MECHANISM OF INDUCED EOSINOPENIA

802 it is important to minimise blood-loss when the effective volume of blood circulating to vital organs is minimal. For this reason it is a wise precaution to make a practice of having available suitably matched blood for transfusion. should the necessity arise. As Dr. Enderby points out, the surgeon should avoid injecting local vasoconstrictors (e.g., weak solutions of adrenaline) as experience has shown that even small quantities may raise the blood-pressure sufficiently to counteract the hypotonus and defeat the object of the technique. Like Dr. Hughes, I have found the method helpful for fenestration surgery ; but other surgeons whom I have seen operating get equally satisfactory results using other techniques. In my opinion it is very helpful in major neck surgery, such as laryngectomy, where the bloodless field makes for a marked reduction in operation-time, and in such operations as external ethmoidectomy where the surgeon is working in a deep dark hole, the bloodless field permitting more precise surgery with less risk to important anatomical structures. It is most useful in operating on toxic goitres which have been previously treated with. thiouracil; with ordinary anaesthetics these are notoriously "bloody"; but to operate on these cases using this technique is relatively easy and practically bloodless. As you so rightly point out in your annotation this is not a technique for the inexperienced ; and much further investigation and experience is needed before pronouncing final judgement on its safety, advantages, and disadvantages. F. BOYES KORKIS. London, W.I.

as

FUNCTION OF MAST-CELLS

Sn:,—The ground substance of connective tissue is thought by someto be derived from the metachromatic granules of mast-cells. Others,2 on the other hand, interpret such granulations as heparin." Apart from the still undecided question as to the nature of these granules, it seems to me that if these and the ground substance of connective tissue are really related, the metachromatic granules of the mast-cells should be regarded as a product of the metabolism of the free mucopoly"

saccharides of the connective tissue in consequence of some further chemical modification ( sulphuration). This concept is supported by the fact that in embryonic well as in the granulation tissue of wounds,44 ground substance invariably appears first, and the mast-cells afterwards. Furthermore, no parallelism exists between the number of mast-cells and the amount of the ground substance. As a matter of fact, where the ground substance is very abundant-e.g., in the pathological tissue of " localised pretibial myxaedema "-the mast-cells may be comparatively few 5 ; whereas in " urticaria pigmentosa,"6 as well as in certain tumours consisting only of mastcells,7 such cellular elements are very numerous and the ground substance is scanty. Bunting and White8 detected no relation between the number of mast-cells and the ground substance of the granulation tissue in wounds. This interpretation of the function of mast-cells does not impair the theory of the origin of heparin ; but it substantially modifies the hypothesis of Staemmler and Sylven. In fact, mast-cells should be regarded, not as the progenitors of the ground substance of connective tissue (the chief component of which, according to present-day views, is hyaluronic acid), but rather as cells

tissues,3

as

the

1. Staemmler, M. Frankfurt. Z. Path. 1921, 25, 391. Sylvén, B. Acta chir. scand. 1941, suppl. 66, p. 86. Holmgren, H., Wilander, O. Z. mikr.-anat. Forsch. 1937, 42, 242. Jorpes E., Holmgren, H., Wilander, O. Ibid, p. 279. 3. Holmgren, H. Personal communication. 4. Campani, M., Reggianini, O. J. Path. Bact. 1950, 62, 563. 5. Asboe-Hansen, G. Acta derm.-venereol., Stockh. 1950, 30, 221. Campani, M., Pelloja, M. Chirurgia (in the press.) 6. Caccialanza, P., Campani, M. Hautarzt. (in the press). 7. Oliver, J., Bloom, F., Mangeri, C. J. exp. Med. 1947, 86, 107. 8. Bunting, H., White, R. F. Arch. Path. 1950, 49, 590. 2.

able to

modify

both

hyaluronic acid

and the other

components of the ground substance, transforming them into other substances not yet well-defined ( heparin).

On the other hand, it stands to reason that mast-cells have different functions in different organs as well as in different animals. This hypothesis is supported by the fact that the granules from mast-cells of rabbits are soluble in alcohol, whereas the mast-cells of man and other animals do not have this property.9 Institute of General Pathology, University of Modena, Italy.

