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COORDINATED CARE OF THE CHILD WITH SPINA BIFIDA
934
be, when using the E.E.G. to assess cerebral death, to use lateral orbital electrodes and cold caloric stimulation to record the presence (or absence) of evoked eye movement. This work was done at Charing Cross Hospital, London, and I am indebted to Dr. B. G. Parsons-Smith for his encouragement. Institute of Neurological Sciences, Killearn Hospital, D. M. PARK. Glasgow. DERMATOGLYPHICS IN LEUKÆMIA SIR,-In view of the continued interest in this subject, as shown by Dr. Rosner’s excellent summarising letter of Oct. 24 (p. 882), may I mention that, in addition to the letter he cited, my detailed findings, including those on Fig. 1-Corneo-retinal potentials in patient with damage.
severe
brain
defined subcategories of leukaemia, have been published.’2 As regards frequency of abnormal palmar flexion creases, the incidence of Sydney and simian lines in my unrelated British White leukxmia patients was not significantly different from that in the normal control group. Department of Dermatology, St. Bartholomew’s Hospital, London E.C.1.
JULIAN VERBOV.
DELAYED PSYCHOSIS DUE TO L.S.D.
Fig. 2-Corneo-retinal potentials in normal subject.
who, after a cardiac arrest during a surgical operation elsewhere, had been transferred in status epilepticus with barely reacting pupils. His condition continued to deteriorate, so that after 2 days he was totally unresponsive, with fixed dilated pupils and areflexia, though blood-pressure man
and
body-temperature
were
maintained.
appearances were consistent in both cerebral infarction.
cases
Post-mortem with generalised
recordings were made while the patients were on intermittent positive-pressure ventilation, with surface electrodes in standard placings, using a portable eightchannel S.L.E. ’Galileo ’ recorder. In both cases passive eye movement was effected from the infraorbital region, using a polyethylene-handled patella hammer. This technique did not produce a direct field effect. In the first case, two records separated by 24 hours were isoelectric at high gain. In the second case, the initial E.E.G. showed suppression-burst activity similar to that described in this situation by Pampiglione and Harden3 and in other situations by Henry and Scoville4 and Bell.5 4 days later the record was isoelectric at high gain. Fig. 1 shows slow potential changes synchronous with passive eye movement on the otherwise isoelectric E.E.G. from the frontal and, to a lesser extent, anterior temporal leads. Fig. 2 shows, for comparison, the E.E.G. of a conscious subject with passive
SIR,-Dr. Hatrick and Dr. Dewhurst (Oct. 10, p. 742) cite a report that chlorpromazine may have a paradoxical effect in cases of L.S.D. psychosis. This corresponds to my own observations on prolonged L.S.D. reactions. Very small doses of chlorpromazine (e.g., 10 mg. thrice daily) have, however, been found to suppress symptoms without producing the paradoxical effects of large doses. Clinical experience indicates that the smoking of cannabis may aggravate or reactivate psychosis due to L.s.D. for up to two months after the last " trip ". Occasional idiosyncratic reactions to cannabis may be explicable on this basis. One may conjecture that L.s.D. has the property of sensitising the brain to cannabis, perhaps through changes in perceptual thresholds. Herbert Hone Clinic, Brighton BN2 1SL, Sussex.
DENIS PARR.
E.E.G.
eye movements
as
described.
The results of these tests suggest that in these two cases, although the E.E.G. was consistent with cerebral death, there was persistence of the corneo-retinal potential. Eye movement is normally avoided during E.E.G. recording, and after cerebral death spontaneous movement does not occur, but the corneo-retinal potential can nevertheless produce fluctuations on the record. A possible application of this would 3. 4. 5.
Pampiglione, G., Harden, A. Lancet, 1968, i, 1261. Henry, C. E., Scoville, W. B. Electroenceph. clin. Neurophysiol. 1952, 4, 1. Bell, D. S. J. Neurol. Neurosurg. Psychiat. 1970, 33, 231.
