1362 ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE

Miss J. A. OLDAKER produced an analysis of450 consecutive patients at the Royal Free Hos-

pital who had sedatives during labour. Sedativedrugs were given as soon as the patient felt discom-fort during the contractions. Some 170 patients,had no drug of the kind, either because the con-tractions were not very strong or painful, or becausethey were not admitted until the second stage. In60 cases bromide and chloral (grs. 20-30 of each)- were given by the mouth and repeated. Opoidineyl c.cm.) and magnesium sulphate (2 c.cm.) weregiven together by intramuscular injection and therehad been no experience of sepsis at the site of injection...In a certain number of cases forceps were necessaryon account of ineffective uterine contractions in thesecond stage ; some patients were given morphia gr. 4.There had never been cause for anxiety because ofthe child’s condition. 259 patients had intermittentnitrous oxide and oxygen anaesthesia during the-whole of the second stage. When this was given thecontractions were never diminished, but were some-times increased. She had not yet sufficient data toenable her to express an opinion on the chloroformcapsules.

Dr. H. E. BOYLE considered nitrous oxide and

oxygen the ideal anaesthetic for childbirth, adminis-tered by an anaesthetist who knew something of..obstetrics. He was against allowing midwives to,use any dangerous drug. The efficacy of nitrousoxide and oxygen was increased by the judiciousaddition of CO 3.THE ATTITUDE OF THE CENTRAL MIDWIVES BOARD

. Dr. J. S. FAIRBAIRN said that a large proportion.-of working-class women delivered themselves, andjt was highly desirable, from every point of view,- that they should be relieved from prolonged pain.The chloroform capsule promised to be a mostvaluable general means to this end. The questionhad been under discussion at the Central Midwives:Board. He understood that the London CountyCouncil were trying it out in some of their hospitals.’The Central Midwives Board had asked the Section,of Anaesthetics of the Royal Society of Medicineto express an opinion on the safety of the capsule inthe hands of midwives. Small quantities of anaes-,thetic were required over a fairly long time, and tohave a doctor in attendance during all that time was..an expense that most women could not afford;moreover, the doctor could not neglect his otherpractice to that extent.

Dr. HERBERT CHARLES said his experience withchloroform in labour was that the pains were notfelt and the mother remained conscious and couldtalk. Spinal anaesthesia was excellent for Caesareansection, but not for the early stages of labour. Hehad the profoundest respect for chloroform in labour ;it was a boon to the poor woman suffering in child--birth.

Dr. R. A. GIBBONS said he gave chloroform in the

ordinary way with a mask in childbirth, and foundthat in small doses it kept the patient free from pain.No danger attended its use unless it were pushed.If there was exhaustion, a little ether could be given.He hoped it would be possible to sanction the use ofchloroform capsules by midwives.

Mr. EARDLEY HOLLAND agreed there was a greatfuture for chloroform capsules in the second stageof labour, but he doubted whether they were suitablefor administration over many hours. One couldbetter judge of the effects of anaesthetics amongprivate than among hospital patients, for the former<could be followed up. Different women felt labour

pains with varying intensity according to theirtemperament. Much could bt. done without drugsby talking to the patient and reassuring her andurging her to relax and so help the birth. In thefirst stage of labour he relied a good deal on chloral,grs. 40, dissolved in a considerable volume of waterbeing slowly sipped. This medication formed anexcellent basis for scopolamine and morphine.

Mr. A. J. COPELAND thought that with the capsulesof chloroform there should be supplied a slip givinga few warnings&mdash;e.g., to hold the capsule not lessthan two inches from the face, and to place no cover-ing other than the lint or mask over the face, and touse not, more than one capsule at a time. Specialwards might be set aside to investigate the com-parative effects of different anaesthetics in child-birth. He favoured the addition of oxygen whateveranaesthetic was used.

Mr. J. P. HEDLEY thought that, in however smalldoses it was given, chloroform was undesirable inthe first stage of labour. An anxious woman gotmore excited if she had chloroform early, and if shewere given more, which she would certainly demand,the force of the uterine contractions was diminished.

Dr. KELSON FORD said that if midwives generallywere to be allowed to use chloroform capsules he didnot know how the rural chemist was to determinewhether anyone asking for them should be supplied.It would be safer if the medical man could authorise

their use.The PRESIDENT said the suggestion that the

Central Midwives Board should take action in thismatter was a pertinent one. He could endorse theview that there were many difficulties in the way of

authorising midwives to use chloroform.

