Document Y2ewX6Jk4jMm5dgomQJzMRDy

Qscagsnic T:csspoKse cf Sat Skin, Lungs, and Bones to a Vifiv? Chsonile1 f f Z" p. L. Viola, A. Digotti, snd A. Cnpuio 'Vf7 Retina EU-na Jmri.-jtc for Cr.ncer Research, Rome, Italy SUMMAltY Rais (Ar/IRE \Vis;3r strain) exposed for 12 months to vapors of vinyl chloride developed tumors of the skin, lungs, and bones. The cutaneous tumors, which always appeared in the area in which subrr.axillary and parotid elands ere located, have been histologically recognized as epidermoid carcinomas, nnojlumias, and mucoepidermoid carcinomas. Tim morphological characteristics of lung rumors, which occurred in a lower percentage, were mainly of the adenocarcinoma type, with the exception of a silicic epidfnrrofd tumor originating from the epithelial covering cells. In a minor r.uinoc: of ra.is, 2 large prokferzi.-.n of cartil-cmous tissue diagnosed as osteochondroma developed in the metacarpal and metatarsal regions of the four limbs. ;\tr.o *'i ucri0\ The oncogenic proper ties of some chemical organic compounds used for the preparation of "plastics" have been wiiTcIy investigated. ::nd their limits and effectiveness hive been wall .--'i.iidished. Detailed information on this subject may be found the literature (5, 6, b); however, all information and references are exclusively related to highly pc'yrreriacd compounds of roughly the same sir.e as used in various industries. Oncogenic polymers produce sarcomatous tumors, with the exemptin'! of polyuisilntis which, as reported by llucper (6), :;o a.ierner.rcir. .r;.'.;. f-.vvnd.y, i: has been demonstrated tliat sarcomatous tumors fi-4, 7) are rsvwi of the capsule :ha- cevars \ Tim:., c: .?/. ii-'-c oc-s. :vJ areas made of pooriy dtffereritinted fibroblasts 'eh were tirrv.iy atracned to tlie film up to the .'i.Oii:*nn of man.'.iar.t transformation. 1 i>ij t.'tvtitigr.tion demonstrates that ever, fi-e monomer vinyl chloride possesses oncogenic properties when used with an ar.pmpri,tie model different from the mode!? previously reported by several authors (`J-- 12). The carciftojetuc ttsponse * A preliminary rc.pcr! of the results reported here wai given si the Teruh lM.ruato;ul Cancel Coi.j/cs.-.. lloucon, Texas. Mjy 22--24, 1970. Received July 31, 1970; accepted January 12,1971. to vinyl chloride follows a singular pattern foi the different ' tissues and organs of the rat. j MATERIALS AND METHODS | '1 The experiments were performed with vinyl chloride I (CH:=CHCI, the niono<i.'11cgcnate derivative of euiyicne) of a : commercial grade (997* purity) assumed to centum I insignificant amounts of various noncarcinogemc ; contaminants. 1 Three-mcmh-old Wisfar f.Ar/IREl male alb'no rats fab out ! 150 g hctJy wsi.^u) were exposed to vinyl chloride vapors 4 hr a day, 5 days a week, for 12 months. The animals were > kept in metal or plastic, air-rich: eaves m which a constnr.i flow of air, ccntiir.ing }% v/v iTqual to 30.000 ppm) of \:ny*. ` chloride, was introduced. Twenty-five rats of the aame strain were the control group. At the end of the treatment, the t surviving animals were hilled at 20-day intervals, cue the must ; important tissues and organs were examined bistologicatly by standard methods. During the periodof exposure, the ar.irrsais : were slightiy soporific: however, r he fir;; few months ot treatment were well tolerated and no chaises in growth c-i ; behavior were noticed. After 10 months of trcatxvetu, corr.e animals began to show a hard mass in the paraauricular reghv! ; wliich became progressively larger until it reached the size of a 1 walnut or slightly larger. In most cases, the swelling was ' unilateral; it was bilateral in only a few animals. After I or 2 f months, the growing masses became ulcerated and discharged i necrotic debns, while a certain antcuru of tumorous 1 be*an to form on their surfaces. In addition, we observed that : the TOf-e< were or. ;n:e/.ra! part of the par-aur.ettiav :,-eic:\ ar.j could nut be distinguished from the local tissues. Casenus ; necrotic zones were iounu. l"cura ana peucaohun often : showed diffuse inflammation of a fibrous nature and, in many j eases, the* v were covered will; a number cwhite - formations as Lrge as plains of rice or even larger and harder ! than ihc lungs theuisel\es. In 2 