1300 lia with factor-vm inhibitors. If our results in a single case can be confirmed, a valuable new treatment may now be available. P. J. ENGLISH Department of Clinical Hæmatology, E. M. SHEPPARD Royal Infirmary, R. T. WENSLEY Manchester M139 WL
CONTINUOUS CYCLOPHOSPHAMIDE TREATMENT AND ADRENAL FUNCTION
SIR,-Dr Wilson and his colleagues (March 20,
p. 610) deadrenal in of ten patwo out secondary suppression tients receiving intermittent high-dose prednisolone and cytotoxic chemotherapy. However, these disturbances might be part of the malignant disease in itself, and without basic values we believe one should be very cautious before ascribing this
scribed
MEAN PLASMA-CORTISOL
(g/ml)
IN
6
PATIENTS BEFORE
(A)
more frequently in filtrates of E. coli strains isolated from infant diarrhoea. The enterotoxic activity was in many cases lost when the strains were subcultured-i.e., in some strains of freshly isolated E. coli the enterotoxicity of filtrates was easily demonstrated, while with further subcultures the enterotoxicity, tested on ligated rabbit intestinal loops, became negative. Few strains conserved their enterotoxicity when subcultured frequently. Thus in our experience the rabbit ilealloop test is of some use. We would also draw attention to individual differences in biological properties and relative lability of enterotoxin production by E. coli, especially when working
tered
with old laboratory strains.
Institute of Landscape
KAREL RASKA
Ecology,
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague 2, Czechoslovakia
HELENA RASKOVA
AND AFTER
(B) TREATMENT WITH CYCLOPHOSPHAMIDE
ENTEROTOXIGENIC E. COLI IN BANGLADESH
SIR,-In their article
Bangladesh diarrhoeas (March 27, p. 659) Ryder colleagues refer to a conflict with the data reported in a previous study of enterotoxigenic E. coli in Bangladesh.’ However, there is no major conflict between the Dr
suppression to the treatment alone. We have studied adrenal function before and after continuous treatment with cyclophosphamide in six patients, five with advanced breast cancer and one with advanced carcinoma of the prostate. Corticotrophin (A.C.T.H.) tests were done before and after 2 months of treatment with cyclophosphamide 2 mg/kg/day. Concentrations of plasma-cortisol were determined fluorimetrically. Samples were taken before and 10, 20, 30, and 40 mm after increasing doses of A.C.T.H. (62-$nag, 125 ng, 250 ng, 500 ng, and 250 g) injected intravenously through an indwelling cannula at intervals of 60 min. The results (see table) suggest that basic levels before each A.C.T.H. dose and maximum increases after each A.C.T.H. dose did not change, indicating unaltered adrenal function after treatment with cyclophosphamide. Department RII, Finseninstitute, DK 2100
Copenhagen, Denmark
H. T. MOURIDSEN
on
and his
data. The difference between 33% and 56% isolation-rates for LT+ organisms can be accounted for by differences in sample size and are probably not significant. We showed that LT+ isolation-rates were higher among inpatients (33%) than outpatients (15%) and were highest (70%) when one selected only the most severe cases. Ryders’ figure of 56% is within this range. The selection of the first severely dehydrated case each day could account for the difference in means, since milder cases, which less frequently have LT+ fsecal organisms, may come in later in the day since they are less disabled. In our series ST+/0 organisms were much less commonly isolated from patients with truly cholera-like diarrhoea than were ST+/LT+ organisms, so it is not surprising that in a small sample of similar severe cases no ST+/0 organisms were found. Another possible explanation is that by measuring actual absorption in the dog model one can pick up massive decreases in net absorption (50-99%) which do not result in net fluid accumulation. The mouse test measures only actual fluid accumulation, and significant absorptive decreases caused by ST could possibly be overlooked. More significant is the similarity between the two reports with respect to finding no Bangladesh E. coli strains which produce LT alone. Johns Hopkins University,
Hvidøre Hospital, DK 2930 Klampenborg
C. BINDER
School of Hygiene and Public Health, International Center for Medical Research, Baltimore, Maryland 21205, U.S.A.
