CONGENITAL CARDIAC ARRHYTHMIA

CONGENITAL CARDIAC ARRHYTHMIA

648 It is unlikely that this boy had access to drugs before he had symptoms. No evidence of malignancy or chronic infection was found; the spleen was ...

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648 It is unlikely that this boy had access to drugs before he had symptoms. No evidence of malignancy or chronic infection was found; the spleen was not palpable. The diagnosis of idiopathic or primary hypoplastic ansemia was made by exclusion of other known causes of marrow depression. Therefore this patient differed fundamentally from the six patients of Dr. Humble, all of whom showed marrow depression secondary to known causes. Treatment with prednisone was followed by an incomplete remission, but this was not maintained. Testosterone had no effect. Administration of phytohsemagglutinin led to very slight changes in the appearances of the lymphocytes, but absolutely no other detectable result. The study of this one patient suggests that the haematological response to phytohaemagglutinin in primary idiopathic hypoplastic anaemia differs from the response in cases secondary to chemotherapy or irradiation. I wish to thank Dr. P. A. J. Ball for permission to publish details of this patient, who was under his care. Department of Hæmatology, University College Hospital, Ibadan, Nigeria.

A. F. FLEMING.

SIR,-Humble1 has described a therapeutic use in aplastic -ansemia for the phytohoemagglutinin (P.H.A.) derived from red kidney beans. Since few toxicity data are as yet available, we are prompted to report some experiments in which laboratory animals were injected with large doses of P.H.A.. We have found that doses of P.H.A.* of the order of 100300 mg. per kg. body-weight killed twelve out of twelve mice and three out of three rats when injected intravenously, and eight out of eight guineapigs when injected into the heart. These animals died within 2-20 seconds after the injection. Smaller doses, of the order of 50-150 mg. per kg., produced an illness characterised by some or all of the following at varying intervals: inactivity, slumped or hunched posture, increased or decreased respiratory rate, apparent muscular weakness which sometimes amounted to complete paralysis especially of the hind limbs, piloerection, and convulsions. Some of the ill animals died after intervals ranging from 1/2 to 24 hours; some made a complete recovery overnight; and in a few of those which lived, the hindlimb paralysis was only partially reversed. In other experiments we have shown that animals readily make antibodies against P.H.A. In the case of the guineapig, the immune animals responded to intradermal injection of P.H.A. by an immediate Arthus type of reaction which progressed to local necrosis of skin and subcutaneous tissue. This suggests that intravascular injection of P.H.A. into these immune animals might precipitate anaphylactic shock. We have been able to test only one such immune guineapig, and its mode of death and hyperinflated lungs at necropsy suggested that it had died of anaphylaxis. We have also injected P.H.A. into mice in large daily doses (50 mg.) subcutaneously, and this procedure has resulted in the formation of sloughing and ulceration at the injection site.

It is known that commercially available P.H.A. is a mixture of substances,23 but so far there is no evidence to indicate whether the toxin, the factor which stimulates mitosis in lymphocytes,’ and the antigen(s) responsible for hypersensitivity reactions, are one and the same, or whether they are three separable components. It is necessary to stress that the lethal doses reported * ’

phytohasmagglutinin, prepared by Wellcome Research Laboratories, Beckenham, England, is issued as a diagnostic reagent

Wellcome ’ brand

1. 2. 3. 4.

intended for use in in-vitro tests. It is supplied as a dried powder in a bottle of 5 ml. capacity, and this powder contains 50 milligrammes of protein. The doses given above refer to milligrammes of this powder protein, which can, of course, be made up to varying concentrations by varying the amount of diluent added. Humble, J. G. Lancet, 1964, i, 1345. Robbins, J. H., Wachtel, A. W. ibid. 1963, ii, 406. Norins, L. C., Marshall, W. H. Unpublished. Marshall, W. H., Roberts, K. B., Wanless, F., Young, M. R. J. Physiol. 1964. 170, 54P.

above are very much larger than those cited by Humbler who used 1 mg. per kg. or less in his patients. As we fee that P.H.A. is a substance of exceptional interest and potential, we have no desire to dampen enthusiasm for its use in appropriate human disease; but our experiments indicate the need for caution in the use of high doses or repeated administration of P.H.A. in man. We thank the Wellcome Research Laboratories for generous

supplies of their laboratory diagnostic reagent phytohsemagglutinin, and Sir Macfarlane Burnet and Dr. Ian Mackay for their interest and advice. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

L. C. NORINS

W. H. MARSHALL.

CONGENITAL CARDIAC ARRHYTHMIA SIR,-Besides the syndrome mentioned in your annotation (July 4) and in the letter of Dr. Barlow and others (Sept. 5), there exists another genetically determined condition, characterised by a grossly drawn-out QT interval, fainting attacks, and sudden death.I-4 This other syndrome differs from the first in its recessive rather than dominant mode of inheritance, and in its occurrence in profoundly deaf children. Morquio 5 described an Uruguayan sibship in which recurrent and eventually fatal attacks of syncope closely resembled those found in both these conditions. This may therefore represent an early description of one or the other of these syndromes, although electrocardiographic confirmation is lacking. In view of the bizarre and distinctive nature of the E.c.G. tracings in these two conditions, some underlying biochemical disturbance may be common to both. Since breeding tests are their exact genetical relation must remain unclear; nor does the connection with profound perceptive deafness in childhood admit of a ready explanation. As well as causing fatal attacks in childhood and early adult life, these and other genetically determined inborn errors of cardiac metabolism undoubtedly play a part in the causation of sudden unexolained deaths in infancv. Department of Ophthalmology, Royal College of Surgeons, G. R. FRASER. London, W.C.2.

impracticable,

Department of Social and Preventive Medicine, Queen’s University, Belfast.

P. FROGGATT.

TRACHEOSCOPY AND SALINE-SUCTION AFTER TRACHEOSTOMY SIR,-The article by Mr. Thompson and Dr. Pryor (July 4) and the letter by Dr. Broom (Aug. 1) prompt me to record a case which illustrates the value of tracheoscopy 6 for investigating unexplained respiratory obstruction after tracheostomy and the need for improved methods of humidification.7 Tracheostomy was performed on a 10-month-old African baby for severe post-measles laryngotracheobronchitis. A metal tube was inserted, and the infant was nursed in a steamtent. Five days later the airway was completely obstructed, even though the tracheostomy tube was patent. Insertion of a larger one afforded no relief. I then substituted a longer nylon-reinforced latex tube, which only partly relieved the obstruction. After the infant had recovered sufficiently, tracheoscopy through the tracheostome with an auriscope revealed a large inspissated mucous plug adherent to the anterior tracheal wall just above the carina. In addition, tracheal collapse, which must have contributed to the obstruction, was observed during the examination. Under direct vision through the auriscope, the plug was partly removed by repeated saline instillation and 1. 2. 3. 4. 5. 6. 7.

Jervell, A., Lange-Nielsen, F. Amer. Heart J. 1957, 54, 59. Levine, S. A., Woodworth, C. R. New Engl. J. Med. 1958, 259, 412. Fraser, G. R., Froggatt, P., James, T. N. Quart. J. Med. 1964, 33, 361. Fraser, G. R., Froggatt, P., Murphy, T. Ann. hum. Genet. (in the press). Morquio, L. Arch. Méd. Enf. 1901, 4, 467. Smythe, P. M. Brit. med. J. 1963, i, 565. Marshall, M. Lancet, July 25, 1964, p. 186.