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of the Privy Council, it is to make its own rules,deciding for example what rules of evidence should beobserved. Unlike the present council, it may obligewitnesses to testify on oath, and command their

presence by subpoena. It will, like the presentcouncil, be advised by a legal assessor, who will be abarrister, advocate, or solicitor of not less than tenyears’ standing, working under rules made by theLord Chancellor. When the assessor advises thecommittee on any question of law he is to do so in thepresence of all the parties to the proceedings (or theirrepresentatives) ; if the advice is given in camera,the parties shall be told what it was ; and if the com-mittee does not accept his advice the parties mustagain be informed. After so many years in which it

, has been advocated, a right of appeal from thecouncil’s decisions is at last granted; for within28 days of hearing that his name is to be erased fromthe Register the practitioner may appeal to the

Privy Council. These are large and welcome changeseven if they do not at all points fulfil the suggestionsput forward jointly by the defence societies.2 Possiblythe rules the committee will make will cover some ofthese-for example the need to ensure that (apartperhaps from the president) the members formingthe tribunal shall not have previously considered theevidence as members of a penal-cases committee.The defence societies thought it advisable that inall cases the initial complaint should be supportedby an affidavit or affidavits, and that " all evidencebefore the disciplinary tribunal be given orallyon oath, save for good and sufficient reason, exceptevidence as to character which may be given in

writing." More material was their recommendationthat the tribunal should be able to administer other

penalties short of erasure (namely, suspension for

varying periods or censure of varying degrees); andwe cannot help regretting that the Bill retains the

phrase " infamous conduct in a professional respect "with its flavour of hanging, drawing, and quartering,instead of adopting the societies’ term " professionalmisconduct." But with so much to approve thereis no need to emphasise relatively minor points ofdisagreement.

Œstrogen Therapy in Menstrual andPregnancy Disorders

THE limitations of oestrogen treatment in gynaeco-logy and obstetrics are at last being more clearlydefined. On the whole, the views expressed atthe Royal Society of Medicine on March 17 werecommendably cautious.

Dr. A. M. SUTHERLAND, discussing the 1000 casesof abnormal uterine bleeding in which he has examinedthe endometrium, emphasised the need for diagnosticcurettage before endocrine therapy is decided on,for in 14% of the cases organic pathological lesionswere found. On the other hand, of the remainder,nearly two-thirds showed no histological abnormality,and less than a third had any evidence of endometrial

hyperplasia. These findings suggest that it is hardlyjustifiable to claim that some form of treatment has" cured ’’ functional non-ovulatory uterine bleeding onthe basis of normal endometrial or biphasic temperaturepattern rafter treatment unless the non-ovulatory

2. See Lancet, 1946, i, 936.

nature of the cycles was established before treatment.Where curettage reveals endometrial hyperplasia-the"

metropathic " group—SWYER 1 has lately been

advocating oestrogen therapy. The efficacy of highdoses of oestrogen and progesterone in producingimmediate haemostasis during the bleeding phase-KARNAKY 2 originally advocated 10-25 mg. of stil-bcestrol every 15 minutes until bleeding ceased within4-6 hours-has been generally accepted. Such heroicdosage is seldom necessary, though it will often haveto be a good deal higher than the 2-5 mg. dailyrecommended by SwYER to produce " obviousamelioration of the bleeding within 48 hours." -Most English gynaecologists would not expect

more from endocrine therapy in menstrual disordersthan the, ability of oestrogen to check bleedingimmediately, and the ability of progesterone, givenin a non-bleeding phase and repeated at regularmonthly intervals, to cause progesterone-withdrawalbleedings, thereby forestalling the onset of anothermetropathic bleeding phase. But SWYER has reintro-duced the " Hamblen technique," consisting in

cestrogen haemostasis, " cycle development " by theproduction of oestrogen-withdrawal bleedings, and"

pituitary regulation" with oestrogen followed bythe combined administration of oestrogen and pro-gesterone. HAMBLEN 3 claimed that this techniquegives a 45% salvage rate in young women wnnfunctional uterine haemorrhage, and that abouthalf of those who do not react to the oestrogen-progesterone scheme will respond satisfactorily tohis " one-two cyclic gonadotrophin therapy." SWYERhas slightly modified HAMBLEN’S technique, and heof course gives the cestrogens and progestogens bymouth, by which route they have for some time beenproved effective in adequate doses. He has found

