24

physiological saline solution, to mix the emulsion with thecobra poison, and then to test the action of the mixture onguinea-pigs. For inoculation guinea-pigs also were employed,weighing between 250 and 350 grammes. For such animalsthe minimal certainly letha dose was 0-1 milligramme of thedried venom. In these experiments 0-15 milligramme wasinjected, a dose which causes death of the controls in fromtwo to three hours.

Cobra poison belongs to the class of toxins as abovedefined and contains at least two toxic substances. One ofthese is hæmolytic—i.e., it alters the red blood corpuscles,setting free the haemoglobin they contain; the other is anerve poison, which probably acts on the respiratory centre,and possibly also on other parts of the nervous system.Therefore I made a considerable number of experiments onvarious parts of the nervous system-e.g., the medulla, thecerebral cortex, and the spinal cord of the guinea-pig and thebullock. The toxicity of cobra poison is not, however,perceptibly altered by mixture with an emulsion of any partof the nervous system or by mixture with the blood or theserum of a susceptible animal. Calmette 3 independently hasmade similar experiments with the brain of the rabbitand of Bothrops lanceolatus and has obtained similarresults. The liver, too, was subjected to a carefulexamination, because of its action on certain alkaloids 4,

and also because of the impunity with which enormous dosesof snake poison may be given per os. Moreover, as Fraser 5has recently shown, the bile of various animals preventsdeath when injected simultaneously with this poison or

even subsequently into the opposite side of the body. How-ever, in no case did I succeed in averting or delaying deathby the injection of liver emulsion with the venom. On oneor two occasions I found that if a solution of poison be addedto liver substance, and the mixture be ground up andallowed to stand for twenty-four hours, on injection of sucha volume of the supernatant fluid as should contain a lethaldose the animal survives or dies after a longer interval thanthe control. But even by this method a positive result is not- constant and the fallacy of assuming that the poison isequally diffused throughout the mass is obvious. When a

certainly lethal dose is added to liver substance alreadyemulsified with saline solution injection of the mixtureleads to death with the same symptoms and in the sametime as pure cobra poison alone. I have therefore not been.able to confirm Professor Kanthack’s observations, thatliver extract has a marked retarding influence on the actionof cobra venom. But Professor Kanthack himself confessesthat in one case where he was working with the liver extractof a young rabbit lie had obtained no antitoxic effect.

The suprarenal capsules were indeed the only organs whichinvariably influenced cobra poison. With emulsions of bone-marrow, kidney, lymphatic gland, muscle substance, ovary,spleen, testicle, thymus, uniformly negative results wereobtained. In my first experiments on the suprarenals I usedthose of the guinea-pig and found that in most cases theanimals survived, and when death occurred it was con-

siderably delayed. I then tried the suprarenals of the sheepand bullock and found that when fresh they invariably pre-vented death. The medulla is inactive in t7tis respect, therortex alone protecting. This, then, is probably the explana-tion of the variancy in the results with the guinea-pig’s supra-renals which I occasionally obtained. For in these animalsnot only are the capsules small but they consist almostentirely of medulla. Rabbits’ and sheep’s suprarenals alsoprotect.

I then tried the action of tabloids of various organs, usingthe preparations of Messrs. Burroughs, Wellcome and Co.,and found here too that the suprarenal tabloids alone hadany action, though the effect of the tabloids is less certainthan that of the fresh glands.

This action then of the suprarenals is not shared by anyother organ in the body and this fact alone suggests thatmechanical precipitation of the poison is not an importantfactor of their protective power. And as injection of thesuprarenal emulsion either mixed with the poison on thesame side or by itself on the opposite side of the body alikeprevents death, mechanical action, if it even occurs, must

3 Annales de l’Institut Pasteur, tome xii., No. 5. 4 Roger : Archives de Physiologie, 1892. Action du Foie sur les

Poisons. Paris.5 Wiener Medicinische Blätter, 1897, No. 29, p. 481, and Brit. Med.

Jour., 1897, vol. i.6 Twenty-fifth Annual Report of the Local Government Board, 1895-

6, P. 250.

play but a very small part. And since, even when adminis-tered in large quantities, they only influence amounts ofpoison just above the minimal lethal dose, and cannot pro-tect against multiple doses, we must conclude that they donot contain an antitoxin, that is, a substance whichneutralises the poison in vitro.The suprarenal cortex, then, of susceptible animals contains

another of those substances, such as bile salts, cholesterin,tyrosin,7 which somehow raise the natural resistance of theanimal and so prevent death from doses slightly above theminimal lethal. It is noticeable too that the body of theanimal most susceptible to cobra poison-viz., the guinea-pig--contains no substance which will combine with this

poison in vitro, as Wassermann and Takaki 8 and others havefound for tetanus, and more recently Kempner and

Schepile-,v,,,kyl for the" Botulismus-gift." Whether Wasser-mann’s theory will prove valid or not for all toxins with ameasurable incubation period at least it does not agree withthe facts above summarised for poison.Birmingham.

SOME REMARKS UPON A NEWMYDRIATIC.

