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Among 19 controls, 2 developed complications and1 died ; the average duration of the febrile period was17 days.The results of the therapeutic trials were so successful

that prophylactic studies were undertaken. In thefirst field test, 17 out of 24 volunteers in the control

group developed scrub-typhus between the 12th and21st day after initial exposure ; they were admitted tohospital and given specific therapy. The 22 membersof the test groups remained well throughout the periodof prophylaxis and for the following week, but a fewdays later 12 of them were admitted to hospital withscrub-typhus. Four further trials were carried out.The results of the third trial clearly indicated that

chemoprophylaxis of scrub-typhus was feasible. To31 volunteers 4 g. chloramphenicol was given weekly for 4or 6 weeks after exposure to infection. Only 1 developedclassical scrub-typhus during the period of adminis-tration ; of the remaining 30, none developed clinicaldisease after the course was completed. Many, however,had mild febrile phases, during which they were foundto have rickettsaemia. Whether the pronounced anti-genic stimulus provided by the rickettsaemia was

necessary to induce immunity was a point to beinvestigated further.

Dr. Smadel remarked that although the experimentsindicated that chemoprophylaxis of rickettsial diseasewas feasible, its general usefulness was limited bypractical considerations.The possibility of immunising by inoculation with

a living attenuated strain of Rickettsia tsutsugamushiand preventing the development of clinical disease bychloramphenicol was to be investigated.The prophylactic trials provided new information on

the host-parasite-drug relationship. This concernedthe relapses that took place in about half of the 56volunteers who had contracted scrub-typhus and hadapparently responded satisfactorily to specific therapy.Such recrudescence had never been observed in patientswho acquired the disease during normal occupationalduties. The relapses almost always took place duringthe second week after onset and were promptly controlledby another course of chloramphenicol. The immediateproblem was solved by giving a supplementary dose ofchloramphenicol as a prophylactic measure about thetime when a relapse was to be expected. Rickettsemia

unaccompanied by febrile illness was observed not onlyin patients shortly after treatment, but also in ambulatoryvolunteers during chemoprophylaxis and in volunteersshortly before onset of the initial attack or of the relapse.This observation was of fundamental importance tothe understanding of scrub-typhus. - .

Chloramphenicol, Dr. Smadel explained, had a

rickettsiostatic, not a rickettsiocidal, action ; rick-ettssemia, without symptoms, could persist after thedrug had been administered. It was not yet possibleto explain why a single dose suppressed clinical signs ofdisease for approximately a week. Chloramphenicol wasrapidly excreted from the body and was no longer detect-able in the blood 24 hours after a single dose of 3-4 g.Therefore the persistence of appreciable amounts ofthe native antibiotic could not explain the prolongedtherapeutic effect. ’Aureomycin’ produced the sametherapeutic results as chloramphenicol in scrub-typhus;both drugs gave equally rapid defervescence.

Dr. Smadel then described the effect of chloramphenicolon typhoid fever. Here also -the drug suppressed thepathogen and gave the host time to develop the mecha-nisms of resistance. The beneficial results in typhoidfever, however, did not become evident so rapidly as

in scrub-typhus. Little effect was noted during thefirst two days of treatment, but by the third or fourthday the fever abated boy lysis and the rose-spots, if

originally present, disappeared ; headache, cough, and

toxaemia, were ameliorated. From then onwards con-valescence usually proceeded rapidly. Of 45 patients

- with typhoid fever who were treated with chloram- --phenicol during the initial phase of their illness, 44survived.A high relapse-rate might be expected if the drug was

given for 8 days or less and few relapses if it was givenfor 14 days. Whilst it was still too early to set a standardschedule for the treatment of typhoid fever by chloram-phenicol, the last one employed by Dr. Smadel’s groupin Malaya was as follows : an initial dose of 3-4 g.,followed by 1-5 g. at 12-hourly intervals during thefebrile period ; then 1.5 g. in a single daily dose for7 days ; followed by 1 g. daily until the 14th day. Morerecently Dr. T. E. Woodward had given chloramphenicolin similar dosage to that described above, for the first5 days ; he then omitted the drug for 5 days ; and afterthat he repeated the original course. He observed no

relapses in 8 patients treated in this way. Dr. Smadelemphasised that chloramphenicol therapy did noteliminate intestinal haemorrhage or intestinal perforationin typhoid. Patients still required the usual isolationprecautions, but were less of a menace to public healththan untreated patients.

