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FILE NAME State of the Art Literature SAL DATE 1953 July DOC SAL056 DOCUMENT DESCRIPTION Journal Article - The Prevention of the Dust Diseases  THE LANCET ORIGINAL ARTICLES JULY 11 1953 THE PREVENTION OF THE DUST ~" DISEASES In 1912 an excellent translation of this book was made by Herbert Hoover a mining engineer and his wife This was the same Herbert Hoover who later became President A. L. G. McLaughlin M.D. Sydney F.R.C.P. E.M. MEDICAL INSPECTOR OF FACTORIES Sir Malcolm Morris who was on the staff of St. Mary's Hospital for over 20 years was a pioneer in public health as well as being a great dermatologist In the galaxy of great names for which the hospital is notable he holda high place and his contributions both to dermatology and publio health are of enduring value It is common knowledge that dermatitis causes more cases of ill bealth and lost time in industry than any of the other diseases of occupation But it can be said that the diseases of the lungs caused by dust are more dangerous than the industrial dermatoses The pneumoconioses often cause death whereas skin lesions though they are disabling are rarely fatal Again the lung diseases caused by dust are harder to diagnose and in the early stages at least they give no outward sign of the pathological process going on inside the chest A disease of the skin has this advantage that it can be seen even by the novice as soon as it appears But the pneumoconioses come on like a thief in the night or rather like a thief who plies his trade for days nights and years before he is finally caught And by that time the damage is done It is like closing the stable door after the horse stolen In trying to prevent the dust diseases we aim to close the door while the horse is still in the stable or while the man is still in good health An in td his discourse I shall describe some of the ways in which we are trying to close the door of the United States But the outstanding name among the early doctors was Bernardino Ramazzini an Italian who in 1700 published the first textbook De Morbis Artificum on occupational diseases based on hand observations of varied occupations and the maladies which arise from them Ramazzini in justly called the father of occupa tional medicine and it was he who taught that when seeing a patient for the first time one should not only ask him where his pain is but what his job is Even today there are doctors who do not get details of their patients occupations Ramazzini quotes the account of the necropsies carried out in 1649 by Diemerbroeck on atonecutters in whose lungs he found such heaps of sand vesicles that in running the knife through the pulmonary he thought he was outting some sandy body This is the first account of the pathology of silicosis as it is now called In spite of this the earlier doctors confused the dust fibroses of the lungs with tuberculosis But we have to bear in mind that the tubercle bacillus was not dia covered until 1882 and that the study of pathology was century not put on a firm basis until the early part of the 19th . As a point of historical intereat it might be added that Sir Malcolm Morris was present at the first demonstration of the tubercle bacillus in Koch's laboratory in Berlin in 1882 Lancet 1924 The 19th century was notable for the rise of the idea that inhalation of large quantities of dust of any kind can damage the lungs but that some dusts are more harmful than others It was our first great English writer on the occupational diseases who emphasised this He was Charles Turner Thackrah a doctor in Leeds who in * Historical 1831 published his book on the Effects of Arts Trades and Professions The title goes on and of civio states and Before dealing with the prevention of the pneumo- conioses I ought to say something about them For in order to prevent a disease it is obvious that one must first know that it exists and the causes of it To us in the 20th century it may seem strange that at any time it was not known that dust when inhaled into habits of living on health and longevity with suggestions for the removal of many of the agents which produce and disease shorten the duration of life He noted that bricklayers and limeworkers were lived and that sandstone masons usually died before they reached the age of 40. But he was not quite clear in his mind how the lungs could damage them But it took a long time before this fact was established and though the history of the pneumoconioses goes back as far as Hippocrates about 400 B.C. and perhaps earlier they were not Ramazzini's motto was Medici munus plebeios curantis est interrogare quaa artes exerceant TABLE DUST DISEASES OF THE LUNGS charted with accuracy until about 30 years ago Even ) Roundwaf 6 radiologist 1. Manchest pathologist : anesthetist Hospital Hospital ural surgeon now there is a great deal to be learned about them Progress in knowledge is