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cardial infarction must be explained in part by the relative frequency of cardiac failure as the cause of death, for which no more can be offered in the CCU than in the general ward. It is, however, surely important not to discard the opportunity of effective resuscitationthe stakes are high even though the number of patients benefiting may be small. It must also be remembered that the study was undertaken in two hospitals possessing CCUs and, as the authors concede, the CCU provides a valuable training ground for junior medical staff and nurses, so that it is reasonable to assume that the resuscitation in the wards in such a hospital would be better than where no CCU existed. Withdrawal of the CCU or failure to develop such a unit might well result in lower standards of resuscitation and create an entirely new clinical setting which would require further evaluation. We believe that while patients with acute coronary episodes continue to be admitted to hospital it is mandatory to provide the highest standard of care possible. At a time when the availability of doctors and nurses on the ward seems ever-diminishing some form of CCU organisation would appear to be the only answer. We must at least ask that any future studies of this question should define carefully the nursing and medical staffing arrangements involved so that valid comparisons may be made. B L PENTECOST P J CADIGAN General Hospital,
Birmingham
Joint Working Party, Jfournal of the Royal College of Physicians of London, 1975, 10, 5.
Fatal agranulocytosis attributed to co-trimoxazole therapy SIR,-The recent article by Dr W H W Inman from the Committee on Safety of Medicines (11 June, p 1500) concerning drugs which may be related to fatal bone marrow depression is of major interest and importance. In essence Dr Inman has carried out an uncontrolled study of drug use prior to the diagnosis of aplastic anaemia or agranulocytosis, using for his data source the records of the Office of Population Censuses and Surveys (OPCS). While one might argue about the validity of regarding any exposure to bone-marrow depressing agents in the year prior to diagnosis as being causally related to the diseases of interest, this may well be justified in the case of drugs such as phenylbutazone which are well known to cause bone-marrow depression. However, Dr Inman's assertion that over half the fatal cases of agranulocytosis were caused by co-trimoxazole requires more careful scrutiny. Agranulocytosis is a condition which almost invariably is brought to light as a result of infection. Co-trimoxazole is one of the most frequently prescribed antibacterial drugs in the United Kingdom. Therefore one would reasonably expect a strong association between co-trimoxazole and agranulocytosis even in the absence of a causal relationship between drug and event. To prove a causal relationship either a proper case-control study would be required or alternatively much more information on the true relationships and use of other antibacterial agents would be required than has been given by Dr Inman. Thus we feel the case against co-trimoxazole as a common cause of agranulocytosis is as yet
30 JULY 1977
unproved. Nevertheless, since there is some prior suspicion that the drug could cause this disease by virtue of the chemical structure of one of its components, further studies are obviously required. We therefore sought from the OPCS details of the number of patients dying between 1960 and 1974 from all anaemias, aplastic anaemia, and agranulocytosis.' The numbers, divided into five-year periods, are shown in the accompanying table.
in their article are shown in the accompanying table. As the Draeger system under these circumstances had the worst performance we cannot understand the comment by Dr Armstrong and his colleagues (21 May, p 1348) in reply to our original letter that "only the active system supplied by Draeger was effective, the main reason being that this was the only system which did not leak significantly from areas other than the exhaust valve." Drs L Rendall-Baker and R A Milliken (p 1348) Deaths from diseases of blood: England and Wales and Dr B M Wright (11 June, p 1535) argue on intuitive grounds that an active system 1960-1974 must be the most efficient. We agree that a good active system should Cause of death 1960-64 1965-69 1970-74 be better than a good passive system but we All diseases of blood hope that the misleading summary by and blood forming organs 10376 10125 9289 Dr Armstrong and his colleagues does not Aplastic anaemia 1218 1399 1579 lead to this particular paper being quoted as Agranulocytosis 128 123 120 support for active systems when in fact the results given in the paper show that, when If Dr Inman's suggestion that co-trimoxazole tested with similar circuits, passive systems was causally related to over one-half of the were more effective than active systems. fatal cases of agranulocytosis during the D W BETHUNE period of his survey was true, then one would J M COLLIS expect a major increase in the frequency of Papworth Hospital, this condition in the period since its intro- Cambridge duction in 1968. No such increase was observed. Thus either the association between co-trimoxazole and agranulocytosis is a spurious one in that the latter caused the Litholapaxy former rather than vice versa, or it is a real one but physicians do not suspect it and SIR,-Your leading article (9 July, p 79) on therefore do not diagnose it, being content lithotrity contains a repeated mistake in to certify patients dying of co-trimoxazole- spelling of the word litholapaxy (Greek evacuation). To induced agranulocytosis as dying from the ?.3Orj, stone, and i infection which accompanies the agranulo- spell it twice as lithalopaxy shows an ignorance cytosis. We submit that the case against of its derivation. The Russian Urat 1 method, published in co-trimoxazole is unproved as yet and that the USSR in about 1955, of electrohydraulic Dr Inman will have to produce much more disintegration was shown by Yutkin in London impressive data before claiming that a causal nearly 10 years ago and tried out by a member relationship between this drug and agranuloof the Urological Club; it proved to be lengthy cytosis is established. D H LAWSON and uncertain. I mentioned it in an article on D A HENRY the history of lithotomy and lithotrity in 1968.' Its use in 14 cases is well described by Clinical Pharmacology Service, Royal Infirmary and Mitchell and Kerr2 in the account you quote; University of Strathclyde, they stress the cost and the short life of the tip Glasgow of the probe, but perhaps these can be 'Office of Population Censuses and Surveys, Mortality overcome by realistic pricing and careful usage. Statistics 1974 E,?zlaiid anid OPCS Series Wales, DH1, No 1, table 6. London, HMSO, 1977
