Document 5kXx2z3moD4OrGOZQ5daawOJ8

738 OCCUPATIONAL CANCER--H VETER JI.uikA 21M, . A sions occurred in the majority of cases with less than one year's treatment and continued in 8 cases for more than two months is convincing evidence that the remis sion was induced rather than spontaneous. It should be remembered, however, that if treatment is continued for more than eighteen months and then discontinued, the resultant remission might well be a natural one. It has been suggested that thiouracil could not induce a relatively long remission because it produces in the gland a iiyi>crplastic but functionally inefficient state. It has liecn recognized that a hyperplastic state of the thyroid can exist in a patient experiencing a relatively permanent remission of his thyrotoxicosis. This has l>ccn demonstrated by the structure of the remnant of the thyroid gland after thyroidectomy by RienhofT10 and Branch. They examined sections of the thyroid gland removed several months after thy roidectomy and found the characteristic evidence of stimulation of the thyroid. Even though this state of hyperplasia persists, Preston and Thompson*11 con cluded that a single thyroidectomy may accomplish control of the toxic state sufficiently to avoid subsequent operations in 85 jier cent of the patients. Treatment with thiouracil has the same effect as thyroidectomy, at least temporarily. This is accom plished by reducing the function of the thyroid tissue by interference in the iodine concentration and oxida tion process of the gland. It is entirely possible that the hyperplastic state of the thyroid induced by thiouracil changes to a state of normal involution after a variable time. Evidence in support of this is to be found in the rcjxjrt of Shirer and Cohen,15 who observed a normal morphologic picture in a thyroid gland removed from a patient previously treated unsuccessfully for seven months with thiouracil. Further evidence of the active effect of thiouracil in producing a more permanent change in thyroid func tion is found in the case reported by Barr,4 and in 1 observed in our scries in which a thiouracil induced picture of myxedema recovered slowly over a period of six months after treatment with thiouracil was dis continued. In our opinion this evidence indicates that thiouracil docs more than iodine in that it produces a change in the thyrotoxic state which persists after the admin istration of the drug is discontinued. CONCLUSIONS Thiouracil may be used in about one third of the thyrotoxic patients only as preoperative treatment, since these patients possess nodular goiters which might develop a malignant condition. Another 7 per cent of the total number will require thyroidectomy on account of complications which occur during thiouracil therapy. The most serious of these complications to be kept in mind is agranulocytosis.* About 15 per cent of the patient? with thyrotoxicosis will leave the physician's care for personal reasons of the patient, which are in some instances related to difficulties encountered in thiouracil therapy. In the remaining 45 per cent of the total group, made up of those with toxic hyperplastic goiter, thio uracil therapy may be discontinued at the end of a little over an average of ten months with the prospect that GO to 80 per cent of the patients will experience a relatively persistent drug induced remission. For this 10. Kienhcft. cited by Fit*.* 11. Preston, F. W.. and Thompson, W. 0.:_ Persistence and Recurrence of Toxic Goiter Following Subtotal Thyroidectomy, Arch. Int. Med. (iff: 1019 (June) 1942. 12. Shirer, J. W., and Cohen. M.: The Effect* of Thiouracil on the Thyroid Gland, Ann, int. Med. 23: 790 (Nov.) 1945. selected group, at least during the period of observation w hich has continued to date, this result is as satisfactory as that of subtotal thyroidectomyTMmmmm^mm patients with thyrotoxicosis, how5 PLAINTIFF'S by surgical means. Those rcceil | continue treatment with the drug f|f EXHIBIT EPG - 1 0 For these reasons surgery is still tlgg in the management of this condll superior to. iodine, however, as its action and induces a more complete and permanent remission in patients with this disorder. In the treat ment of selected, cases of thyrotoxicosis, therefore, thio uracil treatment must be considered as a form of therapy which has promise, and ultimately it may prove to be as satisfactory as thyroidectomy in this group of patients. INDUSTRIAL MANAGEMENT AND PATIONAL CANCER W. C Hum*. M.D. New Yftfk OCCU The term "occupational cancer" applies to malignant tumors which originate in persons during the course of and as the result of the regular and usually prolonged exercise of certain occupational activities which entail contact with some exogenous, physical or chemical car cinogenic agent acting in proper intensity. Occupational cancers are in general elicited by specific factors which