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PARACETAMOL AND MITOSIS
1084
patient complained of chest pain or was dysrhythmias seen on the E.c.G.
start.
No
aware
contain 6 mg. per 10 ml. The results given here may, therefore, offer some explanation of the cellular damage reported in 1 cases of paracetamol poisoning.
of the
Comment Stimulation of the
sympathetic nervous system increases the sensitivity of the myocardium and can result in heart-rate increase with production of ectopic beats. It is suggested that the E.C.G. changes seen in those patients who received lumbar injections of intrathecal hypertonic saline solution may have been due to a direct osmotic effect upon intradural sympathetic nerve-fibres. Evidence in support of direct sympathetic stimulation rather than general sympathetic effects of the procedure is supplied by the noted segmental distribution of peripheral cyanosis, pilo-erection, sweating, and muscular fasciculation. In the cisternal group, the E.C.G. changes would be compatible with direct vagal stimulation, and this would be supported by evidence of other cranial-nerve stimulation (facial weakness, vertigo, nystagmus, and vomiting). Although the E.C.G. changes were alarming to the observer, they were transient and did not upset the patient. However, no serious dysrhythmias occurred during the procedure, and the E.C.G. abnormalities produced do not contraindicate its use. We should like to thank Dr. Hamish Watson for his helpful advice, and the staffs of the cardiac department, Royal Infirmary, Dundee, and department of surgical neurology, University of Edinburgh, for technical and secretarial assistance.
Department of Surgical Neurology, University of Edinburgh and Western General Hospital, Edinburgh 4.
MORAG C. MCKEAN EDWARD HITCHCOCK.
PARACETAMOL AND MITOSIS SIR,-The article by Dr. MacLean and his colleagues (Oct. 19, p. 849) prompts me to refer to my observations on the effect of paracetamol on the mitosis of phytohxmagglutinin (P.H.A.)-stimulated lymphocytes cultured in vitro. Under sterile conditions, peripheral-blood lymphocytes from 4 healthy adults were incubated with’TC 199 ’ (Glaxo), and P.H.A. P (Difco) at 37°C for 72 hours, at which time 0-2 ml. of demecolcine (’ Colcemid’), at a concentration of 1 mg. per 100 ml. TC 199, was added to each culture. After a further 2 hours at 37°C the cells were treated with hypotonic saline solution for 15 minutes at 37°C, fixed with aceticacid/alcohol, spread on to cold slides, air-dried, and treated with 10% Giemsa’s stain at pH 6-4. Paracetamol, at concentrations of 100, 10, and 1 mg. per 10 ml. culture, was added to the experimental cultures before the addition of the P.H.A. Control cultures without paracetamol were also set up. After staining, 1000 cells from each culture were examined and the number of mitoses determined. MITOSES PER STIMULATED
1000
CELLS AFTER EXPOSURE OF PHYTOHAMAGGLUTININ-
LYMPHOCYTES
TO
PARACETAMOL
(AVERAGE
OF
4
EXPERIMENTS)
The results given in the accompanying table indicate that concentrations of 10 mg. per 10 ml. and above paracetamol is either lethal to the cells or completely inhibits mitosis. At 1 mg. per 10 ml. mitosis is greatly inhibited. A 70 kg. (154 lb.) man taking 1 (500 mg.) paracetamol tablet would, assuming even dispersion, have 1-43 mg. per 10 ml. if it was confined to the plasma, or 0-33 mg. per 10 ml. if it was confined to the extracellular water. Taking 60 tablets (30 g.) raises these concentrations to 85-8 mg. per 10 ml. plasma or 19-8 mg. per 10 ml. extracellular water. Even if the 30 g. of paracetamol was evenly dispersed in the total body water this would still at
University Department of Medical Genetics, Royal Infirmary, Manchester 13.
