Document 702qppvQ6a35ygDZdnED3b2aB

Otrorr-& 4. 1969 V'T THE JIEDICAL JOURNAL OF AUSTRALIA Original Articles 69 IOEH 3208 Ref. Book All, AIII FIFTEEN CASES OF PLEURAL MESOTHELIOMA ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO ASBESTOS L\ VICTORIA James Hilne, b.sc., m.b., b.s., d.p.h. Industrial Hygiene Division, Department of Health, Victoria Fifteen cases of pleural mesothelioma occurring In Victoria are described. Occupational histones and the finding of asbestos bodies in lung tissue Indicate a relationship between occupational exposure to asbestos and induction of pleural mesothelioma many years later. The exposure In tome cases was relatively short but intense. Crocldollte or blue asbestos would seem to be particularly potent in the induction of these tumours. Plectul mesothelioma, once regarded as aa extremely rare tumour, bag been diagnosed during recent years with Increasing frequency the world over. Following the work of Wagner <?t o/ii (1960) In South Africa, who related asbestos exposure to the causation of this turoouT, many investigators bare confirmed their results (Elmes et alii, 1965: Selikoff <t alii, 1964). In Australia, the only sizeable asbestos mine was operated until recently at Wiuenoom In Western Australia, and Inhalatloncl exposures to asbestos fibres were very high. Only one case of mesothelioma has been reported as emanating from asbestos exposure at Wittanuom (McNulty, 1962). but this is not surprising, since the average time taken after exposure for the development of mesothelioma Is of the order of 25 to 30 years, and that period has yet to elapse among3t the majority of Western Australian asbestos miners. Mortimer and Campbell (1963) have recently described two cases of pleural mesothelioma associated v.ith asbestos exposure in Queensland, and predicted that "it Is likely that the association will be encountered with greater frequency in the future". , In Victoria, there has been considerable occupational Industrial exposure to asbestos fibre inhalation In the course of asbestos processing and, although there is no Victorian asbestos mine, industrial conditions of 25 to 10 years (and more) ago were such us to cause exposures In some circumstances of a similarly high order. Hence St la with interest that we have noted. In the smaller, more highly industrialized State, a recent Increased Inci dence of pleural eucsctUi'Uomava. The scries involves 15 patients itii pleural Riewiiict'.oma whose occupational historic* have been investigated. In those casc3 In which Ad'lrtSi for reprints: Vt 3. E. >V.ne. Deparcrntru of Health, tn1miH.il tiypicnc r.'ms.oii, IS *'ark strict, douth Yarra, Victoria 31U. a patient has died, a search has been made, whenever possible, of stained (ur.g-tissue sections for asbestos bodies. MATERIALS Twelve patients presented at the Austin Hospital Thoracic Unit in the period from 1962 to 1968. When the first three cases were noted (Hidden, 1566) between 1962 and 1965, the writer's imere-s*. was aroused in regard to the possibility of their relationship to asbestos exposure, and a search of lung tissue sections showed asbestos bodies. Investigation began of past occupational exposure, and received an impetus wUa the appearance of a further nine eases in the succeeding three years. A surgeon at the unit kindly permitted investigation of a private case. Inquiry was then made of the pathologists of all major public hospitals in Melbourne; tv.