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BRITISH MEDICAL ASSOCIATIONMEETING AT OXFORD

SECTION OF PATHOLOGY ANDBACTERIOLOGY

Dr. E. W. AINLEY WALKER (Oxford) presided overthis section and a discussion on

Disorders of Hæmopoiesis due to ToxicSubstances

was opened by Prof. L. J. WITTS (London), who saidhe proposed to discuss particularly the effect of

therapeutic drugs. He began by pointing out thatthe amount of any drug that will prove poisonousto animals or patients is variable. The range ofvariation is small with certain poisons such as

digitalis, but large with others such as the bar-biturates. The same variability is seen in the reactionof different individuals : thus Dudley found that of30 men exposed to arsine gas, one was not affected,seven had severe anaemia, while others had symptomsof anoxaemia only. The toxic effect of a drug mightbe due (1) to an increased susceptibility, the symptomsbeing those of over-dosage, or (2) to idiosyncrasy, thesymptoms being entirely different from those of over-dosage and not reproducible in animals. Suscepti-bility shaded into tolerance and insusceptibility;idiosyncrasy on the other hand was sharply demar-cated. Prof. Witts illustrated the differences betweensusceptibility and idiosyncrasy by reference to amido-pyrine. The usual symptoms of overdosage withamidopyrine were sleepiness passing into stupor,hyperpncea, tachycardia, sweating, and collapse;whereas the symptoms dependent upon an idio-syncrasy were pyrexia and rapid onset of agranulo-cytosis. A study of coroners’ reports on cases ofsuspected poisoning with amidopyrine, suggested, hethought, that the importance of idiosyncrasy is notsufficiently realised. He fearedithere was" usually alatent period of at least ten years before the toxicproperties of any new drug were appreciated. Thehaemotoxic properties of gold, which had been inuse now for ten years, had, for instance, only recentlybeen recognised. These properties were, he believed,due to the gold itself and not to the sulphur orbenzene ring also present in the preparationsemployed. The haemotoxic accidents of gold therapyfollowed small doses only and were not accompaniedby the ordinary symptoms of gold poisoning. He

quoted figures to show that in half the patients whodevelop a blood dyscrasia the dose has been less than2-0 grammes and in three-quarters less than 4-0 g.

Discussing the nature of the idiosyncratic reactionto drugs Prof. Witts said it probably had no setio-

logical relationship to the toxic idiopathies or asthma-eczema-migraine group of diseases. The occurrenceof agranulocytosis in different members of the samefamily suggested a hereditary liability, while the ideaof a constitutional predisposition was supported bythe occurrence of different types of blood dyscrasiain the same patient after different drugs. He alsospoke of the possible effects of local predispositionand the disease for which therapy is given. In somecases there was a mechanism which he consideredakin to anaphylaxis, since an initial sensitising doseappeared necessary. Both the abrupt fall in whitecells when amidopyrine is ingested by the sensitiveperson, and the allergic type of reaction in thethrombopenic purpuras due to drugs, he regarded ascomparable to blood dyscrasias occurring in peoplewith food allergy. From a medico-legal point ofview it had to be recognised that time may be

required after exposure for symptoms to develop ;injury to the marrow, once started, might progresswithout further exposure. In some cases a second

factor, such as sepsis or menstruation, might benecessary to precipitate the final catastrophe ofhsemotoxic collapse.

In the past, Prof. Witts held, classification had beenbased too closely on changes in the peripheral bloodand too little on the marrow picture. It was amistake to regard the blood dyscrasias caused bychemical substances as different from other blood

dyscrasias. He found it convenient to divide blood

poisons into those which act on the peripheral bloodand those which act on the marrow. Arsine, tolulene-diamine, and lead he grouped as the most importanthsemolytic agents, while the aniline compounds werethe most important of the hsemotoxic. Reactions ofthe marrow could be classified under the followingheads: (1) regenerative hyperplasia ; (2) dysplasia, inwhich the marrow is cellular, but the ripening of thecells is imperfect and few are delivered into thecirculation ; (3) neoplasia or leukaemia ; and (4) aplasia.In the dysplastic marrow he had found the numberand proportion of the different cells the same as inhealth, but varying degrees of degeneration had beenpresent according to the severity of the lesion andfreshness of material. The acute effect of benzol(benzene) and its derivatives, and of nirvanol,thorium dioxide, and gold, he placed in this group.After an acute attack, if the patient survived, themarrow usually recovered, but sometimes theremight be lasting paralysis though the cellular characterappeared normal. Any of the poisons which produceaplasia of the marrow could also, the speakerbelieved, arrest maturation without actual necrosis oraplasia. Usually in dysplasia all the cellular elementswere equally affected, but he described how in

agranulocytosis due to amidopyrine the myeloidelement is involved, in thrombocytopenic purpurathere is an increased number of megakaryocytes,while in the anaemia of radium poisoning the immatureerythroblasts are affected. The possibility of neoplasiaor leukaemia resulting from a hsemotoxic reaction heconsidered important and instanced certain cases ofleukaemia following benzol poisoning or exposure toX rays. Aplasia of the marrow following over-

whelming intoxication with benzol, mercury, sulphur,gold, radium, and X rays he mentioned briefly.Finally he suggested that the part of pathology hehad been dealing with was top-heavy with terminologyand under-ballasted with facts. It was important,not only for haematology, but for students of thewhole problem of idiosyncrasy, that more histologicaldata should be obtained both from serial biopsies andfrom autopsy material.

Dr. J. C. BRIDGE (London) spoke of his experienceof blood dyscrasias as a factory inspector. The firstseven cases of benzol poisoning he had described in1918 were all exposed to the same risk, but onlytwo were fatal, which brought out the importance ofindividual susceptibility. The toxicity of solvents wasstill an unknown field of knowledge, but he thoughtProf. Witts unduly gloomy in his belief that tenyears was the latent period required to assess the

danger of an industrial hazard. Benzol poisoninghad been made notifiable in 1926, since when onlyseven cases had been notified, with five deaths. Astudy of this small group suggested there was nopeculiar age or sex incidence. Dr. Sibyl Hornerhad examined the blood of a group of workers incontact with benzol over a number of years : a bloodcount of 4,800,000 per c.mm. had been found in52-4 per cent., a count between 3,000,000 and

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4,800,000 in 45-2 per cent., and a count of over5,000,000 in 2-4 per cent. The appearance of thered cells was normal in 68 per cent. There was no

leucopenia in 77-4 per cent. The few workers

exposed to radio-active substances in this countryhad been found to show no anaemia. Dr. Bridgeremembered two cases of leukaemia that had beenbrought to his notice but he had not been able tofind any relationship to benzol poisoning. He thoughtthat the so-called late effects of lead poisoning wereoften of doubtful origin and might be due to othercauses.

