1324 the next five days in bed at home. At this time in outpatients and still had slight occipital pain some dizziness on standing. No abnormal physical signs were present, although, on standing from the supine position, the blood-pressure fell from 130/80 to 110/60 mm. Hg. After a total of eight days without drugs, phenelzine was restarted in a dosage of 15 mg. twice daily without untoward effect. Fourteen days later she was quite well and her depression
gradually she and
over
was seen
was
still controlled.
Increasing weight in patients taking monoamineoxidase inhibitors is a common problem because of (a) water retention and (b) increasing appetite as the mood lifts. It is obvious that the use of amphetamine or its derivatives as appetite suppressants is contraindicated in these patients. This report also underlines once more the dangers of prescribing drugs without knowledge of what other therapy the patient may be taking. C. M. TONKS Department of Psychiatry, D. LIVINGSTON. 2. Leeds, SIR,-The letter by Dr. requires some comment.
van
Rossum
(April 27)
I heartily agree that it is desirable to attempt to predict from animal studies the difficulties which may occur in humans when drugs are administered. However, there are certain grave difficulties in relating the results of Dr. van Rossum’s study in mice to possible similar effects in human subjects when oc-methyldopa and pargyline are administered simultaneously in therapeutic doses. The observed excitation in mice has a very logical explanation which is related primarily to the high dosages of the drugs employed. Excitation does not occur when these drugs are administered in therapeutic amounts to patients. Dr. van Rossum does not indicate what dosages he used, but the usual animal experiment involves large parenteral doses compared with recommended oral dosage of the same drugs in humans. x-Methyldopa is more than an inhibitor of dopa decarboxylase ; it also releases noradrenaline from tissue binding sites in the brain similarly to ot-methyl metatyramine and reserpine.I If reserpine is administered in very high doses to animals pretreated with a monoamineoxidase (M.A.O.) inhibitor, severe effects of excitement and piloerection will be observed instead of the usual profound sedation seen with reserpine alone.:! This is the basis of the biological screening test for monoamineoxidase inhibitors, which is called the reserpinereversal test. The explanation for this is that noradrenaline released by reserpine in the animal without pretreatment by a M.A.O. inhibitor is quickly inactivated by M.A.O. In the presence of M.A.O. inhibition, however, the released noradrenaline is allowed to spill out on to receptor sites without M.A.o. inactivation, thus producing excitement and piloerection. The situation with a-methyldopa and ot-methyl metatyramine is
analogous. Many patients have been treated simultaneously with pargyline and reserpine. Maronde3 has just reported on one series of such patients. While the sedative and depressant effects of reserpine can be reversed by pargyline, no unusual excitement or severe reactions have been observed. Clinical experience from concomitant therapy with 7.-methyldopa and pargyline is thus far limited. Gillespie et al. have reported their results of combined therapy with x-methyldopa and pargyline. They encountered no difficulty. Our records describe two patients with simultaneous administration of pargyline and a-methyldopa and another patient treated with pargyline alone when it was substituted for oc-methyldopa. The daily dosage simultaneously administered to one of the two patients receiving combination therapy was 25—87mg. of 1. 2.
3. 4.
Brodie, B. B., Costa, E. Psychopharmacology Service Center Bull. 1962, 2, 1. P. B. B. Proc. Soc. exp. Biol., N.Y. 1957, 94, 433. Shore, A., Brodie, Maronde, R. F., Haywood, L. J., Feinstein, D., Sobel, C. J. Amer. med. Ass. 1963, 184, 7. Gillespie, L., Jr., Oates, J. A., Grout, R. Jr., Sjoerdsma, A. Circulation, 1962, 25, 281.
and 250-750 mg. of at-methyldopa over a period of eleven weeks.5 No unusual reactions or toxic effects were encountered either with this patient or with the other two patients. Kinross-Wright and Charolampous had administered both drugs orally as well as intravenously to non-hypertensive patients and they did not encounter adverse effects.6
pargyline
In summary, oc-methyldopa and pargyline will frequently be administered to patients simultaneously since both drugs are indicated for the treatment of hypertension. Furthermore, simultaneous administration of these drugs increases the hypotensive response.4 Dr. van Rossum’s animal studies cannot be directly interpreted to predict difficulty with the combined use of these drugs clinically when they are administered to patients in recommended dosages. Medical Division, Abbott Laboratories, North Chicago, Illinois, U.S.A.
