49 examination of the literature has not been exhaustive, and it is therefore possible that other cases exist. Anaphylaxis to 3 trasvlol may occur with the first course of treatment. Trasvlol may turn out to be a useful drug in acute pancreauus. fhe manufacturer’s indications for trasylol are very wide, and we would remind all users of the drug to bear in mind that its use carries definite risks. These risks will become more apparent if the drug becomes more widely used. The drug is still under evaluation by the M.R.C. so it cannot be considered to be of proven value. Thus particular care in its use is advisable, and we recommend that if there is any doubt about potential allergy intradermal skin testing should be carried out.’ In view of the fact that allergy may appear on a first course there is probably a case for skin-testing all patients before administering the drug. We also suggest that the data sheet and prescribing information supplied with the drug be revised. Department of Surgery, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
G. PROUD
J. CHAMBERLAIN
TRANEXAMIC ACID AND INTRACRANIAL THROMBOSIS
SIR,-Fibrinolysis is the process by which fibrinogen and are degraded by the proteolytic enzyme plasmin, promoting the resolution of thrombi. Activators in the plasma and in vessel walls convert plasminogen to plasmin. Antifibrinolytic drugs might upset this mechanism by their inhibitory effect on the activation of plasminogen. Theoretically, therefore, the administration of antifibrinolytic agents could facilitate the development of a thrombosis. fibrin
We have seen two cases of intracranial arterial thrombosis in young women taking the antifibrinolytic drug tranexamic acid (’Cyklokapron’). In both cases the drug had been prescribed for menorrhagia and had been taken during the days of
Case 2
32-year-old woman, with no previous illnesses apart from migraine since puberty, had been taking 0.5-1 g tranexamic acid/day during her menstrual periods for about a year. At midcycle in June, 1975, she woke up one night with a severe headache, and her left arm and leg felt "numb". The next day she developed a left-sided hemiparesis and a homonymous hemianopia to the left. Carotid angiography revealed thrombosis of the right posterior cerebral artery. c.s.F. was normal. Thrombocytes 1 week later were 540x 109/1, otherwise the laboratory findings were normal. In September, 1975, some left-sided weakness, dysaesthesia, and hemianopia still perA
sisted. At that time her laboratory tests, including thrombocytes (18410"/1), were normal. Both our patients had an initial thrombocytosis which in itself could have predisposed to thrombosis. The ansemia and bronchopneumonia in case 1 might have explained the reversible thrombocytosis. In neither case did we find evidence of any underlying disease that could have been thrombogenic. The connection between the taking of tranexamic acid and the vascular lesions in these patients may have been fortuitous. So far we have been unable to find any earlier reports of cerebral lesions in young women taking antifibrinolytic drugs. When given after a subarachnoid haemorrhage, however, they have been reported to increase the risk of "ischaEmic complications".’.1 Tranexamic acid, at least in Sweden, is given to an increasing number of young women routinely to prevent uterine bleeding in connection with intrauterine contraceptive devices (LU.D.S). Ironically one reason for a change from oral-contraceptive drugs to LU.D.S is the fear of side-effects of the pill, mainly thromboembolic diseases. Department of Neurology, University Hospital, Fack, S-750 14, Uppsala, Sweden