ERIC RICHES
London W1
Anaesthetic waste gas scavenging systems SIR,-We feel that the point that we made (21 May, p 1348) regarding the article by Dr R F Armstrong and others (9 April, p 941) has not been fully appreciated by the other correspondents on this subject. They have ignored the results quoted by Dr Armstrong and his colleagues who, for the five systems tested, showed definite superiority for passive systems when all systems were used with similar fresh gas flows on open circuits. The relevant figures extracted from the table
2
Riches, E W, Annals of the Royal College of Suirgeons of England, 1968, 43, 185. Mitchell, M E, and Kerr, W S, jun, 'ournal of Urology, 1977, 117, 159.
Stress incontinence
SIR,-Your leading article on stress incontinence (2 July, p 2) makes no reference to exercise as one form of treatment that may be of value. Women who have suffered from difficult deliveries, chronic illness, malnutrition, exhaustion, old age, and so forth often have attacks of bladder instability.
Atmospheric pollution with halothane, all readings when using open circuits Active systems
Passive systems
Mean (± SE) halothane level during session (ppm)
Enderby valve
PenlonPapworth system
Coaxial circuit with Penlon valve
BOC with open circuit
Draeger with open circuit
4-6 ±0 34
3-4 ±0-42
1 9 a- 0-14
4 0 +0-32
5 3 ± 0 41
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30 JULY 1977
This is often improved if the patient can be persuaded to exercise the sphincters and pelvic muscles persistently and repeatedly. I have no claim to specialised knowledge in this field. But I have been consulted informally by embarrassed women and in many countries-and often with apparently good results-so that I feel the reference to the possibility of exercise should not be neglected. CICELY D WILLIAMS London SE24
SIR,-In your leading article on this subject (2 July, p 2) you rightly point out that urge incontinence may wrongly be interpreted as stress incontinence, with poor results from surgery. In this connection I would like to draw attention to the role of oestrogens in the control of urinary disorders in postmenopausal women and their beneficial effect in the treatment and prevention of these disorders. The distal part of the urethra is of the same embryological origin as the vagina, is lined with a similar epithelium, and is under the same hormone control. Oestrogen deficiency during the menopause leads to atrophic changes in both organs; there is a decrease in elastic tissues and muscular tone. Oestrogen replacement, especially in the form of implants, improves menopausal symptoms, including urinary disorders.' Among 300 menopausal women specially studied, 160 complained of urinary troubles, chiefly of dysuria and incontinence. Of these, 90 underwent various repair operations with a 20°' failure rate, and the majority of these women had been previously treated with antibiotics for recurrent attacks of cystitis. Oestrogen replacement alone, or with dilatation of the sphincter, achieved a definite improvement in urinary disorders in 70 % of the patients. The remaining 300% had to have surgical repair of the vaginal prolapse with elevation and support of the urethrovesical angle. The relatively high failure rate (20-30 %) of repair operations is partly due to the fact that no distinction was made postoperatively between urge and stress incontinence. Oestrogen implants may also be helpful if given before the operation. They improve the condition of the vagina, make dissection easier, and promote healing. Similar observations have been made by other workers in this field.'-4
imipramine, desipramine, and clomipramine. The doses I refer to are in the range of 300-450 mg a day, and although this may be higher than the therapeutic range of some psychiatrists, such doses are justified in unresponsive patients with endogenous depression. I agree that the nature of the dysarthria described is very similar to a stutter, but I do not think it has the characteristic pattern of a cerebellar dysarthria and would personally regard it as an involuntary movement which interrupts the normal process of speech and is most likely of basal ganglion origin. Indeed, I would most liken it to a very localised form of chorea. In conclusion, I think it would be incorrect to say that this was a hitherto undescribed side effect, although it has certainly not been my experience to see it associated with the small doses used by Dr Quader. MICHAEL SAUNDERS Department of Neurology, Middlesbrough General Hospital, Middlesbrough, Cleveland
SIR,-I read with interest the case reports from Dr S E Quader (9 July, p 97) of dysarthria in two patients taking therapeutic doses of tertiary amine tricyclics. At the Regional Poisoning Treatment Centre, Edinburgh, in 1967, during clinical studies of tricyclic poisoning, scanning speech was noted in a high proportion of patients after consciousness was regained following moderate or severe poisoning. The pace and rhythm of syntax were altered so that speech came in bursts or "runs." This persisted for up to 48 hours. Speech changes following tricyclic overdose were commented on by Lewis and Oswald in 1968.1 The overdosed patients had high plasma levels of tricyclics and derivatives but more recent work has shown that plasma levels of these drugs may differ widely among individuals following a fixed dose.2 The tricyclics resemble chlorpromazine in chemical structure and share some pharmacological properties. High plasma levels of phenothiazines have been associated with adverse reactions, including speech disturbance ranging from aphonia to mutism.1 It is suggested that dysarthria associated with tricyclics is related to high plasma levels and it would be of interest to measure these in future patients showing this unwanted E SCHLEYER-SAUNDERS effect. London Wl JOHN N M MCINTYRE Unit Command BAOR, Psychiatric the American Geriatric Schleyer-Saunders, E,Journal of British Military Hospital, 2
3
Society, 1976, 24, 337. 1976, 2, 941. Smith, P, British Greenblat, R B, Geriatrics, 1955, 10, 165. and Gynecology, Obstetrics Greenhill, J P, Clinical 1972, 15, 1083.