form an integral part of the ordinary working conditions and thus are not the result of some unforeseen, acci dental injury sustained while at work. Although a few of the cancers so far recognized as of occupational origin have been known or have existed without correct recognition prior to the advent of the modern industrial era, such as the soot cancer of the chimney sweeps and the cancer of the lung of the cobalt and uranium miners in Schnceberg and Joachimsthal, the great majority of occupational cancers appeared after the start of the present industrial development and as a result of it. During the last century there occurred not only a constant rise in the absolute number of these malignant growths but also a decided increase in the types of organs affected by them, in the number of exogenous occupational agents involved in their pro duction and in the variety of manufacturing establish ments in which workers were afflicted with them. An analysis of the available data on occupational cancer has shown that the type of the resulting tumor, the length of the latent period preceding its manifesta tion, the organ affected and the age of the person involved depend on the character of the carcinogenic agent, the type and intensity of exposure and the age: of the person when the first exposure takes place. The soot cancer of the scrotum found in chimney sweeps, for instance, was observed some hundred and twenty-five years ago even in children, since boys as young as 4 years were used in England at that time for cleaning chimneys. The exposure to the carcinogenic soot dur ing this operation was severe, and the degree of clean liness among these unfortunate youth was very low. When, during the middle of the last century, the English government repeatedly raised the age limit of the apprentices of this trade, there followed a gradual rise of the age range at which the scrotal cancers appeared among chimney sweeps. At the same time the institu tion of better hygienic conditions and the improvement of working tools and of chimney construction reduced From the Warner Institute for Therapeutic Research. ,- VKetf"'* P9 1 OCCUPATIONAL CANCER--HUEPER 739 the degree of exposure to soot. As the result of these changes the scrotal cancer of chimney sweeps in England now appears at the same age as that found in members of the general population affected by cancer of the scrotum of unknown etiology. Only the increased incidence of this particular type of tumor among chim ney sweeps has remained as evidence of the action of an occupational carcinogenic agent. However, not all occupational cancers iiave followed such a favorable development. Whenever the managers of new plants and their medical advisers have neglected to profit, in the construction and operation of their estab lishments, from the adverse experiences previously had by other manufacturers in the same fields, there has appeared some ten to fifteen years later a renewed, acute and sometimes epidemic-like occurrence of occupational cancers in these industries. Such a course of events is exemplified by the incidence of cancers of the urinary bladder in workers of the aniline dye industry. These tumors were first observed in 1895 in German dye works and were later found among the chemical workers of other countries, such as Switzerland. Italy, England. Japan and the United States. The time of appearance of cancers of the bladder of this origin followed closely the time of large scale development of chemical indus tries in the countries mentioned. Thus the first cancers of the bladder in chemical workers of this country were noted in 1932. that is. approximately fifteen years after the American dye industry had reached large propor tions. Within the short period of six years thereafter almost 100 cases of this industrial cancer occurring in men of relative youth were placed on record from one single chemical concern, attesting to the presence of a relatively massive exposure of the workers to the causative agents--that is, bctanaphthylaminc and benzi dine. The full significance of this incidence figure becomes apparent from the fact that there were only about 300 cases of this particular occupational cancer reported, according to the statistics of the German gov ernment. front the entire German chemical industry within a period of forty years, that is. from 1893 to 193a. Although no authentic data arc available as to the occur rence and the incidence of tumors of the bladder among tile workers of other American chemical concerns, the existence of such cases is known. Cancers resulting from contact with radiant energy-- that is. the rays front radioactive substances and roent gen rays, illustrate strikingly the influence which the type atid intensity of contact exert on the formation of the ensuing tumor. It appears that the inhalation of radioactive gases or radioactive