330

led to dehydration and weight-loss to between - and- 6·3 standard deviation from the mean on the first ad-mission. No general malabsorption was found and theproximal jejunal mucosa was completely normal. Abnormallactose-tolerance tests and low lactase activities suggestedcongenital lactose malabsorption.4,5 On a recent admissionwe made another mucosal biopsy from the proximal jejunumand measured the activities of the different small-intestinalP-galactosidases with specific methods. In 3 of the patientsno brush-border lactase activity at all was demonstrable.In 1 patient a very low activity (0-5) was registered, butthe biopsy was too small (3 mg.) to permit repetition of theanalysis or characterisation of the possible residual activity.The activities of maltase and other fx-glucosidases werehigh and within the normal range on the recent as well ason the first admission. The activities of acid P-galacto-sidase and hetero P-galactosidase were also normal.Our findings are in agreement with those of Lojda et al. 6.7 7

who used a histochemical staining method specific for thebrush-border lactase. In samples from children with

congenital lactose malabsorption these workers found notrace of brush-border lactase, but in adults with specifichypolactasia a fraction of the enterocytes displayed somelactase activity indicating that the deficiency was not

complete.The finding of undetectable brush-border-lactase

activity in the children with congenital lactose malabsorp-tion, in contrast to the clearly measurable residual activityof this enzyme in adults with specific hypolactasia, couldbe discussed in terms of different genetic mechanismsinvolved in these two forms of low intestinal lactase. Asdiscussed above, acquired specific hypolactasia is obviouslya regulatory " defect ". Congenital lactose malabsorption,on the other hand, could be due to a structural mutationwith inability to synthetise the proper enzyme protein.Another possibility that cannot be excluded is that congeni-tal lactose malabsorption represents an extremely early andcomplete " switch off " of the lactase production.

Chemical Centre,Department of Nutrition,

P.O. Box 740, S-220 07 Lund 7,Sweden.

Children’s Hospital,University of Helsinki,

Stenbäckinkatu 29,SF-00290 Helsinki 29, Finland.

N.-G. ASPA. DAHLQVIST.P. KUITUNENK. LAUNIALAJ. K. VISAKORPI.

MAGNESIUM DEPRIVATION IN SUDDENUNEXPECTED INFANT DEATH

SIR,-Since the appearance of Caddell’s hypothesis 8Swift and Emery 9 reported that the magnesium concen-tration in vitreous humour in 4 cases of cot death waswithin the range which characterised 12 recent childdeaths (2-2-5-3 mg. per 100 ml.); and Sturner 10 found thatmagnesium concentration measured by atomic absorptionspectrometry in vitreous humour from 7 cot-death infantsranged between 2-1 and 3-5 meq. per 1. 13 non-cot-deathinfants had concentrations ranging from 2-0 to 3-9 meq.per 1.We have measured the magnesium concentration by

atomic absorption spectrometry in vitreous humour from 5cases of sudden-infant-death syndrome (S.I.D.s.) and from 7

4. Launiala, K., Kuitunen, P., Visakorpi, J. K. Acta pœdiat. scand.1966, 55, 257.

5. Launiala, K. ibid. 1968, 57, 425.6. Lojda, Z., Frič, P., Jodl, J. Dt. Z. Verdau. Stoffwechselkr. 1972, 32,

163.7. Lojda, Z. Personal communication, 1973.8. Caddell, J. L. Lancet, 1972, ii, 258.9. Swift, P. G. F., Emery, J. L. ibid. p. 871.

10. Sturner, W. Q. ibid. p. 1150.

infants dying of other causes in Seattle, with the followingresults:

Magnesium concentration in vitreous humour in mg. per 100 ml. (meq. per I.)

Our results seem similar to those just cited not only inthe range of values but also in the lack of difference be-tween S.I.D.s. babies and those without the syndrome.These three small but independent assessments from

geographically distant sites, taken together, do not supportthe hypothesis that S.I.D.s. babies suffer chronic magnesiumdeprivation. On the other hand, they cannot be construedas evidence against acute deprivation because of the

relatively long ionic turnover-time imputed to vitreoushumour.

Because magnesium and calcium have reciprocal func-tions, calcium measurements were made on the same

specimens used for magnesium determinations with thefollowing results:

Calcium concentration in vitreous humour in mg. per 100 mi. (meq. per 1.)

The arithmetic mean for S.I.D.s. babies was 7-7 mg. per100 ml. and for non-s.i.D.S. babies 9-1 mg. per 100 ml. Thisdifference is not statistically significant. These calciumconcentrations, therefore, tend to confirm those for mag-nesium.