Dr. L. E. H. WHITBY (London) spoke of the effectsof X rays and radium on those employed in radio-logical departments. His conclusions were based onobservations made over a ten-year period at theMiddlesex Hospital where lately there had been50 people working with X rays and 10 with radium.Complete blood counts had been made on theseworkers every three months and latterly there hadalso been a control count made before any exposure.He had seen one case of acute leukaemia in a medicalman who had worked with X rays before strictprotection was adopted. He regarded a total whitecount below 5000 with a neutrophil granulocytecount below 3000 per c.mm. as a danger sign, anddescribed three types of reaction. As an example ofthe first type he mentioned a woman who had anormal picture for a relatively long period afterwhich her count started to fall; the fall was not

immediately appreciated and she did not leave workfor some time, with the result that recovery tookseveral months. In the second group he describedthe case of a man who having worked with X raysfor a long time developed a leucopenia at once whentransferred to manipulation of a large radium bomb,he was immediately sent away and recovered rapidly.In the third group Dr. Whitby placed people who on

first examination had a low white count and whohad been shown by experience to be unsuitable forX ray work. His experience had been that radiumwas more dangerous than X rays. Of the’ threeworkers in X rays who had developed leucopeniatwo had been in the deep X ray therapy department.Dr. JANET VAUGHAN (London) discussed the disorders

of haemopoiesis due to toxic substances produced to alarge extent within the body-i.e., the dyscrasiasassociated with sepsis and azotaemia. It was oftenstated that the anaemia of sepsis was dependentupon marrow aplasia, but such reports as she hadbeen able to trace suggested rather that there was ahyperplasia of erythropoietic tissue. She wonderedtherefore whether sepsis might not be associated witharrest of maturation in the marrow. There was noevidence that sepsis increased blood destruction

except in rare conditions like Bacillus welchii infec-tions or Oroya fever. The available evidenceindicated that it inhibited erythropoiesis. In supportof this Dr. Vaughan quoted the well-known clinicalfact that haemopoietic principles lose their thera-peutic effect in the face of sepsis, and the observationsof Fairley that removal of the parasites alone in theanaemia of malaria suffices to promote blood produc-tion. Experimental observations of Robscheit-Robbins and Whipple had, she thought, shown thatthis inhibitory action of sepsis is exerted rather onthe internal metabolism of haemoglobin than uponperipheral blood or marrow. Whether the changesin the marrow in agranulocytosis of sepsis are similarto those in amidopyrine poisoning appeared ques-tionable. Probably in sepsis myeloid degenerationwas greater, while in amidopyrine poisoning lympho-cytic proliferation seemed to be characteristic.

Certain cases of thrombocytopenic purpura shedescribed as due to sepsis. Turning to the anaemia.associated with azotasmia, she described five cases inwhich, irrespective of the total red cell count, therewas a reticulocytosis. Three of these at autopsyhad proved to have hypoplasia of the marrow. Shepleaded for complete skeletal examination in alldisorders of haemopoiesis at autopsy.

Dr. S. C. Dye (Wolverhampton) instanced thediscovery of amidopyrine as an aetiological factor inthe development of agranulocytosis as an example ofthe value of the deductive method in medicine. In1922 Schultz had first described cases of agranulo-cytosis. It had subsequently been noted to be morecommon in America, Germany, and Denmark thanelsewhere and to have a particular affinity for medicalmen and their families. These peculiar facts hadmade independent observers suspect the sample drugtraffic and had led to the incrimination of amido-

pyrine. He considered that elderly people were

most commonly affected, especially women after themenopause, and he thought some change in thebalance of the sex hormones was partly responsiblefor the disease. He did not believe the benzene ringto be the toxic agent in amidopyrine, since bothaspirin and phenacetin contain a benzene ring butdo not cause agranulocytosis. He discussed the possiblechemical nature of the toxic agent at some length.

Prof. D. F. CAPPELL (Dundee) emphasised the

importance of idiosyncrasy in all toxic reactions. Itwas, he thought, insufficiently appreciated by medico-legal experts.-Dr. J. V. DugrG (Brisbane) describedhis observations on employees on a large lead-miningand smelting plant. He had found in addition toclassical plumbism two curious types of response:(1) a rapid and severe intoxication indicating specialsusceptibility or idiosyncrasy, and (2) a permanentand incurable secondary anaemia. He was preparedto accept long delayed lead poisoning only with greatreserve.-The PRESIDENT spoke of the advantage ofjudging the effects of any drug in relation to surfacearea rather than to the weight of the experimentalanimal or patient. In assessing the toxicity of

diphtheria toxin for guinea-pigs, it had been foundthat there was no individual variation in suscepti-bility when the dose was regulated by surface areaand not by body-weight.-Dr. R. E. LANE (Man-chester) suggested that in lead poisoning at leastthere was possibly a familial idiosyncrasy ; he hadseen three brothers affected. He was sceptical aboutdelayed lead poisoning. The patient whose case hadbeen reported by Waterfield was afterwards found tohave been ingesting large quantities of lead at thetime of observation.-Prof. W. CAMPBELL (CapeTown) said that in his experience agranulocytosis didnot occur among South African natives. He hadbeen unable to reproduce the condition in animalsby injection of organisms from fatal cases.-ColonelF. P. MACKIE (London) emphasised the need for furtherknowledge of the normal distribution of marrow inthe skeleton. He drew attention to the occurrence of

agranulocytosis in patients with trypanosomiasis.In reply to questions, Dr. WHITBY said he had seen

one case of an X ray worker who had developedleucopenia, gone off on leave, and on return hadmaintained a satisfactory count. Patients with a

primary leucopenia were advised not to start workin the department.-Prof. WITTS described his

technique of bone-marrow puncture and quotedColonel L. E. Napier as saying that pentose nucleotideis valueless in the treatment of the leucopenia ofkala-azar.

