- Email: [email protected]
BETA-BLOCKER WITHDRAWAL SYNDROME?
387 of control and treatment groups with regard to cause and duration of renal failure, the wider use of propranolol as a treatment for the hyperparathyroidism of renal failure would appear to be premature.
parability
Department of Medicine, Charing Cross Hospital Medical School London W6 8RF
J. B. EASTWOOD
taking beta-blockers (oxprenolol in two and metoprolol in in none was the beta-blocker stopped when nifedipine but one) was started. It is clearly not possible to say whether either withdrawal of metoprolol or institution of nifedipine played any part in the sequence of events described by Meinertz et al. but the case against nifedipine is at least as good as that against withdrawal of metoprolol. were
West Midlands Adverse
Drug Reaction Study Group, Department of Therapeutics Queen Elizabeth Hospital,
Department of Therapeutics and Clinical Pharmacology,
THYROXINE-REPLACEMENT THERAPY, ALDOSTERONE, AND CARDIAC FAILURE et al.’ have demonstrated that plasma-aldosconcentrations and aldosterone-excretion rates in hypothyroid patients are increased by treatment with thyroxine. This observation may be very pertinent to the genesis of cardiac failure during replacement therapy when viewed in conjunction with data on the effects of thyroxine on mineralocorticoid-responsive cells. Such cells are present in the renal tubule and the colon. They do not depend on thyroxine for their basal sodium-retaining activity; however, response to stimulation by aldosterone is thyroxine dependent.2 Impairment of the sodium-transport mechanisms in hypothyroidism occurs in association with a reduction of ouabain-sensitive adenosine tnphosphatase activity3 and a negative sodium balance.’ It is rapidly reversed by administration of triiodothyronine.2 The sodium retention caused by the relatively small increase in plasma aldosterone demonstrated by Marks et al. is likely to be augmented therefore by a simultaneous enhancement of tissue sensitivity. If sodium retention occurs during thyroxine replacement of hypothyroid patients as a result of increased tissue sensitivity as well as increased aldosterone secretion, then a trial of a spirolactone diuretic which would inhibit ouabain sensitive A.T.p.ase activity peripherally, and also inhibits aldosterone synthesis5 may be appropriate in an effort to prevent
SIR,-Marks
NEURONOPHAGIA?
terone
rt;;lrr4<:l(, f’.1l11rp.
Guy’s Arthritis Research Unit, Guy’s Hospital Medical School, London SE1 9RT
G. HUSTON
BETA-BLOCKER WITHDRAWAL SYNDROME?
SIR,-We were interested to read the letter from Dr Memertz, and colleagues (Feb. 3, p. 270) but we feel they may be incriminating the wrong drug. Their patient’s symptoms coincided not only with the withdrawal of metoprolol but also with institution of treatment with nifedipine. Two reports early in 1978 described four patients in whom severe central chest pain appeared to be associated with the use of nifedipine. Three of these were taking 10 mg three times daily and in the fourth the symptom occurred only when the dose was increased to 20 mg three times daily. Of the three patients reported by Jariwalla and Anderson6 one had been on metoprolol which was discontinued but, from the information given, the increase in anginal pain seems to have coincided closely with the administration of nifedipine. The other two were not stated to have been on beta-blockers. The patient reported by Rodger and Stewart’ had been on oxprenolol but this was stopped 6 weeks before an increase in his dose of nifedipine appeared to produce severe chest pain. During 1978 we received four reports of patients whose angina became more severe when they were treated with nifedipine.8 Three of these 1. Marks, P., Anderson, J., Vincent, R. Lancet, 1978, ii, 1277. 2. Edmonds, C. J., Thompson, B. D., Marriott, J. J. Endocr. 1970, 48, 189. 3. Thompson, B D , Edmonds, C. J. ibid. 1974, 62, 489. 4. Fregly, M J., Brimhall, R L., Galindo, O. J. Endocrinology, 1962, 71, 693.
5. Erbler, H C, Wernze, H., Hilfenhaus, M. Eur. J. clin. Pharmac. 1976, 9, 253 6.
Jariwalla, A. G, Anderson, E. G. Br. med. J. 1978, i, 1181. 7. Rodger, C., Stewart, A., ibid 1978, i, 1619. 8. Beeley. L, Talbot, J. Adverse Reaction Newsleter, December, 1978.
LINDA BEELEY LINDA BEELEY
JOHN TALBOT
Birmingham B 15 2TH
SIR,—In their paper Accelerated Ageing or Selective Neuras an Important Cause of Dementia? Dr Bowen and colleagues (Jan. 6, p. 11) suggest neuronophagia as the process onal Loss
whereby neurons
the nerve-cell population is reduced. Phagocytosis of in senile dementia of the Alzheimer’s type is not a part
of the histopathological picture. In my own experience—and, to the best of my knowledge, in the experience of others, as reported in the literature, and personally—such a process has not been observed in this disorder. Perhaps Bowen et al. were using the term neuronophagia in a context unfamiliar to me and could explain what they meant or provide an illustration. Kingsbrook Jewish Medical Center and Department of Pathology, State University of New York Downstate Medical Center, N.Y. 11203, U.S.A.
