265
SiR,—Dr Compston and her colleagues found that half their patients with jejunoileal bypasses for gross obesity had histological osteomalacia with evidence of secondary hyperparathyroidism. The plasma-25-hydroxyvitamin-D (25-OHD) did not correlate closely with the histological findings, and Compston et al. suggested that low circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) might contribute to the development of bone disease.
chaired, and the Guild of Catholic Doctors, of which I
am
welcome the bishop’s letter and commend it and its conclusion to your readers. As we see it no woman who objects to abortion in principle should ever undergo routine procedures that could lead to pressure being put upon her to be aborted or cause unnecessary worry about the possibility of giving birth to an abnormal child. master, I would like
to
21 Devonshire Place, London W1N 1PD
JONATHAN GOULD
MECHANISM OF CIMETIDINE-INDUCED FEVER
SiR,—Fever has been reported as a side-effect of cimetidine.’-3 We have experimental evidence that stimulation of histamine H2 receptors in the hypothalamus produces sleep4 and hypothermia, and other reports suggest involvement of H1 and H2 receptors in thermoregulation.s6 In adult fowls (Gallus domesticus) with cannulae implanted into the hypothalamus or the third cerebral ventricle7 microinfusion of ’Dimaprit’, a selective H2 agonist,8 produces a significant fall in body temperature (see table) continuously recorded via a thermistor inserted under the skin in the interscapular region. BODY TEMPERATURE EFFECTS AFTER INTRAVENTRICULAR OR INTRAHYPOTHALAMIC INFUSION OF DIMAPRIT OR CIMETIDINE IN ADULT FOWLS
Serum 25-OHD and
1,2S-(OH)D
in
patients with jejunoileal
bypass operation. Solid and broken lines indicate mean + s.D. for healthy controls.
We have studied forty patients 2-6 years after jejunoileal bypass. As shown in the figure the 25-OHD values were very low in many patients, confirming the findings of Compston et al. Furthermore circulating 1,25-(OH)2D concentrations (measured by competitive protein-binding assay) were also low, and they did not correlate with serum 25-OHD, calcium, magnesium, or parathyroid hormone or loss of bone estimated by
photon absorptiometry. We agree with Compston
et al. that the problem of postis and our results indicate that bone disease complex, bypass treatment with lot-hydroxyvitamin D3 or 1,25-(OH)D is worth trying.
Department of Orthopædic Surgery, Frederiksborg County Hospital, 3400 Hillerød, Denmark
BJARNE LUND
Department of Medicine, Nykøbing Falster
H. HEY
Frederiksborg University Hospital, Copenhagen
BIRGER LUND
Herlev
University Hospital,
Copenhagen
O. H.
SØRENSEN
of Clinical
Department Chemistry, Glostrup University Hospital, Copenhagen
M. S. CHRISTENSEN
ETHICAL PROBLEMS OF SCREENING FOR NEURAL-TUBE DEFECTS to
SIR,-Your readers may be interested to know, in relation the Bishop of Durham’s letter (July 15, p. 148), that, deli-
from a different denominational standpoint, a joint ad-hoc committee of the Catholic Union and the Guild of Catholic Doctors, meeting on June 29 and consisting of lawyers, laymen, and doctors of differing disciplines, came to exactly the same conclusion as did the bishop’s ethical working-group. On behalf of the joint ad-hoc, committee, which I
berating
1. Eisman, J. A., Hamstra, A. J., Kream, B. E.,
Biophys. 1976, 176, 235.
DeLuca, H. F. Archs Biochem.
Results as mean + S.E.
