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CHLORPROPAMIDE AND HYPONATRAEMIA
386
consultants said that they did not normally attend meetings of the medical committee (chiefly because their other duties were too heavy). In other words, not all the consultants who regarded the administration of their hospitals as inefficient were using the existing machinery for making their opinions known. Two other aspects of the consultant’s managerial role bearing directly on patient care-outpatient appointments and visiting hours in wards-were also examined in the questionary. Opinions varied about whether control of these matters rightly belonged to the consultant; the young consultants tended to be more tolerant of delays in giving appointments than their seniors, while only 25 of the sample said that they played a part in determining the visiting-hours for patients in their wards. Anderson et al .2conclude that " some consultants are more complacent about what they regard as short-comings in the management of hospitals than others ", but they suggest that consultants might well feel that the present machinery was so ineffective that any attempt on their part to remedy the situation On the whole, however, conwas doomed to failure. sultants seemed prepared to cooperate in surveys of this kind, and such inquiries could be useful in assessing the effect of any further efforts made to influence the attitudes of hospital consultants towards management.
CHLORPROPAMIDE AND HYPONATRAEMIA
SEVERAL unrelated compounds have an antidiuretic action in patients with diabetes insipidus, including chlorothiazide,3metformin,and paracetamol.5 Arduino et al.1-first described a similar action of chlorpropamide in 3 patients with diabetes insipidus, after a patient with polyuria due to this condition had treated himself with the drug because of a possible diagnosis of diabetes mellitus. Other investigators 7,8 confirmed these observations, and although many different mechanisms of action have been proposed, the most probable seems to be that chlorpropamide potentiates the effect of vasopressin to increase water permeability and hence reabsorption in the distal nephron.99 If that is what happens in subjects whose secretion of vasopressin is normal, as well as in those with diabetes insipidus, then it might be postulated that a hyponatraemic syndrome might be produced similar to the " inappropriate antidiuretic-hormone (A.D.H.) syndrome ",10described in a variety of conditions, including carcinoma of the bronchus. Weissman et al.ll recorded their findings in 5 patients who were receiving chlorpropamide for diabetes mellitus, and in whom a syndrome of hyponatrxmia and serum hypo-osmolality developed, with continued sodium Crawford, J. D., Kennedy, G. C. Nature, 1959, 183, 891. Katsuki, S., Ito, M. Lancet, 1966, ii, 530. Nusynowitz, M. L., Forsham, P. H. Am. J. med. Sci. 1966, 252, 429. Arduino, F., Ferraz, F. P. J., Rodrigues, J. J. clin. Endocr. Metab. 1966, 26, 1325. 7. Meinders, A. E., Touber, J. L., de Vries, L. A. Lancet, 1967, ii, 544. 8. Hocken, A. G., Longson, D. Br. med.J. 1968, i, 355. 9. Earley, L. New Engl. J. Med. 1971, 284, 103. 10. Bartter, F. C., Schwartz, W. B. Am. J. Med. 1967, 42, 790. 11. Weissman, P. N., Shenkman, L., Gregerman, R. I. New Engl. J. Med. 1971, 284, 65. 3. 4. 5. 6.