Finally Dr. Smadel mentioned the efficacy of chloram-phenicol in another rickettsial disease, Rocky Mountainspotted fever, and in venereal diseases of varied aetiology—gonorrhoea, lymphogranuloma venereum, lympho-granuloma inguinale, and syphilis. Benefits derivedfrom its use in brucellosis and tularaemia were worth

noting ; and laboratory studies suggested that a numberof other infectious diseases of man might be controlledby this antibiotic.

ROYAL SOCIETY OF MEDICINE

Recent Work on Vitamin B12THE society’s section of experimental medicine met

on Feb. 14 under the presidency of Prof. G. W. PICKERING.Mr. E. LESTER SMITH, D.sc., described the steps

by which he fractionated liver extract to obtain the

anti-pernicious-anaemia factor in crystalline form. All

assays had been made on man. The crucial procedureswere physical rather than chemical and included adsorp-tion on charcoal and partition chromatography. It wasnoticed that the active fractions were red, and thishelped in following the active principle. He showed theelegant microbiological assay methods now used, and how,coupled with partition chromatography, they revealedthe presence of at least three active substances :the vitamin B12, an allied B12b, and thymidine. Heannounced that from Streptomyces griseus he had obtainedin crystalline form another substance which, tested onpatients, had proved as effective as vitamin B12. Ithad not yet received an official name, and he referredto it as ’’ the unnamed substance." Its chemical and

physical properties were very close to those of vitamin B12’The investigation of the chemical structure ’of the

vitamin was proceeding. One atom of cobalt was con-tained in its molecule; also a dimethylbenzimidazolegroup and probably a pyrrolic substance. On the

physiological side Ternberg and Eakin 1 had lately foundin normal gastric juice a non-dialysable, heat-labilesubstance which combined quantitatively with vitaminB12; the gastric juice of patients with pernicious anaemiacontained a great deal less than the normal amount ofthis substance. Vitamin B12 thus combined was notavailable to micro-organisms, and was more resistantto alkali and oxidative agents. It was thought thatthis substance might be either Castle’s intrinsic factoror an important component thereof.

-

The cases on which Dr. C. C. UNGLEY had investigatedthe action of vitamin B,,, and some of the kindred sub-

1. J. Amer. chem. Soc. 1949, 71, 3858.

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stances isolated by Dr. Lester Smith, fell into two groups :(1) idiopathic addisonian anaemia with gastric atrophy ;and permanent loss of Castle’s intrinsic factor, which,he said, led to deficient absorption of vitamin B12;and (2) non-addisonian megaloblastic anaemias such as :

those associated with pregnancy and intestinal disorders,where a different mechanism was at work.With a single initial dose varying from 5 to 80 .g.,

the actual increase of red blood-cells on the 15th day wasproportional to the logarithm of the dose used ; withall doses there was little effect by the 5th day, and

generally after the 15th-20th day the red-cell curve

flattened. In a number of cases a dose varying from15 to 140 .g., given over a period varying from 15 to118 days, raised the red-cell level above 4,500,000 perc.mm. For maintenance Dr. Ungley found that in theabsence of subacute, combined degeneration of the cord,10 (Lg. every two weeks sufficed over periods rangingup to 18 months.A system of scoring the extent of neurological defects

