909

MEDICAL SOCIETIES

LONDON ASSOCIATION OF THE MEDICAL

WOMEN’S FEDERATION

AN open meeting was held on March 28th, whenProf. M. LUCAS KEENE, the president, took the chairand a paper on the

Action of Radium as Seen in the Pelvis

was read by Dr. B. DAVIDINE PULLINGER. Thispaper appears on p. 902.

Prof. SIDNEY Russ said that Dr. Pullinger hadnot attempted to explain selective action but ratherto ’ explain it away. It seemed an extraordinarything to him for anyone to challenge the main factsof selective action, for they formed the basis of thewhole of radiotherapy. So many examples layin front of one, that he was rather at a loss to under-stand the attitude taken in the matter. He was

frankly critical, in view of the complete lack ofinformation on the quantitative side, of the claimswhich the speaker had made for the part played bythrombosis in the reaction of tumours to radiation.

Prof. E. H. KETTLE said he had been extremelyinterested in Dr. Pullinger’s paper and he thoughther work was a valuable contribution to the subject.He had always felt a little sceptical about the selectiveaction of radium upon the malignant cell, for itseemed to him that the wish was possibly fatherto the thought. He did not know of any essentialreason why the malignant cell should be especiallyvulnerable to rays, and in many conditions it seemedto tolerate insults which non-malignant cells werenot able to resist. In some tumours he had examinedsome weeks after irradiation, for example mammarycancer, he had found apparently healthy malignanttissue which had a very different appearance from thedegenerated cells of the remaining breast acini.There was a good deal of evidence to show thatlymphatic tissue and bone-marrow were especiallyvulnerable and he would like to hear Dr. Pullinger’sviews on this selectivity. No one deriied that radiumhad a remarkable local effect on malignant tumours,but this did not necessarily imply a specific actionon the tumour cell, which would seem to be essentialif radium therapy was to deal successfully withanything more than purely local growth. He thoughtthat such studies as Dr. Pullinger’s were likely to beof great help in the interpretation of the action ofradium, and of consequent benefit to radium therapy.

Dr. HELEN CHAMBERS said that Dr. Pullingerdid not discuss dosage although the problem oftissue reactions to radiation was entirely dependentupon dosage. It was a commonplace that anyliving tissue could be necrosed by radiation if

sufficiently heavy doses were employed and from thesections shown the tissues looked as if they had beenheavily overdosed. With interstitial treatment itwas unavoidable that the tissues close to the radiumtubes received much heavier doses than were necessaryto kill cancer cells ; the dose might be as much asten times the lethal. Such tissues were unsuitablefor studying radiosensitivity. The presence ofvascular lesions was to be expected as a result ofdirect injury or as an after-effect of the necrosisproduced and could not be looked upon as a necessaryprecursor to the malignant cells disappearing. Theproblem could be studied by the experimental method,with careful measurement of the radiation, using onlyjust enough to cause tumours to disappear. When

this was done necrosis of the tissues did not occurand the overlying skin of a tumour need not evenbe permanently epilated ; the tumour cells could bekilled and the skin through which the radiation hadbeen applied, which had consequently received thelargest dose, could be left undamaged. Dr. Pullingerspoke of erythema as an essential precursor in thedisappearance of malignant growths, but was its tAlthough temporary erythema was looked uponas correct treatment at the present time, in Dr.Chambers’s experience the growth cells often beganto disappear before the erythema had developed.The tendency of clinicians was to push the radiationdose to the limit of tolerance of the skin and normaltissues, to give the maximum doses from which theycould recover. Surely the object of research in radio-therapy was to arrange spacing and dosage so as toavoid these injuries and make the greater use ofthe facts of radiosensitivity. Dr. Chambers statedthat her experience at the Marie Curie Hospital hadincluded very few post-mortems ; the only ones werethose of immediate deaths. She had done only fivealthough the hospital had treated over 900 cases ofuterine cancer.

Dr. DOROTHY RUSSELL said that it seemed to herthat Dr. Pullinger had given an extremely common-sense presentation of her subject, giving a reasonableidea of how the process worked. The only clinicalmaterial to which the speaker had had access consistedof gliomas exposed to radiation. It was well knownthat the most malignant form, medulloblastoma,was particularly susceptible to radium. This wasdifficult to get going in culture. Capillary hsemangio-blastomas when plugged with radon seeds showedextraordinary regression. The form of glioma knownas spongioblastoma multiforme, which was also

susceptible to radiation, was generally very vascular.Dr. Pullinger had shown a circumspect unorthodoxyin her survey of the material at her disposal.