-o further cases came to light, making a total of 15 in all. So far as I am aware, these represent the tctal of ail cases of pleural meso thelioma diagnosed over the period 1962 to 1553 in Melbourne public hospitals. RESULTS The series consists of 15 patients, five of whom are still alive. There were nine males and six females. Autopsies were performed on nine of the 10 patients who died, and the diagnosis was made in the remaining six cases by examination of tissue removed at thoracotomy (Table 1). The original diagnosis was not made in all cases by the same pathologist, but two pathologists have since examined all the tissue sections and are agreed that the diagnosis In each case Is pleural mesothelioma. Asbestos Bodies Of the nine cases In this series which have come to autopsy, asbestos bodies have been seen in routine stained lung-tissue sections in seven. and digestion-concentration' extraction of lung tissue revealed asbestos bodies in the other two. In the remaining six cases, search waa made of diagnostic lung and pleural biopsy sections and no asbestos bodies were seen. History of Occupational ExposurOccup.itioual histniic* are detailed in so fur as the availability of facts allowed, and In 13 eaiies there wli evidence of asbestos exposure. 0049-0293 [61] 670 THE MEDICAL JOURNAL OF AUSTRALIA October 4, 1363 Case Somber 1 t S t 8 7 8 10 11 17 IS 14 IS PfttiCEt'4 Sex Occupational Exposure Tms l . Asbestos Bodies' It Truck driver for firm handling asbestos + F Winding abe*lcs *lriag oft to *c!JJo; rod ; bulling 7 Munitions factor)-, Australia +++ + ++ 7 Denied by relatives ++ (by fiigutioo-coacea* uatioal H Munitions factory. India No sectloos available F Winding a<bc>tas trlng on to welding rod; buffing >0 sections available F Father worked in tbetoj cemec*. factory >* sections available F Winding asbestos trmg oa to weliiar rod: biffing Not available X Naval dockyard wvrfccr la Scothrd and Australia M Denied by patient Not va.table 4(by dlgestion-roncen- tratiog) U Winding asbestos string on welding rod ; maintaining sad aetiiog winding machine ++++ 11 Naval dockyard worker + + + -T u Xavsl dock-yard, Malta u bagger SI Carding asbestos fibres ++ , + + J- + Not available Intensity of Exposure Mild Heavy Unknown Unknown - Unknown Heavy Very mild Heavy Heavy Unknown Heavy Beas-y Heavy Heavy Heavy Asbestos bodies classified 11 follows: Duration (Approximate) 1940 to 2983 1942 to 1945 1941 to 19(3 Unknown ? 1910 ' - 194S to 1947 f 1930 1VX7 to 1Q39 1939 to iaca Unknown 1935 to 1950 m; to 1908 1930 to 1942 1920 to I960 1942 (8 months) One fact worthy of note Is that four of those with unequivocal evidence of asbestos exposure had been employed at the same firm during World War II or soon after. They were each unaware that any co-worker had suffered from a similar condition. Their exposure had been extreme, and the type of asbestos was Cape blue (crocidolite). TUi^ group will be considered in more dotal! In the discussion. Living Four of the five patients still alive at the time of writing bad been first exposed to high concentrations of asbestos fibre about 25 years before. The remaining patient denied exposure, but stated that as a young woman she had cared for her father who worked for a firm manufacturing asbestos-cement sheeting. Dead For the 10 patients who bad died, occupational histories were obtained by Interviewing relatives, friends and acquaintances from work. Five had had severe exposure to asbestos (all showed many asbestos bodies in staiood lung-tissue sections). Of the remaining five patients, one was Interviewed before death and denied ever being exposed to asbestos. His wife subsequently agreed with this. Two patients were said by relatives to have worked In munitions factories, thereby probably being exposed to asbestos. One patient had work'd as a truck driver for the same film previously mentioned as a source of four cases in which heavy exposure had been experienced inside the factory. lie had thus probably been exposed himself, though not to the same extent. One patient bad worked only Jn the clothing