had been worked out in 44 patients treated with liverextract for subacute combined degeneration of the cord.It had thus been possible not only to score improve-ments but also to establish a scale of "expected"improvement with liver extract. Of 8 patients receivingvitamin B12 over periods ranging from 9 to 19 months,2 had slight, 4 moderate, and 2 severe neurologicalsymptoms. In 4, improvement exceeded the expectedrate ; in 2 it attained it ; and in 2 it fell just shortof it. Dr. Ungley concluded therefore that vitamin B12was as effective as liver extract not only in addisonianpernicious anaemia but’in subacute combined degenera-tion of the cord. He found that weekly doses of 40 (Lg.were usually adequate in the first 6 months, with halfthat amount for maintenance. Dosage should beincreased if intercurrent infection or the least sign ofrelapse supervened.

Lester Smith’s , " unnamed crystalline substance,"obtained from Streptomyces griseus, was given to 20 casesof addisonian pernicious anaemia, 3 of them with neuro-logical symptoms. The initial doses had proved as

effective as vitamin B12 as regards the blood picture,glossitis, and neurological symptoms ; but since no casehad been treated more than three months, judgmenton its final effect should be reserved. In one case a goodresponse to the " unnamed substance " was followed by arenewed reticulocyte rise when 10 (Lg. of vitamin B12was given. ’

Dr. Ungley described one patient with what seemedto be a typical addisonian anaemia (complete achlor-hydria and megaloblastic marrow), who had been treatedsix months previously for syphilis but showed normalliver-function tests and had apparently had a satis-

factory diet. His response to vitamin B12 was poor ;but 2-5 mg. of folic acid daily (total 15 mg.) gave asatisfactory reticulocyte rise. When subsequently thispatient was given 10 (Lg. of vitamin B12 of the same batchas before, at a time when the red-cell level was beginningto fall, there was a renewed rise of the level.

Even when 80 pt.g. of vitamin B12 (or of the " unnamedsubstance ") was given by mouth, the response was poor.In one case 1920 ug. by mouth in 24 days gave anincrease of red cells less than that expected from 5 (Lg.in a single injection. When in the same case 1 (Lg. was givenby injection daily for 10 days there was a rise equivalentto what was expected of a single dose of 10 .g.

In another patient 5 (Lg. daily by mouth had provedineffective. When 50 ml. of normal unfiltered gastricjuice was added, there was a satisfactory response in15 days, a total dose of 50 (Lg. of vitamin B12 resulting ina rise of red cells equal to what would be expected of10 (Lg. if injected.

In yet another patient the response equalled thatexpected from the injection of 20 (Lg. One subject who

took 50 tg. by mouth at one time, with 500 ml. of gastricjuice, reacted as he would have been expected to reactto 40 ;jt.g. when injected.

Passing the gastric juice through Seitz filters removedits intrinsic-factor activity. Generally the unaccompaniedoral dose needed to be about 80 times as large as theparenteral one. Dr. Ungley’s efforts to determinewhether gastric juice helped the absorption of vitamin B12or protected it from destruction, so far left the problemunsolved.

Dr. Ungley quoted 3 cases of megaloblastic ansemiawith intestinal disorder in which results were variable.One suffered from intestinal stenosis : a single dose of80 g. gave a response which in addisonian anaemiawould have been expected from 20 (ig. In another casethe rise of red cells obtained with a single dose of 80 (igwould have been obtained with 5 t-tg. A third patient,with steatorrhoea and thyrotoxicosis, was completelyrefractory to vitamin B12 but responded well to folicacid.

Six cases of megaloblastic anaemia of pregnancy weretreated. Vitamin B12 in doses of 65-80 g. was completelyineffective ; subsequently 2.5 mg. of folic acid dailycured the anaemia and restored normoblastic bone-marrow.