J. TIMSON.
ETHICAL AND SOCIAL ASPECTS OF TREATMENT OF SPINA BIFIDA SIR,-As one of a research team which has been studying the stress imposed on a family by the birth and survival of a child with spina bifida, I have been much concerned with the question whether such children are better dead. It seems to me there are two principle reasons, both involving the family, why we should not, in the words of Dr. Haas (Nov. 2, p. 974), " let Nature take its course ". The first concerns the survival of untreated cases. If all untreated cases of spina bifida died quickly, there might be something to be said for withholding treatment. But some patients survive unexpectedly long, and when this occurs the parents may have a burden, and the child a disablement, much more severe than if treatment had been given. This means that the surgeon must weigh the relief he feels is gained by the early death of most patients against the extra distress occasioned by the patients who survive longer-a most difficult judgment. The second reason concerns the prevention of spina bifida. To allow " Nature " to take its course means shutting one’s mind to the problem of causation. But the suffering of both child and parents, which occurs in severe cases even with all possible treatment, demands research into every aspect of spina bifida. Without research children will continue to be born with spina bifida, with more or less distress to themselves and to their parents. With research, we have the hope, not only of further improvements in treatment, but also of finding causal factors and so ultimately of preventing its occurrence altogether. It is important to recognise, too, that research into the specific causes of spina bifida may well yield knowledge relevant to other developmental malformations. The Bethlem Royal Hospital, E. H. HARE. Beckenham BR3 3BX, Kent.
REGIONAL POLICY FOR HOSPITAL DISINFECTION AND STERILISATION SIR,-With reference to your annotation (Nov. 2, p. 961) a memorandum2 such as you recommend has been in force in the area of the Eastern Regional Hospital Board (Scotland) from December, 1966. It was based on our comprehensive survey of the existing disinfection and sterilisation procedures, carried out both by means of a questionary and by direct consultation with the ward sisters and medical staff. When the aim of each procedure was defined as a sterile, disinfected, or clean product it became clear that many articles, particularly those made of heat-labile plastic, were being " cold sterilised " by a variety of dubious procedures, some more noted for their historicity than their bactericidal effect. The introduction of an ethylene-oxide steriliser effectively dealt with this problem, and has also served to offset the increased use of some disposable articles by multiplying the number of times they may be used. The scope of chemical disinfection is as defined in the report of a Public Health Laboratory Service committee,3 and is restricted to environmental and skin disinfection. Broadspectrum disinfectants were chosen to reduce as far as possible the selective effect on the hospital flora so inherent in the use of some disinfectants. The cooperation and good will at all staff levels which Maclean, D., Peters, T. J., Brown, R. A. G., McCathie, M., Baines, G. F., Robertson, P. G. C. Lancet, Oct. 19, 1968, p, 849. 2. Copies are available from the pharmaceutical department, Dundee Royal Infirmary. 3. Report by the Public Health Laboratory Service Committee on the Testing and Evaluation of Disinfectants. Br. med. J. 1965, i, 408. 1.
patient complained of chest pain or was dysrhythmias seen on the E.c.G.
start.
No
aware
contain 6 mg. per 10 ml. The results given here may, therefore, offer some explanation of the cellular damage reported in 1 cases of paracetamol poisoning.
of the
Comment Stimulation of the
sympathetic nervous system increases the sensitivity of the myocardium and can result in heart-rate increase with production of ectopic beats. It is suggested that the E.C.G. changes seen in those patients who received lumbar injections of intrathecal hypertonic saline solution may have been due to a direct osmotic effect upon intradural sympathetic nerve-fibres. Evidence in support of direct sympathetic stimulation rather than general sympathetic effects of the procedure is supplied by the noted segmental distribution of peripheral cyanosis, pilo-erection, sweating, and muscular fasciculation. In the cisternal group, the E.C.G. changes would be compatible with direct vagal stimulation, and this would be supported by evidence of other cranial-nerve stimulation (facial weakness, vertigo, nystagmus, and vomiting). Although the E.C.G. changes were alarming to the observer, they were transient and did not upset the patient. However, no serious dysrhythmias occurred during the procedure, and the E.C.G. abnormalities produced do not contraindicate its use. We should like to thank Dr. Hamish Watson for his helpful advice, and the staffs of the cardiac department, Royal Infirmary, Dundee, and department of surgical neurology, University of Edinburgh, for technical and secretarial assistance.
Department of Surgical Neurology, University of Edinburgh and Western General Hospital, Edinburgh 4.
MORAG C. MCKEAN EDWARD HITCHCOCK.