usually associated with great namea but one should not forget those workers who inade no great splash in history The building of knowledge has been likened to a coral island into the formation of which go the lives of many individual - organisms So it is with our knowledge of the occupational . One of the great names in occupational medicine after Hippocrates was Paracelsus also called Bombast He in 1530 published a book on industrial diseases in which he described the chronic lung diseases of miners as pulmonary consumption and asthma He thought that these diseases were due mainly to the influence of the antral bodies but he added that the climate of the mines might have something to do with them I daresay that in writing about the climate he included dust as one of the possible causes but he did not say so The next great name was Georgius Agricola who in a book called De Re Metallica 1558 said that the inhalation of corrosive dusts a worker to a disease predisposed characterised by exhaustion coughing and that difficulty of breathing which the Greeks called asthma Diseasca Dust or fume 1. Chronic Abroses | Silica Asbestos Coal Talc Bauxite and corundum Beryllium Varisties Siliconia Asbestosis Coal pneumoconiosis Talo preumoconiosis Shaver's disease Beryllium granulomatovia granulomatovia 2. Acute pneumon- || itia demaand Manganese 1 Beryllinm or bronchiolitis Cadmium Vanadium ; their oxidenoxiden Manganese pneumonia Beryllium pneumon itis & Bagasso sugar | Bagnasosia 3. Asthma Wood e.g. Western red cedar Seeds Grain Feathers Wool Double salta of Qum platinum 4. Cancer Arsenic Chromates Nickel carbonyl ) Anbestos Hadioactive emanatioDS ' orthoparorthdopard of hospitas * Based on the Malcolm Morris memorial lecture given under the auspices of the Chadwick Trust at St. Mary's Hospital 5. Chronic bronchitis Cotton -- and emphysema bronchitis Flax and other dusta --... ---- London on Dec. 9 1952 . 8 8770 so we _ Ah pen o.6@ a ra od rr eagtr oe on Pm ie 4s Hy Pa "Boe at tba >a |j : 4! ee ore: 4, e ane ame We * oe gy. Ome tae eS aes . re ee emt iy is ey at pe! ges (ideh ared? a Sw, Lase ee ee a -? < - wi (as rile ete: ' F { 50 THE LANCET ORIGINAL same much the taking of alcohol had to do with these pulmon- ary diseases He was against alcohol in the way that President Coolidge was against sin and no doubt he had good reason to be because it was quite cheap in those days Two other great English names in the history of the pneumoconioses are T. B. Peacock and E. H. Greenhow Peacock a physician on the staff of St. Thomas's Hospital first established between 1860 and 1866 the existence of miners disease as an entity and distinguished it clinically from pulmonary tuberculosis Greenhow 1860 1881 who was attached to the Middlesex Hospital carried out the first large field investigation into the dusty industries such as the potteries metal trades cutlery making tin and copper mining mining lead mining cotton flax silk and woollen manufacture hosiery and lace making making and agriculture In the Transactions of the Pathological Society of London 1860 6a6re to be found excellent clinical and pathological descriptions by both these doctors of the disease which was later to be called silicosis by Visconti in 1870. They even found the dust of free silica in the lungs and examined it under polarised light . ; For about 40 years after this excellent work nothing much was done about the dust diseases But with the turn of the century a new interest began to be taken in - / = Fig Dust of quarts or free silica showing ^ 450 crystalline structure in the problem not only in this country but also in other parts of the world It is significant that about the same time there was a quickening of the tempo of life general The horse began to give way to the motor and soon there came the first aeroplane Then too there was the telegraph and the telephone and all those comforta of present life which give us little or no time to think In the factories and in the mines there was a speeding of output Hand labour began to be replaced by the machine ^ nthe cotton industry the change had come a little earlier But the hammer or the pneumatic tool began to be used more extensively in the early part of the century for such jobs as mining quarrying and the cleaning of castings in foundries There is also the spray gun which is used to spray paint glazes metals and asbestos and was introduced with the idea of speeding up the work This from a health point of view very is a dangerous instrument because it is difficult to control the spray and to prevent its inhalation by the workers If there is one thing certain about increased speed of dusty process production in industry it is that a will become more dusty and that there will be a greater incidence of the dust diseases if attention is not given at the same time to increased control of dust But quite ARTICLES ness A 4 JULY 11 1053 1e-~ egos _ ee ees. oe . Ae T1 \ . we + Fig Quartz crystals and aggregatos of iron ezida fame large black areas in a foundry dust cloed { ^ 1800 chest the al inadequate often the efforts at dust control are inadequate and do not o not keep pace with the increased speed of production For instance silicosis and tuberculosis did not become a problem in h^matitemining until the intro- of duction the pneumatic drill Stewart and Faulds 1934 say that h^matitemining has been carried on in The shown Cumberland since the time of the Roman occupation It was formerly considered a healthy trade but & evidence is accumulating to show that in this respect a definite change for the worse has taken place The miners themselves believe that the trouble started with the fj introduction of the dry mechanical drill in 1913. Previously the ore had been obtained by the old hammer and jumper method : Meiklejohn 1951 1952a and b in his history of lung & diseases of coalminers in Great Britain points out that mechanical cutting and conveying of coal was introduced j present early in the cutting of coal led to century The change an increased dustiness from handof the air in the mines not only at the coal face but & generally through- 8 out the workings He quotes H.M. Chief Inspector of Mines Bryan 1950 as saying There is no doubt that F one result of the adoption of many of the present methods of machine mining is that the production of dust in mines has increased in recent years and is still increasing If we are to get rid of the scourge of pneumoconiosis . this process must be reversed McCallum 1952 also + thinks that mechanised getting has increased the prevalence of pneumoconiosis in the Durham coalfield and that future developments in the coalfield will intensify dust production and the risks of pneumoconio sis unless dust suppression methods are considerably extended considerably - . FR : PUR, af [& GaRae nes ; ; ees . rath EAL eS ats Dy we ea 5 ree MO sk ee pulmont ! rege definet SEGRE this cou ; LN 8 To kleselguhr form of free silica x kleselgkluesehlgruhr & crystalllarcrystalllar OO Tar . The use of the pneumatic tool instead of hand methods 7 fettling of steel castings has also increased the o for the silicosis this occupation McLaughlin et al ) 1950 a. Dust and Dust Diseaser It is commonly thought that the dust diseases are ; pained to a small group of fibroses of the lung caused painedthe inhalation of inorganic dusts such as silica st by bestos and coal That this is not so was clearly shown 7 ma S| : Collis in his Milroy lectures in 1915. He pointed out by an excessive mortality from all respiratory diseases was axperienced by dwellers in dusty atmospheres an which increases with age and with the amount of er op. Na a aa a: present In London at that time 660 tons of dust ultural came down over a square mile whereas in an agri district it was 195 tons & figure which is big nough in all conscience It is interesting to note also thatthe inorganic content of the lungs which largely from inhaled dust also increases with age Radio- * large blog 3 sometimes have difficulty in distinguishing in ngoitsts not deposits best films the shadows thrown by dust deposits from d abnormal shadows seen in films of old people It does te and de often occur to them that the changes associated with duction ss might in fact be partly or even mainly caused by is did : deposits in the lungs disease A The pulmonary disease caused by dust are the Fauld types of .nd Fauld rried on in in shown table . ccupation "et . ; am coalfiel ie Guest of tale or French chalk composed of plates and a small coalfiel Toalfield will propor of t fibireo s ^n 1960 It will be seen that these diseases fall into five broad pe chronio fibrosis acute pneumonia demaand a Chiolitis asthma cancer and chronic bronchitis Wend emphysema There is also a sixth group which hardly uy under the heading of namely the es Dermal ray appearances seen in those workers who Eeeve been inhaling the opaque dusts such as iron emery szides siderosis barium baritosis tin stannosis emery Such cases usually present an abnormal Emy picture without clinical evidence of disease or bility Even these six groups do not complete the bat it will be enough to show that a wide range of diseases can be caused by the inhalation of which may be both organic and inorganic It be remembered too that dusts can convey such as anthrax and tuberculosis and indeed anthrax sorters disease is a well- occupational malady now fortunately rare in m8 country . country Dusts and Fumes 8 ey. c understand the dust diseases it is necessary to know Oe eeneen deal about the chemical and physical properties y caeaners dee sts and fumes the behaviour of dust clouds and action between them and the tissues of the respira Pe ey tnt Intensive research during the past 30 years a i J yl xh salat Fig Oust cloud from asbestos boarding showing asbestos fibrus and amorphous cement duet ^ 150 * has given us a great deal of information