Document pXKOGJXoyNNQaxn8Z9DRjbo7

A1 I -J i PLAINTIFF'S | EXHIBIT I GF-796 NovuKhts 22. 1909 Mr. D.U. I'illa Circulation : D VH/RA.//KCL^ THE MEDICAL JOURNAL Oi' AUSTRALIA (_ < l"6= Division or Tusssculdc* (19C*). .Minimi Rr*ort. Y**ap ftnUinx jun# jo. 1945. Covon^moni Printer. QoMMlnr.J. Dov k P J. nf'02), -Reactions to ARtMuwrculoM Drug*". T-iOcrclc iSdlmb.). Suppl. 43: 75. Fuxokro. S M. iif*50>. *'Dru Alli-ruy -- Somp Clinics! and Iminunol>(:lcal J. .litem;/, lot Fraxci*. n. S.. and C,vrr.\. 8. K. (ltr.>), -Rio V* of Cortlco. ironhln in Rapid Desensitise tin to P.A.a. , Tubercle (f./aib.), SO: 23f. Govinbauaj. nr.. end C*axt. X,. J. "Th Incidence of Drug Hypersensitivity In the Chcr.uaherapy of Tuberculosis . Brit. gr. C7iri lit*.. <S: 2T. HixtKAW. W. C.. and Gablano. L. H. MCI). **X*H. Dl*nB* of ihr Cheat**. Sounder*. Fl\a.vlcl|ih<n. HoG.ve. X. \\\ 115*SC>. "Prednisolone in Treatment of Pulmonarj' Tuberculosis**. Brit. mat. 3: Hoknc, X. TPh ami OIUXT. I. XV. B. -Development of Drue Resistance to Isonlasld durln* DeaeneiUsRtion", Tttbcrclc lEiltnb.). 44: ISO. Hovortox. L. E. (10541. -Combine*! Cortleotrophln Therapy and Chemotherapy in Pulmonary Tuberculosis . Ssweet, 1: SOS. Jokxiox. J. R,, Taylor, B. C.. Mor.r.irrcT. J. F.. JWHt. J. W.. and McDonald. F. M. (1933). -Corticosteroids in Pulmonary Tuberculosis**. Amcr. JScv. reap. 93: 1*4. WALisoWkKi. S. Z.. l-Lorp, T. XV,, and .MoTkb. E. N. ia-I-'*:*. MCemilii'utigns in the Chemotherapy of Tuberculosis . ,t.cr. Rev. rrep. 1**9., 35 l 359. Laxdsttixcr. K. (1930. -The Specificity of Serological h^ctiona**. Tlxomas. Springfield. Maul. M. (19C7). -An I-E. Reaction reilevinj Administration of P.A.S.**. Mco. J. Al'iT., 5: 733. Mkuical Research Council (1933), Emerjvr.ee of li-ciTi.: Resistance in Pulmonary Tuberculosis**. Lc.ncet, S: SIT. National TczererLoiu advisory Council HscouxtN'SAUcxk <19S), Canberra. Rick. A. R. (1943). -Hypersensitivity In Disease'*, linrve.y Led., 43 : 10C. Schwarts. W. 3.: and Moyer, ft. LX (2953). -The Incidence u! Never# Toxin Reactions to Streptomycin and ?.AS.H, in Transactions of ths 11th Conference on Chemotherapy of Tuberculosis. Veterans Administration. Army and Navy: 193. Smith. J. M.. and ti>r. 31. H. (1931). **Toxlc and Allersie Drop Reactions during the Treatment of Tuberculosis**. Tubercle (<(UI).)t 43: 337. Suvtbic, H. C.. and CONNOLX.T. C. K. (1S"*S). -Incidence of Serious Complications of Corticosteroid Therapy in Respiretory Disease'*. Thorax. 33 : 371. THE MANY FACES OF ASBESTOS DISEASE E. O. Longley1 Department of Public Health, Sydney SKAL.C discovery file copy A.be.to.l. it .can a. an. of tha moat .ignficant medic. I problem, deriving from Induatry in tha present age. As not only ssbestosis but also carcinoma of ths lung and masothelloma of the lung are accepted by the New South Wales Workers* Com pensation (Dust Diseases) Board as compensable injuries provided that adequate Industrial exposure to asbestoe can be proven, it is important that all phyaielana should be acquainted with the three conditions and should, when they sde conditions resembling carcinoma or mesothelioma of the lung, be alerted to mako the fullest possible Inquiries into the patient's industrial background and place of residence. The presenee of asbestos bodies in the sputum or In ths lung tissus indicates only that the patient has been industrially or environmentally exposed to asbestos, and not that tha patient has pulmonary asbestosis. .Uucstoa Is one of the most ancient and interesting industrial materials. Actually, asbestos is a name given to a scries of minerals composed of silicates of Iron and magnesium. Cbrysotile is the main asbestos of industry, but amoslte and crocidolite are also used. The Romans mined for asbestos in the Italian Alps o*rer 2.000 years ago. and Kerodoius described in 450 b.c. how the Romans used asbestos for enshrouding corpses before cremation to permit of easy collection of the ashes for burial. Plutarch (aa 70) described how -asbesta" was used for the wicks of the lamps of the Vestal Virgins, the name -asbesta" meaning unquenchable, inextinguishable or inconsumable. 