TIRE4I)STH GR~ADUATENEDlUAL J Ou1?NAL

VOL. V. MAY, 1930. No. 56.

CONTENTSPAGE

THE TREATMENT OF GENERAL PARALYSIS BY MALARIA 1.. .. ... ... 29By THOMAS TENNENT, M. B.GIas.

THE ROLE OF HYDROLOGY IN MEDICAL PRACIICF ... ... ... ... 137By MATTHEW B. RAY, D.S.O., M.D.EDIN.

POST-GRADUATE NEWS ... ... ... ... ... ... ... ... ... 142

N OTICE .... . . . ..... ... ...... ... ... 14 5

FELLOWSHIP OF MEDICINE AND POST-GRADUATFE MEDICAL ASSOCIATION.-SPPECIAL COURSES ... ... ... ... ... ... ... ... ... i;

THE TREATMENT OFGENERAL PARALYSIS BY

MALARIA.By THOMAS TENNENT,

NI.B.GLAS.

Assisttant Medicall Officer, Maudslky Hospital.

ITr has long been regarded that the outlookin general paralysis is most unfavourable,and that it is one of the most fatal diseasesaffecting the human race. Until recently allefforts to treat this condition proved worth-less, and a fatal terminationi within a fewyears was the inevitable outcome. Remis-sions throughout the course of the illnesswere recognized, but aiy claim of recoveryaroused, in the minids of most, giave doubtsas to the diagnosis. Fortunately this stateof affairs has changed and remissionis inaynow be iniduced by prompt and appropriatetreatment.The first cliical accounlt of a case of

genieral paralysis was recorded in 1798 byHaslam, who was then Apothecary ofBethlem Hospital. It was not, however,uLntil 1I822 that the conldition was recognized,by a Fi-ench psychiatrist named Bayle, as adisease entirely based upon a known patho-logy. His description of the pathologicalchanges and of the clinical symptoms holdsgood in its essentials to-day.From this time unitil the discovery of the

true niature of general paralysis many factor-swere elaborated to account for its xtiology,anid equially nLumerous and varied were theremedies suggested. The latter includedsuch diverse methods as venesection, cauteryto the head and spine, baths of varyingtemperature, purgatives and electricity.Iron, potassium bromide, quinine, silvernitrate and digitalis were the more prominentdrugs advocated.These methods of treatment held promill-

ence at various stages and, until a betteruniderstanding of the xtiology was obtained,little lheadway from the therapeutic angle

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130 THE TREATMENT OF GENERAL PARALYSIS BY MALARIA

was made. In I857 the relationship betweengeneral paralysis and syphilis was stressedby Esmarck and Jessen, who reported threecases of syphilis followed by generalparalysis. Thereafter there developed acontroversy as to the nature of the causa-tion which lasted over fifty years, and wasonly settled by the researches of Wassermannand Noguchi.

Meantime treatment had progressedchiefly along two channels, the specific andnon-specific forms of therapy. It is witlhthe chief variety of the latter that I proposeto deal to-day, namely, the treatment by theinduction of malarial fever.The beneficial effect of fever in the

psychoses generally had been recognlizedand observed since the days of Hippocratesand Galen. Many centuries later Pinelelaborated among the conditions tendingto produce a "permanency of cure" aquartan fever. Clouston, a little over fortyyears ago, wrote: " I believe some day weshall hit on a mode of producing a localinflammation or manageable septic blood-poisoning by which we shall cuit short orcure attacks of acute mania." This observa-tion then, that the onset of a febrile illnessduring a psychosis frequently resulted in animprovement in the mental state, suggestedto Wagner vo-n Jauregg, in i887, the possi-biliiy of imitating this experiment of naturefor the cure of the psychosis. At that timehe mentioned malaria as one of the diseasessuitable for such experimentation. He didnot, however, employ this method then, butbegan to induce fever by injections of Koch'stuberculin. In many cases, however, sooneror later the disease recurred, and re-inocula-tion then proved of little value. Conse-quen-tly he endeavoured to find a meanswhich would produce better and more lastingresults, and this led to the employment oftyphus and later typhoid vaccine. In thecourse of these experiments he noted thatthe most complete and lasting remissionswere obtained in patients in whom, duringthe course of treatment, an infectious disease

such as pneumonia had set in, and it sug-gested to him that treattnent might bemore effective still if directly produced byinfectious disease.Other two observations were reported

meantime bearing on this point anid areworthy of note.

