- Email: [email protected]
MORTALITY ASSOCIATED WITH THE PILL
1134 should thus be considered when there is mental deterioration during treatment for hyperthyroidism. Ewen Downie Metabolic Unit, Alfred Hospital, Prahran, Victoria, Australia
DUNCAN TOPLISS RODNEY BOND
pling.
women, aged 22 and 32, presented at our eye with sudden dilatation of one pupil which did not department react to light. They had no history of eye disease and ophthalmological examination was normal apart from a unilateral, almost completely dilated pupil, with no or very slight reaction to either direct or indirect light. The dilatation of the pupil disappeared within a few days and no eye symptoms recurred. Both patients had used ’Ercoril’ lotion (propantheline bromide) as an antiperspirant the day before. One remembered some of the lotion getting into the affected eye and the other, unaware of any risk to the eyes, had not washed her hands after using the lotion. Duke-Elder’ and Gokhale2found that 1% propantheline (’Pro-Banthine’) in the eyes produced mydriasis after 10-15 min which lasted 6-7 days. The accompanying paresis of the accommodation was slight. The effects of propantheline bromide on the eyes should be considered when the drug is used in the treatment of hyperhidrosis.
SIR,-Two
STEEN HOLST NISSEN PREBEN GILBERT NIELSEN
a
relationship between the type of fetal abnormalities produced and the timing of maternal warfarin ingestion is less clearly defined.3 We have seen a newborn male exposed to warfarin early in gestation who had malformations not previously associated with warfarin exposure. The boy was born weighing 3050 g after 39 weeks gestation. The mother, a 21-year-old White woman, had thrombophlebitis and was treated with warfarin and heparin during the first 6 weeks of pregnancy. She took no drugs during the rest of the pregnancy. At birth, the infant was cyanotic with short, broad distal phalanges and hypoplastic nails. Skeletal X-rays showed no stippled epiphyses. The nose structure was normal and there was no evidence of optic atrophy. Cardiac catheterisation revealed complex congenital heart-disease, including a single ventricle, left transposition of a single great artery, pulmonary atresia, patent ductus arteriosus, and partial anomalous pulmonary venous return. Necrotising enterocolitis with Escherichia coli sepsis developed and the infant died several days after birth. Necropsy revealed asplenia and a midline liver with two accessory lobes. The coeliac vessels were atretic, with a poorly developed mesentery and a partial failure of gut rotation. There was also atresia of the left colon. All of these malformations, with the exception of the hand abnormalities, are consistent with the asplenia syndrome." This syndrome has not been previously associated with fetal warfarin exposure. This is the fifth report of fetal warfarin exposure confined to the first trimester. 5--8 2 of the previous cases had phalangeal abnormalities similar to those in our patient. Skeletal X-rays were examined in 3 but only 1 had evidence of epiphyseal stip552. London, 1962.
3. Shaul, W. L., Hall, J. G. Am. J. Obstet. Gynec. 1977,127, 191. 4. Rose, V., Izukawa, T., Moës, C. A. F. Br. Heart J. 1975, 37, 840. 5. Holzgreve, W., Carey, J. C., Hall, B. D. Lancet, 1976, ii, 914.
defect, although
several in-
this exnosure. DAVID R. COX LILLIAN MARTIN BRYAN D. HALL
INDUCTION OF KERNICTERUS BY BUCOLOME IN RATS
SIR,-A barbituric product, 5-n-butyl-l-cyclohexyl-2,4,6trioxoperhydropyrimidine (bucolome), has been used to treat or prevent hyperbilirubinsemia in infants.l.2 We have studied the effects of bucolome in jaundiced rats and find that, thoughh the drug lowers the plasma-bilirubin, it induces kernicterus. 50 mg/kg body-weight sodium bucolome was injected subcutaneously into five 15-day-old jaundiced Gunn rats. Blood was sampled just before and 10 min and 1, 3, 6, and 24 h after the injection. The plasma-bilirubin, measured spectrophotometrically, fell from 10.0 to 2.1 mg/dl within 10 min of the injection and the lower concentration persisted for more than 24 h. At 24 h, two of the five rats were dead, and the remaining three had severe neurological signs. At necropsy, localised yellow staining of the brain including the basal ganglia (kernicterus) was found in all five animals. It is conceivable that bucolome displaced bilirubin from albumin, transferring bilirubin from plasma into tissues, including the brain. Although the drug lowers the bilirubin concentration, its use in the treatment or prevention of hyperbilirubinaemia in infants should be avoided.
ASPLENIA SYNDROME AFTER FETAL EXPOSURE TO WARFARIN
1. Duke-Elder, S. System of Ophthalmology; vol. VII; p. 2. Gokhale, A. M. Br. J. Ophthal. 1970, 54, 683.
heart
to
Department of Pediatrics, University of California, San Francisco, California 94143, U.S.A.