dust causes cancer of the lung, such as that sustained by miners in Schnccbcrg and Joachimsthal, whereas the local action of radioactive and roentgen energy on the skin causes the development of cancers of the skin, such as those seen in radiolo gists, roentgenologists, their assistants, and in x-ray tube manufacturers, physicists and engineers. The ingestion of radioactive matter, on the other hand, causes the development of cancers of the bones, such as those observed several years ago in girls who applied luminous paint to dials. However, in more recent years cancers of the blood, known as leukemias, have been noted in increasing numlxrr among physicians and radium chem ists exposed frequently to relatively small doses of roentgen rays or rays "from radioactive matter. These deleterious effects on the blood-forming tissue have their cancerous equivalents in the leukemias observed among persons cNjioscri to benzene. This organic solvent, like roentgen rays and rays from radioactive substances. causes a destruction of the blood-forming tissue and results in a fatal anemia when acting in large doses, but it may elicit leukemic responses when acting in small doses and in suitable intervals on the blood-forming tissue. In most cases of industrial cancer, experimental research on cancer has succeeded in demonstrating the specific carcinogenic agent involved by using these agents to reproduce similar tumors in animals. Definite proof of carcinogenic properties have thus been obtained for arsenic, tar, pitch, soot, crude mineral oil, crude paraffin oil, anthracene oil. shale oil, sontc fuet and lubricating oils, creosote, benzene, aromatic amines, ultraviolet rays, roentgen rays and rays from radio active substances. In recent years, however, cancers of the lung have been noted among workers in chromate plants, nickel refineries and asbestos-manufacturing establishments. These tumors are either suspected or recognized as being of occupational origin. An inter esting feature of these cancers is represented by the fact that the cancers of the lung in chromate workers were observed only in several German plants, while the can cers of the lung in nickel refinery workers were found exclusively in English plants where the nickel carbonyl process was used. Although the same process is employed in some nickel refineries located in Canada and the United States, cancers of the lung have not been noted among the workers employ evl here if full credence can Ik given to the meager information available on this matter. Cancer of the lung in asbestos workers, on the other hand, lias been reported from Germany. England and the United States. The actual causative agent in the production of cancers of the lung in chro mate. nickel and asbestos workers is still unknown. The rapid increase in the munlicr of recognized and suspected agents causing industrial cancers which have occurred during the last forty years makes it more likely that new and heretofore unsuspected carcinogenic agents of an industrial nature will lie discovered during the coming years. Such a development is foresltadowcd by observations made during recent years by American investigators. It was found that cancers of the liver developed in mice exposed to carbon tetrachloride, a commonly used organic solvent. The inhalation of ethyl carbonate (urethane), which is employed for anes thetic purposes, resulted itt the ap|>caranee of cancers of the lung in ntice. Tumors of the bladder were formed in rats fed diethylette glycol, which is one of the newer widely used organic solvents. Tumors of the peripheral nervous tissue were seen in the cars of rats to which crude ergot, a drug extensively used in obstetric practice, had been fed over long periods. Occupational carcinogenic agents produce cancers in numerous organs. Cancers of the skin are elicited by contact with arscnicals, tar, pitch, soot or carlion black, crude mineral oil, lubricating oil. shale oil, crude paraffin oil. anthracene oil. solar and ultraviolet rays, roentgen rays and rays from radioactive substances. The number of industrial cancers of this organ runs into several thousands. Cancers of the nasal passages have lieen noted after occuixitional exposure to eliminates, nickel carbonyl and radioactive substances. Cancers of the bronchi and lung have been traced to an industrial exposure to arsenicals, chromates, nickel carbonyl, soot. tar. asbestos and radioactive substances. Cancers of the lip have apjKired following contact with tar and after pro longed cxpiuurc to solar ravs. while cancers of the mouth and of the tongue seem to Ik etiologieally related to an industrial contact with tar and arsenicals. Cancers of the bladder, of the ureter and of the kidney have fol-  '<'A. j li I 4 i 4 11 i k f I 740 VCCLT.n IOX.IL CAXaiK--IIlT.rilK I A * Ma 1`Mfc lowed occupational cx]H>surcs to aromatic amines such as naphthylamine, licnzidine and aniline and occasion ally to tar and arscnicals. Cancers of the blood, called leukemias, have resulted front contact with benzene, roentgen rays and rays from radioactive substances. The latter arc also responsible for the occurrence of cancer of the bones. The c.