COORDINATED CARE OF THE CHILD WITH SPINA BIFIDA
SIR,-While we appreciate the possible advantages of " combined clinics " in the management of spina-bifida patientswe wish to record that at Queen Mary’s Hospital for Children, where at present there are some 700 children with this condition under our care, we have not found joint clinics desirable or necessary. However, we are very fortunate in that only three medical specialties-pxdiatric surgeons, orthopxdic surgeons, and an ophthalmologistare closely involved with the care of the vast majority of the children. We depend heavily on our medical-social department as well as on physiotherapists and psychologists, and fortunately these ancillary workers are freely available during our independent clinics. The physiotherapists and social workers provide excellent liaison, and in addition the surgeons lunch together each week as well as meet in the theatre and wards. Parents and children seem to prefer spending less time at the hospital on more frequent occasions, and in fact several activities such as muscle charting, psychological assessments, radiology, and surgical consultations often take 1. 2. 3.
Verbov, J. L. Lancet, 1969, ii, 323. Verbov, J. L. J. med. Genet. 1970, 7, 125. Hide, D. W., Semple, C. Lancet, Sept. 19, 1970, p. 603.
935 one visit. For these reasons we believe that, whereas combined clinics may be satisfactory where few children are seen, they are neither necessary nor helpful where large numbers of patients are involved. D. M. FORREST TREVOR BOWEN Queen Mary’s Hospital for GEOFFREY F. WALKER Children, ELIZABETH D. L. SIMPSON. Carshalton, Surrey.
place during
PRACTOLOL TREATMENT FOR HYPERTENSION IN AN ASTHMATIC SIR,—Whilst I agree with Dr. Bernecker and Dr. Roetscher that there is need for caution when giving practolol to patients with asthma or obstructive bronchitis (Sept. 26, p. 662), in my experience it can be used to reduce raised blood-pressure without seriously intensifying the airways obstruction. A 60-year-old asthmatic woman had mild essential hypertension. On admission to hospital the basal bloodpressure was 175/110 mm. Hg and the forced expiratory volume in 1 second (F.E.V.jL) 1-70 litres (predicted normal 2-01 litres). After a test dose of 100 mg. practolol by mouth, the mean F.E,V’1 (estimated at 10-minute intervals for 3 hours) was 1-65 litres and there was no complaint of dyspnoea or wheezing. Practolol, 100 mg. twice daily, was given for 7 days, and later the dose was increased to 200 mg. twice daily. When she was discharged from hospital on this dose, the blood-pressure was 135/80 mm. Hg supine and 140/90 mm. Hg standing, and the F.E.V.1 1-82 litres. University Department of Medicine, K. N. V. PALMER. Aberdeen.
INTERACTION BETWEEN DEBRISOQUINE AND PHENYLEPHRINE are interested in the report by Dr. Amery and SIR,-We Dr. Deloof (Sept. 19, p. 613) on a reaction to cheese during debrisoquine therapy. We have noticed a drug interaction between debrisoquine and phenylephrine in two different experimental situations: a hypertensive response to phenylephrine in a patient on debrisoquine treatment; and a reversal by phenylephrine of adrenergic-neurone blockade induced by debrisoquine in a sympathetically innervated
preparation.
Hypertensive response.-Phenylephrine 50 mg. may be used orally to induce slight rises of blood-pressure in normal individuals to test the baroreceptor-reflex response.I A 46-year-old man was taking debrisoquine 20 mg. thrice daily for hypertension, with satisfactory control (mean bloodpressure 145/95 mm. Hg supine and 120/85 mm. Hg standing). After 6 months’ treatment with debrisoquine, the patient consented to the phenylephrine test to enable us to examine the interaction between these drugs, there being no reason then to suspect that he would experience any more than a transient return of his former moderate hypertension or, at most, an exaggerated response due to receptor hypersensitivity readily terminable by phentolamine. The outcome is shown in the accompanying figure. His blood-pressure rose rapidly till the diastolic level reached 180 mm. Hg. At this point he was given phentolamine 5 mg. intravenously and the blood-pressure immediately fell to 172/100 mm. Hg. It then continued to rise to a systolic maximum of 260 mm. Hg and diastolic of 160 mm. Hg after 75 minutes. More phentolamine was drawn up, but at this point the patient was asked to stand up, and the blood-pressure was found to have fallen to 180/110 mm. Hg with no postural symptoms. When he resumed the recumbent posture the bloodrose again, but only to 218/124 mm. Hg, and slowly
pressure 1.
