TRANYLCYPROMINE

388

individual is only fitted

spend his own money on fripperies. self-indulgence Rather than doing away with the visiting-list and doing away with the morning surgery, let us do away with some of the political humbug which surrounds the National Health Service, and let us see it for what it really isa safe, unimaginative, and uninspiring refuge for the dullest forms of mediocrity. As I bow my head to the approaching storm, and as the planners march, and the machines are calibrated, will anyone, just anyone, join me in Dr. Atkinson’s Ark ? to

and useless

PATRICK WOOD.

affects fatal crown-rump measurements, but the evidence suggests that continued foetal growth, perhaps for some time, followed infection. Pathology Department, King Edward Memorial Hospital, London, W.13.

TRANYLCYPROMINE SiR,-The letters of Dr. McCormick and Dr. Blackwell (Jan. 19) prompt me to describe two cases treated with tranylcypromine in the past year who had intracerebral

bleeding. aged 47, had a history of recurrent depression. He in outpatients on Jan. 15, and was treated with tranylcypromine 10 mg. and trifluoperazine (’ Parstelin’) 1 mg. t.d.s. He continued on this treatment, and had no headaches, until April 4 when he complained of sudden severe occipital headache, nausea, and sweating. The headache persisted, and he was admitted on April 5 to another hospital, where examination showed pronounced neck stiffness, a dilated left pupil, and diminished reflexes on the left side. The blood-pressure was not recorded on admission; three weeks later it was 125i85 Lumbar puncture showed slightly bloodstained mm. Hg. cerebrospinal fluid. He was referred the same day to a neurosurgical unit for angiography, which proved normal. He made a rapid and complete recovery. A woman of 59 had glaucoma and cataract which had apparently precipitated a reactive depression in December, 1961. In June, 1962, she was readmitted because she had again become depressed. She was overweight, and her bloodpressure was 170/90 mm. Hg. She was treated with tranylcypromine 20 mg. t.d.s. and chlordiazepoxide 10 mg. q.d,s. She improved, and was discharged, after a month, on tranylcypromine 10 mg. q.d.s. In August, 1962, she relapsed, and the dose of tranylcypromine was raised to 20 mg. t.d.s. on Aug. 8. She was also on chlordiazepoxide 10 mg. t.d.s. Her family doctor noted that she had several paroxysmal headaches, and on the evening of Aug. 18 she complained of sudden onset of severe frontal headache and vomiting. She was incontinent of urine, and her husband noticed that her speech was incoherent, and she was unable to move her left arm and leg. On admission on Aug. 19, she was found to have a left hemiparesis and her blood-pressure was 185/95 mm. Hg. Lumbar puncture showed bloodstained cerebrospinal fluid, and a right A man,

was

GENERAL-PRACTITIONER HOSPITALS

SIR,-Iagree with all the information given by Dr. Clyne and his colleagues (Feb. 2), and I think their section entitled Advantage of General-practitioner Hospital is of paramount importance. For about six years (1928-34) I was on the medical staff of a similar hospital -the Kingston Victoria Hospital-and I can confirm from personal experience the truth of what your contributors say. The Minister of Health’s intention to close such hospitals is another example of the harm that can be done to medical practice in this country by the actions of politicians and Civil Servants. R. F. GUYMER. PRENATAL VACCINIA

SIR,-The recent article by Dr. Naidoo and Dr. Hirsch (Jan. 26) prompts me to report what is almost certainly another example of this condition. A 22-year-old woman was successfully vaccinated for the second time (the first time was in infancy) on Jan. 16, 1962, when nearly 12 weeks pregnant (last menstrual period, Oct. 25, 1962). The " take " made her feel very ill with a high temperature for two days. She had had one previous full-term pregnancy. The patient was admitted to hospital with a threatened abortion on Feb. 1, 1962, and discharged on Feb. 27. Vaginal bleeding began again on March 21, and the abortion was complete ten days later. Pathological examination.-The faetus and placenta were received in formol saline. The foetus, with a crown-rump length of 13 cm., appeared much macerated and showed numerous evenly distributed haemorrhagic spots in the skin, up to 0-8 cm. in diameter. The placenta, measuring 12 cm. in diameter, was pale and appeared thicker and firmer than would be expected. The maternal surface appeared unusually smooth, but the striking feature was the presence on the cut surface of numerous small pale yellow foci resembling miliary tubercles.