(i) Bercovitz pointed out that neuro-syphilis was extremely rare in certain areasof China, although syphilis was extremelycommon ; malaria in these districts wasendemic.

(2) In I9I3 Pilcz and Mattauscliekanalysed the case histories of over fourthousand officers and men of the Austrianarmy who had become infected with syphilis.They pointed out that those who during theirfirst year after infection had developed anacute febrile illness such as pneumonia orer-ysipelas did not later develop neuro-syphilis. On the other hand, practicallywithout exception, those who developedneuro-syphilis had not suffered from an acutefebrile illness during the first year afterinfection by syphilis. Fortified by theseobservations von Jauregg, in I917, thirtyyears after his original suggestions, inocu-lated his first series of nine cases of generalparalysis with malaria, from a soldier whohad not been treated with any quinine.Since then several thousands have been sotreated.

TECHNIQUE.

The patient may be inioculated by either-of two methods, namely, by mosquito bite,or by blood inoculation.

If the former mpethod is adopted, thenfemale mosquitoes of the anopheles groupare employed and are allowed to feed on thepatients. Such mosquitoes are readilyobtainiable through the Ministry of Health.They are taken to the bedside in a glass con-tainer, the top of which is covered withmuslin. The glass vessel is inverted overthe area of skin selected and the mosquitoesallowed to bite. It may be, however, thatthe mosquito does not choose to feed at

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THE TREATMENT OF GENERAL PARALYSIS BY MALARIA 131

this moment, and so further attempts maybe necessary.The other method, by blood inoculation,

has generally proved to be more advani-tageous; 2 to 5 c.c. of blood are taken froma patient either immediately before or duringa febrile attack. If the inoculation is donein hospital, or in such circumstances thatthe two patients may be brought together,then the blood may be transferred direct.if, howvever, the blood has to be transported,then clotting must be prevented. This maybe accomplished by adding an equal quantityof 5 per cent. sodium citrate. Successfulresults are obtained if the blood is simplydehbrinated. The blood is transferredimmediately from the syrinige into a steriletest tube, and stirred briskly with a sterileglass rod. It should be stirred continuouslyfor twelve minutes, at the end of whichperiod the fibrin is usually found collectedalong the rod.The actual inioculationi may be given

subcutaneously, intramuscularly or intr-a-veniously. The site usually selected for sub-cutaneous inoculation is that betweena thescapula, but it mnatters little where the bloodis injected. It is desirable to move theneedle about under the skin prior to with-drawal, thereby injuring some of the super-ficial vessels. The intramuscular methoddoes not differ materially from the subcu-taneous. Either are useful where it isdesired to keep the strain of the par-asitealive for the maximum period.The intravenious metlhod is usually adopted

where the saving of time is important. Theinicubation period is frequently shortened,and in my opinion the results of infectionare more dependable. Of course, one mnusttake all precautions in such injectionisagainst introducing air or blood-clot whichwould result in embolus formation.The causes of failure to develop malaria

may result from faulty administration, ormay rest in the patient himself.With regard to the administration, it is

important to remember that antiseptics may

have a deterrent effect on the inoculation.It is therefore advisable to sterilize instri-inents, &c., by boilinig, but such must becooled prior to use. The exposure of theparasites to the influence of heat is inadvis-able. Rudolf founid that they were killedif exposed to a temperature of 1200 F. for aperiod of three minutes. Another cause offailure is the delaying of the inoculation afterthe blood has been withdrawn. If -such adelay is necessary the blood should be kepton ice. It should, of course, be rememberedthat a few people possess an immunity tomalaria which may account for the failure,as also may any antimalarial drugs takenjust before or at the time of the inoculation.The incubation period is a variable factor