ROBERT L. HERTING.
SCURVY IN THE AGED
SIR,-It would be interesting to learn whether others have noticed an increase in the number of elderly patients suffering from scurvy after the past severe winter. It might be worth giving old-age pensioners vouchers for free vitamin C. ALEX FRANKLIN. London, W.2. A PHYSICAL SIGN IN THYROTOXICOSIS
SIR,-Dr. Mills’ article on cervical murmurs in thyrotoxicosis (April 6) and the letters of Dr. Gimlette (April 20) and Dr. Lewes (April 27) prompt me to draw attention to a report by Jones,’ who found a cervical venous hum in 27°o of 250 healthy people. I listened for this sign in 62 adults and found the typical elements in 12 (19%). Though the hum may be commoner in thyrotoxicosis (Mills found it in 16 of 20 patients), it is doubtful whether a sign found in 27% of a group of healthy people can be useful in diagnosis. The suggestion that toxic and non-toxic goitres may be differentiated by the presence indeed. Staten
absence of
or
a
venous
Island, New York,
hum is
tenuous
JAMES STREETO.
U.S.A.
THE STOVE-IN CHEST to Mr. Maitland’s letter (June 1), the reported in my letter of May 18 were patients with multiple rib fracture, associated with dyspnoea and paradoxical movement of the chest wall; and qualify for the label " flail chest ". We prefer to use a less precise label " injury to the chest with severe respiratory symptoms " because emphasis on the " flail segment " tends to obscure the basic cause of the trouble, which is dyspnoea, with or without respiratory insufficiency.11 The causes of the dyspnoea may be obstruction of the
SIR,-In reply
cases
trachea and bronchi with
blood, vomit, or secretions, contusion,
infection of the
lung, reduced diaphragmatic movement, pain, and finally paradox. The degree of paradox is related to the increased respiratory effort, and treatment of the causes of dyspnoea will reduce or control the paradox. Thus, adequate tracheobronchial toilet, reinflation of a collapsed lung for pleural drainage, and relief of pain will in many patients abolish dyspnoea and control paradox. If, however, complications such as lung cedema, infection, bronchospasm, abdominal distension, fever, or urxmia develop in the days that follow, dyspnoea and paradox will return. In collapse, oedema,
5. 6. 7. 8.
Lee, Richard.
or
Personal communication.
Kinross-Wright, J., Charolampous, K. D. Clin. Res. 1963, 11, Jones, F. L., Jr. New Engl. J. Med. 1962, 267, 658. J. Bone Jt Surg. 1961, 43B, 623.
177.
1325 with a reduced respiratory reserve prior to injury or those who suffer severe damage to the lung at the time of injury, the dyspnoea and paradox will persist. These are the patients in whom intermittent positive-pressure ventilation is injuries lifesaving. They constitute a small proportion of all " of the chest. These are the patients we define as injury of the chest with severe respiratory symptoms ". These are the patients in whom mechanical fixation of the chest is likely to fail, because it cannot influence the cause of the dyspnoea and
patients
associated respiratory insufficiency. H. W. C. GRIFFITHS.
Edinburgh.
COMPENSATED ADRENOCORTICAL FAILURE my paper of
SIR,-In
May
18 the
term
plasma-corti-
costeroids was used; while the meaning is fairly clear, it has been pointed out that " plasma-corticotrophin ", if substituted, leaves no room for ambiguitv. Royal Free Hospital, London, W.C.1.
HILLAS SMITH.
MISUSE OF SECTION 29
SiR,ŅLegal phraseology is by no means precise and unambiguous, as Dr. Lowe (June 1) would have us believe. Anybody can confirm this by spending a day in a Court of Law. I am not at all convinced that the law is being broken. The phrases " urgent necessity " and " undesirable delay " are obviously being interpreted in different ways by psychiatrists all over the country, hence the wide variations in procedure. In 1962 the number of patients admitted to Park Prewett Hospital under section 29 was 336. Of these, 174 became informal after three days. By avoiding section 25 they were saved a grand total of twelve years’ detention. If a similar policy were followed in all other psychiatric hospitals, I estimate that the " misuse of section 29 " would avoid a thousand years of detention every year. I consider this is in the best interests of patients ", and I cannot understand anybody thinking otherwise. "
Park Prewett Hospital, Basingstoke, Hampshire.