despite hyponatraemia and an impaired achieve maximum urinary dilution and to excrete a water load. Clinical features included anorexia, profound muscle weakness, cardiac enlargement, and oedema. The clinical and chemical abnormalities disappeared when chlorpropamide was withdrawn, but they appeared again when it was restarted. A survey at a diabetic clinic showed that about 4% of patients receiving chlorpropamide had hyponatrxmia, which, if the finding is confirmed, means that many patients may be ill from this cause. Considering the reasons why a few patients respond in this way to chlorpropamide, Weissman et al. suggest that, although in most people A.D.H. secretion is completely suppressed by such conditions as severe serum hypo-osmolality, there may be a group in whom the mechanism for turning off A.D.H. secretion is imperfect, and these people may therefore continue to secrete small amounts of A.D.H. despite the existence of conditions that should completely suppress its release. It is this group among a population of diabetics who would be at risk of a syndrome of positive water balance and hyponatrxmia if treated with chlorpropamide. Weissman et al. emphasise that chlorpropamide must be used cautiously in patients with incipient or overt congestive cardiac failure, and in others who are given water loads therapeutically for urinary-tract infection or before cystoscopy and other examinations of the urinary tract. In view of the similar effect of metformin in diabetes insipidusthe incidence of hyponatrsemia in diabetic patients treated with this drug should be determined. excretion
ability
to
DIPHTHERIA AGAIN
THIS week, 3 Manchester children are in hospital with mild diphtheria, and 32 carriers have so far been traced. Most of the children go to Stanley Grove Junior School, Longsight, but one of the carriers has a brother at Spurley Hey High School, Gorton. When the outbreak came to light, the children from the Gorton school were on holiday, and this has delayed screening. Most of the diphtheria outbreaks in England in the past ten years have been north of a line joining the Wash and the Severn. And it is in the North of England that immunisation-rates tend to be lowest. In Manchester only 67% of the children born in 1967 had been immunised against diphtheria by the end of 1969, as against the average rate for England of 83 %.12 Opinions differ on the immunisation-rate needed to prevent epidemic spread of diphtheria: 70% is widely accepted,1but some put it as high as
90 %.14 The lesson of this outbreak is that parents
must
be
badgered still harder to get their children immunised. Special measures-such as computer harassment 15 or home visits-are needed to eliminate the areas of low immunity. Diphtheria is not the only worrythe next outbreak may be poliomyelitis or smallpox. 12. On the State of the Public Health; p. 230. H.M. Stationery Office, 1970. 13. See Lancet, 1970, i, 1215. 14. Zalma, V. M., Older, J. J., Brooks, G. F. J. Am. med. Ass. 1970, 211, 2125. 15. See Lancet, 1970, ii, 865.
consultants said that they did not normally attend meetings of the medical committee (chiefly because their other duties were too heavy). In other words, not all the consultants who regarded the administration of their hospitals as inefficient were using the existing machinery for making their opinions known. Two other aspects of the consultant’s managerial role bearing directly on patient care-outpatient appointments and visiting hours in wards-were also examined in the questionary. Opinions varied about whether control of these matters rightly belonged to the consultant; the young consultants tended to be more tolerant of delays in giving appointments than their seniors, while only 25 of the sample said that they played a part in determining the visiting-hours for patients in their wards. Anderson et al .2conclude that " some consultants are more complacent about what they regard as short-comings in the management of hospitals than others ", but they suggest that consultants might well feel that the present machinery was so ineffective that any attempt on their part to remedy the situation On the whole, however, conwas doomed to failure. sultants seemed prepared to cooperate in surveys of this kind, and such inquiries could be useful in assessing the effect of any further efforts made to influence the attitudes of hospital consultants towards management.