cases, trie lur.?s wore ; hemorrhagic with milky, thick fluid in the pleural cavities. The : liver was sometimes 'ased in size and very fragile. The , animal:- were subjected to X-ray analyses at different intervals I from the !vr:nr.: ;g of ircarmcnt in order to ccrttrid :r,^ state of the skeletal lcr.:s. * All the animals that i.fltaled vinyl chloride showed ?. series * of parenchyma-' lesions. Among these, most prominent were i the disappearance of granular and Purkinje ceils, degeneration ilS CANCER RESEARCH VOL. 31 ; RSV 0012246 + * liz cerebellum, severe chronic hepa. tnicmjjjii] Warty suhauricular grow. occurred in some rats. The -rurr.onuf, nJ moderate swelling of the kidney pSjgnchyira, histological picture allowed papular epithelial proliferation, zfua assuming the pattern of tubuioaephrosis. with progressive increase in the thickness of the epidermis (FI* I). The papillary warts of exophytic type had a fibrous vascular stroma and various degrees of inflammatory lymphocytic The rates of survival and the main findings arc summarized - Table 1. Almost all the animals developed tumor* of the !;i.i and lungs. Very few animals developed bone tumors; in ..* cases, the tumors were localized in the metacarpal and -.statarsal bones of all 4 extremities. Skin tumors were by far fl:osf frequent, amounting to 65 or 70,". fkin Tumors. The tumor that developed inert frequently in vpiraauricular region was the epidermoid carcinoma, but we -rs> observed papillomas and rarely mucoepidermoid rjrciaonus. In aU cases, the nei>j'.MTt; weic of epithelial r.iture. Tjic 3 patterns noticed cannot be compared to various .. .totypes but rather to a transition of one type into the other k. and which is more likely, to different stapes of the same :>,-oii;crative type. infiltration, marked hyperkeratosis, parakeratosis, -`-r.thosis, and areas of individual dyskeratosis or pearl horny formations. The epithelial celis of the penetrating columns (Fig. 2) were irregularly arranged and were frequently accompanied by an inflammatory infiltration of the dermis. The typicai features of the Malpighian layer and of the stratum corneum of the prickle cells and of germinal layers were easily recognized (Fig. 3). The horny layer was composed largely of cell nests, whieh appeared at certain points within the epithelial masses and assumed the well-known appearance of "horny pearls'* (Fig. 3, arrows}', they were made of'flattencd and compressed prickle cells without nuclei and were located around a central core of keratin. , Tabic I OncOAfri'. effects ofhhclcd vinyl chloride as a function of time The animals were exposed to vinyl chRSrt'Jc vapors for 4 hr a aay, S days a week, for a touJ of 12 months, in s constant fidw of air containing 3 v/v vinyl chloride. Rat 1 2,3 4 5 6 7 8 14 16, 17 :i 22 23 24 25 26 Survival rate 300 280-300 310 333 337 347 347 354 359 350 380 380 380 380 380 Tumors Skin Lungs Dorics Mac..epidermoid carcinoma Epidermoid carcinoma. kera tinizing type Epidermoid carcinoma, kera tinizing type Papilloma, kcratoiic type Epidermoid carcinoma Epidermoid carcinoma Mucoepidermoid carcinoma Epidermoid carcinoma Epidermoid carcinoma Epideimoiu carcinoma EpidernioiJ carcinoma Epidermoid carcinoma Epidermoid carcinoma Epidermoid carcir.i' ... Epidermoid carcinoma Adcnoacar.U'omn No tumor Adenocarcinoma No tumor No tumor No tumor No tumor No tumor Adenocarcinoma No tumor Adenocarcinoma No tumor Mucus-producing adenocarcinoma (alveolar cell carcinoma?) No tumor Squamo... cell carcinoma Osicuchor.droma No tumor No tumor Osteochondroma Osteochondroma No tumor Osteochondroma No tumor No tumor No tumor Osteochondroma No tumor No tumor No tumor No tumor Y 1971 517 RSV 0012247 / L. Viola, A. BigOtii. and A. Capu * Kcratfnization was irregular and often parakeratosis was cartilaginous zones possessing regressive features, such as observed in the areas of the tumor in which the cells were fibrosis and hyalinosis. The perichondrium appeared often as a loosely aggregated and undergoing an individual rather than a collective type of keratinization (Pig. 4). !n dyskeratotic areas, a few epithelial cell; tended to form pearls. The tumor seldom showed an undifferentiated growth with cellular pleomorphism and several mitotic figures (Fig. 5). A few