I. ATKIN. NALORPHINE
SIR,-In
a
recent
paperand in a letter2 various as an analeptic. Surely this
authors refer to nalorphine classification is incorrect.
Such a careless description of nalorphine predisposes to misunderstanding and untimely administration. The proper use of nalorphine is to antagonise morphine and morphine-like drugs only. When nalorphine is given in the absence of morphine it will act in a manner less intense than but similar to that of morphine. Thus the respiratory minute volume is moderately reduced.3 (Neostigmine is never classified as an analeptic, although it may restore breathing after the use of curariform drugs.) When treating a case of acute chlorpromazine poisoning Dilworth et al.l administered the non-specific analeptics picrotoxin, bemegride, and amiphenazole. Since no specific phenothiazine antagonist is available this is a rational procedure ; but it is not easy to understand why they also tried nalorphine, which would not be expected to have any action antagonistic to chlorpromazine, and possibly could increase respiratory depression. It is not surprising, then, to read: " Nalorphine produced no response."
NewDunedin, Zealand. 1.
Dilworth,
2. 3.
Davies, D. Goodman,
N. M.,
p. 137.
R. V. TRUBUHOVICH. Dugdale,
A.
disease. these accusations I must refer him to the data of mortality and morbidity with hypopublished tensive anarsthesia in a large series of nearly 10,000
to coronary
In
answer to
patients.’i
Department of Anaesthetics,
Royal Infirmary,
HYPOTENSIVE ANÆSTHESIA SIR,-Dr. Osborn’s indictment (May 25) of hypotensive anaesthesia seems to be twofold: (1) many patients do not survive the postoperative period; (2) it predisposes
E., Hilton,
H. B.
Lancet, Jan. 19, 1963,
M. ibid. March 30, 1963, p. 726. L. S., Gilman, A. Pharmacological Basis of p. 254. New York, 1950.
Therapeutics;
These results show a low overall mortality, and the total absence of coronary thrombosis as an immediate cause of death, or during the immediate postoperative period in hospital. For longer periods than this after operation no figures are available, but it would appear unjustifiable to make accusations of this nature if they cannot be supported by facts. Investigations into controlled hypotension 2-4 as well as those now reported by Slack and Walther (May 18), support the view that blood flow to vital organs is more important than pressure, and that flow can be adequate even with very low pressures. Dr. Osborn appears to have ignored the basic requirements for safe hypotension-which are vasodilatation, full oxygenation, and normovolasmia. From the examples he quotes I can only infer that he mistakenly considers all hypotensive conditions to be comparable, and that they should all be looked upon as equally dangerous. G. E. HALE ENDERBY. London, W.l. HYPOTENSION FROM ABSENT CIRCULATORY REFLEXES
SIR,-Dr. Barraclough and Professor Sharpey-Schafer (May 25) draw attention to the dangers of hypotension from absent circulatory reflexes, such as occurs in certain
pathological states and after treatment with certain drugs. They rightly stress that surgical procedures carry special hazards in these patients; for the lack of circulatory reflexes may not be recognised, nor the dangers appreciated before serious collapse has occurred. The practice of controlled hypotension by autonomic blockade with controlled posture and respiration has taught anarsthetists the value of continuous bloodpressure monitoring during anaesthesia. This practice should not be reserved for this technique only; it should be used widely, and more especially when circulatory reflexes are weak or the operation is of sufficient magnitude to affect circulatory stability. Unexpected hypotension is encountered not infrequently in the anaesthetised patient, when it may be due to the effects of drugs or other mechanisms. It is often observed in those patients who have- suffered prolonged immobility, as in spinal caries and poliomyelitis, and in elderly patients in poor physical condition. These patients react to anaesthetic drugs by developing a mechanical circulation similar to that exhibited by normal patients after ganglion-blocking drugs. This hypotension can usually be controlled by the same mechanical factors of posture and respiration so as to ensure a safe
hypotension, or a return to more normal according to the dictates of the surgery and of the patient.
pressures,
the
safety
G. E. HALE ENDERBY. London, W.1. G. E. H. Brit. Anœsth. J. Enderby, 1961, 33, 109. Eckenhoff, J. E. Proc. R. Soc. Med. 1962, 55, 942. Stone, H. H., Mackrell, T. N., Wechsler, R. L. Anesthesiology, 1955, 16, 168. 4. Finnerty, F. A., Witkin, L., Fazekas, J. F. J. clin. Inves.t 1954, 33, 1227. 1. 2. 3.