RECOGNISING EPIDEMIC STRAINS OF E.COLI
SiR,—We
interested in the paper
and his colleagues (March 20, p. 629). These workers used tissue-culture testsl-3 and the infant-mouse test4 with negative results in the attempt to prove enterotoxin production by Escherichia coli strains from infantile enteritis outbreaks, kept several years on Dorset egg medium. Working on the ecology of E. coli strains, circulating in human and animal populations, we have isolated several hundred strains from infantile diarrhoea (infants, calves, chicks). The presence of enterotoxin was assayed on ligated rabbit intestinal 100ps.5 Heat-labile activity (18 h loop exposure) was found mainly in calves, exceptionally in humans. Heat-stable activity (6 h loop exposure) was encounwere
by Mr Gross
1. Donta S. T., Moon, H. W., Whipp, S. C. Science, 1974, 183, 334. 2. Sack, D. A., Sack, R. B. Infect. Immun. 1975, 11, 334. 3. Guerrant, R. L., Moore, E. A., Kirschenfeld, P. M., Sande, M. A. New Engl. J. Med. 1975, 293, 567. 4. Dean, G. A., Chang, Y. C., Williams, R. G., Harden, L. B. J. infect. Dis. 1972, 125, 407. 5. Evans, D. G., Evans, D. J., Jr., Pierce, N. F. Infect. Immun. 1973, 8, 731.
DAVID R. NALIN
DIAGNOSIS OF AUTONOMIC DYSFUNCTION
SIR,-Your editorial (May 22, p. 1115) was right not to mention intradermal injection of histamine as a test of autonomic integrity. The test depends on the integrity of pain fibres and does not involve autonomic nerves. Dr Burton (June 5, p. 1248) will find an account in the review you kindly (if not quite accurately) refer to in your editorial.1 Department of Neurology, Radcliffe Infirmary,
J. M. K. SPALDING
Oxford to Dr his work.-ED.L.
***We apologise to
1.
Spalding
for
our
ambivalent reference
Nalin, D. R., McLaughlin, J. C., Rahaman, M., Yunus, M., Curlin, G. Lancet, 1975, ii, 1116. 2. Pierce, N. F., Wallace, C. K. Gastroenterology, 1972, 63, 439. 3. Dean, A. G., Ching, Y. C., Williams, R. G., Harden, L. B. J. infect. Dis. 1972, 125, 407. 1. Johnson, R. H., Spalding, J. M. K. Disorders of the Autonomic Nervous System; p. 124. Oxford, 1974.
CONTINUOUS CYCLOPHOSPHAMIDE TREATMENT AND ADRENAL FUNCTION
SIR,-Dr Wilson and his colleagues (March 20,
p. 610) deadrenal in of ten patwo out secondary suppression tients receiving intermittent high-dose prednisolone and cytotoxic chemotherapy. However, these disturbances might be part of the malignant disease in itself, and without basic values we believe one should be very cautious before ascribing this
scribed
MEAN PLASMA-CORTISOL
(g/ml)
IN
6
PATIENTS BEFORE
(A)
more frequently in filtrates of E. coli strains isolated from infant diarrhoea. The enterotoxic activity was in many cases lost when the strains were subcultured-i.e., in some strains of freshly isolated E. coli the enterotoxicity of filtrates was easily demonstrated, while with further subcultures the enterotoxicity, tested on ligated rabbit intestinal loops, became negative. Few strains conserved their enterotoxicity when subcultured frequently. Thus in our experience the rabbit ilealloop test is of some use. We would also draw attention to individual differences in biological properties and relative lability of enterotoxin production by E. coli, especially when working
tered
with old laboratory strains.
