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or six months during a medical registrarship. This wouldhave the advantage of attracting some into the exciting andrewarding field of dermatology.With all other branches of medicine, dermatology has shared

in the remarkable progress of recent years. There is immense

scope for profitable and fascinating work for the scientist inthe skin which is unique in ease of approach and suitability forexperimental study. There is a place for the research-minded,lay and medical, to pass directly into dermatology early intheir careers. They are sadly needed. But the clinician shouldcome through the field of general medicine, and whether heenters as registrar or senior registrar will depend on his experi-ence and on circumstances.

Unless there is such a flow into dermatology now therewill be a dearth of trained personnel to fill the many poststhat will arise in the near future.

Department of Dermatology,The Royal Victoria Infirmary, JOHN T. INGRAM.Newcastle upon Tyne, 1.

1. Crigler, J., Najjar, V. A. Pediatrics, 1952, 10, 169.2. Watson, D. Clin. chim. acta, 1961, 6, 700.

JOHN T. INGRAM.Department of Dermatology,The Royal Victoria Infirmary,

Newcastle upon Tyne, 1.

EXCITEMENT RELATED TOHYPERBILIRUBINÆMIA

SIR Dr. Cates and Dr. Crawford (Aug. 12) putforward an original idea associating abnormal excitementwith changes in serum-bilirubin concentration. Theydescribe a most interesting case of familial hyperbili-rubinxmia " of the group to which Gilbert’s disease

belongs but with distinctly higher serum-bilirubin levelsthan are reported in that condition ". Their patient wasundoubtedly one of a type first studied by Crigler andNajjar.1 The individuals so far described are either

mentally defective with brain damage associated with

jaundice from shortly after birth, or they may be

intensely jaundiced but mentally and otherwise normal.Their hepatic uptake of bilirubin and their uridine-

diphosphate glucuronyl transferase system are defectiveso that the occurrence of a non-haemolytic jaundice is dueto an accumulation of unconjugated bilirubin derivedfrom a normal turnover of hxmoglobin.The case described is atypical in that the mental illness took

the form of schizophrenic and manic attacks, and that abnormalsigns in the central nervous system were not observed untilafter puberty, although the patient had been jaundiced frombirth. The levels of " directly reacting " pigment in thepatient’s blood-serum probably do not represent conjugatedbilirubin since they were at all times sufficiently low as to be anartefact of the method.2 Thus there is no evidence of a defectin the biliary excretion of conjugated bilirubin.

Dr. Cates and Dr. Crawford do not attempt to account forthe changes in the serum-bilirubin levels (6-16 mg. per 100 ml.)observed over a period of 14 months. Instead, they considerthat the coincidence of a lowered level of pigment at about thetime of increased excitement and overactivity is to be explainedas cause and effect. They assume that bilirubin damages thehypothalamic nuclei, and since it would seem more reasonablefor high rather than low bilirubin concentrations to interferewith the metabolism of the hypothalamus, an ingenious butimprobable hypothesis is invented to fit the facts. It is postu-lated that the toxicity of hyperbilirubinsemia is reversible forthe posterior centre but is irreversible in the case of theanterior centre. Hence, a temporary depression of plasma-bilirubin releases the posterior hypothalamus to an activitywhich is no longer inhibited by the anterior hypothalamus.This release produces the excitement " characterised bygarrulousness, restlessness, and hallucinations ".

It seems to me, however, that equally plausible and muchsimpler explanations of the biochemical and clinical data canbe given. I have observed cases of obstructive and hepato-genous jaundice in which the minor portion of the plasma-

total-bile-pigment reached 16 mg. per 100 ml. unconjugatedbilirubin, and in which there was no apparent central-nervous-system involvement. Could it be that there is no importantconnection between the pigment fluctuations and the mentalattacks in this case ?

In this respect, at least three reasons can be given toaccount either singly or together for the changes in serum-bilirubin levels:

(1) Variations were due to analytical error.3 Some tech-

niques are not reliable, being adversely affected by manyfactors even when performed by the same individual. A lossof bilirubin of up to 30% per hour would occur if the serumspecimens were not protected from light before analysis. 4

(2) Fluctuations were due to a combination of seasonalchanges in hxmopoietic activity and hepatic enzyme activity.

(3) Administration of drugs may have caused a temporaryshift from the blood-plasma to the erythrocytes and tissuecells.5 It is assumed, of course, that each of the blood speci-mens was obtained at about the same time of the day, sincemorning plasma in the case in question would be expected tocontain 15-3 mg. per 100 ml. more than afternoon specimens.