BY SYDNEY STEPHENSON, M.B., C.M., F.R.C.S. EDIN.,OPHTHALMIC SURGEON TO THE EVELINA HOSPITAL AND TO THE

NORTH-EASTERN HOSPITAL FOR CHILDREN, ETC.

THE claims of ephedrine hydrochloride as an agent fordilating the pupil have been before the profession for

several years, but apparently without attracting anythinglike general attention. The first communication upon the

subject was made by a Japanese physician, Kinnosuke

:Miura,l and this was soon followed by papers from the pensof J. Inouye 2 and A. de Vriese.3 3 From these contributions,however, it was clear that the dilatation of the pupil inducedby ephedrine was of moderate extent only, although it

possessed the great practical advantage of passing off ratherquickly (in from 1 to 20 hours). Later it was foundthat the action of ephedrine could be enhanced by theaddition of a trace of homatropine hydrochlorate in the

proportion of a hundredth part of the latter to one part ofthe former substance. This observation led E. Merck, thewell-known Darmstadt pharmacist, to combine the twomedicaments. The new agent, which is known as "mydrin,"is a white powder, readily soluble in water. Its physio-logical action has been reported upon by Groenouw 4 inGermany, by Suker 5 in America, by Cattaneo 6 in Italy, andby Mr. Simeon Snell in this country. These variousobservers find that a 10 per cent. aqueous solution when

dropped into the eye has the power of dilating the pupilmoderately within a few minutes, without affecting accommo-dation in the least. They also agree that the action of thepupil to light is to some extent retained while the eye isunder the influence of the drug, the effects of which passaway within from 4 to 6 hours. In no instance havethey seen any irritation or inflammation result from theapplication. Groenouw, who experimented on 100 patients,found that the dilated pupil had an average diameter of5’6mm. Suker speaks of mydrin as "an ideal mydriaticfor diagnostic purposes," and Mr. Snell’s experiences appearalso to have been equally favourable.These claims seemed to me too strong to be set on one

side without investigation. Accordingly for some time pastI have used a 10 per cent. watery solution of mydrin for thepurpose of dilating the pupil, when I wished to explore allparts of the fundus oculi with the ophthalmoscope or to

examine the cornea carefully in order to ascertain the

presence or absence of slight changes. Moreover, for the

7 Phisalix: Comptes Rendus de la Société des Sciences Naturelles,1897.

8 Berliner Klinische Wochenschrift. 1898, No. 1.9 Zeitschrift für Hygiene, 1898, No. 11.

1 Berliner Klinische Wochenschrift, No.38, 1887.2 Klinische Monatsblätter für Augenheilkunde, Band xxvii. (1889), p. 376.

3 Annales d’Oculistique, tome ci. (1889), p. 182.4 Deutsche Medicinische Wochenschrift, No.10, 1894, p.161 (quoted

in Jahresbericht der Ophthalmologie, 1895, p. 265).5 New York Medical Journal, June 8th, 1895, p. 714.

6 La Clinica Moderna, June, 1896 (quoted in Merck’s Annual Reportfor the year 1896).

7 Clinical Journal, Nov. 13th, 1895.

25

purposes of more exact study I have recently taken 20

patients and noted in each one (a) the near and distantsight, and (b) the diameter of the pupil. A single drop ofmydrin solution (10 per cent.) was then placed in the con-junctival sac, after which the following points were

observed: (a) the time at which the pupils became dilated ;(b) the transverse diameter of the pupils ; (e) the near anddistant vision ; and (d) the time at which mydriasis passedaway.The results obtained in this way may be thus briefly

related. The pupil became dilated in a period whichvaried, according to the individual, from 15 to 68minutes, the average of the 20 observations being 29’35minutes. The mydriasis was found to ensue more speedilyif patients kept their eyelids closed after the application hadbeen made. Owing to the fact that the iris did not com-

pletely lose its action to light, there was some little difficultyin measuring the size of the dilated pupil, the transversediameter of which ranged from 5 to 7’5 mm., and averaged6 mm. For a similar reason it was not altogether easy tosay with precision when mydriasis had passed away. Butin no instance did the maximum time (after full dilatation)exceed 4 hours, while the minimum stood at 75 minutes.The average worked out at 184’84 minutes-that is to say, atrifle more than 3 hours. In no case did sight, either fordistant or near objects, show any alteration when the eyewas fully under the influence of mydrin, a remark whichapplies also to the position of the punctum proximum.Lastly, it is practically important to note that the agent setup neither discomfort nor irritation.As the result of my observations I have reached the

conclusion that mydrin is capable of doing all thatwriters have claimed for it-namely, that it causes a

moderate dilatation of the pupil without involving thefunction of accommodation. It cannot but prove, there-

fore, a valuable agent in the hands, not only of the ophthal-mic surgeon, but also of the physician, who must often bedesirous of exploring the fundus oculi with a dilated pupil.Welbeck-street, W.

A MirrorOF

HOSPITAL PRACTICE,BRITISH AND FOREIGN.

ROYAL FREE HOSPITAL.A CASE OF MALIGNANT PUSTULE ; DEATH ; NECROPSY.

(Under the care of Mr. E. W. ROUGHTON.)

