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POTENTIATION OF INSULIN HYPOGLYCÆMIA
770 I estimate that pandemics of poliomyelitis will affect the North Atlantic community at intervals of roughly 40 years, and that they will have maxima over about 12 years. So, although minor epidemics of infantile type might afflict the poorer parts of our industrial cities, no major epidemic of the lethal adult type is likely before 1975-and the protection of the adult is the problem to be solved. It would be inadvisable to make specific claims for Sabin vaccination before 1980. After all, no one claims that smallpox vaccination is 90% effective, nor that it has abolished epidemics. Law Hospital, T. W. LEES. Carluke, Lanarkshire.
POTENTIATION OF INSULIN HYPOGLYCÆMIA SIR,-We were interested to see the preliminary communication by Dr. Cooper and Dr. Ashcroft (Feb. 19) on the potentiation of insulin-induced hypoglycaemia by monoamine-oxidase inhibitors. We have performed almost identical experiments, using rabbits weighing between 1.5 and 2-5 kg. We have studied the effects of subcutaneous mebanazine oxalate and tranylcypromine sulphate on insulin tolerance. A control insulin-tolerance test was done using intravenous insulin, 0-24 units per kg. Four rabbits were given mebanazine 3-0 mg. of base per kg., and another four tranylcypromine 3-7 mg. of base per kg.
The insulin-tolerance test was repeated after 3 weeks’ treatment, and thus each rabbit acted as its own control. Blood was obtained from the rabbits’ ear veins, and glucose was measured by the glucose-oxidase method of Marks.1 The figure shows the effect of these drugs on the blood-glucose response to insulin. At no point was there a significant change in the insulintolerance curves after treatment (p > 0-05). The dose of tranylcypromine used was comparable with that used by Dr. Cooper and Dr. Ashcroft, and yet we found no potentiation of insulininduced hypoglycxmia. We gave our drugs subcutaneously, however, rather than intramuscularly. Our dose of mebanazine (3-0 mg. per kg.) was roughly half that used by Dr. Cooper and Dr. Ashcroft, and this may account for our failure to induce hypoglycaEmic unresponsiveness with mebanazine. Further experiments are in progress using higher doses of these
drugs. Manchester Royal Infirmary, and the Department of Pharmacology,
Manchester University.
P. I. ADNITT S. OLEESKY H. SCHNEIDEN.
PHYTOHÆMAGGLUTININ IN APLASTIC ANÆMIA
SIR,-Humble2 suggested that phytohtmagglutinin (P.H.A.) might be effective in aplastic anaemia. The results of Baker and Oliverare in favour of Humble’s hypothesis, while Fleeing,4 Retief et al.,5 and Mehra et al.have had disappointing experiences with P.H.A. Papac, in her article (Jan. 8), writes that on the basis of animal studies " the use of P.H.A. in aplastic states in man seems to be tenuous ". Robinson’s letter (Feb. 12), describing another series of tests, is in contrast, and shows some protective effect on the leucocyte-count in rats after irradiation. In all these reports P.H.A. has been given by injection. Because we have no knowledge about the action of P.H.A. in the human or in the animal body we found it logical to give this drug by infusion. A 56-year-old housewife had a febrile tonsillitis beginning on Nov. 1, 1965. She was treated with chloramphenicol for 4 days, receiving a total of 4 g. Penicillin was not given because the patient had had urticaria after an injection of this antibiotic 10 years before. From Nov. 5 she received oxytetracycline, and was
very ill and febrile.
On Nov. 9 her blood-count
was:
haemoglobin 72"o (11-4 g. per 100 ml.), white blood-cells 1100 per c.mm. (neutrophils 0, lymphocytes 1050, monocytes 40, plasmocytes 10), thrombocytes 240,000 per c.mm., reticulocytes 7%. The bone-marrow was severely hypoplastic, with few lymphocytes and plasmocytes, normal megakaryocytes, and diminished erythropoiesis. She was isolated, and received oxytetracycline, and 50 mg. prednisone 8-hourly. On Nov. 10 leucocytes were down to 700 per c.mm., and later to 500 per c.mm., with no neutrophils. 38 hours after the first blood-count we started continuous intravenous infusion, giving a total of 5 ampoules of P.H.A. (Burroughs Wellcome & Co.), dissolved in about 2 litres of equal parts of physiological saline solution and 50;, glucose, over the next 50 hours (until Nov. 13). No particular side-effects. The day after starting the treatment the white blood-cells were 900 per c.mm. (neutrophils 4); on Nov. 14 they were 1300 (neutrophils 90); Nov. 16,3600 (neutrophils 170, reticulocytes 13%); Nov. 18, 7900 (neutrophils 1400); Nov. 20, 20,400 (neutrophils 7100); Nov. 22,17,800 (neutrophils 10,700); and in the next days the white blood-cells were down to
7600 per
c.mm.
On Nov. 14,
we
noted the appearance of the
cells, described by Humble, with lymphocyte nucleus and granular cytoplasm; their numbers reached their height on Nov. 19 with about 3200 per c.mm., at which level they persisted for about 3 weeks. The thrombocytes went up to 720,000 per c.mm. on the 5th day after starting the treatment, and had gone down to 200,000 when the patient left the hospital in good
(b) tranylcypromine
on insulin tolerEffect of (a) mebanazine and ance. (Mean of results in 4 animals [standard error] for each
drug.) Drug effects shown lines.
as
interrupted, and control effects as continuous,
Marks, V. Clinica chim. Acta, 1959, 4, 395. Humble, J. G. Lancet, 1964, i, 1345. Baker, G. P., Oliver, R. A. ibid. 1965, i, 438. 4. Fleming, A. F. ibid. 1964, ii, 647. 5. Retief, F. P., Wasserman, H. P., Hofmeyer, N. G. ibid. p. 1343. 6. Mehra, S. K., Davies, D. M., Bell, S. M. ibid. 1965, i, 1165.
