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clearly defined conditions part of the wave front tendsto become unstable. This causes a turbulent motionof the fluid in the tube, comparable to the formationof breakers in a wave on the sea-shore. Similarphysical phenomena may develop within the arteriesof the living body.

Observations on an artificial schema of the eireiila-tion and graphic records of the Korotkow sounds inman show that the change in the sounds whichaccompanies deflation of the armlet is determined bythe change in form of the pulse wave as it passesthrough the compressed segment of the brachialartery, and that the distinctive cracking character ofthe third-phase sounds is due to the development ofbreakers " in the pulse wave.

EFFECT OF COMPRESSION

It only remains for me to explain how deflation ofthe armlet leads to the formation of breakers in the

pulse wave. The experiments on the change in formof the pulse wave in the course of transmission showed

FiG. 15-Diagram showing pressure changes during defla-tion of armlet: A, compressing pressure ; B, diastolicpressure ; and C,

" effective pressure."

that the higher the initial pressure in the tube, thegreater was the distance which the pulse wave hadto travel before becoming unstable. In all patients,except those with a very low diastolic pressure, thedistance from heart to periphery is insufficient toallow the pulse wave to become unstable; but, ifwe can reduce the tension of the arterial wall byartificially lowering the diastolic pressure, we willrender the conditions favourable for the formation ofbreakers. This is exactly what happens when weapply external pressure with the cuff.

In the living body, the arterial wall is kept undertension by the pressure of the blood within the artery.When we inflate the armlet we apply counter-pressurefrom outside, which tends to neutralise the pressureexerted from within. The tension of the arterial wallis then correspondingly reduced, for what we may callthe " effective pressure " acting on it is the differencebetween the external and the internal pressures.When the external compressing pressure is exactlyequal to the internal distending pressure, the " effec-tive pressure " is zero and the arterial wall in a stateof complete relaxation. When the compressingpressure is higher than the diastolic pressure it causescollapse of the artery during part of the pulse cycle(fig. 15). During deflation of the armlet, as theexternal pressure falls, the artery first resumes its

cylindrical shape and then, as the effective pressurerises, the tension of the arterial wall increases, andconditions become less favourable for the formationof breakers. Thus it is only during the intermediatestage of decompression, when the effective pressureis still very low, that breakers form and the loud,sharp sounds characteristic of the third phase areheard.

I am indebted to the publishers of Heart and theJorirraal of Physiology for permission to reproduce

figures which have previously appeared in my originalpapers published by them, and to Dr. W. C. Alvarezand Group-Captain H. A. Treadgold for figs. 1 and 3respectively.

REFERENCES

Alvarez, W. C. (1920) Arch. intern. Med. 26, 381.Bramwell, C. (1925) Heart, 12, 225.- (1937) Lancet, 2, 301, 366.- Downing, A. C., and Hill, A. V. (1923) Heart, 10, 289.- and Ellis, R. (1931) Quart. J. Med. 24, 329.- and Hickson, S. K. (1926) Heart, 13, 109, 129.- and Hill, A. V. (1923) J. Physiol. 57, Proc. Physiol. Soc.— — and McSwiney, B. A. (1923) Heart, 10, 233.

Brit. Heart J. (1939) 1, 261.Erlanger, J. (1924) personal communication.Hilton, R. (1936) Practitioner, 136, 729.Korotkow, N. (1905) Mitt. kaiserl. milit.-mediz. Akad. St.

Petersburg, 11,Rook, A. F., and Dawson, D. J. (1938) Lancet, 2, 1503.Thompson, R. J. C., and Todd, R. E. (1922) Ibid, 2, 503.Treadgold, H. A. (1933) Ibid, 1, 733.Wiggers, C. J., and Dean, A. (1917) Amer. J. med. Sci. 153, 666.