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SECTION OF PHYSICAL MEDICINE

THE meeting of this section on July 24th, withDr. W. J. TURRELL (Oxford) in the chair, beganwith a discussion on

Ultra-Wgh FrequencyDr. PHILIPPE BAUWENS (London), in giving the

opening paper, said that a short-wave therapyaimed at making selected tissues of the body theseat of electrical oscillations of very high frequency.To attain this the tissues were included in an oscil-

lating circuit in which, subsequently, conditions

required to bring about resonance with a high-frequency generator were satisfied. He then con-

sidered the various parts of the resonating circuitof a short-wave machine. Tissues could be subjectedto high-frequency oscillations by inserting thembetween the plates of the condenser of the resonatingcircuit and tuning in by means of a variable induct-ance. This method was used in certain machines,but disadvantages inherent in variable inductanceswere likely to appear. More often the machine hadtwo leads ; the therapeutic use of such circuitsrequired the recognition of its characteristics ; themaximum potential difference was obtained if theseleads were in length one quarter of the wave-length.As the highest possible electromotive force shouldbe applied to the patient, particularly when usingsmall electrodes, the length of the lead should bearthis relation to the wave-length. In an apparatusso constructed the electromotive force measuredacross the plates of the variable condenser wasdirectly proportional to the current developed inthe patient’s condenser when the latter was acrosshigh-tension nodes. By using this fact it was pos-sible for the current in the condenser field to beestimated by direct reading. When the condenserfield incorporated a load in the shape of living tissueit was the most important and the most perplexingcomponent in the resonating circuit. The highdielectric constant of the tissue fluids bestowed onthem the property of increasing the capacity of thefield into which they were introduced, and of causingdistortion, more especially when the space betweenelectrodes and tissues was small. A heterogeneousdielectric, such as a tissue, produced an uneven

field distribution, and so mechanical stresses varyingwith field density. Mechanical strains were boundto occur at high frequency when tissues were sub-mitted to short-wave therapy. Dr. Bauwens postu-lated that this irritative process of strains producedat high frequency was responsible for lowering thethreshold at which defensive tissue reactions tookplace ; there was in deep tissues an effect similarto that termed " esophylaxis," which resulted fromthe " insulting effects of ultra-violet irradiationon the skin. These uneven stresses should not bevisualised as causing coarse cellular movement, butrather as producing fine vibrations of smaller particlesin various histological structures, calling forth non-specific defensive reactions. He considered thatalthough this effect probably invested ultra-short-wave therapy with its advantage over diathermy,the thermal component of the treatment should notbe overlooked. Since a rise in temperature wouldcause an acceleration of pathological as well as ofdefence processes, in a large number of conditionsbetter results were obtained in fields capable of pro-ducing only minimal or no rise in the temperature.Short-wave therapy was a therapeutic agent capable,primarily, of making tissues react against antigens,and, secondarily, of causing local pyrexia, thus

accelerating biochemical activity. It was importantto decide in each case whether the therapy was tobe used for its heating or for its effect in initiatingreactions. When used for the second purpose verygreat care in administration was required to avoiddeterioration in the patient’s condition.Dr. JUSTINA WILSON (London) said that depth

effect and directability were two. most importantaspects of short-wave therapy. The depth effect

depended largely on the distance of the electrodesand the air spacing. This had been explained interms of diverging lines of force. In the treatmentof the chest and abdomen, depth effect was of para-mount importance. Given an apparatus of constantoutput and wave-length the best effect was producedby making the skin area as large as possible. Layersof gamgee tissue, paper, clothing, felt or rubberbetween the electrode and the patient all reducedthe depth effect. There was, she said, a certainamount of clinical evidence that the wave-lengthhad a selective action. For instance, she had had aman and a woman patient with bronchial asthma,both having attacks by night and day. Neither hadresponded at all to 30, 12, or 6 m. wave-lengths norto mild fever therapy (1° F. rise for one hour). Whentreated with a wave-length of 4-5 m. to the base ofthe brain, neck, and back they had cleared up, thewoman’s recovery being dramatic. For gynaeco-logical cases short-wave diathermy was infinitelysafer than ordinary diathermy, for it was good inacute cases, though risky in subacute ones. Shehad seen good results with it in gonococcal infectionsof the adnexa, in parametritis, and mastitis.

Dr. G. COOPER mentioned how the ease of appli-cation and simplicity of control of the short-wavetherapy had led people to imagine that it could beapplied without care or knowledge ; that was thereverse of the truth. Experience had shown thatresults were uneven. The age of the patient, thedose and the time between applications were amongthe factors to be considered. He thought the therapymight be most effective when combined with otherforms of treatment such as X rays and vaccines;in combination with X rays it had appeared successfulin arthritis.

Dr. KERR RussELL (London) had treated severalcases of sinusitis with short-wave therapy and hadfound it especially effective for infections of ethmoidalcells. They improved sometimes as late as six weeksafter treatment; the patients should return whenthey caught a cold, since in the congestive stage thecold could be dispelled. One case of osteomyelitisseemed to have benefited. Of the 16 post-encep-halitics treated 2 had apparently been uninfluenced ;the others showed varying degrees of improvementin salivation, spasticity, tremor, eye symptoms, andsleeplessness. He had also had good results withcases of chronic osteo-arthritis but he had seen abso-lutely no improvement in those of otosclerosis. Heconsidered the chief indications for short-wavetherapy included general paralysis, parkinsonism,chronic infective arthritis, disseminated sclerosis,asthma and, above all, gonococcal infection.

