- Email: [email protected]
TRANYLCYPROMINE
414
preparation containing a number of other components of the clotting system besides fibrinogen and A.H.F. We believe, therefore, that the omission of washing the fraction i precipitate not only simplifies the procedure but also gives to the preparation a broader spectrum of activity. Gugler also points out that the frequency of unwanted reactions on infusion of our fraction i is very low (below 1%). Good results in the clinical treatment of haemophilia A patients with our preparation have also been reported by van Creveld and Mochtar.1 They end their paper with the statement: " On the basis of clinical impressions and of the results of laboratory studies, it is concluded that the effectiveness of each injection of this ’ two-donor ’ fraction i is not inferior to results obtained elsewhere with the so-called I-O products, prepared from a much greater quantity of blood plasma." Ledermann 6 investigated the risk of transmitting hepatitis by studying patients who have received the Swiss fraction i. He came to the conclusion that the frequency is-as could be expected-very low, certainly below 1% per unit. In this respect the two-donor preparation is superior to a Swedish preparation derived from larger plasma pools.7
2 who developed the attack within 5 minutes of each other after the only cheese meal of the week. All 3 had pronounced hypertension and severe throbbing occipital headache. There are several possible explanations for this interesting association which I hope to discuss later. Meanwhile I would be glad to hear of further cases in the London area. The implications of this finding are of some interest in the relation of drug efficacy and diet hinted at by Coppen et al. and in the association of vascular changes and headache. Furthermore if this or any other dietary links can be substantiated the only serious side-effect of an otherwise valuable drug mav be eliminated. Maudsley Hospital, B. BLACKWELL.
wish to state that fraction i prepared Summarising, according to Nitschmann et awl. by the Swiss Red Cross blood-transfusion service during the past seven years has apparently satisfactorily fulfilled all the demands in the clinical treatment of haemophilia and some other blood-clotting disorders. we
Zentrallaboratorium des
Blutspendedienstes
des
Schweizerischen Roten Kreuzes, Berne, Switzerland.
HS. NITSCHMANN P. KISTLER.
TRANYLCYPROMINE AND INTRACRANIAL BLEEDING letter SIR,-In my (Aug. 10) describing a patient who had suffered a cerebral haemorrhage whilst being treated with ’Parstelin ’, I stated that no other cases of intracranial bleeding in association with tranylcypromine had
been reported. The medical services department of Smith Kline & French Laboratories have pointed out that three other cases in which intracranial bleeding occurred have been recorded. 1-4-111 One of these patients had had methylamphetamine concomitantly, and another had a congenital aneurysm of a cerebral artery. I am informed that there are also reports of four other cases in which intracranial bleeding has occurred but which have not been published. I would like to thank the manufacturers for this information. Department of Psychological Medicine, The Middlesex Hospital, London, W.1.
TRANYLCYPROMINE
SIR,-In an earlier letter8reviewed the reports concerning the side-effect of paroxysmal hypertension and headache due to tranylcypromine. The risk of intracranial bleeding was particularly stressed, and since then Dr. Dorrell (Aug. 10) has reported 3 further cases in which this complication has occurred. In a series of 12 incidents which I hope to publish shortly there have been 3 intracerebral bleeds proven by lumbar 9 puncture, including 1 death. In 1962 McClure also reported a death due to ’ Parnate ’ at this hospital. The only prospective trial of the drug in this country " revealed that of 60 patients 11 (18%) had this side-effect without neurological sequelx. The lower incidence reported by other clinicians 11 12 may be due partly to the data being retrospective and the fact that parnate andParstelin’ are prescribed to a population in which the incidence of tension and migraine headaches is high. The occurrence of another headache is attributed to functional causes and soon forgotten. The random appearance of the symptoms on any dosage and after very variable duration of medication strongly suggests that an exogenous factor may provoke the syndrome, particularly since patients have been known to continue the drug without a recurrence. The role of the amphetamines in this respect is already recognised, but until now no precipitating factor has been evident in the majority of patients who are taking the drug by itself. Shortly after my first letter I received a personal communication from a pharmacist who observed that his wife, who was taking parstelin, developed typical symptoms shortly after eating cheese. Despite the unlikely nature of this observation, dietary histories have been taken from all my patients. Of the 10 in whom recent and reliable information could be gathered, 8 had eaten cheese within two hours of the onset of the headache. This association has been noted in 3 cases seen as inpatients of this hospital within the last month, including 6. Ledermann, K. L. Praxis, 1960, 11, 273. 7. Cronberg, S., Belfrage, B., Nilsson, I. M. Lancet, 8. Lancet, 1963, i, 167. 9. McClure, J. L. ibid. 1962, ii, 1351. 10. Lees, C. W., Burke, C. W. ibid. 1963, i, 13. 11. MacDonald, R. ibid. p. 269. 12. Milligan, L. W. ibid. p. 442.