CHLORPROPAMIDE AND HYPONATRAEMIA
SEVERAL unrelated compounds have an antidiuretic action in patients with diabetes insipidus, including chlorothiazide,3metformin,and paracetamol.5 Arduino et al.1-first described a similar action of chlorpropamide in 3 patients with diabetes insipidus, after a patient with polyuria due to this condition had treated himself with the drug because of a possible diagnosis of diabetes mellitus. Other investigators 7,8 confirmed these observations, and although many different mechanisms of action have been proposed, the most probable seems to be that chlorpropamide potentiates the effect of vasopressin to increase water permeability and hence reabsorption in the distal nephron.99 If that is what happens in subjects whose secretion of vasopressin is normal, as well as in those with diabetes insipidus, then it might be postulated that a hyponatraemic syndrome might be produced similar to the " inappropriate antidiuretic-hormone (A.D.H.) syndrome ",10described in a variety of conditions, including carcinoma of the bronchus. Weissman et al.ll recorded their findings in 5 patients who were receiving chlorpropamide for diabetes mellitus, and in whom a syndrome of hyponatrxmia and serum hypo-osmolality developed, with continued sodium Crawford, J. D., Kennedy, G. C. Nature, 1959, 183, 891. Katsuki, S., Ito, M. Lancet, 1966, ii, 530. Nusynowitz, M. L., Forsham, P. H. Am. J. med. Sci. 1966, 252, 429. Arduino, F., Ferraz, F. P. J., Rodrigues, J. J. clin. Endocr. Metab. 1966, 26, 1325. 7. Meinders, A. E., Touber, J. L., de Vries, L. A. Lancet, 1967, ii, 544. 8. Hocken, A. G., Longson, D. Br. med.J. 1968, i, 355. 9. Earley, L. New Engl. J. Med. 1971, 284, 103. 10. Bartter, F. C., Schwartz, W. B. Am. J. Med. 1967, 42, 790. 11. Weissman, P. N., Shenkman, L., Gregerman, R. I. New Engl. J. Med. 1971, 284, 65. 3. 4. 5. 6.
despite hyponatraemia and an impaired achieve maximum urinary dilution and to excrete a water load. Clinical features included anorexia, profound muscle weakness, cardiac enlargement, and oedema. The clinical and chemical abnormalities disappeared when chlorpropamide was withdrawn, but they appeared again when it was restarted. A survey at a diabetic clinic showed that about 4% of patients receiving chlorpropamide had hyponatrxmia, which, if the finding is confirmed, means that many patients may be ill from this cause. Considering the reasons why a few patients respond in this way to chlorpropamide, Weissman et al. suggest that, although in most people A.D.H. secretion is completely suppressed by such conditions as severe serum hypo-osmolality, there may be a group in whom the mechanism for turning off A.D.H. secretion is imperfect, and these people may therefore continue to secrete small amounts of A.D.H. despite the existence of conditions that should completely suppress its release. It is this group among a population of diabetics who would be at risk of a syndrome of positive water balance and hyponatrxmia if treated with chlorpropamide. Weissman et al. emphasise that chlorpropamide must be used cautiously in patients with incipient or overt congestive cardiac failure, and in others who are given water loads therapeutically for urinary-tract infection or before cystoscopy and other examinations of the urinary tract. In view of the similar effect of metformin in diabetes insipidusthe incidence of hyponatrsemia in diabetic patients treated with this drug should be determined. excretion
ability
to
DIPHTHERIA AGAIN
THIS week, 3 Manchester children are in hospital with mild diphtheria, and 32 carriers have so far been traced. Most of the children go to Stanley Grove Junior School, Longsight, but one of the carriers has a brother at Spurley Hey High School, Gorton. When the outbreak came to light, the children from the Gorton school were on holiday, and this has delayed screening. Most of the diphtheria outbreaks in England in the past ten years have been north of a line joining the Wash and the Severn. And it is in the North of England that immunisation-rates tend to be lowest. In Manchester only 67% of the children born in 1967 had been immunised against diphtheria by the end of 1969, as against the average rate for England of 83 %.12 Opinions differ on the immunisation-rate needed to prevent epidemic spread of diphtheria: 70% is widely accepted,1but some put it as high as
90 %.14 The lesson of this outbreak is that parents
must
be
badgered still harder to get their children immunised. Special measures-such as computer harassment 15 or home visits-are needed to eliminate the areas of low immunity. Diphtheria is not the only worrythe next outbreak may be poliomyelitis or smallpox. 12. On the State of the Public Health; p. 230. H.M. Stationery Office, 1970. 13. See Lancet, 1970, i, 1215. 14. Zalma, V. M., Older, J. J., Brooks, G. F. J. Am. med. Ass. 1970, 211, 2125. 15. See Lancet, 1970, ii, 865.