1104
consent ’and confidentiality, are adequately addressed. To avoid increasing their task unduly and to prevent long delays (a criticism previously levelled at ethics committees1) protocols could be screened by a member of the committee. Screening by the medical audit advisory committee is another
including patients’
option. South Tees Health Authority, Poole Hospital, Middlesbrough TS7 ONJ, UK 1. Madhok
RAJAN MADHOK
R, McEwan RT, Bhopal RS, McCallum A. Too many ethical committees.
BMJ 1991, 302: 180.
Euthanasia SIR,—Iagree with Mrs Brahams (Sept 26, p 782) that any further action by either the General Medical Council in respect of Dr Cox’s registration, or by the health authority in respect of his continuing employment is totally unwarranted. As a physician who regularly looks after dying patients, I was appalled by the verdict of the court and feel deeply for Cox in his predicament. Under my guidance, treatment of various forms (ventilation, oxygen, inotropes, antibiotics, parenteral and enteral feeding, and so on) is frequently withdrawn from hopelessly ill patients in our intensive care unit, and large doses of opioids and sedatives are given to ease suffering and hasten death. Potassium chloride and muscle relaxants (in the absence of mechanical ventilation) have never been used in this process but there is no doubt that my motivation in many cases has been not only to ease suffering but also to shorten life. Throughout my medical training, compassion and care for the individual patient-as was practised by Cox-was always emphasised as the first priority in medical practice and I hope that the medical profession of this country will now stand by Cox at this terrible time.
Since mutation is an important component of the carcinogenesis processthese results have implications for cancer risk associated with butadiene exposure. Abelson’ has recently stated that cancer data in the mouse should not be used to estimate cancer risk to man.
Yet, the US Occupational Safety and Health Administration proposed 2 ppm exposure limit,6 based on the mouse data, seems too high in view of our findings of HPRT mutations in workers
exposed
to
butadiene levels close
to
this exposure concentration.
Thus, the conclusion drawn by Abelson,’ that cancer risk in man with respect to butadiene is slight, not only ignores recent epidemiological data but also is contradicted by the increased
frequencies
of gene mutation
exposure in
our
seen
in association with butadiene
study.
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas 77555, USA
JONATHAN B. WARD JR MARINEL M. AMMENHEUSER MARVIN S. LEGATOR
1. Abelson PH Exaggerated carcinogenicity of chemicals. Science 1992; 256: 1609. 2. Dahl AR, Bechtold WE, Bond JA, et al. Species differences m the metabolism, and
disposition of
inhaled 1, 3-butadiene and
isoprene. Environ Health Persp 1990; 86:
65-69.
3. Landrigan PJ. Critical assessment of epidemiologic studies on the human carcinogenicity of 1, 3-butadiene. Environ Health Persp 1990; 86: 143-48. 4. Bechtold WE, Strunk MR Biological exposure indices for butadiene: the analysis of1, 2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane and (1 or 2)-hydroxy-(Nacetylcysteinyl-S-)-3-butene in the urine of workers exposed to butadiene. Presented at American Industrial Hygience Conference and Exposition, Work and Health Tradition and Revolution, June 1-5, Boston, 1992: 58. 5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-67. 6.
Occupational Safety and Health Administration. Occupational exposure to 1,3butadiene, proposed rule and notice of hearing. Fed Reg 1990; 55: 32736-826.
"Blind" bronchoalveolar
lavage
Directorate of Adult Intensive Care,
Guy’s Hospital, DAVID BIHARI
London SE1 9RT, UK
Carcinogenicity of 1, 3-butadiene SIR,-Dr Melnick and colleagues (Sept 19, p 724) in their response to an editorial by Abelson,l correctly indicated the relevance of mouse carcinogenicity data for human risk assessment. They also assert that metabolic studies with 1, 3-butadiene in various species do not alter the validity of the mouse carcinogenicity data. Although the metabolism of butadiene does vary across speciesMelnick et al correctly indicate that butadiene is metabolised to mutagenic and carcinogenic epoxides in liver tissue in all species studied, including man. They also note that the methods used so far in metabolic studies are inadequate for quantitative comparisons. Furthermore, there is at least limited evidence that butadiene is a human carcinogen, producing haemopoietic cancer. We have further evidence to indicate that not only was past exposure sufficient to be detected as inducing cancer in man, but also that the present proposed exposure limit of 2 parts per million (ppm) may not be sufficiently low to protect workers from the detectable health risks associated with butadiene. We have investigated the frequency of mutations in lymphocytes from workers exposed to butadiene (unpublished results). Eight workers in a butadiene production plant were evaluated for the frequency of lymphocytes containing mutations at the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus. They were compared with five workers from areas of the same plant where exposures to butadiene were lower, and with six individuals who were not occupationally exposed to butadiene. Average butadiene values in the higher exposure areas were about 35 ppm, with most samples below 1 ppm, whereas exposures in the other areas were about 0 03 ppm. The workers in the exposed areas had significantly higher frequencies of mutant lymphocytes than both the less exposed and non-exposed subjects (p < 0-05). A collaborating laboratory identified a single butadiene-specific metabolite (1,2-dihydroxy-4-(N-aceryl cysteinyl-S-) butane in urine samples from these subjects obtained at the same time as blood samples.4 Urinary metabolite concentrations were highly correlated with the mutant frequencies (r 0-85), indicating that a biomarker of low butadiene exposure in man is associated with gene mutation. =
