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phencyclidine, the compound from which ketamine isderived, produced massive increases in plasma-c.p.K.activity in rats subjected to restraint stress. 6 There issome evidence that stress is important in precipitating anepisode of M.H. in vulnerable patients.’ We found thatintravenous ketamine (2-5 mg. per kg. body-weight) didnot increase plasma-c.p.K. activity in ten of eleven normalvolunteers in whom C.P.K. activity was studied at -20,- 10, 0, +2, +5, +15, +30, +60, +90, and +120minutes before and after ketamine. Plasma-c.p.K. activityincreased from 25+s.D. 1 milliunits per ml. (in fivesamples from -20 minutes to +5 minutes) to 72+s.D.7 milliunits’ per ml. (in five samples from + 15 minutes to+120 minutes) in one volunteer. Plasma-c.p.K. activitywas still increased at 24 hours. Intravenous thiopentone(2-5 mg. per kg. body-weight) did not increase plasma-C.P.K. activity in thirteen volunteers. There was no

statistically significant difference between the frequency ofincreased serum-c.p.K. activity after ketamine administra-tion and after thiopentone administration in normalindividuals.

Departments of Psychiatry andAnesthesiology,

University of Chicago,Pritzker School of Medicine, andIllinois State Psychiatric Institute,

Chicago, U.S.A.

H. Y. MELTZERS. Z. HASSANR. MORETTIC. HENGEVELDD. BRUCKNER.

ZINC DEFICIENCY AND CELLULAR IMMUNEDEFICIENCY IN ACRODERMATITIS

ENTEROPATHICA

SIR,—Moynahan 8 and Portnoy and Molokhia 9 suggesta role for zinc deficiency in the pathogenesis of acroderma-titis enteropathica. In 1973 Kirchner and Riihl 10 observedthat in zinc deficiency lymphocytes are less able than usualto undergo blastic transformation. This indicates a

cellular immune deficiency. Julius et al.11 and Rodin andGoldman 12 found signs of cellular immune deficiency inacrodermatitis enteropathica, but their observations werenot supported by lymphoblast transformation.

,

In 1973 we found hypoproteinsmia (presumably due tomalabsorption) in a patient with acrodermatitis enteropathica,in whom considerable zinc deficiency was observed in theparenchymatous organs post mortem (brain 82 (Ag. per g.,intestine 44 tg. per g., spleen 59 fj.g. per g., liver 97 4g.per g., lung 63 g. per g., kidney ,90 g. per g. (deter-mined by polarography). In-vitro blastic transformationof blood-lymphocytes by phytohaemagglutinin (P.H.A.)was pathologically low. (The spontaneous blastictransformation-rate without mitogen was higher thannormal; the cause of this is not known at present.)The patient’s state was aggravated by very ’frequentlyrecurring pneumonia, otitis, and upper respiratorycatarrh, and death was due to sepsis associatedwith pneumonia. Specific changes indicative of cellularimmune deficiency could not be identified in the germinalcentres of the spleen and lymph-nodes. The patient hadgeneralised lymphadenitis, which presumably developedduring the sepsis (Dr Fodor, Department of Pathology,University Medical School, Szeged).

In our view the cellular immune deficiency, confirmedclinically and by P.H.A. stimulation, observed together witha normal lymphocyte count and nearly normal germinal

6. Meltzer, H. Y. Res. Commun. chem. Path. Pharmac. 1972, 3, 369.7. Wingard, D. W. Lancet, 1974, ii, 1450.8. Moynahan, E. J. ibid. p. 399.9. Portnoy, B., Molokhia, M. ibid. p. 663.10. Kirchner, H., Rühl, H. ibid. 1973, i, 1317.11. Julius, R., Schulkind, M., Sprinkle, T., Rennert, O. J. Pediat.

1973, 83, 1007.12. Rodin, A. E., Goldman, A. S. J. clin. Path. 1969, 51, 315.

i centres, may be due to functional damage of the T lympho-, cytes arising from a malabsorption zinc deficiency (the; immunoglobulin levels and thus the function of the Bi lymphocytes were normal). Infections resulting from this: cellular immune deficiency are important for prognosis inl acrodermatitis enteropathica and may be the cause of death.

Department of Pædiatrics,University Medical School,

Szeged, Hungary.

