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CLINICAL EFFECTS OF OVARIAN HORMONE

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586 usually followed by re-admission with recurrence of the symptoms, sometimes in an aggravated form ; in no case was a lasting benefit or a cure obtained. The cases in which the greatest improvement-sometimes amounting to cure-was obtained were those which were treated by prolonged restriction to a fluid diet, without the passage of bougies. Only two of these came to autopsy ; in one of them the symptoms had been cured at the age of 3, and death from tubercu- losis occurred later, the oesophagus being found to be absolutely normal. Sheldon and Ogilvie make some interesting sugges- tions on the pathology of this type of oesophageal obstruction. They believe that the abnormality is congenital. This conception is supported by a high incidence in premature children and a four-to-one ratio of males to females, as well as by the onset of the symptoms in early infancy. They suggest that a narrowing may take place at the junction of the two segments (retropharyngeal and pre-gastric) of the foregut by the union of which the oesophagus is developed, or that the lower segment may be narrowed as the result of inadequate growth. If suitable conditions can be maintained-the most important being a purely fluid diet-spontaneous cure of the symptoms may be achieved by the growth of the oesophagus to a calibre adequate for the transmission of solids. They have certainly made out a case for regarding the majority of cesophageal defects in children as something different from achalasia, and for giving prolonged trial to this method of treatment. LIVER IN ANÆMIA. WITHIN the last four years a great deal has been added to our knowledge of the use of liver in the treatment of anaemia, and Dr. Janet Vaughanl finds a general consensus of opinion that it is a certain remedy for those forms associated with a megalo- blastic hyperplasia of the bone-marrow. The best known of these is, of course, " pernicious " anæmia, but a good deal of evidence has now accumulated tending to bring under this heading the anaemia of sprue and also the type described by Channing, in the ’forties of last century, as the " grave anaemia of pregnancy." It has still to be directly proved whether there is megaloblastic hyperplasia of the bone-marrow in this last type of anaemia, but the condition is characteristically associated with a high colour-index, and this is indirect evidence of such hyperplasia. In all these states there are signs that the therapeutic action of liver is seriously inhibited by sepsis, but this is not to be taken as an indication that sepsis is in any way their cause. It is further generally agreed, says Dr. Vaughan, that liver is useful in the treat- ment of anaemia secondary to gastric and other haemorrhage, and that in these conditions its action is enhanced by simultaneous administration of iron. It is also of value in certain of the nutritional anaemias. Whether the principle effective in anaemia of the megaloblastic type is the same as in the others remains uncertain. There is little doubt that in the megalo- blastic forms the effective principle is the polypeptide isolated by E. J. Cohn ; in the secondary anaemias the inorganic salt content of the liver may be of import- ance, and this may explain the observation that liver extracts are useless in certain types of anaemia, particularly those with a nutritional basis, which respond well to whole liver. On the evidence to date Dr. Vaughan comes to the conclusion that pernicious anaemia must be regarded as a, deficiency disease, having as its basis the absence of some principle normally present in both liver and kidney, without which the bone-marrow cannot produce or liberate its normal quota of red cells. As to the mode of action of the liver, two different views are held. J, Muller believes that pernicious anaemia is due to over-action of the reticulo-endothelial system, resulting in the production of megalocytes at the 1 Quart. Jour. Med., January, 1930, p. 213. expense of normal red cells ; he thinks that liver acts. by inhibiting the megalocytic hyperplasia and giving, an opportunity for formation of normal red cells.- G. R. Minot believes that the primary deficiency is failure of the red cells to attain maturity and that liver acts by stimulating the cells to complete their- growth cycle. His view gains much support from embryology, and bids fair to be established. But even so. the nature of the force causing this abnor-- mality in the growth of the red cells remains obscure.. CLINICAL EFFECTS OF OVARIAN HORMONE. IN a preliminary communication to the Royal Society of Medicine (Section of Therapeutics and Pharmacology), on Tuesday last, Prof. E. C. Dodds and Dr. J. D. Robertson put the landmark in the- history of ovarian hormone research at the time when Allen and Doisy first standardised the material by the vaginal smear method. Characteristic cells. appear in the smear during the three stages in the.. cyclical changes, and Allen and Doisy showed that the injection of extracts made with the use of volatile- solvents would cause these changes to reappear. As there is a definite quantitative relationship between the amount of hormone injected and the changes in, the vaginal smear the biochemist is now able to estimate the strength of his preparations. This has enabled him to proceed with the purification of the material so that whereas in former years the preparations were in the form of a stiff oil, insoluble in. water and with a rat-unit of only 10-15mg., nowadays it is possible to obtain a water-soluble material containing several hundred rat-units to the milli- gramme. In this form it can be injected into human. beings without causing any of the severe local and- general reactions that it produced in the past. When injected subcutaneously oestrin has been known to produce: (1) oestrus in ovariectomised animals, (2) premature puberty in young immature female animals, and (3) abortion of pregnant animals. It. does not follow, however, that it will therefore cause menstruation and abortion in women, and it is not fair to expect it to induce processes in human beings- which possibly bear only a distant biological relationship to those occurring in the lower animals. The preparation employed in the clinical experiments.. related by Prof. Dodds and Dr. Robertson was made by the process already published from the Courtaulcl’ Institute of Biochemistry and contained 10 rat-units per c.cm. Since the investigators were quite in the dark on the dosage all the patients received 1 c.cm. par day for two months. It was thought that the- best results would be obtained by giving a series of small doses over a considerable period, as it had been shown in animal studies that a better response was evoked by small doses spread over a period of days than by one large dose. The patients injected were cases of amenorrhcea in both married and unmarried women, patients from whom both ovaries had been removed, and attempts at the induction of labour- The following table summarises the results, cases which could not take the full two months’ course having not been further analysed. Unmarried. Married. In the successful cases slight bleeding usually occurred. within a week or ten days of the treatment, sometimes amounting to a full period, and this was followed in three or four weeks’ time by a perfectly normal period. After two months’ treatment the periods continued to appear regularly and the patients all. felt much better. This improvement in health, however, as also in the cases when menstruation did not occur, was partly due to psychological causes as excellent tonic effects were observed in many cases receiving normal saline injections who thought they were getting the active preparation. In three
Transcript
Page 1: CLINICAL EFFECTS OF OVARIAN HORMONE