anid usually extends from four to twenty-fivedays. If the patient's condition otherwiseis good, there is no necessity to keep him inbed durinig the day while the fever is devel-oping. The temperature during the firstseveni days should be recorded at least twicedaily, and thereafter every four hours, untilthe onset of the fever. This is usuallypreceded by headache, malaise and thecomplaint by the patient. of feelinig out ofsorts. He then welcomes bed. During therigor the temperature should be taken everythirty minutes, and it is not uniusual tor-ecord temperatures over I050 F. No drugsshould be administered to control thepyrexia. Tepid sponging of the patient isadvocated if the degree of fever exceedsI05° F.As to the nature of the fever, this depends

largely on the strain of parasite used. Asthe benign tertian variety is that mostfrequently employed, one expects the patienitto have a rigor every second day. Witlhthe passage of the infection through variouspatients and re-inoculation of some of these,a double infection is frequiently obtainied,the febrile attacks occurring daily. Thisallows the patient little time to recover fromhis attacks and is very exhausting. Morer-ecently the quartan variety has beenemployed, and its use is advocated in

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132 THE TREATMENT OF GENERAL PARALYSIS BY MALARIA

debilitated subjects. Here there is aninterval of two days between the rigors,.most valuable where the general conditionis not very good. Attention at this timeshould be paid to the condition of thebowels and a look-out kept foir retention ofurine. Cardiac drugs, such as (ligitalis,str-ophanthus or caffeinie, are giveni regularlyduring the fever. Von Jauregg advocatestheir administration at the beginning of therigor and again when the fever reaches itshighest peak. Blood-films should be ex-amined at daily intervals throughout thepyrexia. The number of parasites foundvaries greatly in different subjects. Somehave few parasites in a field, and yet aremore uLpset clinically by the fever thanothers who show numerous parasites. Ofgreat value, however, is a rapid increase inthe number of parasites seen in each field,and it should be taken as a warning sign.

If the general condition remains satis-factory the fever is allowed to continue untilthe patient has had ten rigors. Thereafterit is discontinued by the administrationi ofquinine sulphate or hydrochloride, io gr.being given three times a day for a few days.The effect is rapid, the fever subsides andthe parasites disappear from the blood.

Attached to this form of treatment thereare certain dangers which must be fullyappreciated, and for these onie must be con-stantly on the look-out, prepared to abortthe fever. A most important indication forstopping the fever is a sudden drop instrength, characterized by apathy andlistlessness in the interval between theparoxysms. Cardiac weakness is the fre-quent cause of death, and shows itself asan irregularity or weakness of the pulse,weakened heart sounds, cedema and pul-monary congestion. An increase in thepulse-rate of over i6o beats a minute, orin the respiratory rate of over 6o a minuteshould be taken as danger signals. A smallquantity of albumin is found in the urineduring the fever and need not be regardedseriously unless the amount increases, when

it is of great imnportance. The appearanceof jaunidice is also an indication for delayingthe next paroxysm.

If it is desired to cur-tail the fever then itmay be accomplished by the adtinlistratioinof a small dose of quinine, 3 or 4 gr. ofquininie sulphate. This will temporar-ilyarrest the fever. There is no further pyrexiaas a rule for at least seven days, and if thepatient's general condition improves duringthat period the fever may be allowed tocontinue again. If such is consideredinadvisable, fturther doses of quinine maybe administered and the fever stopp)edaltogether.

It should be borne in minid, however, thatthe best results are usually obtainied follow-ing a series of ten to twelve pyrexial attacks.

Re-inoculation with malaria is possible inmany cases and a further course of fevermay be given if no improvement followsthe original fever. In some, however, it isimpossible to re-inoculate with malaria;immunity develops after one attack. Onlyrarely are patients immunie to the originalinoculation, and, as a rule, such patientshave been resident in tropical countriesduring some period of their life. It isclaimed for quartan fever that inoculationby this strain is frequently possible after aninitial course of fever of the tertian variety.

Recurrence of the fever is rare followingupon blood inoculation. It is more frequentafter inoculation by mosquito bite and mayoccur several months after the originalfever.

EFFECT OF THE FEVER.

