1091 of the reports of unusual blood-pressure changes in patients. Liver function should also be monitored. Department of Medicine, Department of Microbiology and
Immunology, U.C.L A. Medical Los Angeles,
Center,
California 90024, U.S.A. Division
of Urology,
U.C.L.A. Medical Center, Los Angeles.
some
R. CLIFFORD OSSORIO J. L. FAHEY W. WILSON D. PLOTKIN S. BROSSMAN D. SKINNER
goal of cure in myeloblastic leukaemia is almost certainly still outside the limits of our knowledge and concepts. The right ideas or discoveries will come in their own time, and bluster is more likely to delay than accelerate their arrival. Bashing away with the proud claim that it’s aggressive and therefore better, seems a less promising approach than Dr Burge and his colleagues have adopted. The
Department of Hæmatology, St George’s Hospital, London SW17 0QT.
MICHAEL ROSE
ESCHERICHIA COLI K1
SIR,-We were interested in the article by Sariff et al.’ dealSURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-Unfortunately, Dr Clink and Dr Douglas, and Dr Baccarani (Nov. 15, p. 98.8) have missed the point of our paper (Oct. 4, p. 621). Many physicians look to M.R.C. reports for guidance in treatment of their leukaemia patients. We believe that current regimens are too toxic in relation to their effectiveness for general use, and that, in the absence of any chance of producing a cure, it is inhuman to expect patients to be treated far from home in a special centre, when a more appropriate and effective treatment can be given locally. "Remission" (no evidence of disease with a normal marrow) is an artifactual event as it may only represent a reduction in malignant cells of two or three orders of magnitude; on stopoccurs. Our patients with a remission-rate of 6-3% survived at least as long, in all age-groups, as those treated by the M.R.C. protocol which achieved a 60% remission-rate. The difference was that with our induction regimen 11 % of patients died, whereas with the other 33% died. Undoubtedly centres are needed which aim to improve the treatment of acute myeloid leukaemia, but we suggest that new drugs or new approaches are needed before large-scale trials are indicated again. In the meantime treatment of acute myeloid leukaemia outside special centres should be more closely related to the patients’ welfare. P. S. BURGE University College Hospital, T. A. J. PRANKERD London WC1E 6AV.
ping maintenance therapy, relapse invariably
StR,-Unlike Dr Clink and Dr Douglas (Nov. 15, p. 988) and Dr Baccarani (p. 989), I found the paper from Dr Burge and others (Oct. 4, p. 621) among the most important I have ever read on leukaemia. The widely used expression "aggressive treatment" is linked to a pioneering, fearless assault upon disease. If it is a virtuous approach then we must have evidence that it works. Would the doctors who administer the treatment accept the treatment? It seems that therapeutic aggression comes from commercial and political agencies which want to see actionany action. As such, it seems a clinical approach to be resisted until we have either the facts and concepts on which to construct management or the empirical evidence that benefit exists and that the cost is worth while. Before we get carried away with admiration for all this machismo, perhaps we may consider who is being aggressive against what and to what end. Firstly, the patients with myeloblastic leukaemia who survive long enough to benefit from the care of doctors with a wide experience of this disease are probably a minority in the U.K.’ Aggression directed against a disease which we only partly understand is an exhibition of frustration and an anathema to the classical dictum of medicine-that we treat people not diseases. "Therapeutic aggression", if misconceived or misguided, becomes a total contradiction.