Institute of Landscape
KAREL RASKA
Ecology,
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague 2, Czechoslovakia
HELENA RASKOVA
AND AFTER
(B) TREATMENT WITH CYCLOPHOSPHAMIDE
ENTEROTOXIGENIC E. COLI IN BANGLADESH
SIR,-In their article
Bangladesh diarrhoeas (March 27, p. 659) Ryder colleagues refer to a conflict with the data reported in a previous study of enterotoxigenic E. coli in Bangladesh.’ However, there is no major conflict between the Dr
suppression to the treatment alone. We have studied adrenal function before and after continuous treatment with cyclophosphamide in six patients, five with advanced breast cancer and one with advanced carcinoma of the prostate. Corticotrophin (A.C.T.H.) tests were done before and after 2 months of treatment with cyclophosphamide 2 mg/kg/day. Concentrations of plasma-cortisol were determined fluorimetrically. Samples were taken before and 10, 20, 30, and 40 mm after increasing doses of A.C.T.H. (62-$nag, 125 ng, 250 ng, 500 ng, and 250 g) injected intravenously through an indwelling cannula at intervals of 60 min. The results (see table) suggest that basic levels before each A.C.T.H. dose and maximum increases after each A.C.T.H. dose did not change, indicating unaltered adrenal function after treatment with cyclophosphamide. Department RII, Finseninstitute, DK 2100
Copenhagen, Denmark
H. T. MOURIDSEN
on
and his
data. The difference between 33% and 56% isolation-rates for LT+ organisms can be accounted for by differences in sample size and are probably not significant. We showed that LT+ isolation-rates were higher among inpatients (33%) than outpatients (15%) and were highest (70%) when one selected only the most severe cases. Ryders’ figure of 56% is within this range. The selection of the first severely dehydrated case each day could account for the difference in means, since milder cases, which less frequently have LT+ fsecal organisms, may come in later in the day since they are less disabled. In our series ST+/0 organisms were much less commonly isolated from patients with truly cholera-like diarrhoea than were ST+/LT+ organisms, so it is not surprising that in a small sample of similar severe cases no ST+/0 organisms were found. Another possible explanation is that by measuring actual absorption in the dog model one can pick up massive decreases in net absorption (50-99%) which do not result in net fluid accumulation. The mouse test measures only actual fluid accumulation, and significant absorptive decreases caused by ST could possibly be overlooked. More significant is the similarity between the two reports with respect to finding no Bangladesh E. coli strains which produce LT alone. Johns Hopkins University,
Hvidøre Hospital, DK 2930 Klampenborg
C. BINDER
School of Hygiene and Public Health, International Center for Medical Research, Baltimore, Maryland 21205, U.S.A.
RECOGNISING EPIDEMIC STRAINS OF E.COLI
SiR,—We
interested in the paper
and his colleagues (March 20, p. 629). These workers used tissue-culture testsl-3 and the infant-mouse test4 with negative results in the attempt to prove enterotoxin production by Escherichia coli strains from infantile enteritis outbreaks, kept several years on Dorset egg medium. Working on the ecology of E. coli strains, circulating in human and animal populations, we have isolated several hundred strains from infantile diarrhoea (infants, calves, chicks). The presence of enterotoxin was assayed on ligated rabbit intestinal 100ps.5 Heat-labile activity (18 h loop exposure) was found mainly in calves, exceptionally in humans. Heat-stable activity (6 h loop exposure) was encounwere
by Mr Gross
1. Donta S. T., Moon, H. W., Whipp, S. C. Science, 1974, 183, 334. 2. Sack, D. A., Sack, R. B. Infect. Immun. 1975, 11, 334. 3. Guerrant, R. L., Moore, E. A., Kirschenfeld, P. M., Sande, M. A. New Engl. J. Med. 1975, 293, 567. 4. Dean, G. A., Chang, Y. C., Williams, R. G., Harden, L. B. J. infect. Dis. 1972, 125, 407. 5. Evans, D. G., Evans, D. J., Jr., Pierce, N. F. Infect. Immun. 1973, 8, 731.
DAVID R. NALIN
DIAGNOSIS OF AUTONOMIC DYSFUNCTION
SIR,-Your editorial (May 22, p. 1115) was right not to mention intradermal injection of histamine as a test of autonomic integrity. The test depends on the integrity of pain fibres and does not involve autonomic nerves. Dr Burton (June 5, p. 1248) will find an account in the review you kindly (if not quite accurately) refer to in your editorial.1 Department of Neurology, Radcliffe Infirmary,
J. M. K. SPALDING
Oxford to Dr his work.-ED.L.
***We apologise to
1.
Spalding
for
our
ambivalent reference
Nalin, D. R., McLaughlin, J. C., Rahaman, M., Yunus, M., Curlin, G. Lancet, 1975, ii, 1116. 2. Pierce, N. F., Wallace, C. K. Gastroenterology, 1972, 63, 439. 3. Dean, A. G., Ching, Y. C., Williams, R. G., Harden, L. B. J. infect. Dis. 1972, 125, 407. 1. Johnson, R. H., Spalding, J. M. K. Disorders of the Autonomic Nervous System; p. 124. Oxford, 1974.
