TREATMENT OF THYROTOXICOSIS

258 to this question which many of considered. A definitive answer cannot be of their current information. answer

Milwaukee Children’s Hospital, Wisconsin 53233.

us

have

given

on

seriously the basis

FRANK A. WALKER.

IRON BINDING BY GASTRIC JUICE SiR,—The papers by Wynter and Williams,! and Luke et al.,2 and the previous works by Davis et al.,3 and Luke et a1.4 prompt us to report here the results of our studies on the iron-binding capacity of the gastric juice in children. Gastric juice was collected after an overnight fast and care was taken to exclude the saliva. The iron-binding capacity was determined by a slight modification of the radioiron-solubility test of Davis.5 To 1 ml. of gastric juice diluted with 3 ml. of distilled water we added 5 ml. of OOO1M [59Fe]-ferric-chloride (specific activity 0- 1 ,C per ml.) and concentrated hydrochloric acid (generally a drop) to bring the pH to 2. The pH was adjusted with 2M ammonia solution to 8 and the assay mixture brought to a volume of 10 ml. with water. The rest of the method was the same as that described by Davis.5

The iron-binding capacity of the gastric juice of normal children was always less than 5 f1.moles (0-275 mg. of iron) per ml., while that of some ansemic children, in whom 0-002M [59Fe]-ferric-chloride was used, was more than 5 f1.moles per ml. In two groups of normal children, the first aged 4 months to 3 years, and the second 4 years to 13 years, the values were 0-155:0-054 and 0-1470-077 moles per ml., respectively. Children, aged 9 months to 3 years, with hypochromic, hyposideracmic anxmia due to prematurity and/or insufficiency of iron in their diet, had values of 0-263:0-104 f1.moles per ml. (see accompanying table). The difference between the average IRON-BINDING

CAPACITY

OF

GASTRIC

JUICE

IN

NORMAL

CHILDREN

AND IN CHILDREN WITH HYPOCHROMIC HYPOSIDERPEMIC ANEMIA

(VALUES S.D.)

Effect of increasing concentration of added [Fe]-ferric-chloride on amount of iron bound to gastric juice (assay-volume 10 ml.).

Our results in children with

hypochromic

anxmia up

to

the

by Luke et awl. in adults with hypochromic anxmia. The interpretation of these age of 3 years contrast with those obtained

data from the results we have obtained so far is not easy. We think that further research is necessary to elucidate the nature of the iron/gastric-juice bond and its significance in vivo. G. Russo S. MUSUMECI D. MAZZONE.

Department of Pædiatrics, University of Catania, Italy.

TREATMENT OF THYROTOXICOSIS

SIR,-Dr. Philp and his colleagues1 conclude that " there is place for external irradiation in the treatment of thyrotoxicosis ". I should like to point out that their patients treated with 60Co received a dose of y-radiation (115-900 rads) much lower than the dose with 131I (2400 rads); no wonder they observed such a high rate of relapse in those treated with 60CO. From their table I cannot make out whether they report the total amount of y-radiation for those who received two doses; but even assuming that some of the patients listed as receiving 900 rads actually got 1800 rads, that is still below the therapeutic value of those treated with 1311. Besides, they draw a comparison between two different situations: in patients treated with 131 the ionising effects were spread over some time, whereas in those treated with 60CO, even when two doses were given, the effect was short-lived. Since 1939 I have treated more than 1000 patients with X rays. The thyroid region is divided into three areas, and 100 rads are given every other day to one area each time. In all, every area is treated four times to give a total of 1200 (400 x 3) rads spread over 24 days. At the end of the first cycle the patients are followed up and, if necessary, a new cycle is started after a month of rest. Up to five cycles are needed for complete recovery, the average being three. Complete treatment includes administration of reserpine (up to 1.5 mg. per day), barbiturates, bed rest, and a high-calorie diet. In the overwhelming majority of patients cure is obtained; relapses are not many (about 10%), and can always be successfully treated by repetition of one or more cycles of X-ray therapy. No skin

no

values of the first group of normal children and that of the children with hypochromic anaemia was statistically significant

