789

THE

BRITISH MEDICAL ASSOCIATION.SEVENTY-SEVENTH ANNUAL MEETING

AT BELFAST.

THE SECTIONS.

THERAPEUTICS AND PHARMACOLOGY.

THURSDAY, JULY 29TH.

President, Professor R. STOCKMAN (Glasgow).Professor W. E. DIXON (Cambridge) and Dr. H. H. DALE

(London) gave a demonstration on theAotion of the Pressor Su.b8tanoes in P1drrid Meat, Plaaenta,

and Ergot on the Sl(r1’iving Mammalian Orrgans-Heart and Uterus.

Dr. DALE, in reviewing the history of the recognition ofthese substances, said that it was to Abelous that they owedthe observation of the effect upon the blood pressure ofcertain substances in putrifying meat. Later, ProfessorDixon and Dr. F. E. Taylor had found a similar adrenalin-likeaction in extracts of placenta, and Rosenheim showed thatin all probability this action was not present unless a slightamount of putrefaction had taken place. More lately, hischemical colleagues, Barger and Walpole, had isolated twosubstances, both of which exercised this action, to whichthe names iso-amylamine and para-hydroxylphenylethylaminehad been given. Their chemical structure closely resembledthat of adrenaline. These bodies had also been obtained byadding a culture of micro-organisms obtained from humanfseces to a solution of broth containing tyrosin. It was not

unlikely that they were actually formed in the body in caseswhere there was stagnation of the flow of the intestinalcontents. The substances were also found in the liquidextract of ergot, and they came to the conclusion that theactivity of the liquid extract was due to them. Similarbodies were produced in the ripening of cheese and in themanufacture of cod-liver oil by the old method.Professor DIXON then demonstrated the action of the drug

upon a rabbit’s heart perfused through the coronary arterieswith Ringer’s solution. A small dose caused marked accele-ration and increased amplitude of the beat. Later he

injected adrenalin and compared the results recorded. Thesubstances in question had a similar action to adrenalin,differing only in two points : (a) the action was much moreprolonged, and (b) the effect was produced when the drug wasgiven by the mouth. Dr. Dale had himself taken a consider-able dose by the mouth, and his blood pressure had under-gone a great and long-continued rise. The point of action ofthe drug was the same as in adrenalin, at the peripheralendings of the sympathetic nerves. Dr. Dale showed in a

pregnant uterus of the cat that the drug caused a markedcontraction and rise of tone.

Dr. J. C. McWALTER (Dublin) said that it was interestingto note that alcoholic extracts of ergot were clinically inert,while ordinary fluid extracts of ergot underwent a kind ofauto-infection. Even when the fluid extract had undergoneapparent decomposition it remained as active as ever. This

suggested some identity between its active principle and thatof putrid meat.

Dr. H. C. CAMERON (London) said that the use of adrenalextract to combat the symptoms of Addison’s disease hadbeen disappointing because of the rapidity with which theeffects of the drug passed off, and because it was impossibleto give the drug by the mouth. It was in just these twopoints that the action of the drug under discussion differed-it could be given by the mouth and its action was slighter butlonger sustained.

Professor BENJAMIN MOORE (Liverpool) read a paperentitledA New ltTeraber of the Saponi1’,-d’igitalin Grozy, its

Chenaistry and Physiologicccl Aotion."He associated in the work the names of Dr. F. W. BakerYoung and Miss S. C. M. Lowton (Liverpool). He was able todemonstrate the action of the drug upon the mammalianheart to the meeting, making use of the apparatus which hadbeen used by Professor Dixon. The substance had beenobtained from the seeds of Bassia longifolia, popularly knownas mowrah seeds, which were largely used in the manufacture -

of the better class of soaps. The glucoside isolated fromthese seeds had an intensely irritating action locally upona cut surface or when it reached the mucous membrane ofthe nose or throat or the conjunctiva. It was while