Dr. PULLINGER, in reply to Prof. Russ, said thatshe had been dealing with lethal action, which inher opinion was not selective for tumour cells, andthat she had endeavoured to show that normalstructures also are destroyed. Thrombosis couldbe found in tissues treated by the therapeutic dosescommonly used. She had not had time to discussthe immediate cause of the hyperaemia. She agreedthat it might be evidence of a high degree of selectivedamage to endothelium and vessel walls, but shewas of the opinion that it was a response to somechemical substance of histamine-like nature producedin the irradiated area. Replying to Dr. Chambers,Dr. Pullinger said that hyperaemia followed doses

commonly used in therapeutic irradiation. It wasthe first morphological change and preceded visibledamage to tumours. It was the condition under-

lying erythema, which occurs in the skin, but whenhyperaemia occurs in deeper structures it cannotbe seen. It was a change visible with the aid of themicroscope. Dr. Pullinger agreed that her material wasderived from human sources alone, but after all radio-therapy had been devised for the human subject.

At a meeting on April 11th, with Dr. LETITIAFAIRFIELD, vice-president, in the chair, an address on. The Endocrine Basis of Uterine Bleedingwas given by Prof. OSKAR FRANKL of the UniversitatsFrauenklinik in Vienna. Uterine bleeding, he said,was an important factor in the lives of both the

910 LONDON ASSOCIATION OF THE MEDICAL WOMEN’S FEDERATION

gynaecologist and the general practitioner. At onetime the treatment was stereotyped, but nowadayswe knew more about the causation of uterine bleeding,and could differentiate the treatment accordingly.In order to have a proper understanding of patho-logical bleeding it was necessary to consider the

origin of menstrual bleeding. The old physiciansused to say : " The uterus makes woman what she is."Later they modified their view, and said : " The

ovary makes woman what she is." We knew nowthat the ovary was not an independent gland ; bothovaries might be congenitally absent and yet thesecondary sexual characters might appear. To-daywe could say: "The pituitary makes men andwomen what they are."

After menstruation, the uterine mucous membraneremained quiescent for a day or two, and then beganto grow thicker ; the glands increased in size, andduring the second half of the intermenstrual periodbegan to secrete. In the ovary, maturation of anovum was initiated as soon as a menstrual periodended, and ovulation occurred as a rule between thetwelfth and fourteenth day of the menstrual cycle.The corpus luteum developed during the second halfof the cycle, and degenerated before the onset ofthe next menstrual period, unless the ovum was

fertilised ; degeneration of the corpus luteum,and the termination of its function as an endocrinebody, followed upon death of the ovum. TheGraafian follicle produced a hormone which hadbeen named severally folliculin, progynon, cestrin,and theelin ; the corpus luteum produced luteo-hormone. Every month one of the primordialfollicles in the ovary developed into a Graafianfollicle ; at the same time five or six other primordialfollicles began to develop but failed to mature ;instead they formed cystic atretic follicles, whichsecreted folliculin like the mature follicle.Two or three days after the end of a menstrual

period the folliculin secreted in the ovary stimulatedthe resting mucous membrane of the uterus byimproving the blood-supply, and, as a result, theglands began to show signs of activity. When theGraafian follicle ruptured a corpus luteum was formedin the ovary and secreted luteohormone into the bloodstream. Luteohormone consisted of two principles-hyperemmenin, which caused hyperaemia of the uterinemucous membrane, and progestin, which stimulatedthe development of the glands and prepared themucous membrane for the reception of the ovum.These processes did not occur independently, buttook place under the influence of hormones derivedfrom the anterior lobe of the pituitary. The anteriorlobe hormones were ossein, prolan A, and prolan B.Prolan A controlled the maturation of the Graafianfollicles and the development of cystic atretic follicles,and prolan B governed the development of the

corpus luteum." Why, then, did menstrual bleeding occur ? 1 Itfollowed upon death of the ovum and involutionof the corpus luteum. As the corpus luteum

degenerated the stimulus of luteohormone to themucous membrane ceased. It was not, therefore,hyperaemia, as was formerly supposed, which provokedthe menstrual flow, but the sudden onset of anaemia.The secretion of the glands digested the vessel wallsand liberated the blood.

At one time chronic metritis was regarded as acommon cause of pathological bleeding, but thiscondition was now known to be rare ; it was usuallya sequel of abortion or sepsis, and commonly fatal.The cases formerly grouped under this heading werenow classed as cases of haemorrhagic metropathia.