Finally, the possibility that biochemical disturbancesoccurring during schizophrenic attacks can influence theplasma-bilirubin level should not be overlooked. In thisconnection it is of interest that physiological amounts ofadrenaline given intravenously can bring about a sub-stantial fall in the plasma-bilirubin level.5 6

Royal Women’s Hospital, D, WATSON.Melbourne, Victoria. D. WATSON.

3. Watson, D. J. clin. Path. 1961, 14, 271.4. Cremer, R. J., Perryman, P W., Richards, D. H., Holbrook, B. Biochem.

J. 1957, 66, 60P.5. Watson, D. Unpublished data.6. Balzer, E. Acta med. scand. 1953, suppl. 278.7. Crigler, J., Najjar, V. A. Pediatrics, 1952, 10, 169.8. in Recent Advances in Clinical Pathology (edited by S. C. Dyke) London,

1951.9. Crawford, J. P. Amer. J. Psychiat. (in the press).

D. WATSON.Royal Women’s Hospital,Melbourne, Victoria.

*** We showed this letter to Dr. Cates and Dr. Crawfordand their reply follows.-ED. L.

SIR,-We very much appreciate the opportunity to

comment on Dr. Watson’s letter, although it appears tous that he may not have read our letter very closely.Crigler and Najjar’s 7 patients all had abnormal central-nervous-system signs, which our patient did not, andtheir patients’ serum-bilirubin levels all exceeded 20 mg.per 100 ml. at some time, which ours did not. Thislevel of 20 mg. per 100 ml., it seems to us, may in factbe a critical one as far as permanent central-nervous-

system damage is concerned.

If we may deal first with Dr. Watson’s criticisms of theserum-bilirubin estimations, can he tell us whether seasonalchanges apply when all the figures we gave occurred betweenthe middle of April and the middle of August ? Our laboratorytechnician advises us that all our bilirubin estimations were bythe method of Malloy and Evelyn.s All the specimens exceptthe first and second were taken in the morning between 10 and11 A.M. and the estimations were carried out within half anhour of doing so. The first and second specimens were takenat times of day which are now uncertain. None of the speci-mens were especially protected from light. The patient was ontrifluoperazine hydrochloride (’ Stelazine ’) 7-10 mg. a daybetween May 4 and June 8, 1960, and again from Aug. 30, 1960,to the present.As to the hypothesis, we did not mention in our letter that

damage to the anterior hypothalamic centre was irreversible inour patient. It may be of interest, however, to note that thetheory in question has more recently been described under thetitle of cerebral autonomic imbalance,9 and may therefore bearsome relation to adrenaline, as Dr. Watson suggests. PerhapsProf. C. H. Gray could be persuaded to estimate both total

1044

plasma-adrenaline 10 and bilirubin levels in a series of bloodsamples from our patient.

Since we last wrote to you, serum-bilirubin levels have beenas follows:

The levels recorded in June and July, 1961, were accom-panied by a quiet phase in the patients’ behaviour. On Sept. 13,1961, however, a muttering delirium developed, unaccompaniedby overactivity or other manic features of the kind he had shownpreviously when excited, such as a tendency to interfere withothers. Between Sept. 13 and Oct. 7 he either sat in his chairmuttering away or lay quietly in bed doing so. His serum-bilirubin level at the beginning of this period was the highestwe have ever recorded in him and approached the possiblycritical level of 20 mg. per 100 ml. Clinically he was obviouslymore jaundiced than we had ever seen him-a fact whichsuggests that our serum estimations were reliable, especiallysince at the subsequent estimation, which was the lowest wehave ever recorded in him, he was clinically less jaundiced thanwe have known him. We would also point out that our patienthad a family history of mental illness and may have beenhereditarily predisposed to react to bilirubin in this way. Atabout the time of the last estimation, the patient had a shortperiod of overactivity once more.

B. CATES

J. P. CRAWFORD.

10. Weil-Malherbe, H. J. ment. Sci. 1955, 101, 733.

B. CATES

J. P. CRAWFORD.

ADVERTISEMENTS FOR HEALTH

SIR,—I agree with Dr. Kahan (Oct. 28) that thediscussion on this subject covers a wider field than thatconcerned with slimming foods. But since Dr. Mullinsmade a specific statement about one of these which Iconsider wrong, and since Dr. Kahan supports her, I hopeyou will allow me one more attempt to get the matter

straight.The essential fallacy is that of the caloric concentration of

food. Unless a food has something like cellulose added to it,any reduction in the proportion of dry weight contributed bycarbohydrate (4 calories a gramme) must be made up by anincrease in the proportion contributed by protein (also 4calories a gramme) or by fat (9 calories a gramme). Obviouslythen the reduction of starch in a bread substitute cannot resultin a decrease in the concentration of calories, and may evenresult in an increase.The low-carbohydrate diet for the treatment of obesity

which I recommend, and of which Dr. Mullins approves,depends on persuading the patient to eat no more than about50 g. of carbohydrate a day, whilst eating as much protein andfat as he likes. Most patients like to get some of their carbo-hydrate-perhaps 25 g. a day-in the form of bread or a breadsubstitute. This amount is contained in about one and a halfslices of bread, or three pieces of ’ Ryvita ’, or five pieces ofstarch-reduced crispbread, or ten starch-reduced rolls.