trr.de ns a machinist and there was fio history of using asbestos, Hence the total series of 15 consists of nine cases In which there was definite and heavy occupational exposure to asbestos, four cases In which exposure was probable, and two In which no evidence of asbesloi exposure was forthcoming. Occupations The occupations as stated by those Interviewed are tabulated. There are two patients listed as "munitions worker"; the quantitative relationship to asbestos exposure Is not clear, but description of the working conditions by an experienced chemist leaves no doubt but that there was ample opportunity for exposure to asbestos. Ship building and labouring In & naval dockyard are well known to be occupational sources of asbestos exposure. Ashcroft (1368) and Hanles (1368) described mesothellomnta occurring In labourers at the Royal Dockyards, as well as In boilermakers, fitters, shipwrights and welder*. Lagging, asbestos carding and asbestos string winding alt Involved heavy asbestos exposure about 25 years ago, and the truck driver is known to have worked for the asbestos winding firm, though he was generally employed at a different branch. There Is one patient, listed as "domestic'*, whose father worked for on abe$tos-ccmcut firm. It is conjectural as to whether she was thereby exposed to asbestos. She denies evc-r handling very dusty clothes. If she was in fact exposed, a dom^ptic occupation u ip the only source, because she has never been employed anywhere else but at home, and has never lived near any firm processing asbestos. In reference to occupational histories It la pertinent to stress the dilT'-ulty of obtaining on accurate history, especially from friends and relatives. Some patients may 0049*0299 [62] Ociobcb 4, 1969 THE MEDICAL JOURNAL OF AUSTRALIA 671 volunteer a precise history In detail. For example, the asbestos carder, who Is a highly qualified scientist, was employed in a small, poorly ventilated room during war time, carding asbestos fibres tor use as respirator filters, working In a cloud of asbestos dust for six months. How ever, for other patients, the appropriate information often requires very careful elucidation, as the following histories may demonstrate. Csss The patient, a female aged 4fi years, was said to be & '`ledger operator*. She left school at the age of 13 years and worked as a domestic for about seven years. She then Wotkcd, for about five years, for a Arm manu facturing welding electrodes, leaving this to be employed for five year* examining hosiery. She then went to night school, learned typing, and graduated through a series of office Jobs to her present pGliian a* ledger operator. She denied any exposure to nsbetos at first, but when asked to describe what she did at various firms, she recalled that the electrode was required to have asbestos airing wound round the tr.etal core as a binder for the ffux with which it was later impregnated. There had been lots of asbestos dust in the air from the winding spools, and she. in common with three others In our scries, bad worked In this atmosphere subject to he.tvy exposure for a period of about five years, starting about 25 years ago. Investigation confirmed her description, but the whole process ha* since been completely changed: little or no asbestos is r.ou* usc-J depending on the type of electrode, and an efficient exhaust system i* installed. Cub 14.--The patient was a male, aged T5 years at death, whose occupation was listed as "barman''. This patient was thought clinically to have a bronchogenic carcinoma. After autopsy, the pathologist, diagnosed a pleural mesothelioma, and the large, radiological!)