Medical_Journal,
Munster, W Germany
Lewis, S A, and Oswand, I, British Journal of Psychiatry, 1969, 115, 1403. Kragh-Sorensen, P, Asberg, M, and Eggert-Hansen, C, Lancet, 1973, 1, 113. 3British Medical Journal, 1973, 1, 755. 2
Dysarthria with tricyclic antidepressants
SIR,-I was interested to read the report by Dr S E Quader relating to dysarthria as an unusual side effect of tricyclic antidepressants, (9 July, p 97). Although it is unusual for dysarthria to develop on the small doses of antidepressants described in his two case reports, this side effect is not uncommon in patients on much larger doses and I have seen it associated with most of the tricyclic antidepressants, including
SIR,-Dr S E Quader's brief report (9 July, p 97) of two cases of dysarthria in patients receiving tricyclic antidepressants is interesting, but has he produced enough evidence to describe this as a "hitherto unrecognsied side effect" ? It is almost invariable for patients receiving these drugs to complain of a dry mouth and throat and most psychiatrists have seen cases in which salivary secretion is so impaired as to make speech almost impossible. We should
be wary of attributing such symptoms to central action in the absence of more definite evidence of cerebellar involvement. D STORER Doncaster Royal Infirmary, Doncaster
Safety and danger of piped gases SIR,-Piped oxygen in large hospitals is sensible for economical and practical reasons. The safety of patients cannot be decreased but (because oxygen cylinders can empty) is increased. The argument that because oxygen is piped it is sensible to pipe nitrous oxide as well needs further thought. The saving in cost with nitrous oxide is much less than with oxygen and is relatively unimportant. The danger of piping any lethal gas is not, however, unimportant. Tragedies have occurred and will occur again; it does not matter what new "safety" measures are applied, the possibility will continue to exist that somebody, sometime, somehow will be given a gas mixture to breathe that contains no oxygen. May I make a plea that no more piped nitrous oxide systems are installed? Careful thought should also be given to the safety of existing systems. The use of cylinders in operating suites may be inconvenient, but surely this inconvenience ought to be accepted in the interest of safety. The existing piping should either fall into disuse or be used for non-lethal gases. Examples might include compressed air, 28 % oxygen enriched air, Entonox nitrous oxide/oxygen mixture, or extra suction as part of an active gas scavenging system. Anything but 100 % nitrous oxide. J V I YOUNG The London Hospital, London El
Paget's disease of bone SIR,-The report by Dr D J P Barker and others (7 May, p 1181) shows both the high overall incidence of Paget's disease and its regional variation in the 14 British towns which they investigated. By comparison the great rarity of Paget's disease in all Black people of the Bantu tribes throughout southern Africa is as curious, and possibly as significant, as Holmes's dog that failed to bark. In the several years since we reported in the South African Medical Journal the first radiologically and histologically proved case in a Bantu man the great rarity of osteitis deformans in that race has remained very obvious. Nor is that due to failure to look for it. or to identify it properly; because of language communication problems x-rays are over- rather than under-used in the major hospitals which provide specialist services for non-White patients. While the disease is encountered occasionally in persons of mixed race (Coloured, Asiatic, Malaysian, etc), it is exceptional in the Bantu people. As a random example, Livingstone Hospital serves well over one million Bantu from several different tribes in eastern Cape Province and encounters no more than one or two suspect cases per year. Personal experience, supported by several colleagues, indicates that the usual finding in the Bantu is a localised and limited lesion, while the advanced, crippling,