(p < 001). We have not studied iron absorption in these subjects, but Schulz and Smith 6 found that the absorption of food iron and iron salts was increased in children of the same age as ours with hypochromic hyposideraemic anxmia. In 2 patients with hypochromic, hyposidersemic anaemia (1 adult blood-donor and a girl of 11 years who had repeated gastrointestinal haemorrhages) we found values of 0-028 and 0-035 mg. of iron per ml. respectively; an adult patient with idiopathic hsemochromatosis had a value of 0-005 mg. per ml. In further studies on various dilutions of gastric juice of normal children, we obtained generally non-linear values. In 3 normal children, using constant quantities of gastric juice and increasing quantities of [59Fe]-ferric-chloride, we have obtained data similar to those of Wynter and Williams 1: on increasing the concentration of ferric-chloride we obtained an initial increase of bound iron followed by a sharp decrease (see

accompanying figure). 1. 2. 3. 4. 5. 6.

Wynter, C. V. A., Williams, R. Lancet, 1968, ii, 534. Luke, G. C., Davis, P. S., Deller, D. J. ibid. p. 844. Davis, P. S., Luke, G. C., Deller, D. J. ibid. 1966, ii, 1431. Luke, G. C., Davis, P. S., Deller, D. J. ibid. 1967, i, 926. Davis, P. S. Proc. Aust. Ass. Biochem. 1965, 1, 190. Schulz, J., Smith, N. J. Am. J. Dis. Child. 1958, 95, 109; ibid. p. 120.

lesions

occur.

Never in 29 years have I observed

a case

of

hypothyroidism. Radiobiological work in animals is 1.

very

respectable,

Philp, J. R., Duthie, M. B., Crooks, J. Lancet, 1968, ii,

but in

1307.

259 the light of my successful experience in man I do not exactly know what to make of that cited by Dr Philp and his colleagues. Policlinico Umberto I, Istituto di Patalogia Speciale Medica e Metodologia Clinica I, University of Rome.

M. BUFANO.

needs a two-tier administration; that the lower local, districthospital and health-centre group, should be controlled by elected bodies; and that the regional planning authority should be representational, built up of elements from the local committees and representatives of the health workers, the medical profession, the universities, and the Ministry. There is just no possibility of a British-type democracy agreeing to what you bluntly but correctly say is no guarantee of cooperation without medical hands on the levers of power ". I cannot recall in my forty years of membership of the B.M.A. any expression of such an utterly undemocratic and unrealistic nature as that which has been made in the policy statement on this subject. "

DETECTING HYPOTHYROIDISM

SiR,—The article by Dr. Philp and his colleagues,’ which refers to the large numbers of individuals with undetected iatrogenic hypothyroidism, a potentially curable disease, prompts me to point out that there is another large number of individuals with undetected hypothyroidism-those with infantile hypothyroidism. This is especially important, since the disease is detectable in the first few days of life and is, again, in most cases potentially curable. With the estimated lifetime cost, in the United States, of$500,000 for each mentally retarded person, one would think, from a simple economic standpoint, that a greater effort should be made to detect infantile hypothyroidism as a potentially preventable cause of mental retardation. Health agencies launch great to detect other campaigns preventable causes of mental retardation-e.g., phenylketonuria and galactosoemia-but no major programme exists to uncover infantile hypothyroidism, which presumably has an incidence at least as high, or higher. One might point out, finally, that replacement therapy for hypothyroidism involves a simple preparation-one of the most benign agents in our therapeutic armamentarium-and not a difficult-to-prepare diet, or hazardous drug. JAY S. SKYLER. Philadelphia, Pennsylvania.

