386 able to the inhibitory action of cyclic A.M.P. Cyclic A.M.P. is considered to be inhibitory, particularly to suppressor T cells,1O so increased sensitivity to cyclic A.M.P. should result in an imbalance between suppressor and helper T cells. A failing regulatory T-cell function might first affect the synthesis of IgE antibodies since this synthesis seems to be more dependent on T-cell regulation than is the formation of other immunoglobulins." The end-result will thus be overproduction of IgE (reaginic) antibodies and atopic disease. A vicious circle might be established because the manifestation of allergy is accompanied by histamine liberation and hence production of intracellular cyclic A.M.P. Atopic allergy is not invariably accompanied by hyperproduction of IgE. Atopic disease is really ultimately a consequence of the action of vasoactive amines, and it would be surprising if the chain of events described above were the only pathway for the development of atopic disease. However, our hypothesis would explain the features of the most usual forms of hereditarily determined, atopic hypersensitivity to common
allergens. Department of Virology, Institute of Medical Microbiology, University of Umeå; and Pædiatric Clinics, Universities of Göteborg and Umeå, Sweden
Ö. STRANNEGÅRD I.-L. STRANNEGÅRD
P. JUTO
TYRAMINE AND M.A.O. INHIBITORS IN POSTURAL HYPOTENSION
SIR,--The conclusions drawn by Dr Davies and his colleagues (Jan. 28, p. 172) concerning the use of tyramine and monoamine-oxidase inhibitors in the management of postural hypotension are unduly pessimistic, and may discourage a trial of this treatment in severely disabled patients. In the past two years four patients with severe orthostatic hypotension have been referred to this unit for consideration of treatment with the combination. All four patients were unable to stand without fainting. Three .patients had already been treated with fludrocortisone, postural training, and elastic stockings for several years without persistent benefit. After detailed tests of autonomic function the patients were given tranylcypromine, and the dose of tyramine was gradually adjusted to that which enabled each patient to remain standing for at least 5 min.’ Our practice was to keep each patient in bed in the morning until 15-30 min after the first dose of tyramine and to adjust the frequency of dosage depending on return of symptoms of postural hypotension. The last dose of tyramine was taken so that symptoms were again apparent before the patient went to bed at night. The three patients receiving the combination treatment have all been able to resume an upright posture at home, and two now leave their homes without fear of fainting. All are aware, and were warned before treatment, of the dangers of lying down after taking tyramine. Treatment has been continued for 5, 10, and 12 months, in the three patients and all continue to wear elastic stockings and take fludrocortisone. Mean sitting blood-pressure has risen from a pre-treatment level of 125/87 to 143/93 mm Hg, and mean standing blood-pressure is now 86/52 mm
Hg. The fourth patient responded to postural training and elastic support stockings, and this should always be tried before therapy with tyramine and monoamine-oxidase inhibitors. However, a trial of this drug therapy should not be denied patients with intolerable postural hypotension. M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT 10. 1.
PATRICK M. TRUST
Teh, H.-S., Paetkau, V. Cell. Immun, 1976, 24, 220. Nanda, R. N., Johnson, R. H., Keogh, H. J.Lancet, 1976, ii, 1164.
CARDIORESPIRATORY ARREST IN DIABETIC NEUROPATHY
SIR,-The paper by Dr Page and Dr Watkins (Jan. 7, p. 14) prompts us to report a case. A 31-year old insulin-requiring diabetic female was admitted for nausea, vomiting, and dehydration. 5 years earlier she had had a hypophysectomy in an unsuccessful attempt to halt severe diabetic retinopathy. She was taking adequate amounts of thyroid and hydrocortisone. Her history showed no clear cause for the emesis, but was positive for both peripheral parsesthesia and diabetic autonomic neuropathy (orthostatic hypotension and abnormal sweating). She had hypotension (blood-pressure 80/40 mm Hg), normal heart and lungs, no evidence of gastrointestinal obstruction, much decreased sensation in the lower extremities with no peripheral reflexes, and a gag reflex. The intial diagnosis was either "’flu-like illness" or "gastroparesis diabeticorum". She was given large amounts of cortisol, and hydrated. She did very well; the emesis stopped, and she was about to be transferred from intensive care when she suddenly became apnceic while maintaining a palpable carotid pulse which subsequently disappeared. Her mouth and trachea were found to contain large amounts of stomach contents upon emergency endotracheal intubation. (Blood-sugar 30 min before the arrest had been 156 mg/dl.) She was easily resuscitated, but had moderately severe aspiration pneumonitis. She was vigorously treated with antibiotics and 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.
