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REVIEW OF CLINICAL NEURO-OPHTHALMOLOGY
31 REVIEW OF CLINICAL NEURO-OPHTHALMOLOGY
SIR,-It would
that there has been some mispurpose of the textbook of Clinical which was reviewed in your issue
seem
understanding of the
Neuro-Ophthalmology of Dec. 8 (p. 1302). The review states that " no clear impression emerges as to the intended readership ". Yet a glance at the first page of the book would reveal the answer that " it is intended primarily for post-graduates who are training in ophthalmology, neurology, neuro-surgery, and related fields ". Its scope and limitations the introduction. 36 Barnton Court, Edinburgh EH4 6EH.
are
defined in
BRYAN ASHWORTH.
CLOMIPHENE AND ANENCEPHALIC BIRTHS 1-3
of anencephalic births to mothers who had received clomiphene as an ovulatory stimulus are of interest. Dr Jamessuggested that mothers of anencephalics may be subfertile, thus explaining the association with clomiphene indirectly, on the basis of a lower incidence of anencephaly in illegitimate births and evidence for a longer marriage to conception interval in primiparous mothers of
SIR,-The reports
Data on the occurrence of both types of abnormal pregnancy in the same families would clarify this. With regard to the evidence for subfertility in mothers of anencephalics, this is as yet only suggestive. Record and McKeown 16 showed that 2-2% of 366 anencephalic births were illegitimate compared to 6-1% of all births, but the differences seen in the larger studies 1’ua are smaller and not statistically significant, although full correction for age, parity, and social class, which was not possible, would probably have increased the differences. The original suggestion 16 that such differences may reflect higher early abortion-rates in abnormal illegitimate pregnancies seems still likely, especially in view of the recent demonstration that differing early abortion rates can have large effects on the prevalence at birth of anencephaly." Obviously more information on the relationships between twinning, fertility, and neural-tube defects is desirable, and the possibility of a teratogenic effect of clomiphene should not be ignored. This work is supported by National Health and Welfare, Canada, and the Physicians’ Services Incorporated Foundation, Ontario. Department of Epidemiology, Ottawa University, 1145 Carling, Ottawa, Canada K1Z 7K4.
J. MARK ELWOOD.
anencephalics. This suggests an interesting contrast with mothers of dizygotic twins, who seem to be more fertile than normal. Dizygotic twinning has been shown to be more common in illegitimate births,5,6 in births conceived in the first three months of marriage, and in the early stage of the rapid rise in birth-rate in California in 1946 associated with the return of Servicemen from broad 1; and mothers of dizygotic twins have more pregnancies than others.8 This evidence has led to the concept that mothers of twins are more fertile than normal and this concept has provided an explanation for the rapid decreases seen in dizygotic twinning rates in the United Statesand in Canada 9 since the 1950s; these decreases have been associated with a rapid fall in birth-rate due to increasing use of all forms of contraception-a situation in which the excess contribution to total births previously made by this highly fertile group is diminished. If mothers of anencephalics are subfertile, their contribution to total births during this period of increasing birth control would be expected to increase, causing a rise in the incidence of anencephaly; however, the incidence is falling both in Canada 10 and in the United States,l1,l2 although it is rising in some other places-e.g., Chile 13 and Dublin. 14 Also dizygotic twinning rates and anencephaly incidence would be expected to be negatively correlated between populations, whereas in the only international15study where a positive both were ascertained by similar methods correlation of 0-578 (r < 0.01) between 24 centres was found. This latter finding suggests the alternative hypothesis that dizygotic twinning, which is due to double ovulation, and anencephaly may be associated, and perhaps clomiphene acts via a mechanism which increases the risk of both. 1. Dyson, J. L., Kohler, H. G. Lancet, 1973, i, 1256. 2. Sandier, B. ibid. 1973, ii, 379. 3. Barrett, C., Hakim, C. ibid. p. 916. 4. James, W. H. ibid. 5. Eriksson, A. W., Fellman, J. Hereditas, 1967, 57, 395. 6. Bulmer, M. G. Ann. hum. Genet. 1958, 23, 454. 7. Allen, G., Schachter, J. Soc. Biol. 1971, 18, 18. 8. Wyshak, G., White, C. Hum. Biol. 1969, 41, 66. 9. Elwood, J. M. Br. J. prev. soc. Med. 1973, 27, 236. 10. Elwood, J. M. Unpublished. 11. Gittelsohn, A. M., Milham, S. Br. J. prev. soc. Med. 1962, 16, 153. 12. MacMahon, B., Yen, S. Lancet, 1971, i, 31. 13. Cruz-Coke, R. ibid. 1972, ii, 1094. 14. Elwood, J. H. Int. J. Epidem. 1973, 2, 171. 15. Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., Golding, D. R. Bull. Wld Hlth Org. 1966, 34, suppl. 81.