SIR,-A 4-month-old boy was admitted with a high temperature and respiratory distress. He also had oral candidosis and was failing to thrive. A chest radiograph showed left lower lobe consolidation. He did not respond to conventional antibiotics. Testing showed him to be HIV positive, and a presumptive diagnosis of Pneumocystis carinii pneumonia was made and high-dose co-trimoxazole was started. Despite this treatment respiratory failure progressed and he needed mechanical ventilation. Deep endotracheal tube aspirates were taken, but did not reveal any pathogen. Diagnostic bronchoscopy was available at the local teaching hospital, but this option would have meant transporting a very sick child some 40 miles. I had used "blind" bronchoalveolar lavage in newborn babies, and decided to try this technique with this patient. Normal saline was drawn into two syringes, and two 5 FG endotracheal tube suction-catheters (Vygon) were preloaded with 1 ml/kg normal saline. It is suggested that 5 ml should be the maximum volume used. The infant was pre-oxygenated with 100% oxygen for 2 min. The endotracheal tube was disconnected from the ventilator, and with the patient lying supine with his head turned to the left, the first suction catheter was introduced into the tube until it became wedged. The saline was then introduced, and with the suction catheter still in situ, the ventilator was reconnected. The suction catheter was then connected to a modified trachea suction set (Unoplast), which was in turn connected to wall suction, at 8 kPa. After 30 s dwell time, the ventilator was disconnected again, and suction carried out. The suction catheter was removed, and the ventilator reconnected. After 2 min to allow recovery, the procedure was repeated with the second syringe. The lavage was well tolerated. The washings were positive for both P carinii and cytomegalovirus. Despite further intensive care, the child died 10 days later. Bronchoscopy, with lavage and/or biopsy, will continue to be the investigation of choice in the sort of case I outline. I cannot say on the basis of one case that the technique I used is reliable in this situation, but I suggest that when facilities for paediatric bronchoscopy are not available locally, then "blind" bronchoalveolar lavage could be attempted to make a microbiological diagnosis and to avoid transfer of a sick child. Poole Hospital NHS Trust, Poole, Dorset BH15 2JB, UK
MARK R. ASHTON
consent ’and confidentiality, are adequately addressed. To avoid increasing their task unduly and to prevent long delays (a criticism previously levelled at ethics committees1) protocols could be screened by a member of the committee. Screening by the medical audit advisory committee is another
including patients’
option. South Tees Health Authority, Poole Hospital, Middlesbrough TS7 ONJ, UK 1. Madhok
RAJAN MADHOK
R, McEwan RT, Bhopal RS, McCallum A. Too many ethical committees.
BMJ 1991, 302: 180.
Euthanasia SIR,—Iagree with Mrs Brahams (Sept 26, p 782) that any further action by either the General Medical Council in respect of Dr Cox’s registration, or by the health authority in respect of his continuing employment is totally unwarranted. As a physician who regularly looks after dying patients, I was appalled by the verdict of the court and feel deeply for Cox in his predicament. Under my guidance, treatment of various forms (ventilation, oxygen, inotropes, antibiotics, parenteral and enteral feeding, and so on) is frequently withdrawn from hopelessly ill patients in our intensive care unit, and large doses of opioids and sedatives are given to ease suffering and hasten death. Potassium chloride and muscle relaxants (in the absence of mechanical ventilation) have never been used in this process but there is no doubt that my motivation in many cases has been not only to ease suffering but also to shorten life. Throughout my medical training, compassion and care for the individual patient-as was practised by Cox-was always emphasised as the first priority in medical practice and I hope that the medical profession of this country will now stand by Cox at this terrible time.
Since mutation is an important component of the carcinogenesis processthese results have implications for cancer risk associated with butadiene exposure. Abelson’ has recently stated that cancer data in the mouse should not be used to estimate cancer risk to man.
Yet, the US Occupational Safety and Health Administration proposed 2 ppm exposure limit,6 based on the mouse data, seems too high in view of our findings of HPRT mutations in workers
exposed
to
butadiene levels close
to
this exposure concentration.
Thus, the conclusion drawn by Abelson,’ that cancer risk in man with respect to butadiene is slight, not only ignores recent epidemiological data but also is contradicted by the increased
frequencies
of gene mutation
exposure in
our
seen
in association with butadiene
study.
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas 77555, USA
JONATHAN B. WARD JR MARINEL M. AMMENHEUSER MARVIN S. LEGATOR
1. Abelson PH Exaggerated carcinogenicity of chemicals. Science 1992; 256: 1609. 2. Dahl AR, Bechtold WE, Bond JA, et al. Species differences m the metabolism, and
disposition of
inhaled 1, 3-butadiene and
isoprene. Environ Health Persp 1990; 86:
65-69.
