HYDROFLUMETHIAZIDE

462 .

works. The best authorities define Marjolin’s ulcer as a carcinoma occurring in scar tissue, particularly scar tissue following burns.

Marjolin’s

HAMILTON BAILEY. ACUTE ANHIDROTIC HEAT EXHAUSTION

I report a case of " acute anhidrotic heat exhaustion " which occurred in London this year ? Mrs. T., aged 45, underwent bilateral oophorectomy and

SiR,-May

for carcinomatosis on May 6, 1959. In the middle of the afternoon of May 8 she suddenly became drowsy and confused, in spite of adequate steroid replacement. Her oral temperature was 101°F, and her skin was flushed, hot, and bone dry. She recovered within 12 hours. May 8 had been a sunny and windless day, and the ward was hot and rather humid. The patient weathered the summer heatwave without discomfort, sweating normally. On September 8, a very warm day, she was readmitted to another department with severe neck pain due to bony deposits. That evening she had a temperature of 104°F, and she was noticed to be sweating very little. She had recovered by the next day. Testing with intracutaneous methacholine on May 10 had suggested a deficient sweat-gland response; but this was not borne out by her condition during the summer. The other complication in this lady is that intracranial deposits have been suspected, and a hypothalamic lesion cannot therefore be ruled out. The Middlesex Hospital, P. MESTITZ.

adrenalectomy

very slow administration of a further 1 ml. he became very suffused after only 0-2 ml. had been given. The injection was immediately stopped and the subsequent development of collapse, sweating, and severe pain in the loins was treated with adrenaline and intravenous hydrocortisone. Complete recovery took place after a few hours and there was no subsequent rise in serum transaminases (S.G.O.T. and S.G.P.T.). Before the second injection of iron-dextran the serum-iron level was 130 g. per 100 ml. and the total iron-binding capacity was 310 g. per 100 ml. We consider that these two reactions are truly anaphylactic and not " toxic on the following grounds :

during the

"

surprised to learn from Dr. Bannister’s paper (Sept. 12) how recently this condition has been described. It would seem to have been familiar to AngloIndians of an earlier generation, however, because it is clearly indicated by Kipling in his short story At the End of the Passage (Life’s Handicap, 1891). The scene is set at night with the thermometer reading 104° and the doctor says: " ‘it occurs to me that unless I drink something I shall go out before my time. I’ve stopping sweating, and I wear a seventeen-inch collar.’ He brewed himself scalding hot tea, which is an excellent remedy against heat-apoplexy if you take three

iron.

(d) The intravenous injection of 1 ml, iron-dextran without reaction a fortnight previously. Several other elderly patients have been given, without reaction, two intravenous injections of iron-dextran at an interval of7 to 8 days and repeated therapeutic doses of intravenous iron-dextran. have been given safely to many younger subjects. The development of

a suitable skin test may provide a it but until then would seem prudent to restrict the safeguard use of intravenous iron-dextran to subjects who have had no iron-dextran in the past, whether intravenously or intramuscularly. In such subjects the use of .intravenous irondextran should be limited to within a period of 7 or 8 days. A. MACKENZIE General Hospital, IAN R. LAWSON. Sunderland.

was

four cups of it in time."

or

(a) The nature of the reactions and the time relationship of the injections. (b) The small amount of iron given, particularly in case 2. (c) The evidence that in case 2 the serum was not saturated with

two

London, W.1.

SIR,-I

13 days later

imferon intravenously without any ill effect.

W. BRIAN GOUGH.

Solihull.

REACTIONS AFTER INTRAVENOUS IRON-DEXTRAN

SIR,-During investigations of plasma volume using intravenous injection of iron-dextran complex (’Imferon’), as described by MacKenzie and Tindle,l of severe we have recently encountered two cases anaphylaxis. In both cases an intravenous injection of imferon had been given 2 weeks previously without any

the

ill effect. CASE l.-A man, aged 65 years, suffering from polycythaemia given 1 ml. imferon intravenously to estimate plasma volume. There was no ill effect of any kind. 14 days later a further intravenous injection of 1 ml. was slowly given: after 5 minutes the patient became extremely suffused and had a very full bounding pulse: this state lasted for about 4 minutes and was followed by collapse, pallor, sweating, a rapid, feeble pulse, and severe pain in the loins. He was given subcutaneous adrenaline and intravenous hydrocortisone and gradually recovered. CASE 2.-A male volunteer aged 71 years who had had a myocardial infarction 3 days previously was given 1 ml. vera was

1.