\|)Osure time necessary for eliciting cancer ous reactions in c.\|>oscd workers varies greatly with the tv|>c and potency of the carcinogenic agent, with the intensity of exposure and with the susceptibility of the individual. The range is front six months to three to four decades, while the average exposure lime is from five to fifteen years. In most instances occupational cancers appear in a younger age group than that found for the same cancer of unknown etiology in the general population. Age and sex factors do not, as a rule, play any role in the production of industrial cancers. The incidence rate of these tumors shows decided varia tions not only for the difTcrcnt carcinogenic agents but also for the different operations and is directly propor tional to the latency of the carcinogenic agent and the intensity and length of exposure. Cancer of the bladder thus affects from 30 to 90 per cent of the severely exposed dye workers, while cancer of the lung kills from 75 to SO jier cent of the cobalt miners of the Sclmecbcrg mines. Carcinogenic agents eliciting occu pational cancers of the skin, on the other hand, have a lower morbidity and mortality rale because the prccanccrous changes of the skin preceding the apjjcarance of the tumors gives amide wanting, as a rule, of the threatening malignant condition, while the ready accessi bility of the skin to thera|>euiic measures enhances the prognosis of cure. It is of a certain importance from an industrial point of view that the skin of colored workers is less susceptible to the canccrigcnic action of solar rays and of tar, pitch and similar substances than that of white, and especially of fair-skinned, workers. The total numticr of occupational cancers placed on record is small when comjarcd with the large number of cancers ot unknown etioiogy. It is obvious, however, that the latter group contains an undetermined number of cancers of occupational origin, as many of them either are not properly recognized or are not made a matter of public information. Although today a great deal of evidence on the causes of uccujiational cancer and the conditions under which it develops is available, relatively little effort has been made to spread this knowledge among parties who are vitally concerned with this information, namely the man agers and physicians of industrial concerns, although they carry the main load of controlling this preventable type'of cancer. This situation is the more deplorable because the present rapid development of industry tends to extend the hazards of the known industrial carcino genic agents while at the same time creating new ones which may cause the appearance of cancers ten to twenty years hence, unless concerted efforts are made in time to discover and control such dangers by appropriate countermeasures. It is essential that industry should devote considerably more effort than heretofore to deter mining the cancerous or noncancerous nature of such of its numerous products as may be suspected on general grounds of canccrigcnic properties. As occupational cancers are chance experiments on cancer in man, con ducted by modern industry on a large scale, which render direct, reliable and conclusive information as to the cause and mechanism of human cancer, the inves tigative study of these conditions deserves a great deal more consideration than it has Ik'cii given in the past. The experience gained from the study of occupational cancer, and especially of its causative mechanism and its prevention and control, should prove of great value in the future in fighting cancer in general at its source; that is. it should aid in the elimination of the causes of cancer before they are capable of initiating the malig nant growths. In waging this camjiaign it should lie realized that a well planned, systematic and, probably, prolonged attack must be launched if worth while results are to be exacted. However, I am convinced that with the necessary perseverance and determination this battle against occupational cancer in particular and against cancer in general can be won, if every one concerned aids in the effort. If industry can be persuaded to finance the foundation and maintenance of an organization exclusively devoted to the study of the causation and control of industrial cancers, not only will industry be the main beneficiary of this move, but also it will greatly advance the fight against cancer in general, which is of direct concern to every one, unless it is forgotten that every tenth adult dies from this disease. KECOM mendations for the control of OCCUPATIONAL CANCER 1. riant management officials, industrial workers and members of the medical profession must be made increasingly aware of' the fact that numerous agents of our new industrial environment possess carcinogenic properties. 