3. Landrigan PJ. Critical assessment of epidemiologic studies on the human carcinogenicity of 1, 3-butadiene. Environ Health Persp 1990; 86: 143-48. 4. Bechtold WE, Strunk MR Biological exposure indices for butadiene: the analysis of1, 2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane and (1 or 2)-hydroxy-(Nacetylcysteinyl-S-)-3-butene in the urine of workers exposed to butadiene. Presented at American Industrial Hygience Conference and Exposition, Work and Health Tradition and Revolution, June 1-5, Boston, 1992: 58. 5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-67. 6.
Occupational Safety and Health Administration. Occupational exposure to 1,3butadiene, proposed rule and notice of hearing. Fed Reg 1990; 55: 32736-826.
"Blind" bronchoalveolar
lavage
Directorate of Adult Intensive Care,
Guy’s Hospital, DAVID BIHARI
London SE1 9RT, UK
Carcinogenicity of 1, 3-butadiene SIR,-Dr Melnick and colleagues (Sept 19, p 724) in their response to an editorial by Abelson,l correctly indicated the relevance of mouse carcinogenicity data for human risk assessment. They also assert that metabolic studies with 1, 3-butadiene in various species do not alter the validity of the mouse carcinogenicity data. Although the metabolism of butadiene does vary across speciesMelnick et al correctly indicate that butadiene is metabolised to mutagenic and carcinogenic epoxides in liver tissue in all species studied, including man. They also note that the methods used so far in metabolic studies are inadequate for quantitative comparisons. Furthermore, there is at least limited evidence that butadiene is a human carcinogen, producing haemopoietic cancer. We have further evidence to indicate that not only was past exposure sufficient to be detected as inducing cancer in man, but also that the present proposed exposure limit of 2 parts per million (ppm) may not be sufficiently low to protect workers from the detectable health risks associated with butadiene. We have investigated the frequency of mutations in lymphocytes from workers exposed to butadiene (unpublished results). Eight workers in a butadiene production plant were evaluated for the frequency of lymphocytes containing mutations at the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus. They were compared with five workers from areas of the same plant where exposures to butadiene were lower, and with six individuals who were not occupationally exposed to butadiene. Average butadiene values in the higher exposure areas were about 35 ppm, with most samples below 1 ppm, whereas exposures in the other areas were about 0 03 ppm. The workers in the exposed areas had significantly higher frequencies of mutant lymphocytes than both the less exposed and non-exposed subjects (p < 0-05). A collaborating laboratory identified a single butadiene-specific metabolite (1,2-dihydroxy-4-(N-aceryl cysteinyl-S-) butane in urine samples from these subjects obtained at the same time as blood samples.4 Urinary metabolite concentrations were highly correlated with the mutant frequencies (r 0-85), indicating that a biomarker of low butadiene exposure in man is associated with gene mutation. =
SIR,-A 4-month-old boy was admitted with a high temperature and respiratory distress. He also had oral candidosis and was failing to thrive. A chest radiograph showed left lower lobe consolidation. He did not respond to conventional antibiotics. Testing showed him to be HIV positive, and a presumptive diagnosis of Pneumocystis carinii pneumonia was made and high-dose co-trimoxazole was started. Despite this treatment respiratory failure progressed and he needed mechanical ventilation. Deep endotracheal tube aspirates were taken, but did not reveal any pathogen. Diagnostic bronchoscopy was available at the local teaching hospital, but this option would have meant transporting a very sick child some 40 miles. I had used "blind" bronchoalveolar lavage in newborn babies, and decided to try this technique with this patient. Normal saline was drawn into two syringes, and two 5 FG endotracheal tube suction-catheters (Vygon) were preloaded with 1 ml/kg normal saline. It is suggested that 5 ml should be the maximum volume used. The infant was pre-oxygenated with 100% oxygen for 2 min. The endotracheal tube was disconnected from the ventilator, and with the patient lying supine with his head turned to the left, the first suction catheter was introduced into the tube until it became wedged. The saline was then introduced, and with the suction catheter still in situ, the ventilator was reconnected. The suction catheter was then connected to a modified trachea suction set (Unoplast), which was in turn connected to wall suction, at 8 kPa. After 30 s dwell time, the ventilator was disconnected again, and suction carried out. The suction catheter was removed, and the ventilator reconnected. After 2 min to allow recovery, the procedure was repeated with the second syringe. The lavage was well tolerated. The washings were positive for both P carinii and cytomegalovirus. Despite further intensive care, the child died 10 days later. Bronchoscopy, with lavage and/or biopsy, will continue to be the investigation of choice in the sort of case I outline. I cannot say on the basis of one case that the technique I used is reliable in this situation, but I suggest that when facilities for paediatric bronchoscopy are not available locally, then "blind" bronchoalveolar lavage could be attempted to make a microbiological diagnosis and to avoid transfer of a sick child. Poole Hospital NHS Trust, Poole, Dorset BH15 2JB, UK
MARK R. ASHTON
![[Bronchoalveolar lavage].](/assets/img/hold.png)
