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ORAL HYPOGLYCÆMIC AGENTS
929
We believe that the study of sex chromosomal anomalies is entering a phase in which it may be eventually possible to classify the anomaly in relation to the clinical picture. It is therefore important, in our present state of knowledge, to be precise in our recording and diagnosis of those cases about which we have reasonable knowledge of the clinical condition. In our opinion the case reported is a typical case of true hermaphroditism and does not show anv of the classical features of Klinefelter’s syndrome. Guy’s Hospital, London, S.E.1.
P. M. F. BISHOP P. E. POLANI.
OBSTETRIC
FLYING-SQUADS SiR,-Mr. Stabler (Oct. 8) delightedly supports Dr. Walden’s suggestion that women can be as safely confined at home as in hospital. Of course, but why stop here ? We must all agree that obstetrics is the least predictable of all medical subjects; therefore, presumably it should be meritorious to have one’s tonsils out on the as I did 45 years ago, and why not do all hernias, appendices, varicose veins, &c., there also ? 28 years ago, I gave blood in a private house in Bracknell where the late Sir Thomas Dunhill assisted by Mr. Paterson Ross (now Sir James) was doing a gastrectomy. Why not pull down all the hospitals and go back to the " good old days ", or has the spirit of pioneering died ? even more
kitchen table,
KEITH VARTAN. ORAL HYPOGLYCÆMIC AGENTS SiR,-We read with interest the letter of Sept. 10 from Dr. Locket and Dr. Brown, because we have recently encountered two instances of coma in diabetic patients receiving chlorpropamide. In both the coma proved to
bility of severe hypoglocsemic reactions to chlorpropamide. Because of the prolonged action of chlorpropamide, the possibility of recurring hypoglycaemia should be kept in mind.
J. BRADLEY M. G. FITZGERALD D. J. SCOTT.
General Hospital,
Birmingham.
RADIOCHEMICAL SYNTHESIS OF TRIIODOTHYRONINE
SIR,-We have read with interest Dr. Deutsch’s
(Sept. 10) letter on the possible formation of 1311-labelled triiodothyronine from 131I_labelled thyroxine after the decay of one 131J atom to l31Xe. We should like to make the following comments. In the work of Gross and Pitt-Rivers,1-3 cited by Dr. Deutsch, synthetic radioactive thyroxine, labelled in the 3’ and 5’ positions only, was not used. Human subjects and experi" mental animals were given " carrier-free Na131I, which was hormones in their converted to labelled thyroid glands. According to present concepts of thyroid hormone biosynthesis, iodide after entering the gland is first incorporated into the iodotyrosines; these are then converted by a coupling mechanism to thyroxine and to a lesser extent to 3,5,3’-triiodothyronine. The thyroxine thus formed from 131I-labelled diiodotyrosine will be uniformly labelled; that is, all four iodine atoms in the thyronine molecule have an equal chance of being labelled. Now the decay of any one 1311 atom in the thyroxine molecule is not affected by its position; therefore the following products of decay should all be theoretically produced:
be due to hypoglycxmia, and we wish to draw attention to the possible effect of the usual therapeutic doses of the drug. CASE l.-An obese alcoholic man of 55 was treated for diabetes of a year’s known duration by a low-carbohydrate diet and a daily dose of 250 mg. of chlorpropamide. His symptoms of diabetes were relieved, and when seen on five subsequent occasions the urine was sugar-free and the early afternoon blood-sugar varied between 85 and 115 mg. per 100 ml. The day he was admitted to hospital, he left for work without breakfast. At midday he was brought home unsteady and aphasic. An hour later he became unconscious. When admitted at 5 P.M. the same day he was in coma, and the plantar reflexes were extensor. The blood-glucose level (autoanalyser) was 30 mg. per 100 ml. on admission, and he rapidly regained consciousness after an intravenous injection of 40 ml. of 50% glucose. Six hours later he became restless and
mentally confused, but again rapidly improved following a further intravenous injection of 20 ml. of 50% glucose. At this time his serum-chlorpropamide level was 8-5 mg. per 100 ml. (therapeutic range 2-5-17-5). CASE 2.-A spare man of 62 was treated for mild diabetes of a month’s known duration by 250 mg. of chlorpropamide daily. A month later, when his wife went to wake him, he was found in bed semiconscious and aphasic. He had been well the evening before, and had eaten his supper. When seen at hospital he was semiconscious and had a right hemiparesis. Since he was not known to be a diabetic, hypoglycaemia was not seriously considered. Blood for glucose estimation was taken at 10 A.M., however, and found to be 18 mg. per 100 ml. This reading was not known by us until 3.45 P.M., when his clinical condition was unchanged, and the blood-sugar at that time was 22 mg. per 100 ml. Given intravenous glucose, he quickly revived, but remained dysphasic for a further two days.