School of Public Health andCommunity Medicine,

University of Washington,Seattle, Washington 98105,

U.S.A.

DONALD R. PETERSON

J. BRUCE BECKWITH.

WORK OF THE CONSULTANT

GERIATRICIAN

SIR,-Dr Wright (Aug. 4, p. 252) argues that con-sultants in geriatrics should concern themselves withteaching and administration and not with the day-to-dayrunning of their departments nor with the care of theindividual patient.

Although one would accept that if facilities were adequatethe consultant should not in an administrative role beconcerned with the admission of a patient, he surely mustat all times be responsible for the care of the individual,but this Dr Wright delegates to the house-officers.The care of the elderly in a geriatric department is not

solely a matter of arranging for rehabilitation to be carriedout by paramedical personnel but necessitates a standardof diagnostic ability that one would not expect a newlyqualified doctor to possess. It also requires a knowledge ofthe changing pattern of drug absorption, metabolism, andexcretion that occurs with age, and, in view of the presentpractice of polypharmacy, which reaches its height in thevery old, a knowledge of the side-effects and inter-reactionsof a wide variety of drugs. It also requires an ability toevaluate the benefits to be gained by scientific investigationand to weigh up the advantages and disadvantages to begained from different courses of action.

331

Junior doctors are attached for training purposes, andthe consultant must at all times ensure that each individual

patient has the correct medical diagnosis and the correcttreatment plan. The amount of time that he must give tothis is dependent upon the quality and quantity of thejunior medical staff, and this must surely always be hisfirst priority.Education and training are essential for the development

of services for the elderly patient both at home ’and inhospital, but these must be based upon the maintenanceof the high standards of care of the individual, for theoutcome of this training must be an improvement in thecare of the individual and not its decline.

’

Geriatric Department,St. George’s Hospital,

London SW17. PETER H. MILLARD.

SEROTONIN, LITHIUM, AND HUNTINGTON’SCHOREA

SIR,-Sourkes 1 suggested that serotonin metabolism isdisordered in Huntington’s chorea (H.c.). 5-hydroxy-tryptophan (5-H.T.P.), a precursor of serotonin or 5-hydroxy-tryptamine, was found to worsen choreiform movements inpatients with H.C.2,3 3 A reduction in cerebrospinal-fluid5-hydroxyindoleacetic acid (5-H.I.A.A.), a metabolite ofserotonin, was generally but not always associated with animprovement in the patient’s condition, and an increase inc.s.F. 5-H.I.A.A. levels was seen as the patient’s conditionbecame worst. Preliminary findings in animals suggestedthat lithium has its primary interaction with the sero-

toninergic system.5 Lithium seems to increase serotoninturnover in the central nervous system. 6 Preliminaryfindings showed that c.s.F. 5-H.I.A.A. level decreased in 2out of 3 patients during lithium therapy.4 Lithium doesnot influence the content of dopamine in the brain. 6 C.S.F.homovanillic acid (H.v.A.), a metabolite of dopamine, re-mained unchanged during lithium therapy in a patientwith H.C.4 All these data suggest that the mode ofaction of lithium in H.c. involves serotonin, but furtherwork is required to understand the exact mechanism.

Department of Neurology,V.A. Hospital, Wood,

Wisconsin 53193, U.S.A. N. V. B. MANYAM.

METHOTREXATE AND ALOPECIA

SIR,-Loss of hair has been reported to be one of thecommon symptoms of toxicity in cancer patients duringprolonged treatment with the folic-acid analogues.1-9 Inan attempt to investigate the effect of methotrexate on thehepatic microsomal enzymes in normal rat, we accidentallyobserved that the animals treated with both methotrexateand phenobarbitone simultaneously produced severe

alopecia. This was not, however, observed in the animalstreated either with methotrexate alone or with pheno-

1. Sourkes, T. L. in Basic Neurochemistry (edited by R. W. Albers,G. J. Siegel, R. Katzman, and B. W. Agranoff); p. 574. Boston,1972.

2. Lee, D. K., Markham, C. H., Clark, W. G. Life Sci. 1968, 7, 707.3. Barbeau, A. Lancet, 1969, ii, 1066.4. Mattsson, B. ibid. 1973, i, 718.5. Ho, A. K. S., Loh, H. H., Craves, F., Hitzeman, R. J., Gershon, S.