B.M.A. AND THE-GREEN-PAPER SIR, Your annotation last week (p. 196) quite rightly says " that what the B.M.A. is asking doctors to consider is not so much ... shaping administration as defending the doctor’s interests ". It is even more depressing than that: for the B.M.A. is attempting to defend imaginary interests, or perhaps one should say defending interests against imaginary dangers. The general practitioner is only technically still an independent contractor "; in almost every respect he is an employee of, and receives the bulk of his income from, the National Health Service-and increasingly is becoming a salaried officer of that Service like all other doctors. A trade-union (or the B.M.A.) must protect its members; but it does this better by recognising and accepting the realities of the situation and then arguing on that basis. The B.M.A. has lost every battle it has fought on the basis of preserving the past. The green-paper is accepted by no-one; but it has given us an opportunity to discuss N.H.S. administration and to make new proposals. Our democratic concepts require two things: (1) at some point the citizens, who pay for the Service, must have control over elements of policy susceptible to local variation within the national strategy and not beneficially under Parliamentary control; (2) workers in the industry must be able to advise controlling bodies on both the content and the operation of the Service. The medical profession may claim, and has had, an important place in this machinery, but it cannot claim a unique position. If worker participation is as important as the B.M.A. claims it is when the workers are doctors, then the " all staffs which same ability to tender advice must be given to are large enough and cohesive enough to act ", as my Association has put it in evidence to the Department of Health and Social Security.2 In that we have discussed what the B.M.A. cannot seem to grasp, the difference between medical administration-the day-to-day task of professional administrationand the giving of professional advice by the profession collectively. We have also suggested that the N.H.S., once unified, ...

"

1. Philp, J. R., Duthie, M. B., Crooks, J. Lancet, 1968, ii, 1336. 2. Socialism and Health, January/February, 1969, suppl.

D. STARK MURRAY Richmond, Surrey.

President, Socialist Medical Association.

ALTERATIONS OF FIBRINOLYSIS AND BLOOD COAGULATION SIR,-The study reported by Dr. Cohen and his colleagues1 and your editorial comments2 prompt me to write. I was not particularly surprised by the lack of significant difference in platelet-counts observed under the conditions of the study. Five healthy young active males rested supine for only 20 minutes before their blood was drawn, then they exercised strenuously for 5 minutes and blood was drawn again. Several years ago I studied3 six somewhat older individuals, the majority in their late twenties, who were medical personnel at our hospital. Three were rested with 8 hours’ sleep and, before they were permitted out of bed, blood was drawn for indirect platelet-counts on fingertip blood and Lee-White coagulation-times on venous blood. Then they were exercised according to the Master two-step routine, and platelet-counts and Lee-White coagulation-times were repeated. There were significant differences in plateletcounts of 50-100%. Lee-White coagulation-times were shortened (3, 31/2, and 4 minutes)-the hypercoagulable state ? The remaining three individuals were laboratory personnel, studied as controls, who went about their daily routine and were studied after little or no rest. They showed no significant difference in the same blood-values before and after the Master two-step exercise. A rabbit study reported by Scardino and 4 me further confirmed these findings. It showed that ten animals active in their cages had no significant difference in platelet-counts done on blood drawn from the right and left ventricles, whereas ten winter-hibernating animals immobilised for several days had platelet-counts in the blood of their left ventricles up to or over 100% greater than in the blood of the right ventricles. This indicated that: (1) the lung vessels were a source of platelets, presumably from the pulmonary megakaryocytes; (2) inactivity, as in long-continued immobilisation with its lowered heart action, caused the megakaryocytes to increase in number, with the lung vessels acting as a place of storage, as often observed in lung sections of individuals dead of thromboembolic disease.5 With exercise or sudden increased heart-action these accumulated megakaryocytes are forced through the pulmonary capillaries, broken into platelets, and released to the peripheral circulation as fresh platelets and platelet factor. In the conditions of the study by Dr. Cohen and his colleagues there was no such opportunity to build up the number of megakaryocytes in the lung capillaries, and therefore no significant difference in platelets could be

expected. It is more reasonable to assume that daily exercise will stimulate sufficient increased heart action to prevent the increase in number of pulmonary megakaryocytes and thereby avoid the sudden release of fresh platelets causing a 1.

2. 3. 4. 5.

Cohen, R. J., Epstein, S. E., Cohen, L. S., Dennis, L. H. 1968, ii, 1264. ibid. p. 1283. Sharnoff, J. G. Unpublished. Sharnoff, J. G., Scardino, V. Nature, Lond. 1960, 187, 334. Sharnoff, J. G. J. Am. med. Ass. 1959, 169, 688.

Lancet,