tumors showed little nests of isolated pale cells (Figs. 6 and 7) of 3 types: mucin-producing ceils (originating from the duct epithelium of sweat glands or salivary glands); squamous cells; and intermediate culls with minor tendencies towards differentiation. Respiratory Tract. These tumors, although occurring rarely, were mainly adcnocarcinomruous. Only in ! rat did wc observe an epidermoid tumor originating from the epithelium-covering celts. Sometimes, the tumors were seen in their early development and consisted predominantly of cubic or columnar cells arranged as regular or irregular tubular ?nd papillary elements (Hv. 8) mid supported by poorly developed fibrous stroma (Fig. V). In other cases, glandular structures were often imperfectly formed and appeared as sheet-like proliferations of undifferentiated or pleomorphic character. The cells showed a compressed and structurally altered fibrous tissue. In some cases, the tumor growth was rehted to the stage of the endochondral ossification occurring below the ^epiphysial plate.** Ossification was irregular, so that osseous trabeculavaried greatly in thickness and contours. In other cases, foci ot active cellular proliferation, cartilaginous areas, cnor.droid developmental nests, and calcified bones occurred in the deeper portions of the trabeculae (Fig. ! 8). The new formation appeared to be an osteochondroma and consisted essentially of a bony protuberance capped by cartilage and a fibrous layer, which represented the perichondrium. The fibrous layer was continuous with the periosteum of the adjacent cortical bone and extended inward to form septa separating and enclosing lobules of cartilage. Control Animals. The control rats were kept under the same conditions as the experimental rats and at the appropriate time were subjected to a constant flow of air without vinyl chloride. None of these animals developed tumors or the types of parenchymal lesions developed by the rats that inhaled vinyl chloride. In a very few of the control rats, there was a tendency to extend into the pulmonary parenchyma, thus swelling of the liver and kidneys. simulating the microscopic features of the so-called alveolar cell carcinoma (Fig. 10). Sometimes, this was the prevailing pattern. The pulmonary ai: sacs were limited by l or more DISCUSSION layers of cubic, columnar, or polyhedral ceils with abundant cytoplasm that was faintly eosinophilic (Fir'.. 1 ), frequently, As in m3tiy carcinogenesis studies in which multiple turner; adenopapillnry excrescences spreading into the alveolar spaces arise in different tissues and organs, the data must be evaluated were present. *** in terms of 2 more prompt positive response to be obtained In some areas, foci of cellular polymorphism with with the ideal concentration of the carcinogenic compound. hypercliromatic nuclei were noticed; mucin was produced in The cutaneous system is the most susceptible to the oncogen:; varying amounts and secreted into the lumen of the tubules effects of vinyl chloride. and acini. There were small poois of mucin in which signet ring Our experimental data do not explain why' the cutaneous cells occurred, either alone or in small clusters (Fig. J2). The tumors developed in the same site, /.<?., the region inciudir.: alveolar walls were often quite thick and, at times, showed an the area in which the submaxillary and parotid gia.nds are inflammatory infiltration. located. It is possible that the salivary glands may by involved As mentioned before, a single tumor showed squamous in the concentration or excretion of vinyl chloride or some 0: structures and appeared to have been formed mainly by its active decomposition products. This hypothesis is strong!)' spindle and oval undifferentiated cells (h'ij. 1 2). supported by morphological findings showing the spcctfi* Bones. In the metacarpal and metatarsal regions of the 4 tendency of the developed tumor to appear as a limns, a large proliferation of o.rtilacaicus v.tmvs arose mucoepidermoid carcinoma, which indicates the icm-' outward from rhe periosteum and, l'ruro the nppearar.ee of its conuihuiion of the mucus glandular ceils to the tumorous cells, seamed to derive Cirecr'y from the corner;! bone (Fig. growth Such kinds of Imtotypcs are often related to s-tv.5 14) . The periosteum also grew and in some areas spread as glandular aggregates, and. therefore, the histogenesis o: huma* fingcr-like prolongations into rhe newly formed cartilage (Fig. mucoeptdeTmoid carcinoma has been restricted to the cells ot 15) . In these places, a gradual transition between fibrous intercalated ducts. " hypothetical interpreiion must z- cartilage, periosteum, and bone could be noticed. confirmed by future ^..periments in which the action of tr.