Prof. E. WEISSENBURG (Vienna) reported his

experiences of treating certain painful conditions.He had found that patients with neuritis were oftenadversely affected by ordinary full treatment buthad responded favourably when the intensity of theshort-wave diathermy was directed to the affectedpart only, and had been such as to produce no riseof temperature. With similar limited doses reliefwas also obtained in neurosyphilis, bronchitis, and

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pneumonia with a hard cough. The pain of otitismedia and of sinusitis could be diminished by lowintensity treatment. Neuralgia, neuritis, migraine,angina pectoris, spastic colon, and dysmenorrhoeaalso responded to the treatment. He thought thatthe action of the therapy bore some resemblance tothat of atropine and other alkaloids. The rise of

temperature was so weak that the results could notbe attributed to it; they were apparently attributableto a specific and calming effect on the trophic nervoussystem. He had tried many experiments which hadshown him that these effects of low intensity treat-ment could not be due to suggestion. He had obtainedexperimental evidence that the amplitude of a nerve’saction current was reduced by ultra-short-wave

therapy.Prof. F. N. NAGELSCHMIDT (Manchester) thought

that the distortion effects referred to by Dr. Bauwensmight be utilised. In America simpler and cheapermeans tended to replace short-wave therapy. Elec-

trically heated blankets, although theoretically dif-ferent in action, seemed to give the same results.He too had found that neuritis reacted badly to heat.He had been considering the distribution of linesof force in a condenser field and had concluded thatwhen the electrodes were larger than a dielectricplaced in the field, the lines of force were clusteredinto the dielectric. For these reasons he believed thatto obtain depth effect the condenser plate should belarger than the part to be treated and should beplaced at a distance from the skin.The CHAIRMAN said that the frank confession of

errors did much to clear away the confusion of

thought which had surrounded the subject of short-wave therapy.Dr. BAUWENS did not believe that short-wave

therapy could have molecular or atomic effects suchas ultra-violet might be expected to have. He hadfound the therapy successful in rhinological work,osteomyelitis, and in parkinsonism, but the unhappycondition of the parkinsonians who reverted to theirformer condition on cessation of treatment haddriven him to stop treating them at all.

Dr. F. HOWARD HUMPHRIS (London) then read apaper on

Mild Radium TherapyHe said that treatment by radium emanation wasalso called mild radium therapy, radon therapy, andemanotherapy. It had been used empirically for

ages, and scientifically for 30 or 40 years, yet it waslittle known in this country, although abroad it wasnow employed extensively in compresses, sprays,subcutaneous injections, baths, inhalations, and

drinking water. It was used in 20 hospitals in Paris,and at a thousand clinics in Germany, in Italy,Czechoslovakia, Spain, Portugal, and the U.S.A.,and he wished to see the therapy adopted by hospitalsand spas in this country. He also wished to clearthe widespread error that radon was dangerous.Radium and radium emanations were distinctlydifferent, yet many people even in the profession stillimputed the dangerous properties of radium to theemanation which, he said, could not possibly bedangerous. The legend of the dangers of radiumemanation had arisen partly from confusing itwith radium itself in interpreting the incident at afactory in New Jersey. Several girls occupied inpainting luminous paint on to watch and clock handshad pointed their camel-hair brushes with theirlips, had thus come to swallow small amounts ofradium and its congener mesothorium, and haddied ultimately of carcinoma. The other example

so often quoted was of a gentleman of Pittsburgwho for a considerable time drank a solution ofradium and mesothorium thrice daily in an endeavourto rejuvenate himself and to improve his golf. Hedeveloped carcinoma and died. These cases had beendue to radium or its salts and had nothing to dowith mild radium therapy. Radium salts if ingestedwould leave deposits in the bones which wouldremain active for 1750 years; radium emanationwas all gone in 3’85 days. His reference to theempirical use of emanotherapy had been to the"holy earth" which could be seen in the leatherbags of Bohemia; they were the forerunners of theradium pad of to-day. Other examples of the valueof emanation therapy occurred in history. The heal-ing qualities of Bad Gastein were described a centuryago ; the waters were subsequently found to containradio-active gas. Spas, more especially in Germany,had such names as " The spring of eternal youth,"" The spring of rejuvenation and regeneration,"" The spa for the ancients." In this country Bathstood almost alone in its radio-activity. Abroadthe higher the radio-activity the more health givingthe spring was reputed to be, and in a great measurespa treatment was mild radium treatment. Recentlyradon emanators had been constructed, capable ofpreparing active water with greater standardisationof dosage than was attained at spas.The emanations were administered in drinking

water, by subcutaneous injections, by rectal insuf-flations (used largely for gynaecological conditions),as a spray by means of blowing a gas through watercontaining the emanation, by radium pad, and byan expensive pomade. Inhalation was a method usedby the Romans in their emanatoria; nowadayspatients received an hour’s treatment in a roominto which the gas was pumped. The dosage wasliable to be inaccurate as the emanation tended to

gravitate to the floor.Radium emanation therapy had been found bene-

ficial in gout, in rheumatisms, in certain gynaeco-logical conditions-notably pelvic pain and con-

gestion, salpingitis, and sterility-in psoriasis, mycosisfungoides, and eczema, and in respiratory catarrh.He considered that its " revitalising " quality madeit useful in convalescence and in the complaints ofmiddle and old age. The therapy was believed toact theoretically by stimulating the metabolism andactivating the oxidative processes.

Prof. SIDNEY Russ (London) took " mild therapyto mean a form of treatment in which the agent wasused so that it could not possibly do harm. It wasa question, he said, whether radium in mild dosescould be useful in the treatment of disease. Muchthat had been written on the subject before wassimply surmise and opinion. The radium in spawaters was supposed to have therapeutic value.

Actually spa waters often contained radium or

radon or both, but so did practically every river,lake, and ocean in the world. For some reason whichhe had found hard to understand, the minute traces-and they were always exceedingly minute-in spawaters had been put forward as a reason for some ofthe therapeutic value of the drinking water of thespa. If this were true the spa waters richest inthese elements might reasonably be expected to beamong the most noted, but they were not. Swedenhad many spas, but their healing properties couldscarcely be connected with their radio-activity, forthe drinking water from artesian borings in theStockholm granite was far more radio-active thanthat of any of the spas, information for which hewas indebted to Prof. F. Soddy. If indeed the curative

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value of spa waters was due to their radio-activitytheir value as health resorts might disappear veryeasily ; for radium or radon impregnated watercould be made at trifling cost. Calculation showedthat an outlay of E240 would buy enough radium toactivate 2,250,000 million litres daily to the strengthof the K.W. Gas at Bath almost indefinitely.