MacKenzie, A., Tindle, J. Lancet, 1959, i,

333.

HYDROFLUMETHIAZIDE

SlR,łThe three papers in your issue of Sept. 12 describe the properties of hydroflumethiazide and show that it is a diuretic of considerable potency with properties and dosage range very similar to those of dihydrochlorothiazide. At Whittington Hospital Dr. H. E. S. Pearson and I have used hydroflumethiazide for over six months in the treatment of oedema due to congestive cardiac failure with considerable success. It soon became important to ascertain whether hydroflumethiazide shares with chlorothiazide the property of enhancing the hypotensive action of ganglion-blocking drugs. This may be on occasion a useful property but it is not without its dangers to the unaware, since interrupted treatment with this group of oral diuretics given to patients who are also under treatment with ganglion-blocking agents for hypertensive heart-disease may have dire consequences. For some time I have felt that the routine addition of chlorothiazide to ganglion-blocking agents is not justified, as potassium deficiency must be guarded against with the addition of potassium salts, and estimations of the serum-electrolytes are prudent at least at monthly intervals, thus adding to the complexities of the regime. At the time when the first experiments were performed the tertiary amines, mecamylamine and pempidine tartrate, were in

In eight acute experiments on inpatients, common use. hydroflumethiazide in dose of 100 mg. in the morning proved to have, in five cases, a similar but not so powerful enhancing action on mecamylamine and pempidine as 1 g. of chlorothiazide. In the other three cases little enhancing action was noted with both drugs. In twelve more chronic experiments (the patients being followed up at fortnightly intervals in the hypertensive clinic), hydroflumethiazide in daily dose of 50 mg. in the morning appeared, when substituted for chlorothiazide 0-5 g., to have a similar but slightly less powerful enhancing

action. When

mecamylamine and pempidine

are

the

ganglion-

463

blocking

agents used

in conjunction

with chlorothiazide,

two

different mechanisms come into play. In the first place hypovolsemia is produced by the diuretic and, as Dollery, Harington, and Kaufman1 have shown, it is in the main the hypovolsemia which enhances the hypotensive action of all ganglion-blocking drugs. Dunstan et al.,2 who reported similar findings, observed that hypovolaemia leads to a compensatory neurogenic vasoconstriction-a situation in which arteriolar tone is more exposed to the action of ganglioplegic drugs. On the other hand Harington, Kincaid-Smith, and Milne 34 showed that the shift of urinary pH to the alkaline side after chlorothiazide, retards the urinary excretion of mecamylamine and pempidine and thus enhances their action. It is not surprising that hydronumethiazide, which has a smaller carbonic anhydrase inhibitaction than chlorothiazide and does not change the pH of the urine, should have a similar but smaller enhancing effect on these ganglion-blocking drugs than chlorothiazide. When bretylium tosylate (’Darenthin’) became available for clinical trials, it was thought useful to determine whether hydroflumethiazide has an enhancing hypotensive effect on this drug. Rosenheim et al. in one case5 and in others (personal communication) have already shown that chlorothiazide in dose of 1 g. has an enhancing effect on bretylium tosylate. Dollery et al.l reported postural hypotension following chlorothiazide alone in a patient who had previously sustained a thoracolumbar sympathectomy-a situation very similar to that obtained after administration of bretylium tosylate. I can now confirm in eight cases that hydroflumethiazide potentiates the hypotensive action of bretylium tosylate similarly to chlorothiazide when given in equivalent doses of 1 : 10.

The prospect of bretylium tosylate and hydroflumethiazide will shortly become drugs of moderately wide application seems a sufficient reason to request so much of your valuable space to make known these observations at an early date. My thanks are due to Dr. H. E. S. Pearson for permission to mention his findings on the diuretic action of hydroflumethiazide in congestive cardiac failure, to Dr. T. Binns, of Glaxo Laboratories, for generous supplies of hydroflumethiazide (’ Naclex’), and to Dr. P. 0. Jones, of the Wellcome Foundation, for supplies of bretylium tosylate (’ Darenthin ’). Whittington Hospital, London, N.19.