< The newly formed cartilage appeared irregular with atypical vinyl chloride should be restrict;, to the salivary system. A areas; the cells, which had nuclei larger than the normal the concentrations used, saturation and wetting! of the tV chondrocytes, lay in well-formed, capsulated lacunae. The cells might well be expected. Under these circumstances. th< occurred singly, in pairs, or in tetrads and. although of nature! c.uiiing habit of iho rat might acd a sicui.'ic.u. different size and shape, they usually contained a single, ingestion problem wit., subsequent concentration 0; viuy darkly stained nucleus. The cartilaginous growth w..: not chloride in the salivary glands. The local cxircm homogeneous, as shown by the extension of the firyr-like concentration could * . the result of the difficulty of 1 piolongations into the boundaty of newly for::;... tissue. complete cleansing by the rat. Besides the chondroblastic, chondrocyttc, and angiomatous The neoplastic response of the lower respiratory trad areas which indicated a rapid growth, there were also although of lesser magnitude, is of rchvant interest, since sew 518 CANCER RESEARCH VOL. 3 RSV 0012248 6*r??T00 6!? 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"3 `oanmomtN *596i YCt-SK -7 MOpsrN 'fujiirpcK '{fanJtMJ uamXjoj :';aqiuXs Xq painty sstauaBouioicqu (tiu.MUfjadY^ y `ucdojf *9 0i6l `C6i-f84 :tp `uruj wjtq *nN *f *xas put 'uicus OfnojV *ad.<. cv 01 sdtqsuetic;a>j '.cncidoauaij X|JC3 Susinp satuai>^i;tQ Ic?5oioqjcdofi|f jo uoucuiuuai?Q |tuod stfouaduouinx utuXsoj 'o *puwg put **| `pw- -4-j `usong `uoiuiiof 'L '**961 'iCOI-SOOl Xf **wuj jaaue^ ijcn f taieu auoci^tX^o.^ put ut>nain.<)oj Xq vraianpui laouo *5 m^\ `iadsnu *$ *1561 *v`6C-se .7 -t|ao.|-iaiji--iautJV *Su!ii\ uauaJutRoico zap SRuain^tV taiw*. adaeaip tiatuauiMactx^ *ti *? ct*: *6i9-199 :6f Jaotre^ `jjcn [ *Xautu2nt59/X 3inp spS Ufii|itiirc|dsueix P* icusosoiuono uio:r sjaaciv incn^ssj aatuXioj (uo;i stsaurdoutris^) 1 [ `putju put *'7 *'3 T1'"-'5 `L961 '.V"St9 U1 "PW Td'** ^ :<5t* trsauodijotanx ic*uX|ox suunp *j;a^ 9u:p:A!p*uoA* at uont;s:t put uoitcuaoj^ucix iuc2ij*i^ ] `pn put **3 `uaong "0 'put-" " S96s 4;5If-5I[ -SZf "pfJV `IOn T^2 *"? aoij 'uotiiqniui icuojj i{ha\ jopio Xjsjouj ui sauoo |d|?!n< :*Ktua2iJOiunx jauiXioj -3 'uaony pus "O `."^"-2 gU*. `E95-J55 :OZ *wau*j -f TiJt] `seuioares Xrtuitij pa?npuj-sS;sj anvrjx ui Xpiofdojaian ja aauajtAajj -jj laity put "lt *- ( t s<jnn; f V-r. |A5| aqj ib uappu? snoaorijmuis'jiaip joi poo sjcxumr^ atji ;o irtouoSoqjcd aqi joj paimtiai sr uoiieiojdJdiOr l07^-'- v AfsnotAqo *woui o?uo lucAOtat sq 01 um$ *'**!!' " uotjisoduiopnn ssi jo apiJOjip SoiujtioJ J *<i2w5:**' Xctu ttpp f ipoid-snoniu injj j:7au;oi<t aqj **' Pomt OunCaiM Nippon Shohi Keizai Shinbun (Nippon Consumer Economy Press) - Jan. 26, 1976 i 1. iv Seminar on Safety of Food Containers to be held by Association of Housewives on 28th The Association of Housewives (Shuhuren) which has been boycotting polyvinylchloride food containers plans to take up the problem of food containers as a subject of this year's 19th annual Consumer's Seminar and look into the safeties of plastic food containers J not limited to those of polyvinylchloride. i This Seminar is held in late January every year by the delegates representing various branching organizations that exist in the country and it carries out a thorough research and discussion on a subject that is most important in that year. In the past the subject i of the Seminar not only became the main theme of the Shuhuren's movement for the year but also put important influences on the movements of other organizations. In this year's Seminar which will be held on 28th between 10:30 and 3:30 p.m. the theme will be focused on the problems of safety, label specification and disposal treatment of the plastic containers . 