Small quantities of radium were said to invigoratethe body ; the energy produced by the maximumamount of radium which a man might be assumedto tolerate in his body amounted to about a ten-millionth of the heat requirements of the body.The rationale of radon treatment had also beenstated to be the promotion of oxidation ; a typicaloxidation process was the production of hydrogenperoxide from acidulated water, and this could bebrought about by beta radiation from radium. Insome quantitative experiments Mr. G. W. Spicerhad found that the amount of hydrogen peroxidewhich would be produced by a litre of the K.W. Gasat Bath was one hundred millionth of a milligramme.This small quantity could not possibly have anyeffect on the metabolic processes of the body. An

ordinary peroxide mouth wash would quite swampany such therapy.

In the last four years Prof. Russ, working withDr. Howitt, had tried to find out what physiologicaland biochemical changes might be induced in patientsby such comparatively small doses of radon wateras would be included under the term " weak doses."In a paper on the subject, which had just been com-pleted, Dr. Howitt had concluded that in the syste-matic treatment of cases of rheumatism and alliedaffections no demonstrable change was found intheir clinical condition during treatment, and thatpatients seen two years later did not ascribe anypermanent amelioration of symptoms to the treat-ment. When dosage was pushed to much higherfigures no improvement had been produced. Therewas, however, a tendency towards a fall in the

erythrocyte count ; with the occurrence of systemicdamage there was no justification for treatment onsuch lines.Dr. Humphris had said that radium emanation

could not be dangerous. He himself had had experi-ence of breathing radon in the war ; he and his

colleagues had had no doubt that the effect wasdeleterious.

Dr. F. D. HowiTT, speaking of his clinical in vestiga-tion, concluded that in small doses emanation therapywas of no great value. In larger doses, even whenvery well controlled, it might be dangerous.

EXHIBITION BY COMBINED SECTIONS

ON July 23rd a large demonstration was given toa meeting of the sections of Physiology and Bio-chemistry, Pathology and Bacteriology, Anatomy,Pharmacology and Therapeutics with Anaesthetics.The principal exhibit, which was watched also bythe section of obstetrics and gynaecology, was a filmby Sir JOSEPH BARCROFT and Dr. H. BARRON

(Cambridge) entitled

Origins of Movements in the FoetusThe film had been taken during Sir Joseph’s experi-ments, and for the most part showed close-ups ofthe foetus lying on an observer’s hand and con-

nected by the umbilical cord to the placenta in theuterus. The audience was, however, also shown onemore distant view of a ewe under spinal anaesthesia

lying in a bath of warm saline, and accepting lumpsof sugar while Coasarean section was performed.

Sir Joseph explained that he and his collaboratorhad set out to investigate the earliest movementsof which the sheep embryo was capable. The storyof the development of the movements had been

pieced together from observations on a series of ewes.While at the thirty-sixth day, the earliest date at

which they had elicited movement, the embryo had givensingle movements, a few days later the same stimulus(a poke on the nose) had caused the same movement tobe repeated rhythmically. A little later still the embryowas found to be moving in the same rhythmical waywithout any particular stimulus and, indeed, as soon as

the uterus was opened. At first the movement appearedto be extensor, but by the forty-first day it had becomeflexor in type. By the forty-sixth day the rhythm thathad also involved the neck, limbs, and tail became con-

fined to the trunk, and closely resembled normal inspira-tion. The rhythmic descent of the diaphragm was shownby the depression of the liver and the drawing in ofthe chest wall which at that stage was quite soft. Noappreciable negative pressure was set up in the thorax.

Sir Joseph said that these observations seemedto throw light on the essential nature of respiratoryrhythm. The explanations which had in the past beenput forward had grouped themselves round threeprincipal conceptions : (1) Each phase of respira-tion initiated a message to the brain checking thatparticular phase and initiating its opposite. (2) Inthe central nervous system there was a continual

urge to inspire but the very act of inspirationset up sensory impulses which checked the effort,the lung then reverting passively to its unexpandedcondition. (3) Respiration was due to rhythmicactivity of the central nervous system. This lastview was suggested by these observations of the

sheep’s foetus and by the description by Adrian andBuytendijk of an inherent rhythm in the centralnervous system of the goldfish with the same

frequency as that of the gill movements.Sir Joseph went on to describe how, when an asym.

metrical stimulus had been given to a fcetus at aboutthe thirty-eighth day, asymmetrical movement hadresulted in and been followed by a symmetrical rhythmicmovement. When the foetus was on its side gravityseemed to be a component of tactile stimuli at about thatstage, so that on stimulation the initial movement tendedmore and more to be one in which the crown of the headwas directed upwards. In fact, by the forty-seventhday if the foetus was tapped vigorously on either thesnout or the tail it made a movement suggesting aneffort to get up, followed of course by the rhythm. Onsubsequent days this aspect of activity became accen-tuated till, about the fiftieth day, the movement producedby tapping the foetus closely resembled that often madewhen a new-born lamb rises from the ground. About the

forty-ninth day the foetus was so lively that it was diffi-cult to manipulate it at all without consequent slightmovements taking place, each followed by a rhythm.The result was that rhythmic movement scarcely ceasedand the foetus presented the general appearance of anordinary animal breathing naturally. But when energeticmovement took place as the result of a considerablestimulus the rhythm quickened and deepened, givingthe appearance of an animal out of breath as the resultof the effort it had made.

It had been shown conclusively that in humanbeings a quickening and deepening of respirationoccurred immediately on effort, and it had beenconcluded that the ventilation was produced byradiation of impulses from the motor cortex. SirJoseph considered that that radiation rather thanany chemical mechanism appeared to be the funda-mental regulatory mechanism. After the fiftieth

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day the reflexes became more difficult to elicit, butthe fcetus could be made to behave as if it were rather

younger by inducing an appropriate degree of asphyxia.Up to the forty-ninth day pinching of the umbilicalcord had no other effect than to slow the heart andkill the foetus.

Sir Joseph said that a controversy had arisenround the subject of the initiation of mammalianmovement. One view maintained that ordinarymovements had individualised out of a generalmass movement, the other that they had started ina localised way and become integrated into more

generalised manifestations. The two conceptionshad been assumed to be alternatives, but to himthey seemed to represent successive stages in develop-ment, at least in the sheep.

