PSYCHIATRIC UNIT IN A DISTRICT GENERAL HOSPITAL

214 PHENOBARBITONE AND THE NEONATE SIR,-The account by Dr. Ramboer and his colleagues (May 10, p. 966) of a trial of phenobarbitone for treatment of neonatal hyperbilirubinaemia is of great interest. The significance of their observations with regard to the therapy of hyperbilirubinaemia in newborn infants is evident, but the frequency and severity of the non-bilirubin effects of phenobarbitone on the fetus and the newborn infant remain to be assessed. These workers noted that infants exposed to phenobarbitone (whether when they were inside or outside the uterus) had no increased frequency of respiratory distress, abnormal changes in birth-weight, low Apgar scores, feeding difficulties, or failure to gain weight; but that does not exhaust the possibilities of untoward effects. For example, the period of observation may have been much too short to detect some of the side-effects of the drug. Phenobarbitone possibly induces changes so subtle that abnormalities do not become evident until adolescence or adult life. For this reason I argue for further cautious study before the drug is used widely. Further controlled trials should now be conducted with a relatively large number of pregnant mothers and infants to determine whether humans are subject to the remote and multiple actions of phenobarbitone which have been recorded in laboratory animals. A fundamental concept of drug therapy in paediatrics must be applied by all those who use phenobarbitone in the perinatal period-that drug-induced alterations in the normal progress of biochemical events may prevent full and normal development. In a recent review Wilson1 described some of the many actions of phenobarbitone in man and animals. Among these was an affect on steroidhormone metabolism. In lower mammals the presence or absence of a sex hormone at a particular time may determine the development of mental processes, especially with regard to male or female behaviour.23 The increase in steroid metabolism noted in phenobarbitone-treated animals4 may, in the absence of a concomitant increase in hormone production, alter events in development which are dependent on both the quantity and quality of a hormone for their activation. The interruption of neural organisation may cause abnormalities of brain function which are subtle and which appear only in later life. Such malfunctions may not be limited to neural tissue. Denef and DeMoor,5 for example, demonstrated permanent changes in hepatic steroid metabolism in female rats which had been treated with testosterone. These adult female rats, which had been castrated and injected with testosterone during the first week of life, showed a steroid metabolism not unlike that foundin the livers of adult males. These changes were permanent, whereas testosterone administration in later life caused similar but only temporary alterations in steroid metabolism. The development of certain hepatic enzymes thus appears to be hormone-dependent, and the effect of phenobarbitone on this system must be considered. Phenobarbitone treatment may also have a long-lasting effect on the liver enzyme systems responsible for drug metabolism. In a study of adult rats rendered barbituratedependent by the administration of barbitone in their drinking water, Stevenson and Tumbill6 found a decrease in hepatic drug metabolism for 22 days after cessation of barbitone treatment. Hypersensitivity of rats to hexobarbitone anaesthesia was also found after barbitone was discontinued. These and other studies in animals may not 1. 2. 3. 4. 5. 6.

Wilson, J. T. Pediatrics, Baltimore, 1969, 43, 324. Bronson, F. H., Desjardins, C. Science, N.Y. 1968, 161, 705. Edwards, D. A. ibid. p. 1027. Conney, A. H., Klutch, A. J. biol. Chem. 1963, 238, 1611. Denef, C., MeMoor, P. Endocrinology, 1969, 83, 791. Stevenson, I. H., Turnbill, M. J. Biochem. Pharmocol. 1968, 17, 2297.

be applicable to man, but the results allow speculathe potential side-effects of phenobarbitone in man. Clinical trials must take account of the information available from animal studies, so that specific questions can be asked and answered. Some useful information may be obtained from a retrospective survey of children born to epileptic mothers who received phenobarbitone during pregnancy; but the number of children available for study may well be too small, and the validity of neural-function data obtained from children of epileptics may be questioned. Only if a controlled trial is undertaken will the large-scale use of phenobarbitone during pregnancy provide sufficient numbers for prospective evaluation of side-effects.

always tion

on

Perinatal Health Center, Children’s Hospital of San Francisco, San Francisco, California.

JOHN T. WILSON.

