PORPHYRIA

916

cephaloridine, desensitised

to

she it.

seems

to

have been

successfully

J. H. MITCHELL. PRE-EMPLOYMENT MEDICAL EXAMINATION

SIR,-Dr. Todd’s views (April 10) examinations

on

pre-employment

interest those who, like myself, practise occupational medicine, and are entrusted with the dual responsibility of advising employers and employees about suitability for employment; I am confident that the great majority of these doctors would not regard themselves as competent for these tasks until they had acquired an intimate knowledge of all the jobs available within their are sure to

organisation-knowledge not usually possessed by general practitioners or consultant physicians. Dr. Norman’s sentimentsare widely shared, and the larger industrial organisations fully recognise the need to employ rather than reject. Placement is the important point, and the medical officer should be able to advise on alternative jobs which are suitable. He should know which of his patients have what disabilities, and precisely what work they are doing; there is no need for him to disclose his diagnosis to any third party (employer or otherwise), unless there is an obvious need, as in epilepsy, for the patient’s consent. A man’s work-record is not necessarily helpful. He may have done none of the type of work now proposed; he may be seeking his first job; or his previous employers may have failed to provide suitable conditions. The extraordinary suggestion that fitness for a job should be assessed by allowing a man to " have a go brings to mind "

the

following: one-eyed

1. A

man not

wearing protective glasses, chipping

concrete, and thereby losing his good eye. 2. A colour-blind handyman connecting up electric cables

incorrectly. going into hypoglycs’mic

3. A diabetic

coma

while

operating

a crane.

Such circumstances, others as well as the

by no means hypothetical, endanger employee himself. It is absurd to rely on an applicant’s own statement of his fitness, without examination. But men with a variety of serious disabilities can be safely employed if conclusions reached at a pre-employment examination are wise and based on practical experience. After some twenty years in industry, one still finds these examinations interesting and not at all "a very tedious exercise ". They can be carried out quite quickly and amicably, and should indicate whether the patient-for he is exactly that, whatever Dr. Todd’s reading of the Hippocratic Oathis fit for the proposed work. Any cause for total rejection (and this is very rare) is explained to the patient and his doctorpartial rejection (i.e., placement in a different job) normally causes no

trouble

at

all.

Dr. Todd’s examples of rejection for clearly unnecessary reasons arose in banks (3), the Services (1), nationalised industry (1), and Government departments (2)there were none in so-called private industry. Perhaps there is a moral in this. The fault highlighted by Dr. Todd’s contribution seems to lie in (a) deplorably rigid requirements for any job in an organisation, and (b) pre-employment examinations by doctors with inadequate experience of what faculties a job really demands. GERALD OLLERENSHAW. Esher, Surrey.

SIR,-I

was

observations examinations

on

to

pleased to read Dr. Todd’s the unnecessary number of medical

very

which

people

are

subjected.

This reaches almost absurd heights in the nursing profession, where intending entrants appear to require a certificate that 1.

Norman, L. G. in Modern Trends in Occupational Health (edited by R. S. F. Schilling). London, 1960.

they have been examined by their doctor, is repeated when they start nursing.

and this examination

any nurse decide to extend her training by of midwifery or tropical medicine, she is required to have a further routine medical examination. Sometimes this has to be done in duplicate as before entering the

Further, should

doing

a

course

profession. While chest X-rays are vital in this group of I suggest that the medical profession should

people, set an

example. St. Pancras

London,

Hospital,

D. SHARLAND.

N.W.1.