586

usually followed by re-admission with recurrence ofthe symptoms, sometimes in an aggravated form ; inno case was a lasting benefit or a cure obtained. Thecases in which the greatest improvement-sometimesamounting to cure-was obtained were those whichwere treated by prolonged restriction to a fluid diet,without the passage of bougies. Only two of thesecame to autopsy ; in one of them the symptoms hadbeen cured at the age of 3, and death from tubercu-losis occurred later, the oesophagus being found to beabsolutely normal.

Sheldon and Ogilvie make some interesting sugges-tions on the pathology of this type of oesophagealobstruction. They believe that the abnormality iscongenital. This conception is supported by a highincidence in premature children and a four-to-oneratio of males to females, as well as by the onset ofthe symptoms in early infancy. They suggest thata narrowing may take place at the junction of thetwo segments (retropharyngeal and pre-gastric) ofthe foregut by the union of which the oesophagus isdeveloped, or that the lower segment may be narrowedas the result of inadequate growth. If suitableconditions can be maintained-the most importantbeing a purely fluid diet-spontaneous cure of thesymptoms may be achieved by the growth of theoesophagus to a calibre adequate for the transmissionof solids. They have certainly made out a case forregarding the majority of cesophageal defects inchildren as something different from achalasia, andfor giving prolonged trial to this method of treatment.

LIVER IN ANÆMIA.