ASPIRIN, PROSTAGLANDIN, AND GESTATION SIR,-Dr Lewis and Dr Schulman (Nov. 24, p. 1159) discussed their demonstration that gestation is prolonged in patients with arthritis taking aspirin in terms of prostaglandin metabolism at the end of pregnancy. On the other hand, perhaps the delay came much earlier, during the peri-implantation period. For example, when rats were fed a saturated solution of sodium salicylate acid, the development of the decidual cell reaction was much reduced on day 7 of pregnancy (day 0 was the day of sperm in the vagina).2O This experiment was performed because the decidual cell reaction to the invading blastocyst seemed to resemble the physiology of acute inflammation elsewhere in the body, as evidenced by the suppression of the increased capillary permeability to Evans-blue characteristic of the early hours of nidation 21 by sodium salicylate. 20 It may be that arthritics on aspirin have a decreased rate of deciduoma growth in the early weeks of gestation, as did the rat. The Willows, King’s Highway North, Westport, Connecticut 06880, U.S.A. 131
ANTHONY H. HORAN.
PSYCHIATRIC-GERIATRIC JOINT PATIENT UNIT p. "
SIR,-We congratulate Dr Arie and Dr Dunn (Dec. 8, 1313) on their initiative in solving the problem of misplaced " old people by developing a " joint patient
unit".
They mention
subject,
and
other methods of dealing with the should like to describe our arrangement, which is equally costless in money and personnel. In Brighton there is a unit for mentally ill old people, consisting of a day hospital and a 20-bed mixed inpatient ward. A system has been evolved in which there is close day-to-day liaison between the unit and the geriatric we
16. Record, R. G., McKeown, T. Br. J. soc. Med. 1949, 3, 183. 17. Edwards, J. H. Br. J. prev. soc. Med. 1958, 12, 115. 18. Record, R. G. ibid. 1961, 15, 93. 19. Roberts, C. J., Lloyd, S. Br. med. J. 1973, iv, 20. 20. Horan, A. H. Fertil. Steril. 1971, 22, 392. 21. Psychoyor, A. C.R. Acad. Sci. Paris, 1961, 252, 1515.
SIR,-It would
that there has been some mispurpose of the textbook of Clinical which was reviewed in your issue
seem
understanding of the
Neuro-Ophthalmology of Dec. 8 (p. 1302). The review states that " no clear impression emerges as to the intended readership ". Yet a glance at the first page of the book would reveal the answer that " it is intended primarily for post-graduates who are training in ophthalmology, neurology, neuro-surgery, and related fields ". Its scope and limitations the introduction. 36 Barnton Court, Edinburgh EH4 6EH.
are
defined in
BRYAN ASHWORTH.
CLOMIPHENE AND ANENCEPHALIC BIRTHS 1-3
of anencephalic births to mothers who had received clomiphene as an ovulatory stimulus are of interest. Dr Jamessuggested that mothers of anencephalics may be subfertile, thus explaining the association with clomiphene indirectly, on the basis of a lower incidence of anencephaly in illegitimate births and evidence for a longer marriage to conception interval in primiparous mothers of
SIR,-The reports
Data on the occurrence of both types of abnormal pregnancy in the same families would clarify this. With regard to the evidence for subfertility in mothers of anencephalics, this is as yet only suggestive. Record and McKeown 16 showed that 2-2% of 366 anencephalic births were illegitimate compared to 6-1% of all births, but the differences seen in the larger studies 1’ua are smaller and not statistically significant, although full correction for age, parity, and social class, which was not possible, would probably have increased the differences. The original suggestion 16 that such differences may reflect higher early abortion-rates in abnormal illegitimate pregnancies seems still likely, especially in view of the recent demonstration that differing early abortion rates can have large effects on the prevalence at birth of anencephaly." Obviously more information on the relationships between twinning, fertility, and neural-tube defects is desirable, and the possibility of a teratogenic effect of clomiphene should not be ignored. This work is supported by National Health and Welfare, Canada, and the Physicians’ Services Incorporated Foundation, Ontario. Department of Epidemiology, Ottawa University, 1145 Carling, Ottawa, Canada K1Z 7K4.