In this condition the mucous membrane of theuterus was usually thickened-often enormously so-and so irregular as to appear polypoid ; the musclewall was hypersemic. Most cases of haemorrhagicmetropathia were due to a superficial inflammationof the ovary, but a small number were due to pituitaryconditions. Inflammation of the ovary acted as

a stimulus and provoked the development of 50 to 100primordial follicles at the same time ; these activefollicles all produced folliculin in the same way asthe four or five cystic atretic follicles in the normalovary. In consequence a lasting hypersemia of theuterine mucosa was set up, and this continuouspassive congestion ultimately injured the vesselwalls and led to bleeding. In the small group ofcases due to pituitary conditions the enlarged pituitarysecreted an abundance of prolan A, which provokeduterine bleeding by its influence on the ovaries.Another example of bleeding due to endocrine actionwas to be seen in Graves’s disease, where the abnormalthyroid secretion might provoke first spontaneousuterine bleeding and later amenorrhcea.

There remained various causes of uterine bleedingwhich were not endocrine in origin. Adenomyosiswas a condition in which hyperplastic glandulartissue developed in the muscle of the uterus. Inthese cases, Prof. Frankl believed, bleeding was

produced mechanically ; the glandular tissue pressedon the vessels, and by inducing a continuous hyper-semia, eventually caused degeneration of the vesselwall and bleeding. Nor did he think that hemorrhagedue to myoma was endocrine in origin, although therewas probably some relation between the developmentof fibroids and the endocrine system ; bleeding,however, was probably produced mechanically bypressure on the vessels. Carcinoma, sarcoma, andtuberculosis of the uterus had no connexion with theductless glands. Granulosa-cell tumours, occurringin the ovary, sometimes caused intense uterine

haemorrhage. These tumours arose from cell groupshaving the same histological origin as the lining ofthe Graafian follicles ; they consisted of round or

spindle cells surrounding lacunae, which contained

homogeneous material and had rather the appearanceof ova. The resemblance to ovarian tissue was alsofunctional, for these tumours produced folliculin andgave rise to a condition of the uterus identical with

haemorrhagic metropathia. Tumours of the thyroidmight also provoke uterine bleeding through theirendocrine action.When the patient could afford it, haemorrhagic

metropathia might be treated by rest, and extractof ergot given hypodermically. Corpus luteumextracts had not fulfilled the hopes entertained forthem. X ray treatment gave beneficial results, butthe flushes, sweats, and tachycardia attendant onan artificially induced menopause were so much worsethan the condition itself that he had abandonedthis form of treatment. Poorer patients who wereanxious to return to work should be treated byvaginal hysterectomy. In adenomyosis surgical treat-ment was again necessary. X rays and radium shouldbe used for the treatment of myomata only whensurgical treatment was refused. Carcinoma, sarcoma,and tuberculosis should be treated by operationwhenever possible.

Mr. T. G. STEVENS said that there were a largenumber of cases in which bleeding appeared inmultiparse between the ages of 40 and 50. He had

always taught that these were the result of chronicsubinvolution. On microscopical examination themuscular coats of the smaller arteries were found tobe replaced by elastic tissue, and he had always

911ROYAL SOCIETY OF MEDICINE : MEDICINE

considered that the bleeding was mechanical in origin,the arteries having lost their muscular control.He did not think that these cases could be explainedon an endocrine basis.-Prof. FRANKL said that theycould be regarded as a late result of haemorrhagicmetropathia. On examination a fine superficialoophoritis was usually found in such cases ; but theactive stage-and, with it, the exaggerated productionof hormone and the hyperaemia of the uterine mucosa-might have subsided before the patient came fortreatment. He had found no increase in elastictissue in the walls of the arteries, but had observedan increase of connective tissue. Subinvolutioncertainly existed but was not to be identified withfibrosis.

Dr. G. F. STEBBiNG was inclined to agree with Mr.Stevens that many cases of bleeding resulted fromsubinvolution. The patient usually had a history ofabortion or complicated delivery followed later

by haemorrhage. The uterus was then found tobe enlarged, and had the appearance of an organwhich had suffered for years from passive congestion.Whatever view was taken of the cause, he sharedProf. Frankl’s opinion on treatment, though he tooka more favourable view of the value of radium andX ray therapy.

Dr. A. N. MACBETH, referring to the findings inhsemorrhagic metropathia, asked whether the " activefollicles " mentioned by Prof. Frankl were all cysticatretic follicles without luteinisation.-Prof. FRANKLreplied that normal Graafian follicles were also to befound. In reply to Dr. Stebbing he said that acertain number of cases of bleeding were due tosubinvolution, but the importance of these mustnot be exaggerated, as cases due to haemorrhagicmetropathia were much more numerous.