Microscopically the organs appeared much macerated, the liver and kidneys showing subcapsular calcification. The lungs were less macerated and there was no evidence of an infection. In the skin epidermal loss was complete and there was superficial focal haemorrhage, a remarkable number of red cells having survived. There was a high concentration, in the deeper part of the dermis, of basophil material, perhaps indicative of an inflammatory cell infiltration. The placenta showed widespread focal necrosis with a histiocytic reaction and polymorphonuclear leucocyte infiltration. Eosinophilic inclusions were present but scanty. The placental changes were, in fact, as described by Entwistle et al.1 Proof of a vaccinial infection is lacking but the evidence is very strong. The foetus clearly died in utero some weeks before the abortion was complete. Infection, initially of the placenta, probably occurred at about the thirteenth week. Because of the maceration of the foetal organs it is impossible to say whether or not the infection was confined to the skin. One does not know how maceration 1.

Entwistle, D. M., Bray, P. T., Lawrence, K. M. Brit. med. J. 1962, ii, 238.

W. S. KILLPACK.

seen

/

postparietal which

was

intracerebral hsmatoma, excellent recovery, and of the left arm and leg.

burr-hole revealed

an

aspirated. She made

regained almost normal

use

an

impossible with certainty to attribute the intrableeding in these two cases to the effects of tranylcypromine. In the first patient the two may quite possibly have been unconnected; but in the second patient, in whom the intracranial bleed was preceded by paroxysmal headaches (described by the patient’s doctor as typical of those he had seen in patients on tranylcypromine), a connection between the drug and the disaster seems likely. Hypertensive attacks caused by tranylcypromine, which have been described as mimicking subarachnoid hxmorrhage, may possibly cause intracranial bleeding. It is cranial

Middlesex Hospital, London, W.1.

W. DORRELL.

SiR,-The article by Dr. Lees and Dr. Burke (Jan. 5) us to report the following case of habituation to tranylcypromine and trifluoperazine (’ Parstelin’, each tablet of which contains tranylcypromine sulphate 10 mg. and trifluoperazine 1 mg.).

prompts

The patient was a 24-year-old married woman who had a basically hysterical personality. She had had periods of tension and depression for twelve months, which had been treated initially with 4 tablets of parstelin daily. After three months she felt she needed

more

because the beneficial effects

wore

389 off and she had exacerbations of her symptoms. She increased her consumption of parstelin to 8 and, then to 14, tablets per day. To keep up her supply she persuaded her general practitioner to give her further prescriptions, saying that she had mislaid or lost her tablets. When this failed, she began to change general practitioners to gain further supplies. Outpatient management of this habituation failed, and she The parstelin was was admitted to the psychiatric unit. stopped; an acute tension state with hysterical behaviour followed and she threatened suicide unless she was put back on

parstelin.

She improved after psychotherapy and a course of electroconvulsive therapy. She remained well for two months following discharge, after which her symptoms recurred. When last seen in the outpatient department, she had rather ominously changed her general practitioner again. Oldham and District General Hospital,

J. MIELCZAREK J. JOHNSON.

Oldham,

Lancashire.

SlR,—The correspondents

on

tranylcypromine and its

side-effects of, inter alia, severe headache and hypertension have not recorded their treatment for them,

though Mr. Day and Mr. Rand1 list tranylcypromine among the monoamineoxidase antagonists of guanethidine and bretylium. I wish to report a case of overdosage with four tablets of ’Parstelin’ (a tablet contains 10 mg. of tranylcypromine and 1 mg. of trifluoperazine) which was treated with

pentolinium

tartrate.

A girl of 19 had migraine with teichopsia and occipital headache for eight years. One week before admission she complained of depression due to migraine, chilblains, and menorrhagia, for which her general practitioner prescribed parstelin. Having omitted the previous day’s dosage she took four tablets 9t4p.M., followed one hour later by severe headaches " worse than any migraine", with a feeling of great anxiety. She was admitted to hospital three hours later; her bloodNeck pressure was 184/110 mm. Hg and pulse-rate 54. stiffness was absent, but she had photophobia and was in distress. Lumbar puncture was not performed because the syndrome was recognised. She was given pentolinium tartrate 3 mg. subcutaneously with immediate fall in bloodpressure to 120/80, pulse 106, 11/2hours later. Headache was relieved.

The severity of a hypertension and headache which has elsewhere led to diagnoses of subarachnoid haemorrhage, and the actual danger of intracranial haemorrhage in these circumstances, warrant the use of hypotensive drugs in the acute stase. Royal Devon and Exeter Hospital, Exeter.

