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ASPIRIN DOSE IN PREVENTION OF TRANSIENT ISCHÆMIC ATTACKS
830 tients has proved a useful, if rough, guide for those concerned with anticoagulant control in this laboratory. Department of Pathology, Royal Victoria Hospital, Bournemouth BH1 4JG
P.
J. GREEN
this suggests potential synergy between caffeine and theophylline in respect of toxic effects. During treatment with theophylline in the neonatal period the plasma concentrations of the different methylxanthines should be carefully monitored.
MARIE-JEANNE BOUTROY PAUL VERT PIERRE MONIN RENÉ JEAN ROYER
Service de Médecine Néonatale, Maternité Régionale,
METHYLATION OF THEOPHYLLINE TO CAFFEINE IN PREMATURE INFANTS Claudette SIR,-Like Bory and her colleagues’ we too have observed the biotransformation of theophylline to caffeine in the premature infant. We used to give theophylline orally as a 10% alcoholic solution for the treatment of idiopathic apnoea of prematurity. We have studied the kinetics of methylxanthines in plasma in 25 infants treated with theophylline. The infants had had a mean gestational age of 31±2 weeks (±s.D.); a mean birth-weight of 1636+328 g; and their age at the onset of therapy was 60±120 h. Methylxanthines were investigated by gas chromatography, before and after flash methylation, on 100 ul
of plasma.
University of Nancy I, 54042 Nancy, France
i .
MARIE-JOSÉE ROYER-MORROT
ASPIRIN DOSE IN PREVENTION OF TRANSIENT ISCHÆMIC ATTACKS SIR,-Aspirin has been introduced as a potent inhibitor of atelet aggregation and the dosage has been discussed by ’Grady and Moncada’ and by Rajah et al.1 Low doses, at ast below 1 g daily, have been recommended selectively to inibit thromboxane Az more than prostacyclin. Aspirin can lower the frequency of transient ischxmic :tacks (T.I.A.)3 and prevent cerebral infarction in patients ith T.I.A.4 We usually give T.I.A. patients prophylactic treatient with dicoumarols but in some patients we have een trying prophylaxis with aspirin combined with dipyridaole after a short initial period with anticoagulants.
elderly
rig.
jl-iriasma
treatment
Fig.
ileveis
oi
memymaninmes
oeiofe
ana
aurmg
with theophylline.
1
..a...ca.
l’AI.L."".a.-U
T.I.A.S
2-Plasma levels of caffeine in toxic and non-toxic infants.
indicated
av
aayu-au
uvace
by arrows.
One patient showed a remarkable sensitivity to aspirin dose; In 24 cases out of 25 there was a steady increase in plasmacaffeine during the administration of theophylline (fig. 1), consl ie had new T.I.A.S when the salicylate level of blood deccentrations rising from 1-3±1-2 mg/1 before treatment (reri ased. At a dose of 2 g daily the patient has always been free 0 ’ T.I.A. (see figure). T.I.A.s appeared when the patient had flecting the maternal caffeine acquired transplacentally) to 3-9+2.0mg/1 after five days of treatment (p<0-001). The lackr :ceived L 0 or 1 - 5 g aspirin daily for some months. The blood of an increase in plasma-caffeine in a group of 12 premature 1 vels of salicylate decreased and T.I.A.s appeared usually when babies fed human milk for 6 days and not receiving theophylt Ie level was at or below 0. 1 mmol/l. The T. I.A. ceased when line rules out exogenous (nutritional) caffeine as the explanat e aspirin was increased. The need for increasing dosages of aspirin to keep patients tion. Premature babies given blood-transfusions would not f ’ee from T.I.A.s has been noticed in other patients, and in receive more than 0-13 mg/day of methylxanthine in this way. c inical practice it seems that some patients will need higher We have also studied the consequences of this methylation c oses than those commonly recommended on the basis of of theophylline to caffeine on the toxic manifestations usually 1 boratory tests. attributed to theophylline (gastrointestinal problems, tachycardia, jitteriness). We found2 that plasma-caffeine, though 1 epartment of Neurology, within the therapeutic range, was significantly higher 1 Department of Neurology, (P<0.01) in the infants with signs of toxicity than in those University Hospital, without such signs (5-5±2-1 versus 3-1+1.3 mg/1). The S-221 85 Lund, Sweden JAN-EDVIN OLSSON plasma concentrations of theophylline and total methylxan1. O’Grady, J., Moncada, S. Lancet, 1978, ii, 780. thines were not significantly different between the two groups; 2 Rajah, S M., Penny, A., Kester, R, ibid. p. 1104. 3 Fields, W. S., Lemach, N. A., Frankowski, R. F., Hardy, R. J. Stroke, 1977. 1 Bory, C , and others. Laucct, 1978, ii, 1204. 8, 301 1 Bory, C , and others. Lancet, 1978, ii, 1204. 4. Barnett, H. J. M., and the Canadian Cooperative study Group New Eng 2 Boutroy, M J , Vert, P., Royer, R. J., Monin, P., Royer-Morrot, M. J J. J. Med. 1978, 299, 53. Pediat. in the press). 5 Olsson, J. E , Muller, R., Berneh, S. Stroke, 1976, 7, 444. -
P.