WITHIN the last four years a great deal has beenadded to our knowledge of the use of liver in thetreatment of anaemia, and Dr. Janet Vaughanl findsa general consensus of opinion that it is a certainremedy for those forms associated with a megalo-blastic hyperplasia of the bone-marrow. The bestknown of these is, of course, " pernicious

" anæmia,but a good deal of evidence has now accumulatedtending to bring under this heading the anaemia ofsprue and also the type described by Channing, inthe ’forties of last century, as the " grave anaemia ofpregnancy." It has still to be directly proved whetherthere is megaloblastic hyperplasia of the bone-marrowin this last type of anaemia, but the condition ischaracteristically associated with a high colour-index,and this is indirect evidence of such hyperplasia.In all these states there are signs that the therapeuticaction of liver is seriously inhibited by sepsis, butthis is not to be taken as an indication that sepsis is inany way their cause. It is further generally agreed,says Dr. Vaughan, that liver is useful in the treat-ment of anaemia secondary to gastric and otherhaemorrhage, and that in these conditions its action isenhanced by simultaneous administration of iron.It is also of value in certain of the nutritional anaemias.Whether the principle effective in anaemia of themegaloblastic type is the same as in the others remainsuncertain. There is little doubt that in the megalo-blastic forms the effective principle is the polypeptideisolated by E. J. Cohn ; in the secondary anaemias theinorganic salt content of the liver may be of import-ance, and this may explain the observation thatliver extracts are useless in certain types of anaemia,particularly those with a nutritional basis, whichrespond well to whole liver. On the evidence todate Dr. Vaughan comes to the conclusion thatpernicious anaemia must be regarded as a, deficiencydisease, having as its basis the absence of someprinciple normally present in both liver and kidney,without which the bone-marrow cannot produce orliberate its normal quota of red cells. As to the modeof action of the liver, two different views are held.J, Muller believes that pernicious anaemia is dueto over-action of the reticulo-endothelial system,resulting in the production of megalocytes at the

1 Quart. Jour. Med., January, 1930, p. 213.

expense of normal red cells ; he thinks that liver acts.by inhibiting the megalocytic hyperplasia and giving,an opportunity for formation of normal red cells.-G. R. Minot believes that the primary deficiency isfailure of the red cells to attain maturity and thatliver acts by stimulating the cells to complete their-growth cycle. His view gains much support fromembryology, and bids fair to be established. Buteven so. the nature of the force causing this abnor--mality in the growth of the red cells remains obscure..

CLINICAL EFFECTS OF OVARIAN HORMONE.

IN a preliminary communication to the RoyalSociety of Medicine (Section of Therapeutics andPharmacology), on Tuesday last, Prof. E. C. Doddsand Dr. J. D. Robertson put the landmark in the-history of ovarian hormone research at the timewhen Allen and Doisy first standardised the materialby the vaginal smear method. Characteristic cells.appear in the smear during the three stages in the..cyclical changes, and Allen and Doisy showed that theinjection of extracts made with the use of volatile-solvents would cause these changes to reappear.As there is a definite quantitative relationship betweenthe amount of hormone injected and the changes in,the vaginal smear the biochemist is now able toestimate the strength of his preparations. This hasenabled him to proceed with the purification of thematerial so that whereas in former years thepreparations were in the form of a stiff oil, insoluble in.water and with a rat-unit of only 10-15mg., nowadaysit is possible to obtain a water-soluble materialcontaining several hundred rat-units to the milli-gramme. In this form it can be injected into human.beings without causing any of the severe local and-general reactions that it produced in the past.When injected subcutaneously oestrin has been knownto produce: (1) oestrus in ovariectomised animals,(2) premature puberty in young immature femaleanimals, and (3) abortion of pregnant animals. It.does not follow, however, that it will therefore causemenstruation and abortion in women, and it is notfair to expect it to induce processes in human beings-which possibly bear only a distant biologicalrelationship to those occurring in the lower animals.The preparation employed in the clinical experiments..

related by Prof. Dodds and Dr. Robertson was madeby the process already published from the Courtaulcl’Institute of Biochemistry and contained 10 rat-unitsper c.cm. Since the investigators were quite in thedark on the dosage all the patients received 1 c.cm.par day for two months. It was thought that the-best results would be obtained by giving a series ofsmall doses over a considerable period, as it had beenshown in animal studies that a better response wasevoked by small doses spread over a period of daysthan by one large dose. The patients injected werecases of amenorrhcea in both married and unmarriedwomen, patients from whom both ovaries had beenremoved, and attempts at the induction of labour-The following table summarises the results, cases

which could not take the full two months’ coursehaving not been further analysed.