E. RYDIN P. O. LUNDBERG
bleeding. Case1 A 31-year-old woman, previously healthy, developed uterine myomas with menorrhagia, resulting in severe anaemia. For one year she had been taking tranexamic acid (3-4. g/day) during the days of blood-loss. In the middle of June, 1975, the was treated with doxycycline (’Vibramycin’) for bronchopneumonia. Her menstruation started on June 18 and from June 19 she took tranexamic acid continuously until June 27. On June 20 she experienced a transitory weakness of her left hand, lasting a few minutes. On June 27 she woke to find that she could not move her left arm and leg. The skin sensibilItv on the same side was also impaired. On admission to hospital on the same day the symptoms had already regressed considerably, but parmsthesia and numbness in her left cheek persisted for several days. An E.E.G. on arrival confirmed a right-sided cerebral lesion, and showed clear regression when repeated 3 days later. Carotid angiography on July 16 revealed circulatory impairment within one of the posterior peripheral branches of the right middle cerebral artery. The results of relevant laboratory tests on admission were: Hb 9.22 edl, E.S.R. 67 mm in lst h, thrombocytes 700x 109/1, C.S.F. normal. Coagulation tests on July 8, including a test of thrombocyte function, revealed a slight increase in fibrin-degradation products, 10-20 mg/1 (normally less than 10 mg/1), indicating fibrinolysis. This was interpreted as a physiological response to the vascular lesion. Otherwise coagulation tests were normal. The patient’s hospital course was uneventful. She was discharged after 1 month with no residual symptoms. Hb at that time was 10.2 g/dl, E.S.R. 37 mm in lst h and plate-
patient
n-count 232x10/1.She has remained well and has a
rv,5trcctomy. 5 Br. med. J 1966, ii, 1580
now
CORTICOSTEROIDS, SALBUTAMOL, AND R.D.S. SIR,-I wish to contribute to the discussion opened by Weiss and Pughabout the prevention of respiratory-distress syndrome (R.D.S.) by corticosteroids and/or beta-sympathomimetic drugs. In a 24-year-old nullipara, whose pregnancy had been induced by human menopausal gonadotrophin, twins were diagnosed by ultrasound echography at 15 weeks’ gestation. A previous hysterography had revealed an incompetent cervix, and Shirodkar’s technique had been done at 16 weeks’ gestation. The patient was followed up twice a month and the pregnancy proceeded normally until the 29th week, when spontaneous rupture of the membranes occurred. An intramuscular dose of 12 mg of betamethasone was given immediately and repeated 48 h later. High doses of salbutamol were also administered intravenously for 3 weeks, to a total dose of 210 mg. The patient went into labour at 32 weeks gestation. The first twin was a 1620 g girl with no respiratory problem. The second twin, whose amniotic sac was intact, weighed 1990 g and developed R.D.S. (state 2). In this case neither corticosteroids nor high doses of a betasympathomimetic drug administered continuously for 3 weeks were able to prevent R.D.S. in the second twin. On the other hand there is strong evidence that prolonged rupture of the amniotic membranes of the first twin induced fetal lung maturation and that this does prevent R.D.S.3 This case does not permit any conclusions to be drawn about the efficacy of corticosteroids in the prevention of R.D.S. (the
had 1. Kågström, E. Ospedale Miulli, 1971,1, 16. 2. Weiss, D. B., Pugh, C. Lancet, 1976, i, 1296. 3. Rouvillois, J. L., Papiernik, E., Amiel-Tison, C. repr. 1973, 2, 271
J. Gynec.
Obstet. Biol.