Dr. Ungley insisted that vitamin B12 is quite as

effective as liver extract in the treatment of all manifesta-tions of addisonian anaemia ; but as a reminder of howfar we are from a complete solution of the physiologicalproblem he quoted the following observation: in

pernicious anaemia a remission could be brought aboutby giving yeast by mouth-120 g. of Marmite ’ daily.One-tenth of that dose was effective if gastric juice wasgiven with it ; and this smaller dose was all that was

required in non-addisonian anaemias. Yeast extracts

appeared to contain no vitamin B12 when tested eithermicrobiologically or in animals ; yet it seemed to actas a source of extrinsic factor.

Dr. J. V. DACIE reported on 30 cases of true perniciousanaemia treated with liver extract, vitamin Bz2, andLester Smith’s " unnamed substance." It was a studyof the finer relations between the histological picture ofthe bone-marrow, the size of the reticulocyte response,and the increase in the red cells. With a single dose of20 tg. of vitamin B12 the marrow became normoblasticin the first five days, and reticulocytes might accountfor nearly all the red-cell increase. In some cases themarrow reverted to an " intermediate " stage as early as.the 5th day and was megaloblastic by the 10th day.Dr. Dacie found that the red-cell response was biphasic,with a shelf between the 5th and the 9th day. Duringthe second rise there were fewer reticulocytes, and almostall the increase was due to cells already mature as theyreached the blood-stream. The size of the second rise

depended on the dose And could be correlated with themarrow picture. A single initial dose of 30-40 ,g.caused the marrow to remain normoblastic to the 15th

day ; 20 jjLg. gave a satisfactory response in the bloodbut allowed a regression of the marrow to the megalo-blastic stage in the same period.

Dr. J. N. M. CHALMERS said that in his clinic a main-tenance dose of 20-40 .g. fortnightly had mostly provedsatisfactory ; in a few cases 60 (JLg. had been needed.In his experience vitamin B12 did everything that liverdid and it had proved useful in patients who hadrelapsed on unsatisfactory liver extract. Eight cases

treated with the " unnamed substance " were doing well.Vitamin B12 was satisfactory in 4 patients allergic toliver extract ; 1 of these, who suffered from cripplingsubacute combined degeneration, was restored to activelyearning a living.

Dr. A. G. SiGrrY reported what he thought was aneffect on the bone-marrow one hour after injection in apatient in whom the marrow was studied hourly. The

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PRESIDENT and Dr. P. L. ’VIoLr,isot commented on theeffect of vitamin B12 on the survival time of transfusedblood-cells which Dr. Ungley had described in some ofhis patients.

HepatitisON Feb. 17 Prof. JOHN R. PAUL (Yale University)

addressed the section of epidemiology on Endemic

Hepatitis Among United States Troops in Post-war

Germany. Afterwards he received the honorary member-ship of the section from Dr. W. H. BRADLEY, presidentof the section. Honorary membership has also beenconferred on two other Americans-Prof. JOHN E.GORDON and Dr. JOHN GRANT.Professor Paul began by recalling contributions to ,the

study of hepatitis by British workers since the war. Theincidence of hepatitis among U.S. troops at home hadbeen steadily declining ; the rate in Japan, which startedat a relatively high figure, was also going down. But in

occupied Germany the incidence had been steadilyrising, until it was comparable with that in combatareas during the war-around 14 per 1000 per annum.In the late war hepatitis " fell like a bombshell " on

the U.S. Army, which was unprepared for it ; prepara-tions had been made on the lines of the 1914-18 war. Firstthere was the outbreak of homologous-serum jaundicein 1942, due to yellow-fever vaccine. Then in 1943came an outbreak of infective hepatitis in which theBritish Forces were also involved.At least two viruses appeared to be concerned. First

there was that of infective hepatitis, the naturallyoccurring disease ; secondly, that of serum hepatitis,which was readily produced artificially. The diseaseswere almost the same clinically. Although the viruseswere not identical, it seemed that they were of the samegroup. The infective type had an incubation-period asshort as 15 days ; contact cases were common ; and thevirus was found in the faeces during the acute stage andcould be transmitted orally. With serum jaundice theincubation-period was 60 days ; contact cases were

uncommon ; the virus was present in the blood duringthe incubation-period as well as the acute stage ; andthere was only parenteral infection. There was nodemonstrable cross-immunity. Both diseases could betransmitted by needles. Whilst the origin of infectivehepatitis was known, that of serum jaundice was not.Both infections often appeared at one time and place.