CELESTIAL PATHOLOGY SIR,-Dr. Eirian Williams raises some important points against centralisation of pathology services (July 12, p. 106). One of the arguments being used in favour of centralisation is that " we can’t afford " to have laboratories in the smaller hospitals. With centralisation, however, there is bound to be some delay in reports reaching the peripheral hospitals; and if only one patient per day is kept in a hospital bed for

day longer than necessary, waiting for the pathology result, the annual cost to the hospital will be equal to that of the salaries of 2 basic-grade biochemists, or 3 junior

one

technicians. This increase in expenditure for the National Health Service will not show up in the laboratory costs, so it is ignored by the advocates of centralisation. 9 Clifton Place, London W.2

FREIDA YOUNG.

PSYCHIATRIC UNIT IN A DISTRICT GENERAL HOSPITAL SIR,-I have been much interested in Dr. Baker’s paper1 and the subsequent correspondence. No-one who has visited his unit at St. Mary Abbots could fail to be impressed. His reply to his critics (July 5, p. 58) raises an urgent problem. Which elderly patients need mental, as opposed to geriatric, hospital treatment ? Are all elderly patients with dementia to be excluded from mental hospitals and transferred to geriatric care ? This seems to be the trend. Yet the present allocation of beds and staff to geriatric units is still based on the assumption that they care for the physically disabled, while the psychiatric unit looks after the mentally disabled. This is, of course, an unreal distinction since there is a vast degree of overlap. Many geriatricians would agree that a well-equipped and well-staffed geriatric unit, supported by day care, psychiatric advice, and adequate welfare services may well be the right department to undertake the care of demented patients, especially since so many also have gross physical

disability. If, however, geriatric departments are to cope with this problem as well as continuing to carry the burden of physical illness in old age, there will need to be a great expansion of their facilities-in staff, beds, and day units. There is urgent need for a policy decision to determine who should do what, and for cooperative research between sociologists, geriatricians, psychiatrists, and local authorities to determine what additional resources will be needed if the mental hospital is to be relieved of its historic role in 1.

Baker, A. A. Lancet, 1969, i, 1090.

215

elderly demented patients. Additional funds to be made available for long stay of a result the Ely Hospital report. This would as patients the

care

are,

we

still infected by their teens at a time when might be practicable. Many hospitals skin-test all their child patients, and it might be worth extending this routine to general practice now that there is no need for syringe, gun, or plaster. (4) Ensuring that all young children with positive tuberculin tests are treated effectively, no matter how fit they seem at the time. This could often be done equally well by general practitioner, chest physician, or peediatrician, but perhaps the notified authority should check that someone has taken on the task. T. H. HUGHES-DAVIES. Downton, Wiltshire.

of

children who

understand,

tracing the

be a sood use for them. St. Helen’s Hospital,

Hastings.

R. E. IRVINE.

SKINS AND NEEDLES

SIR,-I should like to record my whole-hearted support for Dr. Dann’s suggestion (July 12, p. 96) that routine skin preparation before injections is unnecessary. About twelve years ago I stopped preparing the skin before venipuncture. Since then, working as an anaesthetist, I have given many thousands of intravenous

injections

and have set up many hundreds of infusions

without any ensuing infection. Ightham, Kent.

DAVID G. HURTER.

TURPENTINE AND THROMBOCYTOPENIC PURPURA SIR,-Turpentine is a well-known cause of cutaneous reactions; but we are not aware of any reports indicating

that it may SIR,-Dr. Dann remarks, " it seems hardly likely that dry swabs... would do any better, and no-one has suggested that they do." They have. Eighteen years ago my pathology demonstrator clearly showed that firm rubbing with a dry swab desquamated the epidermis to an extent that left it, not sterile, but more nearly so than cleansing with the usual alcohol. Since then I have always used dry cylindrical dental swabs, without a single case of infection. In general practice these dental rolls are very handy: they small container and save the nurse’s time balls unnecessary. My only cotton-wool by making exception to dry " swabbing " is when I use iodine before venepuncture for blood-culture. Some years ago a practitioner in Zululand reported similar findings in a series of 20,000 injections. A bolder man than Dr. Dann or I, he took the experiment to its logical conclusion and used the same needle throughout. During this time the needle remained capable of penetrating the skin, and infected only one patient. JOHN STEVENS. Aldeburgh, Suffolk. stow

