Feb 7, 1981 - Bartholomew's Hospital from 1971 to 1975. .... Royal Hospital for Sick Children, .... Petersfield, Hants ... Sydney, New South Wales, Australia.
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VOLUME 282
there is no standard doctor. Might not reluctance to discuss the problem represent an understandable failing in the physician co come to terms with the illness ? In our experience there is no substitute for the truth when communicating in medicine and it should very rarely be necessary to tell lies to patients. What is required is the ability to explain the nature of the problem clearly and sympathetically in terms that the patient and the relatives can understand and accept. A series of interviews is necessary and it is particularly helpful when husband and wife (or a close relative) can share in some of the discussion. We all know of the pain and suffering caused by acute leukaemia and these can extend far beyond the patient to affect relatives, loved ones, doctors, nurses, medical students, and anyone with whom the patient has contact. When communication has been successful the mututal atmosphere of fear, suspicion, and mistrust which ignorance produces can be dispelled and everyone concerned can concentrate on looking after the patient. A C NEWLAND B T COLVIN Department of Haematology, London Hospital, London E 11BB
Pneumonia during treatment of acute leukaemia
7 FEBRUARY 1981
473
will lead to a reduction in the incidence of fatal pulmonary infection. M SLEVIN AMA ROHATINER J S MALPAS ANDREw LISTER
haemoperfusion was justifiable in this situation. With supportive treatment alone Dr Canalese and his colleague have shown that mortality in "high-risk" patients may be as great as 68%, and accordingly we are planning a prospective clinical trial of charcoal haemoperfusion versus supportive therapy in patients Imperial Cancer Research Fund Department of Medical Oncology, who present late (after 15 hours) after ingesting St Bartholomew's Hospital, potentially hepatotoxic quantities of paraLondon ECIA 7BE cetamol. lTobias JS, Wrigley PFM, O'Grady F. EuropJ Cancer M HELLIWELL 1978 ;14 :383-91. JOHN PRIOR 2Slevin ML, Lowes JA, Bell R, et al. Leukaemia Research (in press). GLYN N VOLANS
Paracetamol-induced hepatic failure SIR,-The paper from the King's College Hospital liver unit by Dr J Canalese and others (17 January, p 199) highlights the risk of severe hepatic damage and death from paracetamol in those patients who present to hospital at a time when specific antidotes such as N-acetylcysteine (NAC) or methionine may be ineffective. We have recently reviewed the outcome of 67 patients, referred to the poisons unit of Guy's Hospital from 1975 to 1979, who had been admitted to hospital later than 10 hours following an overdose of paracetamol and had received supportive treatment only. Plasma paracetamol concentrations were measured in each case and all but two patients were in the so-called "high-risk" category defined by Prescott et al.' Fifty-one patients (76%) developed severe hepatic damage (maximum serum aspartate transaminase (AST) > 1000 IU/1), of whom 10 (15%) died. As a result of this high incidence of severe or fatal hepatic damage we have since carried out charcoal haemoperfusion on eight patients presenting to hospital later than 10 hours following a large paracetamol overdose, in the hope that the removal of further quantities of the unchanged drug, even at a late stage, might confer some therapeutic benefit. Details of some of these patients have recently been reported2; the toxicological and haemoperfusion data and the maximum recorded serum AST levels are shown in the table. In all cases there was a rapid fall in the plasma paracetamol concentrations during haemoperfusion and no complications resulted from this procedure. In some instances significant amounts of the drug were removed (cases 4, 5, 7, and 8). Severe hepatic damage occurred in one patient and another died despite further haemoperfusion for acute hepatic failure; the remainder developed only minor disturbances of liver function. Since the efficacy of NAC in preventing paracetamol-induced liver damage diminishes after eight hours and is completely absent after 15 hours we consider that charcoal
Poisons Unit, New Cross Hospital, London SE14 5ER Prescott LF, Illingworth RN, Critchley JAH, Stewart MJ, Adam RD, Proudfoot AT. Br Med Y 1979; ii :1097-100. 2Winchester JF, Gelfand MC, Helliwell M, Vale JA, Goulding R, Schreiner GE. Arch Int Med (in press).
