2
1037 is made the subject of a general discussion. For those who seek a wider mathematical training Prof. Pearson’s Institute offers a rich choice of lectures and practical classes. Neither the National Institute of Medical Research now, nor the School of Hygiene in the future, will claim to be able to produce by this method professional statisticians. A foreigner who wishes to master the general theory of mathe- matical statistics must betake himself to Prof. Pearson’s Institute or to Mr. Udny Yule, at Cambridge. I and my colleagues are only competent to help those who wish to emplov the statistical method as a useful tool in epidemio- logical and public health investigations. In a word, we are not epidemiological statisticians but statistical epidemio- logists." No doubt this method will be continued by Prof. I Greenwood when he formally assumes the professorial functions, and it appears to be suited to the require- ments of most medical post-graduates. DANGERS OF THE BARBITURIC HYPNOTICS. SINCE 1902, when the barbituric acid group of drugs was first introduced, there has been a steadily increasing stream of hypnotic preparations of this class. The number of proprietary remedies now on the market indicates the rapidity of their rise to popularity and the extensive use which is being made of them by practitioners throughout the world. Veronal, medinal, dial, and the like have a certain and speedy narcotic action which is eminently satisfactory, and after their use the patient wakes without objectionable sequelæ. Yet prolonged use of these drugs has at times produced symptoms almost identical with those of disease of the central nervous system, and Sir William Willcox, speaking at a meeting- of the Section of Therapeutics and Pharmacology of the Royal Society of Medicine on May 10th, was able to recall two cases, one of allonal and one of veronal poisoning, which had been sent to him by a neurolo- gist as undoubted cases of organic nervous disease. Ocular palsies, nystagmus, paralyses of the facial nerve or of a limb, polyneuritis, ataxia, remarkable hypotonia of the muscular system, scanning speech, faults of memory and marked emotional instability have all been recorded again and again in chronic cases of poisoning. The literature on the subject is indeed enormous, as Dr. Helen Young found when collaborating with Sir William Willcox and Dr. F. A. Pickworth in the preparation of the paper presented at this meeting. Most regrettable of all is the pre- dominance of mental symptoms, and especially of depression, leading to frequent suicides. The first case of directly fatal poisoning occurred in 1905. and the numbers rapidly increased until 1913, when the group was put on Part II. of the Poisons Schedule ; in 1918 it was transferred to Part I., and this resulted in a distinct drop, but in 1925 the numbers rose again to 22, as the public began to find out the possibility of using medical prescriptions. Sir William Willcox said that he regards these statistics as incomplete, for additional fatalities from these drugs may be hidden in the class of " narcotic poisoning " or in that of " broncho-pneumonia," since the comatose condition so lowers the resistance of the lungs that a true terminal broncho-pneumonia almost always s occurs. Most practitioners consider these drugs almost harmless and prescribe them freely, but certain investigators have always had their suspicions, and Sir William Willcox has already sounded a note of warning. Never before, however, has he been so itncompromisingly backed by the weight of solid laboratory evidence. Dr. Pickworth reported the experiments carried out, under rigid control conditions, in Sir Frederick Mott’s laboratories at 13irirnin-haiyi. and showed that continued administration of these - drugs produces pathological changes in the central nervous system which, although they usually dis- appear when the dose is discontinued, may neverthe- less become permanent. The chief phenomenon