50 dose might have been insufficient for a twin pregnancy), and further studies will certainly be of great interest. However, I do not think that this case supports the hypothesis of a determinative role for beta-sympathomimetic drugs in fetal lung maturation. Service de Gynécologie Obstétrique, Höpital Antoine Beclère, 9240
Clamart, France
LUCIEN SCHNEIDER
PRENATAL DIAGNOSIS OF MAROTEAUX-LAMY SYNDROME
SIR,--The Maroteaux-Lamy syndrome,
or
mucopolysac-
charidosis type vi (M.P.S. vi), is an autosomal recessive disorder characterised by severe skeletal deformities, growth retardation, and corneal opacity. The basic defect is a deficiency of the lysosomal enzyme arylsulphatase B (A.S.B.).1 Both A.s.B deficiency2 and an accumulation of sulphated mucopolysaccharides3 have been demonstrated in cultured skin fibroblasts from ht.P.s. vi patients. Since A.s.B activity is measurable in cultured amniotic-fluid cells4 prenatal diagnosis should be possible. We have investigated the second pregnancy of a woman whose first child had M.P.S. vi, established by the demonstration of A.s.B deficiency in leucocytes (Dr K. 0. Liem, Free ARYLSULPHATASE A AND B ACTIVITIES IN CULTURED AMNIOTIC-FLUID CELLS AND FIBROBLASTS
4 days of incorporation, fibroblasts from the index patient and amniotic-fluid cells from the pregnancy at risk showed a threefold raised level of labelled intracellular mucopolysaccharides as compared with controls. The parents decided on termination of pregnancy at the 20th week. Confirmatory studies were done on fetal liver and skin by separation of A.s.A and A.s.B2 on a D.E.A.E.-column and measurement of activities with 4-methylumbelliferyl sulphate as the substrate. In a control fetal liver 58% of the total A.S. activity was found in the B peak. In contrast the A.s.B activity in the liver of the affected fetus was reduced to 8% of the total arylsulphatase activity. Similar results, confirming A.s.B deficiency in this fetus, were obtained with the fetal skin. These results demonstrate that a reliable prenatal diagnosis ofM.p.s. vi is possible and can be completed within 2-3 weeks after amniocentesis if microtechniques are used. Dr
J. J. M.
van
Gemund (University Hospital, Leiden), referred this financed in part by Het Praeventiefonds, the
family. This study was Hague, Netherlands.
Department of Cell Biology and Genetics Erasmus University Rotterdam, P.O. Box 1738, Rotterdam, Netherlands
W. J. KLEIJER G. M. WOLFFERS A. HOOGEVEEN M. F. NIERMEIJER
CHOLINERGIC SIDE-EFFECTS ASSOCIATED WITH DEANOL
SIR The drug deanol (2-dimethylaminoethanol) has been reported to be useful in the management of several neurological problems, including learning disorders and hyperkinesis of childhood, levodopa-induced dyskinesias, Huntington’s chorea, and
some cases of tardive dyskinesia.1-3 Deanol is be effective in these conditions through its conversion in vivo to choline and acetylcholine. High doses (above 1 g per day in adults) given for at least 3 weeks are required before the efficacy of the drug can be determined.’ Side-effects have not been prominent with this drug. We wish to report the occurrence of serious cholinergic side-effects in one patient. The patient was a 37-year-old woman who had tardive dyskinesia of 4 years’ duration, which had not responded to other drugs. She had grotesque oral, lingual, and buccal movements which had caused her to break several teeth and to bite her tongue occasionally. These movements would cease temporarily upon voluntary actions such as forced protrusion of the tongue, but she experienced difficulty with chewing and swallowing, and she would frequently spit rather than swallow her saliva. Deanol was given for 19 days in increasing doses. After 17 days, while receiving 1500 mg per day, the patient began to have increased nasal and oral secretions. Within 2 more days she complained of dyspnoea and was having obvious respiratory difficulty. Examination disclosed rhinorrhcea, sialorrhoea, a respiratory-rate of 25/min, a pulse-rate of 100/min, and unchanged blood-pressure. Diffuse rhonchi and moderate expiratory wheezing were heard in both lung fields; many upper airway sounds also were present. She was afebrile, and a blood-count revealed no evidence of infection. A chest film taken at the time showed only changes consistent with chronic obstructive pulmonary disease (the woman was a heavy smoker). Deanol was discontinued, and within 16 h the patient reported improvement in her symptoms; objectively the lungs had cleared considerably. By the second day after the drug was stopped the lungs were clear, the rhinorrhoea and sialorrhœa had stopped, and the patient had returned to her previous
thought
*Average activity (nmol h-l mg ’ protein of triplicate determinations). tCultures used in the analyses were matched for duration of cell-culture and number of subcultures.