- visible pleural risque* were recalled. Asbestos exposure was considered and a retroapecUve search through the lung sections revealed asbestos bodies. No next of kin was known, but contact was eventually made after some months with a friend at the club where the patient had worked as a barman for the previous ]$ years. The friend, on questioning, recalled that the patient had been a tagger for 30 years before this, and had proudly exhibited a gold presentation watch as evidence of his long service. Search of'the relevant firm's records and discussion with the medical officer confirmed these facts. Asbestosls No patient was regarded clinically' or radiological!)* as offering from osbestosis, but pleural plaques were radio* logically visible In one case, that of the lngger mentioned above. In which the duration of exposure and time-lapse since its inception wete by far the longest of the series. These plaques are strongly suggestive of asbestosls (Oosthuizen ef alii, 1964), or at the least, of severe occupational exposure to asbestos. Duration of Exposure All those known or presumed to have been exposed to asbestos began their exposure either during or before 1942. The longest exposure was 3) years,-but Jt is noteworthy that five patients had been exposed for five years or less, one of them for only six months. , DISCUSSION The association of asbestosls and asbestos exposure with bronchial carcinoma is generally accepted. Whilst acknov.lod^ir.g the general critical comments of Willis (1963), it la suggested that the tumours In this scries have a pattern quite distinct from pulmonary carcinoma In many ways, namely, macroscopic appearance, hlstopathologlcal characteristics, clinical picture and symptom atology, and, finally, In postoperative course, so that they represent a different type of asbestos-induced malignant disease from the more common bronchogenic carcinoma. Histologically, the picture is consistent with pleural meso thelioma (R. J. Riddell, personal communication), and despite careful search no autopsy revealed evidence of other primary tumours or of metastatic sptead from other tumours either Into the thorax or out to the pleura. The acceptance of mesothelioma cs an occupational hazard of asbestos is now becoming widespread (Leading Article, 1966). It is Important to note the work of Gross et :fii (19G8), who have shown that the term "asbestos body" is a generic one describing a microscopic body whose longitudinal nucleus is a single fibre, very commonly but not always asbestos, on which a yellow-brown coating has been deposited in bcad-like form. The resultant club-shaped or beaded body they prefer to call a "ferruginous body" and they have shown that an assiduous search of lur.g tissue (that is, by lung digestion and concentration fol lowed by microscopic examination of the liquid concen trate as a smear) reveals these "'ferruginous bodies'* almost invariably in every autopsy. However, the lungs of those patients previously exposed in life to asbestos produce Urge numbers of ferruginous bodies, whereas It may- require diligent searching of the concentrate to find a single body in others previously ur.exposod to asbestos. The searching of a lung section obtained as a routine at autopsy and stained with hematoxylin ar.d eosln is obviously far less efficient term the digestion and cca- centratfon method of Gross et and may be expected to give point to the quantitative difference between the unexposed and exposed. Thus in our series there was no difficulty in finding, by means o: a simple search of stained tissue, asbestos bodies in those known to have been exposed (Figure 1). Nevertheless, before the taking of full and careful occupational his'ories, m some cases, the presence of asbestos bodies h&l not been remarked on, even though retrospective search revealed then, sometimes in abundance (Figure 2). There are at least