ing with neonatal infections caused by certain serotypes of Escherichia coli possessing the Kantigen, as we have recently had an outbreak of infection due to E. coli 018 ac in our special care baby unit which supports and illustrates some of the suggestions made in the paper. A baby of birth-weight 1400 g with mild respiratory distress was transferred to the unit from an outlying hospital within hours of birth. He recovered rapidly but a routine rectal swab taken on the 4th day of life showed the presence of E. coli 018 ac. He did not have diarrhoea but was treated with oral neomycin 40 mg/kg/day. On the 7th day of life his temperature rose to 38°C, and E. coli 018 ac was cultured from his blood, throat-swab, urine, and feeding-tube. His cerebrospinal fluid was normal and sterile and there was still no diarrhoea. As soon as all samples had been taken, parenteral penicillin and kanamycin were given. This was changed to ampicillin and gentamicin when the results of blood-culture were known. He received 10 days’ treatment and recovered, sterile blood-cultures being obtained after treatment was
mycin, chloramphenicol, neomycin, ampicillin, polymyxin, and gentamicin. None of these babies had diarrhoea but all were transferred out of the special care unit. One of them, an infant of a diabetic mother who had recovered from his neonatal problems, developed meningitis two days later. E. coli 018 ac was cultured from the c.s.F. and blood, for which parenteral and intrathecal chloramphenicol and gentamicin were given with success. The other three babies with E. coli 018 ac have remained well, although they were all of low
birth-weight. Following transfer of the affected infants, the unit was closed and sterilised, using vapourised formaldehyde solution. All staff on the unit and staff and babies from the outlying hospital submitted rectal swabs for culture. Only one was positive for E. coli 018 ac, a member of nursing staff who was not on duty at the time of admission of the index case, and who had probably had acquired the organism from the babies. Since reopening of the unit, routine rectal swabs have not shown the presence of the organism. The final episode in this epidemic occurred when our initial case, having been well for a month following cessation of treatment, although he continued to carry E. coli 018 ac in his stool, suddenly became ill. E. coli 018 ac was grown from the blood and c.s.F. Despite appropriate antibiotic therapy, which was given intrathecally as well as parenterally, he died. Strains from this epidemic were studied for the possession of the Kantigen by agglutination techniques and by immunoelectrophoresis. Agglutination tests indicated the presence of Kl, but this finding was not confirmed by immunoelectrophoresis. This apparent anomaly reflects the current unease over the methodology for the detection of E. coli surface antigens. This experience in the United Kingdom illustrates some of the points made by Sariff et al.’ Firstly, it supports their finding that Kl-positive strains can spread rapidly within a neonatal unit, but it also demonstrates that prompt action can curtail an epidemic of this kind. Secondly, it emphasises the in1
1. Parker-Williams,
J. Personal communication.
discontinued.
Rectal swabs from the other babies in the unit were cultured. Four yielded E. coli 018 ac, and four had no enteric pathogens. All strains were sensitive to sulphonamide, strepto-
Sariff, L. D., McCracken, Jr., G. H., Schiffer, M. S., Glode, M. P., Robbins, J. B , Ørskov, I., Ørskov, F. Lancet, 1975, i, 1099.
1092 vasiveness which the possession of K1 antigen confers on the organism. Thirdly, it supports their suggestion that strains of E. coli 018 ac are likely to possess the K1antigen and if so are likely to be virulent. Our experience with the first case indicates the need for continued surveillance after apparently successful treatment. Departments of Pædiatrics and Microbiology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
C. J. BACON A. P. KENNA H. R. INGHAM
Salmonella and Shigella Reference Laboratory, Central Public Health Laboratory, London NW9 5HT.
R. J. GROSS B. ROWE
BLOOD VISCOSITY IN THE "ISCHÆMIC" EXERCISE E.C.G.
Ischaemic Exercise E.c.G. Changes in Symptom-free Men ... -the depressed ST segment in the exercise cardiogram is widely accepted as the pre-eminent E.c.G. sign of myocardial ischaemia.’ Other factors, such as drugs, electrolytes, and pectus excavatum, may occasionally be held responsible.2 We present evidence that this change is highly correlated with blood-viscosity factors. 56 men, both fit and ill, were subBLOOD-VISCOSITY PRODUCTS AND ST-DEPRESSION AREA
cP
(37°C)
x
blood
viscosity, cP (at
180
s-’,37°C)
x
fibrmo-
gen/albumin ratio.
jected to submaximal work-output testing and subsequently tc blood-viscosity estimation. The average area of sT depression’ was determined in the leads showing such changes where the j point depression was equal to, or greater than, 2 mm and the sT take-off was delayed more than 0.08 seconds and thereafter ran horizontally or downwards. Where there was j-poim depression only, such cardiograms were scored zero. Blood-viscosity, plasma-viscosity, and fibrinogen/albumin ratio were estimated and their product was used for correlation. In those patients not on drugs, the significance level was p
Immunology, U.C.L A. Medical Los Angeles,
Center,
California 90024, U.S.A. Division
of Urology,
U.C.L.A. Medical Center, Los Angeles.
