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I wish t6 thank’Prof. Samson Wright and Dr. D. Slome formuch help and encouragement. The expenses of this researchwere partially defrayed by a grant from the Medical ResearchCouncil to Prof. Samson Wright. ,,

REFERENCES

Breedis, C., Flory, C. M., Furth, J. (1943) Arch. Path. 36, 402.Courtois J., Biget, P. (1943) Bull. Soc. Chim. biol. 25, 103.Demuth, F. (1925) Biochem. Z. 159, 415.Dmochowski, A. (1933) C.R. Soc. Biol. Paris, 113, 956.Folin, O., Denis, W. (1915) J. biol. Chem. 22, 305.Gutman, A. B. (1942) J. Amer. med. Ass. 120, 1112.

— Gutman, E. B. (1938) Proc. Soc. exp. Biol., N.Y. 39, 529.— — (1941) Endocrinology, 28, 115.

King, E. J., Armstrong, A. (1934) Canad. med. Ass. J. 31, 376.— Wood, E. J., Delory, G. E. (1945) Biochem. J. 39, 4.

Kutscher, W., Wolbergs, H. (1935a) Naturwissenschaften, 23, 558.— — (1935b) Z. physiol. Chem. 236, 237.— Wörner, A. (1936) Ibid, 239, 109.

Rabaté, J., Courtois, J. (1941) Bull. Soc. Chim. biol. 23, 190.Scott, W. W., Huggins, C. (1942) Endocrinology, 30, 107.Theis, R. C., Benedict, S. R. (1924) J. biol. Chem. 61, 67.Waldschmidt-Leitz, E., Nonnenburg, H. (1935) Naturwissenschaften,

23, 164.Wilmer, H. A. (1944) Arch. Path. 37, 227.Wolbergs, H. (1936) Z. physiol. Chem. 238, 107.

Preliminary Communication

ACTIVITY OF PENICILLIN ESTERS

AMONG the various procedures for prolonging the timeduring which penicillin remains in the blood-stream at atherapeutic level, with an accompanying reduction inthe rate of urinary excretion, the use of water-insolublepenicillin esters has been suggested. I have made adetailed study of the methyl and benzyl esters of " pure "penicillin, having an activity of 1500 f.-u.1/mg. The detailsof this work will be published elsewhere in full 1 ; mean-while the general conclusions may be of interest to

penicillin users.I find that some species of animals, including mice,

rats, and guineapigs, have in their sera an esterase thathydrolyses the methyl and benzyl esters of penicillinin 10 minutes. This enzyme, or complex of enzymes, isabsent from the sera of rabbits and mail. When theesters are injected into the rabbit or man no therapeuticeffect is exerted. No penicillin can be detected circu-lating in the blood of rabbits or men during periodsbetween 1 and 48 hours after injection. Furthermore, itappears that the ester, though it exerts no antibacterialeffect, is destroyed in the body, for it cannot be found inthe blood or urine of rabbits and men after injection. Onthe other hand, the enzymatic hydrolysis of these estersin mice, rats, and guineapigs, with the resulting liberationof penicillin, confers on them an antibacterial action of the,same order as that of corresponding quantities of the free- antibiotic.

,

These conclusions have consequences both in appliedtherapeutics and in laboratory technique. It is clear thatthe esters cannot have any value as compounds forprolonging the penicillin effect when injected into man,because, not being hydrolysed, they have no anti-bacterial effect at all. On the other hand, the existenceof a penicillin esterase in the sera of mice, rats, andguineapigs makes these sera, particularly those of guinea-pigs, useful agents for investigating the effect of theesters in various species of animals. Incubation at37°C with guineapig serum, for example, causes liberationfrom the methyl and benzyl estexs of free penicillin, whichcan then be estimated in the usual manner. This methodgives a convenient and quick method of detecting

. penicillin esters in different organs and body fluids,and should also prove useful in testing therapeuticagents.

