888

contamination with carcinogens cannot be entirelyexcluded in any surroundings where they have beenused, so readily do they become dispersed. Merecontamination was, however, an unlikely explanationof the malignant change in untreated cultures ; forprecautions were taken to avoid it, and FIROR andGEY 3 found, by chance, a similar transformation inthe course of experiments requiring continuous cultureof rat mesenchyme. This occurred in a laboratoryinto which no chemical carcinogen had knowinglybeen introduced. These workers also noticed altered

appearances which led them to suspect malignantconversion. On inoculation into rats malignanttumours developed. In this case stray gamma radia-tion due to storage in the laboratory, at the time ofearly cultivations, of 50 mg. of well-shielded radiumhad to be considered as the effective cause of the

change. On measuring the radiation in the regionof the roller-tube drum about 1/20 rontgen per daywas detected ; this applied to two out of threeinstances of malignant change but not to the third andpossibly more.

Yet another example of malignant change in vitro,associated this time neither with chance nor withknown carcinogen but with a deliberate attempt byother means, has now been reported by GOLDBLATTand CAMERON 4 in two cultures derived from 5-day-oldrat heart. The means used to effect the change wereintermittent deprivation of air and the substitutionof nitrogen during prolonged propagation. Work wasbegun by GOLDBLATT in 1930 on a theoretical basisderived from WARBURG’S studies of metabolism ofvarious normal and malignant tissues in vitro. Thiswork was abandoned and could not again be resumeduntil 1949, when GOLDBLATT and CAMERON started totest the idea that because surviving or temporarilygrowing tumour cells characteristically use the

glycolytic mechanism as a source of energy, theenforcement of this mechanism on growing normalcells might impose the malignant conversion. It now

appears that intermittent exposure to anaerobic con-ditions, with replacement of air by nitrogen in theculture-tubes, has twice, short of killing the cells,brought about, or been attended by, eventual malig-nant change. Five cultures of myocardium so treateddied or were discarded on account of poor growth.A sixth culture was divided, and from it three sub-strains were grown. One line of cells was propagatedin the usual way and never exposed to nitrogen. It

eventually developed into a strain of pure fibroblastswhich served as controls throughout the experiments.Its progeny underwent no further unusual morpho-logical variation and did not give rise to tumours oninoculation into rats ; the other two strains were

deprived of air and exposed to nitrogen intermittently,the second being derived from the control subcultureone year later than the first. The cells of both developedstriking morphological alterations in about a yearand, after several unsuccessful attempts, gave riseon inoculation, using a special device, to seriallytransplantable fibrosarcomas. The special device,due to a technique used by H. S. N. GREENE, was theinclusion with the test inoculum of a small fragmentof embryo rat lung from the same rat strain. Sub-

3. Firor, W. M., Gey, G. O. Ann. Surg. 1945, 121, 700. Gey, G. O.,Gey, M. K., Firor, W. M., Self, W. O. Acta Un. int. Cancr.1949, 6, 706.

4. Goldblatt, H., Cameron, G. J. exp. Med. 1953, 97, 525.

cutaneous nodules then became visible and palpablein 3 or 4 days and grew progressively and in serialtransplants.GOLDBLATT and CAMERON suggest, but do not

claim to have proved, a causal relationship betweenintermittent anaerobiosis and malignant conversion.They recognise the difficulty of reconciling their

findings after deliberate intervention with the appar-ently spontaneous transformations of EARLE and ofGEY and his associates. They think that in factGEY’S cultures may often have been exposed inad-vertently to oxygen lack under the experimentalconditions used. Some morphological and biologicalobservations by LUDFORD and BARLOW 5 on culturesof mammary carcinomas of mice under ordinaryconditions must also be taken into account. Theseobservations suggested-though they never finallyproved-that accompanying connective-tissue cells hadundergone sarcomatous transformation. Only furtherwork undertaken to test whether results are repeatablesufficiently often to be relied on and duly controlledwill settle the relation of anaerobiosis to malignantconversion. As in the natural history of malignantdisease, time again appears to play a ruling part.Perhaps epithelium and cells from animals other thanrats will now be tested by the same methods. Malig-nant change is notoriously easily induced in ratconnective tissues, but this does not detract from thevalue of these stimulating experiments.

