TABLET IDENTIFICATION

212 have

of bone than hypoparathyroid postremains true. Although the mean external diameter in the hyperparathyroid group (7-34 mm.) is higher than the mean in the hypoparathyroid group (7-04 mm.), the mean C.A. is lower in the hyperparathyroid group, when normally a larger C.A. would have been expected for a larger external diameter. Parathyroid activity and its relation to the menopause, however, does not explain the overall age-related loss of bone in men and women from the age of 35 years onwards. Department of Internal Medicine, Academic Hospital St.-Rafael, JAN V. DEQUEKER. Leuven, Belgium. a

smaller

menopausal

amount

women

PLASMA-PHOSPHATE AND TUBULAR REABSORPTION OF PHOSPHATE SIR,-The letter from Dr. Bijvoet and Dr. Morgan1 calls for a factual answer. Their hypothetical person with a Tm/G.F.R. of 2-5 mg. per 100 ml. of G.F. is, in our opinion and according to our data, in a state of hyperparathyroidism, possibly resulting from parathyroid stimulation produced by the phosphate infusion itself. Previous workers have commented on the falling Tm produced by phosphate infusions exceeding 150 minutes.2 The simple fact is that in the 95 normal

subjects reported by us,3 phosphate excretion, even at a plasma-phosphate of 5 mg. per 100 ml., never exceeded 0-7 mg. per 100 ml. of G.F. This contrasts with the figure of 2 mg. per 100 ml. of G.F. which Bijvoet and Morgan claim to be normal at a plasma-phosphate of 4-5 mg. per 100 ml. Thus, their calculation will tend to classify as normal, values which we never see in fasting normal subjects and which we would regard as abnormal and generally due to primary or secondary hyperparathyroidism. It is quite incorrect to say that the diagnostic value of our index of phosphate excretion stems from the fact that it compounds a low Tm/G.F.R. and a high UV/G.F.R. Our figure is no more influenced by absolute phosphate output than theirs, since the term which we call PE (mg. per 100 ml.) is of course the same as the term which they call UV/L (mg. per litre). Both procedures in fact come down to exactly the same concept-an attempt to establish whether a given rate of phosphate excretion is normal, too high, or too low relative It is to the prevailing plasma-phosphate concentration. true that the slope of urine on plasma phosphate which we use as our reference standard is not as steep at high plasmaphosphate levels as their mean normal curve-in fact it is a tangent to their curve at the normal plasma-phosphate level -but our range is virtually identical with theirs between plasma-phosphate concentrations of 2 and 4 mg. per 100 ml. At higher plasma levels the two lines differ significantly, and which is the more correct in practice must surely depend on observations made on normal individuals in the fasting state. As we have said, by this criterion our reference standard is the better of the two. In fact, our line would correspond more closely to the normal Tm established by Anderson and Parsons2 than to that of Morgan and Bijvoet. Finally, we can only repeat our previous statement that calculation of Tm/G.F.R. by Bijvoet and Morgan’s method involves an extrapolation from a single point. We do not doubt-in fact we have always assumed-that there is a relationship between basal phosphate excretion (relative to filtered load) and the Tm/G.F.R., just as there is a relation between basal acid output and maximum acid output in This of course permits a rough normal individuals.4 1. 2. 3. 4.

Bijvoet, O. L. M., Morgan, D. B. Lancet, 1970, i, 1345. Anderson, J., Parsons, V. Clin. Sci. 1963, 25, 431. Nordin, B. E. C., Bulusu, L. Postgrad. med. J. 1968, 44, 93. Baron, J. H. Clin. Sci. 1963, 24, 357.

estimate of Tm/G.F.R. from a single point, just as it permits a rough estimate of maximum acid output from a single observation of basal acid output, but in simple English this is an extrapolation and not a measurement. We insist that tubular maximum reabsorptive capacity can only be measured by a procedure which actually saturates this

capacity. M.R.C. Mineral Metabolism Unit, General Infirmary, Leeds.

