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international units of crystalline oestrone). Thenext object is to induce growth of the kind ofendometrium associated with normal menstrual

bleeding. In an adult uterus this can almost

always be done by giving the corpus luteum

hormone, progestin, in doses of 5-50 rabbit units.Assuming success in these two aims, the primarydefect-ovarian deficiency-remains to be over-

come ; for the injection of ovarian extracts is

merely substitutive treatment, and it is doubtfulhow far it can initiate spontaneous menstrual

cycles. The fundamental object is to convert theinfantile ovary into an adult ovary with normalfunction. In immature animals this can be done

by injecting gonadotropic (gonad-stimulating)principles derived either directly from the pituitarygland or from urine excreted in pregnancy. Itwould therefore be reasonable in primary amenor-rhoea to follow treatment of the uterus (with oestrinand progestin) by administration of gonadotropicextracts ; and there is in fact evidence that in afew cases this has led to the onset of cyclicalmenstruation. It has to be acknowledged thatthe extracts at present in use are seldom potentenough to produce any lasting effect on a seriouslyundeveloped ovary. But where the deficiency isnot so great, and we have merely the conditionof secondary amenorrhoea, treatment is more

promising ; and in oligomenorrhcea-so oftenassociated with dysmenorrhcea or sterility-theoutlook is far more hopeful. The principles oftreatment here are much the same, but someauthorities such as CLAUBERG claim that oestrinby itself suffices for cure. He finds that inimmature mice its injection may actually lead tothe formation of corpora lutea, and since it iswell established that oestrin has no direct actionon the ovary this effect must, it seems, be dueto stimulation of the pituitary. It has becomeevident that the ovary and anterior pituitaryare complementary in action ; too much cestrin

depresses pituitary activity while too little makesit unusually apparent. CLAUBERG describes thisas the " pituitary release phenomenon -" ; hebelieves that large doses of oestrin promote pituitaryquiescence and that sudden cessation of them

brings about abnormal pituitary activity sufficientto cause formation of corpora lutea in the ovaryand consequent changes in the uterine endometriumleading to pregnancy. The dysmenorrhcea oftenassociated with scantiness of menstruation responds,it is said, to cestrin therapy in some 30-50 percent. of cases.

There are two other important conditionsin which treatment with ovarian hormonesis especially satisfactory. First, oestrin isfound useful-in less heroic doses, and even bymouth-at the menopause. Hot flushes sometimes

yield readily to relatively small doses such as

500-3000 international units of oestrone daily bymouth. Treatment induces a sense of well-beingand may relieve associated disorders such as

pruritus or kraurosis vulv2e and acne rosacea.

Secondly, progestin finds rational employment in

2 Clauberg, C. : Deut. med. Woch., 1935, lxi., 1189.

cases where repeated abortion in early pregnancyhas no apparent cause, and the proportion ofsuccessful results is too high to be fortuitous.A theoretical objection to using gonadotropic

extracts (prolan) is that they may over-stimulatethe ovary and thereby damage its function

irreparably. This danger will certainly haveto be reckoned with when extracts of greaterpotency become available, but those who haveso far used such hormones-chiefly for excessivebleeding-do not seem to be much impressedby it. The results they record vary consider-

ably. HENDERSON,3 for instance, says that hehas treated 39 cases of menorrhagia and metror-rhagia with " anterior pituitary-like hormones,"of which 31 were relieved and 25 returned to normalmenstruation ; of the 8 patients who failed tobenefit 4 were proved to have local pelvic lesionssufficient to cause the complaint. GEIST andSPIELMAN,4 on the other hand, found that thishormone brought about improvement in only 2out of 14 cases of the same kind, and concludepessimistically that " the present widespread useof endocrine ’ products in menstrual disturbancesseems to us unwarranted." Excessive uterineloss is attributed to lack of some anterior pituitaryfactor, or to insufficient pituitary stimulation ofthe ovary. Ripe Graafian follicles fail to ruptureand luteal tissue is absent ; the ovary is studdedwith relatively small follicular cysts ; and the. endometrium proliferates unduly and bleeds pro-fusely. It is with the object of inducing luteiniaa-tion of the ovarian follicles and a progestationaltype of endometrium that gonadotropic hormonesand/or progestin are administered. Three factors

commonly militate against their success. In thefirst place the patient often presents herself toolate ; the cases which respond best are those ofbleeding at puberty, which are usually puremenorrhagia. Secondly, the doses of gonado-tropic extracts at present available may oftenbe too small to achieve their purpose. Finally,the present preparations may not contain the

principle which is most effective in controllinguterine hoemorrhage.

MEDICINE AS A USEFUL ARTIN a bookseller’s catalogue which came by the

same post as a copy of the inaugural lecture givenby the new professor of medicine in the Universityof Liverpool, medicine and surgery are classedunder the " useful arts," and Prof. ConEN’saddress gives good grounds for reflection as tohow far such a definition is or ought to be true.What in short is the prime concern of a professorof medicine ?-a question which is being discussedmore and more as the academic equipment of thesubject is being expanded in so many places.It is, without doubt and as the regulations of hischair likely enough prescribe, to advance medicineby teaching and research ; the two are intimatelyconnected, for nothing but second-rate teachingwill be found in an atmosphere where there is

3 Henderson, D. N. : Canad. Med. Assoc. Jour., 1935, xxxii., 617.4 Geist, S. H., and Spielman, F.: Amer. Jour. Obst. and

Gyn., 1935, xxix., 518.