L. ENDREZ. KATONAK. GYURKOVITS.

INCREASED COPPER/ZINC RATIOS INACRODERMATITIS ENTEROPATHICA

SIR,-Zinc therapy is rapidly replacing di-iodohydroxy-quinoline for the treatment of acrodeimatitis enteropathica(A.E.). In 1973, Moynahan and Barnes reported lowplasma-zinc levels in a child with lactose-intolerant A.E.,and they stated that small zinc supplements of 35 mg. ofzinc sulphate daily completely cleared the skin lesionsand restored normal bowel function. Moynahan 2 laterdescribed 9 other patients with A.E. successfully treatedwith zinc sulphate. He suggested an optimum dose of150 mg. of zinc sulphate in divided doses, preferably takenwith fruit juices and the like, for control of A.E. His

findings were confirmed by several groups of workers.3-KWe investigated the benefits of zinc-gluconate therapy

in a 6-month-old male who had all the classic symptoms ofA.E. This infant had high serum-copper and low serum-zinc concentrations before zinc medication, and theseconcentrations seemed to become normal as a result ofzinc therapy. Normal values for serum-copper and zincvalues in infants are not available, although data fornewborn infants indicate concentrations equal to or greaterthan those in adults.9-11 In our laboratory normal copperand zinc concentrations are 10010 and 125±18 tg. per100 ml., respectively, giving a normal copper/zinc ratio of0-82.

Serum-copper and zinc were measured by atomic-

absorption spectroscopy using a Perkin-Elmer Model 503.On Feb. 28, 1974, when the child was maintained ondi-iodohydroxyquinoline (325 mg. four times a day),serum-copper was 140 g. per 100 ml. and zinc 35 )g.per 100 ml.-i.e., a copper/zinc ratio of 4. Just after

beginning zinc-gluconate therapy (7-5 mg. of zinc threetimes a day) on April 4, 1974, serum-copper was 105 andserum-zinc 20 g. per 100 ml., with a copper/zinc ratioof 5-25. Within 16 days of starting zinc-gluconate therapy,while di-iodohydroxyquinoline medication was continued,serum-zinc rose to 130 jj.g. per 100 ml. and serum-copperremained at 125 g. per 100 ml. (copper/zinc ratio

0-96). The infant continued on mother’s milk from a milkbank during zinc-gluconate therapy.The aetiology of A.E. is obviously complex. Discovery

of the high copper/zinc ratio in A.E. may help to define theinborn metabolic error of this disease. High copper/zincratios have been reported in bronchogenic carcinoma 12and in dermatological, neoplastic, pancreatic, and neuro-

1. Moynahan, E. J., Barnes, P. M. Lancet, 1973, i, 676.2. Moynahan, E. J. ibid. 1974, ii, 399.3. Hjort, A. Cited by Moynahan, E. ibid. p. 399.4. Krogh, H. K. in Symposium om Zink (edited by B. Zederfeldt);

p. 98. Lund, 1974.5. Michaelsson, G. Acta derm-vener., Stockh. 1974, 54, 377.6. Thyresson, N. ibid. p. 383.7. Portnoy, B., Molokhia, M. Lancet, 1974, ii, 663.8. Portnoy, B., Molokhia, M. Br. J. Derm. 1974, 91, 701.9. Berfenstam, R. Acta pœdiat. scand. 1952, 41, suppl. 87, p. 3.

10. Henkin, R. I., Marshall, J. R., Meret, S. Am. J. Obstet. Gynec.1971, 110, 131.

11. Kurz, D. L., Eyring, E. J., Roach, J. E. Biology of the Neonate (Basel),1973, 23, 180.

12. Strain, W. H., Mansour, E. G., Flynn, A., Pories, W. J., Tomaro,A. J., Hill, O. A., Jr. Lancet, 1972, i, 1021.

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logical diseases, as well as iron-deficiency anaemia 13 andsickle-cell anaemia.11-16 Raised serum-copper concentra-tions are also seen in other hsematological disorders, suchas thalassaemia, aplastic anaemia, pernicious anaemia,17,18and other carcinomas.19-21

Department of Surgery,Cleveland Metropolitan General

Hospital.

Department of Dermatology,University Hospitals,

Case Western Reserve UniversitySchool of Medicine,

Cleveland, Ohio 44106,U.S.A.

WILLIAM H. STRAIN.

FRED S. HIRSHBENO MICHEL.

PATIENT RESPONSE TO INDUCTION OF

LABOUR

SiR,—We have carried out a prospective survey on 200women to determine their reaction to induction of labour.Antenatal patients, between the 34th and 36th week ofpregnancy, were invited to answer a questionnaire. Thepatients were delivered either spontaneously or afterinduction. A further questionnaire was then answered, andeach patient was interviewed.80% of patients attending mothercraft classes knew about

induction of labour, compared with 37-5% who did not attendclasses. Only 9% of patients with a knowledge of inductionactively disliked the idea, compared with 19% of patients whohad not been told of induction (14% of whom were unable toanswer this question, compared with 2% of the patients with aknowledge of induction). The two groups of patients answeredas follows when asked to compare the expected length of labourif induced with expected length of spontaneous labour:

When questioned similarly about expected pain, the resultswere:

72% of patients knowing about induction believed that labourwould be shorter, and 44% believed labour would be morepainful.When questioned after delivery there was little difference in

reaction to labour between those who were induced and thosewho had spontaneous labour. In both groups about one-third

*

of patients found labour easier than expected, and about one-third of patients found labour harder:

13. Fell, G. S., Canning, E., Husain, S. L., Scott, R. in Trace Substancesin Environmental Health (edited by D. D. Hemphill); vol. v,p. 293. Columbia, Mo., 1972.