4 Specialist in Occupational Health. Division of Occupational Health, and Chairman, Dust Diseases Medical Authority. Address for reprints: Dr EL O. Dongley, Division of Occupa tional Health, Joooph Street. Udcomlx. N.S.W. 3141. It lias only been during the lost 36 years that asbestos has been nsed to any great extent for Industrial purposes. World production of asbestos in 1330 was only 500 ions, whereas by 1950 production had Increased to 1.300.000 tons. Asbestos dust was not recognised as a dangerous hazard until 1900. when a case of asbestosis was described in a man who died in Charing Cross Hospital. By 1923 there were still only 10 cases of asbestosis on record. Industrial exposure to the harmful effects of asbestos dust occurs not only In mining, but also in crushing and refining processes, textile manufacture, lagging, manufacture of brake linings and. very importantly in Australia, the manufacture of asbestos cement products. Asbestos in recent years has come to be accepted as having significance not only in the industrial fields, but also In the larger field of environmental health. Con tamination of city air by minute quantities of asbestos dust has caused great concern. Whereas long periods of exposure to high concentrations of asbastos dust are necessary for the development of asbestosis. mesothelioma of the pleura and peritoneum can occur after only minimal exposure of short duration. Fortunately, only crocidolite or -blue asbestos** has been positively incriminated as a cause, and although "blue asbestos" was used in New South Wales to some extent in days gone by. it is rarely used today, despite the fact that it Is mined in Australia. Ample evidence exists that asbestos Is truly a ubiquitous material, os. for example, the fact that asbestos bodies were reported In 46<Tc of autopsies in the Pittsburgh area :n 1905 (Cauna <*r alii. 1065;. Asbestos bodies are also found in the sputum of a large percentage of patients attending pulmonary clinics in industrial cities, without there being any evidence of industrial exposure. 522239  i mi THE MEDICAL JOURNAL OF AUSTRALIA NovEMnt* 22. 1369 The effects of aibcstSi on tho klisu organism will he adequate exhaust ventilation and substitution of wet pro discussed under the headings (I) asbestos hodlei. (11) cesses frr dry have all considerably improved the work asbestosis, (111) asbestos cartinoms of the lung and peri situation. toneum, end (It) asbestos mesothelioma of the pleura Unfortunately, many asbestos workers were exposed for and peritoneum, although, to complete the picture. It long periods to hazardous concentrations of asbestos in the ahould be mentioned that asbestos (amoslte) Is even of last two or three deeades, and we are still seeing a con Intereit to the dermatologist, as "asbestos warts", showing siderable "hack-log" of patients exposed during this time. histologically a picture of extreme keratosis, are commonly For the development of asbestosis It Is necessary for seen in asbestos workers. the worker to be exposed to extremely high concentrations ASBESTOS BODIES of dust for relatively short periods of time, or to lower The older textbooks frequently refer to the presence of asbestos bodies in the sputum and make no reference to the appearance of bodies In the lung tissue. Today, however, the presence of asbestos bodies in the lung tissue is fre quently described and, in fact, thousands of asbestos bodies may be risible in a section of lung tissue not more than 1 cm* in area. concentrations of dust for much longer periods. V.'hllst In the development of any o( the pneumoconioses there