386

able to the inhibitory action of cyclic A.M.P. Cyclic A.M.P. isconsidered to be inhibitory, particularly to suppressor T cells,1Oso increased sensitivity to cyclic A.M.P. should result in an im-balance between suppressor and helper T cells. A failing regu-latory T-cell function might first affect the synthesis of IgEantibodies since this synthesis seems to be more dependent onT-cell regulation than is the formation of other immunoglob-ulins." The end-result will thus be overproduction of IgE (rea-ginic) antibodies and atopic disease. A vicious circle might beestablished because the manifestation of allergy is accom-

panied by histamine liberation and hence production of intra-cellular cyclic A.M.P.

Atopic allergy is not invariably accompanied by hyperpro-duction of IgE. Atopic disease is really ultimately a conse-quence of the action of vasoactive amines, and it would be sur-prising if the chain of events described above were the onlypathway for the development of atopic disease. However, ourhypothesis would explain the features of the most usual formsof hereditarily determined, atopic hypersensitivity to commonallergens.Department of Virology,Institute of Medical Microbiology,University of Umeå;

and Pædiatric Clinics,Universities of Göteborg and Umeå,Sweden

Ö. STRANNEGÅRDI.-L. STRANNEGÅRD

P. JUTO

TYRAMINE AND M.A.O. INHIBITORS IN POSTURALHYPOTENSION

SIR,--The conclusions drawn by Dr Davies and his col-leagues (Jan. 28, p. 172) concerning the use of tyramine andmonoamine-oxidase inhibitors in the management of posturalhypotension are unduly pessimistic, and may discourage a trialof this treatment in severely disabled patients. In the past twoyears four patients with severe orthostatic hypotension havebeen referred to this unit for consideration of treatment withthe combination. All four patients were unable to stand with-out fainting. Three .patients had already been treated withfludrocortisone, postural training, and elastic stockings forseveral years without persistent benefit.

After detailed tests of autonomic function the patients weregiven tranylcypromine, and the dose of tyramine was grad-ually adjusted to that which enabled each patient to remainstanding for at least 5 min.’ Our practice was to keep each pa-tient in bed in the morning until 15-30 min after the first doseof tyramine and to adjust the frequency of dosage dependingon return of symptoms of postural hypotension. The last doseof tyramine was taken so that symptoms were again apparentbefore the patient went to bed at night. The three patientsreceiving the combination treatment have all been able toresume an upright posture at home, and two now leave theirhomes without fear of fainting. All are aware, and werewarned before treatment, of the dangers of lying down aftertaking tyramine. Treatment has been continued for 5, 10, and12 months, in the three patients and all continue to wear elas-tic stockings and take fludrocortisone. Mean sitting blood-pres-sure has risen from a pre-treatment level of 125/87 to 143/93mm Hg, and mean standing blood-pressure is now 86/52 mmHg.The fourth patient responded to postural training and elas-

tic support stockings, and this should always be tried beforetherapy with tyramine and monoamine-oxidase inhibitors.However, a trial of this drug therapy should not be denied pa-tients with intolerable postural hypotension.M.R.C. Blood Pressure Unit,Western Infirmary,Glasgow G11 6NT PATRICK M. TRUST

10. Teh, H.-S., Paetkau, V. Cell. Immun, 1976, 24, 220.1. Nanda, R. N., Johnson, R. H., Keogh, H. J. Lancet, 1976, ii, 1164.

CARDIORESPIRATORY ARREST IN DIABETICNEUROPATHY

SIR,-The paper by Dr Page and Dr Watkins (Jan. 7, p. 14)prompts us to report a case. A 31-year old insulin-requiringdiabetic female was admitted for nausea, vomiting, and dehyd-ration. 5 years earlier she had had a hypophysectomy in an un-successful attempt to halt severe diabetic retinopathy. She wastaking adequate amounts of thyroid and hydrocortisone. Herhistory showed no clear cause for the emesis, but was positivefor both peripheral parsesthesia and diabetic autonomic neuro-pathy (orthostatic hypotension and abnormal sweating).

She had hypotension (blood-pressure 80/40 mm Hg), nor-mal heart and lungs, no evidence of gastrointestinal obstruc-tion, much decreased sensation in the lower extremities withno peripheral reflexes, and a gag reflex. The intial diagnosiswas either "’flu-like illness" or "gastroparesis diabeticorum".She was given large amounts of cortisol, and hydrated. She didvery well; the emesis stopped, and she was about to be trans-ferred from intensive care when she suddenly became apnceicwhile maintaining a palpable carotid pulse which subsequentlydisappeared. Her mouth and trachea were found to containlarge amounts of stomach contents upon emergency endotra-cheal intubation. (Blood-sugar 30 min before the arrest hadbeen 156 mg/dl.)

She was easily resuscitated, but had moderately severe aspir-ation pneumonitis. She was vigorously treated with antibioticsand steroids with resolution of the aspiration pneumonitis.Electrocardiograms remained normal. 13 days after the"arrest" she was transferred from intensive care.We were unsure whether the "arrest" had been caused by

or had caused the aspiration. Throughout the 13-days of inten-sive-care, vomiting was not a problem.

1 day after transfer the patient had another cardiorespira-tory arrest. (Blood-sugar 1 h earlier had been 180 mg/dl.)Again, aspiration occurred. She was successfully resuscitated;however, the aspiration pneumonitis resulted in severe

hypoxia, necessitating the use of a respirator with high oxygenconcentration. Adult respiratory-distress syndrome developedand the patient died 26 days after her original admission.We are not clear what caused these cardiorespiratory

arrests. The patient was in metabolic balance and had noevidence of significant cardiac or respiratory disease before-hand. At first we thought that the earlier episode was second-ary to aspiration of gastric contents. Diabetics may have

gastric retention’ and abnormal motor. oesophageal function,2and the combination of these two disorders could have resultedin vomiting, though we knew of no reports of aspiration indiabetics. Diabetics can have vocal-cord paralysis.3 We couldfind no reports of aberrant epiglottal function. Dudley’ hasshown that vagal denervation of the oesophagus in pigs canresult in aspiration pneumonia. We therefore felt that perhapsaspiration had been the problem, and that we could explain theaspiration on the basis of diabetic autonomic neuropathy. Wesimilarly explained the second cardiorespiratory arrest,

although we were unsure whether the patient had vomitedbefore or after the "arrest".

This report provides an additional case of sudden death ina patient with diabetic autonomic neuropathy. As in the casesof Ewing et aJ.3 and Page and Watkins, we are unsure whatcaused the catastrophe. We agree that impairment of respira-tory reflexes is an interesting possibility. What role mightaspiration have played in the twelve cardiorespiratory arrestsreported by these workers? Diabetics may have abnormalsweating patterns; might they also have an abnormal reflexresponse to small amounts of aspirated stomach contents?

1. Kassandar, P. Ann. intern. Med. 1958, 48, 797.2. Silber,W. Br. med J., 1969, iii, 688.3 Rucente, F E. Ann Otolar. 1973, 82, 131.4 Dudley, N. E. Aust.pœdiat. J. 1973, 9, 289.5 Ewing, D. J., Campbell, I. W., Burt, A. A., Clarke, B. F. Lancet, 1973, ii,

1354