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11 PU.NT^n 11 EXHIBIT 1 U ft5 -2311 NCLA-N'D JOUJ^A^O^lLUlUIMi 5 ^ r-s/ M. 18, j>_. , 272 No. 11 \M M 1 ykorroR ,,7 ASBESTOSIS AND MALIGNANT DISEASE -rept In assessing present knowledge is described * Chile -a Journal or ! C-2 a$ VL 1 of Jouxxac on Fvol;cat:ons SoCJtTY P. MfCon.bt M.D. S. Jtrllftjs, M.D. V4v` * J. D* Croat, M^- Clinician and pathologist must add a new mimade etiology when a chest tumor presents {.. for diagnosis. Dating from 1938.* evidence has L-, i ; j t Watner* as follows: an asbestos worker may die ,0r pulmonale due to pulmonary insufficiency con;,-nt on the pulmonary fibrosis of asbestosis. If he this hazard he may die of bronchogenic can accumulating that there is a significant increase - * mused by asbestos. Finally, with no evidence of bronchogenic carcinoma in workers suffering Ut ashestosis. Between 1960, when VVagner et al.s d* . mented 33 cases of pleural mesothelioma associavwith asbestos exposure from one geographic area South Africa, and the report of Selikoff, Chur? a,-. Hammond in the current issue of the Journal, i~ pressive data have been collected on this subjrn j ; I ! j . . .tosis. a worker or a person with a seemingly level of exposure or an exposure remote in time, h as those described by Slccgs, Marchand and ...t.-ncr'* earlier and by Selikoff and his associates . where in this issue of the Journal may die of :ral or peritoneal mesothelioma, Wagner* has shown that this disease can be pro- These reports reveal a demonstrable rise in cases : . -.d in animals, an important aid to further study. carcinoma of the June in workers exposed to asbev.-* the search for a chemical carcinogen as cause for but not giving evidence of asbestosis. The preser* reported mesotheliomas due to asbestos. Haring- and earlier papers of Selikoff. Churg and Hammond * 1 -`s discovery of polycyclic aromatic hydrocarbons' . r.:k. M.D.-, L. C.'vsnnn./ji.S. 4iUn. M.D together with reports presented at an October, 19V- > a number of different asbestos materials in immeeting on the biologic effects of asbestos, suppor j .riant.1-9 Observations by Wagoner et al.'* that iron "to M.D. the conclusion that certain exposures to asbestos v.--;; miners', underground metal miners, foundry work cause pleura! and peritoneal mesotheliomas and jy-- sibly gastrointestinal cancer. s' < and metal workers have an excessive mortality -.:e from lung cancer may also be of significance >we*r M.D. There is much work to be done to discover whs* -.v*e iron is present in most geographic areas where 7 _L: biblicsrashy, exposures precisely are responsible. It is importan: for the physician, not trained as a geologist^to kno*.* that to date most of the exposures causing me.vw -:tmos is found. In the lung asbestos bodies and .-'cstos fibers are easily detected by means of stains 1th an affinity for iron. It is tempting to speculate r ::*.:;:rc .11 criei* theliomas have been from crocidolite, one form <>: these findings may eventually be connected by y i:yie o/ \ asbestos. Data in the present article confirm- the far: v titl; et a vms-j and \hat exposures to a mixture of materials, one of whir: nropriate evidence scientifically collected. The morbidity and mortality of asbestos exposures * "'fcrr in which * tPthe ..ill tuuiiiy be section of the is'dnrysoHte^inother form of asbestos chiefly used i.\ j .plied by the work of Selikoff and Wagner and their the United States, are correlated with an increase it. Ileagues are a matter of grave concern. The as- the incidence of mesothelioma. Amostte. the third -uos-using industry is very large, and its activities the pertinent vTrirtms ciosciy n;u;e is rarely commercially used form of asbestos, has yet to be in* criminated, but there are no definite studies to da:r despread. Certain industrial operations using asc.uos can be made safe by engineering control. In ; esse report or to confirm or deny such a connection. It cannot K :her operations this may be so difficult that substitu- .hiication as a too strongly emphasized that careful work historic* . dcuble*spced of patients suffering from asbestosis or asbestosis and ' of a safer material must be considered. The recent report will stimulate clinicians and patholo- .