will always be some individual susceptibility, the development of asbestosis depends upon concentration multiplied by time. The recommended maximum allowable concentration of asbestos dust in the worker1! brcetlilng zone is set et 5 million particles per cubic foot, although local experience would indicate that control of the environment to this These unique bodies may vary In length from 20a to over level does not offer adequate protection. In the spray 200a. An asbestos fibre forms the central core In eaeh of application of asbestos to ceilings, concentrations of up the bodies, which are beautiful golden-yellow-to-amber to 200 million particles of asbestos per cubic foot have coloured structures in a multiplicity of shapes. Beger been found in Sydney. Without adequate respiratory (1933) showed that the asbestos fibres are coated with protection, such as would be provided by an air-supplied protein from tissue fluid until completely ensheathed, and respirator, asbestosis eonld be expected to develop in such that the granules within the gel coating are ferric ' a situation In an appallingly short space of time. compounds. Typically, the asbestos bodies have an appearance like beads strung on a fibre, this being a result of surface tension effects. They are characteristically dumb-bell The presenting symptom of asbestosis is almost always dyxpnsa. This occurs early in the disease, it conspicuous, and is practically always out of proportion to the signs found In the chest There may or may not be a productive shaped. cough, but if there Is, asbestos bodies may be found from The bodies appear to be Innocuous, their coating of time to time in the sputum. protein reducing their capacity to cause fibrosis. When asbestos bodies were injected lntratracheally. no fibrosis was produced. The disintegration of the bodies increases their flbrogenlclty. Frequently, the patient may state that he hat had repeated attacks of acute pleurisy, but In most cases ao pleura! effusion has ocearred. Figure 1* shows a typical clamping of asbestos bodies On ellnleal examination, abnormalities may be con In the lung tissue and surrounding diffuse fibrosis, which spicuous by their absence. Occasionally cyanosis Is noticed, is markedly different from the more discrete areas of but it U usually of slight degree. Clubbing of the fingers ''M flbrosis seen in silicosis, with their typical wborled is found In some cates. Even when the condition Is structure. Numerous phagocytes can be seen containing advanced, the percussion note is never seriously impaired, products of disintegration of the asbestos bodies. breath sounds are vesicular ami a few rales and crepita tions may be heard, scattered particularly at the lung It should be pointed out quite positively that the finding bases. Some authors consider basal crepitations to be a of even large numbers of asbestos bodies in the sputum constant finding la early esbettetU. I myself arree with dots not necessarily mean that the pctlent is suffering Hunter (1939) ("Diseases of Occupation") that crepita from a degree of asbestosis which could be recognised tions are beard la two-thirds of all cases of early clinically or radiologically, or which would cause even asbestosis. but not in all. minimal disability. Asbestosis is similar In its pathology to any other inter I have deliberately described these bodies as "asbestos" stitial pulmonary fibrosis. Fibres! s interferes with gaseous bodies rather than the more commonly accepted "asbet* exchange. ar.C for this reason the most important pul tosls" bodies, because I believe that the latter term is monary function test is carbon dioxide uptake: misleading, tending to Indicate that these bodies are found only when there Is a condition of pulmonary asbestosis. In marked contrast to the usual absence of physical signs. X-ray examination of the chest often