In proposing a vote of thanks, Lady BARRETTsaid that when she was in Vienna in 1914 Prof.Frankl was already teaching that menstrual haemor-rhage was due to the digestive action of the glandsand not to hyperoemia.-Dame LOUISE MCILROY,who seconded the vote of thanks, said that the teachingmaterial at the Universitats Frauenklinik was

unequalled in this country.

ROYAL SOCIETY OF MEDICINE

SECTION OF MEDICINE

AT the meeting of this section, held on April 25thunder the presidency of Dr. H. MORLEY FLETCHER,three short communications were read and discussed.

Dr. G. J. LANGLEY read a paper on

Bacteraemia in Pnepmoniabased on a study of cases at the Hope Hospital,Manchester. He said that Procheska regardedpneumonia as a blood stream infection, comparableto enteric fever, with a local fixation in the lung ata later stage. This observer had obtained evidenceof bacteraemia in all the 50 cases investigated byhim, which showed a mortality of 24 per cent. Theproportion of cases in which bactersemia was foundvaried greatly with different observers, but allagreed that its presence rendered the prognosismuch graver. Much work on this subject was donein America, where the mortality from the diseaseappeared to be about 30 per cent. higher than inthis country, but even in New York there was agreat difference in the mortality, according to thephysician in charge and the particular hospital.Coloured people seemed to show a very low tolerance

to the disease. Dr. Langley could not subscribe tothe pessimistic view held by some that bacteraemiawas a sign pointing to a fatal issue. The practiceoften followed of making a culture immediately onthe patient’s admission, and not repeating it unlessthe progress of the case was unsatisfactory or apositive result had been obtained, was of no helpin showing what course bactersemia might followthroughout the disease. In Dr. Langley’s ownseries there had been some recoveries, whether thebacteraemia occurred early or late in the pneumonia.His patients ranged between 16 and 60 years of age.He believed that the disease in America was verysimilar to. that seen in this country. In some cases

organisms disappeared from the blood in the absenceof any serum therapy ; hence it was not justifiableto use the disappearance of bacteraemia as a criterionof the potency of a serum treatment. It was not

possible to form a reliable opinion at the bedside.whether bacteraemia was or was not present.

Prof. F. R. FRASER said that any guide as to whento give and when to abstain from giving serum treat-ment in cases of pneumonia must be of the greatestpractical value. He gathered that Dr. Langley’s.studies had not yet enabled him to suggest any-working rule on this matter. No standard methodexisted of ascertaining whether or not bactersemiawas present. It was probable, however, that the,complication when it occurred early in the pneu-monia had not the same evil significance as when itoccurred at a later stage, for in the former case it.

might represent a natural order of occurrence,whereas when appearing later it might indicate abreaking down of the resistance agencies of the body.In answer to a question by the President, Dr. Langleysaid that he had not found leucocytosis in associationwith the bactersemia. One or two of his patientshad had ulcerative endocarditis, apparently arisingfrom the pneumonia itself.Dr REGINALD HILTON read a contribution on

The Action of Artificial Pneumothorax on theLung Lymphatics.

He described an investigation which was- still improgress into the working of the lymphatics of thelung, as shown by the removal of carbon particlesfrom a collapsed lung as contrasted with their removal’from a healthily functioning normal lung. In the12 animals investigated a difference- in the behaviourof the collapsed and the uncollapsed lung was notice-able. The pigment was- retained to some extent onboth sides, but in every case the collapsed lungshowed a far greater quantity of carbon, chieflygathered round the vessels. In the collapsed lungthis picture was seen even four months after the

injection, and the lymphatics were grossly dilated.Collapsed lungs collected from human subjectsshowed a similar dilatation of the lymphatics, alsosome fibrosis. Hence in both the experimentalrabbits and in human subjects there must exist, inthe collapsed lung, some hindrance to the lymphaticflow. Dr. Hilton suggested that this mechanism

might play a large part in the observed clinicalaction of therapeutically induced pneumothorax.In the first place this lymphatic stasis might lessenthe mobilisation and absorption of tubercle bacilli,,and so lessen the spread in the patient of his tuber-culosis ; and possibly also there might be a reducedabsorption of the products of the tubercle bacillus.If these surmises were correct, they afforded anexplanation of the striking effect on the temperatureand general condition sometimes noted in febrilepatients within a short time of the beginning off