M. CAMPANI.

PRISCOL IN OBSTETRICS work at this hospital it has been found that SiR,-In Priscol ’ can be a potent oxytocio drug. It is completely different from other oxytocics in general use, however, in that tonic contractions of the uterus have Within a minute or never been observed after its use. two of administration it can produce regular, strong, and frequent contraction and relaxation of the uterus indistinguishable from normal labour. In the small number of cases so far observed, it has been used with success in the induction of labour (in one case where enema, castor oil, and quinine, followed by the insertion of a stomach-tube into the lower segment, had failed), and in the treatment of primary and secondary uterine inertia. Contrary to what might be expected with a vasodilator, it appears to reduce bleeding in the third stage and to shorten this stage. No depressant effects on the foetus have been noticed, and when born the child is usually very active, has a good colour, cries well, and in fact resembles one that is several days old. When priscol is used with pethidine, analgesia seems to be enhanced, although the strength and frequency of uterine contractions increases. In the treatment of late toxaemia this compound again appears to be of value, judging by the lessening of retinal vasospasm and general improvement in symptoms. In one case of hydramnios the patient began to secrete very large quantities of chemically normal urine; immediately after delivery the volume returned to normal. P. A. FOSTER. St. Monica’s Maternity Hospital, Cape Town, South Africa.

MECHANISM OF INDUCED EOSINOPENIA

SIR,-Some of the drugs inducing eosinopenia have been compared in your columns 10; but little is

already

known about the mechanism 11 by which this effect is brought about. We have found in dogs that significant and regular eosinopenia resulted from administration of picrotoxin, a central excitant, in doses of 0-5 mg. per kg. bodyweight. This dosage was well tolerated and caused no noticeable change in the animals’ behaviour. In further experiments we found that picrotoxineosinopenia was inhibited when the animal had been narcotised with soluble hexobarbitone. Soluble hexobarbitone itself causes no significant change in circulating eosinophils. With such narcosis there was no inhibition of the eosinopenia evoked by A.C.T.H. (Armour) 15 mg. or by formalin stress. Thus it seems to us reasonable to assume that picrotoxin-eosinopenia is abolished during narcosis with soluble hexobarbitone by action on the suprahypophyseal

region.

A.C.T.H.

and

formalin,

on

the other

hand,

seem

eosinopenia by acting on lower structures (hypophysis and/or adrenal cortex). Surprisingly,Cortisone’ acetate-’ Cortone’ (Merck) 15 mg.-did not cause eosinopenia in any of eight

to

cause

animals narcotised with soluble hexobarbitone.

This

9. Campani, M. Rass. Biol. umana, 1949, 4, 12. 10. Kelemen, E., Majoros, M., Tanos, B. Lancet, 1950, ii, 457. 11. Sayers,G. Physiol. Rev. 1950, 30, 241. Rosenthal, H. L., Wald, N. Yager, A., Litwins, J. Proc. Soc. exp. Biol., N.Y. 1950, 75, 240. Mach, R. S., Brügger, Y., Della Santa, R., Fabre, J. Schweiz, med. Wschr. 1950, 80, 5.

803

suggests that cortical hormone(s)

mobilised after injection Our from commercial cortisone. observation corresponds with that of Nelson et al.I2 So far as we know, no method will regularly inhibit cortisone-eosinopenia. On the other hand, our investigations suggest that the controversy over the hypophyseal of stresses 13 could or suprahypophyseal regulation perhaps be settled by recognising that each mechanism may operate ; and that the various substances causing eosinopenia may produce this effect by either the one mechanism or the other. A.C.T.H. and formalin may act through the first, and picrotoxin through the second, of

A.C.T.H.

differ

mechanism. University Medical School, Szeged, Hungary.

F. OLÁH V. VARRÓ

M. MAJOROS D. BACHRACH K. KOVÁCS.

ENURESIS some years of research into The experience described here is recorded in the hope that it may provoke correspondence. Following a period of gross overwork, anxiety, and some physical strain I, having retired to bed under orders, found myself sleeping abnormally heavily ; and, apart from sundry emergencies which could not be disregarded, I spent the greater part of the time asleep. One night when sleep was abnormally heavy (checked by not rousing with the normal stimuli which occur in my house at certain hours) the following dream occurred :

SIR,-I

am

completing

nocturnal enuresis.