J. MARK ELWOOD.
anencephalics. This suggests an interesting contrast with mothers of dizygotic twins, who seem to be more fertile than normal. Dizygotic twinning has been shown to be more common in illegitimate births,5,6 in births conceived in the first three months of marriage, and in the early stage of the rapid rise in birth-rate in California in 1946 associated with the return of Servicemen from broad 1; and mothers of dizygotic twins have more pregnancies than others.8 This evidence has led to the concept that mothers of twins are more fertile than normal and this concept has provided an explanation for the rapid decreases seen in dizygotic twinning rates in the United Statesand in Canada 9 since the 1950s; these decreases have been associated with a rapid fall in birth-rate due to increasing use of all forms of contraception-a situation in which the excess contribution to total births previously made by this highly fertile group is diminished. If mothers of anencephalics are subfertile, their contribution to total births during this period of increasing birth control would be expected to increase, causing a rise in the incidence of anencephaly; however, the incidence is falling both in Canada 10 and in the United States,l1,l2 although it is rising in some other places-e.g., Chile 13 and Dublin. 14 Also dizygotic twinning rates and anencephaly incidence would be expected to be negatively correlated between populations, whereas in the only international15study where a positive both were ascertained by similar methods correlation of 0-578 (r < 0.01) between 24 centres was found. This latter finding suggests the alternative hypothesis that dizygotic twinning, which is due to double ovulation, and anencephaly may be associated, and perhaps clomiphene acts via a mechanism which increases the risk of both. 1. Dyson, J. L., Kohler, H. G. Lancet, 1973, i, 1256. 2. Sandier, B. ibid. 1973, ii, 379. 3. Barrett, C., Hakim, C. ibid. p. 916. 4. James, W. H. ibid. 5. Eriksson, A. W., Fellman, J. Hereditas, 1967, 57, 395. 6. Bulmer, M. G. Ann. hum. Genet. 1958, 23, 454. 7. Allen, G., Schachter, J. Soc. Biol. 1971, 18, 18. 8. Wyshak, G., White, C. Hum. Biol. 1969, 41, 66. 9. Elwood, J. M. Br. J. prev. soc. Med. 1973, 27, 236. 10. Elwood, J. M. Unpublished. 11. Gittelsohn, A. M., Milham, S. Br. J. prev. soc. Med. 1962, 16, 153. 12. MacMahon, B., Yen, S. Lancet, 1971, i, 31. 13. Cruz-Coke, R. ibid. 1972, ii, 1094. 14. Elwood, J. H. Int. J. Epidem. 1973, 2, 171. 15. Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., Golding, D. R. Bull. Wld Hlth Org. 1966, 34, suppl. 81.
ASPIRIN, PROSTAGLANDIN, AND GESTATION SIR,-Dr Lewis and Dr Schulman (Nov. 24, p. 1159) discussed their demonstration that gestation is prolonged in patients with arthritis taking aspirin in terms of prostaglandin metabolism at the end of pregnancy. On the other hand, perhaps the delay came much earlier, during the peri-implantation period. For example, when rats were fed a saturated solution of sodium salicylate acid, the development of the decidual cell reaction was much reduced on day 7 of pregnancy (day 0 was the day of sperm in the vagina).2O This experiment was performed because the decidual cell reaction to the invading blastocyst seemed to resemble the physiology of acute inflammation elsewhere in the body, as evidenced by the suppression of the increased capillary permeability to Evans-blue characteristic of the early hours of nidation 21 by sodium salicylate. 20 It may be that arthritics on aspirin have a decreased rate of deciduoma growth in the early weeks of gestation, as did the rat. The Willows, King’s Highway North, Westport, Connecticut 06880, U.S.A. 131
ANTHONY H. HORAN.
PSYCHIATRIC-GERIATRIC JOINT PATIENT UNIT p. "
SIR,-We congratulate Dr Arie and Dr Dunn (Dec. 8, 1313) on their initiative in solving the problem of misplaced " old people by developing a " joint patient
unit".
They mention
subject,
and
other methods of dealing with the should like to describe our arrangement, which is equally costless in money and personnel. In Brighton there is a unit for mentally ill old people, consisting of a day hospital and a 20-bed mixed inpatient ward. A system has been evolved in which there is close day-to-day liaison between the unit and the geriatric we
16. Record, R. G., McKeown, T. Br. J. soc. Med. 1949, 3, 183. 17. Edwards, J. H. Br. J. prev. soc. Med. 1958, 12, 115. 18. Record, R. G. ibid. 1961, 15, 93. 19. Roberts, C. J., Lloyd, S. Br. med. J. 1973, iv, 20. 20. Horan, A. H. Fertil. Steril. 1971, 22, 392. 21. Psychoyor, A. C.R. Acad. Sci. Paris, 1961, 252, 1515.