UNILATERAL MYDRIASIS AFTER USE OF PROPANTHELINE BROMIDE IN AN ANTIPERSPIRANT
SiR,—The teratogenic potential of warfarin is known but
a
warfarin for longer times during pregnancy have had minor cardiac abnormalities. 9, 10 The asplenia syndrome is though to result from damage to the fetus at about 30 days of gestation." Our patient was exposed to warfarin at this time, making it likely that all his malformations were due to
Department of Ophthalmology, Central Hospital, 6700 Esbjerg, Denmark
None of the 4 had
fants exposed
Department of Perinatology, Institute for Developmental Research, Aichi Prefectural Colony,
REIJI SEMBA
Kasugai, Aichi 480-03, Japan
HIROSHI SATO
Department of Anatomy, Mie University School of Medicine
HIDEKI YAMAMURA
MORTALITY ASSOCIATED WITH THE PILL
SIR,-Iwas glad to see some figures for the risks of oral contraceptives in your issue of Oct. 7. This is far better than qualieither that the pill is dangerous, which it is or that it is safe, which it is comIn view of the way in which the Press and television handle such news, however, a comparison which could be understood by ordinary people would have been useful. The overall risk of 1 death per year in 5000 women on the pill would, in twenty-five years, give a total of 1 in 200. This is about the same as the risk resulting from smoking three cigarettes a week. If you are a regular smoker and knock off one cigarette for each time you take a pill, you will be ahead on the deal. Doubtless there are people who prefer the cigartative
statements
compared with the sheath, pared with rock-climbing.
ettes, but others who do
not
do
so
may like
to
know the
rate
of exchange. Department of Physics, University of Birmingham, Birmingham B15 2TT
J. H. FREMLIN
6. Barr, M., Burdi, A. R. Teratology, 1976, 14, 129. 7. Holmes, L. B. ibid, 1975, 11, 22 (abstract). 8. O Connor, N. Unpublished. 9. Tejani, N. Obstet. Gynec. N.Y. 1973, 42, 785. 10. Collins, P., Olufs, R., Kravitz, H., Babakitis, M.
Am. J. Obstet. Gynec. 1977, 127, 444. 11. Landing, B. H., Lawrence, T. K., Payne V. C., Wells, T. R. Am. J. Cardiol. 1971, 28, 456. 1. Baba, K. Pediatrician, 1972, 1, 109. 2.
Segni, G., Polidori, G., Romagnoli, C. Archs Dis. Childh. 1977, 52, 549.
DUNCAN TOPLISS RODNEY BOND
pling.
women, aged 22 and 32, presented at our eye with sudden dilatation of one pupil which did not department react to light. They had no history of eye disease and ophthalmological examination was normal apart from a unilateral, almost completely dilated pupil, with no or very slight reaction to either direct or indirect light. The dilatation of the pupil disappeared within a few days and no eye symptoms recurred. Both patients had used ’Ercoril’ lotion (propantheline bromide) as an antiperspirant the day before. One remembered some of the lotion getting into the affected eye and the other, unaware of any risk to the eyes, had not washed her hands after using the lotion. Duke-Elder’ and Gokhale2found that 1% propantheline (’Pro-Banthine’) in the eyes produced mydriasis after 10-15 min which lasted 6-7 days. The accompanying paresis of the accommodation was slight. The effects of propantheline bromide on the eyes should be considered when the drug is used in the treatment of hyperhidrosis.
SIR,-Two
STEEN HOLST NISSEN PREBEN GILBERT NIELSEN
a
relationship between the type of fetal abnormalities produced and the timing of maternal warfarin ingestion is less clearly defined.3 We have seen a newborn male exposed to warfarin early in gestation who had malformations not previously associated with warfarin exposure. The boy was born weighing 3050 g after 39 weeks gestation. The mother, a 21-year-old White woman, had thrombophlebitis and was treated with warfarin and heparin during the first 6 weeks of pregnancy. She took no drugs during the rest of the pregnancy. At birth, the infant was cyanotic with short, broad distal phalanges and hypoplastic nails. Skeletal X-rays showed no stippled epiphyses. The nose structure was normal and there was no evidence of optic atrophy. Cardiac catheterisation revealed complex congenital heart-disease, including a single ventricle, left transposition of a single great artery, pulmonary atresia, patent ductus arteriosus, and partial anomalous pulmonary venous return. Necrotising enterocolitis with Escherichia coli sepsis developed and the infant died several days after birth. Necropsy revealed asplenia and a midline liver with two accessory lobes. The coeliac vessels were atretic, with a poorly developed mesentery and a partial failure of gut rotation. There was also atresia of the left colon. All of these malformations, with the exception of the hand abnormalities, are consistent with the asplenia syndrome." This syndrome has not been previously associated with fetal warfarin exposure. This is the fifth report of fetal warfarin exposure confined to the first trimester. 5--8 2 of the previous cases had phalangeal abnormalities similar to those in our patient. Skeletal X-rays were examined in 3 but only 1 had evidence of epiphyseal stip552. London, 1962.