Mr. RIVETT, in his reply, said he regarded normallabour as labour in which the woman succeeded in

delivering herself without extraneous assistance. He

always regarded it as a disgrace if the perineum wasinjured. If ether were given for several hours therewas a risk at least of bronchitis, possibly of pneumonia.The law was that if a person could be shown to be

competent, and trouble arose, she could not be

prosecuted for negligence, but if the person concernedwas shown to be incompetent, prosecution mightfollow. The issue of the capsules would depend onthe doctor in any particular case. Chloroform wasnot included in the schedule of dangerous drugs,but hyoscine was.

ROYAL SOCIETY OF TROPICAL MEDICINE

AND HYGIENE

AT a meeting of this society held at Manson Houseon June 16th, with Dr. G. CARMiCHAEL Low, thepresident, in the chair, the Manson medal wasawarded to Prof. Theobald Smith, of New York,and was received on his behalf from the president byDr. G. K. Strode, of the Rockefeller Foundation. Adiscussion on

Synthetic Antimalarial Remedies and Quininewas opened by Colonel S. P. JAMES. The malariacommission of the League of Nations, he said, aimedat providing a cheap and abundant supply of a

remedy which would limit attacks and prevent deathsfrom malaria by planting cinchona trees in malariousdistricts. The aim of chemotherapy was to providea remedy for cases in which quinine was known tofail, a remedy which would supplement, but which

1363ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE .

would not replace quinine or injure the cinchonaindustry. Quinine might be effective with some

strains of parasite, and synthetic drugs, such as

plasmoquine, effective with others. Therapy mustbe studied not only in terms of the strain of parasiteto be overcome but in terms of the different phasesof each species of parasite recognised ; plasmoquinehad a selective action on gametocytes, but littleeffect on schiz-onts, while the opposite appeared tobe true of quinine. The selective action of drugsindicated differences in the biological properties ofthe parasite in different phases. Therapy must alsobe studied in terms of the geographical distributionof strains, for the virulence of the parasite variednot only with the species but with different geogra-phical strains of the same species. In some partsof Italy a more effective drug than quinine wasalready needed, and atebrin seemed to fulfil this

need. Among a series of seven cases infected on

the same day, five treated with atebrin were cured,while two treated with quinine were not cured.

Contradictory observations on the properties of

plasmoquine were probably due to the use of differentgeographical strains. With some strains plasmoquineprevented relapse. After infection with a Madagascarstrain of benign tertian malaria, plasmoquine andquinine were found to be more effective in preventingrecrudescence than plasmoquine alone. The toleranceor immunity acquired by the patient before treatmentwas begun were also factors to be taken into accountin estimating the action of drugs, and the dose ofinfection, depending on the number of mosquitobites, also made a difference ; even atebrin wouldnot cure outright a severely infected case. Experi-ments were made with plasmoquine in the preventionof infection. With a dose of 0&deg;06 g. of plasmoquinegiven daily for six days it had been found possible toprevent malignant tertian in every subject treated.No failures had been recorded with benign tertianuntil an experiment was made on nine or ten studentsat St. Mary’s Hospital ; the primary attack wasprevented in every case, but five of the patientsdeveloped attacks of malaria between seven and ninemonths later. Plasmoquine was a causal prophy-lactic agent, but the dose necessary was too large tobe taken for more than three or four days. A similarbut less toxic drug was needed.

Dr. C. A. HENRY reminded his hearers that thealkaloids of cinchona bark were quinine, quinidine,cinchonine, and cinchonidine. In their effect on

malaria, he said, quinine and quinidine were aboutequal; cinchonine and cinchonidine were probablyinferior to the other two. The malaria commissionof the League of Nations had decided that it wouldbe sufficient to provide a mixture of all the crystal-lizable alkaloids of cinchona bark instead of quinine,this preparation to be called totaquina, and tocontain 70 per cent. of the crystallizable alkaloids,of which 15 per cent. must be quinine. Totaquinecould be made in one of two ways ; the productof the first method contained 77-9 per cent. of

crystallizable alkaloids, of which 30-4 per cent. wasquinine. The second product, made from manu-facturers’ residues, contained 78-5 per cent. of

crystallizable alkaloids, of which only 20-7 per cent.was quinine, and more than 40 per cent. was cincho- Inine. The second product was far less effective effective than the first, but at the present time it was the the only type available. The cinchona industry had been 1

rationalised to make the supply meet the demand i95 per cent. of the cinchona bark used was grown in ]Java. Suggestions were sometimes made thatcinchona planting should be revived in the British

Empire, but this would only reproduce the disorderof 20 years ago when too much bark was placed,on the market.