some
R. CLIFFORD OSSORIO J. L. FAHEY W. WILSON D. PLOTKIN S. BROSSMAN D. SKINNER
goal of cure in myeloblastic leukaemia is almost certainly still outside the limits of our knowledge and concepts. The right ideas or discoveries will come in their own time, and bluster is more likely to delay than accelerate their arrival. Bashing away with the proud claim that it’s aggressive and therefore better, seems a less promising approach than Dr Burge and his colleagues have adopted. The
Department of Hæmatology, St George’s Hospital, London SW17 0QT.
MICHAEL ROSE
ESCHERICHIA COLI K1
SIR,-We were interested in the article by Sariff et al.’ dealSURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-Unfortunately, Dr Clink and Dr Douglas, and Dr Baccarani (Nov. 15, p. 98.8) have missed the point of our paper (Oct. 4, p. 621). Many physicians look to M.R.C. reports for guidance in treatment of their leukaemia patients. We believe that current regimens are too toxic in relation to their effectiveness for general use, and that, in the absence of any chance of producing a cure, it is inhuman to expect patients to be treated far from home in a special centre, when a more appropriate and effective treatment can be given locally. "Remission" (no evidence of disease with a normal marrow) is an artifactual event as it may only represent a reduction in malignant cells of two or three orders of magnitude; on stopoccurs. Our patients with a remission-rate of 6-3% survived at least as long, in all age-groups, as those treated by the M.R.C. protocol which achieved a 60% remission-rate. The difference was that with our induction regimen 11 % of patients died, whereas with the other 33% died. Undoubtedly centres are needed which aim to improve the treatment of acute myeloid leukaemia, but we suggest that new drugs or new approaches are needed before large-scale trials are indicated again. In the meantime treatment of acute myeloid leukaemia outside special centres should be more closely related to the patients’ welfare. P. S. BURGE University College Hospital, T. A. J. PRANKERD London WC1E 6AV.
ping maintenance therapy, relapse invariably
StR,-Unlike Dr Clink and Dr Douglas (Nov. 15, p. 988) and Dr Baccarani (p. 989), I found the paper from Dr Burge and others (Oct. 4, p. 621) among the most important I have ever read on leukaemia. The widely used expression "aggressive treatment" is linked to a pioneering, fearless assault upon disease. If it is a virtuous approach then we must have evidence that it works. Would the doctors who administer the treatment accept the treatment? It seems that therapeutic aggression comes from commercial and political agencies which want to see actionany action. As such, it seems a clinical approach to be resisted until we have either the facts and concepts on which to construct management or the empirical evidence that benefit exists and that the cost is worth while. Before we get carried away with admiration for all this machismo, perhaps we may consider who is being aggressive against what and to what end. Firstly, the patients with myeloblastic leukaemia who survive long enough to benefit from the care of doctors with a wide experience of this disease are probably a minority in the U.K.’ Aggression directed against a disease which we only partly understand is an exhibition of frustration and an anathema to the classical dictum of medicine-that we treat people not diseases. "Therapeutic aggression", if misconceived or misguided, becomes a total contradiction.