I was in my mother’s bedroom at the family home in which I had lived from the age of 2 to 22 years. Many persons, whose as not clear, were in the house. The dream was identity " a long dream "-that is to say, it appeared to occupy some time, and continuity seemed unbroken. After some appreciable time the desire to micturate became apparent and I left the bedroom, crossed a large landing, and went down a corridor to the lavatory, where I micturated. After the dream act had been initiated for some appreciable time I became " enuretic " to the extent of voiding approximately a drachm and a half of urine ; I woke immediately and took appropriate action.

recognise that the phrase " appreciable time " is relatively meaningless, but it is included in an attempt to give a true " dream picture." The cerebral mechanics of nocturnal enuresis have long I

been debated. I suggest that the mechanism may well be that the stimulus, rising to subcortical level, produces " dream activity " but, failing to rise to cortical level, does not explode in appropriate action. I should be interested if readers could contribute any similar reminiscence. ENURETICUS SENEX. CARCINOMATOUS OBSTRUCTION OF THE COLON SiR,—I regret to inform you that your leading article last week does not give an accurate account of what I recommended when the treatment of this condition was discussed recently before the section of surgery of the Royal Society of Medicine. What I stressed at that meeting, and at the meeting of the section of proctology a fortnight earlier, was that the outlook and management of these cases depends chiefly on the absence or presence of concomitant small-intestinal distension, and I was pleased to hear Professor Morley also mention this point. As the bulk of cases do not show- small-bowel distension, very little, if any, intravenous fluid is required ; whereas in the distended cases the proper management of fluid therapy is all-important and, to my mind, is of more consequence than the particular type of operation performed, provided that this can relieve the obstruction. You say that " every speaker agreed that this [the Miller-Abbott tube] may lose valuable time but I recommended its use in patients with small-intestinal distension while the correct type of fluid is being administered prior to operation. Incidentally, I do not use the 12. 13.

Nelson, D. H., Reich, H., Samuels, L. T. Science, 1950, 111, 578. Ingle, D. J. J. clin. Endocrinol. 1950, 10, 1312.

Miller-Abbott tube but, like a true Scot, prefer a long of ordinary rubber tubing, size 10EG, fitted with side eyes and indestructible markings by myself at great saving of cost. I must also point out that I did not say " that the potassium values were high in these cases." In the nondistended case the value is low, and it is raised only in the distended cases. The result is that if potassium salts were to be given in the former cases and the patient were to become distended, there would be a considerable risk of causing potassium intoxication of the heart. To my mind, Ringer’s or Hartmann’s solution must be used with extreme caution ; and their use is rather like shutting the stable door, because the real trouble is protein breakdown. A later passage in your article possibly suggests that I recommended daily electrocardiographs. While I am aware of the electrocardiographic changes in both hyperpotassaemia and hypopotassscmia, I did not mention the electrocardiograph nor the daily estimation of the serum-potassium-a most time-consuming procedurebecause I feel that the serum-potassium concentration is being unduly pushed to the fore at present, and that it is only another indication of protein katabolism, correction of which will correct the potassium level. ERNEST W. GRAHAMS. Middlesbrough.

length

Medicine and the Law A Doctor’s Successful Appeal A SCOTTISH doctor has won his appeal in the Court of Session in a case which contains an element of proHe had sued fessional as well as personal interest. a hospital board for damages for breach of contract. He claimed that the board had agreed in 1947 to appoint him to an infectious-diseases hospital at a basic salary of :E900 as resident physician-superintendent. Four months later, he alleged, the board informed him that he would not be appointed ; meanwhile, he said, he had refrained from undertaking other commitments so as to hold himself available for the appointment. The board, it seems, terminated their agreement on the ground that the doctor had in 1941 been suspended from the office of county medical officer in England and had, after an inquiry held by the Minister of Health, been dismissed from his post some eight months after.wards. On the other hand, he had subsequently been appointed to the position of chief medical officer in a Scottish county and had held that office till 1944. In answer to the doctor’s claim for damages the hospital board pleaded, among .other things, that the of 1947 was subject to a suspensive conagreement dition " pending the formality of an agreement in writing which had never in fact been sent to him, and that, in making the agreement, they had acted under essential error brought about by his false representations. Last November Lord Sorn dismissed the doctor’s action. On March 28 the First Division of the Court of Session reversed that decision and sent the case back The Lord President (Lord Cooper) said to be tried. that the post in an infectious-diseases hospital at a salary of £ 900 was obviously different in character from that of chief administrative officer of the medical services of In his opinion, failure in a large county in England. the latter capacity in the year 1941 did not necessarily, or even probably, imply the doctor’s incapacity for the lesser post to which he was appointed in 1947. The Lord President could not accept the board’s apparent view that the episode of 1941 entailed permanent disqualification for any appointment, however minor, in the service of a health authority. The board’s contention that they acted in the interests of the public in breaking their agreement, he observed, was untenable. "