PORPHYRIA their letter of Feb. 6 Professor Smart and his

SIR,-In colleagues mention

patient with acute porphyria with four sibs of whom three had high levels of stool coproporphyrin. During the past three years we have systematically studied fxcal porphyrin in all our porphyrics and their relatives and have found a similar family from Jutland. The

a

had febrile disease of considered because of disand because increased porphobilinogen (P.B.G.) (1-0 mg. per 100 ml.) was found in her urine; 8-aminolevulinic acid (A.L.A.) was normal; and highly increased coproporphyrin, but no protoporphyrin, was found in the fxces. The connection between her symptoms and her porphyric anomaly was far from clear. All her eight sibsaged 45-65-were studied, and in 6 of the total of 9 sibs 2001000 jj!.g. coproporphyrin per g. of dry substance was found in the faeces. No protoporphyrin was present. Crystalline coproporphyrin in ester of more than 90% purity was prepared from fxces of three of the sibs. In two of the six " positive " sibs increased urinary P.B.G. was found, and in two increased A.L.A., but the increases were all below 1 mg. per 100 ml. ; in the others no precursors could be demonstrated in the urine by ion-exchange chromatographic methods. None of the sibs complained of any symptoms characteristic of porphyria, nor of abdominal, nervous, cutaneous symptoms, or discoloration of urine-and no porphyric attacks were known in the family. Some interesting questions arise by comparison with

proband,

uncertain origin. coloured urine

a

woman

Porphyria

aged 64, was

porphyria, which also manifests itself chemically mainly by faecal excretion of porphyrins, in South African

the

common type of acute intermittent of porphyria (A.I.P.) Northern Europe, in which urinary excretion of P.B.G. and A.L.A. dominates and faecal porphyrins are only sporadically increased. There are, however, two important differences: (1) The Jutland family excrete coproporphyrin III and no protoporphyrin, while the South Africans excrete both; (2) the Jutland family cannot be very sensitive to barbiturates because several of them cannot have avoided these substances and have not exhibited attacks; in contrast, South African carriers almost invariably develop serious attacks after small doses of barbiturates. The sensitivity to barbiturates of North European carriers of A.I.P. is probably higher than that of the Jutland family, but must be much less than that of South African carriers; at least in Denmark many porphyrics and carriers have taken barbiturates without developing attacks.2 In A.I.P. the connection between barbiturates and attacks is surprisingly irregular. If analysis of fxces for porphyrins was as common as analysis of urine for P.B.G. and porphyrin, it might be found that farcal porphyrin excretors such as the Jutland family were much commoner than we believe today. No

contrast

to

1. 2.

Dean, G. The Porphyrias. London, 1963. With, T. K. Z. klin. Med. 1963, 5, 134.

917

study of faecal porphyrins on a large group of normal subjects outside South Africa has, to my knowledge, been performed; at present such a study is in progress in Copenhagen. Whatever the result of this study, it is important in the investigation of porphyria to perform faecal analysis routinely on the same indications as urine analysis. We should seek to discover apparently harmless anomalies of porphyrin biosynthesis like that of the Jutland family, for nowadays anyone with a metabolic anomaly may unexpectedly be endangered by some new drug. Svendborg County Hospital,

T. K. WITH.

Denmark.

GLUCOSE-6-PHOSPHATE-DEHYDROGENASE ACTIVITY AND AN OSMOTIC ABNORMALITY OF ERYTHROCYTES Baikie and Norma Lawson (Jan. 9), studying SIR,-Dr.

subjects with a high activity of glucose-6-phosphate dehydrogenase (G.-6-P.D.) in the erythrocytes, " found a rough correlation between the level of G.-6-P.D. activity and the reduction in osmotic fragility on incubation ". Working on the osmotic fragility of G.-6-P.D.-deficient erythrocytes I obtained resultsthat are in agreement with, and complete, their observation. I found a considerable increase of the osmotic fragility in the deficient erythrocytes and a moderate reduction of that in the normal ones after incubation for 48 hours at 37°C (see accompanying figure). The importance of incubation-time is indicated by the fact that the differences become significant only after 48 hours of incubation-they are not significant when the erythrocytes are incubated for other periods. I found that, after 24 hours of incubation, the osmotic fragility was increased, and after 72 hours it was diminished, in both normal and deficient erythrocytes. Thus the changes in osmotic fragility of G.-6-P.D.deficient erythrocytes observed after incubation differ from those of normal erythrocytes only in the dynamics. Furthermore, both G.-6-P.D.-deficient and normal erythrocytes showed a similar increase in their osmotic fragility after 48 hours’ incubation with a sufficient quantity of glucose

(5 1

mg. per

ml.).