is the deposition of a homogeneous mucinoid substance in the white matter of the central nervous system, This is believed to be a product of neural meta- bolism, so that it must have an inhibitory effect on the life of the cells. Moreover, it is present in considerable quantity, and probably causes pressure and affects the intracranial circulation. Conduction along the nerve-fibres is interfered with, and a large part of the narcotic effect is due to the damping down of visceral afferent impulses. When administration of the drugs is still further continued, the cerebral cells shrink, lose their processes and stain poorly, and the Nissl substance is found to be reduced or even absent. It has been shown that these lipoid-soluble drugs render the lipoid envelope of the cell less permeable, so that tissue-respiration is embarrassed throughout the body. There is a capillary dilatation, an increase in the flow of blood. and a slowing of the pulse. The resemblance between the comatose condition induced by them and the condition of normal sleep is only superficial, and Dr. Pickworth found that under the influence of these drugs the margin between sleep and fatal coma in cats was a very narrow one. The peripheral parts of the nervous system are most easily affected, and the centre more slowly. There was definite evidence of a cumulative action, and of the existence of addiction Sir William Willcox had no doubt whatever. Nor, he maintained, is tolerance ever established. He felt strongly that the danger of these drugs was not properly recognised. They should be ordered only on a prescription marked " not to be repeated " and covering only six doses. The patient should be warned against daily doses, and preferably only one should be given each week. He desired to warn practitioners most solemnly against advertise- ments, which urged the value and ignored the dangers of preparations of the barbituric acid group. The poisonous constituent was often concealed under a fancy name, and a note in very small print. He regarded the continued introduction of new prepara- tions, and the glowing advertisements accompanying them, as seriously misleading to the profession and a grave danger to the public. E 107. THE new anaesthetic, E 107 or avertin, to which we alluded in a recent annotation (THE LANCET, April 2nd, p. 718) is further described in the Deutsche Medizinische Wochenschrift of April 22nd, and we are informed of its chemical nature, hitherto not divulged. The substance is tribromethylalcohol (CBr3CH2OH). It. decomposes on long exposure to light or in alcoholic solution. From experiments with rabbits it appears that avertin is rapidly eliminated by the kidneys. 50 per cent. of the amount administered being passed out into the urine in combination with glycuronic acid. The narcotic action of the anaesthetic is very rapid, and, when it is injected intravenously, is almost instantaneous. With excessive doses the respiratory centre is rapidly paralysed. Further clinical evidence is wanted before the drug can be tried with confidence for operations. _____ SOCIETY FOR RELIEF OF WIDOWS AND ORPHANS OF MEDICAL MEN. THE annual general meeting of this Society was held at 11, Chandos-street, London, W. 1, on May llth, when the report for the year 1926 was presented. The Society has scored in its long wrangle with the Inland Revenue Authorities for refund of income-tax as a charity under the Finance Act. In 1925 the Commissioners of Inland Revenue dissented from the decision of the Special Commissioners to grant rebate, and requested them to state a case for hearing in the High Court. With income-tax at 4s. in the pound the annual tax would amount to some £940, and the directors of the Society were compelled to reduce the Christmas present in December, 1925, and the grants from the Brickwell Fund in January, 1926. In June, 1926, however, when the case came up for hearing before Mr. Justice Rowlatt in the High Court, the Society obtained