Prof. N. H. SWELLENGREBEL described an attemptcarried out at Amsterdam to prevent the outbreak-of fever and the appearance of benign tertian byprotecting subjects with plasmoquine. Doses of0-03 g. were given daily for six days, beginning on-the day before exposure to infection. The attemptfailed ; all the patients except one developed malariaat the usual time, and the one who failed to do so-developed an attack some months later. Of thosewho developed the primary attack, some were treatedwith plasmoquine, some with plasmoquine andquinine, and some with quinine only. All relapsed’or else developed recurrences more than 24 weeksafter the primary attack. Dr. Piebenga, working.elsewhere in Holland, had reported a series of casestreated with quinine and plasmoquine in a largeproportion of which there were no relapses or recur-’rences. Dr. Piebenga had been working with thehome strain of benign tertian, using naturally infectedmosquitoes. Prof. Swellengrebel said that in hisown cases. artificially infected mosquitoes were used,and the strain was the Madagascar strain of benigntertian obtained from England. The home strain-was less reliable in causing malaria and was probably’of a lower vitality than the Madagascar strain. Thenumber of infecting bites in Piebenga’s cases, more-over, was not known, but it was unlikely that theyexceeded one bite per patient in that region y hisown cases had averaged a large number of bites.-The relapse-rate for Holland as a whole was 50 per’cent. ; the fact that 100 per cent. of Prof. Swellen--grebel’s experimental cases relapsed seemed i()J’.indicate that the strain of malaria used was excep-tionally refractory to plasmoquine. His resultsdid not contradict those of other observers, but

only served to show that treatment with plasmoquinemight break down where there were large numbers’.of infecting bites, or where the strain was particularly virulent.

Sir HENRY DALE said that the method of testing,,antimalarial drugs had advanced; it was now

possible to differentiate between the different phases.of the parasite, so that the drug to be tested couldbe made to intervene at any stage.

Sir DAVID PRAIN said that technical chemists-used to interest themselves in the synthetic product-tion, at a cheaper rate, of substances found in nature..They now followed another principle and attempted-to provide a substitute which was an improvement,on the natural substance. The idea was not a newone, but went back 600 years to a king of Castile,.who shocked his priests by remarking that if he had.been present at the creation he could have preventedmany blunders. As soon as the chemist could

provide the perfect substitute we should be ableto dispense with cinchona, and we must already:, cadvise against any extension of the cinchona I,

industry.Dr. W. D. NICOL described the natural clinical

course of 161 cases of benign tertian malaria which.had been under observation for a year or more atHorton. They were infected with the Madagascarstrain, and 140 developed fever at the end of thenormal incubation period; 21 developed latentmalaria 25 to 40 weeks after infection. In 110 cases..the primary attack was terminated with quinine,in 18 with some quinine preparation, in 6 with,plasmoquine, and in 6 with plasmoquine and quinine ; samong these, 29 had recrudesced within eight weeks,13 relapsed between the eighth and the twenty-fourth’

1364 NORTH OF ENGLAND OBSTETRICAL AND GYNAECOLOGICAL SOCIETY

week, and 39 recurred after the twenty-fourthweek.

Dr. PHILIP MANSON-BAHR mentioned a case ofsevere malignant tertian malaria with cerebralcomplications seen first on May 18th of this year.The patient was treated with one injection of quinineand then with atebrin for five days ; he had madea good recovery, and appeared at the meeting inperfect health.

Prof. W. SCHULEMANN said that it had never

been the intention of workers at Elberfeld to producea drug to contend with quinine. The aim was toproduce new drugs which would give results whichquinine could not achieve. It had been shown thatin certain circumstances plasmoquine reduced relapsesand recurrences ; these findings needed confirmationwith the same strains in tropical and subtropicalcountries. In subtertiary malaria plasmoquine didnot appear to reduce the number of relapses, but therelapses with this strain were in any case few. Inrecent experiments made at Elberfeld by Dr. Kikuthon various species of avian malarial parasites ithad been possible to study the action of drugs onseparate phases in the life of plasmodia ; he hadfound that atebrin acted on schizonts but not on