offers quite 1 ASBESTOSIS distinctive evidence of the disease, ever, before symptoms It is not surprising that a number of cases of asbestosis have developed. are found in New South "Wiles, in view of the tact that a Classically, in an advanced case all the following features number of large asbestos plants manufacture a wide range will be found: of asbestos products in the Sydney metropolitan area. In I. A ground-glass appearance, especially of the lower these factories, control of the working environment has proceeded as more hss been learnt of the human response to exposure to asbestos. Isolation of dusty processes. half of each lutig. This may be sometimes difficult to detect, unless one places a ruler across tie lungs and then compares the upper and lower halves. `For Figures i. 2, 3 and S see art-paper supplement. I. A "shaggy" heart outline. 522240 ay Nr. XovEUoQt 22. 19C9 THE MEDICAL JOURNAL OF AUSTRALIA IOCS 3. Obliteration of the cardio-pkrenic angle*. 4. Obliteration of the costo-phrcnie angles. 5. ~Ten:tng" of the diaphragm and other evidence cf previous pleurisy* Whilst all these features are seen la e classical case, one or store features may be missing. Opacities is the luag may resemble those of silicosis more closely than the usual ground-glass appearance. AS5ESTOS CARCINOMA OF THE LUNG AND PERITONEUM Doll (1955) reached the conclusion that asbestos workers faced a risk of cancer of the lung 10 times os groat as that faced by the general population. In one series. 1$% of 3C5 patients with asbestosis had cancer of the lung. The carcinogenic effects of asbestos arc not confined to the lungs, for Keal (1960) found a high Incidence of peritoneal carcinoma in women with asbestos!*. It is thought that when asbestos fibres are inhaled and swallowed, they may penetrate the bowel wall to involve tbe peritoneum. It has also been reported that the possibility of car cinoma of the lung in asbestos workers Is greatly Increased in those who are cigarette smokers Carcinoma has occurred in Industrially exposed asbestos workers even though a> recognizable degree of asbestosis could not be confirmed by X-ray examination. In most cases a considerable number of years (between 30 and 50) has elapsed from the time of first exposure to asbestos until the discovery of the tumour, and in other cases carcinoma has appeared many years after exposure to asbestos has eeased. In all the cases in my experience, the patient had reached, or was approaching, retiring age. Careful environmental control . should practically eliminate this tumour as a problem In asbestos factories, as It has been shown to be related to high dust dosages. A typical asbestos carcinoma Is shown in Figure 3. Mesotheliomas are primary tumours of tl.t* serosal surfaces, and the first was described by von Rokitansky in 1$54. Von Rokitansky called the growth a "CuiloJd cancer'* of the peritoneum. There was much disagreement amongst the experts until Godwin (1957) set out striet criteria for the diagnosis of pleural tumours, and Winslow and Taylor (19C0) did the same for peritoneal tumours. Since these two dates the diagnosis of mesothelioma has become much more common. Sorow (1067) states that the Incidence of primary meso thelioma has varied statistically from 0*03% to 0*2<r< of all autopsies, with a ratio of 1:2 in favour of the mole. The Pneumoconiosis Research Unit at Johannesburg, South Africa, described, in 1057, the first largo series of cases of diffuse mesothelioma diagnosed histologically. Wagner et alii (1960) were able to establish that 32 of their original scries of 33 patients with proven pleural mesotheliomas had been exposed to crocidollte tr* or around the Cape of Good Hope asbestos fields or in industry. Some patients had left the area of exposure as young children, and the average period between exposure and development of the tumour was 