: Studies of Calcium and Phos phorus Metabolism: V. A Study of the Bone Tralieculae as a Readily Available Reserve Supply of Calcium, J. Exper. Med. 0:145. 1929. and conti increased ler heavy ohs. The the radius ,ub * indi p a r k n r .I/..-sir.in cu rs r n o n r c n n n v u u n m account tor the latter ( tigs. 4- and 5 ). 1'hc trabeculae were far more numerous than normal and in consequence more closely (Kicked together. In the aggregate these tralieculae. so greatly increased in number, must have licen capable o f obstructing the passage o f the x-ravs and o f producing the shadows. So far as it is (lossible to b e influenced toward any conclusion from our two cases, we should suppose that the lead modified endochondral ossification in such a wav that the trabeculae formed under the cartilage a much more dense thicket than normally, anil that these formations of densely packed trabeculae were the cause o f the iKiudlike shadows. On the other hand, we admit the probability that lead itself was in the tralieculae, and that it may have been partly responsible for the shadows. In. any event, an anatomic explanation fo r the shadows was present in the only two cases which permitted o f histologic study. In. some cases o f congenital syphilis the columns o f calcified intercellular substance o f th e cartilage accumulate in a. thick, interlacing network almost undisturbed in the shaft. These columns of calcified intercellular substance are capable o f casting dense homogeneous shadows in x-ray pictures, and the dense homogeneous shadows which become visible after the prolonged ingestion o f elementary phosphorus depend on an "osteosclerotic** condition in the bone which, a s described by W egner and also by Bless,* seems to consist merely in dense io rmations o f tnilieculae similar to those which we have described a s result in g from lead. In the first two cases (fig; Z and 3 ) , the shadows were narrow anil intense, the children were young, and death occurred. From the facts that death took place ami that th e shadow in the bone was- intense, one might think that the amount o f lead eaten was large, and from the fact that the band was narrow one might in fer that the period o f poison ing w as o f short duration. In case I the eating o f lead was pronounced and hail been in progress four months. In case Z the amount o f lead continually eaten must have been large, and the duration o f the habit was six weeks. The failure o f the shadow in case t to involve homogeneously the entire end of the Nine must mean that the ingestiolr o f lead w as irregular o r intermittent. Rut there are no statements in tlie history in case 1 to indicate this. Unfortunately, in case 3 we could get n o history o f lead poisoning, although the evidence o f the presence o f the condition in the child w as entirety satisfactory. In thi* case ( fig. 6 ) , however, the breadth o f the shadow in the rapidly growing H. H o ii A. F, and Wriiistmk, Mildred.: Tin- Value pluirm in Rickets: Alt Fx|>eriniental Study. Am. J. Div iMi.h-ic.ix j o r r . x . i r o r iHSE isns o r ch iimkhx end o f the hone (from 1 to 1.5 cm .) o t a child,'*a g e d / j y e a r s , indicates that the hal>it m ust have been in progress for two years o r more, and the position of the shallow immediately under the cartilage, i. e,, the iuvolvemeut o f the m ost recently formed trabeculae, m akes one think; that the poisoning lasted to the time o f the patient's admission to the 9. Dr. Martha M. Eliot and Dr. Susan P. Souther furnished Us with the data at their disposal resulting: from the study of rickets in New Haven, Conn., hy the United States Children's Bureau, concerning the rate of growth of the radius and' ulna in young children. Dr. Souther writes: *`l collected as many cases as t.could in which the ages lay between eighteen and twenty-four months,(betwcen twenty-? four and twenty-seven ntdhths, and also lietwcen twenty-four and thirty months, in- order to see what.variations there were in rate between those periods. The measurements have not been worked out statistically, in relation to age periods, and there are not many cases falling in the different periods, but they do show at about what rate the tapes of the average child of two years are growing. These measurements are for total growth and not for the lower ends of the bones. The few measurements we had in which we could measure from a' definite line indicated: that about-three fourths of the total growth occurred at the lower ends. 18-21 m onths (3 9 children) Range in growth ot radius between 1.05 cm. and 0.45 cm. Average for group. 0.73 cm. in 6 months period 24-2T months (13 children) Range in growth of radius between 0.58 cm. and 0.2 cm. Average for group. 0.33 cm. in 3 months period 2 t-30 m onths (14* children} Range ia growth of radius between .9 cm. and .5 cm. Average for group. .64 cm. in 6 months period "L collected the figures for the ulna at the same time, and it is interesting that there is a variation between the two Nines in the eighteenth to.twenty-fourth month period 18-24 m onths (12 children) Range. 1.2cm. to 0.6 cm. Average, 0.79 cm. Z4-2T months: (16 children) Range. 0.55 cm. to 0.17cm. Average, 0.334- cm. 24-30 m onth? (21 children) Range. 0.85 cm. to 0.4 cm. Average, 0.63 cm. "Because of the smalt number of cases I do not know how much value can he placed on this variation.' L thought, however, that yon might he interested in the radius. PARK l:T Al..--SHADOWS P R o i U d l ) HY t.I.A If A'/t hospital. In the last case, the history indicates that the eating o f lead was marked for one year Ik-fore the child came under observation and was continue^ up to the time when she was admitted to the hospital and the x-ray pictures were taken. W e know that the child was young, 2*4 years, and that the poisoning was sufficient to injure the m entality but was never o f such intensity as to cause death. The shadows in the bones in this instance were not as heavy as the history might lead one to expect, but their breadth (from 1 to 1.5 c m .)a was in keeping with the long duration o f the poisoning ( l year), and their position just under the cartilage corroborated the statement that the habit of eating lead continued to the time when the pictures were taken. There are pertinent questions that we cannot answer. Since the phenomenon seems to be dependent on growth, one would expect it to occur less and less frequently with increase in age, and never to occur in the fully grown person. Wegner stated that phosphorus produced its effect only in the growing organism. W e feel certain from theoretical considerations that lead can affect the skeleton in the way described onlyin the case o f children, and w e believe that the phenomenon will be the more strikingly developed, the younger the subject. W e are influenced in so thinking by the confinement o f the lesion to the growing parts of the skeleton, and, in a given case, by the correspondence between the degree o f involvement of the ends of the long bones and the growth at those ends. Another question is the constancy o f the phe nomenon in cases o f lead jwisoning in children. In the four cases o f lead poisoning in which x-ray pictures were available, the shadows in the long bones were present. W e do not believe, however, that the shadows will be foutyl in all cases, though we guess that they will be found in most cases o f severe poisoning in young children. At any rate, the clouding o f the rapidly growing ends o f the long bones as seen in x-ray photographs ought to be a useful, corroborating, or perhaps suggestive, sign o f lead poisoning in children.10 T he action o f lead on the growth o f bone is now being made the object o f special study. 10. A word of caution i necessary. In the very young infant the outline of the rapidly growing end of the shaft of a long hone is not marked by a dense shadow unless it is the seat of congenital syphilis or rickets in a state of active lime salt deposition fhealing). But in the normal child of 1 or 2 years or older, the outlines of the fast growing ends of the long bones are marked by dense shadows, so dense that if they were seen in the young baby they would at once suggest previous rickets or coiigraitn! syphilis. These normal shadows at the ends of the tibia and fibula or the lower ends of the femur or radius and ulna in older children must not lie miMAkcit for the phenomenon described as produced hv lead.