GILBERT B. SOLITARE
Brooklyn,
**This letter has been shown
to
Dr Bowen and Professor
Davison, whose reply follows.-ED.L. SIR,-Dr Solitare is quite
correct in stating that there is no of evidence phagocytosis of neurones in senile histological dementia. However, the biochemical data (e.g., raised cathepsin A activity,1,2 a possible microgial marker2,3) may be interpreted in terms of phagocytic action on the neuronal perikarya, as well as the neurites. We are not aware of other mechanisms by which nerve cells may be removed4 in this disorder. Miriam Marks Department Institute ofNeurology, London WC1N 3BG
of Neurochemistry,
D. M. BOWEN A. N. DAVISON
UNCLASSIFIED MENTAL RETARDATION
SIR,-Your editorial (Feb. 3,
p. 250) was mainly concerned neonatal head circumference and the treatment of maternal hypertension.s Infants whose mothers had received methyldopa had smaller heads than those whose mothers had no specific treatment, but the effect was only present among those entering the study between 16 and 20 weeks’
with
a
paper of
ours on
gestation. The title chosen for your editorial suggests an association, among the infants in our study, between head size and mental development. There was no such association. A higher proportion (23-3%) of the neonates in the untreated group were assessed as neurologically "questionable" than in the treated group (14-9%);’’ and the difference between the untreated group and a sample of the hospital population (8.6%) was sig1 Bowen, D. M., Smith, C. B., Davison, A. N. Brain, 1973, 96, 849. 2. Bowen, D. M., Smith, C. B., White, P., Flack, R. H. A., Carrasco, L. H., Gedye, J. L., Davison, A N. ibid. 1977, 100, 427. 3. Bowen, D. M., Davison, A. N. J. neurol. Sci 1974, 21, 227. 4. Ball, M. Acta neuropath., Berlin, 1977, 37, 111. 5. Moar, V. A., Jefferies, M. A., Mutch, L. M. M., Ounsted, M. K., Redman, C. W. G. Br. J. Obstet. Gynæc. 1978, 85, 933. 6. Mutch, L. M. M., Moar, V. A., Ounsted, M. K., Redman, C. W. G. Early hum. Devel. 1977, 1, 47.
parability
Department of Medicine, Charing Cross Hospital Medical School London W6 8RF
J. B. EASTWOOD
taking beta-blockers (oxprenolol in two and metoprolol in in none was the beta-blocker stopped when nifedipine but one) was started. It is clearly not possible to say whether either withdrawal of metoprolol or institution of nifedipine played any part in the sequence of events described by Meinertz et al. but the case against nifedipine is at least as good as that against withdrawal of metoprolol. were
West Midlands Adverse
Drug Reaction Study Group, Department of Therapeutics Queen Elizabeth Hospital,
Department of Therapeutics and Clinical Pharmacology,
THYROXINE-REPLACEMENT THERAPY, ALDOSTERONE, AND CARDIAC FAILURE et al.’ have demonstrated that plasma-aldosconcentrations and aldosterone-excretion rates in hypothyroid patients are increased by treatment with thyroxine. This observation may be very pertinent to the genesis of cardiac failure during replacement therapy when viewed in conjunction with data on the effects of thyroxine on mineralocorticoid-responsive cells. Such cells are present in the renal tubule and the colon. They do not depend on thyroxine for their basal sodium-retaining activity; however, response to stimulation by aldosterone is thyroxine dependent.2 Impairment of the sodium-transport mechanisms in hypothyroidism occurs in association with a reduction of ouabain-sensitive adenosine tnphosphatase activity3 and a negative sodium balance.’ It is rapidly reversed by administration of triiodothyronine.2 The sodium retention caused by the relatively small increase in plasma aldosterone demonstrated by Marks et al. is likely to be augmented therefore by a simultaneous enhancement of tissue sensitivity. If sodium retention occurs during thyroxine replacement of hypothyroid patients as a result of increased tissue sensitivity as well as increased aldosterone secretion, then a trial of a spirolactone diuretic which would inhibit ouabain sensitive A.T.p.ase activity peripherally, and also inhibits aldosterone synthesis5 may be appropriate in an effort to prevent
SIR,-Marks
NEURONOPHAGIA?
terone
rt;;lrr4<:l(, f’.1l11rp.
Guy’s Arthritis Research Unit, Guy’s Hospital Medical School, London SE1 9RT
G. HUSTON
BETA-BLOCKER WITHDRAWAL SYNDROME?