investigating certain cases of sore-throat, conjunctivitis, &c.,among those engaged in manipulating the meal after theexpression of the oil, that his attention had first been calledto the substance. He did not think it was as well known asit ought to be that the local action of digitalis was also

highly irritative. It was easy to obtain the active substancein a state of purity by taking it out in a saturated alcoholicsolution from the meal, decolourising with charcoal, pre-cipitating with excess of ether, filtering, and drying in thedesiccator over sulphuric acid. This process, repeated threeor four times, yielded a pure white product, analysis ofwhich showed it to consist of carbon (51’9 per cent.),hydrogen (6’ 85 per cent.), and oxygen (41’25 per cent.),without a trace of nitrogen. It was a glucoside yielding onethird its weight of glucose, which was found to be a hexoseyielding typical glucosazone crystals. One-third, approxi-mately, consisted of an organic acid, which had been calledmowric acid, and which possessed all the active properties ofthe mother substance. This acid is readily soluble in alcoholand insoluble in water. It can be obtained in a state of puritybut has not yet been obtained in crystalline form. Its sodiumsalt, which is soluble in water, gives, like the glucoside, a solu-tion possessing all the physical and many of the physiologicalproperties of a soap solution. Although the salts of theseparated mowric acid are strongly hasmolytic, this action ismuch more intense in the case of the glucoside. In this respectit is equalled only by saponin. The digitalis-like action ofthe drug upon the isolated mammalian heart when used invery dilute solutions was very striking, and was illustratedby tracings. The force of the beat was increased and theheart slowed.

Dr. F. J. CHARTERis (Glasgow) read a paper entitled" The Effect on the Le1woeyte Cm6nt prrod1wed by Thiosinamine

Injections, Leoithin, and N1wleinate of Soda. "

He said that in 1892 Hebra advocated the use of thiosinaminein lupus, claiming that it prevented the formation ofcicatrices. In 1902 Teleky began to use the drug incicatricial contractions of the gut and claimed good results.Merck in 1904 introduced a soluble double salt under thetrade name of fibrolysin, and from that time it had beenlargely used and the most extravagant claims made for it inpractice. The preparation consisted of two molecules ofthiosinamine combined with one molecule of sodium

salicylate, was soluble in water, and non-irritating. It hadbeen recommended for use in Dupuytren’s contraction,obstruction to the pylorus or in the intestine, in urethralstricture, in arthritis, in myositis ossificans, in locomotorataxia, and in optic neuritis. No claim was made that itremoved fibrous tissue. Its advocates only asserted that itsoftened cicatrices in such a way that they might be morereadily stretched. He had used thiosinamine in a numberof different conditions. His experience did not substantiatethe glowing accounts of other observers; he had never seenany benefit result. In cases of fibrous ankylosis of jointsinunction, injection, and oral administration had alike beenuseless, though carried out for several months. He hadcombined the treatment with massage and with rupture ofthe adhesions under an anaesthetic. In animals poisoned bythiosinamine there were marked fatty changes in the

epithelial and glandular cells but no alteration in the fibroustissue. It had been often suggested that thiosinamine actedby causing some alteration in the blood, probably throughthe agency of the white cells. He had inserted sterile glasscapillary tubes, containing the drug in solid form and in

solution, into the peritoneal cavity of frogs, but had foundno evidence of a positive chemiotaxis. In no instance couldthe presence of leucocytes be demonstrated in the tubes. Hehimself had taken large doses of thiosinamine (six grains),and had found no alteration in the total or differential countof the leucocytes. The maximum result obtained was in apatient suffering from chronic rheumatoid arthritis. At11 A.M. the white blood cells were 5200 per cubic millimetrewhen 2’3 cubic centimetres of fibrolysin were injected, andat 5 30 P.M. they numbered 10,400. Such cases were

rare. The counting was continued in some cases for 48hours.The PRESIDENT spoke of the great utility of such work

L 3

790

as Dr. Charteris had done at a time when extravagant claimswere often made for proprietary articles.