two reasons for this. Histopathologlcal diagnosis is generally made on low-power examination and rarely does the pathologist find the need to search carefully a whole section under high power, which he usually must do to find those asbestos bodies that are discrete and not clumped. Also, the asbestos body, as Beattie (1961) has shown In experi ments using animals, is not an unchanging thing, but varies la form from a fine filament with a greenish-yellow eoatlng to a comparatively short, thick, dark-brown, seg mented, sometimes dubbed body which can very easily be missed. What Is the significance of finding asbestos bodies at autopsy Id seven out of nine cases of mesothelioma, by simple search of routinely stained sections? The first factor to bear in mind Is the apparently trite but Important statement that the method of making the slide lias a groat influence qti the number of cases in which these bodies can he Identified. The figures vary from 957C (Gross ft u!ii, 1966) to >'**? (Hourihane, 1961), but no comparison is possible because of the diifercnt tech niques employed. Obviously, the larger the amount of MIIIIIIIIII 0049-0300 [63] er THE MEDICAL JOURNAL OF AUSTRALIA Octree 4,1969 long digested or volume of luog searched, the greater trill be the yield; with regard to smear techniques, the number obtained from a basal smear could prima facie be expected to be greater than thet from, say. lateral or ftplcal smears because, firstly, "asbeslosis is most frequently found In the lower parts of the lungs, but may Involve the The series of Ashcroft (156S) provides tbe only work with which some comparison with our results may be made, inasmuch as be also assessed the presence of asbestos bodies in a scries of cases of mesothelioma In which "lung tissue was available for histological examin ation". He found asbestos bodies in 21 cases out of 23 (91%). A majority (15 out of 21) showed only "scanty asbestos bodies in lung sections". In our series, seven out of nine (77%) showed asbestos bodies, but on'y one could be described as scanty, and the majority (five out of seven) were comparatively plentiful. Ashcroft com pared bis mesothelioma series with a concurrent series of asbestos body counts taken by smear as a routine at autopsy, and found the difference to be highly significant. We have as yet no series for comparison but our figures, being of the same order as these of Ashcroft, suggest a similar interpretation. Taken In conjunction with the fact that all seven patients had definite or presumptive evidence of asbestos exposure, the relationship of asbestos inhalation to mesothelioma seems clear In this group. c The type of asbestos may be important. It is generally agreed that of the three common types of asbestos, namely, f Fjccro 1 : Asbestos bodies In lung tissue o. former asbestos winder (Case 2). Some are fragraen.lng Into granules. (Oil immersion.) midzones and the upper lobes" (Gough, 1965) and secondly, radiological evidence shows that asbestosis occurs pri marily at the lung bases. Random lung sections could be expected to yield the least number of all, so that our finding of seven cases out of nine appears very significant. amosite, chrysotlle and trocidc'.ite, the last named, often called "blue asbestos", Is the most potent in mesothelioma production (Wagner, 1965). Other sorts of asbestos may possibly be incapable of inducing mesotheliomatous growths. Cape blue asbestos, the South African form of crocidollte. which Wagner found to be the causal factor In his original series, was the only type of asbestos used by the small firm of welding-rod manufacturers previously mentioned. Apart from the series as a whole, tbe discovery of the small subgroup of four patients who, having been diag nosed as suffering