Prof. H. BECKWITH WHITEHOUSE, who had takenthe chair during the showing of the film, consideredthat movements, similar to those that the film hadshown, might account for the claims some womenmade of feeling movements before the establisheddate.-To this Sir JOSEPH replied that in the earlystages of pregnancy the fcetus was so free in liquorthat its movements were usually unlikely to be

perceptible to the mother.Dr. J. C. WINDEYER (Sydney) said that he had

observed continuous and apparently purposivemovements in anencephalic infants.-Sir JOSEPH

. said that in one experiment cutting off the cerebrumhad had no effect on the foetal movements, but whenthe medulla was removed by a second cut the foetusapparently started running away.

Prof. FARQUHAR MURRAY (Newcastle) consideredthat towards term a feetus began to have some sortof character.

Prof. W. H. WILSON (Cairo) asked whether therhythmic movement was kept up independently ofmuscular tone and whether it was inherent.-SirJOSEPH replied that it appeared to be inherent.

EmbryologyOne group of exhibits was concerned with widely

different problems of development. Mr. JOSEPHNEEDHAM, Sc.D. (Cambridge), showed photomicro-graphs of embryonic epidermal tissue, which hadbeen caused to differentiate into neural tube tissue

by the introduction of crude glycogen. Some lightwas shed on the nature of the substance causing thisorganised phenomenon by the fact that the resultwas still produced though the crude glycogen hadbeen boiled-thus excluding any vitalistic explana-tion-or subjected to saponification. It was not

produced by pure glycogen.An inherited skeletal anomaly which had arisen

presumably by mutation in a previously healthystock of mice was shown by Dr. HANS GRiiNFBFRG(London). The lesions appeared to be essentiallya failure of resorption of bone both in the cartila-ginous and membranous bones. In the skull andelsewhere the bones were deformed and the marrowcavity of the long bones was non-existent. In addi-tion calcification was imperfect and the teeth failedto erupt. The affected mice died on weaning, appa-rently of starvation. At first this had been thoughtto be due to the lack of teeth, but attempts to keepthe animals alive on a liquid diet had failed. Theincidence of the condition tallied completely withthat to be expected from a Mendelian recessivecharacter. In all, over 300 cases had occurred andthe lesion had been unvarying in them.

Structures resembling the carotid body but relatedto the aorta and pulmonary arteries, that is to say

the fourth and sixth branchial arch arteries, weredemonstrated in sections of embryos by Dr. J. D.BOYD (Cambridge). The structures were related tothe vagus nerve, the aortic bodies being supplied bybranches of the depressor nerve. They persisted inthe adult and were presumably chemoreceptors.

Dr. P. N. B. ODGERS (Oxford) showed an earlyhuman embryo.-Drs. KATHERINE TANSLEY, F. G.SPEAR, and A. GLÜCKSMANN demonstrated the effectof radium in the developing retina.-Dr. JOHNKiRK showed a series of photographs concerning thegubernaculum and the descent of the testis.

Experimental PhysiologyProf. T. NICOL (London) gave a demonstration

of his researches into hormone influences on theendometrium shown by intra-vitam staining. Dyewhen injected into a guinea-pig was taken up byendothelial cells in the uterine tissues in differentamounts at different phases of uterine activity.From such experiments he deduced that oestrinacted on the endometrium by stimulating the reticulo-endothelial cells. The corpus luteum hormoneinfluenced the production of fat, especially in theuterine epithelium, but only in a uterus previouslysensitised by oestrin as in the normal luteal phaseof the cycle. The fat was presumably for the nourish-ment of an early ovum, and he thought that a defi-oiency of that hormone might often be the cause ofdeath of a young embryo. Sections during earlystages of pregnancy showed a fatty substance abun-dant in the endometrium. This food materialappeared to be taken up by the yolk sac wall in theperiod before the placenta was fully formed. Therewas, however, no destruction of the capillariescoursing through it, and the solution of the endo-metrium must have been due to some agent such asan enzyme. In the guinea-pig there was no definiteevidence that any fcetal elements persisted capableof producing such an enzyme. Prof. Nicol con-cluded that the changes might be initiated anddirected from the ovary.Mr. R. M. RANSON and Mr. J. TYNEN showed a

method of estimating the relative spermicidal powersof many chemicals used in contraception.

Prof. H. H. WOOLLARD (London) gave a demon-stration of the peripheral nerve-endings in humanskin. The exact position of the different types ofnerve-endings had been mapped out in an area.

The skin had been removed, sectioned, and photo-graphed, and the series of photographs pieced to-gether, like an aerial map, to show the course of thenerve-fibres and their endings. Each sensation hadbeen found to have its own specific type of endingand each ending its own fibre. The different typesof ending had already been described to the sectionof anatomy. The demonstration included the scaron the arm from which the skin had been removed.

Dr. J. C. ECCLES and Mr. J. W. MAGLADERY(Oxford) showed records of electrical response andcontractions of smooth muscle. These showed thatwhen the nerve to the muscle was stimulated theaction current and the contraction rose in regularincrements over a considerable period of time. These

suggested that the contraction of smooth musclewas of the nature of a tetanus, the augmenting con-traction being caused by repeated and increasingchemical stimuli fired off initially by the nerve.Dr. H. M. CARLETON and Dr. E. G. T. LIDDELL

(Oxford) demonstrated a surgical procedure to bringa cat’s external carotid to the exterior. They alsoshowed a cat which had been operated on some

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years ago and on which they had been studyingchanges in blood pressure. They had found that inthe cat the blood pressure rose on a milk diet andwent down if the cat lived on meat. The pressurealso went up very rapidly from emotional causes,such as attention from some people, the sound ofrustling paper or, most of all, the sight of a mouse.