Professor DIXON read a paper entitled

I I Facts and 11’aneies in Pharniaeology. "

Tie said that many of our explanations of disease and ofthe action of drugs were not dependent upon sound physio-logical experiment. We had all been brought up in a schoolof dogmatism and taught to accept certain statements as

proven. The length of time occupied in the teaching ofanatomy and of materia medica dated back to an age whenthese formed almost the whole of the preliminary training-of the student. We no longer collected our own simples orprepared our galenicals, and yet we had not materially-altered our teaching. In this way a useful knowledge of the Itrue action of drugs was excluded. Tradition still endowed- certain drugs with actions which they did not possess.Opium was devoid of local action, yet there were in the

Pharmacopoeia three preparations for local application.Hydrocyanic acid was prescribed for the local relief of gastricpain in doses far too small to have any action at all. In thecase of digitalis, modern research had succeeded in alteringthe accepted views. In 1851 Neligan stated that digitalisenfeebled the action of the heart, and this was at the time:generally accepted. The same could not be said in the caseof ether and strychnine. Neither had any direct stimulatory:action on the heart as was often supposed and taught.Belladonna had no action in stopping the secretion of milk,for atropine could only act upon nerve endings, and themammary gland was without nerves. Salts of potash wereregarded as depressant, yet vegetarians were accustomed totake as much as 80 grains per diem. Potash was onlypoisonous in a certain concentration, and experiments whichhe had carried out showed that when given by the mouth itwas excreted more rapidly than it was absorbed, so that theconcentration in the blood increased very little. Calciumgiven by the mouth is also slowly absorbed and rapidlyexcreted. Injected under the skin, on the other hand, it mayhave a powerful effect in increasing the coagulation time ofthe blood.

Dr. J. C. McWALTER, in a paper entitled" We Regulation of Quack Medioine Trraffia,"

said that since the British Medical Association last met2,400,000 had been spent on quack medicines in GreatBritain and Ireland. The gain to the Government bad been300,000. The concurrence of the Government in this traffichad become a national scandal. Other countries had beencareful to legislate on the matter and the colonies weregrappling with the problem. The solution of the trouble wasthat makers of nostrums should be compelled to set forth theingredients on the label. To attain this an Act of Parlia-ment would be necessary, and he feared that the profits ofthe Government were too large to render it likely that itwould so legislate. He thought that the greatest servicehad been done by the British Medical Association in pub-lishing, as it had recently done, the composition and costof certain of the most widely advertised drugs. He regrettedthat it was difficult to bring these results before the publicbecause newspapers, whose advertisement columns were

profitably filled by the proprietors of secret remedies, werelittle likely to join in the crusade. He believed that thebest means of attack was by cooperation with the medicalofficers of health. Already a notable beginning had beenmade in Liverpool, where Dr. E. W. Hope had prosecuted aproprietor of a patent medicine. He was charged under theSale of Fond and Drugs Act for selling drugs not of the

nature, substance, and quality demanded, and a convictionwas obtained. If such action became general, and the publica-tion by the Association of the composition of so many undulyadvertised drugs had made that possible, he thought thatmuch might be done to control the traffic.

FRIDAY, JULY 30TH.Dr. H. D. ROLLESTON (London) opened a discussion upon

The Treatment of oedema.He adopted the following classification of oedema. 1. Theoedema of venous obstruction and cardiac disease, primarilymechanical and due to hydrostatic factors, as was partlyshown by the influence of gravity. Hydrasmia and mal-nutrition of the capillary endothelium were active agentsalso in its production. 2. Renal dropsy, though sometimesmainly cardiac, as in granular kidney, was in its proper