secretory endometrium in all of his 8 cases in whichinitial biopsy showed a proliferative endometrium orcystic glandular hyperplasia. Unfortunately he doesnot tell us the interval between the two biopsies orthe ages of the 8 patients. A claim of 100%success for any treatment is so impressive that itwould have been interesting to know the details ofeach case. The basis of the cyclical progesterone-withdrawal treatment is the production of artificial"

periods," as a substitute for irregular metropathicbleeding, until the metropathic condition undergoesspontaneous remission.. Puberty bleeding is especiallyprone to such remissions ; indeed, there are manycases in which only one prolonged and excessive boutof bleeding has ever occurred. Fortunately the metro-pathic type of maturity bleeding is also likely toundergo spontaneous remission. The possibility ofthese remissions must be borne in mind in evaluatingthe results of any form of treatment, and statisticalanalysis might sometimes be admissible.Much has been written about the endocrine treat-

ment of dysmenorrhoea. It seems clear that spasmodicdysmenorrhcea occurs only in ovulatory cycles, andthat if ovulation is inhibited by giving oestrogen inthe first half of the cycle the resulting withdrawalbleeding will be painless. (This simple fact has beenamply proved by endometrial biopsy and by basaltemperature records.) Many workers believe that

1. Swyer, G. I. M. Brit. med. J. 1950, i, 626.2. Karnaky, K. J. Sth. med. J. 1940, 33, 1285.3. Hamblen, E. C. Endocrinology of Woman. Springfield, Ill.,

1945.

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this is the most that endocrine therapy can offerin dysmenorrhoea. At the meeting Mr. T. N.MACGREGOR claimed to have produced painlessperiods in 38 patients with spasmodic dysmenorrhoeaby giving them oestrogen in the second half of thecycle. It is less easy to understand the underlyingrationale of this method, especially as it is generallyagreed that cestrogens given after the tenth day of thecycle have no demonstrable effect on the remainingevents of the cycle and will not prevent menstruationfrom taking place at the expected time. It is probablethat in the presence of progesterone exogenousoestrogens are in some way " inactivated," as

they may be, and for the same reason, in

pregnancy. -

Prof. T. N. A. JEFFCOATE made some soberingremarks on the use of cestrogens in pregnancy. Hehad reached the conclusion that they are fully effectiveonly in preventing lactation and are less reliable in thesuppression of established lactation. He doubtedwhether breast engorgement will respond to an

occasional dose. If one was prepared to give themfor up to seven days, he thought that oestrogens mightassist in evacuating a missed abortion. He was

convinced that oestrogen therapy has no part to playin the induction of labour ; as much as 500 mg ofcestradiol intravenously had been ineffective in a

case of inertia. However, considerable interest hasbeen taken in the work of the SMITHS 4 on the

oestrogen treatment of threatened and repeatedabortions, toxaemia, and pre-eclampsia, and inPRISCILLA WHITE’S 5 report of a 90%, fcetal survival-rate in 300 deliveries where the diabetic mothers hadbeen treated with oestrogen during pregnancy.OLIVE SMITH 6 claims success-rates of 72% in 219cases of threatened abortion treated with oestrogen; 78% in 272 cases where the oestrogen was givenprophylactically, on the basis of previous history,to prevent abortion ; and 75% where it was givenprophylactically again on the previous history, to

prevent complications of late pregnancy. For

prophylaxis the SMITHS insist on a rigid, graduallyincreasing, dosage schedule reaching 125 mg. of stil-bœstrol daily by the’ 35th week. This is a verydifferent schedule from that proposed by CHRISTIEBROWN 7—0.6 mg. of dienoestrol and 10 mg. ofethisterone daily up to the 18th week, after whichthe embryo should " plough its own furrow." Since0-6 mg. of dienoestrol is equivalent to about 0-15 mg.of stilboestrol the -discrepancy is very Wide. CHRISTIEBROWN suggests that larger doses or a longer courseof oestrogen may give rise to abnormality in thefcetus. He gives similar doses during the secondhalf of the menstrual cycle in all cases of infertilityshowing no gross disease, to " secure firm implanta-tion of the ovum," and 34% of 111 patients so treatedbecame pregnant within six months. Here again isa method of treatment whose rationale is difficult toreconcile with the accepted physiology of the reproduc-tive cycle, especially in relation to the behaviourof exogenous oestrogens and progestogens in thesecond half of the cycle. Yet it has yielded such4. Smith, O. W., Smith, G. van S., Hurwitz, D. Amer. J. Obstet.