It is important to remember that mentalphenomena may be exhibited during thefever attributable to the malaria. Mostfrequently this is a state of cotnfusion withhallucinations, usually auditory in type.Delusions, persecutory in nature, sometimesoccur and the patient may become restlessand excited. As a r-ule the confused stateclears when the fever is discontinued. Themore marked physical effects are a marked

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THE TREATMENT OF GENERAL PARALYSIS BY MALARIA 133

anaemia and a distinct loss of weight. Thedegree of anaemia may be profound. ColonelJames has stated that in primary attacks ofthe naturally acquired disease the loss ofred cells may be from 250,000 to overi millioni during a single febrile paroxysm.Improvement in this respect is ustually rapiddutring convalescence, when tonics of iroinand arsenic are valuable. With regard toloss of weight, this is as a rule also rapidlygained. This regain of weight is sometimesof prognostic value. It has frequently beenfound that those who do not regain all orpart of the weight lost do niot show a markedimprovement in their menital state.The assessment of results obtained follow-

ing this treatment is complicated by the factthat spontaneous remissions have long beenknown to occur in the course of the illness.Patients improved and were well enough tobe discharged from hospital. Some resumedwor-k and appeared to their friends to lhaverecovered. Their improvemnent was in-variably ascribed to whatever treatment hadbeen given. As a rule, however, theirremission was only of short duration,necessitating their re-admission to hospital.A study of the literature shows that

spontaneous remissions occurred in aboutio per cent. of general paralytics. Somerecord figures slightly above this, othersbelow. The duration of such remissionslasted as a rule a matter of monthls, and onlyin a very few cases did they extend into afew years. Meagher has recently made adetailed study of the cases of generalparalysis admitted to the English Countyand Borough Mental Hospitals in I923 and1924, and his results are very interesting.He investigated the subsequent histories ofall certified cases of general paralysis ad-mitted to these hospitals in that period whohad not been treated with malaria. Thenumber of cases so invest'igated was 1,173.He found that of those there had beendischarged from hospital a total of sixty-sixpatients, or 6'2 per cent. Of these onlyseventeeni were discharged as recovered,

forty as relieved and nine as not improved.Twenty-six of tlhese, between 1924 and I927,lhad either died at home or had been re-admitted to hospital, so that onily fortypatients were alive and not under care in amental hospital three or four years after theyoriginally came under certificate. Of thetotal number I,I73, only 157 or 14 per cent.were alive in I927, and i,oi6 were dead.These figures show that long-lasting spon-taneous remissions in general paralysis arerare.He made similar investigations of all cases

of general paralysis who had been treated bymalaria in the same period. The number ofcases so treated was 438. Of these he foun-dthat there were livitng, in I927, 247 6f whomio8 had been discharged from hospital; 191patients had died in the interval.

It will be seen from these figures that 56per cent. of the treated cases were alive,whereas only I4 per cent. of untreated caseswere alive in I927. Conclusive evidence isthus furnished that treatment by malariadoes extend life.

It is interesting to note the results reportedin the first cases of general paralysis treatedby malaria. Of the nine cases treated inI9I7 by Wagner von Jauregg, three patientshave maintained a state of good remissionfor over a period of ten years. Of twenty-five cases treated between September, I9I9,and March, I920! eighteen were originallydischarged enjoying a remission of varyingdegree, seven of whom had a full remission.In I928 only one of these seven had relapsedand died. The remaining six were stillenjoying a full remission. Thus of the firstthirty-four cases treated between I9I7 andMarch, 1920, nine, or 26 per cent., were en-joyinig a full -remission in 1928 after periodsvarying from eight to eleven years.

Altogether several thousand cases havebeen submitted to this treatment in all thestages of the disease. A rough analysis ofthe results shows that one-tlhird of thepatients improve sufficienitly to leave hospital,one-third show improvement but require to

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134 THE TREATMENT OF GENERAL PARALYSIS BY MALARIA

remain in hospital, and the remaining thirddie.The questioni that now arises is, are there

any factors which help to determine theeffect of treatment ? There are. Whatappears to be the most important factor isthe duration of the illniess before treatment.Von Jauregg has stated that improvementmay be obtainied in ioo per cent. of patientsif only early cases are treated. I should like,therefore, at this point to stress the value ofa diagnosis while the disease is in its earlystages. The type of illniess in which thegreatest number of remissions occurs is theexalted manic variety. It is quite likelythat the fact that such patients come uniderobservation at a muclh earlier period thanithose presentinig depressive or neurasthenicsymptoms partly accounts for this. A similarreason might partly explain the relativegreater frequency of remissions among menthan women. The age factor has beenadvanced by some investigators, who statethat increase of age is a deterrent factor.This, however, does not appear to begreater than what would be expected at aniage when the recuperative powers are not soactive as formerly, and I have obtained afull remission in a man over 6o years of agetreated within the first month of presentingsymptoms.