E. MONTUSCHI.

A COLLEGE OF PATHOLOGISTS

SIR,-Before

well-intentioned

pathologists college no-one wants, it might be explained that we psychiatrists have, in effect, had our College (and a Royal one at that) for well over a hundred years. Although the premises in Chandos Street lack something of the grandeur which regal recognition deserves, the Royal Medico-Psychological Association surely meets most of the needs of psychiatrists for congregation, education, and representation-though the latter point is perhaps open to debate. It has no academic barrier, which is surely right (there are too many diplomas already); it is as easy to join as the Royal Society of Medicine and a good deal cheaper. The Association also has its own periodical (the Journal of Mental Science) and four active sections-mental deficiency, research and clinical, psychotherapeutic and social, and child psychiatry. Learned meetings are quite frequent and very well attended, yet many of the luminaries are proud to take an active interest in the affairs of the Royal College of Physicians. One never has the sense of the R.M.P.A. being a splinter group, nor of divided loyalties. Dr.

force upon

any

more

us a new

Dollery, C. T., Harington, M., Kaufman, G. Lancet, 1959, i, 1215. Dunstan, H. P., Cumming, G. R., Corcoran, A. C., Page, I. H. Circulation, 45, 360. 3. Harington, M., Kincaid-Smith, P. Lancet, 1958, i, 403. 4. Harington, M., Milne, M. D. ibid. 1958, ii, 6. 5. Boura, A. L. A., Green, A. F., McCoubrey, A., Laurence, D. R., Moulton, R., Rosenheim, M. L. ibid. July 11, 1959, p. 17.

1. 2.

J. A. U. Morgan was surely joking when he said (Sept. 19) that our claims to autonomy were " nearly as good " as theirs: pathology has always been far closer, surely, to internal medicine both in science and administration and pathologists numerically fewer. But if pathologists want their own organisation they could do worse than consider a Medico-Pathological Association along the lines of ours. RICHARD Fox. London, S.E.5. PERCEPTUAL ISOLATION USING A SILENT ROOM

SIR,-The interesting findings of Dr. Smith and Mr.

Lewty (Sept. 12) raise the study of hypnosis such

a

silent

room as

number of questions relevant to and the possible extended use of a therapeutic aid. a

Working daily on research in hypnosis, or with hypnosis as research tool, I have come to regard the hypnotic trance as resulting, in part at least, from a limitation of perceptual experience through a process of sensory " takeover " by the hypnotist. This is achieved by suggestion, and what the hypnotist takes over are in effect the subject’s channels of communication with the outside world, or his contacts with the available sources of information in his environment-to use current terminology. In most techniques of hypnotic induction this is done through the sense of hearing. When, for example, the hypnotist implies in his induction monologue that the smarting of the eyes consequent upon an unblinking stare is due to his suggestions, he takes over responsibility for whatever Lockean " ideas " on corneal and conjunctival experience are then being received at the perceptual level. The hypnotist thus goes on record as having caused the smarting by his suggestions. Similarly, the inevitable fatigue of the levatores palpebrarum superiores when the upper eyelids are hyperelevated for periods up to one minute or more is easily accepted as being the result of the hypnotist’s timeworn suggestion: "Your eyelids will get heavy and will want to close..." In the same way, during deepening of the trance, proprioceptive impulses are taken over when slight and unconscious movements of the fingers are " fed back " by suggestion as being the results of previous a

suggestions. By means

,

of such techniques practised on suitable subjects, the information capacity of the total sensory mechanism would seem to be reduced and a large part of the perceptual experience of the subject can eventually become dependent upon the hypnotist’s suggestions via the 8th cranial nerve. Something akin to " unconsciousness " then prevails-in many cases complete, with loss of hearing for anything but the voice of the hypnotist, loss of time-sense, and total amnesia for all events during the trance, plus some seconds of retrograde amnesia covering the period of induction. By means of the silent room, Dr. Smith and Mr. Lewty seem to perform a somewhat similar operation-in their case by takeover of the sources of information, rather than the channels of communication. If as a result of these experiments (and those at McGill and Princeton) actual unconsciousness was not reached, it may very well be that total isolation has not yet been achieved, as would be demanded by the quoted theories of Grey Walter and interpretations of clinical evidence by Sir Russell Brain.

It would, however, be interesting to determine how easily hypnosis can be induced under such conditions of perceptual isolation. From these findings it seems possible, if nothing more, that a silent room might prove to be a simple means of hypnotising the unhypnotisable 10% of the population, or making light-trance and medium-trance subjects, said to be each 35%of the population, into deep-trance subjects who normally constitute only 20%-or even into " very deep trance " subjects capable of eidetic imagery and regression, who apparently make up less than 2%. The hope is that