generation of otologists may be trained. From .... Robson. J. M.. Lancet, 1963, 2, 553. Old People in the Cold. SIR,-Dr. G. S. Crockett in his letter. (4 January, p.
8 February 1964
Correspondence
Mr. R. G. Macbeth (21 December, p. 1587)-as an examiner-is concerned to defend the F.R.C.S. as a worthy hallmark for an otologist. I am concerned with what I as a teacher believe to be the far more important matter of the education available for the aspirants to that hallmark. I have suggested: (1) that the Royal Colleges should standardize their requirements. (2) That they should provide far more systematic tuition, which should set the standard for provincial teaching centres. (3) They should do far more to stimulate and co-ordinate the efforts of provincial centres. This would help us all enormously, but as Mr. Macbeth so rightly says, we are desperately in need of a number of full professorial units in our specialty, and this, of course, brings us to the problem of academic otology and research. He goes on to attribute the moribund condition of academic otology in this country to the failure of our universities and Medical Research Council to provide large-scale foundations and endowed fellowships on which research can be carried out. He concludes despondently, "As usual it turns on finance." I utterly disagree. Having enjoyed the support of the M.R.C. for many years, not to mention my own university, the Regional Board, Board of Governors, and the Department of Scientific and Industrial Research, I assert confidently that no worth-while project need ever founder for lack of finance. Moreover the sort of foundations and fellowships for which he yearns do actually exist. Yet they are empty because we cannot find otologists to man them. How is it that learned societies with prizes to award periodically for original work in our specialty have the utmost difficulty in finding worthy recipients? The fault lies neither in our patrons nor in our students-but ourselves-in the work we do, the standards we set, and, above all, in the training we offer to our successors. Let us shed some of our complacency and, in recognizing our own shortcomings, seek to ensure that our successors shall receive a better training than we did. I join Mr. Macbeth in pleading for more professorial units, not, however, as research centres-we could not man them on that basis -but as centres of learning wherein a new generation of otologists may be trained. From their ranks would emerge the otological physicians and the research workers as well as the clinical craftsmen of the future. Then research could be undertaken on a scale to satisfy even Mr. Macbeth and oto-rhinolaryngology could acquire its proper stature. -I am, etc., A. TUMARKIN. Department of Oto-rhino-laryngology, University of Liverpool.
been noticed that a marked lymphopenia develops. In the case of S.L.E. described, which was not controlled with large doses of prednisolone, it was hoped that by using a cytotoxic agent antibody-forming tissue would be inhibited. This goal was, to some extent, achieved. Mrs. S., a 27-year-old Jamaican, was first seen on 24 February 1961, when a diagnosis of S.L.E. was made, when she was given prednisolone, 15 mg. q.d.s. She responded dramatically with
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Cytotoxic Drugs for Systemic Lupus SIR,-We would like to report the following case of systemic lupus erythematosus (S.L.E.) treated with a cytotoxic agent. It is current practice to give corticosteroids in this type of disorder in an attempt to prevent the abnormal antibody-antigen reaction, and it probably also inhibits, to some extent, the antibody-forming tissue. However, in the experimental animal cyclophosphamide has been shown to prevent the formation of immunologically committed lymphocytes and large pyronophilic cells. While treating cases of reticuloses with cyclophosphamide it has
the disappearance of all her symptoms, a fall in the E.S.R., and the disappearance of the L.E.-cell phenomenon. During the next two years it was found impossible to reduce the dose of prednisolone. Any attempt to do this was followed by a recurrence of her symptoms, a rise in the E.S.R., and the reappearance of the L.E.-cell phenomenon. She was found to require increasing doses of prednisolone, and 21 months after diagnosis she required prednisolone, 50 mg. daily, and A.C.T.H., 40 units twice per week, to keep her symptom-free. Unfortunately, during the two years following the diagnosis she developed serious side-effects, attributable to the steroid dosage. She developed a meningococcal meningitis, cellulitis of the face, a gastric ulcer, hypochromic anaemia, and rupture of the extensor tendon of the right middle finger. The attacks of sepsis were always accompanied by a hypoadrenal crisis. She became extremely Cushingoid. In view of these serious side-effects it was decided to use a cytotoxic agent in an attempt to withdraw prednisolone. She was given cyclophosphamide intravenously to a total of 5.2 g. (200 mg. per day). A lymphopenia of 320 cells/ c.mm. was obtained. Oral cyclophosphamide was given at a rate of 100 mg. per day for three months, and the white blood-cell count maintained at approximately 4,000 cells/c.mm. She was given, initially, three months' treatment. During the last week of this three-month course she developed a sterile chemical cystitis and mild epilation. Both these side-effects disappeared on stopping the drug. During the treatment with cyclophosphamide it was possible gradually to reduce the dosage of prednisolone to nil. The A.C.T.H. was gradually withdrawn also. Seven months after starting the cyclophosphamide therapy the patient remains symptom-free and is at present not taking any prednisolone or cyclophosphamide. The E.S.R. is 37 mm. in the first hour and has remained steady for five months. The haemoglobin is 75% and the total white count 3,700 cells per c.mm., with 36% polymorphs and 35% lymphocytes. No L.E. cells can be detected. The blood urea is 45 mg. per 100 ml., and the urine shows an albuminuria of 200 mg. per 100 ml.