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1037

is made the subject of a general discussion. For those whoseek a wider mathematical training Prof. Pearson’s Instituteoffers a rich choice of lectures and practical classes. Neitherthe National Institute of Medical Research now, nor theSchool of Hygiene in the future, will claim to be able toproduce by this method professional statisticians. Aforeigner who wishes to master the general theory of mathe-matical statistics must betake himself to Prof. Pearson’sInstitute or to Mr. Udny Yule, at Cambridge. I and mycolleagues are only competent to help those who wish toemplov the statistical method as a useful tool in epidemio-logical and public health investigations. In a word, weare not epidemiological statisticians but statistical epidemio-logists."No doubt this method will be continued by Prof.

I

Greenwood when he formally assumes the professorialfunctions, and it appears to be suited to the require-ments of most medical post-graduates.

DANGERS OF THE BARBITURIC HYPNOTICS.

SINCE 1902, when the barbituric acid group of

drugs was first introduced, there has been a steadilyincreasing stream of hypnotic preparations of thisclass. The number of proprietary remedies nowon the market indicates the rapidity of their rise topopularity and the extensive use which is being made ofthem by practitioners throughout the world. Veronal,medinal, dial, and the like have a certain and speedynarcotic action which is eminently satisfactory, andafter their use the patient wakes without objectionablesequelæ. Yet prolonged use of these drugs has attimes produced symptoms almost identical withthose of disease of the central nervous system, andSir William Willcox, speaking at a meeting- of theSection of Therapeutics and Pharmacology of theRoyal Society of Medicine on May 10th, was able torecall two cases, one of allonal and one of veronalpoisoning, which had been sent to him by a neurolo-gist as undoubted cases of organic nervous disease.Ocular palsies, nystagmus, paralyses of the facialnerve or of a limb, polyneuritis, ataxia, remarkablehypotonia of the muscular system, scanning speech,faults of memory and marked emotional instabilityhave all been recorded again and again in chroniccases of poisoning. The literature on the subjectis indeed enormous, as Dr. Helen Young found whencollaborating with Sir William Willcox and Dr. F. A.Pickworth in the preparation of the paper presentedat this meeting. Most regrettable of all is the pre-dominance of mental symptoms, and especially ofdepression, leading to frequent suicides. The first caseof directly fatal poisoning occurred in 1905. and thenumbers rapidly increased until 1913, when the groupwas put on Part II. of the Poisons Schedule ; in 1918it was transferred to Part I., and this resulted in adistinct drop, but in 1925 the numbers rose again to22, as the public began to find out the possibility ofusing medical prescriptions. Sir William Willcoxsaid that he regards these statistics as incomplete,for additional fatalities from these drugs may behidden in the class of " narcotic poisoning " or inthat of " broncho-pneumonia," since the comatosecondition so lowers the resistance of the lungs that atrue terminal broncho-pneumonia almost always soccurs. Most practitioners consider these drugsalmost harmless and prescribe them freely, butcertain investigators have always had their suspicions,and Sir William Willcox has already sounded a noteof warning. Never before, however, has he been soitncompromisingly backed by the weight of solidlaboratory evidence. Dr. Pickworth reported theexperiments carried out, under rigid control conditions,in Sir Frederick Mott’s laboratories at 13irirnin-haiyi.and showed that continued administration of these- drugs produces pathological changes in the centralnervous system which, although they usually dis-appear when the dose is discontinued, may neverthe-less become permanent. The chief phenomenon isthe deposition of a homogeneous mucinoid substancein the white matter of the central nervous system,This is believed to be a product of neural meta-

bolism, so that it must have an inhibitory effect onthe life of the cells. Moreover, it is present inconsiderable quantity, and probably causes pressureand affects the intracranial circulation. Conductionalong the nerve-fibres is interfered with, and a largepart of the narcotic effect is due to the damping downof visceral afferent impulses. When administrationof the drugs is still further continued, the cerebralcells shrink, lose their processes and stain poorly,and the Nissl substance is found to be reduced or evenabsent. It has been shown that these lipoid-solubledrugs render the lipoid envelope of the cell lesspermeable, so that tissue-respiration is embarrassedthroughout the body. There is a capillary dilatation,an increase in the flow of blood. and a slowing of thepulse. The resemblance between the comatosecondition induced by them and the condition of normalsleep is only superficial, and Dr. Pickworth found thatunder the influence of these drugs the margin betweensleep and fatal coma in cats was a very narrow one.The peripheral parts of the nervous system are mosteasily affected, and the centre more slowly. There wasdefinite evidence of a cumulative action, and of theexistence of addiction Sir William Willcox had nodoubt whatever. Nor, he maintained, is tolerance everestablished. He felt strongly that the danger of thesedrugs was not properly recognised. They should beordered only on a prescription marked " not to berepeated " and covering only six doses. The patientshould be warned against daily doses, and preferablyonly one should be given each week. He desired towarn practitioners most solemnly against advertise-ments, which urged the value and ignored the dangersof preparations of the barbituric acid group. Thepoisonous constituent was often concealed under afancy name, and a note in very small print. Heregarded the continued introduction of new prepara-tions, and the glowing advertisements accompanyingthem, as seriously misleading to the profession and agrave danger to the public.

E 107.