>:.nps done in Jaheied. :trel ef Meer- crKitJ f-r cor- carcinoma of the lung, pleura, peritoneum and gastrr* 'ts to study cases of pulmonary fibrosis, broncho- intestinal tract, be recorded. Exposures to more than j '-rue carcinoma and mesothelioma of presently un- one dust, significant inhalation of chemicals or v*wn cause looking for significant asbestos exposure vc r'?v.r::>ui?d mzr.e! d<*ej no: and cigarette smoking habits must be tabulated. Sue: j information is needed to discover whether or not or.t die patient's work history. by any cor- form of asbestos is the sole carcinogen or whether the References h.'gJd be re dust may be acting with some other agent as a co* - "rcks before carcinogen, as several authors have suggested.' tndumint Meiitrine and H*ti**r- Vol. 3. Ed'itrd . ft. A. j Mfrt-MKrr. 6i* pp. LomJaa: Bunerfth. J9iw. Pp. 21C-7IS. advertising parent qualitv Discovery of a greatly thickened pleura or pul I J, C.. Sl<w. C. A.. P. pleural monary fibrosis a; biopsy or autopsy support? trv ] ' >het>iheliaRia snt in Xnh Weatcrf) Cape <*,<*(. Bnl. J. furil. M'<i. 17:200-271. 1900. its yrrsen'(tlyrtj nm<: ITfsai nar.f-s, 3.id the recu be lacteal. diagnosis of asbestosis. A diagnostic aid in cases /'- ; I ' Sf!ikrt/T. J. J.. Cliure, J.. aHa^tmpne. H. . C. .Aabeitoa * Pteure a*d aeeplaau. f.AJJ.A. l*:22-2a. iSSe. pleural mesothelioma is supplied by the observa'-lo* , 4 Har;n$tsn, J. S . Wjpur, J. C.. and Ssith. M. D?ci>an o< of Harington ct aL4 that there is an increase ; | IwaiurenK acid in pleural fluids et eaiey with di.*:uM pleural Dtm.'iiiiomu. Snr. J. &tp<r. ftlk. C4*.Sl-tS. 1S3. hyaluronic acid in the pleural fluid. . j' J. C. PcrMnaJ cemviunkacnm. .* .ntrndre s A point of confusion in the current literature , 5>rpw, C. A.. KUcchand. P.. and Warner. J. C. Dinux plrural | mneihriiama <fl South Africa. SuafA Airtrcn ./. /. 3S:2*?4. -ire does nc: . tc- -> nr- Lj'e.iern ' *U. 2 tn >V Cower- /-ir-4. r; * CO the significance of finding asbestos either as fibers o' I > ir. die so-called asbestos body in a diseased lung. Tm \ <cnr. J. C. *rrnmcnul producticn e( ri p<>ura Sr imnlanuiian dwu ia ladoraiary animaia. Stturt annHen) US: 160-131. IPO. . best judgment while further investigation is in pro: 1 Il^nncten. j. S.. and Smith. M. Sud n et h^drecarann* on I nunerai duaia. Artk. anr. Httilk l?vi. ress is that such findings arc reflections of exposwf i ' Hattopnn. j. S. Ocnrrrncc ti eil caraintns not of disease. It is reasonably clear that a series o' . l rrUwd Hihuirn in aahcMM. Skiutt ;Landn) D3.43.4j. IP'jl intense exposures or exposure of some duration c.u , ' he related to the production of asbestosis. A usefu- | iiiuMr, J. K., Miller. R. W*., Lundin. f. ., Jr., rraumeni J. I., and Ilaii. M. . Unuiual ifr eienafiw a.non{ c.-aun t underground metal aioan. New *f. J. .Uri. 2tJ;264-.ii, 19S3. C 3 C t a * C w y s; fi c: te li hi F: sr: A ei ri' re T: J its fic sht CO' att unof "as hr asp sat tuh by cot cnl afu sue dia C exp in i dec: ton of j cut befc *t t,, 1080 THE NEW ENCLAND JOURNAL OF MEDICINE T> lV May 20, 15': 272 and successful delivery at thirtv.jcven wrefct. However, this seriously compromised oaidiac patient should not have been discharged on the fourth post-partum day since sud den puerperal deaths from heart disease are not uncom mon and the burdens of early motherhood at home are notoriously heavy. On the other hand, since .she - subse quent admission occurred fully (our weeks later, one can not honestly say that this influenced the ultimate outcome though more rigorous management (and co-operation; might have warded on the evil day a little longer. The post-mortem findings suggest irreversible coronary and myocardial changes that would probably have progressed regardless of management John Ficcis Jlwztt, M.D. Chairman DEATHS BtNNtrr -- Hamlin P. Bennett. M.D.. of Swampscott died on April 26. He was in his eighty-fourth year. I Dr. Bennett received his degree from Dartmouth Medica School in 1906. He was a member of the American Mcdi ca] Association and a fifty-year member of the MassaehuJ setts Medical Society. He is survived by his widow and a sister. Liavjtt -- Henry E. Leavitt, M.D., of Stonehare, died April 27. He was in nii sixtieth year. Dr. Leavitt received his degree from Middlesex University School of Medicine in 1938. He was school physiciap fort Stonenam and was a member of the American Medical^Asso ciation. He is survived by his widow, a daughter, three brothers, three sisters and bis mother. . Morrin -- Harry J. Morrin. M.D., of Ro.xbury, died on April 22. He was in his sixty-third year. Dr. Morrin received his degree from Middlesex University School of Medicine in 193-i. He was a member of the Ameri can Medical Association and a former councilor of the Mas sachusetts Medical Society. He is survived by his widow and a daughter. Zjolkowskj --- Henry J. ZlolkowskL M.D., of Chicopee, died on April 17. He was in his fifty-second year. Dr. Ztolkowski received his medical decree from Middlesex University School of Medieine in 1942. He was a staff mem ber of the Health Department's Wei] Baby Clinic, school-physiciar. in both public and parochial schools and formerly city physician of Chicopee. He was a member e/ the American