BRITISH EMPIRE CANCER CAMPAIGN

A LARGE number of specialties now contribute toprogress in cancer research. Clinicians, pathologistsand statisticians vie with chemists, biochemists, physi-cists, biophysicists, radiologists, virus workers, endo-crinologists, geneticists and many others in the

discovery of significant facts. No longer is it thoughtthat further progress towards a true understandingof cancer must await the discovery of the "mysterioussecret of life." Today the immediate objectives ofresearch are much less elusive. The present phaseof fruitful activity is attributable mainly to the

discovery of filtrable tumours and of carcinogenicchemicals in the field of causation and the discoveryof the curative value of X rays and radium on theclinical side. These are the first thoughts arousedby the sixteenth annual report of the British EmpireCancer Campaign. This volume of some 360 pages,edited by Mr. J. P. Lockhart-Mummery, summarisesthe work done under the auspices of the Grand Counciland its many branches and affiliated organisations athome and throughout the Empire Australia, NewZealand, Canada and South Africa. One commend-able feature of the report is that differences of opinionhave not been suppressed, so that the reader can seescience actually in the making, and can appreciate howdifferent underlying conceptions of the nature ofcancer and the mechanism of curative measures deter-mine the different directions in which new knowledgeis sought.

SOME SAMPLES OF THE WORK

At St. Mark’s Hospital, London, Cuthbert E. Dukesand J. P. Lockhart-Mummery have continued theirstudies of several generations of ten human familiesafflicted with familial adenomatosis of the colon andrectum. I The disease, in which an apparently simplepolyposis of the intestinal mucous membrane regu-larly becomes carcinomatous, is rare but instructive.There can now be no reasonable doubt that the con-dition is truly familial and may be transmitted byeither parent. What is transmitted 7 What relation-ship subsists between the simple state and themalignant? 7 Dukes and Lockhart-Mummery take theview that an inherited instability of epithelial cells ofthe large bowel renders their nuclei particularly liableto mutation for excessive growth, and that this exces-sive growth renders the cells particularly liable toa second mutation, a mutation to malignancy. Prob-

ably some such underlying view of the nature ofcancer has other adherents, for gene mutations andchromosome rearrangements seem to be the main

1 This study appeared, fully illustrated, in Lancet, 1939, 2, 586.

189

interest of H. J. Muller and his collaborators at theInstitute of Animal Genetics in the University ofEdinburgh. They have irradiated the mature

spermatozoa of Drosophila melanogaster and analysedthe subsequent generations, thus throwing light onthe tendency of broken chromosomes to join up incertain definite ways.Workers at the Cancer Hospital, London, have con-

tinued the production and study of new chemicalcarcinogenic compounds. One of those tested was5 : :19 - trimethyl - 1 : 2 - benzanthracene, which is

thought to have the highest known cancer-producingpotency when applied to the skin of mice. Whatcommon action substances of such varied chemicalstructure as the known carcinogenic compounds canhave on the cells of the animal body is still difficult toimagine. But such substances do produce tumours,and inquiry is being pushed on at the Cancer Hos-pital and elsewhere into the mechanism of production.Meanwhile, the substances already brought to lightare being used for the production of tumours neededin investigating other problems associated with thecause and cure of cancer. In Glasgow, P. R. Peacockand his colleagues have continued their studies of theabsorption and elimination of the carcinogenic agentbenzpyrene in various animals. Much is excreted inthe bile in somewhat altered form.

Stimulated by the knowledge that animals treatedwith natural aestrogenic compounds show a materialincrease in the incidence of mammary tumours, andby the reflection that epithelial proliferation takingplace in the female genital tract during various stagesof activity resembles the early stages of malignantdisease, E. C. Dodds of the Middlesex Hospital andhis associates have continued their work on syntheticcestrogenic compounds. Further new compounds havebeen produced, including one in which a hundredmillion international units are contained in a singlegramme. The biological effects of such compoundshave been studied. This work, already well known,has a clinical importance wider than that of cancer-ology. Other workers too, including those at theCancer Hospital, have studied the action of oestro-

genic compounds. One outstanding considerationwhich places the oestrogens in a different class fromthe chemical carcinogens is the fact that oestrin itselfoccurs naturally in the animal body.A number of workers-e.g., those at the Royal