on these matters and a few points may be mentioned here Both dusta and fumes are composed of particles which when airborne can be inhaled into the lungs Dusts which may be organic and inorganic or animal vegetable and mineral are mechanically formed by vigorous action such as grinding rubbing crushing drilling hammering and sawing and in general are of the same chemical composition as the substances from which they come Fumes the term is often used incorrectly are the result of condensation of particles from the gaseous state and in industry are usually the oxides formed from hot or boiling metals Iron oxide for instance when it comes hot off the welding arc is a fume but when it is in the form of rust knocked off an iron girder it is a dust In a dust cloud fig 1 the particles remain separate but in a fume they tend to flocculate and form large masses composed of very small particles It has been shown that most of the particles of dust or fume which get into the lung tissue are about 3 or less in diameter and it is often assumed that anything larger cannot get into the alveoli But these structures measure up to 100 across and there seems to be no reason why particles much larger than 3 cannot get into them The factor which determines the size of dust particles found in the lungs is the diameter of the lymphatic channels through which they are taken by phagocytes It is true however that many of the larger particles are trapped in the nose and the upper respiratory passages Gane, BAe 1 . =, wee = 3 Varraw + Fig Leather dust composed mainly of striped ^ 240 muscle mt wh.ren- wt 2"BCE 8 ale - e meefC: mm come i we cn be pyaty ene Ser twa ODtna 0h CSR Pits rm set ne Sem parte 4% * nate. na + ee gt tT pater eye 4 byby wha SSMS Soke PE R, TanTe pont beak = RS AkaOM | a | ost or | eT t a 52 THE LANCET ORIGINAL ARTICLES JULY 11 1953 TABLE DEATH FROM ALL Types of pneumOCONIOSIS IN England and wALES 1940 51 Industry 1040 | 1841 | Potteries .. 00 Sandstone metals 6. wd metals 3 109 45 82 | Grinding of metals & |: att 26 Refractories oe Miscellaneona os Cosimining rr Other mining . Asbestos : Cotton byselnosis os 18 o- T ottf 232 61 re 12 5 196 40 1 7 oe occupational 533 423 | 850 | 481 | 1942 41 54 26 7 ? 130 4a | 11 434 443 | 1943 41 21 7 5 276 43 8 ? 485 493 | 1944 32 24 6 13 | 311 39 10 1 493 531 | 1945 | 1948 | 1947 | 1948 | 1949 | 3950 | 1951 Totala 64 49 18 63 73 63 608 65 {| | 81 55 88 81 29 Tl 779 | 22 33 21 26 37 22 21 325 8 10 13 13 & 117 | | | | | | | | 19 387 40 14 421 61 26 877 50 27 639 48 25 756 84 70 848 42 129 937 81 347 5808 679 11 16 15 15 17 38 14 361 10 3 8 INGSK47 11 8 65 604 855 818 893 1033 1113 1305 3789 529 568 | 610 | 851 | 554 | 879 | 732 | 8907 Each dust cloud has its own characteristic under the microscope appearance In fig 1 is shown the dust of quartz or free silica which It is composed of small crystals remain separate in the dust cloud By contrast the appearance of iron oxide fume is shown in fig 2. The large black masses are made up of hundreds of small particles Fig 3 shows the microscopic appearances of kieselguhr or diatomite a crystalline form of free silica Fig 4 shows the dust of tale or Freach chalk which is composed of plates and a few fibres while in fig 5 asbestos dust is seen to be made up mainly of fibres Leather dust is shown in fig 6 to be made up of non- striped muscle ; wood dust fig 7 has characteristic transverse striations The Body's Defence Mechanisms Against Dust If a man's lungs are healthy they can deal with a good deal of dust or fume without becoming damaged The body's defence mechanisms against dust are briefly a the vibriss^of the nose which act as a partial filter for the larger particles ; b the mucous secretions of the nose and the upper respiratory passages in which a large proportion of the particles is trapped and then expelled by c the wave action of the cilia of the nasal and bronchial epithelium Below the respiratory bronchioles where there are no cilia d the phagocytes come into play They engulf the dust particles and take them up.to the area of ciliary action or into the lung lymphatics Recent work has cast doubt on the hypo- thesis that dust is taken into the lung parenchyma by phagocytic action but the fact remains that dust does get into the lungs whatever may be the exact method of locomotion The concentration of dust which can be inhaled without danger varies according to the nature of the dust and also to the length of time that a man is breathing it Again the intermittent exposure to high concentrations of dust may be more dangerous than exposure to lower concen trations over a longer period The harder the job is the more deeply will a man have to breathe and in conse quence he will breathe more dust Individuals too vary greatly in their capacity to deal with dusts and of two men who have been working at the same job for the same length of time one may get a disease of the lung and the other