In contrast intraventricular infusion of cimetidine, an Hz antagonist9 (dissolved in 0.1 moVl hydrochloric acid and pH adjusted to 7), besides behavioural and electrocortical arousal
associated with vocalisation,
tachypnoea (120-180/min) and "escape responses", produced an intense hyperthermic response ; this was not dose-related, much larger increases being sometimes observed after smaller doses. Although the mean maximum increase was 1.80°C, in one bird we observed an hyperpyretic reaction and the body temperature rose by 3°C which is the upper limit tolerated in fowls. Defervescence usually occurred within 5 h of administration of cimetidine, but in a few cases fever persisted for up to 48 h. No significant changes in body temperature were observed -after infusion into the cerebral ventricle (n=6) or hypothalamus (n=6) of the same volumes (5 or 1 .1) of distilled water adjusted at the same pH as dimaprit or cimetidine. These findings suggest that fever after cimetidine is due to a blockade of histamine H2 receptors in the thermoregulatory areas of the hypothalamus, and this may help us to understand the mechanism underlying the fever reaction to cimetidine in man. Although cimetidine does not easily cross the blood/brain barrier’O tiny amounts might reach the hypothalamus and proRamboer, C. Lancet, 1978, i, 330. McLoughlin, J. C., Callender, M. E., Love, A. H. G. ibid. p. 499. Corbett, C. L., Holdsworth, C. D. Br. med. J. 1978, i, 753. Nisticò, G., De Sarro, A., Rotiroti, D., Naccari, F. Paper read at VIIth International Congress of Pharmacology, held in Paris on July 16-21, 1978. 5. Clark, W. G., Cumby, H. R.J. Physiol. 1976, 261, 235. 6. Green, M. D., Cox, B., Lomax, P. Neuropharmacology, 1976, 15, 321. 7. Marley, E., Nisticò, G. Br. J. Pharmac. 1972, 46, 619. 8. Parsons, M. E., Owen, D. A. A., Ganellin, C. R., Durant, G. J. Age. Actions, 1977, 7, 31. 9. Brimblecomble, R. W., Duncan, W. A. M., Durant, G. J., Emmett, J. C., Ganellin, C. R., Parsons, M. E.J. int. med. Res. 1975, 3, 86. 10. Cross, S. A. M. in Proceedings of the European Society for Drug Toxicology, 1. 2. 3. 4.
(Edinburgh, 1976). (In the press).
SiR,—Dr Compston and her colleagues found that half their patients with jejunoileal bypasses for gross obesity had histological osteomalacia with evidence of secondary hyperparathyroidism. The plasma-25-hydroxyvitamin-D (25-OHD) did not correlate closely with the histological findings, and Compston et al. suggested that low circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) might contribute to the development of bone disease.
chaired, and the Guild of Catholic Doctors, of which I
am
welcome the bishop’s letter and commend it and its conclusion to your readers. As we see it no woman who objects to abortion in principle should ever undergo routine procedures that could lead to pressure being put upon her to be aborted or cause unnecessary worry about the possibility of giving birth to an abnormal child. master, I would like
to
21 Devonshire Place, London W1N 1PD
JONATHAN GOULD
MECHANISM OF CIMETIDINE-INDUCED FEVER
SiR,—Fever has been reported as a side-effect of cimetidine.’-3 We have experimental evidence that stimulation of histamine H2 receptors in the hypothalamus produces sleep4 and hypothermia, and other reports suggest involvement of H1 and H2 receptors in thermoregulation.s6 In adult fowls (Gallus domesticus) with cannulae implanted into the hypothalamus or the third cerebral ventricle7 microinfusion of ’Dimaprit’, a selective H2 agonist,8 produces a significant fall in body temperature (see table) continuously recorded via a thermistor inserted under the skin in the interscapular region. BODY TEMPERATURE EFFECTS AFTER INTRAVENTRICULAR OR INTRAHYPOTHALAMIC INFUSION OF DIMAPRIT OR CIMETIDINE IN ADULT FOWLS
Serum 25-OHD and
1,2S-(OH)D
in
patients with jejunoileal
bypass operation. Solid and broken lines indicate mean + s.D. for healthy controls.