4? . * - I upon which the concern has rapidly built up in connection with the carcinogenicity of vinylchloride monomer. Representatives from the related government offices such as I Department of Health, Department of Industry and Commerce and Department of Agriculture will attend the Seminar. From the industry side the Polyvinylchloride Association and Polyolefin Association will attend. Also including the experts, they will pursue a comprehensive investigation of the problem of food containers. RSV 0012250 Nippon Consumer Economy Press - 1/26/76 Shuhuren has been boycotting foods in polyvinylchloride containers since last year on the ground that they have a risk of containing the monomer which is regarded as carcinogenic. The organization has decided to hold this special seminar in order to investigate whether the containers made of other materials than polyvinylchloride, such as polyethylene and polystyrne, are actually safe or not. Some of the people have the opinion that not only polyvinylchloride but also other poly-type containers contain toxic materials. Thus the opinion has begun to emerge that a direction has to be taken in the future toward the ban of all the plastic food containers. In view of this it is noteworthy that Shuhuren has started a serious study of the safety problem of the plastic containers. It seems that the safety problem of the plastics is going to be a major topic of the consumer's movements this year. RSV 0012251 Vol. 295 No. 4 CORRESPONDENCE^ 233 lienii with normal cycles. We do suspect that their hypcrandrogenism arises from the ovaries (even with normal menstrual cycles), since wc do not find high androgen gradients in their adrenal veins, we do find androgen gradients in their ovaries and we cannot ac count for the testosterone coming from prehormone metabolism. I agree with Dr. Rosenfield that it would be very helpful if we could catheteriae these women before and after dexamethasone; however, "horse sense" prevents us from doing multiple catheter, izations. Newark, NJ Marvin A. Kirsch.ser, M.D. Newark Beth Israel Medical Center 1. Bardin CW, Hembree WC, Upset! MB: Suppression of testosterone and androstenedione production rates with deximethuone in women with idiopathic hirsutism and polycystic ovaries. J Clin Endocrinol Metab 28:1300, 1968 2. Kirschner MA. Zucket IR, 3espersen D: Idiopathic hirsutism: an ovari an abnormality. N Engl 1 Med 294:637-640, 1976 3. Huq MS. rfaff M. Jesperscn D. et al: Concurrence of aldosterone, androgen, and cortisol secretion in adrenal venous effluents. 3 Clin En docrinol Metab 42:230. 1976 4. Rosenfield RL. Ehrlich EN. Cleary ER: Adrenal and ovarian contribu tions to the elevated free plasma androgen levels in hirsute women. J Gin Endocrinol Metab 34:92, 1972 INDUSTRIAL EXPOSURE TO VINYL CHLORIDE To the Editor: The recent article by VVegman et al. entitled "Vinyl Chloride: Can the worker be protected?" (N Engl J Med 294:653, 1976) clearly describes one of the most serious health hazards faced by American workers today. Indeed, the incidence qf occupational diseases has been rising, and the passage ot the Occupational 'Health and Safety Act ot 1970 has done little to thwart the trend. Today, five years after the Act, there arc only about 2000 safety in spectors to inspect four million workplaces.1 At the current rate of inspection, it would take 230 years to visit each plant once! Moreover, protective clothing, masks and adequate safety educa tion are rarely provided; when they are. they are often severely inadequate or interfere enough with work as to create new dangers. Fines levied for violations of safety standards arc such that it is often much cheaper for a company to pay the fine than attempt tocorrect the violation. The example given by Boden of compensation costs for workers dead of poiyvinyi-chloride-associated disease amount ing to a mere fraction of profits vividly illustrates the problem.