2. Construction and chemical engineers should design buildings, machinery and apjiaratus with this hazard in mind--that is, they should try to favor the closed system of production, the installation of adequate exhaust ven tilation, the use of building material which does not absorb carcinogenic substances, the avoidance of nooks, crevices ami ledges where carcinogenic dust can be dcjiositcd, and the employment of wall and floor cover ing that can be thoroughly and repeatedly cleaned with water and stcain used in connection with cleansers. 3. Adequate provision must be made for the removal of carcinogenic material from waste gases, fumes, waters, dust and the like before these waste products are released into the air, public waters or other chan nels affording the contact of the general population with carcinogenic industrial wastes. 4. Carcinogenic material must be packed in leakproof containers. 5. Similar appropriate protective technical measures should guard the persons handling roentgen rays and radioactive substances from being exposed to deleterious^ quantities of radiant energy. , 6. These measures must be sufficiently extensive to protect also persons working or living in the immediate - environment where physical or chemical carcinogenic agents are handled. 7. Whenever the use of carcinogenic material in industry cannot be eliminated by the use of substitutes, workers should lie protected from contact with carcinov. genic agents by suitable protective clothing, gkw*J masks and the like and by the enforced observance adequate hygienic measures, such as the use of washinjj facilities, showers and special robins for storing street clothes and for taking meals and frequent changes ol working clothes. , S. Frequent and experienced medical supervision the workers exposed to carcinogenic material is imp xr X'OLUME 131 Nl'MVEl 9 ACUTE SYPHILITIC NEPHROSIS--BARR ET AL. 741 * tivt'tor effective control of the liazard. This supervision n;usr also extend to workers who have left the employ ment after having been exposed to carcinogenic agents forta sufficiently long time or who have been shifted to Clinical Notes, Suggestions and New Instruments ncarcinogenic operations. , A nationwide survey by skilled investigators should be made to determine the actual scope of the problem of industrial cancer. Representatives of management, industrial physicians, members of the Public Health ACUTE SYPHILITIC NEPHROSIS SUCCESSFULLY TREATED WITH PENICILLIN J. K. SARR JR. M.D.; H. N. COII. M.D.; J. R. DRIVIR, M.D.; ROSCOI D. LIAS. M.O.; MAX MIU.tR, M.O., Service and of departments of industrial hygiene and possibly also representatives of the workers should par ticipate in such a survey. L C. STRAUSS. M.D. CMotlanS 10. Precanccrous and cancerous industrial diseases should be made notifiable to the departments of indus trial hygiene of the various states. 11. Adequate compensation laws for occupational diseases should be passed for the protection of both management and workers against excessive awards or inadequate compensation. rcs|>ectively, for claims that result from the production of occupational cancers. 12. Government inspectors should examine all indus trial plants at regular intervals to determine whether or not they meet the essential safety requirements nec The nephrotic syndrome is defined as a clinical symptom complex characterized by profuse proteinuria, hypoalbumincmia and edema without serious renal insufficiency or hypertension. It may be seen in a variety of conditions and has been observed in connection with acute syphilis.*1 RETORT Of CASE History.--]. V., a white man aged 31, was first admitted to University Hospitals July 18. 1945 with a chief complaint of generalized edema and genital ulcerations of approximately one week's duration. In the early part of June 1945 several superficial lesions developed in the coronal sulcus of the penis. These gradually essary for minimum protection of the workers against the hazards of industrial cancer. 13. An institute for the study of industrial cancer should be founded and should be attached to or coordi nated with one of the existing large cancer research centers, in order to provide for pro|>er integration of the results obtained by such investigations with those produced by cancer research in general. Such an enlarged, with siihsetpicnt ulceratioa July 2 he was seen hy one of us (L. G. S.), who made the diagnosis of chancroid of the penis and started the patient on sulfathiazole two tablets four times daily. This was continued until July (i, when the result of the serologic test for syphilis drawn at the first interview was reported as strongly positive. On July 7 he was given 0.04 Gm. of oxophenarsine hydrochloride (Mapharsen) intravenously, with no immediate reaction. However, eight to twelve hours later he had a shaking chill and tempera organization would serve industry for consultative and investigative purposes on matters of occupational cancer.' 