Zacchello, F., Porqueddy, G.

Acta

15, 440

pædiat. lat., Reggio Emilia, 1962,

This last observation seems to accord with the statement of Dr. Baikie and Norma Lawson that a different speed of utilisation of glucose may be responsible for the observed behaviour. Paediatric Clinic, University of Pavia, Italy.

FRANCO ZACCHELLO.

GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY IN FILIPINOS SIR,-Recent studies have shown a high frequency of

glucose-6-phosphate dehydrogenase (G-6-P.D.) deficiency among Filipino subjects.l Erythrocyte G.-6-P.D. activity in affected males is approximately 1% of normal, and appears to be quantitatively similar to the severe enzyme deficiency found in Mediterranean populations. Among 22 Filipino adults (15 males and 7 females) temporarily residing in Baltimore, 2 males were found to have much-reduced G.-6-P.D. activity in erythrocyte lysates; the activity of leucocyte extracts and sonicates of skin-cell cultures was approximately 10% of normal. In addition, vertical starch-gel electrophoresis of cell-free extracts from the deficient subjects showed a G-6-P.D. which was qualitatively different from that observed in the normals. With erythrocyte lysates from the latter, the mobility of the enzyme resembled that of the B variant found in normal Caucasians and in enzyme-deficient Mediterranean subjects.2 In contrast, the mobility of G-6-P.D. from both deficient Filipino males was faster than the B variant but slower than the A variant observed in normal and enzyme-deficient Negroes.2 Although the mobility appears to resemble that of the Canton variant,3 the enzyme activity of erythrocyte lysates is much lower in affected Filipino males. A more detailed report of these findings will follow. Departments of Pediatrics, Sinai Hospital of Baltimore and the Johns Hopkins University School of Medicine, Baltimore, Maryland.

HAROLD M. NITOWSKY DENIS D. SODERMAN FRITZ HERZ.

" IMMUNOLOGICAL

ORGANISATION ", PHYTOHÆMAGGLUTININ, AND PERIPHERAL-CELL CULTURES

SiR,ņThe comments of Dr. Lycette and Mr. Pearmain (Feb. 20), regarding my joint articleon the production of macrogammaglobulin (rheumatoid factor) in vitro, are

appreciated. Although we did not have phytohsemagglutinin (P.H.A.) in our medium, it was used in the separation process, and we suggested, as they do, that P.H.A. could be a non-specific stimulator of immunologically competent cells. Elves et al.5 reported that y-globulin produced by a sensitised patient’s cells cultured in media containing P.H.A. was non-specific, since they found that this y-globulin did not react with fluorescent antigen originally causing sensitisation in vivo. They found, however, that, when the sensitising antigen was in the medium, specific antibody was formed and this was in the nature of a secondary reaction. The suggestions of Lycette and Pearmain, that rheumatoid peripheral cells be culture

cultured with denatured y-globulin without P.H.A. in the medium and normal homologous serum with P.H.A., should be extended to include aggammaglobulinasmic serum and P.H.A., because immunologically competent peripheral-cell cultures of rheumatoid patients could treat " normal " y-globulin as an

antigen.

Lycette and Pearmain’s comment, that the immunological roles of lymphoblastoid and macrophagic cells appearing in such cultures " are distinct as well as 1. 2.

tnerement-haemolysis

curves

for fresh

hour-incubated (continuous G.-6-P .D.-deficient subjects.

and 48normal and

(interrupted line)

line) blood from

3. 4. 5.

Motulsky, A., Stransky, E., Fraser, G. R. J. med. Genet. 1964, 1, 102. Boyer, S. H., Porter, I. H., Weilbaecher, R. G. Proc. nat. Acad. Sci. Wash. 1962, 48, 1868. Kirkman, H. N., McCurdy, P. R., Naiman, J. L. Cold Spr. Harb Symph. quant. Biol. 1964, 29. Bartfeld, H., Juliar, J. F. Lancet, 1964, ii, 77. Elves, M. W., Roath, S., Taylor, G., Israels, M. C. G. ibid. 1963, i, 1292.