Infective hepatitis was geographically widespread, andits diffusion was aided by poor sanitary conditions. Itwas prevalent particularly in China, the Eastern Mediter-ranean, and, it seemed, Southern Germany. In the armiesin North Africa and Italy there was a sharp autumnalpeak; and this seasonal incidence was seen in thecivilian records of Denmark and Sweden. From thecivilian point of view, infective hepatitis was essentiallya children’s disease.

It was common in the civilian population of Germany,where little attention was paid to it. The incidence inthe old Imperial German army had been twice as highin Bavaria as in Prussia. The American occupationzone of 42,000 sq. miles was composed mostly of Bavaria ;and, as he had stated, the incidence of hepatitis amongthe U.S. occupation troops was very high. The diseaseoccurred in the younger individuals who had been inthe area a relatively short time, cases developing aroundthe 9th-lOth month of service there and being sporadic indistribution. There were slightly higher rates amongtroops in Berlin and Trieste. The incidence was aboutthe same among coloured as among white troops, andbore no special relation, as in the war, to Service rank.While the British experience in Germany showed a normalseasonal swing, the incidence among the Americansshowed two peaks-in October and February. This wasin keeping with Ruge’s observations on ’ Salvarsan’

hepatitis in the German navy about twenty years ago,

and might possibly imply a relationship between infectiveand serum hepatitis.

Investigations were made to try to determine whetherimmunisation or the administration of penicillin couldhave contributed to the spread. There was some evidencethat men with hepatitis had a greater penicillin historythan others, but it was not completely significant andthese were the men who might have got the disease bycontact with German homes.

Since infective hepatitis had been endemic in the areafor many years, it was not unlikely that it should becommon among the occupation troops ; but that itshould be so common and increasing was surprising.

Prof. E. T. C. SPOONER referred to the differencesbetween the situation in the U.S. Army in Germanyand that among British troops in the Middle East in1942-43. In the latter epidemic the incidence was

higher and there was a strong seasonal trend. In the8th Army following El Alamein, the incidence reached15 per 1000 per month, against 14 per 1000 per yearamong the American Forces in Germany. A greatmany of the cases were widely distributed, but therewere a number of units recently arrived in the area among.which true explosive epidemics occurred at a time whenthey had been isolated from the outside world.

Dr. KLINT, of the World Health Organisation, remarkedthat the Royal Medical Board of Sweden had askedW.H.O. to take international action on infective andserum hepatitis. Dr. Klint wondered whether a particulartype of food could have something to do with the spread.It seemed that the virus might be preserved in tinned food.

Dr. W. G-UNN said that infective hepatitis was moreserious in adults than in children, whereas with serumjaundice the reverse was true. He believed there wereno known cases of serum hepatitis where dry serum,prepared in the L.C.C. laboratories, had been used.In measles cases they had never had any serum hepatitis,and the reason might be that 0-5% phenol was mixedwith antimeasles serum. Had the use of ultraviolet radia-tion to inactivate serum become a practical proposition ? ‘

Dr. F. 0. MACCALLUNI observed that in Great Britainthe incubation-period following the parenteral inocu-lation of volunteers with serum had never beenless than 30 days. He agreed that there were

probably two viruses or strains of virus, and he thoughtthe present terminology should be changed in favour ofA and B infections, as in influenza. He recalled that ina number of inoculees who had received serum from

patients with presumed syringe-transmitted hepatitis,the virus had been found in nasal washings in the pre-symptomatic, long incubation period. He suggestedthat homologous-serum jaundice (hepatitis virus B)was a naturally occurring disease with a long incubation-period and a droplet spread, and that this was whyit was not found ordinarily and the virus maintaineditself in nature.

