NUCLEATED RED-CELLS IN THE NEWBORN

1293 GASTROINTESTINAL BLEEDING

SiR,—Concerning your leading article (May 30, p. 1157) we should like to make the following comments. It was found in Oxford that 40% of the men and 60% of the women were over 60, while in Ontario 10% of the patients were over 80. In a recently published survey 68 out of 110 patients were found to have low Thrombotest ’.1 Many patients with gastrointestinal bleeding of unknown cause may have a low thrombotest and this simple test should be routine, especially in the elderly. In both the Oxford and Ontario trials, 1 in 6 patients needed about 5 litres of blood. In our department we have never needed to use more than 2 or 3 litres, since every patient is given vitamin K. By this means, circulatory overload and other complications of blood-transfusion are avoided. It was interesting to read that aspirin was the commonest drug associated with bleeding. Smith and McKinnon2 found that aspirin under certain conditions could cause hypoprothrombinsemia, a finding confirmed by our own survey. Other drugs that may lower thrombotest are chloroquine, quinine, and phenylbutazone,3 and tranquillisers in common use, such as chlorpromazine, promazine, trifluoperazine, and pecazine, also lower thrombotest. Emphasis should therefore be put on the drug-taking history. At this point we repeat your question: will the outlook be improved with a different therapeutic approach ? The approach we suggest is: (1) routine thrombotest in all patients with gastrointestinal bleeding; (2) administration of vitamin K during the bleeding episode; (3) stop all drugs that may promote bleeding. Department of Geriatrics, St. Mary’s Hospital, Colchester, Essex.

K. H. BALOCH K. HAZELL.

THE DURATION OF PREGNANCY

SIR,-My article4 prompted a few interesting letters in your columns, but, like your first correspondent,5 I am surprised that there has not been a greater response from leading obstetricians. It is interesting that I have had a very large personal correspondence from all over the world and at least two professors of obstetrics have agreed entirely with my thesis but have not felt strongly enough to take further action. Nobody has disagreed absolutely. I realise that my figures are very different from those of other workers, 6.7but it seems to me to be quite clear why this is so. All the figures include only patients who started labour spontaneously, but the difference lies, I think, in the fact that in the figures of other workers the number of patients who were induced because of the time factor alone are not included. These are the patients who, in my view, would have had normal spontaneous labour if they had been left a little longer. I would be very happy to agree that I was mistaken if there was convincing evidence, but while my results continue to be good in terms of morbidity and mortality, I do not think it would be reasonable to change my policy of vigilant non-intervention. Even if I am entirely mistaken about the duration, I still think that there is considerable confusion in our terminology and in our teaching. I agree, of course, with your correspondents that there are variations and that we have to make allowances for patients with longer or shorter cycles, but I am sure that everyone will agree that the great 1. 2. 3. 4. 5. 6.

Hazell, K., Baloch, K. H. Geront. Clin. 1970, 12, 10. Smith, J. M., Mackinnon, J. Lancet 1951, ii, 569. Mandel, E. H. J. Mt Sinai Hosp. 1962, 29, 71. Park, G. L. Lancet 1968, ii, 1388. White, J. ibid. 1969, i, 201. Eastman, N. J., Hellman, T. M. Williams’ Obstetrics; p. 219. New York, 1966. 7. Rodrigo, G., Florez, P. E. Lancet, 1969, ii, 268.

majority of patients have 28-day cycles and therefore ovulate at approximately the 14th day of the cycle. Whatever is decided in future about the duration of pregnancy, I still feel that when we say a patient is 20 weeks’ pregnant we should mean 20 weeks from conception and not 20 weeks from the first day of the last menstrual

period. G. L. PARK.