It is therefore of extreme importance thatsuch cases should come under treatment atthe earliest possible moment. Only too fre-quently, when taking the anamnesis of suchpatienits, one hears from the relatives thatthey have been complaining for a period ofyears. The symptoms frequently are veryvague. The most frequent early menitalphenomenia involves changes in c-haracterand mood. Irr.itability, restlessness, memorychanges and defective judgment are theearliest features in some; others again be-come indifferent, apathetic, and desire to beleft alone. That suchlymptoms are not patho-gnomonic of general paralysis is granted,but their incidence in this condition shouldalways be remembered in the investigationof any indefinite nervous complaint in a

patient after 30 years of age. If accom-panied by any neurological signs such as in-equality, or irregularity in outline of thepupils, fine tremors around the angle of themouth, or of the fingers or tongue, or anyspeech defects, a blood Wassermann oughtto be done. If this gives a positive result,then examination of the cerebrospinal fluidis essential in the best interests of thepatients.

Another point of value is the frequency ofthe inicidence of congestive and convulsiveattacks of general paralysis. The onset ofsuch attacks inl persons in the forties andfifties is to be remembered and investiga-tions made as to their real nature.

In this connectioon greater use might bemnade by general practitioners of the psychi-atric out-patient depairtments now -attachedto nearly all general hospitals, or the out-patients departments of neurological andpsyclhiatric hospitals. It is recognized thatthere has been difficulty in obtainingadequate treatment for patients who werenot certifiable. It was impossible for suchto enter, eveni as voluntary boarders, any ofthe rate-aided mental hospitals, had they beenwilling to do so. This state of affairs maybe retnedied under the new Mental Treat-ment Bill tnow before Parliament. As it iseasy for patients who are certifiable to re-ceive proper treatment, we have at theMaudsley Hospital restiricted our admissionto those cases in the early stages who wouldnot be admitted to a mental hospital. If, how-ever, careful observation is made patientsmay be treated at home, in nursing homes,or in general hospitals. If treated at home,a day and a night nurse would require to beprovided. It is, of course, advisable, andduiring the sumnmer months essential, to pre-vent mosquitoes getting in contact with thepatients during the fever. This may be donieby fixing suitable netting over the windowsand door. It may be accomplished moresimply by erecting a wooden frame aroundthe bed, which may then be enclosed withsuitable gauze netting.

Is it then desirable or expedient to treat

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THE TREATMENT OF GENERAL PARALYSIS BY MALARIA 135

all cases of general paralysis by malaria,whatever the stage of the illness ? Mostobservers are agreed that it is, provided thereare no signs of disease which contra-indicateits use, such as renal or cardio-vasculardisease. Surprising results are sometimesobtained in those who appear to be advancedcases, and consequently the ultimate out-come is a matter of doubt. It is alsoimportant to remember that the rate ofimprovement following treatment may bevery slow, anid is only manifested in its fulldegree many months after the treatment isconcluLded. As a rule, in advanced casesone can onily hope to arrest the disease, andit is a matter of opinion whether the gain tosuch patients who are transferred to whatare regarded in mental hospitals as " good-working dements" is a material one.

MECHANISM OF MALARIAL THERAPY.

The mechanism of malarial therapyremains a matter of conjecture. Varioustheories have been elaborated but none aresatisfactory. It has been suggested that theeffect may be a direct result of the highteinperature obtained during the fever,which thereby directly destroys the para-sites. The degree of fever attained durinigthe course of the illness is very rarely thatrequired experimentally to prevent develop-ment of the spirochaete.That the improvement may be due to

metabolic changes with a quickening ofmetabolism and removal of waste productshas been suggested. If this were the realexplanation, one might reasonably expect are-accummulation within the period duringwhich many of the remissions have lasted,and their relapse ere this.A further theory suggested is that the

improvement results from a mobilization ofthe defensive powers of the body resultingfrom a vital reaction of the total organismto the infectious disease.