Unmarried. Married.

In the successful cases slight bleeding usually occurred.within a week or ten days of the treatment, sometimesamounting to a full period, and this was followed inthree or four weeks’ time by a perfectly normalperiod. After two months’ treatment the periodscontinued to appear regularly and the patients all.felt much better. This improvement in health,however, as also in the cases when menstruation didnot occur, was partly due to psychological causesas excellent tonic effects were observed in manycases receiving normal saline injections who thoughtthey were getting the active preparation. In three

Page 2: CLINICAL EFFECTS OF OVARIAN HORMONE

587

- Attempts at producing premature labour only one was- definitely effected and the experiments were abandoned.Five cases of menopause were treated with definite’improvement in all.

It will be seen from the summary that only 30 outof nearly 80 cases treated showed objective improve-ment, and the investigators expressly stated theirfeeling that the series was too small to form the basisof a valid opinion, and that at least 1000 cases ofamenorrhoea should be treated before the material-could fairly be assessed. Much larger doses must be

given, they thought, particularly in the attempts atproducing premature labour, before discarding thesubstance as useless, but this was impossible atpresent owing to the expense and labour involvedin producing the material. They concluded bypleading for a thorough trial with objective results.

NEW METHODS IN SPINAL ANALGESIA.

Two papers at the Section of Anaesthetics of the’Royal Society of Medicine last Friday produced somesound evidence of the value of spinal injections inthe present state of knowledge. The first by Mr.Charles Donald gave a judicious and well-balancedaccount of the value of spinocain, the merits of whichhave been, as is so often the case with a new method,suffering from over-statement. Mr. Donald showedthat in most respects spinocain is neither better nor’worse than novocain. It has the advantage of beingmore slowly absorbed and therefore less toxic, butthe extravagant claims made for it as regards exactlocalisation of analgesic effect and as regards absence’of fall of blood pressure, or of subsequent ileus, wereshown to be unfounded. In the other paper Dr.Howard Jones trod new ground with the use of large- quantities of percain in dilute solution as an intra-thecal injection. He stated that his account must- only be regarded as a preliminary, but the resultshe detailed were excellent, and were borne out bythe testimony of other speakers. Dr. HowardJones’s method is based on principles determined bythe specific gravities of the cerebro-spinal fluid andof the injected liquid, and provide a logical means ofaffecting the anterior and posterior roots in accord-ance with the decubitus of the patient, and of localisingthe upward extension of the analgesia with sufficientaccuracy for practical purposes. In upper abdominalwork he cannot eliminate vagal effects when the-stomach is handled (e.g., retching), but he can pro-duce at will a perfect block of spinal nerve rootsup to the second dorsal vertebra. The value ofpercain lies largely in the extreme dilution in whichit is effective and the consequent absence of toxiceffects from absorption into the general circulation.The condition of patients with percain is superior tothat usual with novocain or stovaine. The after-headache does occur, but this and after-vomiting arecertainly not more severe than those not uncommonlymet with after the use of the former drugs and maybe even less severe.

____

CONGRESS OF DERMATOLOGY AT

COPENHAGEN.