Clinical ApparatusThree exhibits were of methods of administering

oxygen. Each had a very large cylinder of oxygen,some means of judging the flow of gas, some tubing,and a device for delivering the gas to the patient.Dr. E. P. POULTON showed the freedom permitted tothe patient, and the control of atmospheric conditions,in his type of oxygen tent.-Dr. H. L. MARRIOTT’Sand Dr. KENNETH ROBSON’s apparatus, by includinga special device for measuring the flow and by deliver-ing the oxygen to the patient by two nasal catheters,permitted the delivery of oxygen to be correctlygauged. It also allowed the patient to read and tomove about.-The third exhibit, by Prof. J. ARGYLLCAMPBELL, was of two portable box masks : one

was of light metal and the other-the original-acardboard box cut up. The demonstration althoughmainly concerned with the method’s efficiency alsoshowed how easily this type might be constructedin an emergency.-Dr. MARRIOTT and Dr. A. KEKWICKshowed continuous-drip blood transfusion being given.The Bragg-Paul pulsator for maintaining prolongedartificialrespiration, shown by Dr. PHYLLIS KERRIDGE,was of interest because it was being tried out in polio-myelitis and diphtheria in some institutions.

Nutrition

A series of exhibits were concerned with thevitamin-B complex. Mr. J. R. O’BRIEN (Oxford)exhibited two rats with dermatitis (an erythema ofthe paws, ears, and snout) due to lack of vitamin Be.The symptoms were curable by a diet of fish andcereals as well as by yeast and ox liver. Their rela-tion to human pellagra was still obscure. It was

explained that vitamin Be together with octoflavinconstituted the original vitamin B2.Two methods of estimating vitamin Bl were shown.

Schopfer’s test, which assayed vitamin Bby the growthof a mould on a special medium, had been utilisedby Dr. A. P. Meiklejohn (Oxford) to test the vitamin-B, 1content of blood. The ease of performing the testclinically made it available for all with simple bac-teriological technique ; it required no incubator buttook ten days to perform.-The second methodof estimation, shown by Mr. H. W. KINNERSLEYand Mr. O’BRIEN, depended on a colour re-

action given by the pure vitamin in solution.

Crystals of vitamin B were also provided for

inspection.Other demonstrations dealt with desensitisation with-

out shock (Dr. J. W. de W. G. Thornton, Bristol) ; themetabolism of creatine by the perfused heart (Dr. R. B.Fisher and Mr. A. E. Wilhelmi, Oxford); experimentson crystalline pepsin (Mr. J. St. L. Philpot and Mr. B. R. S.Mainwaring, Oxford) ; bacterial metabolism of cellulose(Dr. E. Walker, Oxford); dietary heart-block in pigeons(Dr. C. W. Carter, Oxford) ; estimation of pituitaryextract on the guinea-pig uterus ; vaginal smears forestimation of oestrus-producing hormone (Prof. J. H.Burn, London) ; action of drugs on trypanosomes ; actionof drugs on exsected human tissues (Prof. J. A. Gunn,Oxford); action of drugs on the uterus in situ (Dr. T. B.Heaton, Oxford) ; the application of the Marchi techniqueto the reptilian brain (Dr. F. Goldby, Cambridge) ; and theexperimental study of reproduction in monkeys (Dr. S.

Zuckerman, Oxford).

SECTION OF PUBLIC MEDICINE

A MEETING of this section was held under the

presidency of Dr. W. M. WILLOUGHBY.Shell-fish

Dr. R. W. DODGSON (London) opened a discussionon Shell-fish and the Public Health. For forty years,he said, sewage-polluted molluscan shell-fish had beenknown to be capable of transmitting typhoid feverand other diseases to the human consumer. Shell-fish from unclean beds were manifestly a dirty foodsince an average-sized mussel or oyster could in

twenty-four hours filter out, and retain within itself,almost all the suspended matter from at least 10 gallonsof water. Sir George Newman had said in 1920 thatas long as sewage-polluted shell-fish were consumedby large numbers of the population it was doubtfulwhether the incidence of the typhoid fever would bemuch reduced. Since that date the amount of

sewage discharged near shell-fish beds had increased.Attempts to grapple with the situation had been made,but the measures adopted had been ineffective.So-called purification of sewage offered no solutionof the problem. Removal of pollution by deviationof sewers and sterilisation of sewage effluents weremethods made impracticable by expense. Closureof polluted fisheries by Administrative Order, underthe Ministry of Health Shell-fish Regulations (1915and 1934) had been resorted to on a considerablescale, approximately two-thirds of the mussel bedsin England and Wales being closed. The resultant

gap in supply was filled largely by imported shell-fish ; but these in turn were often seriously pollutedand came from countries in which the incidence oftyphoid was much greater than in our own. Wholesaleclosure of shell-fish beds, while crippling the homeindustry, failed to provide adequate protection ofpublic health. Anyone could still collect shell-nshfor his own consumption or for sale for bait and therewas good reason to believe that mussels taken

ostensibly for these purposes found their way tomarkets.

Experience had convinced him that the onlysolution of the problem lay in an unfailing system ofpurification under stringent government control.The alternative seemed to be that sooner or latermolluscan shell-fish as a whole would have to beofficially banned as a food. Any system of purificationhad to be a satisfactory safeguard, simple and notdisproportionately expensive. Dr. Dodgson thenshowed a film of the systems of purification of musselsat Conway and oysters at Brightlingsea. The musselswere spread about two deep in tanks, hosed and thenflooded with water which had been sterilised withbleaching-powder and neutralised with sodium hypo-sulphate. This water was drained off after twenty-four hours and more sterile sea-water run in for another

day. Then in a final bath the mussels were exposedfor one hour to active chlorine (three parts per million)in order to clean their shells. The process for oysterswas similar but in the winter the water had to beheated slightly to get them to open and pass the waterthrough. Precautions were taken to sterilise thefisherman’s boots and other articles which mightcontaminate the shell-fish once it had been purified.An additional precaution taken at Conway was theinstallation at the local isolation hospital, the effluentof which discharged into the estuary, of a plant forthe incineration of dejecta, and the sterilisation bychlorine of sullage from the typhoid block.A station for the purification of mussels had been

set up in the season 1916-17 after an initial experi-

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mental stage. The content of lactose-fermentingbacteria was found to be reduced by the processfrom some hundreds to five or less per cubic centi-metre of tissue.