* Another particularly disturbing fact that readers of the Journal must realize all too well is that training for physicians in occupa tional diseases is virtually nonexistent in medical-school curricula. Though in no way solving the problems of occupational diseases, efforts by physicians and students to obtain training in diagnosis of such problems, and support of workers' efforts to have legal protec tions enforced by the Occupational Safety and Health Administra tion will help to improve the health of millions of American people. Boston, MA DAVto C. Christian! Tufts University School of Medicine 1. Fans and Analysis'. Occupational health and safety. Industrial Union Department of the AFL-CIO. December. 1974 2. Wegman DH. Peters 3M, Jaeger RF. et at: Vinyl chloride: can the worker be protected? N Engl J Med 294:6)3-637, 1976 MANAGEMENT OF HEMOPHILIA WITH ATRIAL CATHETER To the Editor; The letter from Flessa et al. (N Engl J Med 294:1240. 1976) describes the use of the Cimino arteriovenous fis tula as a method of circulatory access for the chronic self-adminis tration of clotting factors to patients with hemophilia. In the event that the vasculature becomes so damaged that it becomes impossi ble to construct an arteriovenous fistula, the all-silicone rubber right atrial catheter,1 which wc use for self-administered home par enteral nutrition,* will serve very well as a safe, semipermanent route of injection of these clotting factors into the bloodstream. Seattle, WA BtLDiHG H. Scribner. M.D University of Washington 1. Broviae JW, Cole JJ. Scribner BH: A silicone rubber atrial catheter for prolonged parenteral alimentation. Surg Gynecol Obstel 136:602-606. 1973 2. Broviae JW, Scribner BH: Prolonged parenteral nutrition in the home. Surg Gynecol Obstet 139:24-28, 1974 "JOGGERS' TOXICOSIS" To the Editor: The recognition of thyrotoxicosis is usually not dif ficult when many features of the hypermetaboiic state are present. The tachycardia and other hemodynamic changes are the most common and frequently stressed clinical manifestations of the thy rotoxic patient. In fact, hyperthyroidism is often not apparent, es pecially in elderly persons, except for tachyarrhythmias and con gestive heart failure.' Cardiovascular changes may be less marked, however, in young, physically active persons, and if relied upon too strongly, could prevent proper diagnosis, particularly in those who jog for physical fitness. A 37-year-otd physician, accustomed to jogging a total of 60 km per week for several years, was seen by his own physician because of weight loss, heat intolerance, fatigue, muscle weakness and loose stools. On examination he had no lid lag or stare, and no tremor or thyrotoxic skin changes, and his thyroid gland was barely palpable. The heart rate was 80 per minute and was assumed to be "normal" even though he reported that his usual resting pulse was 48 to 52 per minute. After a gastrointestinal work-up, a second physician, impressed with the "relative" tachycardia, ordered a determination of thyroxine level which was 17.4 ug per 100 ml. An additional his tory obtained by still a third physician suggested a viral prodrome with some initial thyroid tenderness, and further studies confirmed a diagnosis of subacute thyroiditis: a sedimentation race of 38 mm per hour; and 24-hour uptake of radioactive iodine (```l) of < l per cent. The patient recovered after several months with a return in his resting pulse to 56 per minute, thyroxine level of?.4 ng per 100 mi and a 24-hour uptake of radioactive iodine of 44 per cent. Although the eventual diagnosis in this patient was subacute thyroiditis, the presenting thyrotoxic features were noi immediately recognized in the absence of tachycardia although the heart rate was in fact "relatively'' rapid for this jogger. Because athletes and physical-fitness enthusiasts often have slow heart rates at rest.* and unlike this physician, may be unaware of their actual resting pulse, and thus unable to provide this useful information, the absence of tachycardia may be used as evidence against the diagnosis of thy rotoxicosis, as initially occurred in the case. Physicians should be aware of their patients' exercise habits so as not to miss a case of what might be called "joggers' loxicosis." Cambridge, MA Daniel L. Arons, M.D. Mount Auburn Hospital 1. Davis PJ. Davis FB: Hyperthyroidism in patients over the age of 60 years. Medicine (Baltimore) 33:161-181, 1974 2. Frick MH; Coronary implications of hemodynamic changes caused by physical training. Am J Cardiol 22:107-116, 196S