THE eighth International Congress of Dermatology:and Syphilology is to be held in the ChristiansborgPalace at Copenhagen from Monday, August 4th, toSaturday, August 9th, under the patronage of theKing of Denmark and the presidency of Prof. C.Rasch. After a meeting of delegates on Monday- afternoon and a reception in the evening, the Congresswill be opened by the King at 9 A.M. on Tuesday, tobe followed by a discussion on the Etiology andPathogenesis of Eczema, introduced by Darier{Paris) and Jadassohn (Breslau). On Wednesdaymorning the subject of Syphilis : Immunity, Reinfec-tion, Superinfection, will be introduced by Truffi(Padua) and Wade Brown (New York). On Thursdaymorning dermatological cases will be demonstratedat the Rigshospitalet, and on Friday morning a dis-cussion on Tuberculosis of the Skin and its Treatment

will be introduced by Adamson (London) and Reyn(Copenhagen). Every afternoon except Thursdayindividual papers will be read and discussed ; intend-ing readers are asked to communicate before April lstwith the Secretary-General of the Congress, Dr.Svend Lomholt, Raadhuspladsen 45, Copenhagen,and to state if any projection apparatus is desired.A maximum of 15 minutes will be allowed for thereading of these papers, of which a short summaryin English, French, German or Italian should be sentto the Secretary before June 15th. Foreign memberswishing to take part in the Thursday demonstrationof cases should apply to Dr. H. Haxthausen, Finsensmed. Lysinstitut, before June 30th ; accommodationfor such patients will be provided gratis for twodays in the skin department of the Rigshospitalet.A scientific exhibition will be held during the wholeperiod of the Congress from 9 A.M. to 6 P.M. in theKongens Ridehus at the Palace, the manager beingMr. C. B. Ingwersen, Danasvej 30, Copenhagen V..to whom applications for participation should beaddressed. The Dansk R,ejsebureau has undertakento make arrangements for the accommodation ofmembers of the Congress at very moderate figuresand there will be a travel bureau enabling visitorsto make tours in Coperfhagen and excursions toBornholm, Jutland, and Odense. The Danish StateRailway is offering members of the Congress a reduc-tion of 50 per cent. on their return tickets. TheBritish delegates to the Congress are Dr. H. G.Adamson and Dr. Arthur Whitfield, Dr. A. M. H.Gray being local secretary.

THE ACTS OF RAHERE.UN Marcn iltn a cast or actors, wnose names are

not announced, gave the first performance of the" Acts of Rahere," a play depicting the foundationof St. Bartholomew’s Church and Hospital 800years ago. Rahere was one of those " fiery particles "which have a lasting hold on the imagination. Hewas officially the Court jester of Henry I., and attainedmuch influence while still a young man. Afterreligious conversion he went on pilgrimage to Rome.and there during illness had a vision of St. Bartholo-mew, who told him to build a church and hospitalin the Smooth Field, one of the most depressing anduseless spots in the neighbourhood of London, adeserted swamp near the public execution ground.He promptly returned to England, discovered thatthe site he wanted was the King’s and boldly askedfor it, in spite of Henry’s anger at his desertion.He not only gained his point but his Sovereign’sinterest and practical help, and he soon drew supportin money and personal service from a large sectionof the population of London. This is the dramathat the actors of St. Bartholomew’s, reconstructevery evening at 6 o’clock in aid of the projectto build a new surgical wing holding 250 beds andan operation block with six theatres. The stageis the sanctuary of the old church itself beside Rahere’sown tomb ; the performance, in the candle-lit settingof this perfect Norman fabric, is extremely impressive.

Dr. Norman Scott Carmichael, Physician to theRoyal Hospital for Sick Children, Edinburgh, hasbeen appointed Surgeon Apothecary to the King’shousehold at the Palace of Holyroodhouse.

THE William Mackenzie Medal for 1929 for originalcontributions to ophthalmology of outstanding merithas been awarded by the custodians, The GlasgowEye Infirmary, to Prof. J. van der Hoeve, ofLeiden, Holland. ---

Dr. Carey F. Coombs will deliver the LumleianLectures at the Royal College of Physicians of Londonat 5 P.M. on March 20th, 25th, and 27th. Hissubject will be Syphilis of the Heart and GreatVessels, and members of the medical profession willbe admitted on presentation of their cards.


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