SIR,-I read with interest the recent article by Dr J Canalese and colleagues (17 January, p 199) discussing factors contributing to mortality in paracetamol-induced hepatic failure. The authors warn that delay in administration of hepatoprotective agents in cases of suspected severe paracetamol overdose while awaiting the results of plasma paracetamol concentrations may adversely affect the ultimate prognosis. They advocate the immediate administration of protective drugs until the plasma paracetamol concentration is known. Since initial suspicion of "severe" paracetamol poisoning is relatively common in clinical practice such a course of action will inevitably result in a large number of patients receiving inappropriate therapy. However, the toxicity of paracetamol in overdosage in the adult population is such that their advice is
SIR,-We read with interest the comments of Professor F G J Hayhoe and Dr J K N Rees (6 December, p 1566) on your leading article entitled "Pneumonia.during the treatment of acute leukaemia" (8 November, p 1235). While we wholeheartedly agree with them probably justified. that an intimate knowledge of the pathogens I would caution against the same clinical in the hospital environment in question is approach in the paediatric age group. Paraessential and at least as important as knowing cetamol ingestion is common in children, who the site of colonisation, our experience with accounted for 18% of inquiries regarding the site of infection is in complete contrast paracetamol poisoning received by the London with theirs. At St Bartholomew's Hospital, centre of the British National Poison Informapneumonia is both the most frequently docution Service during 1975.1 There is a significant mented manifestation of bacterial infection lack of correlation between the reported and the commonest cause of death in patients amount ingested and subsequent plasma receiving remission induction therapy for levels.2 In addition, hepatic toxicity is usually acute myelogenous leukaemia (AML). Tobias mild even with plasma paracetamol levels et all found 105 episodes of pulmonary commonly lethal in adults. Elimination infection, of which 32 were fatal, compared kinetic studies of paracetamol metabolism in with 55 documented septicaemias (of unknown children3 indicate relatively more sulphate source), of which 21 were fatal, in an analysis than glucuronide formation, but how this of 200 patients with AML treated at St relates to the apparent resilience of the liver in Bartholomew's Hospital from 1971 to 1975. children is unclear. A. subsequent analysis (not yet published) The adverse effects of these antidotes can confirms these results. Three hundred and be significant and experience of their use in ninety febrile episodes occurred in 168 patients children is limited. In view of the difference with AML treated from November 1974 to in tolerance, these drugs should be withheld May 1980. Eighty-five of these episodes were in children until the plasma paracetamol level caused by pneumonia and 23 were fatal, whereas septicaemia was recorded in 42 patients and was fatal in 12. The frequency with which chest infection Details of eight patients treated with haemoperfusion after paracetamol overdose occurs and our belief (shared by Professor Maximum Amount of Duration of Plasma paracetamol Hayhoe and Dr Rees) that it is essential to Patient Age Dose serum haemoperfusion paracetamol concentration (h) removed (mg) AST (IU/i) (g) know the infecting organism as early as No (y) (mg/i) (hours after ingestion) possible prompted us to introduce transtracheal 349 837 5 42 30 262 (14) 1 327 380 5 ? 245 (16) 2 69 aspiration into the investigation of suspected 30 178 (11-5) 4-5 365 24 3 24 pneumonia in 1979.2 Experience with this 150 (13) 6 ? 4747 393 4 69 2920 10 6699 50 250 (18) safe and simple technique has shown that 5 30* 401 5 742 149 (24) 49 75 6 even in the absence of abnormalities on chest 343 4 3129 27 174 (24-5) 30 7 > lOOOt 50 169 (16-5) 2-5 1966 21 radiograph a pathogen can often be isolated 8 when either sputum is unobtainable or culture = aspartate transaminase. is negative. It is hoped that this technique, by AST *Patient died of fulminant hepatic failure.
providing an early bacteriological diagnosis, tDilution of serum not performed.
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is known and unless it suggests that their use is appropriate. J 0 BEATTIE
C02
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460mmn----
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University Department of Child Health, Royal Hospital for Sick Children, Glasgow G3 8SJ Crome P, Vale JA, Volans GH, Widdop B. Br MedJ7 1976 ;ii :475. Rumack BH, Peterson RG. Pediatrics 1978;62, suppl: 898-903. 3 Miller RP, Roberts RJ, Fischer LJ. Clin Pharm Ther 1976;19 :284-94.
AIR
POLYPROPYLENE TUBES
2
I----,
36mm Petersfield hypothermia tube Mk X.
Urban hypothermia SIR,-It was with interest that we read the paper by Dr K J Collins and others (17 January, p 175) giving support to a preferred environmental temperature of approximately 22°C irrespective of age. A random age- and sex-stratified sample of over-65s living in the community and on the list of a large central Glasgow practice were visited during the mornings between midNovember and mid-December 1980. Information from 220 individuals was obtained and the findings support those of previous surveys,1 indicating that a large majority do not have an environmental temperature anywhere near their comfort zone. Living room temperatures measured by a portable digital thermistor thermometer (Clandon Scientific Ltd) showed that 96% were below the recommended temperature of 21-10C.2 If we take 18 3°C as a minimum acceptable level,3 84% were recorded as below this minimum level. A total of 61% failed to reach 16 0°C, the minimum temperature specified in the Offices, Shops and Railways Premises Act 1963. During the survey period outside temperatures were milder than the seasonal average. Further data from this study will be available later, but it is apparent that large numbers of the elderly continue to live at uncomfortably low temperatures. The combination of poor health and housing, financial stringency, and a compromised behavioural and physiological cold-adaptive response must contribute to considerable discomfort and occasional misery -and indeed mortality-in the elderly population. W R PRIMROSE L R N SMITH Govan Health Centre, Glasgow G51 4BJ Fox RH, Woodford PM, Exton-Smith AN, et al. Br MedJ7 1973;i:200-6. ' Department of Health and Social Security. Keeping warm in winter. London: DHSS, 1971. 3Ministry of Housing and Local Government Homes for today and tomorrow. London: HMSO, 1961.