Patient and relatives should be warned of the
possi-
Thyroxine would first yield the two isomers of triiodothyronine, 3,5,3’-T3 and 3,3/,5/- T (the abbreviations used are those recommended by Harington et al. 4) These would give rise to the three isomeric diiodothyronines 3,5-Ts, 3,3’-T2, and 3’,5’; T2 which in their turn would give the two monoiodothyronines 3-T, and 3-Tl. Complete decay would finally give unlabelled thyronine. In short time intervals after z1 administration (1-24 hours) to animals, the thyroid gland would contain only minute amounts of the di- and mon-iodothyronines formed by decay. However, 4 days after thyroxine biosynthesis, decay alone would result in the production of 12-0% each of the triiodothyronines ; 1-0% each of 3,5-T2 and 3’,5’-Tz; 2-0% of3,3’-Ta; and 0-45% each of 3-T, and 3’-T2. Four days after a dose of 100 mC 1311 to a human subject or 100 C to a rat, the two triiodothyronines, three diiodothyronines, and two monoiodothyronines should be detectable if formed by decay of thyroxine 131Ialone. In fact, most of these partially iodinated thyronines have not been detected in thyroid hydrolysates at any time interval after the administration of 1311 to 1. 2. 3. 4.
Gross, J., Pitt-Rivers, R. Lancet, 1951, ii, 766. Gross, J., Pitt-Rivers, R. ibid. 1952, i, 439. Gross, J., Pitt-Rivers, R. Biochem. J. 1953, 53, 645. Harington, C. R., Pitt-Rivers, R., Querido, A., Roche, Nature, Lond. 1957, 179, 218.
man or
J., Taurog, A.
We believe that the study of sex chromosomal anomalies is entering a phase in which it may be eventually possible to classify the anomaly in relation to the clinical picture. It is therefore important, in our present state of knowledge, to be precise in our recording and diagnosis of those cases about which we have reasonable knowledge of the clinical condition. In our opinion the case reported is a typical case of true hermaphroditism and does not show anv of the classical features of Klinefelter’s syndrome. Guy’s Hospital, London, S.E.1.
P. M. F. BISHOP P. E. POLANI.
OBSTETRIC
FLYING-SQUADS SiR,-Mr. Stabler (Oct. 8) delightedly supports Dr. Walden’s suggestion that women can be as safely confined at home as in hospital. Of course, but why stop here ? We must all agree that obstetrics is the least predictable of all medical subjects; therefore, presumably it should be meritorious to have one’s tonsils out on the as I did 45 years ago, and why not do all hernias, appendices, varicose veins, &c., there also ? 28 years ago, I gave blood in a private house in Bracknell where the late Sir Thomas Dunhill assisted by Mr. Paterson Ross (now Sir James) was doing a gastrectomy. Why not pull down all the hospitals and go back to the " good old days ", or has the spirit of pioneering died ? even more
kitchen table,
KEITH VARTAN. ORAL HYPOGLYCÆMIC AGENTS SiR,-We read with interest the letter of Sept. 10 from Dr. Locket and Dr. Brown, because we have recently encountered two instances of coma in diabetic patients receiving chlorpropamide. In both the coma proved to
bility of severe hypoglocsemic reactions to chlorpropamide. Because of the prolonged action of chlorpropamide, the possibility of recurring hypoglycaemia should be kept in mind.
J. BRADLEY M. G. FITZGERALD D. J. SCOTT.
General Hospital,
Birmingham.