may be unaffected This is one reason why I am not greatly impressed by the validity of what are known as the maximum allowable concentrations of dusts M.A.C. of which lists have been drawn up in various countries The M.A.C.s seem to be based on the assumption that man is a standardised machine which clearly he is not The reasons for the differences in individual reaction to dust are not accurately known but it is likely that they depend on anatomical physiological and biochemical variations from one person to another It MINING SILICOSIS & PNEUMOCONIOSIS 1946 1947 1949 1951 1940 1941 1943 1944 1946 1947 1948 1949 1950 1951 237 187 FACTORY PROCESSES 157 143 sO : re 317 92 192 184 207 214 225 it 61 1945 os & 1949 1950 1941 0 & BY 1945 COC AR wD 1949 1961 vr i 1961 1941 61 1941 -_= - ~ 1949 1961 1945 -_ - -= 1949 1950 1961 showing trends Fig Chart of deaths from fibrosis of the lungs in coalminers and factory workers during the period 1948-31 inclusive Fig Dust of wood ^ 300 is known however that previous damage to the lungs i a factor which leads to the retention of dust in them In any case there are instances where people have spent long years in the dusty trades and have died from cauBE other than the dust diseases On the other hand many thousands have died as a direct result of the inhalation of dust . : The Size of the Problem . How many deaths have occurred from the dust in diseases Our information is incomplete many respects but table 1 gives at least some idea of the size of the problem It is based on figures supplied to the Factory Department by the Registrar and it shown the number of deaths from fibrosis of the lung from 1940 to 1951 inclusivo In all industries there were 8789 deaths from tional fibrosis of the lung in the year period occupa and it will be seen that the total yearly figures are going up Over the same period there were 8907 deaths from nop- NVA Fem fede SEER ORC AE RS AS Aa . RGOR hares, Seater a Rae Sedilt iettonese= yee Se Noe : RAF y a pow abPec ; re Ee ee Mi OGs Se Pars crear ig: Sa JULY 11 1953 q F 5 om E fe... : al 10 ' 199 | 937 | 18 8 wy Totals | 2 608 j 7 779 w 395 | 347 q my 5808 308 161 sf 65 SB 1305 . 732 ' 8789 | : |8907* 7 Oe aluals too vary ists and of two THE LANCET ; ORIGINAL occupational fibrosis of the lung It should be that the deaths occurring each year in the emphasised group are the result of conditions which oocbctuapianteidonainl industry some years previously possibly 10-20 aven longer About thirds of the total years or Maths occurred in coalminers and the number of = aceply from 232 in 1940 to 937 in 1951. figures It is rose part of the increase is due to likely that At least to more accurate diagnosis or in the greater interest pneumoconiosis problem ongst coalminers In fig 8 is shown a sed on the crude figures from table 11 betweencodmepaartishosn :: coalminers and factory workers In factory processes yearly number of deaths was going down until 1943 a it there has been slight rise in the later years To be concluded ARTICLES JULY 11 1953 53 incubation by estimation of turbidity in the medium and the amount of folic acid in the urine may easily be calculated difficulties has The test has many but when it been successfully initiated it is satisfactory giving reproducible results Iffurther work confirms the value of the folic excretion test the diagnosis of sprue instances should at least in some be easier rendered in that special diet is not required and specimens of urine can be sent for assay from other to hospitals laboratories in which folic tests are being done It is not yet possible to say whether a positive balance test may be associated with a negative folic excretion test in the malabsorption syndrome No cases of for chronic pancreatic disease have been available study me job for the Serany ase of the lung one reason why ity of what are ncentrations of B 1 drawn up in e based on the frene machine which rene SRE differences in ely known but 1. physiological Me to another It ee GR by -9 i] Py a: i 317 i] i to the lungs is ff in them In de have spent from causes ran er hand many the inhalation Peay i n the dust many respects size of the " the Factory . it shows the tre1940 to la . { . cupa ing Over 15 from noti A FOLIC EXCRETION TEST IN THE INVESTIGATION OF INTESTINAL MALABSORPTION RONALD H. GIRDWOOD M.B. Ph.D. Edin F.R.C.P.E. M.R.C.P. .NIOR LECTURER IN MEDICINE IN THE UNIVERSITY OF EDINBURGH 1.