London, S.E.5.
1963, i, 967.
WILLIAM DORRELL.
IMMUNOASSAY OF INSULIN WITH INSULINANTIBODY PRECIPITATE
SIR,-Iwas
very interested in the letter
by Dr. Ekins and Dr. Samols (July 27). Over the range of insulin standards I have used, the results obtained have always been, experimentally at least, best represented by a straight line. I note from fig. 2 of Ekins and Samols that it would be difficult to argue that their data could not equally be represented by a straight line. Of course, I accept their theoretical objections, but over the very wide range of standard insulins I have used (25-1000 fLU per ml.) this close approach of the data to linearity allows far greater accuracy of insulin measurement. of Colorado Medical Center, 4200, East Ninth Avenue, Denver 20, Colorado, U.S.A.
University
LEO STIMMLER Research Fellow.
CONVERSION OF ATRIAL FIBRILLATION TO SINUS RHYTHM BY DIRECT-CURRENT SHOCK
SIR,-We read with great interest the paper by Dr. Oram and his colleagues (July 27). Their results are impressive and the method clearly deserves more intensive trial. Cardiac output is known to be reduced by atrial fibrillation, and it is therefore
patients was immediately
an
disturbing to note that in only 3 of their improvement in cardiac output recorded
after conversion. Their table III, however, shows that in 4 of their patients the cardiac output before switching was 1-2 litres per minute or less, and the cardiac index must therefore have been considerably less than 1-0 litre per minute per sq. m. We have never encountered patients with cardiac outputs of this order, and therefore doubt the accuracy of these particular observations. Their findings suggest that the shock itself depresses myocardial function; if confirmed, this could limit the usefulness of the method. The effect on cardiac output of conversion to sinus 13. Coppen, A., Shaw, D. M., Farrell, J. P. ibid. p. 79. 14. Zeck, P. Med. J. Aust. 1961, ii, 607. 15. Mason, A. Lancet, 1962, i, 1073. 16. McClure, J. L. ibid. p. 1351.
preparation containing a number of other components of the clotting system besides fibrinogen and A.H.F. We believe, therefore, that the omission of washing the fraction i precipitate not only simplifies the procedure but also gives to the preparation a broader spectrum of activity. Gugler also points out that the frequency of unwanted reactions on infusion of our fraction i is very low (below 1%). Good results in the clinical treatment of haemophilia A patients with our preparation have also been reported by van Creveld and Mochtar.1 They end their paper with the statement: " On the basis of clinical impressions and of the results of laboratory studies, it is concluded that the effectiveness of each injection of this ’ two-donor ’ fraction i is not inferior to results obtained elsewhere with the so-called I-O products, prepared from a much greater quantity of blood plasma." Ledermann 6 investigated the risk of transmitting hepatitis by studying patients who have received the Swiss fraction i. He came to the conclusion that the frequency is-as could be expected-very low, certainly below 1% per unit. In this respect the two-donor preparation is superior to a Swedish preparation derived from larger plasma pools.7
2 who developed the attack within 5 minutes of each other after the only cheese meal of the week. All 3 had pronounced hypertension and severe throbbing occipital headache. There are several possible explanations for this interesting association which I hope to discuss later. Meanwhile I would be glad to hear of further cases in the London area. The implications of this finding are of some interest in the relation of drug efficacy and diet hinted at by Coppen et al. and in the association of vascular changes and headache. Furthermore if this or any other dietary links can be substantiated the only serious side-effect of an otherwise valuable drug mav be eliminated. Maudsley Hospital, B. BLACKWELL.
wish to state that fraction i prepared Summarising, according to Nitschmann et awl. by the Swiss Red Cross blood-transfusion service during the past seven years has apparently satisfactorily fulfilled all the demands in the clinical treatment of haemophilia and some other blood-clotting disorders. we
Zentrallaboratorium des
Blutspendedienstes
des
Schweizerischen Roten Kreuzes, Berne, Switzerland.
HS. NITSCHMANN P. KISTLER.