RADIOCHEMICAL SYNTHESIS OF TRIIODOTHYRONINE
SIR,-We have read with interest Dr. Deutsch’s
(Sept. 10) letter on the possible formation of 1311-labelled triiodothyronine from 131I_labelled thyroxine after the decay of one 131J atom to l31Xe. We should like to make the following comments. In the work of Gross and Pitt-Rivers,1-3 cited by Dr. Deutsch, synthetic radioactive thyroxine, labelled in the 3’ and 5’ positions only, was not used. Human subjects and experi" mental animals were given " carrier-free Na131I, which was hormones in their converted to labelled thyroid glands. According to present concepts of thyroid hormone biosynthesis, iodide after entering the gland is first incorporated into the iodotyrosines; these are then converted by a coupling mechanism to thyroxine and to a lesser extent to 3,5,3’-triiodothyronine. The thyroxine thus formed from 131I-labelled diiodotyrosine will be uniformly labelled; that is, all four iodine atoms in the thyronine molecule have an equal chance of being labelled. Now the decay of any one 1311 atom in the thyroxine molecule is not affected by its position; therefore the following products of decay should all be theoretically produced:
be due to hypoglycxmia, and we wish to draw attention to the possible effect of the usual therapeutic doses of the drug. CASE l.-An obese alcoholic man of 55 was treated for diabetes of a year’s known duration by a low-carbohydrate diet and a daily dose of 250 mg. of chlorpropamide. His symptoms of diabetes were relieved, and when seen on five subsequent occasions the urine was sugar-free and the early afternoon blood-sugar varied between 85 and 115 mg. per 100 ml. The day he was admitted to hospital, he left for work without breakfast. At midday he was brought home unsteady and aphasic. An hour later he became unconscious. When admitted at 5 P.M. the same day he was in coma, and the plantar reflexes were extensor. The blood-glucose level (autoanalyser) was 30 mg. per 100 ml. on admission, and he rapidly regained consciousness after an intravenous injection of 40 ml. of 50% glucose. Six hours later he became restless and
mentally confused, but again rapidly improved following a further intravenous injection of 20 ml. of 50% glucose. At this time his serum-chlorpropamide level was 8-5 mg. per 100 ml. (therapeutic range 2-5-17-5). CASE 2.-A spare man of 62 was treated for mild diabetes of a month’s known duration by 250 mg. of chlorpropamide daily. A month later, when his wife went to wake him, he was found in bed semiconscious and aphasic. He had been well the evening before, and had eaten his supper. When seen at hospital he was semiconscious and had a right hemiparesis. Since he was not known to be a diabetic, hypoglycaemia was not seriously considered. Blood for glucose estimation was taken at 10 A.M., however, and found to be 18 mg. per 100 ml. This reading was not known by us until 3.45 P.M., when his clinical condition was unchanged, and the blood-sugar at that time was 22 mg. per 100 ml. Given intravenous glucose, he quickly revived, but remained dysphasic for a further two days.
Patient and relatives should be warned of the
possi-
Thyroxine would first yield the two isomers of triiodothyronine, 3,5,3’-T3 and 3,3/,5/- T (the abbreviations used are those recommended by Harington et al. 4) These would give rise to the three isomeric diiodothyronines 3,5-Ts, 3,3’-T2, and 3’,5’; T2 which in their turn would give the two monoiodothyronines 3-T, and 3-Tl. Complete decay would finally give unlabelled thyronine. In short time intervals after z1 administration (1-24 hours) to animals, the thyroid gland would contain only minute amounts of the di- and mon-iodothyronines formed by decay. However, 4 days after thyroxine biosynthesis, decay alone would result in the production of 12-0% each of the triiodothyronines ; 1-0% each of 3,5-T2 and 3’,5’-Tz; 2-0% of3,3’-Ta; and 0-45% each of 3-T, and 3’-T2. Four days after a dose of 100 mC 1311 to a human subject or 100 C to a rat, the two triiodothyronines, three diiodothyronines, and two monoiodothyronines should be detectable if formed by decay of thyroxine 131Ialone. In fact, most of these partially iodinated thyronines have not been detected in thyroid hydrolysates at any time interval after the administration of 1311 to 1. 2. 3. 4.
Gross, J., Pitt-Rivers, R. Lancet, 1951, ii, 766. Gross, J., Pitt-Rivers, R. ibid. 1952, i, 439. Gross, J., Pitt-Rivers, R. Biochem. J. 1953, 53, 645. Harington, C. R., Pitt-Rivers, R., Querido, A., Roche, Nature, Lond. 1957, 179, 218.
man or
J., Taurog, A.