from mesotheliomota, were later found to have worked together, about 25 years before, at tbe same firm for a relatively short period under conditions of heavy exposure to Icbalcd crocidolite dust, reinforces the findings of overseas workers that these conditions are casually related to tbe development of pleural mesothelioma. ACKNOWLEDGEMENTS FlCL'HE I: Asbortcs body In lung tissue of former sb*tu winder unose occupation was said to have been "Invalid pensioner for scars" (Cae 2). Note Hark, discrete beading over whole length of fibre. lOH Immersion.) Tbe second factor to consider Is thM. the patience and experience of the viewer In relation to asbnslos bodies must have a bearing on the findings. Some cvper truce tu viewing sputum smears of asbestos workers was found to be advantageous In Identifying csbodos bodies. My gratitude is expressed to the following, who have assisted In many and various ways with the development of this paper; Professor H. Attwood, Dr J. Hidden, Dr A. Cooper, Dr A. Parkin. Dr G Price, Dr F. X. Hurley, Dr A. Garten. Dr A. J. Christophers. Dr S. Weiner, Dr A. Campbell, Dr J. Cinrebrouuh, Dr A. Davis and members of the staff of the Au.-tin Hospital Thoracic Unit. Dr F. O'Rourke, Medical Superintendent. Austin Hospital, per mitted the perusal of hospital records, and Dr R. J. Fambuch, Chief Health Ollicer, has kindly given permission to publish this report. ` REFERENCES Ashcroft, T. (15CJ). "Asbestos Bodies in Routine Necropsies on Tyneside; A Pathological and Social Study", JJrit. mtd. J.. 1 : 614. Beattie, J. (lPCl). "Inhaled Particles and Vapours", edited by C. N. Davies, rergnmon. New York: 434. Elsies, P. C., McCacohkt, W. T. F., and Wads. O. L. (12C5), "Diffuse .Mesothelioma of the Pleura and Asbestos", Brit. mtd. J., ] : 350. Couch, J. fl?C5), "Biological Effects of Asbestos", Ann. S.T. Acad. Sci.. IJ2: 366. Cross, P.. Utiujias, M.. and on TnuwLLc. R. (!9CS), "Ferru ginous Bodies in Human Lungs", Arch cnviro/:m. //Jib, 17 : 327. llAuitrrs, r. O. (tf-'tS). "Aho<-tr>s Hazards in Naval Dockyards", dun. oc'-i.p. il'jfi., 11: IJ'. Hoihiiast. D (12C4). "The I'aih-.l.gy of M< ro-hrlmmafa and an Annlv*;* "( their Association with Asbestos Exposure", Thorar, Hi: 2C8. Leading Ai:tict : (19CC), "Health Hazards . f Asbestos", Lnncct. 1 : 530. . 0049-0301 [64] OcioJUJt 4. 1969 THE ilEDICAL JOURNAL OF AUSTRALIA 7} HcNcltt, J. C. (Z9s:>. "Malignant Pleural Mesothelioma In an Asbestos Worker", Mito. J. Acst., 5: 951. UoSTiXER, K. H, and Campbell, C. B. (1963), ''Asbestos Exposure and Pleural Mesotheliomas", Meo. J. Acst., 1: 720. Oostrciiev, S. P., ThejiOn, C. P.. and SLcrs-Caeuta, G. K. (194$), "Calcified Pleural Plaques In Asbestosis", S- A/r. Meditae By-lracs-. 10: 416. Riddell, R. J. (19$$), "Three Cases of Mesothelioma", Mm. J. Acst., 2; SSI. Ssljkopv, 1. J.. Ctr?c. J., and Kamxos'd, E. C. (1944), "Asbestos Exposure and Neoplasia", /. Iwr. mCd. At.t US: 142. Wagner, J. C. (1965). "Epidemiology of Diffuse Mesothcllal Tumours". Ar.n. .V.J". Acad, den, 132 : 575. Wacnc*. J. C., Slegos, C. A., and Marckano, P. (1960), "Diffuse Pleural MT.'-Khelioma and Asbestos Exposure la the North Western Cape Province", Ent. J. induatr. J/cd., 17 : 260. Willis, R. A. (1963), '`Pathology of Tumours", fourth edition. Buttenvorlh, London: ISl. ANAEMIA IN PREGNANCY IN WESTERN AUSTRALIA A. F. Fleming, m.d., m.c.path.,1 and X. S. Stexuocse, if..sc.5 Department of Obstetrics and Gynaecology, and Department of Medical Statistics, Vniversiti/ of Western Australia. Children and pregnant women in any community are the first to show signs cf poor nutrition, and the picture presented by the public patients attend ing the antenatal clinic in Perth, Western Australia, gives no cause for complacency. Nutritional anaemia U