Victoria Hospital, Newcastle-on-Tyne, and at the

Strangeways Research Laboratory, Cambridge, andMrs. Barbara Holmes at the Sir William Dunn Insti-tute of Biochemistry, Cambridge—have studiedintensively the respiratory, glycolytic and other meta-bolic functions of cancer cells. No absolute differencesbetween malignant and normal cells have been recog-nised as yet. Underlying these researches is, perhaps,the view that cancer cells are not just normal cells

being provoked in some way to an unwonted activity,but are so altered in some essential morphologicalfeature that their metabolic processes are likely to bequalitatively different from those of normal cells.Some such conception of the fundamental nature of

cancer may influence the work of P. A. Gorer at theLister Institute, London, who reports efforts toproduce genetically pure strains of mice so that, inexperiments with tumours propagated by the graftingof tumour cells, complications due simply to the" foreign character " of the grafted cells shall bereduced as far as possible. This however is notthe sole reason for the use of pure strains in cancerresearch. Some workers use pure strains because ofthe regularity with which they respond under givenconditions or because of some inbred peculiarity, as

in the strains of mice showing high or low incidenceof mammary cancer. A. W. Greenwood of the Insti-tute of Animal Genetics, University of Edinburgh,mentions the scheme for the production of carefullybred strains of brown leghorn fowls, so that if pecu-liarities in reaction are observed by workers to whomthe birds have been supplied they may be investigatedgenetically. One investigation on these lines is nowin progress, a certain strain having shown considerableresistance to injections of the infective agent of theRous fowl tumour No. 1.In their attempts to determine whether or not

tumours produced by chemical agents are also virustumours workers at the Middlesex Hospital have con-tinued observations on tumours produced in fowlsby means of tar. McIntosh and Selbie now reportthat in their series the total number of these tumoursso far found propagable has been raised to nine, andthat five of these have proved transmissible by meansof cell-free filtrates. Failures to filter they attributeto technical difficulties, and suggest that all inducedsarcomata in fowls are filtrable tumours and thereforevirus-tumours.Much of the work is more clinical in bearing. The

most effective ways of applying radiant energy are

being looked into at many institutions, and an under-standing of the mechanism by which cell death isbrought about has been studied by animal experiment,by in-vitro experiments with tissue cultures, bacterialsuspensions and organic colloids, as well as by examin-ation of human tumours removed at operation afterirradiation. Histological studies of tumours havebeen made with a view to improved classification,diagnosis and prognosis. Elaborate statistical reviewshave been made of the geographical distribution ofcancers in various parts of the body. The clinicalresearch committee reports progress in their schemeby which hospitals will record case-histories on a

uniform plan so that information about diagnosis,treatment, prognosis and the like can be more readilyextracted.

The campaign intends to carry on as far as it canduring the war, in spite of difficulties created by priorclaims which the country has on the services of itsworkers. For the coming year its grants for researchtotal 1::35,000, a figure which does not include the sumsraised and spent locally by branches and affiliatedorganisations.

IRELAND

(FROM OUR OWN CORRESPONDENT)

MARROWBONE LANE 71

THERE has been much discussion of a play, writtenby Dr. Robert Collis, a Dublin physician, which wasrecently produced at the Gate Theatre, and was so

successful that it was put on for a second run. The

play is illustrative of Dublin slum life and to manyit has recalled the work of Mr. Sean Casey, whoseplays on the life of the slums attracted much attentiona few years ago. It traces the career of a youngwoman brought up in a modest but respectable countryfamily, possessed of the dignity and good breedingwhich is a feature of peasant life in Ireland. Shemarries into a working-class family in the city slums,with the result, almost inevitable in present conditions,of a descent into poverty and misery. The play, apartfrom its artistic qualities, is forcibly propagandist, inthat it exhibits two of the great faults in the care forhealth in Dublin-the intolerable condition of many