Eur. J. Pharmac. 1970, 10, 72.6. Schou, M. Lithium in Psychiatry. Public Health Service Publication

no. 1836, p. 701. U.S. Government Printing Office, Washington,D.C., 1968.

7. Schoenbach, E. B., Colsky, J., Greenspan, E. M. Cancer, 1952,5, 1201.

8. Condit, P. T. ibid. 1960, 13, 222.9. Berlin, N. I., Rall, D., Mead, J. A. R., Freireich, E. J., Van Scott,

E., Hertz, R., Lipset, M. B. Ann. intern. Med. 1963, 59, 931.

barbitone alone. In this experiment, a total of 45 maleweanling Sprague-Dawley rats were divided into threegroups of 15: groups A, B, and C were treated respectivelywith intraperitoneal methotrexate (5 mg. per kg.), pheno-barbitone (100 mg. per kg.), and methotrexate plus pheno-barbitone, on three successive days. This experiment wasrepeated three times, and each time alopecia on the backand neck of the animals was observed in group C only.

Since most of the cancer patients are treated withmethotrexate while they are also taking barbiturate drugsfor sedative purpose, it is probable that the toxic sign isan effect of the combined drugs rather than of metho-trexate alone. Nevertheless, our observations are sufficientlyinteresting to merit further investigation.

Marie Curie Memorial Foundation,The Chart,

Oxted, Surrey.

T. K. BASUD. C. WILLIAMSR. W. RAVEN.

HYPOTHYROIDISM AND HYPERPARA-

THYROIDISM ASSOCIATED WITH

LITHIUM

SIR,-We wish to describe a patient with longstandingbipolar affective disorder treated with lithium carbonate inwhom hypothyroidism and later hyperparathyroidism wereassociated.

A married woman aged 52 was admitted to the Clarke Instituteof Psychiatry in November, 1966, because of manic excitementof three weeks’ duration. Her affective disorder dates back toage 29 when, six months after the birth of her second child, shebecame depressed and was treated successfully with electro-convulsion therapy. Shortly thereafter she was diagnosed ashaving thyrotoxicosis and treated with iodine daily for twomonths. After remaining well for five years, she had a total ofabout 5 episodes of elation and 11 episodes of depression overthe next 15 years.At the time of admission, she was physically normal and the

thyroid gland was not palpable. The laboratory findings were:protein-bound iodine 6-5 pLg. per 100 ml. (normal 4-8); serum-cholesterol 277, 296, and 320 mg. per 100 ml. (normal 150-250);serum-calcium 9-5 and 10-3 mg. per 100 ml. (normal 9-5-10-5).An electrocardiogram was normal. An electroencephalogramshowed bilateral slow waves (3-5 per sec.) in the frontal region.She was successfully treated with thioridazine (100 mg. fourtimes daily) and was started on prophylactic lithium carbonate(300 mg. three times daily). The serum-lithium was stabilised atbetween 1-0 and 1-2 meq. per 1. and she has been maintained onLiCOs since her discharge in March, 1967.During the summer of 1967 she became depressed and re-

sponded to tranylcypromine (10 mg. three times daily), whichwas given in addition to the LiCOg. In the autumn, she wastreated for cheilosis by her dentist and for hypercholesterola:miaby her family physician. She was seen by an ophthalmologistwho performed cosmetic surgery for " bags under her eyes ".She remained well until July, 1968, when, on a vacation, she tookan over-the-counter sleep preparation (’ Sleepeze ’) and developedan acute brain syndrome. She then became depressed and againresponded to added tranylcypromine. In April, 1969, she had amild depression with insomnia for which diazepam 20 mg. at

bedtime was added. Her mood lifted, but she experienced side-effects (nystagmus, slurred speech, tremor) and all medicationsbut LiCO3 were discontinued. Over the next year she had threefurther manic episodes and two depressions, even though shewas maintained on LiCO3 and imipramine was added for de-pression. Clearly, the LiCOg was not controlling her moodswings. In March, 1970, she became severely depressed and hadto be readmitted to hospital.

Examination at that time showed moderate obesity. The

thyroid was not palpable; pulse was 96 and regular. Laboratorytests were: P.R.!. 76, 7-3 u.g. per 100 ml.; T3-resin uptake 23%retention (normal 26-34); T4 2-5 µg. per 100 ml. (normal 4-11);serum-cholesterol 310 mg. per 100 ml. E.E.G. showed bilateraldiffuse slow waves. E.C.G. was normal. She was maintained onLiCOg and given six E.c.T. which resulted in some improvementof mood.