Mentcal Association and the Association of Military Surgeons of the United States and was president of the Chicopee Medical Association. Dr. Ziulkowski is survived by his widow, four sons, three daughters, a brother and his mother. CORRESPONDENCE Letters to the Editor are welcomed and will be published, if /ound~u:rable. as space permits, l.ike other material sub mitted for publication, they should be typewritten double spaced, should be of reasonable length (not over l/a pages) and will be subject to the usual editing. ST. GEORGE'S MISSION HOSPITAL To the Editor: This institution, as its title indicates, is a mission hospital working in a rural area. It is doing great sendee to the poor and needy in this place and suburbs. It also carries on evangelical work through the hospital evangelist. He regularly distributes tracts, booklets, oiele portions, bibles. pictorial folders and so forth. But on die whole we art handicapped very much for lack of equipment We need an x-ray generator for our chest clinic, surgical instruments, medical appliances, aa electro- rardiocraph. physimherapv apparatus, medical books a: journals. Briefly used articles are quite enough for purpose. We also require a tape recorder and lCmm. sound pru>. ior for our mass educational program. A few friends 1:". America base helped us all alone. We are indeed gra:'. to them. But it is with great confidence that we^ wish to proath our friends and sympathizers in the United Sv~. for the required help. The most urgent and immediate a*-. Is an x-ray generator. _ Valuable donations and useful equipment relating to p- needs mentioned above may be forwarded to Mr. Raym.-.-. Knighton. Executive Director, Christian Medical Soeien 1122 Westgate, Oak Park, Illinois * T. K. Tmom< _ Dirret:- ' . St. George's Mission Hoiphi r, Kerala State, S. India >> s*i >n .-j i tVtl* CHRYSOTILE, NOT CHRYSOLITE To the Editor: The editorial, "Asbestosis and Maliena- Discase," in the March 18 issue of the Journal makes rr: ence to a preceding article by Selikoff et ai., '`Reis:-.- between Exposure to Asbestos and Mesothelioma/* in it- same issue. The editorial states. "Data in the present art: confirm the fact that exposures to a mixture of materials. of which is chrysolite, another form of asbestos chiefly m in the United States, are correlated with an increase in - incidence of mesothelioma.'' I assume that the t and ih- were inadvertently interchanged so that chrysotiie_ appear as chrysolite. Chrysolite {synonym, olivine or peridot) is ; green magnesium iron silicate /ten found in small grx*- or granular masses and certainly not considered asbeit In contrast chrysorile, a ftm of serpentine, is the best ktw- source of asbestos HrRMA.v L. Pxtsrrr Captain, MC, U5.\i Medical-Sen*-- Ch*arTxT_NI. Bocx, Px n . Comultant CteU-i 6310th United States Air Force Hos;~ Edwards .Air Force Base, California USE OF VITAMIN E IN CHRONIC CYSTIC MASTITIS To the Editor: Chronic cystic mastitis is the most C;moo benign lesion of ths female breast and is palpable s- microscopically present in approximately 30 per cent of ; women during the reproductive cycle. The oecurrer.tr M cancer in these patients is about fourfold the freqt** noted in those free of the disease. Pain, tenderness heaviness of the breasts frequently occur before menstt-i lion in such patients. In some cases spontaneous regrrs-have !>een noted to occur; however, most patients haic't- responoed well to medical treatment ' Vitamin E, which has been used unsuccessfully in the ri for numerous disturbances, appears to have a distinct (' is this condition. Although the nuaflwr of patients served to date is small the results in most have been nn*. Twenty patients twenty-two to fifty-five years of age r* nar ' i of r ar: vr: * o: :cd sc: * in: *r?d :: -n ing had 0 to 5 pregnancies were studied. All had ma.' premenstrual symptom*. In 16 moderate to complete '' J- of symptoms was obtained, and 13 patients had a pah'* softening of the breasts, with reduction in the size cysts to complete absence during treatment. Therapy : t listed of 1 or 2 200-mg. capsules of vitamin E daily *' ' period of three successive months. One patient with a;> cystic changes for years associated with intense disr*r-- "i v '5 *1 had complete subjective and clinical relief under tres*-K_ !t i Within one month after discontinuation of therapy the were again palpable, but she remained symptom free. Physiologically, estrogenic compounds cause in growth of the mammary ducts, with progesterone '' *' ing the growth of alveolar tissue developed under the - "u! 5 ence of estrogen. Estradiol is the most potent and bri to be the pnmarv estrogenic hormone. 1: is largeb verted in the body through oxidation to estrone pfjr * and to esuioL