Onie of the bodily reactions to svphiliticinfection is an increase in the mononuclear

cell-content of the blood. It is kniown thatin both malaria and relapsing fever, whichhas also been employed in the treatment ofgeneral paralysis, the mononuclears areincreased. It has therefore been suggestedthat this increase may partly account forthe benefit which results.Another theory is that the malarial para-

sites may act as antigens and give rise to theproduction of antibodies whiclh may act onthe spirochaete. Plaut suggests, on accountof this possible biological reaction, that aninfecting organism should be employedmore closely related to the spirochoete, andconsequently he has advocated the use ofrelapsing fever.

Various other suggestions have been made,but as yet we are ignorant of the truemechanism. One has to assume that thereis a destructive or at least a deleterious effecton the spirochbtes as a result of malarialtherapy, sinice they are practically neverobtained in the brain of those who haveimproved after this treatment and have laterdied of an. intercurrent disease.

OTHER FORMS OF PYREXIAL TREATMENTEMPLOYED.

The advantages pertaining to treatmentby malaria may be summarized as follows:-

(r) Frequent highi temperatures are pro-duced; (2) a great majority of people aresusceptible to the disease; (3) the rises oftemperature recur at short intervals; (4) thedisease is readily controlled by quinine.

Unfortunately there are several disad-vantages to this form of treatment.

(i) The most important isthat the reactionproduced in some patients is sometimes verysevere and produces a certain mortality.This necessitates a careful examination andselection of cases to be submitted to thisform of treatment. In all patients treatedthere is a severe degree of anasmia due tothe destruction of the red cells, and jaundicemay develop. (2) The infecting organismcannot be kept alive in culture or in labora-

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136 THE TREATMENT OF GENERAL PARALYSIS BY MALARIA

tory animals, and it must be transmitted bythe mosquito or directly from patient topatient. (3) Objection has also been raisedto the carrying over from one patient toanother of syphilitic blood with the infect-ing organism. (4) There is also the practicaldifficulty arising through the fact that someare not susceptible to malaria, anid some haveonly a limited number of paroxysms whichthen spontaneously cease.To overcome these difficulties two other

methods have been advocatedand are worthyof mention. In I9I9, Plaut and Steinerintroduced the treatment by relapsing fever.They thought that the therapeutic actionmight be intensified if a micro-organismwere employed that was closely allied to theSpirochceta pallida.

This they claimed for the infecting organ-ism of relapsing fever, namely, S. duttoni.In addition, this organism could be keptalive in laboratory animals and the fever wasalleged to be less severe than malaria. More-over, the fever was said to be readily con-trolled by the administration of arsenic.This form of treatment was tried at the

Maudsley Hospital in 1926. The infectingorganism was obtained by Dr. Golla, Directorof the Pathological Laboratory, direct fromProfessor Plaut. The strain could be keptalive in mice, but it required to be carriedover from one mouse to another every fourthday. In the inoculation of patients themouse was killed and a small quantity ofblood, i to 2 c.c., was removed asepticallyfrom the heart. This was diluted with salineand injected into the patient. As withmalaria, inoculations could be performed byeither the subcutaneous, intramuscular orintravenous methods. After the fever haddeveloped further inoculations could bemade by direct blood inoculation from onepatient to another. The incubation periodvaried from five to seven days. At theonset of the fever the patient complained ofheadache and general malaise. Thereafterthe temperature rapidly rose to I03° F. andio50 F. and was assQciated with generalized

pain throughout the body. The fever lastedabout four days, during which time thespirochates of relapsing fever were easilyfound in the blood. At the end of thisperiod the temperatur-e fell by crisis withmarked sweating. Thereafter the patientfelt more comfortable, his pains subsided,and he began to take nourishment freelyagain. He improved somewhat until aboutthe sixteenth day, when he had his firstrelapse with the original symptoms. Thiswas expected to last about thi ee or four daysagain and subside as before. Such inter-missions and relapses should follow oneanother regularly, and in the or-dinary in-fection as many as from five to eleven aresaid to occur. I nistead of this, however, anirregular temperature developed, which per-sisted after four days and showed no sign ofabating. The patient complained of severepain throughout the, body and the spleenbecame enlarged. Arsenical compoundswer-e administered, but they did not affectthe fever. This inability to control thepyrexia was obviously a great difficulty' andconsequently this form of treatment wasdiscontinued.