B. E. C. NORDIN L. BULUSU.

COMPLICATIONS OF THYROIDECTOMY SiR,ńIshould like to associate myself entirely with Mr. W. Michie’s remarks in regard to exposure of the recurrent laryngeal nerve in thyroid surgery.1 It is good to see commonsense and logic brought to bear on a subject that has always appeared to me to be unnecessarily controversial. The pros and cons of exposure of the nerve are argued endlessly, almost to the exclusion of other important structures. I would make a plea that all published figures should also indicate the incidence of hypoparathyroidism and of recurrent goitre (or recurrent

thyrotoxicosis). Department of Endocrinology, New End Hospital, London N.W.3.

M. J. LANGE.

DRUGS AND CONGENITAL GOITRE SiR,ńThe article of Dr. Carswell and his colleagues2 is an important warning of the effects of exogenous iodides on fetal-thyroid size and function. The accompanying editorial reinforces the point well. Wolff and Varrone3 have shown that, in rats, methylxanthines are also goitrogenic. While, under the conditions of their investigation, methylxanthines did not augment the effect of iodide on thyroid size, they did produce goitre when given alone. Whether these two drugs act synergistically in man is problematical. It is intriguing that at least half the patients described by Dr. Carswell and his colleagues were taking caffeine as well as iodide. The rat studies of Wolff and Varrone, coupled with these and other clinical observations, should increase astuteness in evaluating goitre development in patients taking iodide alone or iodide and methylxanthine together. University of Connecticut, School of Medicine,

Hartford, Connecticut 06112.

JAMES M. STREETO.

TABLET IDENTIFICATION and more drugs become available, tablets SIR,-As more often have to be identified in casualty departments and outpatient clinics. The method of identification most commonly used is the colour identification chart in MIMS Annual Compendium, but this has drawbacks. Firstly, the colour reproduction is not very good, and secondly, one does not get the three-dimensional view. Both these difficulties can be overcome by mounting the tablets themselves in a polythylene bag. 5 inch x 6 inch polyethylene-film bags are very suitable. Six tablets or capsules are mounted inside the bag and are kept in place with double-sided ’Sellotape ’. The drug names are put on self-adhesive labels. A drying agent in the bag keeps the tablets in good condition. The top end of the bag is left open, since this may provide a better view of the tablet, more

1. 2.

Michie, W. Lancet, 1970, i, 1227. Carswell, F., Kerr, M. M., Hutchison, J. H. Lancet, 1970, i, 1241. 3. Wolff, J., Varrone, S. Endocrinology, 1969, 85, 410.

213 when colours have to be compared; also the tablets can be replaced easily. Tablets and capsules can be arranged according to colour or pharmacological action. Once one has a fairly large collection, identification of a vast number of preparations

particularly

becomes easy. The polyethylene bags drawer of the consulting-room table. Department of Dermatology, Manchester and Salford Skin Diseases, Manchester 3.

Hospital for

be stored in the

can

M. GANPULE.

CONTRACEPTIVES, BRAIN SEROTONIN, AND LIVER TRYPTOPHAN PYRROLASE

SIR,- W have been interested in the correspondence on the relationship between contraceptives and depression.1-6 Because of our interest in brain monoamines, adrenocortical function, and liver tryptophan pyrrolase (T.p.O.),6-12 we have studied the effects of long-term treatment with a combination of norethynodrel and mestranol (N+M) on brain 5-hydroxytryptamine (5-H.T.) and 5-hydroxyindoleacetic acid (5-H.I.A.A.), plasma-corticosterone, and liver tryptophan pyrrolase in rats. Female rats (180-200 g.) received 416 g. per kg. norethynodrel and 16-6 g. per kg. mestranol intramuscularly daily (approximately 10 times the human contraceptive dose) for 10, 20, 30, and 60 days. Control animals received no treatment.

The results of these experiments accompanying table. There was:

are

shown in the

1. A significant fall in brain 5-H.T. after 10 days’ treatment but almost normal values after 20, 30, and 60 days’ treatment; and 2. An increase of plasma-corticosterone and of liver T.P.O. after 10 days’ treatment, followed by a return to normal values with

continuing

treatment.

experiments 9,13 showed that single doses of glucocorticoids induced falls in brain 5-H.T. and 5-H.i.A.A. which were inhibited by allopurinol, a pyrrolase inhibitor. This suggested that the decrease in brain 5-H.T. was the Previous

