1445

eradication must come soon. Not as an alternative but as

perhaps a preliminary to eradication the Ministry ofAgriculture has announced a revised scheme for vac-cination against brucellosis, to begin in 1962.21 Calvesinoculated with a living strain of Br. abortus of low viru-lence (e.g., S.19) are protected throughout their repro-ductive lives against any but an overwhelming infection.This vaccine has been available for at least ten years, andwhere it has been used conscientiously it has dramaticallyreduced the losses of calves. Unfortunately less than halfthe farmers in the country have used it, and then oftenin a haphazard way. Under the new scheme the vaccinewill be available for calves only, without cost but withoutcompulsion. (It is important to limit its use to calves

because, given to. older animals, it is likely to leave aresiduum of circulating antibodies which will hinder

diagnosis in any future scheme of eradication.) The

arguments for and against compulsion have been endless,and we can only hope that the Minister’s decision on thispoint is rewarded by success. There can be no doubtthat wider use of the vaccine will save a lot of calves. Atthe same time it can be expected to reduce the number ofsources of infection-and there is reason to think that

only those cows which excrete the organisms in largenumbers are important in the spread of infection to othercattle, and perhaps to man. On the analogy of otherdiseases there is no more potent way of reducing infectionthan by diminishing the sources of infection, and if thisscheme is accepted by the farming community it maylower the incidence of brucellosis to the point whereeradication will be within our means. Meanwhile the useof S.19 vaccine has introduced another occupationaldanger. Many veterinary surgeons have managed to

vaccinate their own left hands; and the results are, to putit mildly, irritating.

21. Times, Dec. 11, 1961.22. Greenblatt, R. B., Barfield, W. E., Jungck, E. C., Ray, A. W. J. Amer.

med. Ass. 1961, 178, 101.23. Holtkamp, D. E., Davis, R. H., Rhoads, J. E. Fed. Proc. 1961, 20,

419.24. Segal, S. J., Nelson, W. O. Anat. Rec. 1961, 139, 273.

INDUCTION OF OVULATION

CLINICIANS interested in infertility may be heartened bya promising observation made by Greenblatt et al. 22 duringan attempt to evaluate the anti-fertility effect of a com-pound known as MRL/41. This compound, which isstructurally related to the non-steroid oestrogen, chloro-trianisene (’ Tace ’), is known to inhibit pituitarygonadotrophin in rats.23 24 Greenblatt et al. found that

MRL/41 apparently induced ovulation in a high propor-tion of amenorrhoeic women. This effect was judgedlargely by the production of a typical corpus-luteumthermogenic effect, which in some cases was sustained forlonger than the usual fourteen days, by studies on vaginalcells, cervical mucin, and endometrium, and by hormoneassays where feasible.

With commendable caution, these workers remark thatthe only absolute proof of ovulation is the recovery of ovaor the occurrence of pregnancy. Such final proof was infact obtained in 4 cases. 2 of these 4 patients becamepregnant during treatment and 2 after the conclusion oftreatment-in 1 case three months later, after the inductionof a regular ovulatory rhythm. In 4 normally menstruating(and ovulatory) women, administration of MRL/41 pro-duced no evidence of inhibition of ovulation, though in

2 cases there was unexplained prolongation of the thermo-genic effect of the corpus luteum beyond fourteen days.In 3 cases of precocious puberty, ovarian activity, judgedby vaginal cells and menstrual flow, was reduced somewhat;1 child became irritable and rebellious, and treatment hadto be discontinued. In 4 cases of suspected prematuremenopause (the ages of the patients are not stated) and in1 case of ovarian agenesis no effect was noted. This

suggests that a potentially normal ovary is required for thecompound to be effective.

Certain untoward, though not dangerous, side-effectswere noted, including possible allergic manifestations andin 3 cases ovarian cysts which regressed slowly. The

production of hot flushes in several patients, together withthe regression of precocious vaginal mucosal developmentin the children, suggests that the compound is anti-

oestrogenic, and that it probably acts directly on thepituitary-ovarian balance. But no alteration in the urinarygonadotrophin titre was noted in the 4 presumed meno-pausal women; nor was there any evidence, from studiesof 17-ketosteroid excretion, that the drug inhibitedadrenal function.

Ovulation is notoriously difficult to induce in the human.Apparent success sometimes attends cyclical substitutiontherapy, administration of corticosteroids and wedgeresection of the ovaries in the Stein-Leventhal syndrome,and even pituitary irradiation; but on the whole thetreatment of the anovulatory state, with or withoutamenorrhoea, has been disappointing. Several of the cases

successfully treated by Greenblatt et al. had already failedto respond to one or more of these other methods. Theresults so far obtained with MRL/41 seem to give promiseof a major advance in the treatment of ovulatory disorders.

1. Russell, W. R., Smith, A. Arch. Neurol. 1961, 5, 4.2. Jackson, J. H. Selected Writings (edited by J. Taylor). London, 1932.3. Head, H. Aphasia and Kindred Disorders of Speech. New York,

1926.4. Russell, W. R. Brain, 1932, 55, 549.5. Russell, W. R. Brain, Memory, and Learning. Oxford, 1959.6. Scoville, W. B., Milner, B. J. Neurol. Neurosurg. Psychiat. 1957,

20, 11.

THE BEST YARDSTICK WE HAVE

ONE good thing that came out of the 1939-45 war wasa systematic study of the effects of head injury at theMilitary Hospital for Head Injuries, Oxford. In civilianlife trauma to the brain is common enough, but theopportunity of correlating various features is generallylacking. One such correlation-between the duration of

post-traumatic amnesia (P.T.A.) and other data-has beenworked out in detail by Russell and Smithy who remarkthat the period of amnesia should be taken, not as theduration of complete loss of consciousness, but as thetotal period during which normal conscious functioningis impaired-the time taken for a patient to " recover hissenses " 2 or to return to the state that Head 3 describedas

" vigilance ". In this period the patient may be coma-tose or, at the other end of the scale, slightly confused.The importance of its duration was indicated by Russell 4

many years ago. It comprises, as has since been learnt,the interval during which the patient is unable to storeany memory of current events. Russell 5 suggested thatthis ability was associated with the function of the hippo-campus and its connections-a view which accordswith neurophysiological evidence and with clinical

findings. 6

Certain cells in the " Sommer sector " of the hippo-