SiR,-Having read the excellent article by Dr K J Collins and others (17 January, p 175) I am encouraged to write to you, as I am particularly interested in the subject of hypothermia at present and have made a device, with which I have experimented, for its control. On 1 January we had the case of a man who, when returning from a New Year party, fell and knocked himself out while going through the local cemetery. He was found at about 8 am heavily covered all over with frost and was taken to the local hospital; fortunately he survived. This made me think of the many other cases of which one hears in which elderly people suffer from this condition owing to lack of heating. The device which I have made is an airway whereby the patient can rest, or sleep, completely under the bedclothes, thereby prevent-
risk of cancers other than non-Hodgkin's lymphoma and skin and bladder cancers is observed in patients initially treated with cyclophosphamide. This relative risk (13:5-86) is significantly greater (p < 0-03, one-sided) than that observed in the case of azathioprine (14:14-48), but we would otherwise prefer to await the further data which are being collected before drawing aetiological conclusions about this difference. L J KINLEN JULIAN PETO
ing loss of heat from the head and expired breath. I have tried this out on myself repeatedly, remaining completely cut off from the outside air apart from the airway. I have recorded temperatures, respiration rates, etc; and I find that, whereas without this device such a position can be sustained for only about four minutes, with the airway it can be maintained for an indefinite period. I have done this for two-hourly periods at a time, first recording temperatures, etc, and then sleeping comfortably in this position. The bed temperature rises at 2°F a minute for the first 15 minutes, after which it rises a further degree per minute for a further 15 minutes. The respiration rate rises to about 24 per minute and then becomes quieter. By this time the temperature under the bedclothes varies between 270 and 34°C (80-94°F). The feet, which are at first cold in the bed become warmer after half an hour, and one perspires gently in this near-tropical heat. The air intake can be increased at will by a small suction movement of the bedclothes. The device, of which I enclose a sketch, could be usefully employed not only for elderly people but also for earthquake victims who have to live under exposed conditions. I am showing it to the Red Cross Society. It is easily constructed for about £1 with 36 mm polypropylene tubing. Petersfield, Hants
RIcHAiR DOLL Imperial Cancer Research Fund Cancer Epidemiology and Clinical Trials Unit, University of Oxford, Oxford OX1 3QG
A G R SHEIL University Department of Surgery, Sydney, New South Wales, Australia Kinlen LJ, Sheil AGR, Peto J, Doll R. Br Med J 1979;ii:1461-6.
Dementia and cerebral noradrenergic innervation
SIR,-Mr Alan J Cross and his colleagues report (10 January, p 93) that levels of dopamine-f-hydroxylase, a marker enzyme for noradrenergic neurones, is reduced by about 40% in the cerebral cortex of patients REGINALD BoWESMAN dying with Alzheimer's disease. We have previously demonstratedL that substantial loss of protein-synthesising capability is seen in all nerve cells of the locus caeruleus (the main noradrenergic innervation of the central nervous system) in all cases of Alzheimer's disease, accompanied by a severe loss of such cells in many of these cases. These histological findings are matched by reduced tissue levels of noradrenalinel of, on average, 36 %, and urinary levels2 of its major metabolite, methoxyhydroxyphenylglycol, decreased by 39 %. Our findings, together with those of Mr Cross and his colleagues, present clear evidence of an involvement of noradrenergic neurones, within the underlying pathological mechanism of Alzheimer's disease. However, the relationship of these changes to specific clinical features of the disorder is still unrecognised. We have examined the brains of patients dying with other neurological disorders for evidence of pathological changes within nerve cells of the locus
Cancer in patients treated with immunosuppressive drugs SIR,-We reported in the BMJ1 the preliminary results of a collaborative UKAustralasian study of cancer in patients treated with cyclophosphamide, azathioprine, or chlorambucil. We did not then, however, present details of the non-transplant patients who received each of these drugs or, with the exception of non-Hodgkin's lymphoma and bladder cancer, the number of cases of cancer in each drug-use group. As a result of the many inquiries for this information we would like to present the data shown in the accompanying table. An increased
Observed (0) and expected (E) numbers of cases of cancer (excluding cervical patients without transplants Azathioprine Type of cancer
Non-Hodgkin's lymphoma Skin cancer Basal cell carcinoma Squamous cell carcinoma Melanoma Bladder cancer Other Total No of patients
0 3
E
0-23
1-16 0-27 0-10 0 70 14-48 14* 16-94 20 870 1 1 0 1
Cyclophosphamide E
0
0
1
0-10
0
0 47 0-11 0 04 0-29 5-86
0 0 0 0 2 2
430
6-87
Total
Chlorambucil
0 1 0 3 13*
18
carcinoma-in-situ) in UK
E
0
0-01 0-03 0 00 0 00 0-01 0 40
4
0-45 49
1 2 0 4 29
40
E 0-34 1-66 0-38 0-14 1-00 20-74 24-26 1349
*One of the cancers in the azathioprine group and two in the cyclophosphamide group were mesenchymal tumours.