Bristow, J. D., Honour, A. J., Pickering, G. W., Sleight, P., Smyth, H. S. Circulation, 1969, 39, 48.
Hypertensive returned
to a
response to
level similar
ephrine. No symptoms
phenylephrine.
that before ing;estion of phenylexperienced during or after the test,
to
were
pulse-rate fell from 51 to 46 beats per minute. The Long-term control on complexes remained normal. debrisoquine was readily established. The test has been performed many times with other patients who have received no treatment, and on normal volunteers, but no such response has
but the E.C.G.
been observed.
The hypertensive response closely resembles the welldocumented potentiation of effects of pressor amines in patients taking long-term monoamine-oxidase inhibitors.2-4 Pettinger et awl. observed that debrisoquine caused no reduction in intestinal monoamine-oxidase activity, and therefore concluded that oral tyramine (as ingested cheese) is unlikely to be harmful. The observations of Elis et al.2 with our own using oral phenylephrine, a substrate for monoamine oxidase,3 do not wholly support this conclusion. The increase in sensitivity of adrenergic receptors to direct stimulation in patients on adrenergic-neurone-blocking drugs is well known. The hypertensive response to phenylephrine could therefore have resulted from either the monoamine-oxidase inhibitory effect of debrisoquine or sensitisation of adrenergic receptors to phenylephrine or both of these factors.
Reversal of adrenergic-neurone blockade.-We have found that debrisoquine abolishes the relaxation of the isolated rabbit ileum induced by electrical stimulation of periarterial sympathetic nerves, and that this adrenergic-neuroneblocking action of debrisoquine is prevented or reversed by phenylephrine. However, phenylephrine does not prevent the blockade produced by guanethidine, bretylium, and xylocholine.5 The ability of indirectly acting sympathomimetic amines such as amphetamine to antagonise the adrenergic-neurone-blocking effect of bretylium and guanethidine has been observed in man, 6, and in a variety of sympathetically innervated preparations.5,8,9 Possibly indirectly acting amines having similar or higher affinities for receptor sites in the adrenergic neurone but differing efficacies can displace the blocking drugs from these sites. However, it is unusual to find that phenylephrine, a directly acting amine, antagonises the blockade caused by debrisoquine. It is not yet known whether this particular interaction occurs in vivo. In the debrisoquine-treated patient there was a proElis, J., Lawrence, D. R., Mattie, H., Prichard, B. N. C. Br. med. J. 1967, ii, 75. 3. Giachett, A., Shore, P. A. Biochem. Pharm. 1967, 16, 237. 4. Pettinger, W. A., Korn, A., Spiegel, H., Solomon, H. M., Pcelinko, R., Abrams, W. B., Nutley, N. J. Clin. Pharmac. Ther. 1969, 10, 667. 5. Day, M. D. Br. J. Pharmac. Chemother. 1962, 18, 421. 6. Wilson, R., Long, C. Lancet, 1960, ii, 262. 7. Laurence, D. R., Rosenheim, M. L. Adrenergic Mechanisms (edited by J. R. Vane, G. E. W. Wolstenholme, and M. O’Connor); p. 201. London, 1960. 8. Day, M. D., Rand, M. J. J. Pharm. Pharmac. 1962, 14, 541. 9. Day, M. D., Rand, M. J. Br. J. Pharmac. Chemother. 1963, 20, 17.