THE new anaesthetic, E 107 or avertin, to whichwe alluded in a recent annotation (THE LANCET,April 2nd, p. 718) is further described in the DeutscheMedizinische Wochenschrift of April 22nd, and we areinformed of its chemical nature, hitherto not divulged.The substance is tribromethylalcohol (CBr3CH2OH).It. decomposes on long exposure to light or in alcoholicsolution. From experiments with rabbits it appearsthat avertin is rapidly eliminated by the kidneys.50 per cent. of the amount administered being passedout into the urine in combination with glycuronicacid. The narcotic action of the anaesthetic is veryrapid, and, when it is injected intravenously, is almostinstantaneous. With excessive doses the respiratorycentre is rapidly paralysed. Further clinical evidenceis wanted before the drug can be tried with confidencefor operations.

_____

SOCIETY FOR RELIEF OF WIDOWS AND

ORPHANS OF MEDICAL MEN.

THE annual general meeting of this Society washeld at 11, Chandos-street, London, W. 1, on

May llth, when the report for the year 1926was presented. The Society has scored in its longwrangle with the Inland Revenue Authorities forrefund of income-tax as a charity under theFinance Act. In 1925 the Commissioners of InlandRevenue dissented from the decision of the SpecialCommissioners to grant rebate, and requested themto state a case for hearing in the High Court. Withincome-tax at 4s. in the pound the annual tax wouldamount to some £940, and the directors of the Societywere compelled to reduce the Christmas present inDecember, 1925, and the grants from the BrickwellFund in January, 1926. In June, 1926, however, whenthe case came up for hearing before Mr. JusticeRowlatt in the High Court, the Society obtained

1038

judgment with costs. The sum of ;E17ï! has sincebeen received from the Inland Kevenue, being theamount of income-tax withheld during the last twoyears. In October, 192H. it was therefore possible topay the full amount that had been deducted from thegrants to widows and orphans. The legal expenses incurred amounted to £276, of which £130 was

recovered from the Inland Revenue. A legacv,amounting to £3.935, brought up the total of investedcapital to £8138,550. Since the last report four membershave been elected and one has died. The Societv nowconsists of one hon. member, 161 life, and 141 ordinarymembers, making a total of 303. The income frominvestments amounted to £3953, 8371 was receivedfrom subscriptions and donations, and £42 from lifesubscriptions. The working expenses were £514.During the year three widows died and one came onthe funds, the amount distributed in grants during theyear being £5420 8s. At the close of the year therewere 49 widows and seven orphans in receipt of grants.Membership in the Society is open to any registeredmedical practitioner who at the time of his election isresident within a 20-miles radius of Charing Cross.Should a member remove anywhere outside the radius,even beyond the British Isles, he nevertheless remainsa member of the Society, provided he has conformedto the by-laws. Ilelief is granted to the necessitouswidows and orphans of deceased members of threeyears’ standing and of life members. The annualsubscription for a member who at the time of hiselection is under 40 years of age is 2 guineas ; if over40 but under 50, 3 guineas ; and if over 50, 4 guineas.

IN an article published in our issue of April 30thby Sir Arnold Lawson and Mr. A. L. Whitehead,dealing with the protection of the eyes necessary forthose viewing the total eclipse, a description wasgiven of a screen through which observations of thephenomenon throughout all its phases could be made with perfect comfort and safety. We learn, however,that the price of the screen was wrongly stated. Messrs. Hamblin, the well-known firm of opticians of15, Wig’more-street, London, who have placed thescreen,

" Eclipsia," on the market, state that thereare two varieties of the mask which will cost Is. M.and 3s. 6d. respectively, whereas the original articlein our columns gave the price as Is. We are informedthat the cheaper screen is just as effective a filter asthe more expensive one, but whereas the formerconsists of a screen of only one density, the latter.a more elaborate affair, having three grades ofdensity, allows the eclipse to be viewed to the bestadvantage at different stages.