SIR,-We were interested to read the letter from Dr Memertz, and colleagues (Feb. 3, p. 270) but we feel they may be incriminating the wrong drug. Their patient’s symptoms coincided not only with the withdrawal of metoprolol but also with institution of treatment with nifedipine. Two reports early in 1978 described four patients in whom severe central chest pain appeared to be associated with the use of nifedipine. Three of these were taking 10 mg three times daily and in the fourth the symptom occurred only when the dose was increased to 20 mg three times daily. Of the three patients reported by Jariwalla and Anderson6 one had been on metoprolol which was discontinued but, from the information given, the increase in anginal pain seems to have coincided closely with the administration of nifedipine. The other two were not stated to have been on beta-blockers. The patient reported by Rodger and Stewart’ had been on oxprenolol but this was stopped 6 weeks before an increase in his dose of nifedipine appeared to produce severe chest pain. During 1978 we received four reports of patients whose angina became more severe when they were treated with nifedipine.8 Three of these 1. Marks, P., Anderson, J., Vincent, R. Lancet, 1978, ii, 1277. 2. Edmonds, C. J., Thompson, B. D., Marriott, J. J. Endocr. 1970, 48, 189. 3. Thompson, B D , Edmonds, C. J. ibid. 1974, 62, 489. 4. Fregly, M J., Brimhall, R L., Galindo, O. J. Endocrinology, 1962, 71, 693.
5. Erbler, H C, Wernze, H., Hilfenhaus, M. Eur. J. clin. Pharmac. 1976, 9, 253 6.
Jariwalla, A. G, Anderson, E. G. Br. med. J. 1978, i, 1181. 7. Rodger, C., Stewart, A., ibid 1978, i, 1619. 8. Beeley. L, Talbot, J. Adverse Reaction Newsleter, December, 1978.
LINDA BEELEY LINDA BEELEY
JOHN TALBOT
Birmingham B 15 2TH
SIR,—In their paper Accelerated Ageing or Selective Neuras an Important Cause of Dementia? Dr Bowen and colleagues (Jan. 6, p. 11) suggest neuronophagia as the process onal Loss
whereby neurons
the nerve-cell population is reduced. Phagocytosis of in senile dementia of the Alzheimer’s type is not a part
of the histopathological picture. In my own experience—and, to the best of my knowledge, in the experience of others, as reported in the literature, and personally—such a process has not been observed in this disorder. Perhaps Bowen et al. were using the term neuronophagia in a context unfamiliar to me and could explain what they meant or provide an illustration. Kingsbrook Jewish Medical Center and Department of Pathology, State University of New York Downstate Medical Center, N.Y. 11203, U.S.A.
GILBERT B. SOLITARE
Brooklyn,
**This letter has been shown
to
Dr Bowen and Professor
Davison, whose reply follows.-ED.L. SIR,-Dr Solitare is quite
correct in stating that there is no of evidence phagocytosis of neurones in senile histological dementia. However, the biochemical data (e.g., raised cathepsin A activity,1,2 a possible microgial marker2,3) may be interpreted in terms of phagocytic action on the neuronal perikarya, as well as the neurites. We are not aware of other mechanisms by which nerve cells may be removed4 in this disorder. Miriam Marks Department Institute ofNeurology, London WC1N 3BG
of Neurochemistry,
D. M. BOWEN A. N. DAVISON
UNCLASSIFIED MENTAL RETARDATION
SIR,-Your editorial (Feb. 3,
p. 250) was mainly concerned neonatal head circumference and the treatment of maternal hypertension.s Infants whose mothers had received methyldopa had smaller heads than those whose mothers had no specific treatment, but the effect was only present among those entering the study between 16 and 20 weeks’
with
a
paper of
ours on
gestation. The title chosen for your editorial suggests an association, among the infants in our study, between head size and mental development. There was no such association. A higher proportion (23-3%) of the neonates in the untreated group were assessed as neurologically "questionable" than in the treated group (14-9%);’’ and the difference between the untreated group and a sample of the hospital population (8.6%) was sig1 Bowen, D. M., Smith, C. B., Davison, A. N. Brain, 1973, 96, 849. 2. Bowen, D. M., Smith, C. B., White, P., Flack, R. H. A., Carrasco, L. H., Gedye, J. L., Davison, A N. ibid. 1977, 100, 427. 3. Bowen, D. M., Davison, A. N. J. neurol. Sci 1974, 21, 227. 4. Ball, M. Acta neuropath., Berlin, 1977, 37, 111. 5. Moar, V. A., Jefferies, M. A., Mutch, L. M. M., Ounsted, M. K., Redman, C. W. G. Br. J. Obstet. Gynæc. 1978, 85, 933. 6. Mutch, L. M. M., Moar, V. A., Ounsted, M. K., Redman, C. W. G. Early hum. Devel. 1977, 1, 47.