At the beginning of the 1935-36 season (and to a lesserextent in 1934) after one or two exceptionally good results,a period of abnormal bacterial counts had set in lasting,off and on, for about six weeks both at Conway and atLytham. The plate counts were not merely outside thenormal but excessively so ; some hundreds of red coloniescame up on MacConkey plates within twenty-four hours.The problem had been under intensive investigation sincethe outset. From the bacteriological investigation verysuggestive results had been obtained. The main relevantpoints which had emerged were : that the barnacles,with which the mussels were often thickly studded, mightharbour lactose-fractors in excessive numbers ; thatthe lactose-fractor content of stored mussels, for exampleat the markets, might increase significantly, probablyon occasion by reinfection from barnacles crushed intransit or by multiplication of a particular type of organism;that at any rate a large percentage of the " residual "lactose fractors were Gram-negative bacilli morphologicallyresembling B. coli, which grew best at 20° C., were Koser-positive but they liquefied gelatin; that some of thesebacilli not only survived for long periods but might rapidlyincrease in sea-water ; and that these lactose-fermentingbacilli had replaced the staphylococci which had formerlyconstituted the majority of residual organisms. In viewof the facts emerging from this recent work the lactose-fractor criterion ad hoc was no longer adequate as anindicator of pollution of intestinal origin. The liquefactionof gelatin placed these organisms found outside the rangeof coli wrogenes controversies.

In judging a source of supply, Dr. Dodgson con-cluded, epidemiological evidence was one of themost important criteria ; although complaints hadbeen frequent in pre-purification days, only one

(and that had been unproven) had been received in21 years of purification.Dr. H. P. NEWSHOLME (Birmingham) explained the

difficulties of an inland authority which, with nofirst-hand knowledge of the cultivation and thecollection of shell-fish, and no control over it, had tosee that the food came to the consumer sound andfree from risk of infection. For the detection ofunsoundness naked-eye examination of shell-fishwas useless. In bacteriological examination organismsof typhoid, paratyphoid, or dysentery were rarelyisolated from shell-fish and B. coli had to be taken as

presumptive evidence of sewage contamination.For this purpose he had adopted a comparativelylenient standard of B. coli content of over 100 percubic centimetre of oyster. Epidemiological evidencerequired some harm to be done before action couldbe taken. The fourth line of investigation, that oftopography, was beyond the official powers of theinland local authority. Since three of these lines ofinvestigation presented such obstacles to the inlandauthority he thought that a medical officer of healthwas justified in regarding shell-fish showing repeatedsigns of bacterial contamination as a likely cause ofdanger to public health. Dr. Newsholme describedhow Birmingham had taken steps to protect itselffrom polluted shell-fish and some of the difficultiesthey had encountered. Two cases of typhoid, onefatal, had occurred in Birmingham from musselsfrom A. Inquiries had revealed that the so-calledpurification bed at A was exposed to discharge fromthree sewers. Although the M.O.H. had repeatedlydrawn his council’s attention to the risk, nothinghad been done. No further supplies had come intoBirmingham from A, but they might well be goingelsewhere. He cited two other examples where thecoastal authority had taken no action despite

representations about contamination. A fourth

authority had installed highly satisfactory purifica-tion plant. Although in each case the bacteriologicalevidence of pollution had been confirmed by topo-graphical evidence, Birmingham as an inland authorityhad had no power to prevent further sale in its areaof shell-fish from those sources. This power had,however, been obtained in the BirminghamParliamentary Bill. The clause in the Bill enabledthe M.O.H. to take action if consumption of particularshell-fish was likely to cause danger to public health-without waiting for actual illness. The Bill left thenational problem unsolved. He considered that aban should be put on cockles and winkles unless theyhad been steamed and on oysters and mussels unlessthey had been sufficiently cleansed.

Dr. CYRIL BANKS (Nottingham) said that inhis area cases of typhoid arose from shell-fish consump-tion more especially among middle-aged men addictedto beer. He thought the wholesalers in that tradevery shortsighted in taking no action. One smallstatement in a local paper from a medical officeron the dangers of shell-fish killed the trade for theyear.

Dr. J. D. ROLLESTON mentioned that in France

typhoid was so commonly caused by shell-fish thata special name was given to it when so produced.

Prof. J. W. BIGGER (Dublin) said he had foundlactose fractors in sea-water and also in public water-supplies and the Thames.-Dr. C. F. WHITE (London)suggested that a motion urging compulsory purifica-tion should be sent to the public health committeeof the British Medical Association, and the followingresolution was unanimously adopted :-

" That the time has now arrived when the Ministry ofHealth should be requested to make regulations prohibit-ing the sale for human consumption in this country ofmolluscan shell-fish whether home produced or importedwhich are not certified to have been cleansed by a recognisedmethod at a station approved for the purpose by theMinistry of Health."

Dr. DODGSON subsequently pointed out that the

Ministry of Health had power already to make suchan order.

MELKSHAM’S NEW HospiTAL.-A 2200,000 legacyhas made it possible to start work on this hospital atonce, and the first sod was cut recently by the chairmanof the trustees on a site in Spa-road.

FELLOWSHIP OF MEDICINE AND POST-GRADUATEMEDICAL ASSOCIATION.—During September courses will beheld in plastic surgery (Sept. 16th and 17th); infants’ diseasesat the Infants Hospital (Sept. 21st to 26th); chest diseasesat the Brompton Hospital (Sept. 21st to 26th) ; proctologyat the Gordon Hospital (Sept. 28th to Oct. 3rd). Week-end courses have been arranged on general surgery atthe Miller General Hospital (Sept. 19th and 20th) ; on

ophthalmology at the Royal Westminster OphthalmicHospital (Sept. 26th and 27th) ; on fevers at the Park

Hospital, Hither Green (Oct. 3rd and 4th); and on heartand lung diseases at the Royal Chest Hospital (Oct. 10thand llth). A special evening course in anatomy andphysiology in preparation for the primary F.R.C.S.examination will be given at the Infants Hospital fromSept. 14th to Oct. 22nd, and special evening M.R.C.P.courses will be held at the National Temperance Hospital(Sept. 8th to 24th) ; at the Brompton Hospital (Sept. 14thto Oct. 9th); at the Royal Chest Hospital (Sept. 21st toOct. 9th). Demonstrations on pulmonary tuberculosiswill be held at Preston Hall on Saturday, Oct. 3rd. Furtherinformation may be had from the secretary of the associa-tion, 1, Wimpole-street, London, W.I.