J. UNGAR.Glaxo Laboratories Ltd., Greenford, Middlesex.

1. Ungar, J. Brit. J. exp. Path. (in the press).

Medical Societies

ASSOCIATION OF CLINICAL PATHOLOGISTS

THE association’s annual meeting was held in Londonon Jan. 24 and 25, under the chairmanship of Dr. J. G.GREENFIELD.

The Interpretation of Blood-sugar Levels inChildren .

was discussed by Dr. J. L. EMERY, who showed cases ofcoeliac disease with clinical hypoglycaemia despite normalfasting blood-sugar levels. The pallor and sweating arerelieved by glucose without a rise in the blood-sugar,and adrenaline also relieves the symptoms. Clinicalmanifestations should be recognised as real evidence ofhypoglycaemia irrespective of the blood-sugar content,especially since symptoms may occur, even with a risingblood-sugar, following administration of insulin.

Dr. N. F. MACLAGAN described a modification of the.Lange colloidal gold curve using buffered solutions. The

advantages of buffered solutions are that they are moreexactly reproduced and give more dependable results,because they are unaffected by traces of acid and alkaliand because false positives are less common. The standardten tubes are unnecessary since it is only the precipitationin the lower dilutions which indicates globulin increase.

Dr. B. E. TOMLINSON, speaking on the chronic appendix,said that there was no appreciable difference betweenthe appendices in 100 surgical cases and those in 100bodies following sudden death. In the surgical cases,however, localised inflammatory changes were seen inthe internal muscle layer ; these suggested a retrogressinglesion. Local areas of fibrosis and local collections ofeosinophils were demonstrated in the muscle coats ; butas far as the mucosa was concerned eosinophil countswere often higher in the controls than in the surgicallyremoved appendices. He concluded with a plea formore exact pathological appraisal of the surgicallyremoved appendix.

Dr. J. T. DUNCAN described the widespread lesionswhich may be found in torula meningitis. Infection, hesuggested, usually takes place via the tonsil or by traumaof the skin, and the organism, Cryptococcus neoformans,has a predilection for the central nervous system and thelungs. It is hard to recognise this organism unless it isproperly stained, preferably by muci-carmine. Thereare probably more cases of torula meningitis than is

appreciated, for with a careful look-out they are identifiedfairly often.

Dr. V. D. ALLISON and Miss B. HOBBS discussed theepidemiology of pemphigus neonatorum from observation .

of 200 cases seen in one large and two small epidemics,using serological typing of Staphylococcus pyogenes. Thisshowed that the sources of infection are the upperrespiratory tract and skin of carriers. Carriers are

commoner among nurses than the general public ; andone series of cases originated from a carrier whose taskit was to fold clean napkins in a laundry. It is importantnot to incriminate an attendant until it has been provedthat the serological type found in her agrees with thatcausing the epidemic. It may be worth applying penicillinto the anterior nares of chronic tonsil carriers.

Dr. J. G. GREENFIELD, reviewing the causes of cerebralabscess, emphasised the importance, in the differentiationfrom meningitis, of estimating the sugar in the cerebro-spinal fluid ; this is early reduced with meningitis, whilewith abscess it usually remains normal until meningitissupervenes. Usually the cerebrospinal fluid is clear ;the cell-count in his cases varied from 4 to 800 per c.mm.,with lymphocytes predominating ; and protein variedfrom 10 to 200 mg. per 100 ml. The organisms were veryvariable : of 45 cases, 15 were due to staphylococcus,10 to anaerobic streptococcus, 10 to fusiform bacillus,

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6 to pneumococcus, and 6 to proteus. The prognosisis best with pneumococcal a,nd streptococcal infections.