MULTIPHASIC SCREENING To the Editor: The issue of April 22 provides a rare insight into a common medical problem that deserves comment: data collection uncoupled from predefined actions. Olsen et al. --."A Controlled Trial of Muttiphasic Screening" (N Engl J Med 294:925-930, 1976) -- speak of a "collusion of indif ference between patient and physician" in interpreting the lack of effect of screening on health attitudes or status. Their analysts un fortunately precludes identification of obesity or dental canes be cause the authors view height/weight ratio and dental survey as of "questionable value or not easily related to any specific medical problem" even though these two problems are among the most KSV 0012252 *//. - 41 rf/u At./ /' .gaoglc'bio and : vere locally .itial testicular `aior.a or the .ivcr, kidney end or 22 days showed Jfla. There vas doses of 500 or but 50-200 vl/ke/ nlues from vk 5. otes of dogs ;f Jected exceeded the lethal dose. Ylth the exception of EF and IMP, which i appeared to increase growth rate, the compounds tested retarded growth. 1* Eaesatological examination revealed an Increase In leucocytes but no ; effects os erythrocytes, haemoglobin ar haeaatoerlt were observed. The 1 level of calduu in the blood vas increased, sodiua and potassium vere eventually decreased, and analysis of serun proteins revealed in aost cases a decrease in the 7--globulin fraction. Levels of calcium, sodium and potassium In the wine vere decreased. Microscopic examination revealed so lesions In any of the organs examined. In vlev of these results the authors suggested that soma caution should he exercised in the use of foroamlde and its -*lJgrl derivatives as solvents for pharmacologically active materials. s, rats or is and a dcoeon ia rats given I7SS M). Etude 'Us et H. Ethyles. .rial solvents, r/ of the dimethyl . Bull. '9&*, ^ its N-alkyl e have invertig*aide (EF}, jf,*as veil as of repeated Intra- time of 2d hr {? g/ig for iiidings in alee ztramidc appears .-'ris.se paralle_'-ng radical. Of the tfcyj derivative ,,e vas the case delayed effects In mice, the to 6 days with `c-leaco vas sr.. However, with fom^aide svcrsible 1 rats and nice dosec of these changes vere tai amount in- ? 1 \ j t I | ! i i 1 1 2335. TTiVATO TO RATS IBM TDTfL CHLQwrna swrvpras Viola, P.L., Btgotti, 1. A Caputo, 1. (1971). Oncogenic response of rat skin, lungs, and hones to vinyl chloride. Cancer Res. 31. 516* Vinyl chloride monooer does not seem to have been associated in the past with any indication of carcinogenic potential. The inhalation study reported here, however, suggests that this monomer has sene tumourindneing capacity in rats. Bats vere exposed to 30,000 ppm vinyl chloride vapour for 4 hr daily for 5 days/vk for 12 months. After 10 months, sose rats had a bard epi dermal mars in the over the para-auricular region and this gradually enlarged and broke down after a further 1-2 months to an ulcer, which discharged necrotic debris and formed tumour tissue on its surface. Tumours developed in nearly all the treated rato, usually unilaterally although they occurred bilaterally is a few animals. Many of the rats also developed a fibrous inflammation of the pleura and pericardium, and their lungs became covered with hard white adenocarcinomavous nodules. In a few rats a proliferation of cartilaginous tissue (osteochondroma) developed in the metacarpal and metatarsal regions of the limbs. Certain other lesions vere found in the treated animals, notably a disappearance of granular and Purkinje cello, degeneration of the cerebellum, severe chronic hepatitis and interstitial pneumonia. Swelling of the li7er and kidneys vas seen in a few of the control rats as well no in some of the treated animals, but otherwise the control rats vere free of the tumours arid ledicne reported in the rats exposed to vinyl chloride. authors suggest that, in view of the concentration of aV"<n car cinomas pr|d papillomas over the region of the sibmamillary and parotid glands, it ie possible that the ealivaxy glands of the rut concentrate or excrete vinyl chloride or its active metabolites. NATURAL PRODUCTS 2336. THE GREEN POTATO TOXIK Rishie, K., Oumhmann, K.B. & Keyl, A.C. (1971) - Iharaaeology of solanine. Toxic, appl. Pharaac. 19. fll. RSV 0012253