I always give this information to obese patients, togetherwith a list of other foods and their content of carbohydratewhich I have calculated from tables of food analyses such asthose in the classical publication of McCance and Widdowson.Dr. Mullins however suggests that patients will not lose weightwhen they eat starch-reduced crispbread because, althoughthey have relatively little carbohydrate, " they taste like

carbohydrate ". This surprising suggestion has some quiteextraordinary consequences. One is that saccharin must be asfattening as sugar since it

" tastes like sugar ". The second is

that those of us who continue to press for a differentiationbetween nutritionally useful and nutritionally useless foodsneed no longer worry about the fact that many orange drinkscontain no vitamin C; they do after all still taste of orange juice.The third consequence of Dr. Mullins’ suggestion is that

Professor McCance and Dr. Widdowson should abandon theirvery laborious analyses of food and simply report on theirpalatability. We shall then be drawing up low-carbohydratediets, presumably both for the obese and for diabetics, on thebasis of carbohydrate values determined by their " carbo-hydrate-like taste " and not by their actual content ofcarbohydrate.Queen Elizabeth College, -r YUDKIN.London, W.8. JOHN YUDKIN.

1. Official Report of the American Public Health Association.

JOHN YUDKIN.Queen Elizabeth College,

London, W.8.

SIR,-Mr. Stocker (Oct. 14) wonders why Consumers’Association does not accept fees from manufacturers. Weknow from our contact with our members that a very highproportion of them would not renew their subscription ifwe accepted fees or test samples from manufacturers. Weare an organisation of consumers who have pooled theirresources to have us carry out for them research into

products and services that they could not possibly carryout themselves.Mr. Stocker refers to " attacking without adequate

resources those (things) that are worst or inferior". I hopehe was not thinking of C.A. If we found that we could not

manage adequate tests of particular products, we wouldalways decide not to report on them in Which? ?

CASPAR BROOKDirector and Secretary,

London, W.C.2. Consumers’ Association Ltd.

CASPAR BROOKDirector and Secretary,

Consumers’ Association Ltd.

HEPATITIS CAUSED BY THE NEWERAMINE-OXIDASE INHIBITING DRUGS

SIR,-In your issue of Sept. 16 Dr. Holdsworth andhis colleagues wrote on this subject. To the last drug inthe table on p. 621, tranylcypromine, are given the tradenames Parnate’ and ’Parsteleazine’. The first of theseis correct but the second should read’ Parstelin ’. Parstelincontains 1 mg. trifluoperazine (’ Stelazine ’) in addition to10 mg. tranylcypromine (’Parnate’).

I would be most grateful if you could publish a note ofthis correction to avoid any confusion which might arise.

Science Information Department,Medical Services,

Smith Kline & French Laboratories Ltd., N. A HANCOCK.Welwyn Garden City, Herts.N. A. HANCOCK.

Science Information Department,Medical Services,

Smith Kline & French Laboratories Ltd.,Welwyn Garden City, Herts.

CONTROL OF INFECTIOUS HEPATITIS

SIR,-Dr. Stanton (Oct. 21) is of the opinion that theroute of infection is by the gastrointestinal tract, and thisis the generally accepted view. However, according tothe Control of Communicable Diseases in Man,1 the" sources of infection are fxces and blood from infected

persons. Presence of virus in nose and throat dischargesnot proved but commonly assumed on epidemiologicalgrounds ".As stated in my report (Oct. 7) my impression was that the

spread was probably by droplet infection rather than gastro-intestinal. Certainly, the arrangement of the beds occupied bycases in the dormitories and of the seating in the dining-roomindicated spread by personal contact. Against gastrointestinalspread it can be stated that no case occurred among the staff,including kitchen staff, that the hygiene in the kitchen was ofa high standard, and that the incidence of bowel infection in theschool during recent years has been negligible.To comment on Dr. Stanton’s interesting experience, I

could not agree that his conclusions could be entirely validunless he had carried out a survey of the washing-up methodsin all the households on his list. There may well have been anumber of households which escaped hepatitis infection andin which the washing-up was done on the table and not in thesink

County Offices, C. MILLIKEN SMITHNorthampton. County Medical Officer of Health.

C. MILLIKEN SMITHCounty Medical Officer of Health.

County Offices,Northampton.