ERGOTHIONEINE AND THYROTOXICOSIS

602

Annotations ERGOTHIONEINE AND THYROTOXICOSIS

long been familiar to students of because its presence in the red blood-cells interferes with the accuracy of many methods of determining blood-sugar and blood uric acid. Its function, if any, in the red cells has been wholly obscure, and it has been regarded as pharmacologically inert. The work by Dr. Lawson and Professor Rimington, published elsewhere in this issue, entirely alters its status, and raises the question whether the traces of the ergothioneine found in normal blood may not have great importance in connexion with thyroid activity. For the last four years thyrotoxicosis has been treated with a variety of sulphur-containing substances. Thiourea was the first, to be rapidly succeeded by thiouracil and other compounds. The action of these substances is dramatic, and much clinical improvement is produced in most cases of primary Graves’s disease ; but it is not yet clear how far the chemotherapeutic attack is really an adequate alternative to surgery, and certainly it is not entirely free from risk. The effect of treatment with all these drugs is to cause the iodine content of the thyroid to fall, while the gland itself may enlarge. All the most active compounds so far tried contain the and it occurred to Lawson and grouping > NCSN <, Rimington to try the effect of ergothioneine, which also contains this grouping, on the thyroid glands of normal rats. The hoped-for result was realised : when given in similar dosage by injection, ergothioneine, like thiouracil, reduced the iodine content and raised the weights of the rats’ thyroids. The quantitative result of its administration, though resembling closely that of thiouracil in the same dosage, was much more variable -perhaps because of differences in the initial level of ergothioneine in the individual animals. Hunterand Eagles and Va.rs2 noted considerable variation in ergothioneine content not only between different species but also in the same species : thus Hunter recorded a range of 2-5 to 8-0 mg. per 100 ml. red cells in normal men, while pigs usually ranged from 20 to 50 mg. per 100 ml. and cats and oxen all had less than 2 mg. We have as yet no data for ergothioneine levels in thyroid or other disease, but Lawson and Rimington now have this under investigation. One may reasonablv expect that administration of a normal blood constituent in amounts of the same order as those found in normal blood will carry no risk of toxic manifestations. If ergothioneine proves both effective and non-toxic, another great step will have been taken in the medical treatment of thvrotoxicosis. Publication of clinical observations based on Lawson and Rimington’s work will be awaited with great interest. ERGOTHIONEINE has

biochemistry

MORE GERMAN DRUGS

EARLIER accounts of new German drugs3 have been supplemented by a further report.44 The details given in it will doubtless be useful to British manufacturers, but the new preparations discussed may best be described One plant was working on the isolation as small beer. of " thymus hormone," as described by Bomskov, though the very existence of such a hormone seems to have been In other work the quinine molecule was uncertain. modified to produce a compound, namedAmichinazokairolin,’ which, though of low toxicity, proved thirty times as

active

as

quinine in canary-malaria. Unfortunately,

Biochem. J. 1928, 22, 4. 2. Eagles, B. A., Vars, H. M. J. biol. Chem. 1928, 80, 615. 3. See Lancet, Feb. 15, p. 262 ; Ibid, March 29, p. 414. 4. German Medical Targets. Reported by Dr. W. P. KENNEDY (Ministry of Health) and Mr. J. B. M. COPPOCK and Dr. A. C. WHITE (Ministry of Supply). British Intelligence Objectives Subcommittee (32, Bryanston Square, London, W.1) report no. 449. Item no. 24. H.M. Stationery Office. 1. Hunter, G.

clinical trials in Bulgaria showed it to be only as effective in human malaria-too small a gain to compensate for its greater cost. The Schering laboratories in Berlin were very energetic until their work was curtailed by war damage. The firm had concentrated on the freeze-drying of human serum, and by 1944 their output was as high as 607 kg. Laborious investiga: tion of the distribution and fate of sulphonamides in the body seems to have yielded nothing which is not already familiar to workers in Britain and the United States. Perhaps the most interesting revelation concerns a new analgesic compound ’ Hochst 10582’ ; this is

large-scale

four times

1 :

1

diphenyl-l-dimethylaminoethylbutanon-2-hydroThe drug, which has apparently been used

chloride.

extensively in German hospitals, has an action similar pethidine, but its effect lasts somewhat longer. It is made up in 25 mg. tablets, which are taken by mouth. The analgesic effect of each tablet continues for 2-7 hours, and one thrice daily is said to be sufficient for any but the most extreme pain. When the dose is increased to two tablets three times a day some patients experience giddiness and nausea, but these are seldom serious. Animal experiments in Britain have confirmed its analgesic action, but no clinical evaluation has yet been reported here. to that of

DEATH AFTER

DOG-BITE

THE death of

a boy in Hull following the bite of a dog several questions not easy to answer. According to press reports,l the boy was bitten in the leg, and on the advice of his family went to the hospital " to have the wound cauterised." The house-surgeon found a deep punctured wound and ordered the injection of 2 c.cm. of gas-gangrene antiserum. Within a few minutes the boy developed dyspncea, and despite administration of adrenaline and oxygen, he died soon afterwards from anaphylactic shock. This is the third death from a similar cause to be noticed in these pages during the past twelve months,2 and the only essential difference is the positive evidence in this case that most of the possible precautions against the accident were taken : the quantity of serum given suggests that it was a concentrated product and therefore less likely to give rise to an anaphylactic reaction, and adrenaline was used when the boy became ill, though the amount and time of the injection are not mentioned in the account of the inquest. We may well ask how far these tragedies should modify our treatment of the deep, lacerated, and presumably infected wound. It has long been recommended that tetanus and gasgangrene antitoxins should be used prophylactically in these cases. The evidence that the first diminishes the incidence and severity of the specific infection is convincing, and most doctors have at some time had reason to regret that it is not more generally used in civilian practice. It seems desirable, at any rate in rural areas, that active immunisation with tetanus toxoid should be as easily available to the public (and especially to children) as prophylaxis against diphtheria, but a long time will elapse before this practice is sufficiently widespread to justify withholding tetanus antiserum from the potentially infected patient. To obtain proof of the efficacy of gas-gangrene antiserum has been more difficult, though war experience suggested that large prophylactic doses lower the death-rate from this cause. Since antiserum is given in every accident case at some hospitals and in none at others, it might be possible to

raises

1. Hull Daily Mail, March 29 and April 1. 2. Lancet, 1946, i, 694; 1946, ii, 354.