20 to 40 jrears. Wagner later extended his study until he had diagnosed a total of 27 pleural and two peritoneal mesotheliomas, and la only two of these cases was he unable to establish a history of asbestos exposure. The diagram in Figure 4, reproduced with the permission of tbe Archive* of Environmental Sealth, was taken from an article by Lleben and Pistawaka (1967). NiMH * / ASBESTOS MESOTHELIOMA OF THE PLEURA AND THE PERITONEUM Such an asbestos score has been stirred up overseas by reports which confirm the relationship of the development of mesothelioma of the pleura and peritoneum to con tamination of air with asbestos, not only In the working environment, but also In city air adjacent to asbestos works, that an artldo In Prevention Zfapasine in July, 1967, HiieuiwtHl Unit it tuigiiL 1m uiikuAi to visit Kx|m 'U7 bvcaiiK** of the ri*k of ,`ikIk>kioj> in Un air. It might bo wise, therefore, to allay immediately any fears that Inhaling the air of the city of Sydney Is likely to cause a great epidemic of mesothelioma in the future. Practically all asbestos mesotheliomas reported overseas have occurred as a result of exposure to only one variety of asbestos, namely, blue asbestos or crocidollte, and not with amosite or chrysotile. As previously stated, the use of crocidollte has been virtually eliminated in the New South Wales asbestos industry. In the two confirmed and one unconfirmed cases of mesothelioma seen in New South Wales since the new Workers* Compensation (Dust Diseases) Act was put into operation, there had heen a definite period of -exposure to blue asbestos more then 20 years earlier. 4 : rntlMitM :<N' urn) 2-N )i:mI ?,,,- Ll**liwn:ot. while 4..\` )mtl a rMtriton?;tl I'j.lM-jit J.y, u Burxw, ii:ul no history f ;i,i)Hxirml *iit l.cr father nnd brother ha<J worked 'n ax. nst'.Mb*; factory for many years. Patients 3-0 end 3-0 h:.<l both `r.r.d more than ii years' exposure applying asbestos ir.su.a- tlcn. aod both bad pleural mesotheliomas. This diagram depicts pulto strikingly the danger ot wcr!t:r.f la asbestos factories, working adjacent to such faster!**, working within the area in which asbeetos dust could fall out**, or even of coming in contact with the asbestos^ontamlnated clothing of a relatives Figure 5 shows the radiological appearance of a pleural mesothelioma in a person who worked for nearly 30 years in an asbestos cement works in New South Wales. ACKNOWLEDGEMENTS I should like to thank the Director-General of Public Health of How South Wales for his permission to publish this article, and Mr Rend de Vries for the excellent photo graphic reproductions and photomicrography* 522241 Vy-.V'.i-V'r- -- '5 s v,.< -1 ut:.y--y.rrrv , -CVy.i * * 1066 THE MEDICAL JOURXAL OF AUSTRALIA XnvKMnr.li 155? REFERENCES Owns. 31. C. (1111). "Dlftuoa MtaothsUomaa". Cnnccr, H: 233. Him p. J. (llJi}, "Cbtr die itiululiMfyirckn*, Vlrrtnn Htrxrra. D. (IS8S1. "Dlarass* of OcrupnUon". 5th Edition. i J AreA. pot* Anal., 280: 380. Boaotr, 3I,, Coxsvox, and Lrroaxrst, L. L. (1MT), "Maso* thslloma and Its Association with Asbtstnsll". 3. Amcr. died. At*; 11: SI?. Encllsh Unlv. Prrss, London. Rial, E. E. (1*80). "Asbsstosls and Abdominal Neoplasms", Lonrrl. 2: 1311. t RestTAXSKT. C. VO* <13S4). "Manual of Pathological Anatomy", Transactions of the Sydenham Foeletr. London: 26S. Caota. d. Tkviilh. R. S.t and Gao, ?. (1885), -Asbeotos IVAOCtr.. 3. C- Slices, C. A, and Maachaxp, ?. (:?*). Bodies In Human Lancs at Autopsy", /. Aairr. med. Ass.. 153: tU. "Diffuse Pltutal Mcsothrlloma and Asbes-.ciis Exposers In N.TV. Cape Provlr.es'. Jffrlf. /. irduttr. 33rd.. 13: Pau. R_ (1SSS). "MortolHy In X.vnr Cancor In Aabootoo Wlxsiow, D. J.. and Tatior, H. E. (13<if>. --MaWjnan! Worker*', Bril. J isilutr, 3/rd.. 13; 81. Peritoneal Mesotheliomas'', Cancer. 11; 127. Special Article DATA PROCESSING FOR A RESEARCH PROJECT G. Roderick McLeod, r.n.c.s.