T. N. MILLER.

SIR,-In this correspondence it has been suggested that side-effects are more likely if tranylcypromine is taken in conjunction with other drugs. Zeck reported a case of a patient who died after taking 5 mg. of amphetamine sulphate while under treatment with tranylcypromine (10 mg. twice daily) and chlordiazepoxide (10 mg. four times daily). In the following case a man became addicted to tranylcypromine and, as this began to lose its effect, he added an amphetamine-amylobarbitone capsule. The patient, who was born in 1920, has an obsessional personality disorder, but succeeded quite well in the Army during the war,

reaching the rank of sergeant. Shortly before his demobilisation he became depressed and fearful, being obsessed particularly with the fear of death. This depression cleared and he worked for seven years as a postman until the depressive illness returned in 1955. He was then in hospital for 13 months and recovered sufficiently to return to work, but needed further inpatient treatment in 1959, 1961, and 1962. 1.

Lancet, 1962, ii, 1282.

After receiving E.C.T. in 1961 he went home and was started onParstelin ’ (tranylcypromine 10 mg., trifluoperazine 1 mg.) by his G.P. He rapidly felt better with this drug and returned to work until April, 1962, when he again felt depressed, was obsessed with fears of death, and spent most of the day in bed. He was given E.C.T. again and improved slightly, but to ensure his return to work he increased the intake of parstelin to 12 tablets daily, with no side-effects. By July, 1962, he felt unable to continue at work and then began to take ’ Dexytal ’ capsules 4 or 5 daily (sodium amylobarbitone and dexamphetamine sulphate) in addition to his 12 parstelin. There was no improvement and the only untoward effects he noticed were feeling trembly inside and being unable to go to sleep. He continued on this combination for at least eight weeks until his admission to hospital when there was no difficulty in discontinuing all these tablets immediately. Physical examination was quite normal and his blood-pressure was 140/85 mm. Hg. In this case the combination of these drugs did not prove harmful even though large doses of both were taken. Nor did the amphetamine potentiate the antidepressant effect of the tranylcypromine which initially had been effective. University of Manchester.

D. H. MORGAN.

THE ROLE OF THE THYMUS: MIGRATION OF CELLS FROM THYMIC GRAFTS TO LYMPH-NODES IN MICE

SIR,-Dr. Miller (Jan. 5, p. 43) refers to experiments in which chromosomally marked cells from thymic grafts in neonatally thymectomised mice were detected in " lymphoid tissues ". His previous accounts 1-3 provide evidence that, in allogeneic combinations of host and donor, up to 40% of the mitotic cells in the spleen may have come from the graft. There is a strong presumption that cells from a thymic graft would also reach the lymphnodes and proliferate there. We have recently been able to demonstrate that this is indeed so. Mice of the T6 translocation stock have been serially backcrossed by Dr. Mary Lyon to the standard CBA mice of this laboratory and then inbred. The acceptance and retention of reciprocal skin grafts demonstrates that the new inbred stock is effectively syngeneic with CBA. It is designated CBA- T6T6. The animals are homozygous for the translocation and have two short marker chromosomes that in good preparations are easily recognised at mitotic metaphase. CBA mice have normal chromosomes. Mice were thymectomised on the day of birth and, seven or eight days later, grafted subcutaneously in the axilla with a thymus from a one-day or two-day old donor. Hosts were of one syngeneic stock (mostly CBA) and donors of the other. Seven of the grafted mice have now been killed and examined cytologically at thirteen to twenty days after grafting. The grafts were well vascularised and were found to contain a marked preponderance of host-type mitotic cells. This is in agreement with Miller’s findings in allogeneic host-donor combinations. In lymph-nodes the ratio of donor cells identified with certainty to the total number of mitotic cells examined was 0/27, 5/47, 5/31, 9/41, 8/27, and 12/24 in the six animals from which preparations were obtained. In one animal preparations were made separately from peripheral nodes and mesenteric node and cells from the graft were identified in both. The lymph-nodes of these very young animals were difficult to handle technically and some of the mitotic cells chosen for examination (included in the denominators given above) could not be assigned to either host or honor, mainly because of cell breakage. The true proportions of immigrant thymic cells are therefore likely to have been rather higher. In view of this result and Miller’s previous reports,l-3 it 1. 2. 3. 4.

Miller, J. F. A. P. Miller, J. F. A. P. Miller, J. F. A. P. Barnes, D. W. H.

C.N.R.S. Symposium, Paris, 1962. In the press. Ann. N. Y. Acad. Sci. 1962, 99, 340. Proc. Roy. Soc. B. 1962, 156, 415.

Unpublished.