Dr. C. H. ANDREWES, F.R.s., postulated that in thetwo types of hepatitis the same virus, though of differentraces, might be at work.

Dr. A. M. McFARLAN, discussing the sporadic spreadand seasonal variation, said that in 1943-44, whena number of cases were reported among troops in EastAnglia, only occasionally was there more than one

case in a particular unit, and this unit was usually ina town where there was a civilian epidemic ; it did not

appear to be due to spread by contact within the unit.A very different state of affairs prevailed in divisionsbrought back from Scilly before D-day. There hepatitisspread through the units, with a 30-day interval betweencases. In East Anglia, where hepatitis was -notifiable,an abnormal season incidence was noted in 1946, whenthere was a rise in April which went on until August ;this appeared to be an out-of-season epidemic. Apartfrom that one year the rise had always been in theautumn, and it had always been possible to track it

356

down to places where there had been just a few casesduring the summer ; there might be a developmentalcycle in the virus. This would explain many of the factsabout serum hepatitis and infective hepatitis, but inthis event it would be difficult to account for the lackof cross-immunity.

Dr. W. d’A. MAYCOCK referred to the results of the

investigation of serum jaundice in Liverpool. It wasfound that the incidence in persons who had large-poolplasma (that is, from a pool made up of 300-400 dona-tions) -was 10-12%, whilst among persons who had hadsmall-pool plasma (from pools of not- more than 10

donations) it was about 0-15%. Small-pool plasma wasnow being produced in quantities equal to the needsof hospitals, and it was felt that this was a considerableadvance in eliminating serum jaundice. Arrangementswere also being made to irradiate serum.

Dr. W. M. PICKLES said that his records, going backto 1910, showed the autumnal rise. Although the virushad been discovered in the stools of infective-hepatitiscases and no-one would say it could not be transmitted in

that way, Dr. Pickles thought that most cases arose bypersonal contact, probably droplet infection.

, The PRESIDENT remarked that there had been veryfew cases of homologous-serum jaundice among uninocu-lated persons in the environment of the Americansoldiers affected by the yellow-fever inoculation virus.Later MacCallum, investigating some half-dozen womenwho developed serum jaundice following gold injection,found that the bedfellows of two of them developedhepatitis spontaneously after about 50-60 days.

’

Professor PAUL agreed that the terminology repre-sented pegs on which to hang rather vague ideas thatleft much to be discovered.’ Although he had started bysaying that there were two different viruses, he wasrather coming round to the monotheistic point of viewat the end of his paper. He did not know of any foodwhich would harbour the disease ; but that was not tosay there were not some. Sterilisation of serum by

- ultraviolet rays was still in a somewhat experimentalstage ; another method was to add nitrogen-mustard towhole blood and serum ; he had no experience of phenol.He thought that Dr. Andrewes’s suggestion of symbiosis

was very reasonable, if only it could be proved.LIVERPOOL MEDICAL INSTITUTION

Sudden Death in NurslingsAT a meeting on Jan. 12, with Prof. CHARLES WELLS,

the president, in the chair, Dr. F. B. SMITH said that thesudden and unexpected death of nurslings was a recurrentproblem whose suggested solution often lacked conviction.The difficulties were obvious to those who performednecropsies for coroners, but were not so obvious toothers. In his experience these cases formed the secondlargest group of sudden deaths examined for coroners,the first being disorders of coronary arteries.The infants were usually between 4 and 40 weeks of

age, and were regarded as having had normal healthwithin a few hours, or even minutes, of being founddead. In the past smothering, overlaying, and chokingby food had been the commonly accepted causes ; butwith an increase in the number of cases examined

by necropsy an increasing proportion-was being ascribedto natural causes-most often acute infections of the

respiratory tract.Necropsies on infants were often inconclusive ; the

naked eye was more often inadequate than in the

necropsy of an adult. A set scheme was necessary,including the use of the microscope, bacteriology,histology, and, if possible, chemistry. The damage dueto a wrong verdict of unnatural death might be lasting ;and despite the inexpediency of delay, the proper coursemight be a request to the coroner for time for micro-scopical studies. There was need for a series of controlsof the naked-eye and microscopic data often accepted

as explanation of death, whether due to unnatural anoxiaor acute infection.