patient had another cardiorespira(Blood-sugar 1 h earlier had been 180 mg/dl.) Again, aspiration occurred. She was successfully resuscitated; 1
tory
day
after transfer the
arrest.
however, the aspiration pneumonitis resulted in
severe
hypoxia, necessitating the use of a respirator with high oxygen concentration. Adult respiratory-distress syndrome developed and the patient died 26 days after her original admission. not clear what caused these cardiorespiratory The patient was in metabolic balance and had no evidence of significant cardiac or respiratory disease beforehand. At first we thought that the earlier episode was secondary to aspiration of gastric contents. Diabetics may have gastric retention’ and abnormal motor. oesophageal function,2 and the combination of these two disorders could have resulted in vomiting, though we knew of no reports of aspiration in diabetics. Diabetics can have vocal-cord paralysis.3 We could find no reports of aberrant epiglottal function. Dudley’ has shown that vagal denervation of the oesophagus in pigs can result in aspiration pneumonia. We therefore felt that perhaps aspiration had been the problem, and that we could explain the aspiration on the basis of diabetic autonomic neuropathy. We similarly explained the second cardiorespiratory arrest, although we were unsure whether the patient had vomited before or after the "arrest". This report provides an additional case of sudden death in a patient with diabetic autonomic neuropathy. As in the cases of Ewing et aJ.3 and Page and Watkins, we are unsure what caused the catastrophe. We agree that impairment of respiratory reflexes is an interesting possibility. What role might aspiration have played in the twelve cardiorespiratory arrests reported by these workers? Diabetics may have abnormal sweating patterns; might they also have an abnormal reflex response to small amounts of aspirated stomach contents?
We
are
arrests.
1. Kassandar, P. Ann. intern. Med. 1958, 48, 797. 2. Silber,W. Br. med J., 1969, iii, 688. 3 Rucente, E. F 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. 1354
Lancet, 1973, ii,
allergens. Department of Virology, Institute of Medical Microbiology, University of Umeå; and Pædiatric Clinics, Universities of Göteborg and Umeå, Sweden
Ö. STRANNEGÅRD I.-L. STRANNEGÅRD
P. JUTO
TYRAMINE AND M.A.O. INHIBITORS IN POSTURAL HYPOTENSION
SIR,--The conclusions drawn by Dr Davies and his colleagues (Jan. 28, p. 172) concerning the use of tyramine and monoamine-oxidase inhibitors in the management of postural hypotension are unduly pessimistic, and may discourage a trial of this treatment in severely disabled patients. In the past two years four patients with severe orthostatic hypotension have been referred to this unit for consideration of treatment with the combination. All four patients were unable to stand without fainting. Three .patients had already been treated with fludrocortisone, postural training, and elastic stockings for several years without persistent benefit. After detailed tests of autonomic function the patients were given tranylcypromine, and the dose of tyramine was gradually adjusted to that which enabled each patient to remain standing for at least 5 min.’ Our practice was to keep each patient in bed in the morning until 15-30 min after the first dose of tyramine and to adjust the frequency of dosage depending on return of symptoms of postural hypotension. The last dose of tyramine was taken so that symptoms were again apparent before the patient went to bed at night. The three patients receiving the combination treatment have all been able to resume an upright posture at home, and two now leave their homes without fear of fainting. All are aware, and were warned before treatment, of the dangers of lying down after taking tyramine. Treatment has been continued for 5, 10, and 12 months, in the three patients and all continue to wear elastic stockings and take fludrocortisone. Mean sitting blood-pressure has risen from a pre-treatment level of 125/87 to 143/93 mm Hg, and mean standing blood-pressure is now 86/52 mm
Hg. The fourth patient responded to postural training and elastic support stockings, and this should always be tried before therapy with tyramine and monoamine-oxidase inhibitors. However, a trial of this drug therapy should not be denied patients with intolerable postural hypotension. M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT 10. 1.