Solomon, on the other hand, could notobtain a sufficiently virulent strain of relaps-inig fever, and so he commenced the use ofrat-bite fever or soduku. This fever hasbeen met with in Japan and has beenmentioned in their medical books for manyyears. It has been recorded occasionallyin England, France and the United States.Infection results from the bite of a ratinfected with a spirochaete, 7norsus-mnuris.The incubation- period varies considerably,the average duration being about ten to twelvedays. Thereafter at the site of infection asore develops. This area becomes red andswollen and an ulcer forms which is said tobe not unlike a chancre. A lymphangitisoccurs from the infected area to the proximallymph glands, which in turn become enlargedand tender. The temperature now rises andmay reach I050F. or over. It is of the inter-tnittent type and mnay drop within a few

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THE ROLE OF HYDROLOGY IN MEDICAL PRACTICE 137

hours to normal again. An eruption ofpurplish coloured spots spreads over thebody, particular-ly the trunk, quite similarto those found in the secondary stage ofsyphilis. The patient feels ill with pains inthe muscles and joints. The illness maycontinue with febrile exacerbationis for aper-iod of several months. It is said torespond very quickly to arsphenamine, andthe dangers attaclhed to its use are few innumber. It has been found that if theintr-avenous method of inoculation is em-ployed, the occurrence of a primary lesionwith lymphangitis is apparen-tly avoided.The advantages claimed atre that theorganism can be maintained in laboratoryanimals anid consequently they are alwaysavailable for use. The disease is less ex-hausting to the patient than malaria. Itmay be given to patients who are immuneto malaria, and it is apparently possible togive it either before or after malaria withoutmodifying the clinical course of eithercondition. No results are as yet availableas to the efficacy of this treatment, and atpresent malaria remains the safest and- mosteffective form of fever therapy.The present consensus of opinion, howv-

ever, is in favour of a combination of non-specific therapy. Von Jauregg begins thespecific treatment as soon as the fever isstopped. With the first dose of quinine hegives o03 grm. of neosalvarsan, five dayslater o045 grm. is given, and thereafter eightinijections of o-6 grm. are given at intervalsof eight days. Varying doses of neosalvarsan,with or without bismuth, are generallyrecommended to complete the treatment.Personally, I have employed treatment bymalaria in combination with tryparsamide,which is an arsenical preparation with anunusually high degree of penetrability. In-travenous injections of 3 grm. are given assoon as a diagnosis is made. The malarialtreatment is carried out as already described,and the injections are administered through-out the fever and at weekly intervals there-after, so long as the serological findings

remain positive. By this method a relativelyhigher proportion of negative serologicalfindings has been obtained, associated withclinical improvement.

In conclusioni, I would reiterate that thereis no doubt as to the beneficial effects ofmalarial therapy, and also that such are in-creased if combinied with specific treatmenit.A careful physical examination should be

carried out prior to submitting patients tothis treatment, to exclude the possibility ofrenal, cardio-vascular or other disease. Ifthere is no evidenice of such, then withproper skill and nursilng the treatmenit isnot such a serious matter as has sometimesbeen maintained. The factor of great valueis the early diagnosis of such cases, and forthis we must look for the greater co-operationof the general practitioner.

A

THE ROLE OF HYDROLOGYIN MEDICAL PRACTICE.

POST-GRADUATE LECTURE DELIVERED FEBRUARY 11, 1930.

By MATTHEW B. RAY,D.S.O., M.D.EDIN.

Senior Physician, Thte British Red Cross Clinic forRheumatism; Physician, The St. Marylebone General

Dispensary.

(Continued from p. 126.)

VAPOUR BATHS.

The air is charged with water vapour,which has a distinct "thermal" effect onthe skin according to the temperature. Thevapour bath has been in use from timeimmemorial, and the ancient method ofpreparing it was by placing a tub of hotwater in a building and throwing hot glow-ing stones into it. The vapour bath checksevaporation from the surface of the body,itn consequence of which heat is retainedand the bodily tetnperature raised.

After a varying period in the " vapour"

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