1. Price, S. A., Toseland, P. A. Lancet, 1969, i, 158. 2. Winston, F. ibid. p. 1209. 3. Rose, D. P. ibid. 1969, ii, 321. 4. Rose, D. P., Braidman, I. P. ibid. 1970, i, 1117. 5. Green, A. R., Joseph, M. H., Curzon, G. ibid. p. 1288. 6. Preziosi, P., Scapagnini, U., Nistico, G. Biochem. Pharmac. 1968, 17, 1309. 7. Preziosi, P., Nisticò, G. ibid. p. 469. 8. Nisticò, G., Scapagnini, U., Preziosi, P. Lancet, 1969, ii, 159. 9. De Schaepdryver, A., Preziosi, P., Scapagnini, U. Br. J. Pharmac. 1969, 35, 460. 10. Scapagnini, U., Preziosi, P., De Schaepdryver, A. Pharmac. Res. Comm. 1969, 1, 63. 11. Nisticò, G., Preziosi, P. ibid. p. 363. 12. Nisticò, G., Miele, E., Preziosi, P. Paper to be presented at the Seventh Congress of Collegium Internationale Neuro-psychopharmacologicum. Prague, Aug. 11-15, 1970. 13. Curzon, G., Green, A. R. Life Sci. 1968, 7, 657.

EFFECTS OF NORETHYNODREL AND MESTRANOL ON BRAIN

No. of animals shown in

dose/kg./day.

parentheses.

result of a rise in liver T.P.o.14 Moreover, rats under restraint stress (R.S.) showed an increase of plasma-corticosterone, with a consequent rise in liver T.P.o. activity, which was probably responsible for the fall in brain 5-H.T.5,l1,12,15 However, the decrease in brain 5-H.T. after 3 hours of R.s. was followed by a return to normal values after 6 hours of R.s., possibly because of an increase of tryptophan hydroxylase induced by raised plasma-corticosterone levels.ll Daily injections of hydrocortisone for 5 or more days did not reduce brain 5-H.T.13 Chronic treatment with an oestroprogestinic combination in the rat resulted in an initial fall in brain 5-H.T. followed by a return to normal levels. The reduction in brain 5-H.T. possibly resulted from a decrease in tryptophan uptake by the brain induced by kynurenine and other metabolites formed by the action of T.P.O.16 These results may be relevant to the metabolic changes possibly occurring in women taking oral contraceptives. 2nd Chair of Pharmacology, Faculty of Medicine, University of Naples,

GIUSEPPE NISTICÒ* PAOLO PREZIOSI.

Italy.

*Present address: Pharmacology Unit, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London S.E.5.

HEADACHE AND THE EYE SIR,-Ihave read with great interest Dr. W. E. Waters’ account of a community study under this title (July 4, p. 1) and am impressed with his immaculate sampling technique and the high degree of mathematical accuracy with which its results have been assessed. The chief interest of the paper to a clinician, of course, lies in its demonstration of the wide divergence between the conclusions drawn and those which suggest themselves as the result of detailed history-taking, meticulous ocular assessment, and the effects of treatment based on such data over a number of years. It seems to me, however, that this conflict is more apparent than real, for Dr. Waters’ belief that visual defect is regarded, even by the authorities whom he cites, as a cause of headache, is surely mistaken. What is realised by doctors in several clinical disciplines is that difficulty in seeing gives rise to discomforts, one of which is headache. Such difficulty is not always accompanied by defective vision-e.g., in hypermetropic astigmatism-and defective vision, as when it is associated with myopia, renders critical near-vision easier and is seldom associated with any discomfort. Accurate refraction therefore is indispensable to an informed opinion on the relationship between seeing and discomfort, and this examination appears to have been omitted in the investigation by Dr. Waters. Evaluation of Dr. Water’s data on heterophoria would 14. Green, A. R., Curzon, G. Nature, 1968, 220, 1095. 15. Curzon, G., Green, A. R. Br. J. Pharmac. 1969, 37, 689. 16. Green, A. R., Curzon, G. Biochem. Pharmac. 1970, 19, 2061.

5-H.T. AND 5-H.I.A.A., PLASMA-CORTICOSTERONE,

Difference from controls (P<001).

rr=Norethynodzel.

M==Mestranol.

AND LIVER T.P.O. LEVELS

H.C.D.=Human

contraceptive