gametocytes. These findings had been confirmed,but further prolonged experiments were needed.Quinine was not a causal prophylactic : it controlledclinical symptoms only during its administration.Colonel James, by giving 0-06 g. of plasmoquinefor six days had prevented recurrence of attacksin 50 per cent. of his cases. Prof. Swellengrebel,using 0’03 g. for six days, had been unable to confirmthese results. Probably the halving of the dose wassufficient to explain the discrepancy. As ColonelJames had pointed out, the problem of malaria wasbecoming more and more complicated. It was not,however, necessary to test the virulence of everystrain ; laboratory results were not the only criterion,and the resistance of the host was an importantfactor in malarial infection. A detailed comparativeinvestigation was needed to find out whether a strainof the parasite showed the same susceptibility todrugs in a native in the tropics as it did in a patientin a temperate zone. In order to get the best resultswith the drugs available we must take into accountthe variable susceptibility of the parasite to thosedrugs, and also its geographical origin. Atebrinand plasmoquine both had special properties, andclinicians must learn to choose the drug or the com-bination of drugs which would produce the bestresults in a given case. In order to get an ideaof the value of the three drugs now available thecooperation of the laboratory and hospital with thegeneral practitioner was needed. The ideal would bea single drug which was effective against every typeand strain of the parasite, but in default of that wemust learn to use correctly, and to develop, the

weapons at our disposal.Sir MALCOLM WATSON said that atebrin had been

tried on a small series of cases in Malaya, and two outof four had relapsed. A single case treated withatebrin and plasmoquine had also relapsed. Experi-ments were now being performed on three groups ofMalayan children, and results would probably beavailable in six months time. He thought therewas evidence that the virulence of a strain mightvary. Non-immune people entering an area wheremalaria was mild frequently became infected, and inturn infected the Malay population, with malariawhich decimated both the newcomers and the

residents. Presumably the virulence of the localstrain had been increased by passage. I

Sir ALDO CASTELLANI thought plasmoquine cura-tive, but less so than quinine. In acute perniciouscases he would advise the use of quinine in largeintravenous and intramuscular doses rather thanplasmoquine. In relapsing cases plasmoquine wasuseful when combined with quinine, but its specialadvantage lay in the treatment of patients whoshowed idiosyncrasy to quinine, and in black-waterfever. Exceptionally, an attack of black-water

might be started by plasmoquine. The value of

synthetic drugs was that they provided a secondweapon in addition to quinine.

Colonel JAMES, in replying, said that he could notagree with Sir David Prain that synthetic drugswould affect the cinchona industry. Clinicians wouldcontinue to use quinine where it was the most usefuldrug, and the other remedies where they were

applicable.NORTH OF ENGLAND OBSTETRICAL AND

GYNECOLOGICAL SOCIETY

AT a recent meeting of this society held in LeedsDr. S. B. HERD (Liverpool) described a case of

Chorionepithelioma of the Broad LigamentThe patient, aged 48, gave a history of ten normalconfinements and one abortion. She missed threeperiods, and then had continuous bleeding for threeweeks. As the uterus was of the size of, and feltlike, a 12 weeks’ gestation, she was treated as

a threatened abortion, but the bleeding did not

completely stop.When she was next seen the uterus was no bigger, but

the interval after the last normal period was 24 weeks.A diagnosis of carneous mole was made, and the mole wasexpelled spontaneously. It was typically carneous exceptfor a few minute vesicles in one area, and on microscopicalexamination there was evidence of hydatidiform degenerationin this area.For six months there was menorrhagia (no intermenstrual

bleeding), but she then bled constantly for a month. Carefulexamination under anaesthesia, and curettage, failed toreveal any sign of placental tissue or chorionepithelioma,and the irregular bleeding ceased for a further six months,the periods being regular but excessive. Finally, about16 months after the expulsion of the mole, the patientpresented herself with a history of further bleeding for onemonth, and neuralgic pain in the left hip and thigh for thesame length of time. The Aschheim-Zondek test was

strongly positive, and there was a hard fixed mass whichproved to be on the left broad ligament, and to have noapparent connexion with the uterus although the wall ofthe bladder was partly invaded.

This case, said Dr. Herd, was of interest because of :(1) the comparatively long history; (2) absence ofgrowth in the uterus ; (3) doubt as to the origin ofthe growth in the broad ligament ; and (4) questionas to whether earlier operation would have saved thepatient’s life. While extension from a chorion-

epithelioma of the uterus was possible, the growthapparently arose as a primary malignant conditionin the broad ligament.

Dr. Herd also showed a specimen of Epitheliomaof the Vulva removed from a patient aged 25.

Toxsemia of PregnancyProf. CARLTON OLDFIELD described three unusual

cases of toxaemia associated with pregnancy. Thefirst case resembled " milk fever " or " bovineeclampsia." The patient was a primigravida, who,after a low forceps delivery of a healthy child, beganto vomit on the third day. This continued, and thetemperature rose to 101&deg; F. on the following day,and there was epigastric pain and jaundice with