It is too early as yet to evaluate the full effect of the treatment and only time will tell whether the remission obtained is permanent. -We are, etc., R. D. HILL. Guy's Hospital, G. W. SCOTT. London S.E.l.
Serotonin as a Teratogen SIR,-We were very interested in your annotation on " Serotonin as a Teratogen " (21 December, p. 1546) based on the work described by Reddy et al.' It has been known for several years that serotonin (5-HT) can cause death of the foetus in mice very rapidly and that haemorrhagic changes usually develop in the placenta.2 At crucial stages of pregnancy serotonin will produce foetal abnormalities in mice in a large proportion of surviving foetuses.' There is also some evidence about the mechanisms by which these effects are produced. In mice at least they are not due to the contractions of umbilical vessels, which
are unaffected by large concentrations of serotonin,4 though the drug does produce contraction of these vessels in the rabbit.' On the other hand, there is quite clear evidence that serotonin interferes with the blood supply to the placenta and with the nutrition of the foetus,' and it seems likely that this effect is responsible for the development of abnormalities. This view is supported by the observation that the administration of 5-HT antagonists (cyproheptadine, methysergide) together with 5-HT greatly decreases the number of foetal abnormalities and also reverses the vascular and nutritional changes produced by 5-HT in the placenta and
foetus.' Of interest too is the fact that the placentae of animals treated with serotonin show changes reminiscent of those seen in the human placenta in toxaemia of pregnancy. The 5-HT content of human toxaemic placentae is higher than in normal placentae,' and the question arises to what extent abnormal serotonin production and metabolism may be related to deviation from the normal in human pregnancy.-We are, etc., J. M. ROBSON. F. M. SULLTVAN. Department of Pharmacology, Guy's Hospital Medical School. London S.E. 1.
REFERENCES Reddy, D. V., Adams, F. H., and Baird, C., 7 Pediat., 1963, 63, 394. 2 Poulson, E., Botros, M., and Robson, J. M.. Science, 1960, 131, 1101. 3- Robson, J. M., and Sullivan, F. M., ibid.. 1963, 141, 717. Robson, J. M., and Sullivan, F. M., 7. Endocr.. 1963, 25, 553. Pepeu, G., and Giarman, N. J., 7. gen. Physiol., 1962, 43, 575. Honey, D. P., Poulson, E., Robson, J. M., and Sullivan, F. M., unpublished observations. Senior, J. B., Fahim, I., Sullivan, F. M.. and Robson. J. M.. Lancet, 1963, 2, 553.
Old People in the Cold SIR,-Dr. G. S. Crockett in his letter (4 January, p. 61) about- helping " Old People in the Cold" mentions that the voluntary bodies can help in this respect. I enclose a card which we used with great success, mainly in the hilly area around Tiverton, with its widely scattered hamlets and cottages, during the whole of the severe winter of last year, and the use of which we are now extending to the whole county. The card measures 10x7 in. (25 x 18 cm.) and bears a large red cross with the words, " British Red Cross Society. Please Come In, I Need Help." On the reverse side spaces are provided for the addresses and telephone numbers of the police, fire brigade, local doctor, and district nurse. The card is given by doctors, district nurses, or Red Cross personnel to old people living alone who may need help at any time. It is usually kept handy on a shelf or sittingroom mantelpiece. If the "old-un" or " disabled body " needs help, he or she has only to put the card up in a front window where it is- conspicuous to any passer-by who can come in and give or send for any help needed. Particulars for the latter purpose are entered at the time of giving on the back of the card. I think doctors, particularly those in country practices, might find this a most useful help, which the local Red Cross Branch could easily provide. A sample card