4. A committee contused of industrial physicians, .-ucer research workers, industrial physicists, chemists and engineers, compensation lawyers, members of the Public Health Service and of state departments of industrial hygiene, representatives of industrial manage ment and union officials should be created, whose mem bers should act as a body of consultants and s(wcial experts to the Institute for the Study of Occupational Cancer. Art and Anatomy.--Among the great artists who engaged in dissection were Michael Angelo, Raphael anti Albrecht Durcr. Greatest of all was Leonardo Da Vinci (1452-1519). This gifted and versatile artist, a man centuries ahead of his time in original ideas, who visualized aviation and modern metluxls of warfare and who discussed many problems of engineering which were later put into practice, also made discoveries in anatomy, such as tlie maxillary sinus and the moderator band of the heart. He was the first to demonstrate the ventricles of the brain by wax injections and to depict correctly the fetus anil its membranes within the uterus. Originally he set out to study the bones and muscles in their relation to art. but his interest grew, and he pursued his investigation of the deeiier parts, the viscera, the brain, the blood vessels and es|iecially the heart, lie intended to publish ture elevation to 104 F. Within twelve hours the patient was again symptom free. July 10 another injection of 0.02 Cm. of oxophenarsine hydrochloride was given imravenoudy, without ill effect. He returned on July 15 and at that time had mixlcratc edema of the face. legs, penis and scrotum and complained of general malaise, anorexia and luw hack pain. No urine exami nation was dune at this time. On July 17, when lie was seen again, the edema of the faec, legs, penis and serntum was more severe. The urinalysis revealed 4 plus proteinuria and an occasional red blood cell. On July 18 the edema was less severe and the urine contained only an occasional red blood cell, lie was then referred to University Hospitals for study. Physical Examination.--The tcm|>eraturc was 37 C. (98.6 I\), pulse rate 82. respiratory rate 18. blood pressure 124/72, weight 78.1 Kg. He was well developed and well nourished. He did not appear to lie in distress. There were no abnormalities of the skeletal system. The mucous membranes were of normal color with no abnormal lesions. There was slight facial edema, especially noticcahlc about the eyes. There *vas no apparent edema of the upper extremities. There was mixlcratc pitting edema of the sacrum, external genitalia, thighs and legs. The skin was normal in color and texture, with no abnormal lesions. There was a well defined, firm, freely movable nontender lymph node in the right inguinal region measuring 2 hy 2 cm. There were two smaller lymph nodes simitar in character in the left inguinal region. There was no other lymphadcnopathy. There was moderate periorbital edema. The conjunctivas were pale. The corneas ami scleras were normal. The pupils were equal and regular, measured 4 mm. and reacted normally a great work on anatomy in collaboration' with Marco Antonio della Torre of Pavia, but this project was abandoned owing to the death of his co-worker, ft is only within recent years that the value of Leonardo's contribution to anatomy has been fully annreciatcd. He made hundreds of sketches and manuscript s. many of which arc preserved in the Royal Library at .dsor and have only recently appeared in print. This a|>osllc ot naturalism in art must also lie regarded as a leading pioneer in anatomy.--Guthrie. Douglas: A History jf Medicine, I'luUilelphia, J. II. I.ippincoit Company, I'M,,. From the Department of Dermatology ami Srphilnlogy and ihe Depart- ment of Medicine of l*niveraijr Hospital* of Cleveland and Western Krwrve University School of Medicine. The work described in this paper wil done under a contract, recom mended by the committee on medical research, between the Office if Scientific Research and Development and the Western Reserve University. 1. Cole, It. N.: Acute Syphilis of Kidney, Am. J. Syph. 4: <6 (Jan. I I9J0. lUkcr, U. M., Jr.: The Relation of Syphilis to Nephritis, Mull. Johns Hopkins ( sp. I9J5. Herrmann, O., and Marr. W t limeal Syphilitic Nr|'hftpi(hifS, Am. J. Synh. 4 Neurol, tilt I, 19JJ. \|.4rr J >. : The M.-Irrn Treatment of Syphilis, ed. 2. Sprmghrld, III,,,.,,' k ll'ilftmore, fharles C Them**. 1941. Stokes. J. II.; Ileennan, llrmian, and Ingraham, S. K.. Jr.: M.dern Clinical Syphilolo^y, ed. S, IhtUdcIphu s* I..... hit. \S. II. Saunders Company. 1944. p. 11,7,