TRANYLCYPROMINE AND INTRACRANIAL BLEEDING letter SIR,-In my (Aug. 10) describing a patient who had suffered a cerebral haemorrhage whilst being treated with ’Parstelin ’, I stated that no other cases of intracranial bleeding in association with tranylcypromine had
been reported. The medical services department of Smith Kline & French Laboratories have pointed out that three other cases in which intracranial bleeding occurred have been recorded. 1-4-111 One of these patients had had methylamphetamine concomitantly, and another had a congenital aneurysm of a cerebral artery. I am informed that there are also reports of four other cases in which intracranial bleeding has occurred but which have not been published. I would like to thank the manufacturers for this information. Department of Psychological Medicine, The Middlesex Hospital, London, W.1.
TRANYLCYPROMINE
SIR,-In an earlier letter8reviewed the reports concerning the side-effect of paroxysmal hypertension and headache due to tranylcypromine. The risk of intracranial bleeding was particularly stressed, and since then Dr. Dorrell (Aug. 10) has reported 3 further cases in which this complication has occurred. In a series of 12 incidents which I hope to publish shortly there have been 3 intracerebral bleeds proven by lumbar 9 puncture, including 1 death. In 1962 McClure also reported a death due to ’ Parnate ’ at this hospital. The only prospective trial of the drug in this country " revealed that of 60 patients 11 (18%) had this side-effect without neurological sequelx. The lower incidence reported by other clinicians 11 12 may be due partly to the data being retrospective and the fact that parnate andParstelin’ are prescribed to a population in which the incidence of tension and migraine headaches is high. The occurrence of another headache is attributed to functional causes and soon forgotten. The random appearance of the symptoms on any dosage and after very variable duration of medication strongly suggests that an exogenous factor may provoke the syndrome, particularly since patients have been known to continue the drug without a recurrence. The role of the amphetamines in this respect is already recognised, but until now no precipitating factor has been evident in the majority of patients who are taking the drug by itself. Shortly after my first letter I received a personal communication from a pharmacist who observed that his wife, who was taking parstelin, developed typical symptoms shortly after eating cheese. Despite the unlikely nature of this observation, dietary histories have been taken from all my patients. Of the 10 in whom recent and reliable information could be gathered, 8 had eaten cheese within two hours of the onset of the headache. This association has been noted in 3 cases seen as inpatients of this hospital within the last month, including 6. Ledermann, K. L. Praxis, 1960, 11, 273. 7. Cronberg, S., Belfrage, B., Nilsson, I. M. Lancet, 8. Lancet, 1963, i, 167. 9. McClure, J. L. ibid. 1962, ii, 1351. 10. Lees, C. W., Burke, C. W. ibid. 1963, i, 13. 11. MacDonald, R. ibid. p. 269. 12. Milligan, L. W. ibid. p. 442.
London, S.E.5.
1963, i, 967.
WILLIAM DORRELL.
IMMUNOASSAY OF INSULIN WITH INSULINANTIBODY PRECIPITATE
SIR,-Iwas
very interested in the letter
by Dr. Ekins and Dr. Samols (July 27). Over the range of insulin standards I have used, the results obtained have always been, experimentally at least, best represented by a straight line. I note from fig. 2 of Ekins and Samols that it would be difficult to argue that their data could not equally be represented by a straight line. Of course, I accept their theoretical objections, but over the very wide range of standard insulins I have used (25-1000 fLU per ml.) this close approach of the data to linearity allows far greater accuracy of insulin measurement. of Colorado Medical Center, 4200, East Ninth Avenue, Denver 20, Colorado, U.S.A.
University
LEO STIMMLER Research Fellow.
CONVERSION OF ATRIAL FIBRILLATION TO SINUS RHYTHM BY DIRECT-CURRENT SHOCK
SIR,-We read with great interest the paper by Dr. Oram and his colleagues (July 27). Their results are impressive and the method clearly deserves more intensive trial. Cardiac output is known to be reduced by atrial fibrillation, and it is therefore
patients was immediately
an
disturbing to note that in only 3 of their improvement in cardiac output recorded
after conversion. Their table III, however, shows that in 4 of their patients the cardiac output before switching was 1-2 litres per minute or less, and the cardiac index must therefore have been considerably less than 1-0 litre per minute per sq. m. We have never encountered patients with cardiac outputs of this order, and therefore doubt the accuracy of these particular observations. Their findings suggest that the shock itself depresses myocardial function; if confirmed, this could limit the usefulness of the method. The effect on cardiac output of conversion to sinus 13. Coppen, A., Shaw, D. M., Farrell, J. P. ibid. p. 79. 14. Zeck, P. Med. J. Aust. 1961, ii, 607. 15. Mason, A. Lancet, 1962, i, 1073. 16. McClure, J. L. ibid. p. 1351.