14. Olatunbosun, D. A., Isaacs-Sodeye, W. A., Adeniyi, F. A.,Adadevoh, B. K. Lancet, 1975, i, 285.

15. Serjeant, G. R., Galloway, R. E., Gueri, M. C. ibid. 1970, ii, 891.16. Karayalcin, G., Rosner, F., Kim, K. Y., Chandra, P. ibid. 1974, i,

217.17. Cartwright, G. E., Hugnley, C. M., Ashenbrucker, H., Fay, J.,

Wintrobe, M. M. Blood, 1948, 3, 501.18. Prasad, A. S., Diwany, M., Gabr, M., Sandstead, H. H., Mohktar,

N., Hefny, A. E. Ann. intern. Med. 1965, 62, 87.19. Delves, H. T., Alexander, F. W., Lay, H. Br. J. Hœmat. 1973, 24,

525.20. Hrgovcic, M., Jessmer, C. F., Thomas, F. B., Ong, P. S., Gamble,

J. F., Shullenberger, C. C. Cancer, 1973, 32, 1512.21. Ilicin, G. Lancet, 1971, ii, 1036.

There was little difference in response between the inducedand spontaneous groups when the patients were asked how theactual length of labour compared with what they had expected:

When asked specifically about pain, 45 % of the induced

patients reported that labour had been more painful thanexpected, compared with 33% of the spontaneous group.The majority of patients reported that relief from anxiety was

obtained by helpful and sympathetic staff and by the presenceof the husband. These patients were in favour of having asubsequent induction.

This information shows that a high degree of patientacceptability can be obtained by careful explanation ofinduction of labour. Sympathetic support by delivery-suitestaff and the presence of the husband are essential ifanxiety and tension are to be relieved. The main disadvan-tages of induction can be relieved. Amniotomy and oxytocinhave a very low failure rate, and the caesarean-section rateand forceps rate can be kept at an acceptable level.’

Maternity Unit,Watford General Hospital,Watford, Herts. WD1 8HB.

B. V. LEWISS. RANAELIZABETH CROOK.

LINOLEIC ACID IN MULTIPLE SCLEROSIS

SIR,-Several investigators have suggested that linoleicacid (L.A.) has an immunosuppressive effect in vitro 2-6and in vivo. 6,7 Others have claimed that the suppressionis specific to multiple sclerosis (M.S.).8,9 This interest inlinoleic acid was provoked by previous reports 10 that

patients in the acute phase of multiple sclerosis had lowserum levels of L.A. and that dietary supplementation withL.A. might be beneficial.llWe are engaged in a double-blind therapeutic trial of

the effect of linoleic acid in M.S. In conjunction with thistrial we are measuring L.A. levels in serum during thebaseline period and during the trial. We have also studiedthe in-vivo and in-vitro effect of L.A. on these patients’lymphocyte responsiveness to phytohsemagglutinin (P.H.A.).Our data show that the linoleic-acid levels in patients withstable multiple sclerosis (mean=2-81 fjunol. per ml.,n=71) are not significantly different from those in normalcontrols (mean=3-01 mol. per ml., n=31). The linoleic-acid levels of patients with other neurological diseases arelower (mean=2-48 tlmol. per ml., n=62), and patientsgoing through an acute relapse of multiple sclerosis alsohave a somewhat lower level of linoleic acid (mean=2-55jamol. per ml., n=12). This suggests that there is nospecificity i4 the lower levels of linoleic acid in neurologicaldisease, though further analysis of these data is under way.Patients taking L.A. supplements do have raised serum-L.A.levels (mean=3-80 jjunol. per ml., n=23). The P.H.A.

(0-2%) responsiveness of 30 multiple-sclerosis patients, 6normals, and 6 neurological controls was studied andlinoleic acid (80 g. per ml.) depressed the blast-transform-ation response in virtually all patients. There did not seemto be any difference in the reduction of response between

1. Tipton, R. H., Lewis, B. V. Br. med. J. 1974, i, 391.2. Mertin, J., Hughes, D., Stewart-Wynne, E. Lancet, 1974, i, 1005.3. Offner, H., Clausen, J. ibid. 1974, ii, 400.4. Offner, H., Clausen, J. ibid. p. 1204.5. Field, E. J., Shenton, B. K. ibid. p. 725.6. Uldall, P. R., et al. ibid. p. 514.7. Mertin, J. ibid. p. 717.8. Field, E. J., Shenton, B. K., Joyce, G. Br. med. J. 1974, i, 412.9. Jenssen, H. L., Kohler, H., Gunther, J., Meyer-Rienecker, H.

Lancet, 1974, ii, 1327.10. Baker, R. W. R., Thompson, R. H. S., Zilkha, K. J. J. Neurol.

Neurosurg. Psychiat. 1966, 29, 95.11. Millar, J. H. D., et al. Br. med. J. 1973, i, 765.