ROUTINE URINE TESTS IN GENERAL PRACTICE SIR,-Dr. Macleod (May 30, p. 1167) is to be congratulated on his demonstration of the value of these tests, not the least of which was the revelation of " 8 cases of hsematuria where investigation showed no obvious disease ". He suggests " more detailed follow-up study may reveal the significance ... with a negative intravenous pyelogram ". May I suggest the follow-up study should include (unless already completely eliminated) the possibility of analgesic nephropathy ? A relentlessly thorough crossexamination of the patients, and their relatives, may be needed to establish the diagnosis, which if strongly suspected despite the absence of a positive history might be confirmed by bilateral retrograde pyelography, after " negative" ...

intravenous pyelography. East

Glamorgan District General Hospital, Church Village, near Pontypridd, Glamorgan.

J.

DE

SWIET.

NUCLEATED RED-CELLS IN THE NEWBORN SIR,-We have observed high nucleated-red-blood-cell (N.R.B.C.) counts in newborn infants after acute or chronic antenatal hypoxia. The values are given in the accompanying table. None of the children had evidence of isoimmune or other hsemolytic disease. We are puzzled that there have been so few published reports of this phenomenon.1 It seems difficult to account for the rise in the N.R.B.C. count on the basis of the conventional hypoxia/erythropoietin mechanism, since the N.R.B.C. are seen in cord-blood but the reticulocyte response to hypoxia-induced erythropoietin release is not generally seen until the second or third day after hypoxia.2-4 1. 2.

Anderson, G. W. Am. J. Obstet. Gynec. 1941, 42, 1. Siri, W. E., Van Dyke, D. C., Winchell, H. S., Pollycove, M., Parker, H. G., Cleveland, A. S. J. appl. Physiol. 1968, 21, 73. 3. Vogel, J. A., Bishop, G. W., Genovese, R. L., Powell, T. L. ibid. 1968, 24, 203. 4. Halvorsen, S. Acta pœdiat., Stockh. 1963, 52, 425. N.R.B.C. COUNTS IN INFANTS EXPOSED TO ANTENATAL HYPOXIA AND IN NORMAL CONTROLS

1294 Oski and Naiman5 have noted increased numbers of immature forms of erythrocytes in the peripheral blood of the newborn after hypoxia. Finne and Halvorsen 6 suggest that the increase in cord-blood-erythropoietin in anaemic and dysmature infants results from anaemic hypoxia and

hypoxic hypoxia, respectively. We believe that the rise in N.R.B.C. count in neonates who have experienced hypoxia deserves further study. Perinatal Health Center, Department of Pediatrics, Children’s Hospital, San Francisco, California 94119.

GERALD B. MERENSTEIN LILLIAN R. BLACKMON JOSEPH KUSHNER.

PLIGHT OF E.E.G. TECHNICIANS SiR,-Iwish to support Mr. J. A. Robert’s plea for better conditions for E.E.G. technicians (June 6, p. 1224), and to applaud him for the effort he has made in doing the survey. I have found it extremely difficult to recruit staff, and trained technicians are virtually unobtainable. Student technicians cannot live on their salary, and this reduces the field of recruitment to those who can live at home or are otherwise supported by their families. Dissatisfaction among the more senior grades is not, however, confined to salary alone, low though this is. The condition of many departments, including this one, are abysmal-antiquated buildings, undecorated for years, and equipped with out-of-date and worn-out machines. This department serves a large area of North London, and, with the associated department at St. Albans, also covers Hertfordshire and parts of Bedfordshire, including the neurosurgical unit and busy neurological and paediatric departments. In spite of this, effort to get our only 16-channel E.E.G. machine replaced with a new one has not succeeded, although the machine is so old in design and worn out that it is no longer reliable. Bad electroencephalography is worse than useless-it can be positively misleading. The situation is no better in related disciplines. No radioactive scanner is provided for the neurosurgeons, no ultrasound or neuroradiology is available directly to the neurologists, and probably there are similar deficiencies in other fields. The plight of the E.E.G. technician is thus just one, but a serious, sign of inadequate financing of the Health Service at a time of increasing technological achievement. As a result, the majority of E.E.G. departments are functioning at a level appropriate to 20 years ago and not to the 1970s. Department of Clinical Neurophysiology, Whittington Hospital, S. G. BAYLISS. London N.19.