Dr. C. E. DUKES, speaking on the hereditary factor inpolyposis of the intestine, described families in which thedisease was transmitted as a dominant character ; the

gene can be carried by male or female.Dr. S. C. DYKE showed that in the treatment of refractory

anœmia with folic acid there may be a double rise inreticulocytes. In pernicious anaemia and in refractoryanaemias expected reticulocyte and red-blood cell levelsare always reached. In 2 cases of pernicious anaemiawith previous histamine-fast achlorhydria the acidreturned in the gastric secretion after treatment withfolic acid.

In a discussion on the laboratory applications of theRhesus factor a general plea was made for the adoptionof Fisher’s nomenclature. It was considered that everyprospective mother should be Rh-grouped, and thatdifficult cases should be referred to the laboratories atthe Lister Institute.

Reviews of Books

A third edition has appeared of CLINICAL PRACTICE ININFECTIOUS DISEASES (Edinburgh : E. & S. Livingstone,pp. 679, 22s. 6d.) by Dr. E. H. R. Harries and Dr. MauriceMitman. After publication of the second edition in 1943, afire at the printers destroyed the blocks, and made reprintingimpossible. The book has therefore been completely revised,and contains a new chapter on the pneuinonias, and shortsections on the common cold, febrile herpes, epidemic nauseaand vomiting, epidemic myalgia, and infective polyneuritis.The account of penicillin has been expanded, and a noteadded on streptomycin. Social conditions are discussed inrelation to epidemiology, and more space has- been given to" influenzal " meningitis, food-poisoning, homologous serumjaundice, typhus, virus diseases of the nervous system (whichincludes a critical review of the Kenny method of treatingpoliomyelitis), mass chemoprophylaxis, and many other

subjects of recent and growing interest. This valuable workis thus larger by some 100 pages than in its last edition.

Dr. Wilfrid Sheldon’s DISEASES OF INFANCY AND CHILD-HOOD (5th ed., London : J. & A. Churchill, pp. 775, 30s.) bidsfair to become as popular as Still’s. The advent of penicillinis the outstanding new development since the last edition, andits use is well described in a brief appendix. The sections ontuberculosis, coeliac disease, and poliomyelitis have beenrevised, and growing interest in the newborn period is reflectedin the text.

ACIDOSIS (London : W. Heinemann, pp. 225, 18a.) iswritten by Dr. Esben Kirk, chief physician to the medicalservice of Holstebro District Hospital, Denmark, and wasfirst published in 1942 to convince his colleagues of the impor-tance of treating acidosis with isotonic sodium bicarbonatesolution. His specialised approach to the problem detractsfrom the value of his otherwise interesting survey of a per-plexing problem ; and few British clinicians will agree withhis emphasis on isotonic sodium bicarbonate in the treatmentof diabetic coma.

By recording belief as fact and omitting pros and cons,Prof. Rolland J. Main, PH.D., of the Medical College of Virginia,has usefully summarised the salient facts of human physiology.His SYNOPSIS OF PHYSIOLOGY (London : H. Kimpton,pp. 341, 18.s.) is intended to serve as a quick reference bookfor students already acquainted with their subject. It givesplenty of numerical data, supplemented with useful tablesand few but graphic diagrams. While unsuitable for either theadvanced student or the beginner, it is satisfactory for itsown purpose.

Dr. F. M. R. Walshe, F.R.S., writes in the preface to the 5thedition of his DISEASES OF THE NERVOUS SYSTEM (Edinburgh :E. & S. Livingstone, pp. 351, 16s.) that he has made suchminor additions as the advance of knowledge, the flux ofopinion, and the suggestions of correspondents make expedient.The student will again find the principles of neurological diag-nosis and the common diseases of the nervous system welldescribed; but the psychoneuroses are still given only 23pages. It might be better to omit this section from a textbookin which it is hardly at home.

Nineteen new coloured photographs appear in the 3rdedition of Dr. Henry Semon’ unique ATLAS OF THE COMMONER,SKIN DISEASES (Bristol: J. Wright, pp. 343, 50s.), but,unfortunately some of them are below the original highstandard, the colour-values being erratic, or blurred. Thetext is terse and highly informative. It is noteworthy thatDr. Semon roundly condemns the local use of sulphonamidesin skin diseases.