common, sho.vs a distinct seasonal incicence which can be related to a time of comparative feed hortage with high prices, and is prevalent amongst racial minorities, especially the Italian-born. Seven per cent of all patients attending the ante natal clinic are iron deficient and 2/, are folate deficient to a degree that causes the haemoglobin level to fail below 10-0 gm/TCO ml, but the actual Incidence of deficiency may be presumed to be higher. Other causes of anaemia in pregnancy include thalassaemia, chronic pyelonephritis, infec tion and unexplained haemolysis. One patient with megaloblastic anxmia was observed to have a low serum vitamin B., level, but laboratory investigations and her response to mall doses of folic acid indicated that her disturb ance of vitamin 8U metabolism was secondary to folate deficiency. * A scheme is outlined for the prevention, diagnosis and treatment of anaemia in pregnancy. These Is a widely held belief that anatnia In pregnancy U a problem of small importance in Australia, because of a uniformly high standard of living and good nutrition. A review ot tbe patients attending the antenatal clinic of the Department of Obstetrics and Gynecology of the University of Western Australia demonstrates that anamla b a common and serious complication of pregnancy, and one which is not receiving sufficient attention from medical practitioners. MATERIALS AND METHODS 6cven hundred and forty patients presented themselves at the clinic of the Department of Obstetrics and Gynae cology, University of Western Auntr-in, for antenatal super vision during the year 1907. All wre wives of labourerclass husbands earning not more than about 315 (Australian) FellAowrn.old Yetdham and Mary Ilalne Senior Medical Research Director cf Medical Ssallstica. Address for r-prlnts: Dr A. F. Fl.~.Jne, Department of Obstetrics ami Cj na-^ots^y, King Edward Memor; U Hospital for Women, SuUaeo, W.A., $003. per week. Seventy-six (10%) were found to have haemo globin concentrations ct less than 10 gm/100 ml at some stage of pregnancy or the puerperium. and their anaemia was not the result of hemorrhage. Ksematolcglcal Investigations Kwmoglobln concentrations were estimated by the oxy hemoglobin method and the packed cell volume by the Hawksley tnlcrc'r.ma:<:crit (Dacie and Lewis, 1963). Particular attention was paid to the percentage of neutrophil polymorphs with rive or mure lobes to the nucleus (Chanarln et alii, 1963) as a measure of folate deficiency. Bonemarrow specimens were collected from the right anterior Iliac crest, and methanol-fixed smears were stained with ilay-Grur.wold ar.d Giemaa stain and for intracellular iron (Hutchison, 1953). Serum folate activity was assayed with the use ot Z.cto5ciH:iJ casci as the test organbm (Davis ar.d Kelly, 1962), and the serum vitamin D-j level using leug'sr.a gradlia (Nicholas and Pitney. 1935). the lower limits of normal were taken to be 2-7 ng/ml and 160 ps/ml respectively. Hemoglobin electrophoresis was carried out on cellulose acetate by a modification (Lau. L. 5., and Pryor. D. S.. persona.! communication) of the method of Graham and Grunbaum U963); the percentage of haemoglobin A, was measured by elution and the upper limit of normal was taken as 4f. The serum Iron level, total iron binding capacity and percentage saturation of the total iron binding capacity were measured by the method of Kok ar.d Wild (1969). The limits of normality during the third trimester of pregnancy were taken as serum iron, 60 to ISO /ig/100 ml, total iroa binding capacity, 200 to 630 mS/199 ml. with saturation. I4*)e to J07 (Ventura and Kioppcr, 1951). Iron deficiency was diagnosed on the criteria of a hypo chromic blood picture (in the absence of thalasstemla), a high total iron binding capacity, a