Nulla autem est alia pro certo noseendi via, nisi quamplurimas etmorborum et dissectionum historias, tum aliorum tum proprias col-lectas habfre, et inter se comparare.-MORGAGNI De Sed. tt Caus. Morb.,lib. iv. Proœmium.

-

THE methods by which persons become infected bycommunicable diseases are often obscure, but in the follow-

ing case it is practically certain that the patient was infectedfrom one of the hides with which he was working. Attemptshave been made to destroy the bacillus anthracis in bales ofmaterial which may contain it, and these attempts have beenvery successful in the case of wool, for it may be subjectedwithout damage to a temperature sufficiently high to kill thebacillus, but hides are spoilt by this treatment, and, so far aswe are aware, no satisfactory practical method exists of

rendering hides which have been taken from diseasedanimals absolutely free from power of infection. The

negative result of the culture from the blood is hardlysufficient to prove that no bacilli had entered the blood

stream ; in many of the fatal cases death is due to absorptionof toxins and not to the presence of the bacilli in the blood.For the notes of the case we are indebted to Dr. R. P.

Williams, house surgeon.A man, aged fifty-three years, was admitted to the Royal

Free Hospital on April 29th complaining of a sore andswelling of the right side of the neck. The patient was ablacksmith employed at the General Parcels Post Office,Clerkenwell. On April 26th he was engaged in mendingParcel Post baskets with strips of raw cowhide. The cow-hides are imported from various parts of the world and are

chosen by a Government inspector. The particular hide-.which the patient was using probably came from Rangoon orZanzibar. He noticed a pimple on the right side of the backof his neck on the 27th and he scratched it. It did nottrouble him till the night of the 28th when he found a-

swelling round a small sore in the original situation. Onthe following morning (the 29th) he felt so ill that he hadto cease work and he was directed to go to his medicalattendant, who sent him on to the hospital.On admission the patient was found to have a typical

malignant pustule situated on the right side of his neck.The brawny oedema extended above to the parotid and belowto the right clavicle. On microscopic examination of theserum from the vesicles anthrax bacilli were found in largenumbers. His temperature was normal. Mr. Roughtonoperated on the same day, excising the pustule and the skin for1-2L in. around it. The wound was swabbed with pure carbolicacid and left open, being dressed with cyanide gauze soakedin a 1 in 1000 biniodide of mercury solution. This was

changed every four hours.After the operation the temperature rose from normal to,

992° F. and at 10 P.M. it reached 1018°. The patient hadno sleep during the night and in the morning the œdemahad spread down the right side of the chest. The tempera-ture fell to 100° in the evening (the 30th) and he vomitedseveral times. Two bluish patches were noticed in theskin below the right clavicle. These gradually spread, theoedema itself also spreading to the left side of the chest and 1down towards the pelvis. No diarrhoea was present. The

patient gradually became collapsed and, in spite of stimu-lants, died at 1 P.M. on May lst.At 10 P.M. on April 30th two oultivations on gelatin were

made from the blood, one from the left index finger and theother from the oedema on the chest. No anthrax bacilliwere found in either tube. -

-zYeeropsy.-At the post-mortem examination the vessels ofthe pleura and the intestines were injected but no othergross pathological condition was found.

ANCOATS HOSPITAL, MANCHESTER.TWO CASES OF ECTOPIC PREGNANCY ; RECOVERY.

(Under the care of Mr. STANMORE BISHOP.)THE following two cases show clearly the benefit of early

surgical treatment in ectopic gestation. The older methods.

such as electricity, are being discarded, and it is more andmore recognised that the best results are obtainable by earlylaparotomy. The operation should be performed as soon asthe diagnosis is made with any fair degree of probability..Delay of even a few days may lead to a fatal issue.1CASE 1. Hæmatocele in Douylus’s pouch enlarged per-

forated Fallopian tube containing a clot; probable ectopicpregnancy; cœliotomy;; recovery.-A married woman, agedtwenty-eight years, was admitted to the Ancoats Hospital onSept. 14th, 1897. She had been married for eleven years.and had had four confinements and one miscarriage. Herfather died at the age of thirty-seven years from fever andher mother died at the age of sixty-five years from pneu-monia. Nine of her brothers were dead ; the causes of deathwere not known ; two sisters and one brother were alive andin good health. The patient had always been healthy up tothe time of her marriage. Her first labour occurred tenyears ago ; instruments were used, but there was no troublewith the placenta. She got up well, the child living. Hersecond labour occurred nine years ago ; it was easy and herconvalescence was normal; the child died from meningitisdue to a fall. Her third labour occurred six and a half yearsago ; it was easy and her convalescence was normal, thechild living. Her fourth labour (a miscarriage at three

months) occurred five years ago. She got up well, had oneperiod, and then became pregnant again. Her fifth labouroccurred four years ago ; the pregnancy was normal ; theconfinement lasted five days and no forceps were used. Shewas attended by a midwife and had never been well since.She noticed pain in the left iliac region before getting up.She was in bed for two months and pain had been inter-mittent ever since. The pain never occurred on the rightside. The left leg had been painful and aching, but not

1 American Journal of Obstetrics, April, 1895.