Prof. Maurice Loeper is professor of clinical medicine tothe Faculté de Medecine of Paris. His collection of essays(HÉPATITES RARES, Paris: Masson, pp. 214, fr. 290) is notconfined to hepatitis but includes chapters on oxaluriaand liver disease, anaemia in cirrhosis, and cystic disease ofthe liver. The theories presented often seem strange, andmany statements are unsupported by data. The bibliographyrefers mainly to Continental work.Dr. F. M. Pottenger, medical director of his own sanatoriumin California, sets out his views on the reflex action of thespinal and automatic systems in visceral disease. The 6thedition of his SYMPTOMS OF VISCERAL DISEASE (London:H. Kimpton, pp. 442, 25s.) is essentially the same as itsforerunners. He urges the relationship of many apparentlyunconnected symptoms with the morbid process, sometimesusing readily acceptable evidence, at others evidence whichlacks scientific support. The work can only be recommendedto those who know enough to read it critically.

In AMPUTATION PROSTHESIS (London : J. B. Lippincott,pp. 305, 50s.) Dr. Atha Thomas, associate professor of surgeryin the University of Colorado, and Mr. Chester C. Haddan,president of the Association of Limb Manufacturers ofAmerica, have collaborated to discuss the problems faced bysurgeon and limb-maker in fitting prostheses. They coverwell such topics as the moulding of the stump by bandaging,re-education of the stump muscles, functional values of

stumps of various lengths, and the training of the patient inthe use of his limb, and they lay emphasis- on the importanceof fit and alignment. A good section deals with prosthesesin children.

Mr. H. E. Cox, D.SC., is an experienced public analyst, andthe techniques detailed in his CHEMICAL ANALYSIS OF FOOD9(3rd ed., London : J. & A. Churchill, pp. 317, 24s.) are prob-ably those commonly used in his laboratory. Though theyhave stood the test of time, many of them have been super-seded in the eight years since the last edition, and might wellhave been omitted in this one. Thus the Kjeldahl methoddescribed is now out of date, and there is no mention of theselenide catalyst which has accelerated the tempo of all totalnitrogen assays. Fuller accounts of some of the more modernmethods would have been welcome. - The scope of the bookis wide, and there is an appendix on the preservativeregulations and prohibited colouring matters.

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Mr. W. H. Maxwell’s compendious, indeed discursive, guideto the engineering side of water-supply (CURRENT WATER-WORKS PRACTICE, London: B. T. Batsford, pp. 254, 18s.) willbe useful on the M.o.H.’s reference shelf, and rural doctors willfind it interesting in the light it throws on the problem ofgetting pure water into every home, however remote. The factthat gas prefers to run uphill and electricity doesn’t mind ispoor compensation for the fact that water refuses to do so ;and the community is only just beginning to realise that

gravity cannot be made an excuse for penalising the ruralpopulation. Mr. Maxwell might usefully turn his attentionnext to this side of the problem. His photographs of big damsand reservoirs are beautiful.

There are twenty contributors to PREOPERATIVE AND

POSTOPERATIVE TREATMENT (2nd ed., London : W. B.Saunders, pp. 584, 35s.), under the editorship of Lieut.-Colonel Robert L. Mason, of the Cushing General Hospital,Framlingham, Massachusetts, and Dr. Harold A. Zintel, ofthe University of Pennsylvania school of medicine. In thefirst part, which covers such general problems as the manage-ment of the surgical patient with heart disease, the stronginfluence of physiology on American surgery is well seen. Ofparticular interest are the chapters on water balance and onpostoperative venous thrombosis ; in the latter, ligature oflarge veins is freely recommended. Though the second part,arranged under regional headings, is insufficiently concise andhas important omissions-for example, the eye, and electivesurgery of the chest and head are not mentioned-the bookas a whole is interesting and instructive.