well in

a

are

source

hxmatological changes. We have recently of thrombocytopenic purpura possibly induced by turpentine. Case 1.-This was a boy of 15, who had previously been healthy. On Dec. 15, 1968, the floors of the family house were cleaned with turpentine which smelled strongly for about two days. On Dec. 18, punctate efflorescences appeared on both the patient’s legs, and soon spread to the trunk, face, and oral cavity. He was admitted as an emergency on Dec. 22. On admission, there were profuse petechias, 1-3 mm. in diameter, on the patient’s calves, thighs, and upper thorax, both dorsally and ventrally. The buccal mucos2e and tongue were covered with petechiae about 3 mm. in diameter. The spleen was palpable, but not enlarged. The erythrocyte and leucocyte counts were normal. The thrombocyte-count on admission was 69,000 per c.mm., and, on the following day it had fallen to 32,000 per c.mm. The bleeding-time (Ivy) was 36 minutes, and the clotting-time 5 minutes. The bone-marrow was normoblastic with sporadic megaloblastoid traits, and erythropoiesis was abundant. Granulocytopoiesis was ample. The preparation was dominated by promyelocytes. Toxic granulation " of granulocytes was seen. Megakaryocytes were very numerous; they mostly had multilobular and were not surrounded nuclei, by thrombocyte conglomerates. The patient was given prednisolone 15 mg. per day. The bleeding-time and thrombocyte-count became normal within one week, and the bone-marrow changes subsided within two weeks. He has remained healthy during the seen

two

cause

cases

"

TUBERCULOSIS IN CHILDHOOD

SIR,-After years in which tuberculosis in children has become increasingly rare, I have in a few months seen a sixweek-old baby with miliary tuberculosis, a two-year-old boy with paraplegia from tuberculosis of the spine, and a girl of two with tuberculous meningitis. This may be due to chance, but in retrospect all might have been avoided; and their occurrence may be a sign of failing barriers. The baby’s mother had severe tuberculosis of the lungs and spine which in the past would have been found on a routine chest X-ray of pregnancy; the boy with Pott’s disease was known to have a positive tuberculin test when his father’s phthisis was found some months before, but though treatment was started, it was not continued; the girl’s grandfather had been under treatment from years before her birth; his doctors did not know of the child’s existence, nor did the intelligent parents know of B.C.G. As chest clinics close, tracing and chasing contacts becomes more difficult. It might be worth considering: (1) Again taking chest X-rays in pregnancy-at least of women who are not fully well or whose tuberculin tests

strongly positive. (2) Giving printed advice (perhaps annually) to tuberculous patients on the hazards to past and future contacts, especially young children. (3) Extending tuberculin testing, which the Tine (Rosenthal) test makes very simple and painless, to infant clinics and schools in the hope of picking up the 10% of

are

past 6 months without any medication. Case 2.-This was a boy of 9 who had previously been healthy. From Feb. 1, 1969, reddish-brown spots spread from the feet proximally, and his gums bled slightly when he brushed his teeth. After the patient had been admitted, it transpired that he had drunk an indeterminate volume of turpentine, out of curiosity, one or two days before he became ill. On admission, on Feb. 3, 1969, there were abundant petechiae, 1-2 mm. in diameter, on the patient’s arms and legs. There were several bleeding points within the oral cavity, and also a hsematoma (4 x 4 cm.) on the left cheek. The spleen was not palpable. The erythrocyte and leucocyte counts were normal. The thrombocyte-count on admission was 56,000 per c.mm., and, on the following day, 46,000 per c.mm. The bleeding-time (Ivy) was in excess of 35 minutes, and the clotting-time was 6 minutes. In the bone-marrow there was abundant normoblastic erythropoiesis, with a shift to the left. Granulocytopoiesis was ample, and dominated by promyelocytes. There was " toxic granulation". Megakaryocytes were numerous, and were basophilic, had