PARACETAMOL AND MITOSIS SIR,-The article by Dr. MacLean and his colleagues (Oct. 19, p. 849) prompts me to refer to my observations on the effect of paracetamol on the mitosis of phytohxmagglutinin (P.H.A.)-stimulated lymphocytes cultured in vitro. Under sterile conditions, peripheral-blood lymphocytes from 4 healthy adults were incubated with’TC 199 ’ (Glaxo), and P.H.A. P (Difco) at 37°C for 72 hours, at which time 0-2 ml. of demecolcine (’ Colcemid’), at a concentration of 1 mg. per 100 ml. TC 199, was added to each culture. After a further 2 hours at 37°C the cells were treated with hypotonic saline solution for 15 minutes at 37°C, fixed with aceticacid/alcohol, spread on to cold slides, air-dried, and treated with 10% Giemsa’s stain at pH 6-4. Paracetamol, at concentrations of 100, 10, and 1 mg. per 10 ml. culture, was added to the experimental cultures before the addition of the P.H.A. Control cultures without paracetamol were also set up. After staining, 1000 cells from each culture were examined and the number of mitoses determined. MITOSES PER STIMULATED
1000
CELLS AFTER EXPOSURE OF PHYTOHAMAGGLUTININ-
LYMPHOCYTES
TO
PARACETAMOL
(AVERAGE
OF
4
EXPERIMENTS)
The results given in the accompanying table indicate that concentrations of 10 mg. per 10 ml. and above paracetamol is either lethal to the cells or completely inhibits mitosis. At 1 mg. per 10 ml. mitosis is greatly inhibited. A 70 kg. (154 lb.) man taking 1 (500 mg.) paracetamol tablet would, assuming even dispersion, have 1-43 mg. per 10 ml. if it was confined to the plasma, or 0-33 mg. per 10 ml. if it was confined to the extracellular water. Taking 60 tablets (30 g.) raises these concentrations to 85-8 mg. per 10 ml. plasma or 19-8 mg. per 10 ml. extracellular water. Even if the 30 g. of paracetamol was evenly dispersed in the total body water this would still at
University Department of Medical Genetics, Royal Infirmary, Manchester 13.
J. TIMSON.
ETHICAL AND SOCIAL ASPECTS OF TREATMENT OF SPINA BIFIDA SIR,-As one of a research team which has been studying the stress imposed on a family by the birth and survival of a child with spina bifida, I have been much concerned with the question whether such children are better dead. It seems to me there are two principle reasons, both involving the family, why we should not, in the words of Dr. Haas (Nov. 2, p. 974), " let Nature take its course ". The first concerns the survival of untreated cases. If all untreated cases of spina bifida died quickly, there might be something to be said for withholding treatment. But some patients survive unexpectedly long, and when this occurs the parents may have a burden, and the child a disablement, much more severe than if treatment had been given. This means that the surgeon must weigh the relief he feels is gained by the early death of most patients against the extra distress occasioned by the patients who survive longer-a most difficult judgment. The second reason concerns the prevention of spina bifida. To allow " Nature " to take its course means shutting one’s mind to the problem of causation. But the suffering of both child and parents, which occurs in severe cases even with all possible treatment, demands research into every aspect of spina bifida. Without research children will continue to be born with spina bifida, with more or less distress to themselves and to their parents. With research, we have the hope, not only of further improvements in treatment, but also of finding causal factors and so ultimately of preventing its occurrence altogether. It is important to recognise, too, that research into the specific causes of spina bifida may well yield knowledge relevant to other developmental malformations. The Bethlem Royal Hospital, E. H. HARE. Beckenham BR3 3BX, Kent.
REGIONAL POLICY FOR HOSPITAL DISINFECTION AND STERILISATION SIR,-With reference to your annotation (Nov. 2, p. 961) a memorandum2 such as you recommend has been in force in the area of the Eastern Regional Hospital Board (Scotland) from December, 1966. It was based on our comprehensive survey of the existing disinfection and sterilisation procedures, carried out both by means of a questionary and by direct consultation with the ward sisters and medical staff. When the aim of each procedure was defined as a sterile, disinfected, or clean product it became clear that many articles, particularly those made of heat-labile plastic, were being " cold sterilised " by a variety of dubious procedures, some more noted for their historicity than their bactericidal effect. The introduction of an ethylene-oxide steriliser effectively dealt with this problem, and has also served to offset the increased use of some disposable articles by multiplying the number of times they may be used. The scope of chemical disinfection is as defined in the report of a Public Health Laboratory Service committee,3 and is restricted to environmental and skin disinfection. Broadspectrum disinfectants were chosen to reduce as far as possible the selective effect on the hospital flora so inherent in the use of some disinfectants. The cooperation and good will at all staff levels which Maclean, D., Peters, T. J., Brown, R. A. G., McCathie, M., Baines, G. F., Robertson, P. G. C. Lancet, Oct. 19, 1968, p, 849. 2. Copies are available from the pharmaceutical department, Dundee Royal Infirmary. 3. Report by the Public Health Laboratory Service Committee on the Testing and Evaluation of Disinfectants. Br. med. J. 1965, i, 408. 1.