TREATMENT OF CONGENITAL THYMIC APLASIA BY GRAFT OF FETAL THYMUS SIR,-If the proof of the pudding is just in the eating, as is now implied by Dr. August and his colleagues (May 23, p. 1080) with respect to the grafting of fetal thymus, then, there is, in the past literature, a wealth of equally miraculous records and even more remarkable coincidences. Voronow claimed many cures for his sexually-jaded patients after they had passed three score years and ten by grafting simian testis. One’s credibility was stretched in the past when going through the reports7 of cures for Addison’s disease by grafting rabbit and dog adrenals. Even pigmentation disappeared and patients rose from their apparent death-beds and when female patients were 5. 6. 7.

Oski, F. A., Naiman, J. L. Hematologic Problems of the Newborn. Philadelphia, 1966. Finne, P. H., Halvorsen, S. Ann. N. Y. Acad. Sci. 1968, 149, 576. Dempster, W. J. Br. J. Surg. 1955, 42, 540.

involved there are reports of menstruation reappearing after being absent for some months. Similar miraculous coincidences are traceable back to the man who took up his bed and walked. It was Claude Bernard who stressed that a crude fact is not scientific, and a fact whose causation is irrational should be regarded with scepticism. It was my understanding that one of the main lines of thymus research was a study of the stage in ontogeny when the thymus becomes a dominating influence on the immunological function of the fetus. Is it settled, then, that the human fetal thymus at 13-16 weeks is fully capable, in a postnatal sense, of influencing the lymphocytes ? Why, one might ask, are normal children born with normal thymuses and yet still have not developed full adult immunological activity ? How is it that a grafted, partially necrosed fetal thymic fragment can achieve more immunological influence in a few days in the postnatal period of a child than a normal thymus with an engorged venous system (at least one hallmark of an active endocrine gland) can achieve through several months of fetal development? Even the murine thymus, fully supplied with blood, fails to spread effective immunological control until after birth; perhaps the murine fetal thymus can effect remarkable cures in thymectomised murine neonates. If experiments involving grafts of human fetal thymus are to be repeated, it would be worth having some information about the conditions under which the fetus was salvaged. Was it a therapeutic abortion or not ? If not, how long was the thymus exposed to warm ischxmia ? What are the criteria of viability of any given fetal thymus ? Now that a large number of abortions are carried out annually, it should be possible to make extracts of fetal thymus removed at varying ages and, by injecting them into mice, observe whether lymphocytosis results. Finally, I wonder how many doctors, as parents, would give informed consent to permit two experimental skin-grafting procedures and regional lymph-node biopsy in their own children presenting with a history of "... oral moniliasis, otitis media, recurrent upper and lower respiratory tract infections, and a deep-seated abscess of the skin ". Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, W. J. DEMPSTER. London W.12.

***This letter was shown to Dr. H. E. M. Kay, who replies also on behalf of his Boston colleagues.-ED. L. SiR,-Yes, and one might add that the cure of infections by injected extracts of a mould was equally incredible at one time. The final proof of the pudding is indeed in the eating, but, in the present case, there is additional evidence that thymic transplants can at least survive; this evidence

produced1 in answer to Mr. Dempster’s first letter in March last yearand I can only suggest that Mr. Dempster should come and see the slides himself. The main reason for the apparent delay in the development of immune capacity in the normal human fetus seems to be as follows: a measurable potential for immune reactivity is present from about 13 weeks of gestation forwards, but it is not realised before birth because there is very little antigenic stimulus until then. The protected environment of the fetus is seldom disturbed by foreign antigens, but when this occurs, as in toxoplasmosis or syphilis, or even by trespassing maternal serum-proteins of foreign allotype, immune reactions do take place. The situation is similar to that of the germ-free mouse whose lymphoid system does not develop in the same way as in a normal mouse. It would seem that, when all the other components and cirwas

1. 2.

Kay, H. E. M., Soothill, J. F. Lancet, 1969, i, 571. Dempster, W. J. ibid. p. 468.