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no curiosity to know more, and good academicteaching is an almost necessary prelude to worthyresearch. And to carry out this ideal, the

professor’s first business must surely be to knowabout medicine ; he must be what is sometimes

nowadays esteemed rather lightly, a learnedman and a scholar. And this not only for histeaching, for it is as true in medicine as in otherdisciplines of human interest that a good enoughknowledge of what has been said and written

already will give the solution of many problemswhich seem unsolved; we have the data if onlywe had the wit to put them together. About the

necessity for learning there is, we imagine, littledifference of sober opinion, and it is as idle as itis fashionable to waste time finding out what isknown already ; knowledge can be advanced onlyfrom a solid foundation, it cannot start in theair. Granting this, what is the professor to donext ? 1 Is it to be his chief aim to cure the sickand prevent illness or to study the origins, nature,and course of diseases without taking much countof the practical outcome ? 1The two roads have many connexions, but they

are not the same. A pretty complete knowledgeof the natural history of a disease does not

necessarily lead to its prevention or cure, nor doesthe discovery of a cure always wait a knowledgeof what is being cured. Irrational therapeutics(such as aspirin for headache) and rational therapeutics (such as insulin for diabetes) may bothconfer great benefits on the sick and it would bedifficult to make a just estimate of which of these

two instances has been of most benefit to mankind,though there is little doubt as to which would beesteemed most highly by a healthy professor.Advances in medicine come from anywhere andalmost everywhere, and we should say that theprofessors should go along any road which happensto appeal to them. To one it may be an abstractstudy of the chemistry of haemoglobin, to anotherit may be a direct search for a cure of the commoncold; given knowledge, industry, and brainsone is as likely to advance medicine as the other.In the old Italian universities professorships weremade life appointments to secure their holdersfrom undue interference by their colleagues of thefaculty of theology: e equal freedom is needed

nowadays and perhaps a little more sympathybetween those to whom different paths appeal.There is only one thing which should be common tothem all-the problems to which they pay attentionmust come from the study of sick people even ifwe agree with Prof. COHEN in thinking thatSYDENHAM exaggerated the possibility of alwaysfinding the answers in the same way.Clinical study is and will remain, as Prof. RYLE has

reminded us,’ the primary method of attack onclinical problems if only because the setting of asoluble question is generally half the difficultyin finding an explanation. Several of the dramaticadvances of medicine in recent times have comein other ways, but the whole of modern practiceis permeated with clinical improvements whichare at least as grateful to the patient as the moresensational items.

ANNOTATIONS

CARBON DISULPHIDE AND ITS DANGERS

CARBON disulphide is unjustly known as a veryevil-smelling liquid ; the factor is not its own, but isdue to minute quantities of undesirable associates.The B.P.C. remarks mildly : " It should not have afoetid odour." Its dangers however are of a moretangible kind and not realised as fully as they shouldbe. Those who work much with it in the laboratoryhave found it highly innammable ; even evaporationover a hot plate, with the burner turned out, willsometimes cause a fire, made more unpleasant bythe irritating and poisonous sulphur dioxide formedon combustion. Hot steam pipes or electric bulbswill sometimes cause ignition, for its auto-ignitiontemperature is between 125° and 135° C. Specialprecautions are therefore needed when carbon

disulphide is used in industrial operations, which itoften is owing to its useful solvent properties, and itslow boiling-point (46° C.), which enables it to beremoved easily from articles on which it has beenused. The risk of explosion is high as a mixturecontaining only 19 volumes in a thousand of air isexplosive. But when all possible precautions havebeen taken against the risk of fire there is still thedanger from the high toxicity of the vapour. Slightsymptoms are produced after some hours’ exposure toconcentrations as low as 322 to 386 parts per millionin air; the maximum concentration that can beinhaled for an hour without serious disturbance is483 to 807 parts. Exposure for over half an hour toa concentration of 1150 parts is dangerous. Lowerconcentrations lead -to chronic poisoning. The usual

effects of inhalation of the vapour for some weeks arenausea, indigestion, headache, and giddiness, some-times accompanied by emotional disturbances whichmay be frankly hysterical in character. The breathhas a characteristic odour, the tongue is pale andflabby, and there is facial pallor. In cases of mild

absorption of the vapour, an appearance of anxietywith sweating of the hands and forehead is suggestive ;these symptoms indicate a degree of exposure which,if continued, may lead to other effects. The mentaldisturbance increases and is accompanied by impair-ment of memory, mental dullness, and depression.The speech may be affected ; contraction of thevisual fields with diminution of accommodationoccurs later. One of the earliest signs of chronicintoxication is muscular weakness due to a toxicneuritis. First to suffer are the facial muscles or theflexor muscles of the forearms, the lower limbs beingaffected later. Tremor, parsesthesia, and loss ofsensation are also seen, and, as a later complication,optic neuritis. Ultimately there is difficulty in

walking ; the patient may become bedridden and evenunable to feed himself. Recovery is slow and

uncertain ; some effects may remain. In acute poison-ing the mental disturbance may amount to mania.

Since Dec. 31st, 1924, poisoning by carbon disulphidecontracted in a factory or workshop has been com-pulsorily notifiable to the chief inspector of factoriesby medical practitioners, and by occupiers to thedistrict inspectors.2 Since that date 18 cases have

1 See THE LANCET, Dec. 7th, 1935, p. 1301.2 Ibid., 1934, i., 1299.