3. Shaul, W. L., Hall, J. G. Am. J. Obstet. Gynec. 1977,127, 191. 4. Rose, V., Izukawa, T., Moës, C. A. F. Br. Heart J. 1975, 37, 840. 5. Holzgreve, W., Carey, J. C., Hall, B. D. Lancet, 1976, ii, 914.
defect, although
several in-
this exnosure. DAVID R. COX LILLIAN MARTIN BRYAN D. HALL
INDUCTION OF KERNICTERUS BY BUCOLOME IN RATS
SIR,-A barbituric product, 5-n-butyl-l-cyclohexyl-2,4,6trioxoperhydropyrimidine (bucolome), has been used to treat or prevent hyperbilirubinsemia in infants.l.2 We have studied the effects of bucolome in jaundiced rats and find that, thoughh the drug lowers the plasma-bilirubin, it induces kernicterus. 50 mg/kg body-weight sodium bucolome was injected subcutaneously into five 15-day-old jaundiced Gunn rats. Blood was sampled just before and 10 min and 1, 3, 6, and 24 h after the injection. The plasma-bilirubin, measured spectrophotometrically, fell from 10.0 to 2.1 mg/dl within 10 min of the injection and the lower concentration persisted for more than 24 h. At 24 h, two of the five rats were dead, and the remaining three had severe neurological signs. At necropsy, localised yellow staining of the brain including the basal ganglia (kernicterus) was found in all five animals. It is conceivable that bucolome displaced bilirubin from albumin, transferring bilirubin from plasma into tissues, including the brain. Although the drug lowers the bilirubin concentration, its use in the treatment or prevention of hyperbilirubinaemia in infants should be avoided.
ASPLENIA SYNDROME AFTER FETAL EXPOSURE TO WARFARIN
1. Duke-Elder, S. System of Ophthalmology; vol. VII; p. 2. Gokhale, A. M. Br. J. Ophthal. 1970, 54, 683.
heart
to
Department of Pediatrics, University of California, San Francisco, California 94143, U.S.A.
UNILATERAL MYDRIASIS AFTER USE OF PROPANTHELINE BROMIDE IN AN ANTIPERSPIRANT
SiR,—The teratogenic potential of warfarin is known but
a
warfarin for longer times during pregnancy have had minor cardiac abnormalities. 9, 10 The asplenia syndrome is though to result from damage to the fetus at about 30 days of gestation." Our patient was exposed to warfarin at this time, making it likely that all his malformations were due to
Department of Ophthalmology, Central Hospital, 6700 Esbjerg, Denmark
None of the 4 had
fants exposed
Department of Perinatology, Institute for Developmental Research, Aichi Prefectural Colony,
REIJI SEMBA
Kasugai, Aichi 480-03, Japan
HIROSHI SATO
Department of Anatomy, Mie University School of Medicine
HIDEKI YAMAMURA
MORTALITY ASSOCIATED WITH THE PILL
SIR,-Iwas glad to see some figures for the risks of oral contraceptives in your issue of Oct. 7. This is far better than qualieither that the pill is dangerous, which it is or that it is safe, which it is comIn view of the way in which the Press and television handle such news, however, a comparison which could be understood by ordinary people would have been useful. The overall risk of 1 death per year in 5000 women on the pill would, in twenty-five years, give a total of 1 in 200. This is about the same as the risk resulting from smoking three cigarettes a week. If you are a regular smoker and knock off one cigarette for each time you take a pill, you will be ahead on the deal. Doubtless there are people who prefer the cigartative
statements
compared with the sheath, pared with rock-climbing.
ettes, but others who do
not
do
so
may like
to
know the
rate
of exchange. Department of Physics, University of Birmingham, Birmingham B15 2TT
J. H. FREMLIN
6. Barr, M., Burdi, A. R. Teratology, 1976, 14, 129. 7. Holmes, L. B. ibid, 1975, 11, 22 (abstract). 8. O Connor, N. Unpublished. 9. Tejani, N. Obstet. Gynec. N.Y. 1973, 42, 785. 10. Collins, P., Olufs, R., Kravitz, H., Babakitis, M.
Am. J. Obstet. Gynec. 1977, 127, 444. 11. Landing, B. H., Lawrence, T. K., Payne V. C., Wells, T. R. Am. J. Cardiol. 1971, 28, 456. 1. Baba, K. Pediatrician, 1972, 1, 109. 2.
Segni, G., Polidori, G., Romagnoli, C. Archs Dis. Childh. 1977, 52, 549.