Gynec. 1946, 51, 411.5, White, P. Penn. med. J. 1947, 50, 705.6. Smith, O. W. Amer. J. Obstet. Gynec. 1948, 56, 821.7. Brown, R. C. Brit. med. J. 1948, ii, 851.

surprisingly good results that one wishes the serieshad been statistically treated, for instance by givingalternate cases the active material and the placebo.

New Uses for Streptococcal EnzymesTHE liquefying enzymes elaborated by some strepto-

cocci may well find increasingly wide applicationsin surgery and medicine, by aiding the removal ofthick pus or other exudates from body cavities andsurface wounds. Their uses have lately been reviewedby TILLETT and his colleagues,! with striking colourphotographs. TILLETT and GARNER2 first describedthe fibrinolytic action of broth cultures of hæmolyticstreptococci in 1933. Further studies of the liquefyingprocess have shown 3 that the streptococcal fibrino-lysin, which has been named streptokinase or SK,combines or reacts with a globulin factor present inserum or exudate, variously called plasminogen, serumprotease, or activatable fibrin-lysing, system, to formthe active fibrin-lysing system or plasmin. Two yearsago, SHERRY, TILLETT, and CHRISTENSEN,4 demon-strated that the physical characters of thick pusthat make it difficult to aspirate are due not so muchto fibrin as to desoxyribose nucleoprotein, which

forms 30-70% of its total solids. They also showed 5that the organisms producing streptokinase, such asthe group A hæmolytic streptococci, can also producedesoxyribonuclease-now known as streptodornase orSD-which readily liquefies thick pus or viscoussolutions of the nucleoprotein itself. CHRISTENSEN 6

has since described an improved method for purifyingthese two enzymes ; alcoholic precipitation is followedafter solution by precipitation with protamine, anda further precipitation with 20% alcohol then bringsdown ’streptokinase and leaves desoxyribonuelease insolution. He also describes the somewhat formidabletechnique for estimating not only the two enzymesand plasminogen but also antistreptokinase, a normalconstituent of blood-serum which inhibits strepto-kinase. The level of antistreptokinase in the bloodis normally higher in adults than in infants, it israised in rheumatic fever, and it reaches very hightitres after the intrapleural injection of streptokinase.TILLETT and SHERRY 3 have injected the purified

enzymes into the pleural cavity in patients withdifferent types of effusions, and the only toxic effectsnoted were, some transient fever and malaise. Infibrinous pleurisy the aspirated fluid showed a fall infibrinogen and a rise in non-protein nitrogen, some-times accompanied by a leucocytic reaction. In..mostcases of empyema the enzymes rapidly reduced. theamount of sediment in the pus and its viscosity, sothat it could readily be aspirated, but in two casesthe pus was sufficiently acid to inactivate the enzymesand no benefit was obtained. - In postoperativehaemothorax the injection of streptokinase made it

possible next day to aspirate much of the effusionas a thin brownish fluid. In the latest paper, TILLETT

et al.l mention two further cases of haemothorax inwhich loculation or blood-clot hindered aspiration,1. Tillett, W. S., Sherry, S., Christensen, L. R., Johnson, A. J.,

Hazlehurst, G. Ann. Surg. 1950, 131, 12.2. Tillett, W. S., Garner, R. L. J. exp. Med. 1933, 58, 485.3. Tillett, W. S., Sherry, S. J. clin. Invest., 1949, 28, 173.4. Sherry, S., Tillett, W. S., Christensen, L. R. Proc. Soc. exp.

Biol. N.Y., 1948, 68, 179.5. Tillett, W. S., Sherry, S., Christensen, L. R. Ibid, p. 184.6. Christensen, L. R. J. clin. Invest. 1919, 28, 163.