J. GREEN
this suggests potential synergy between caffeine and theophylline in respect of toxic effects. During treatment with theophylline in the neonatal period the plasma concentrations of the different methylxanthines should be carefully monitored.
MARIE-JEANNE BOUTROY PAUL VERT PIERRE MONIN RENÉ JEAN ROYER
Service de Médecine Néonatale, Maternité Régionale,
METHYLATION OF THEOPHYLLINE TO CAFFEINE IN PREMATURE INFANTS Claudette SIR,-Like Bory and her colleagues’ we too have observed the biotransformation of theophylline to caffeine in the premature infant. We used to give theophylline orally as a 10% alcoholic solution for the treatment of idiopathic apnoea of prematurity. We have studied the kinetics of methylxanthines in plasma in 25 infants treated with theophylline. The infants had had a mean gestational age of 31±2 weeks (±s.D.); a mean birth-weight of 1636+328 g; and their age at the onset of therapy was 60±120 h. Methylxanthines were investigated by gas chromatography, before and after flash methylation, on 100 ul
of plasma.
University of Nancy I, 54042 Nancy, France
i .
MARIE-JOSÉE ROYER-MORROT
ASPIRIN DOSE IN PREVENTION OF TRANSIENT ISCHÆMIC ATTACKS SIR,-Aspirin has been introduced as a potent inhibitor of atelet aggregation and the dosage has been discussed by ’Grady and Moncada’ and by Rajah et al.1 Low doses, at ast below 1 g daily, have been recommended selectively to inibit thromboxane Az more than prostacyclin. Aspirin can lower the frequency of transient ischxmic :tacks (T.I.A.)3 and prevent cerebral infarction in patients ith T.I.A.4 We usually give T.I.A. patients prophylactic treatient with dicoumarols but in some patients we have een trying prophylaxis with aspirin combined with dipyridaole after a short initial period with anticoagulants.
elderly
rig.
jl-iriasma
treatment
Fig.
ileveis
oi
memymaninmes
oeiofe
ana
aurmg
with theophylline.
1
..a...ca.
l’AI.L."".a.-U
T.I.A.S
2-Plasma levels of caffeine in toxic and non-toxic infants.
indicated
av
aayu-au
uvace
by arrows.
One patient showed a remarkable sensitivity to aspirin dose; In 24 cases out of 25 there was a steady increase in plasmacaffeine during the administration of theophylline (fig. 1), consl ie had new T.I.A.S when the salicylate level of blood deccentrations rising from 1-3±1-2 mg/1 before treatment (reri ased. At a dose of 2 g daily the patient has always been free 0 ’ T.I.A. (see figure). T.I.A.s appeared when the patient had flecting the maternal caffeine acquired transplacentally) to 3-9+2.0mg/1 after five days of treatment (p<0-001). The lackr :ceived L 0 or 1 - 5 g aspirin daily for some months. The blood of an increase in plasma-caffeine in a group of 12 premature 1 vels of salicylate decreased and T.I.A.s appeared usually when babies fed human milk for 6 days and not receiving theophylt Ie level was at or below 0. 1 mmol/l. The T. I.A. ceased when line rules out exogenous (nutritional) caffeine as the explanat e aspirin was increased. The need for increasing dosages of aspirin to keep patients tion. Premature babies given blood-transfusions would not f ’ee from T.I.A.s has been noticed in other patients, and in receive more than 0-13 mg/day of methylxanthine in this way. c inical practice it seems that some patients will need higher We have also studied the consequences of this methylation c oses than those commonly recommended on the basis of of theophylline to caffeine on the toxic manifestations usually 1 boratory tests. attributed to theophylline (gastrointestinal problems, tachycardia, jitteriness). We found2 that plasma-caffeine, though 1 epartment of Neurology, within the therapeutic range, was significantly higher 1 Department of Neurology, (P<0.01) in the infants with signs of toxicity than in those University Hospital, without such signs (5-5±2-1 versus 3-1+1.3 mg/1). The S-221 85 Lund, Sweden JAN-EDVIN OLSSON plasma concentrations of theophylline and total methylxan1. O’Grady, J., Moncada, S. Lancet, 1978, ii, 780. thines were not significantly different between the two groups; 2 Rajah, S M., Penny, A., Kester, R, ibid. p. 1104. 3 Fields, W. S., Lemach, N. A., Frankowski, R. F., Hardy, R. J. Stroke, 1977. 1 Bory, C , and others. Laucct, 1978, ii, 1204. 8, 301 1 Bory, C , and others. Lancet, 1978, ii, 1204. 4. Barnett, H. J. M., and the Canadian Cooperative study Group New Eng 2 Boutroy, M J , Vert, P., Royer, R. J., Monin, P., Royer-Morrot, M. J J. J. Med. 1978, 299, 53. Pediat. in the press). 5 Olsson, J. E , Muller, R., Berneh, S. Stroke, 1976, 7, 444. -