and in cultured fibroblasts. Amniodone in the 16th week of pregnancy (Dr H. B. Rethmeyer, Sophia Hospital, Zwolle) and amniotic-fluid cells were cultured.5 After 16 days of growth, the cells were harvested, homogenised by sonication, and analysed for A.s.B activity using a micromodification of the method of Baum et al.6 Only 5 jjd of cell homogenate (about 104 cells) was used per incubation with 4-nitrocatechol sulphate as the substrate; the amount of 4-nitrocatechol produced was measured in a final volume of 55 µl.7 The specific activities of A.s.B (table) showed a deficiency in the amniotic-fluid cells from the pregnancy at risk as well as in the fibroblasts from the index patient. The activities of A.s.A, measured as a control lysosomal enzyme, seemed normal. Additional evidence, demonstrating that the fetus was affected, was obtained from the study of 35S-sulphate incorporation into the intracellular mucopolysaccharide pools.8 After
University, Amsterdam) centesis
1.
was
Stumpf, D. A., Austin, J. H., Crocker, A. C., LaFrance, M. Am. J. Dis.
Child.
1973, 126, 747. 2. Fluharty, A. L., Stevens, R. L., Sanders, D L., Kihara, H. Biochim. biophys. Res. Commun. 1974, 59, 455. 3 Barton, R. W., Nuefeld, E. F. J. Pediatrics, 1972, 80, 114. 4. Beratis, N. G., Turner, B. M., Weiss, R., Hirschhorn, K. Pediat. Res. 1975, 9, 475. 5. Niermeijer, M. F., Koster, J. F., Jahodova, M., Fernandes, J., HeukelsDully, M. J., Galjaard, H. ibid. 1975, 9, 498. 6 Baum, H., Dodgson, K. S., Spencer, B. Clinica. Chim. Acta, 1959, 4, 453. 7. Galjaard, H., Hoogstraten, J. J. van, de Josselin de Jong, J. E., Mulder, M. P. Histochem. J. 1974, 6, 409. 8. Fratantoni, J. C., Hall, C. W., Neufeld, E. F. Proc. natn. Acad. Sci. U.S.A. 1969, 64, 360.
to
status.
These side-effects of a cholinergic nature suggest that deanol may indeed act in man by conversion to choline and 1. Re, O. Curr. ther. Res. 1974, 16, 1238. 2. Miller, E. M. New Engl. J. Med. 1974, 291, 796. 3. Escobar, J. I., Kemp, J. F. ibid. 1975, 292, 317.
G. PROUD
J. CHAMBERLAIN
TRANEXAMIC ACID AND INTRACRANIAL THROMBOSIS
SIR,-Fibrinolysis is the process by which fibrinogen and are degraded by the proteolytic enzyme plasmin, promoting the resolution of thrombi. Activators in the plasma and in vessel walls convert plasminogen to plasmin. Antifibrinolytic drugs might upset this mechanism by their inhibitory effect on the activation of plasminogen. Theoretically, therefore, the administration of antifibrinolytic agents could facilitate the development of a thrombosis. fibrin
We have seen two cases of intracranial arterial thrombosis in young women taking the antifibrinolytic drug tranexamic acid (’Cyklokapron’). In both cases the drug had been prescribed for menorrhagia and had been taken during the days of
Case 2
32-year-old woman, with no previous illnesses apart from migraine since puberty, had been taking 0.5-1 g tranexamic acid/day during her menstrual periods for about a year. At midcycle in June, 1975, she woke up one night with a severe headache, and her left arm and leg felt "numb". The next day she developed a left-sided hemiparesis and a homonymous hemianopia to the left. Carotid angiography revealed thrombosis of the right posterior cerebral artery. c.s.F. was normal. Thrombocytes 1 week later were 540x 109/1, otherwise the laboratory findings were normal. In September, 1975, some left-sided weakness, dysaesthesia, and hemianopia still perA
sisted. At that time her laboratory tests, including thrombocytes (18410"/1), were normal. Both our patients had an initial thrombocytosis which in itself could have predisposed to thrombosis. The ansemia and bronchopneumonia in case 1 might have explained the reversible thrombocytosis. In neither case did we find evidence of any underlying disease that could have been thrombogenic. The connection between the taking of tranexamic acid and the vascular lesions in these patients may have been fortuitous. So far we have been unable to find any earlier reports of cerebral lesions in young women taking antifibrinolytic drugs. When given after a subarachnoid haemorrhage, however, they have been reported to increase the risk of "ischaEmic complications".’.1 Tranexamic acid, at least in Sweden, is given to an increasing number of young women routinely to prevent uterine bleeding in connection with intrauterine contraceptive devices (LU.D.S). Ironically one reason for a change from oral-contraceptive drugs to LU.D.S is the fear of side-effects of the pill, mainly thromboembolic diseases. Department of Neurology, University Hospital, Fack, S-750 14, Uppsala, Sweden