ing with neonatal infections caused by certain serotypes of Escherichia coli possessing the Kantigen, as we have recently had an outbreak of infection due to E. coli 018 ac in our special care baby unit which supports and illustrates some of the suggestions made in the paper. A baby of birth-weight 1400 g with mild respiratory distress was transferred to the unit from an outlying hospital within hours of birth. He recovered rapidly but a routine rectal swab taken on the 4th day of life showed the presence of E. coli 018 ac. He did not have diarrhoea but was treated with oral neomycin 40 mg/kg/day. On the 7th day of life his temperature rose to 38°C, and E. coli 018 ac was cultured from his blood, throat-swab, urine, and feeding-tube. His cerebrospinal fluid was normal and sterile and there was still no diarrhoea. As soon as all samples had been taken, parenteral penicillin and kanamycin were given. This was changed to ampicillin and gentamicin when the results of blood-culture were known. He received 10 days’ treatment and recovered, sterile blood-cultures being obtained after treatment was
mycin, chloramphenicol, neomycin, ampicillin, polymyxin, and gentamicin. None of these babies had diarrhoea but all were transferred out of the special care unit. One of them, an infant of a diabetic mother who had recovered from his neonatal problems, developed meningitis two days later. E. coli 018 ac was cultured from the c.s.F. and blood, for which parenteral and intrathecal chloramphenicol and gentamicin were given with success. The other three babies with E. coli 018 ac have remained well, although they were all of low
birth-weight. Following transfer of the affected infants, the unit was closed and sterilised, using vapourised formaldehyde solution. All staff on the unit and staff and babies from the outlying hospital submitted rectal swabs for culture. Only one was positive for E. coli 018 ac, a member of nursing staff who was not on duty at the time of admission of the index case, and who had probably had acquired the organism from the babies. Since reopening of the unit, routine rectal swabs have not shown the presence of the organism. The final episode in this epidemic occurred when our initial case, having been well for a month following cessation of treatment, although he continued to carry E. coli 018 ac in his stool, suddenly became ill. E. coli 018 ac was grown from the blood and c.s.F. Despite appropriate antibiotic therapy, which was given intrathecally as well as parenterally, he died. Strains from this epidemic were studied for the possession of the Kantigen by agglutination techniques and by immunoelectrophoresis. Agglutination tests indicated the presence of Kl, but this finding was not confirmed by immunoelectrophoresis. This apparent anomaly reflects the current unease over the methodology for the detection of E. coli surface antigens. This experience in the United Kingdom illustrates some of the points made by Sariff et al.’ Firstly, it supports their finding that Kl-positive strains can spread rapidly within a neonatal unit, but it also demonstrates that prompt action can curtail an epidemic of this kind. Secondly, it emphasises the in1
1. Parker-Williams,
J. Personal communication.
discontinued.
Rectal swabs from the other babies in the unit were cultured. Four yielded E. coli 018 ac, and four had no enteric pathogens. All strains were sensitive to sulphonamide, strepto-
Sariff, L. D., McCracken, Jr., G. H., Schiffer, M. S., Glode, M. P., Robbins, J. B , Ørskov, I., Ørskov, F. Lancet, 1975, i, 1099.
1092 vasiveness which the possession of K1 antigen confers on the organism. Thirdly, it supports their suggestion that strains of E. coli 018 ac are likely to possess the K1antigen and if so are likely to be virulent. Our experience with the first case indicates the need for continued surveillance after apparently successful treatment. Departments of Pædiatrics and Microbiology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
C. J. BACON A. P. KENNA H. R. INGHAM
Salmonella and Shigella Reference Laboratory, Central Public Health Laboratory, London NW9 5HT.
R. J. GROSS B. ROWE
BLOOD VISCOSITY IN THE "ISCHÆMIC" EXERCISE E.C.G.
Ischaemic Exercise E.c.G. Changes in Symptom-free Men ... -the depressed ST segment in the exercise cardiogram is widely accepted as the pre-eminent E.c.G. sign of myocardial ischaemia.’ Other factors, such as drugs, electrolytes, and pectus excavatum, may occasionally be held responsible.2 We present evidence that this change is highly correlated with blood-viscosity factors. 56 men, both fit and ill, were subBLOOD-VISCOSITY PRODUCTS AND ST-DEPRESSION AREA
cP
(37°C)
x
blood
viscosity, cP (at
180
s-’,37°C)
x
fibrmo-
gen/albumin ratio.
jected to submaximal work-output testing and subsequently tc blood-viscosity estimation. The average area of sT depression’ was determined in the leads showing such changes where the j point depression was equal to, or greater than, 2 mm and the sT take-off was delayed more than 0.08 seconds and thereafter ran horizontally or downwards. Where there was j-poim depression only, such cardiograms were scored zero. Blood-viscosity, plasma-viscosity, and fibrinogen/albumin ratio were estimated and their product was used for correlation. In those patients not on drugs, the significance level was p