2.
be, when using the E.E.G. to assess cerebral death, to use lateral orbital electrodes and cold caloric stimulation to record the presence (or absence) of evoked eye movement. This work was done at Charing Cross Hospital, London, and I am indebted to Dr. B. G. Parsons-Smith for his encouragement. Institute of Neurological Sciences, Killearn Hospital, D. M. PARK. Glasgow. DERMATOGLYPHICS IN LEUKÆMIA SIR,-In view of the continued interest in this subject, as shown by Dr. Rosner’s excellent summarising letter of Oct. 24 (p. 882), may I mention that, in addition to the letter he cited, my detailed findings, including those on Fig. 1-Corneo-retinal potentials in patient with damage.
severe
brain
defined subcategories of leukaemia, have been published.’2 As regards frequency of abnormal palmar flexion creases, the incidence of Sydney and simian lines in my unrelated British White leukxmia patients was not significantly different from that in the normal control group. Department of Dermatology, St. Bartholomew’s Hospital, London E.C.1.
JULIAN VERBOV.
DELAYED PSYCHOSIS DUE TO L.S.D.
Fig. 2-Corneo-retinal potentials in normal subject.
who, after a cardiac arrest during a surgical operation elsewhere, had been transferred in status epilepticus with barely reacting pupils. His condition continued to deteriorate, so that after 2 days he was totally unresponsive, with fixed dilated pupils and areflexia, though blood-pressure man
and
body-temperature
were
maintained.
appearances were consistent in both cerebral infarction.
cases
Post-mortem with generalised
recordings were made while the patients were on intermittent positive-pressure ventilation, with surface electrodes in standard placings, using a portable eightchannel S.L.E. ’Galileo ’ recorder. In both cases passive eye movement was effected from the infraorbital region, using a polyethylene-handled patella hammer. This technique did not produce a direct field effect. In the first case, two records separated by 24 hours were isoelectric at high gain. In the second case, the initial E.E.G. showed suppression-burst activity similar to that described in this situation by Pampiglione and Harden3 and in other situations by Henry and Scoville4 and Bell.5 4 days later the record was isoelectric at high gain. Fig. 1 shows slow potential changes synchronous with passive eye movement on the otherwise isoelectric E.E.G. from the frontal and, to a lesser extent, anterior temporal leads. Fig. 2 shows, for comparison, the E.E.G. of a conscious subject with passive
SIR,-Dr. Hatrick and Dr. Dewhurst (Oct. 10, p. 742) cite a report that chlorpromazine may have a paradoxical effect in cases of L.S.D. psychosis. This corresponds to my own observations on prolonged L.S.D. reactions. Very small doses of chlorpromazine (e.g., 10 mg. thrice daily) have, however, been found to suppress symptoms without producing the paradoxical effects of large doses. Clinical experience indicates that the smoking of cannabis may aggravate or reactivate psychosis due to L.s.D. for up to two months after the last " trip ". Occasional idiosyncratic reactions to cannabis may be explicable on this basis. One may conjecture that L.s.D. has the property of sensitising the brain to cannabis, perhaps through changes in perceptual thresholds. Herbert Hone Clinic, Brighton BN2 1SL, Sussex.
DENIS PARR.
E.E.G.
eye movements
as
described.
The results of these tests suggest that in these two cases, although the E.E.G. was consistent with cerebral death, there was persistence of the corneo-retinal potential. Eye movement is normally avoided during E.E.G. recording, and after cerebral death spontaneous movement does not occur, but the corneo-retinal potential can nevertheless produce fluctuations on the record. A possible application of this would 3. 4. 5.
Pampiglione, G., Harden, A. Lancet, 1968, i, 1261. Henry, C. E., Scoville, W. B. Electroenceph. clin. Neurophysiol. 1952, 4, 1. Bell, D. S. J. Neurol. Neurosurg. Psychiat. 1970, 33, 231.