PATRICK M. TRUST
Teh, H.-S., Paetkau, V. Cell. Immun, 1976, 24, 220. Nanda, R. N., Johnson, R. H., Keogh, H. J.Lancet, 1976, ii, 1164.
CARDIORESPIRATORY ARREST IN DIABETIC NEUROPATHY
SIR,-The paper by Dr Page and Dr Watkins (Jan. 7, p. 14) prompts us to report a case. A 31-year old insulin-requiring diabetic female was admitted for nausea, vomiting, and dehydration. 5 years earlier she had had a hypophysectomy in an unsuccessful attempt to halt severe diabetic retinopathy. She was taking adequate amounts of thyroid and hydrocortisone. Her history showed no clear cause for the emesis, but was positive for both peripheral parsesthesia and diabetic autonomic neuropathy (orthostatic hypotension and abnormal sweating). She had hypotension (blood-pressure 80/40 mm Hg), normal heart and lungs, no evidence of gastrointestinal obstruction, much decreased sensation in the lower extremities with no peripheral reflexes, and a gag reflex. The intial diagnosis was either "’flu-like illness" or "gastroparesis diabeticorum". She was given large amounts of cortisol, and hydrated. She did very well; the emesis stopped, and she was about to be transferred from intensive care when she suddenly became apnceic while maintaining a palpable carotid pulse which subsequently disappeared. Her mouth and trachea were found to contain large amounts of stomach contents upon emergency endotracheal intubation. (Blood-sugar 30 min before the arrest had been 156 mg/dl.) She was easily resuscitated, but had moderately severe aspiration pneumonitis. She was vigorously treated with antibiotics and 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.
patient had another cardiorespira(Blood-sugar 1 h earlier had been 180 mg/dl.) Again, aspiration occurred. She was successfully resuscitated; 1
tory
day
after transfer the
arrest.
however, the aspiration pneumonitis resulted in
severe
hypoxia, necessitating the use of a respirator with high oxygen concentration. Adult respiratory-distress syndrome developed and the patient died 26 days after her original admission. not clear what caused these cardiorespiratory The patient was in metabolic balance and had no evidence of significant cardiac or respiratory disease beforehand. At first we thought that the earlier episode was secondary to aspiration of gastric contents. Diabetics may have gastric retention’ and abnormal motor. oesophageal function,2 and the combination of these two disorders could have resulted in vomiting, though we knew of no reports of aspiration in diabetics. Diabetics can have vocal-cord paralysis.3 We could find no reports of aberrant epiglottal function. Dudley’ has shown that vagal denervation of the oesophagus in pigs can result in aspiration pneumonia. We therefore felt that perhaps aspiration had been the problem, and that we could explain the aspiration on the basis of diabetic autonomic neuropathy. We similarly explained the second cardiorespiratory arrest, although we were unsure whether the patient had vomited before or after the "arrest". This report provides an additional case of sudden death in a patient with diabetic autonomic neuropathy. As in the cases of Ewing et aJ.3 and Page and Watkins, we are unsure what caused the catastrophe. We agree that impairment of respiratory reflexes is an interesting possibility. What role might aspiration have played in the twelve cardiorespiratory arrests reported by these workers? Diabetics may have abnormal sweating patterns; might they also have an abnormal reflex response to small amounts of aspirated stomach contents?
We
are
arrests.
1. Kassandar, P. Ann. intern. Med. 1958, 48, 797. 2. Silber,W. Br. med J., 1969, iii, 688. 3 Rucente, E. F 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. 1354
Lancet, 1973, ii,