E. RYDIN P. O. LUNDBERG
bleeding. Case1 A 31-year-old woman, previously healthy, developed uterine myomas with menorrhagia, resulting in severe anaemia. For one year she had been taking tranexamic acid (3-4. g/day) during the days of blood-loss. In the middle of June, 1975, the was treated with doxycycline (’Vibramycin’) for bronchopneumonia. Her menstruation started on June 18 and from June 19 she took tranexamic acid continuously until June 27. On June 20 she experienced a transitory weakness of her left hand, lasting a few minutes. On June 27 she woke to find that she could not move her left arm and leg. The skin sensibilItv on the same side was also impaired. On admission to hospital on the same day the symptoms had already regressed considerably, but parmsthesia and numbness in her left cheek persisted for several days. An E.E.G. on arrival confirmed a right-sided cerebral lesion, and showed clear regression when repeated 3 days later. Carotid angiography on July 16 revealed circulatory impairment within one of the posterior peripheral branches of the right middle cerebral artery. The results of relevant laboratory tests on admission were: Hb 9.22 edl, E.S.R. 67 mm in lst h, thrombocytes 700x 109/1, C.S.F. normal. Coagulation tests on July 8, including a test of thrombocyte function, revealed a slight increase in fibrin-degradation products, 10-20 mg/1 (normally less than 10 mg/1), indicating fibrinolysis. This was interpreted as a physiological response to the vascular lesion. Otherwise coagulation tests were normal. The patient’s hospital course was uneventful. She was discharged after 1 month with no residual symptoms. Hb at that time was 10.2 g/dl, E.S.R. 37 mm in lst h and plate-
patient
n-count 232x10/1.She has remained well and has a
rv,5trcctomy. 5 Br. med. J 1966, ii, 1580
now
CORTICOSTEROIDS, SALBUTAMOL, AND R.D.S. SIR,-I wish to contribute to the discussion opened by Weiss and Pughabout the prevention of respiratory-distress syndrome (R.D.S.) by corticosteroids and/or beta-sympathomimetic drugs. In a 24-year-old nullipara, whose pregnancy had been induced by human menopausal gonadotrophin, twins were diagnosed by ultrasound echography at 15 weeks’ gestation. A previous hysterography had revealed an incompetent cervix, and Shirodkar’s technique had been done at 16 weeks’ gestation. The patient was followed up twice a month and the pregnancy proceeded normally until the 29th week, when spontaneous rupture of the membranes occurred. An intramuscular dose of 12 mg of betamethasone was given immediately and repeated 48 h later. High doses of salbutamol were also administered intravenously for 3 weeks, to a total dose of 210 mg. The patient went into labour at 32 weeks gestation. The first twin was a 1620 g girl with no respiratory problem. The second twin, whose amniotic sac was intact, weighed 1990 g and developed R.D.S. (state 2). In this case neither corticosteroids nor high doses of a betasympathomimetic drug administered continuously for 3 weeks were able to prevent R.D.S. in the second twin. On the other hand there is strong evidence that prolonged rupture of the amniotic membranes of the first twin induced fetal lung maturation and that this does prevent R.D.S.3 This case does not permit any conclusions to be drawn about the efficacy of corticosteroids in the prevention of R.D.S. (the
had 1. Kågström, E. Ospedale Miulli, 1971,1, 16. 2. Weiss, D. B., Pugh, C. Lancet, 1976, i, 1296. 3. Rouvillois, J. L., Papiernik, E., Amiel-Tison, C. repr. 1973, 2, 271
J. Gynec.
Obstet. Biol.