5. Ludford, R. J., Barlow, H. Cancer Res. 1945, 5, 257.

Puerperal MastitisUNTIL recently interest in the painful condition of

puerperal mastitis was directed more towards treat-ment than towards prevention. Typically mastitisand breast abscess develops rather late in the puer-perium-most commonly in the third and fourthweeks. Thus obstetricians and midwives, whether

they work in or outside hospital, do not see nearly allthe instances of this complication ; it is the surgeonand the paediatrician who are continually remindedof it.

Careful observation has shown that mastitis is closelyassociated with early breast engorgement and feedingdifficulties due to abraded or cracked nipples. Wherelactation starts by sudden engorgement, the nipplesbecome oedematous and thus especially liable to

damage. This liability is further increased because.the baby, unable to get the areola in his mouth,munches the nipple ; and once damaged the nippleis open to infection. Only about 30% of women are sofortunately fashioned that their nipples protract welland there is no obstruction to the outflow of breastsecretion in the later months of pregnancy, or of milkafter delivery. In such cases the baby takes thenipple well into his mouth ; his gums are applied tothe areola, and milk squirts almost effortlessly downhis throat; there is little or no engorgement; andthere is a minimum of friction of, or of danger ofdamage to, the delicate epithelium of the nipple sinceno force is applied to it. The majority of women,however, need help and instruction, not only to

remedy nipple defects antenatally, but also so thatthey may learn in good time how to express secretionin the later months of pregnancy and clear the wayfor the free flow of milk after delivery. Anatomical

889

faults, however small, must first be corrected. Muchcan be achieved even where the nipple is at first soretracted that correction seems well-nigh impossible ;the nipple shields designed by WALLER 1 for wearingduring the antenatal period are effective even whenthere is a severe anatomical fault. In the later weeksof pregnancy the daily manual expression of colostrumseems a reasonable practice, to prepare the breastsfor lactation and to keep open, and even to open up,the milk ducts. Women taught to do this can helpthemselves when engorgement threatens ; this reducespressure on the midwifery staff, who then have moretime for cases of serious engorgement. Furthermore,lactation will have a better start before the motherleaves hospital ; and so she will be very much more

likely to continue breast-feeding at home, and to findit satisfactory. Satisfactory lactation cannot be saidto be fully established until the nursing or draughtreflex is fully conditioned, and in the young primiparathis reflex may take a month or so to become estab-lished ; its inhibition or delay by pain and engorge-ment needs to be more generally recognised. Whenengorgement is severe, the breasts should be well

supported and feeding temporarily stopped ; stil-boestrol in doses of 5-20 mg. helps in the control andprobably does not inhibit lactation, though it maydelay it temporarily. In less severe cases gentleexpression of the breasts relieves the fullness andengorgement, especially around the areola, and soallows the baby to get the nipple well into his mouthand suckle normally. Pain on suckling is a bar to

nursing until the nipples are healed.No less important than antenatal preparation for

lactation is a careful aseptic technique in the lying-inperiod;- and infection, where it does set in, should betreated at once with penicillin or aureomycin, beforeit has passed beyond the stage of cellulitis.2 3 The

organism most often responsible for mastitis is Staphy-lococcu8 aureus,4 though others are sometimes foundalone or in conjunction with it. Mastitis is favoured

by stay in hospital ; and when the carrier-rate ’for

staphylococci among the hospital staff or visitorsreaches a certain level, epidemic outbreaks of mastitisare likely to ensue unless very strict precautions aretaken. Opinion on the mode of infection has varied ;sometimes the baby has been regarded as the mainagent, and sometimes the environment and hospitalpersonnel. In Germany during the late war it wasthought that forcible stripping of the breasts occasion-ally caused trauma and that infection could takeplace with organisms circulating in the blood.5 Itseems certain that milk stasis promotes themultiplication of any infecting organism that maybe about.6 7

A low incidence of mastitis goes hand in hand withsuccessful breast-feeding ; and for this reason, if forno other, everything possible should be done to increasethe proportion of women who successfully suckle theiryoung. Further progress in the prevention of mastitiscalls for close cooperation between the antenatal,lying-in, and- postnatal services.1. Waller, H. Lancet, 1950, i, 53.2. Lepage, F., Granjon, A., Culioli, R. Bull. Ass. Gynéc. Lang.

franç, 1950, 2, 564.3. Isbister, C. Med. J. Aust. 1952, ii, 801.4. Rountree, P. M., Barbour, R. G. H. Ibid, 1950, i, 525.5. Umland, K. Zbl. Gynäk. 1951, 73, 294.6. Walsh, A. Lancet, 1949, ii, 635.7. Newton, M., Newton, N. R. Amer. J. Obstet. Gynec. 1951,

61, 664.