COORDINATED CARE OF THE CHILD WITH SPINA BIFIDA
SIR,-While we appreciate the possible advantages of " combined clinics " in the management of spina-bifida patientswe wish to record that at Queen Mary’s Hospital for Children, where at present there are some 700 children with this condition under our care, we have not found joint clinics desirable or necessary. However, we are very fortunate in that only three medical specialties-pxdiatric surgeons, orthopxdic surgeons, and an ophthalmologistare closely involved with the care of the vast majority of the children. We depend heavily on our medical-social department as well as on physiotherapists and psychologists, and fortunately these ancillary workers are freely available during our independent clinics. The physiotherapists and social workers provide excellent liaison, and in addition the surgeons lunch together each week as well as meet in the theatre and wards. Parents and children seem to prefer spending less time at the hospital on more frequent occasions, and in fact several activities such as muscle charting, psychological assessments, radiology, and surgical consultations often take 1. 2. 3.
Verbov, J. L. Lancet, 1969, ii, 323. Verbov, J. L. J. med. Genet. 1970, 7, 125. Hide, D. W., Semple, C. Lancet, Sept. 19, 1970, p. 603.
935 one visit. For these reasons we believe that, whereas combined clinics may be satisfactory where few children are seen, they are neither necessary nor helpful where large numbers of patients are involved. D. M. FORREST TREVOR BOWEN Queen Mary’s Hospital for GEOFFREY F. WALKER Children, ELIZABETH D. L. SIMPSON. Carshalton, Surrey.
place during
PRACTOLOL TREATMENT FOR HYPERTENSION IN AN ASTHMATIC SIR,—Whilst I agree with Dr. Bernecker and Dr. Roetscher that there is need for caution when giving practolol to patients with asthma or obstructive bronchitis (Sept. 26, p. 662), in my experience it can be used to reduce raised blood-pressure without seriously intensifying the airways obstruction. A 60-year-old asthmatic woman had mild essential hypertension. On admission to hospital the basal bloodpressure was 175/110 mm. Hg and the forced expiratory volume in 1 second (F.E.V.jL) 1-70 litres (predicted normal 2-01 litres). After a test dose of 100 mg. practolol by mouth, the mean F.E,V’1 (estimated at 10-minute intervals for 3 hours) was 1-65 litres and there was no complaint of dyspnoea or wheezing. Practolol, 100 mg. twice daily, was given for 7 days, and later the dose was increased to 200 mg. twice daily. When she was discharged from hospital on this dose, the blood-pressure was 135/80 mm. Hg supine and 140/90 mm. Hg standing, and the F.E.V.1 1-82 litres. University Department of Medicine, K. N. V. PALMER. Aberdeen.
INTERACTION BETWEEN DEBRISOQUINE AND PHENYLEPHRINE are interested in the report by Dr. Amery and SIR,-We Dr. Deloof (Sept. 19, p. 613) on a reaction to cheese during debrisoquine therapy. We have noticed a drug interaction between debrisoquine and phenylephrine in two different experimental situations: a hypertensive response to phenylephrine in a patient on debrisoquine treatment; and a reversal by phenylephrine of adrenergic-neurone blockade induced by debrisoquine in a sympathetically innervated
preparation.
Hypertensive response.-Phenylephrine 50 mg. may be used orally to induce slight rises of blood-pressure in normal individuals to test the baroreceptor-reflex response.I A 46-year-old man was taking debrisoquine 20 mg. thrice daily for hypertension, with satisfactory control (mean bloodpressure 145/95 mm. Hg supine and 120/85 mm. Hg standing). After 6 months’ treatment with debrisoquine, the patient consented to the phenylephrine test to enable us to examine the interaction between these drugs, there being no reason then to suspect that he would experience any more than a transient return of his former moderate hypertension or, at most, an exaggerated response due to receptor hypersensitivity readily terminable by phentolamine. The outcome is shown in the accompanying figure. His blood-pressure rose rapidly till the diastolic level reached 180 mm. Hg. At this point he was given phentolamine 5 mg. intravenously and the blood-pressure immediately fell to 172/100 mm. Hg. It then continued to rise to a systolic maximum of 260 mm. Hg and diastolic of 160 mm. Hg after 75 minutes. More phentolamine was drawn up, but at this point the patient was asked to stand up, and the blood-pressure was found to have fallen to 180/110 mm. Hg with no postural symptoms. When he resumed the recumbent posture the bloodrose again, but only to 218/124 mm. Hg, and slowly
pressure 1.