50 dose might have been insufficient for a twin pregnancy), and further studies will certainly be of great interest. However, I do not think that this case supports the hypothesis of a determinative role for beta-sympathomimetic drugs in fetal lung maturation. Service de Gynécologie Obstétrique, Höpital Antoine Beclère, 9240
Clamart, France
LUCIEN SCHNEIDER
PRENATAL DIAGNOSIS OF MAROTEAUX-LAMY SYNDROME
SIR,--The Maroteaux-Lamy syndrome,
or
mucopolysac-
charidosis type vi (M.P.S. vi), is an autosomal recessive disorder characterised by severe skeletal deformities, growth retardation, and corneal opacity. The basic defect is a deficiency of the lysosomal enzyme arylsulphatase B (A.S.B.).1 Both A.s.B deficiency2 and an accumulation of sulphated mucopolysaccharides3 have been demonstrated in cultured skin fibroblasts from ht.P.s. vi patients. Since A.s.B activity is measurable in cultured amniotic-fluid cells4 prenatal diagnosis should be possible. We have investigated the second pregnancy of a woman whose first child had M.P.S. vi, established by the demonstration of A.s.B deficiency in leucocytes (Dr K. 0. Liem, Free ARYLSULPHATASE A AND B ACTIVITIES IN CULTURED AMNIOTIC-FLUID CELLS AND FIBROBLASTS
4 days of incorporation, fibroblasts from the index patient and amniotic-fluid cells from the pregnancy at risk showed a threefold raised level of labelled intracellular mucopolysaccharides as compared with controls. The parents decided on termination of pregnancy at the 20th week. Confirmatory studies were done on fetal liver and skin by separation of A.s.A and A.s.B2 on a D.E.A.E.-column and measurement of activities with 4-methylumbelliferyl sulphate as the substrate. In a control fetal liver 58% of the total A.S. activity was found in the B peak. In contrast the A.s.B activity in the liver of the affected fetus was reduced to 8% of the total arylsulphatase activity. Similar results, confirming A.s.B deficiency in this fetus, were obtained with the fetal skin. These results demonstrate that a reliable prenatal diagnosis ofM.p.s. vi is possible and can be completed within 2-3 weeks after amniocentesis if microtechniques are used. Dr
J. J. M.
van
Gemund (University Hospital, Leiden), referred this financed in part by Het Praeventiefonds, the
family. This study was Hague, Netherlands.