low serum Iron level, low percentage saturation of the total Iron binding capacity, and absent jr scanty intracellular iron in che bore-marrow; patients were classified as (I) iron deficient, (ii) sidero penic, but with another major causa of antemia. or (Hi) iron sufficient. Similarly, the patients were classified as having (I) folato deficiency as a major cause of anaemia when there was a macrocytic blood picture, more than "r hypcrsegnwntcd polymorphs, low scrum folate activity or Tr.vgaloblastic change in tho bone marrow, (il) folate dellci-.ncy ai a secon 1 try contributory cause cf anamia. when there was another major cau o of ana.mii, but whin there was a!.iO 1" to 0% hyp-.-rs-'imicnced polymorphs, low serum folate activity Or minimal changes In tho bone marrow towards megaloblastosis, and (III) folate sufficiency. 0049-0302 [65] :I ..l'- . JU'fl I 4 u,-li! o;:t.i... a- e.a> AOVA.N inCt'S' Cr VVG_..*,h Ci-07r>ING Si.:- A .-lev -Ip .r. /ini; tv v V p<v.'ii o , tl i,. Y/O 'I 'I n : ..Ufa-V-. i h it . :t d .-:i:., a;.J ti;^ .rt m rs:,,:u [ , ;ir. .'.oi.': . .to 2 ui.v/ .1; .. , <i f 1 1 - it e . i 1 . - . `j. l of o:-i*.v . si t ^ :l'.g :ie * 1 vlr,- n Y h': r-.iut; >_-<f. i & r cot.' ; :'.t. im an.l i.v -.j': t . 1. v*;. 1 n .1.1 '\i ."ti Lnr....-;\ / . \<e ' * - l > - r.i- - : . . -i . no-,i' . v- .Tu \r.V; n. tre 1 . :<h r I.n.v \ .*, ih- c/.e.il l.-ad? ..il ' ' 1 I I u..- - . }:a ; - ine .vt:.-.t .-Lt r.f .r- - :i: tii I tr .-* a .1-r 1:1 oi : r r..a::i-r 0. c:.* I auvc.-.sc.i.vnta .. - c c-.\ :r -1. c. r, ,-jr .>*.1. a . even al.-u'c^ v.vro n. e * rr. . v .u ,P `oitt-t Wv a .`ir*-... :.c her .r .i w.11.1 n a/ .vr. J . ..( r.Mr t.. a v..y r.'r.i... ,-UX: e.ti. . t ai r.^ri'-rer.ce t* Tt.tin <*v . ... w ^ ,'f.. cti-'.i'.eS'-'s `TJ V h... I 1 . v. ncV'.r .v.i.. .-true: a n>'.. n ih.i-.. -> a'.vjro cf ;?.is -- exc *;>t v. . .1 .V.......ps t' ^ W -. :-i> . r-. .''ij].. : e .t *ip t.-.iu- ....1 . &.*!<?.. r. 'it . tvr.: .. 1 ii"G. tvi -ir .v-m,,' ' ..;i ."i- v.x > v. .. v: : Join f> X.-.W t.' M&LVaTiC VAiiJxNiTrilCVCn AGE.W FGfl Trife COf.T.\OU G.- dLiEulXG (\r\iii,_ PSARYi\JO?uASVY v-.t .iv.sS' t. 1 ,vu.>l' ii. * te ; - , ' r, r ,y r < ,< i -i r; .n u:. Ji'. h . n..' il ;iv. 0 v.-i-, i <, .I'-u * ;fc ca..v* ' : -S. .'o ./ .('t ,'-f-r. t.i : ..J .1., 1= r- u-ve.h In :'k ./! . evil \V.I. ..-Ti.-r: ... . .......... O- '.ne v. r..- h pr> >* t-irc.- >. .rs . . i .' It o' ev;.,. ? .p. e, c1. >. . ... f.' -lr\ r.ui; ... ,>m<. `.v. j -vth J 1. .. .v . ... r.. r:. nl - - th , 1^ a} ;'-, r 'I ,.t'<t ij 1. i.i" 1.' tii. - . t. T ..-.0 h.r.k j!,,:, .. .v V..-/. , - I ^ n. hi. t-. l.Kt.t . tn.Id '.c. w,'. -jp .1 - ............ .. .-t h. c ...U <1 .... th . .1 . : th. - .1 > c'-.f-.o .-.fX-' ..er .1 y ' .' , V . . Ia* - . -] Si*.: '..ay 1 '.'or > 1. >>C i>: j.r .>.(.... Mii.lf - i-M-"../-tneti .*. a c- : i->c .'..r. ri.l 1. ' I ii ,'u ... O-i .... .. .1 .`I*. > t' .1 a,- mi. I--.. t> ."C :' 1 .-fii- r ' <i x 1 v*ii.nr. -..t r , : ..;.l .. 'v.'t -I l*i. t p " .. ' .* 1 - .1 ; n.-.'jl . .;t ; . 'jt;. ' .j- n ,. ...` r .. hN ' .o.-'icai f.. 11 v - p.> >) '. *, jn. s ;rn: ;* 1. - J. ; tuU nc i- t .h> . p..it'i r c<' ;n x.>t rver. .. .J. A -.c;. ;h. .1 . r t l:ko t . . u>i a ir.v n-2 w> a V. i.O't : ... \arc-.'.-tn-t.-oi ,t.v. .. anl y*.: tr.e/. arc tom:- v.n *k.l --c l-yp'H.n*.vi d.-v,. du.lr-- ai. a xfithet.o '.-'r e\.r. iUVv'.`/ rntc.or . p.~.iC> wure 1. r-G.`: s a j.n.ution Y. xhrcu r,; . t. i. I> a r. im-' ci :/v ooeon- r. .; .r '.hiea fiit.tiai.-r tin v'-ievic u 'a.I* j i r .. aru ocn - 01, r.-;'- r..< r. . e. 0; ... >> t ;' e 1: >t m t c uv. . 1. .:. ,.'ii vi . Cxi a* '!;!'..> I.i.-., '1.>' ..ti.'-it- `At-.-, tr. . m .iir.it i-.'.- -r. :h.; c 1: -I. ` .<< ' - ` i k' . ! . ' ^ . . .1. :..i.. - .J ..v > iWv 0049-0303