sense of complex pathology. Toxic factors were probablypredominant, but hydraemia and retention of chlorides mustalso be taken into consideration. 3. Toxic oedemas otherthan those due to manifest renal disease. For example, theoedema sometimes seen in infective diarrhoea in children,and the critical cedema seen in rare cases in perniciousansemia. 4. Inflammatory oedema. 5. The cedema dueto thrombo-phlebitis depending on venous and lymphaticobstruction. 6. (Edema due to lymphatic obstruction.7. (Edema due to nervous factors : (a) oedema associatedwith peripheral neuritis and beri-beri ; and (b) hystericalcedema. 8. (Edema of doubtful origin-e.g., chronic troph-cedema, sometimes known as Milroy’s disease. He wouldconfine himself to the treatment of cardiac and renalcedema. 1. In cardiac dropsy, although primarily ofmechanical origin, the treatment was sometimes rendereddifficult because a toxic factor, from intestinal toxaemia, orrenal insufficiency, might be added. The mechanical break-down was to be met by rest and by the use of digitalis.Professor Dixon had shown that samples of the tincture ofdigitalis may be devoid of any active principle, and it wastherefore important to choose the preparation with care. Herecommended the fluid extract of the drug. Nativelle’sgranules were also often successful, as was the combinationof caffeine and digitalis recommended by Sir James Barr, ora similar combination of theocin or diuretin with digitalis.Theocin acetate was less irritating and less likely to pro-duce vomiting-than theocin. Baillie’s pill had a deservedreputation. The restriction of fluid to 25 or 30 ounces in the24 hours was an important part of the treatment. Therestriction should be gradual and progressive so as to avoidthirst and constipation. The intake of salt should also belimited and gentle massage was often useful. 2. The com-

plicated pathology of renal dropsy made it difficult to estimatethe effects of treatment, and sudden improvement might beindependent of treatment. He quoted three cases in whichsudden diuresis and disappearance of dropsy had set in appar-ently independently of the treatment adopted. In four daysin this way a patient had lost four stones and three poundsin weight. The very rapid absorption of a large amount ofcedema fluid was a possible source of danger and mightcause urasmic symptoms. The occurrence of dropsy mightthus be regarded as a conservative process. He believedthat this was true in acute nephritis. Toxins in the circula-tion damaged the walls of the capillaries and so led totransudation of fluid. Removal of these toxins might beattempted by free drinking and the copious fluid regimen,especially milk, might be combined with purgation. Butthis plan would not succeed if the kidneys were incapableof dealing with the increased amount of fluid. There was a

danger of hydrasmia resulting. Copious drinking should beavoided in acute or subacute nephritis. The use of diuretics

required care, for the kidneys might be unable to respond ormight be irritated by the diuretic drug. Caffeine he hadfound more successful than diuretin or theocin. Hebelieved that greater benefit followed the removal of fluidby means of hot-air baths than by means of restrict-ing the intake of fluid. The most satisfactory way ofremoving the toxins was probably by incising the legs.He recommended a single incision on the dorsum ofthe foot. No hard-and-fast rule could be laid downas to the restriction of fluid. In some cases the kidneyscould only deal with a small amount of fluid, and unless theintake was curtailed hydrasmia resulted. In other cases the

kidneys could deal with an increased ingestion of fluid.That chlorides might be retained in cases of parenchymatousnephritis was undoubted, but it was not proved that in allcases the relation of cause and effect was the same. Insome cases the chloride retention was caused by the dropsy,in others it was itself the cause of the dropsy. Itmust be clearly recognised that a salt-free diet was oftendisappointing.

Sir JAMES BARR (Liverpool) said that he divided cedemasinto the following two great groups: (a) Those in whichthere was abnormal transudation from the capillaries withoutapparent obstruction in the absorbents, as in inflammation,in vaso motor paralysis, in anasmia, in Bright’s disease.(b) Those in which there was obstruction to the returncurrent, whether local or general, such as the occlusion of avein or lymphatic, portal obstruction from mitral or tricuspiddisease, or obstructive lung disease. The treatment ofoedema was theoretically one of the simplest problems in