Department of Cell Biology and Genetics Erasmus University Rotterdam, P.O. Box 1738, Rotterdam, Netherlands
W. J. KLEIJER G. M. WOLFFERS A. HOOGEVEEN M. F. NIERMEIJER
CHOLINERGIC SIDE-EFFECTS ASSOCIATED WITH DEANOL
SIR The drug deanol (2-dimethylaminoethanol) has been reported to be useful in the management of several neurological problems, including learning disorders and hyperkinesis of childhood, levodopa-induced dyskinesias, Huntington’s chorea, and
some cases of tardive dyskinesia.1-3 Deanol is be effective in these conditions through its conversion in vivo to choline and acetylcholine. High doses (above 1 g per day in adults) given for at least 3 weeks are required before the efficacy of the drug can be determined.’ Side-effects have not been prominent with this drug. We wish to report the occurrence of serious cholinergic side-effects in one patient. The patient was a 37-year-old woman who had tardive dyskinesia of 4 years’ duration, which had not responded to other drugs. She had grotesque oral, lingual, and buccal movements which had caused her to break several teeth and to bite her tongue occasionally. These movements would cease temporarily upon voluntary actions such as forced protrusion of the tongue, but she experienced difficulty with chewing and swallowing, and she would frequently spit rather than swallow her saliva. Deanol was given for 19 days in increasing doses. After 17 days, while receiving 1500 mg per day, the patient began to have increased nasal and oral secretions. Within 2 more days she complained of dyspnoea and was having obvious respiratory difficulty. Examination disclosed rhinorrhcea, sialorrhoea, a respiratory-rate of 25/min, a pulse-rate of 100/min, and unchanged blood-pressure. Diffuse rhonchi and moderate expiratory wheezing were heard in both lung fields; many upper airway sounds also were present. She was afebrile, and a blood-count revealed no evidence of infection. A chest film taken at the time showed only changes consistent with chronic obstructive pulmonary disease (the woman was a heavy smoker). Deanol was discontinued, and within 16 h the patient reported improvement in her symptoms; objectively the lungs had cleared considerably. By the second day after the drug was stopped the lungs were clear, the rhinorrhoea and sialorrhœa had stopped, and the patient had returned to her previous
thought
*Average activity (nmol h-l mg ’ protein of triplicate determinations). tCultures used in the analyses were matched for duration of cell-culture and number of subcultures.
and in cultured fibroblasts. Amniodone in the 16th week of pregnancy (Dr H. B. Rethmeyer, Sophia Hospital, Zwolle) and amniotic-fluid cells were cultured.5 After 16 days of growth, the cells were harvested, homogenised by sonication, and analysed for A.s.B activity using a micromodification of the method of Baum et al.6 Only 5 jjd of cell homogenate (about 104 cells) was used per incubation with 4-nitrocatechol sulphate as the substrate; the amount of 4-nitrocatechol produced was measured in a final volume of 55 µl.7 The specific activities of A.s.B (table) showed a deficiency in the amniotic-fluid cells from the pregnancy at risk as well as in the fibroblasts from the index patient. The activities of A.s.A, measured as a control lysosomal enzyme, seemed normal. Additional evidence, demonstrating that the fetus was affected, was obtained from the study of 35S-sulphate incorporation into the intracellular mucopolysaccharide pools.8 After
University, Amsterdam) centesis
1.
was
Stumpf, D. A., Austin, J. H., Crocker, A. C., LaFrance, M. Am. J. Dis.
Child.
1973, 126, 747. 2. Fluharty, A. L., Stevens, R. L., Sanders, D L., Kihara, H. Biochim. biophys. Res. Commun. 1974, 59, 455. 3 Barton, R. W., Nuefeld, E. F. J. Pediatrics, 1972, 80, 114. 4. Beratis, N. G., Turner, B. M., Weiss, R., Hirschhorn, K. Pediat. Res. 1975, 9, 475. 5. Niermeijer, M. F., Koster, J. F., Jahodova, M., Fernandes, J., HeukelsDully, M. J., Galjaard, H. ibid. 1975, 9, 498. 6 Baum, H., Dodgson, K. S., Spencer, B. Clinica. Chim. Acta, 1959, 4, 453. 7. Galjaard, H., Hoogstraten, J. J. van, de Josselin de Jong, J. E., Mulder, M. P. Histochem. J. 1974, 6, 409. 8. Fratantoni, J. C., Hall, C. W., Neufeld, E. F. Proc. natn. Acad. Sci. U.S.A. 1969, 64, 360.
to
status.
These side-effects of a cholinergic nature suggest that deanol may indeed act in man by conversion to choline and 1. Re, O. Curr. ther. Res. 1974, 16, 1238. 2. Miller, E. M. New Engl. J. Med. 1974, 291, 796. 3. Escobar, J. I., Kemp, J. F. ibid. 1975, 292, 317.