We have studied forty patients 2-6 years after jejunoileal bypass. As shown in the figure the 25-OHD values were very low in many patients, confirming the findings of Compston et al. Furthermore circulating 1,25-(OH)2D concentrations (measured by competitive protein-binding assay) were also low, and they did not correlate with serum 25-OHD, calcium, magnesium, or parathyroid hormone or loss of bone estimated by
photon absorptiometry. We agree with Compston
et al. that the problem of postis and our results indicate that bone disease complex, bypass treatment with lot-hydroxyvitamin D3 or 1,25-(OH)D is worth trying.
Department of Orthopædic Surgery, Frederiksborg County Hospital, 3400 Hillerød, Denmark
BJARNE LUND
Department of Medicine, Nykøbing Falster
H. HEY
Frederiksborg University Hospital, Copenhagen
BIRGER LUND
Herlev
University Hospital,
Copenhagen
O. H.
SØRENSEN
of Clinical
Department Chemistry, Glostrup University Hospital, Copenhagen
M. S. CHRISTENSEN
ETHICAL PROBLEMS OF SCREENING FOR NEURAL-TUBE DEFECTS to
SIR,-Your readers may be interested to know, in relation the Bishop of Durham’s letter (July 15, p. 148), that, deli-
from a different denominational standpoint, a joint ad-hoc committee of the Catholic Union and the Guild of Catholic Doctors, meeting on June 29 and consisting of lawyers, laymen, and doctors of differing disciplines, came to exactly the same conclusion as did the bishop’s ethical working-group. On behalf of the joint ad-hoc, committee, which I
berating
1. Eisman, J. A., Hamstra, A. J., Kream, B. E.,
Biophys. 1976, 176, 235.
DeLuca, H. F. Archs Biochem.
Results as mean + S.E.
In contrast intraventricular infusion of cimetidine, an Hz antagonist9 (dissolved in 0.1 moVl hydrochloric acid and pH adjusted to 7), besides behavioural and electrocortical arousal
associated with vocalisation,
tachypnoea (120-180/min) and "escape responses", produced an intense hyperthermic response ; this was not dose-related, much larger increases being sometimes observed after smaller doses. Although the mean maximum increase was 1.80°C, in one bird we observed an hyperpyretic reaction and the body temperature rose by 3°C which is the upper limit tolerated in fowls. Defervescence usually occurred within 5 h of administration of cimetidine, but in a few cases fever persisted for up to 48 h. No significant changes in body temperature were observed -after infusion into the cerebral ventricle (n=6) or hypothalamus (n=6) of the same volumes (5 or 1 .1) of distilled water adjusted at the same pH as dimaprit or cimetidine. These findings suggest that fever after cimetidine is due to a blockade of histamine H2 receptors in the thermoregulatory areas of the hypothalamus, and this may help us to understand the mechanism underlying the fever reaction to cimetidine in man. Although cimetidine does not easily cross the blood/brain barrier’O tiny amounts might reach the hypothalamus and proRamboer, C. Lancet, 1978, i, 330. McLoughlin, J. C., Callender, M. E., Love, A. H. G. ibid. p. 499. Corbett, C. L., Holdsworth, C. D. Br. med. J. 1978, i, 753. Nisticò, G., De Sarro, A., Rotiroti, D., Naccari, F. Paper read at VIIth International Congress of Pharmacology, held in Paris on July 16-21, 1978. 5. Clark, W. G., Cumby, H. R.J. Physiol. 1976, 261, 235. 6. Green, M. D., Cox, B., Lomax, P. Neuropharmacology, 1976, 15, 321. 7. Marley, E., Nisticò, G. Br. J. Pharmac. 1972, 46, 619. 8. Parsons, M. E., Owen, D. A. A., Ganellin, C. R., Durant, G. J. Age. Actions, 1977, 7, 31. 9. Brimblecomble, R. W., Duncan, W. A. M., Durant, G. J., Emmett, J. C., Ganellin, C. R., Parsons, M. E.J. int. med. Res. 1975, 3, 86. 10. Cross, S. A. M. in Proceedings of the European Society for Drug Toxicology, 1. 2. 3. 4.
(Edinburgh, 1976). (In the press).