AN address will be delivered bv Sir John RoseBradford to-day, Friday, May 13th, at 8.30 P.M.,at University College, London, the subject being theRelations of the College to Medical Education. Theaddress is the last of four delivered in connexion withthe centenary celebrations of the College, the previouslectures having been delivered by the late Prof. Starling on Feb. 28th, Sir Oliver Lodge on March 14th,and Dr. W. R. Chambers on May 2nd. The chair willbe taken by Sir George Thane and academic dressand decorations will be worn.

Sir Alexander Houston’s twenty-first annual reportto the Metropolitan Water Board, which has just beenissued (Messrs. P. S. King and Son. 21s.). gives theresults of the chemical and bacteriological examina-tion of the London waters for the calendar year 192u,and includes an illustrated account of the water-supplyfrom the Kentish Wells.

THE next session of the General Medical Councilwill commence at 2 P.M. on Tuesday. May 24th. whenthe President, Sir Donald MacAlister, will take thechair and give an address.

Modern Technique in Treatment.A Series of Special Articles, contributed by invitation,

on the Treatment of Medical and Surgical Conditions.

CCXXIII.THE TREATMENT OF LUPUS VULGARIS.

THE successful treatment of lupus vulgaris, whichentails the destruction of the disease with the minimumof scarring, is fraught with difficulty. The clinical typesand phases of the disease are so varied that no singlemethod of treatment is suitable for all cases, and. toobtain the best results, not only a knowledge of thedifferent forms of treatment is necessary, but the rightselection of the method best adapted to thepeculiarities of the individual case. As it is a localdisease of the skin, due to the presence of tuberclebacilli in situ, the treatment is essentially local.At the same time, the value of the local treatment canbe greatly enhanced by combining it with a suitabletonic régime on general. medical principles, withplenty of fresh air, good food, outdoor exercise andsunshine, or, where the last is unobtainable, withartificial sunlight from an arc lamp. There is nointernal specific for lupus. Thyroid extract, whichonce had a reputation in this connexion, has almostbeen forgotten; tuberculin injections have not fulfilledtheir early promise, and since they are liable to light uplatent foci of tuberculosis elsewhere, they are nowcomparatively rarely employed, except in extensiveulcerated cases, where injections of Koch’s tuberculin(T.R.) or tuberculin (B.E.)may be of service in healingthe ulceration.The main objects of local treatment are : (1) the

complete removal of the diseased tissue; and (2) theproduction of as little scarring and disfigurementas possible. The methods employed may be con-veniently considered under the headings of surgical,

physical, chemical, and radiotherapeutic.S’urgicud Methods.

Excision.—Where practicable, when the lesions arenot too extensive, and are situated on covered partsof the body, excision is the most satisfactory treatment,and even on the face, in the hands of a skilled operator,excellent results may be obtained bv it. The incisionshould be made at least a quarter of an inch beyondthe diseased area, and not only the skin, but the super-ficial half of the subcutaneous fat should be removed.After the excision the surface should be grafted.Krause’s deep grafting should be employed rather thanThiersch grafting, since, with the latter, the wound doesnot heal rapidly, and the scar is liable to be uneven,occasionally keloidal, and may be followed by can-traction. Deep grafting consists of transplanting apiece of skin of the exact shape and size of the tissueexcised, taken from some suitable part, such as thethigh. The graft should be cut as deep as the fatlayer, the fat being scraped off before it is put inposition, and it should be slightly larger than therequired size to allow for shrinkage. After beingplaced in position, it is neatly sutured to the edges ofthe wound. Where the lupus occurs about the mouth,eyelids, and nose, it may be difficult to get the graft tohold. and in such cases some form of plastic operationmay be resorted to, employing grafts from a neigh-bouring part with pedicles, which can be severedwhen the graft has healed in place.

Scraping is a siirnpler method than excision, butthe results from it are more uncertain. It is apt toleave unsightlv scars, and if not sufficiently drasticmay lead to a dissemination of the disease by openingup the lymphatics. It should be done under a generalanaesthetic by a Volkmann spoon, methodically,thoroughly, and firmly, and should reach down to thesubcutaneous tissue. Owing to the hemorrhageassociated with scraping, it is difficult to distinguishhealthy from diseased tissue. except by the feeling