- 1850 Manson having anglicised a similar Dutch 1. described sprue as a disease occurring in the ies or subtropics or among persons who had . Jed in warm climates ; the disease was chaprraecvtieroiusseldy Lossitis and stomatitis by the passage of pale copious +fermenting stools and by flatulence wasting and mia The phrase " the sprue syndrome has been ~ in recent years to include the features found in pathic steatorrhea of tropical origin and in pic disease ; since the introduction of the balance ">of Cooke et al 1946 it has been extended to include as where there is inegaloblastic an^miaand deficient corption of fat but little other clinical evidence of estinal malabsorption and the terin " #irome has come into use malabsorption given 1 the diagnosis of sprue the balance test is most ail but it suffers from the fact that the patient has + oe in a hospital where a suitable dict can be at all the food given must be consumed or necessary corrections made and that the stools must be collected Rfoorspisteavlerwalarddasys always a difficult matter in general It has usually been considered rather surprising that enegaloblastic enegaloblastic an^miaof sprue can be treated with olic acid administered by mouth The seeming paradox of successfully treating a condition believed to be due to malabsorption of h^mopoietic factors by giving these site substances orally has led to the hypothesis that the fault in sprue is malabsorption of naturally occurring acid conjugates rather than of folic acid itself In some instances it appears that there is malabsorption of vitamin B1 since therapy with parenterally adminis- tered vitamin B has been effective in a few patients The present investigation indicates that there is in fart considerable deficiener of absorption of folic acid in sprue and that advantage can be taken of this to devise 4. Test of folic absorption and excretion for the iiagnosis of malabsorption by the small intestine The estimation of the acid content of the urine other fluids is usually done microbiologically The growth of a certain strain of a streptococcus or Lactobacillus in a suitable medium depends on the Aloitit of folic acid present in that medium Thus it is possible to set up tubes containing the medium theasured with the amounts of folic acid and others containing medium with various dilutions of urine In both sets of tubes the amount of growth depends on the concentration of folic acid The amount of growth is measured electrically after a suitable period of * METHODS AND MATERIALS The folic acid used in these tests whether it was given by injection ' or by mouth was derived from ampoules of Folvite Lederle Laboratories Ltd. The amponies were taken from batches tested by us and found to contain lmg of folic acid per ml Certain batches were rejected because their content proved to be higher than that stated on the label Most of the ampoules were in fact taken from one batch supplied by Dr. A. T. Mennie of Lederle Laboratories Ltd. London In any one patient the same batch was used for all the tests On two occasions where the intention was to load the tissues by large doses cases 33 and 37 table hospital stock ampoules were used 11 The dose was accurately measured in a tuberculin syringe For tests of excretion following oral therapy this test dose was diluted with a small quantity of water hour collections of urine were made in brown bottles containing toluene and a phosphate buffer of pH 6.8 The greatest possible care was taken to ensure that the urines were total hour specimens Recovery experi- ments in which folic acid was added to urine completely satisfactory results The urines were keptgi avne refrigerator at C and readings were usually made within 3 days All the readings were made at least in duplicate Folic acid was estimated by the method of Teply and tEhlevethejstemor1g9an4i5smStrTehpteoctouccbuess f^calis R being used as for about 16 hours and readingswweerree imnacdubeatbeyd at 37 turbidity estimations in a Spekker electric absorptiometer No correction need be made for the resting urinary content of folic acid since in ten normal persons the mean urinary folic content corrected for citrovorum factor was only 1-7 grange 0-12-3-6 gper 24 hours Urinary citrovorum factor was estimated in instances since citrovorum factor is also most for Strep f^calisthe organism used in a the growth factor Citrovorum factor folic assay was estimated by a modification of the method of Sauberlich and Baumann Leuconostoc citrovorum as the test 1948 with turbidity readings were made afteorrginacnuibsamtioHn earte 3to7o for about 16 hours The mean resting urinary content of citrovorum factor in ten normal persons was 0.84 range negligible amount gper 24 hours g No correction has been made for this in factor readings which are included the citrovorum- interest only for biochemical It will be seen that a sinall administered in these proportion of the folic acid investigations was excreted citrovorum factor or as a substance with similar as biological properties but the micro excretion have figures given for folic not been corrected for this because such a correction would in no way alter the Several of the patients were in conclusions districts where it hospitals in outlying . was impossible to make as full investigations as would have been preferred In it was some instances necessary to collect the urine at the homes ; patients _ re ee es teae wet ave oe) eel eaten on Wop 2. be rt