(EDix.), f.r.c.s.(exc.), f.f-a.c.s.1 Princess Alexandra Hospital, Woolloongabba, Brisbane The development of a system of electronic data processing for the Queensland Melanoma Project Is described, and the plan of the system Is dlseussed. Emcievr data processing Is not something that comes easily to clinicians. At ths outset of most clinical Investigations the information Is tabulated by bend and counted laboriously. Aa the investigation proceeds and it becomes evident that the Initial methods are unsuitable, the next method used Is that of punched cards sorted by means of a knitting needle. There the process often stops. The moss of data accumulated by this time may become overwhelming, so that an attempt le made to convert the findings for computer analysis. At this point difficulties become apparent. It is bard to find people with the time and knowledge to design a system and computer programmes suitable for medical work and to have this work done withls the limits of a research budget. In the Queensland Melanoma Project we hare passed through alt these stages. A report on how the difficulties were overcome, and an outline of the present methods of data processing, may be of help to other clinicians unsure how io proceed In this problem. In the first two years of the Project, data handling was limited to relatively unsophisticated methods. Hand written records provided the only master file of Information about the patients; follow-np letters were typed after the hand-sorting of records: and analysis of information was done with a punched-cord sorting system which proved both cumbersome and liable to error as the * numbrs of patient* increased. It became apparent that much more efficient method* of data processing were necessary. The volume of basis Senior Jlesenrrh Fellow. Queensland Melanoma Prnjec:. .\<V.ro fee reprints: l?r cj. TL MrT.C"d. Q-iecelrnd n'.-r.r 'r*-J-<*t. r.o. ftes-aw-h Volt, rrlnoes* Aivxr-uira Hospital. T.-ooHoor--to*. Qld. 1103. information and the vast amount of up-dating necessary warranted the use of a computer-based tyitem for HI lag and analysis. Because of this relatively late decision, the methods of data processing had to be developed for the existing structure of the Project. Most of the problems experienced occurred la the early stages. Once experience was gained In analysing requirements we were able to progress much taster. In developing the methods. It was considered wise to plan a system which could !> used specifically for the work of the Project, but which, without alteration, would be suitable for use for many other medical isfomatlon processing purposes. IVe required our system to perform certain major functions. These were: j 1. To establish a file of the Information concerning each patient, including (a) patient's name and address, (b) same and address of doctor responsible for the patient, (e) all clinical Information concerning the patient. 2. To be able to update the file by (el checking the correctness of presentation of all new information, (b) adding intormntien about new patients. (c) altering pre-existing information liv changing addresses, respon sible rloc'or or clinical information. (<M adding r.cw clinical Informal ion to existing record*, (<: i-t!ng records where required. 3. To use the file to select patients requiring follow-up and nuiemr.tica'ly prepare the follow-up let-crs. 4. To analyse the information ia any manner considered desirable. FACILITIES Part-time of establish.-"! qul-ment for short periods is all that is require:. 7h* follow'.:-.; facilities are available: 1. Card-punch facilities fer ransferrisg Use Information from code sheet* to "Hollcri::)" I'l-column cavils 'r.vr.iir.V'.e 522242 .. ... : - -/--.:---r--vr~w-------^-'*-rrr--7rr\ '.'-rnypy" -r; - - .'tru :V.' ; j Wv-rl'r.';. / O.vv il'T'-T.'!'1!' --;'-iv::V "fl'--'-Vl>." '