Annotations

MAPS AND MEDICINE

IT was a map drawn by his young stepson that stimu-lated Robert Louis Stevenson to write Treasure Island.Looking at maps can revive memories of past holidaysand work-places and raise hopes of traveller’s joys tocome. There may therefore be pleasant associations atthe back of one’s mind when thinking about the use ofmaps in medicine.The spot map which John Snow drew of cholera cases

in 1854 showed how they were concentrated round theBroad Street pump in Soho. His investigation isrecounted, and his map reproduced in the new editionof Rosenau’s Preventive Medicine and Hygiene.1 By usingSnow’s work on cholera as a model for teaching studentsthe Baltimore School of Epidemiology has honoured hisachievement, as did Underwood 2 in this country. Spotmaps are used routinely in the investigation of epidemics.Recent examples of their use in poliomyelitis,3-5 infectivehepatitis,6 and influenza show how they can reveal ageographical spread and draw attention to the " oddcases out " which often repay close investigation byproviding clues about the mode of spread of infection.Moving, to borrow a phrase from Prof. John Gordon,from " parish pump epidemics " to the study of pan-demics over " several centuries and across the seven

seas," there are maps of the distribution of poliomyelitis 8which show that these can summarise the enormousnumber of data in the records of national and inter-national health organisations.A further stimulus to the use of maps in medicine is

provided by the Climatological Atlas of the British Isles.9The maps in it are models of clarity and set out vividlythe information collected over many years by manyobservers, a large proportion of whom are amateurs.The amount of detail will surprise those who do not knowmuch meteorology. Thirty-year averages of daily means,maxima, and minima for the year and for each monthare mapped for barometric pressure, temperature, rain-fall, humidity, and sunshine. There are also data about

daily variations of temperature, about wind and snow andfrost, and about record rainfalls and droughts. Materialsare here for testing any hunches doctors may have aboutthe effects of the weather on their patients and also forstudies of the sort proposed by Dr. Jacques M. Mayunder the title of Medical Geography.1O ° The necessarymedical data are in the reports of the Registrar-General

and of medical officers of health and in recent studies bythe Social Survey, by regional hospital boards, and bygeneral practitioners. There is here a vast field for studieswhich would be in the lineage of Airs, -9’-aters and Placesand Historical and Geographical Pathology. Recent

papers on the influence of absolute humidity on respira-tory infections il and on the relation of variations in

temperature and humidity to epidemics of polio-myelitis 12 13 encourage the belief that valuable resultswould accrue.The study of interregional and international variations

in the incidence of disease and death has been extended1. Rosenau’s Preventive Medicine and Hygiene. Edited by

K. F. Maxcy. New York, 1952.2. Underwood, E. A. Proc. R. Soc. Med. 1948, 41, 165.3. MeFarlan, A. M., Dick, G. W. A., Seddon, H. J. Quart. J. Med.

1946, 15, 183.4. Sweetnam, W. P. Brit. med. J. 1948, i, 1172.5. Daley, A., Benjamin, B. Med. Offr, 1948, 80, 171.6. MacCallum, F. O., McFarlan, A. M., Miles, J. A. R., Pollock,

M. R., Wilson, C. Infective Hepatitis. Spec. Rep. Ser. med.Res. Coun., Lond. no. 273. H.M. Stationery Office, 1951.

7. Anderson, T., Grist, N. R., Landsman, J. B., Laidlaw, S. I. A.,Weir, I. B. L. Brit. med. J. Jan. 3, 1953, p. 7.

8. May, J. M. Geogr. Rev. 1950, 40, 646.9. Meteorological Office : Climatological Atlas of the British Isles.

H.M. Stationery Office, 1952. Pp. 139. 52s. 6d.10. May, J. M. Geogr. Rev. 1950, 40, 9.11. Waddy, B. B. Lancet, 1952, ii, 674.12. Armstrong, C. Amer. J. publ. Hlth, 1951, 41, 1231.13. Bradley, W. H., Richmond, A. E. Monthly Bull. Minist. Hlth

Lab. Serv. 1953, 12, 2.