Bristow, J. D., Honour, A. J., Pickering, G. W., Sleight, P., Smyth, H. S. Circulation, 1969, 39, 48.
Hypertensive returned
to a
response to
level similar
ephrine. No symptoms
phenylephrine.
that before ing;estion of phenylexperienced during or after the test,
to
were
pulse-rate fell from 51 to 46 beats per minute. The Long-term control on complexes remained normal. debrisoquine was readily established. The test has been performed many times with other patients who have received no treatment, and on normal volunteers, but no such response has
but the E.C.G.
been observed.
The hypertensive response closely resembles the welldocumented potentiation of effects of pressor amines in patients taking long-term monoamine-oxidase inhibitors.2-4 Pettinger et awl. observed that debrisoquine caused no reduction in intestinal monoamine-oxidase activity, and therefore concluded that oral tyramine (as ingested cheese) is unlikely to be harmful. The observations of Elis et al.2 with our own using oral phenylephrine, a substrate for monoamine oxidase,3 do not wholly support this conclusion. The increase in sensitivity of adrenergic receptors to direct stimulation in patients on adrenergic-neurone-blocking drugs is well known. The hypertensive response to phenylephrine could therefore have resulted from either the monoamine-oxidase inhibitory effect of debrisoquine or sensitisation of adrenergic receptors to phenylephrine or both of these factors.
Reversal of adrenergic-neurone blockade.-We have found that debrisoquine abolishes the relaxation of the isolated rabbit ileum induced by electrical stimulation of periarterial sympathetic nerves, and that this adrenergic-neuroneblocking action of debrisoquine is prevented or reversed by phenylephrine. However, phenylephrine does not prevent the blockade produced by guanethidine, bretylium, and xylocholine.5 The ability of indirectly acting sympathomimetic amines such as amphetamine to antagonise the adrenergic-neurone-blocking effect of bretylium and guanethidine has been observed in man, 6, and in a variety of sympathetically innervated preparations.5,8,9 Possibly indirectly acting amines having similar or higher affinities for receptor sites in the adrenergic neurone but differing efficacies can displace the blocking drugs from these sites. However, it is unusual to find that phenylephrine, a directly acting amine, antagonises the blockade caused by debrisoquine. It is not yet known whether this particular interaction occurs in vivo. In the debrisoquine-treated patient there was a proElis, J., Lawrence, D. R., Mattie, H., Prichard, B. N. C. Br. med. J. 1967, ii, 75. 3. Giachett, A., Shore, P. A. Biochem. Pharm. 1967, 16, 237. 4. Pettinger, W. A., Korn, A., Spiegel, H., Solomon, H. M., Pcelinko, R., Abrams, W. B., Nutley, N. J. Clin. Pharmac. Ther. 1969, 10, 667. 5. Day, M. D. Br. J. Pharmac. Chemother. 1962, 18, 421. 6. Wilson, R., Long, C. Lancet, 1960, ii, 262. 7. Laurence, D. R., Rosenheim, M. L. Adrenergic Mechanisms (edited by J. R. Vane, G. E. W. Wolstenholme, and M. O’Connor); p. 201. London, 1960. 8. Day, M. D., Rand, M. J. J. Pharm. Pharmac. 1962, 14, 541. 9. Day, M. D., Rand, M. J. Br. J. Pharmac. Chemother. 1963, 20, 17.
2.