Dr. Smith was loth to accept the view that the averagenursling of this age allowed accidental smothering.Often evidence of both the presence and effect of gastriccontents in the airways was questionable ; for example,vomiting was a symptom of anoxia, and food in theairways was found after death from many naturalcauses. He was not satisfied that small infective fociin the respiratory tract or other sites, found only bythe microscope, could explain sudden and unexpecteddeath. Though serosal and interstitial haemorrhagesoccurred apart from obstructive anoxia, the strikingflea-bitten appearance of one or all of the three organs-thymus, heart, and lungs-had not been seen in othercircumstances. The possibility of chemical, allergic, orendocrine stimulus deserved consideration. Most ofthese infants died in the third or fourth month of life,at which time the thymus was largest in proportion tobody-weight ; the function of the thymus was unknown.About one-third of these infants were found to haveparietal craniotabes but without clear signs of rickets.

In no more than 15 of 60 infants examined after suddendeath was the opinion offered that death was due to aspecific infection ; and in 7 of the 15 the evidence wasslender. Most often the preferable conclusion was thatthe cause of death was unknown.

Dr. Smith concluded with a plea for : (1) avoidingif possible an opinion based on inadequate data ; (2) theuse of - schematic routine histology and bacteriologyafter death ; and (3) the collection and publication ofcriteria for the final medical opinion on the so-called" suffocated " infant.

Reviews of BooksEstudios sobre la Circulacion Renal (Barcelona :

Jose Janes. 1949. Pp. 208. 180 Ptas).-Prof. J. Trueta’soutstanding work, Studies of the Renal Circulation, reviewedin our columns three years ago,’ has now been published inSpanish. It is well that this important contribution to ourunderstanding of the medullary vessels should be easilyaccessible to as wide a circle of research-workers as possible.,His argument is supported by convincing photographs,the beauty of which receives full justice, in this volume,from the excellent surface of the paper.A Text-Book of Surgery by American Authors (5th ed.

Philadelphia and London : W. B. Saunders. 1949. Pp. 1150.65s.).-In its 5th edition this large textbook, edited by Dr.Frederick Christopher, comes fully up to what we have beenled to expect. It gives an authoritative presentation of generaland gynaecological surgery as nowadays practised in America.There is a great deal of new matter and there are many newauthors. The book is so well known, and its reputation sohigh, that praise is superfluous ; but it is worth consideringwhat appeal it may have for the English. It is so completein its range, and reflects so truly the American outlook,particularly the physiological aspects of surgery, that it willbe useful to any surgeon, and especially to those who teach.Also the references at the end of each section will be helpful.Whether our undergraduates will welcome it equally is moredoubtful-for two reasons. In the first place it is a very largevolume for an undergraduate student to read through twoor three times during the time allotted to him for clinicalwork : its mere size is rather appalling in prospect. Secondly,most of the contributors assume a certain ground knowledgeof surgery which English students do not possess when theyenter on their clinical stage of study. For them numerousstatements would have no meaning. Take for instance thesection on prostatectomy. Four methods are mentioned withtheir indications, advantages, and drawbacks. But what useis this if the student has no idea what is meant by the termssuprapubic, perineal, retropubic, or perurethral prostatec-tomy ? The student’s ignorance could be dispersed by adescription in a few sentences of each operation, and he couldthen take an intelligent interest in the discussion. Thisseems a small defect in so magnificent a compilation by nearly200 authors ; yet to the undergraduate student it looms largein a book which would otherwise delight him.

1. Lancet, 1947, ii, 135.