1. 2. 3.
POTENTIATION OF INSULIN HYPOGLYCÆMIA SIR,-We were interested to see the preliminary communication by Dr. Cooper and Dr. Ashcroft (Feb. 19) on the potentiation of insulin-induced hypoglycaemia by monoamine-oxidase inhibitors. We have performed almost identical experiments, using rabbits weighing between 1.5 and 2-5 kg. We have studied the effects of subcutaneous mebanazine oxalate and tranylcypromine sulphate on insulin tolerance. A control insulin-tolerance test was done using intravenous insulin, 0-24 units per kg. Four rabbits were given mebanazine 3-0 mg. of base per kg., and another four tranylcypromine 3-7 mg. of base per kg.
The insulin-tolerance test was repeated after 3 weeks’ treatment, and thus each rabbit acted as its own control. Blood was obtained from the rabbits’ ear veins, and glucose was measured by the glucose-oxidase method of Marks.1 The figure shows the effect of these drugs on the blood-glucose response to insulin. At no point was there a significant change in the insulintolerance curves after treatment (p > 0-05). The dose of tranylcypromine used was comparable with that used by Dr. Cooper and Dr. Ashcroft, and yet we found no potentiation of insulininduced hypoglycxmia. We gave our drugs subcutaneously, however, rather than intramuscularly. Our dose of mebanazine (3-0 mg. per kg.) was roughly half that used by Dr. Cooper and Dr. Ashcroft, and this may account for our failure to induce hypoglycaEmic unresponsiveness with mebanazine. Further experiments are in progress using higher doses of these
drugs. Manchester Royal Infirmary, and the Department of Pharmacology,
Manchester University.
P. I. ADNITT S. OLEESKY H. SCHNEIDEN.
PHYTOHÆMAGGLUTININ IN APLASTIC ANÆMIA
SIR,-Humble2 suggested that phytohtmagglutinin (P.H.A.) might be effective in aplastic anaemia. The results of Baker and Oliverare in favour of Humble’s hypothesis, while Fleeing,4 Retief et al.,5 and Mehra et al.have had disappointing experiences with P.H.A. Papac, in her article (Jan. 8), writes that on the basis of animal studies " the use of P.H.A. in aplastic states in man seems to be tenuous ". Robinson’s letter (Feb. 12), describing another series of tests, is in contrast, and shows some protective effect on the leucocyte-count in rats after irradiation. In all these reports P.H.A. has been given by injection. Because we have no knowledge about the action of P.H.A. in the human or in the animal body we found it logical to give this drug by infusion. A 56-year-old housewife had a febrile tonsillitis beginning on Nov. 1, 1965. She was treated with chloramphenicol for 4 days, receiving a total of 4 g. Penicillin was not given because the patient had had urticaria after an injection of this antibiotic 10 years before. From Nov. 5 she received oxytetracycline, and was
very ill and febrile.
On Nov. 9 her blood-count
was:
haemoglobin 72"o (11-4 g. per 100 ml.), white blood-cells 1100 per c.mm. (neutrophils 0, lymphocytes 1050, monocytes 40, plasmocytes 10), thrombocytes 240,000 per c.mm., reticulocytes 7%. The bone-marrow was severely hypoplastic, with few lymphocytes and plasmocytes, normal megakaryocytes, and diminished erythropoiesis. She was isolated, and received oxytetracycline, and 50 mg. prednisone 8-hourly. On Nov. 10 leucocytes were down to 700 per c.mm., and later to 500 per c.mm., with no neutrophils. 38 hours after the first blood-count we started continuous intravenous infusion, giving a total of 5 ampoules of P.H.A. (Burroughs Wellcome & Co.), dissolved in about 2 litres of equal parts of physiological saline solution and 50;, glucose, over the next 50 hours (until Nov. 13). No particular side-effects. The day after starting the treatment the white blood-cells were 900 per c.mm. (neutrophils 4); on Nov. 14 they were 1300 (neutrophils 90); Nov. 16,3600 (neutrophils 170, reticulocytes 13%); Nov. 18, 7900 (neutrophils 1400); Nov. 20, 20,400 (neutrophils 7100); Nov. 22,17,800 (neutrophils 10,700); and in the next days the white blood-cells were down to
7600 per
c.mm.
On Nov. 14,
we
noted the appearance of the
cells, described by Humble, with lymphocyte nucleus and granular cytoplasm; their numbers reached their height on Nov. 19 with about 3200 per c.mm., at which level they persisted for about 3 weeks. The thrombocytes went up to 720,000 per c.mm. on the 5th day after starting the treatment, and had gone down to 200,000 when the patient left the hospital in good
(b) tranylcypromine
on insulin tolerEffect of (a) mebanazine and ance. (Mean of results in 4 animals [standard error] for each
drug.) Drug effects shown lines.
as
interrupted, and control effects as continuous,
Marks, V. Clinica chim. Acta, 1959, 4, 395. Humble, J. G. Lancet, 1964, i, 1345. Baker, G. P., Oliver, R. A. ibid. 1965, i, 438. 4. Fleming, A. F. ibid. 1964, ii, 647. 5. Retief, F. P., Wasserman, H. P., Hofmeyer, N. G. ibid. p. 1343. 6. Mehra, S. K., Davies, D. M., Bell, S. M. ibid. 1965, i, 1165.
1. 2. 3.