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ABSORPTION OF HEXACHLOROPHANE FROM INFANTS' SKIN
384 CONGENITAL MUSCULAR DYSTROPHY
SIR,—We
were
interested
to see
the letter
by Joseph
and
Netsky1 extending the studies which have been undertaken
this
in
laboratory
on
the motor
neuron
in muscular
They confirmed our finding in murine muscular dystrophy5 of no structural abnormality at the light microscopic level in the anterior-horn cells of the spinal cord, and similarly found no abnormality in the dystrophic hamster. Our recently completed ultrastructural study has also failed to show significant abnormalities in
dystrophy.2-5
dystrophic-mouse anterior-horn cells. Joseph and Netskyalso state that
no
abnormality
was
in the nerve-roots, and we wish to report that this is not so in our material. Both dorsal and ventral roots of the lumbar area, and the upper part of the sciatic-nerve plexus, show dramatic changes reminiscent of the appearances seen in developing fetal nerve. 6-8 There is a gross reduction in the number of Schwann cells and myelin sheaths, most of the axons lying packed in groups without intervening Schwann-cell cytoplasm. These non-myelinated axons range in diameter up to 6 {.L, which is much larger than in the normal (up to 1-5 (.L). This change is present at all ages. It appears that these dystrophic mice have an arrest of Schwann-cell division and myelination in the upper parts of the axons. It would be intriguing to know the physiological effects of this change. Would the extensive area of non-myelination of large axons produce conduction block Would the conduction as occurs in de-myelination ? velocity of these large non-myelinated axons be of the order of normal non-myelinated fibres as might be expected from the absence of a myelin sheath, or would it be of the order of normal myelinated fibres in keeping with their large axonal diameters ? We should emphasise that these findings of peripheralnerve abnormalities in murine muscular dystrophy do not prove the neuropathic theory of muscular dystrophy.2,3 Such changes have not been seen in human or hamster It seems more likely to us that, in the murine nerves. disease, the genetic lesion produces an abnormality of the peripheral nerves unrelated to the primary muscle disease, in the same way as the genetic lesion in Duchenne-type muscular dystrophy produces a cardiomyopathy also unrelated to the primarv muscle disease. seen
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE.
W. G. BRADLEY MARGARET JENKISON.
ADENOVIRUSES IN HUMAN CANCER SiR,-Dr. McAllister and his co-workerspresented data controverting the view that adenoviruses are probable xtiological agents in human cancer. They specifically mention our inability to provide serological evidence of neoplastic-adenovirus infection of human beings in mass sero-epidemiological studies. I wish to add that we have further looked for the presence of adenovirus-induced T (tumour) antigens in commonly occurring tumours of man. Specific adenovirus-tumour sera were tested using indirect fluorescent-antibody techniques versus tissuecultured and cryostat-sectioned human tumours. These 2very sensitive and preliminary results were reported. This study and further work have not been fruitful in demonstrating such antigens in human tumours with the sera we used. I would hasten to add, however, that studies using groupB adenovirus anti-tumour sera and sera directed against tumours and T-antigens induced by adenoviruses of non-human species seem to be in order.
specific
University of Connecticut School of Medicine, Farmington, Connecticut 06032,
M. J. CASEY.
U.S.A.
MEASUREMENT OF ARTERIAL BLOOD-PRESSURE
SIR,-In reply to Dr. Hull’s letter3 concerning the expression of the mean of several blood-pressure readings to one decimal place in our study of a and P adrenergic blockade,4 individual blood-pressures were recorded to the nearest 1 mm. Hg, using a cuff-deflation rate of around 1 mm. Hg per 2 seconds, with the arm at the level of the heart. We are surprised that Dr. Hull inferred that the individual pressures were read to 0-1 mm. Hg. It provides more information to express the mean of a series of whole numbers to a decimal place rather than rounding off to an integer, and it is standard statistical practice to do so. Furthermore, we were anxious that the data we presented should be suitable for further calculations by the reader. We imply no more in the use of the decimal point than does the Registrar-General when referring to an average family size of 2-8 children. Department of the Professor of Medicine, Radcliffe Infirmary,
Regius
L. J. BEILIN B. E. JUEL-JENSEN.
Oxford OX2 6HE.
STERILISATION
SIR,-Mr. Diggory and Mr. Craft (July 8, p. 87) ask if the exclusion of sperm on the examination of uncentrifuged semen is a satisfactory procedure from the legal point of view. The law requires that the surgeon should act in accordance with a practice adopted by a responsible body of surgeons with experience in the particular field, and, as is pointed out, many surgeons consider that microscopical examination of a slide made from an uncentrifuged ejaculate is adequate. Medical Defence Union, Tavistock House South, Tavistock Square, London W.C.1.
PHILIP H. ADDISON, Secretary.
Joseph, B. S., Netsky, M. G. Lancet, 1972, i, 1347. McComas, A. J., Sica, R. E. P. ibid. 1970, i, 119. McComas, A. J., Sica, R. E. P., Currie, S. Nature, 1970, 226, 1263. Bradley, W. G. Dvl. Med. Child Neurol. 1971, 13, 528. Papapetropoulos, T. A., Bradley, W. G. J. Neurol. Neurosurg. Psychiat. 1972, 35, 60. 6. Peters, A., Muir, A. R. Q. Jl exp. Physiol. 1959, 44, 117. 7. Gamble, H. J. J. Anat. 1966, 100, 487. 8. Ochoa, J. ibid. 1971, 108, 231.
1. 2. 3. 4. 5.
ABSORPTION OF HEXACHLOROPHANE FROM INFANTS’ SKIN 5
that small amounts of absorbed into the blood of infants whose skin was washed with hexachlorophane solution has aroused interest and some alarm in view of the toxic actions attributed to hexachlorophane.6There is no information about the absorption of hexachlorophane from powder (’ Ster-zac ’), which has been widely used in this country since its introduction about fifteen years ago in Bristol to prevent staphylococcal infection in infants.7 The matter was therefore investisated in 15 healthv infants in the
SIR,-The demonstration
hexachlorophane
are
McAllister, R. M., Gilden, R. V., Green, M. Lancet, 1972, i, 831. Casey, M. J. in Immunity and Tolerance in Oncogenesis (edited by L. Severi); p. 147. Perugia, Italy, 1970. 3. Lancet, 1972, i, p. 1399. 4. ibid. p. 979. 5. Curley, A., Hawk, R. E., Kimbrough, R. D., Nathenson, G., Finberg, L. ibid. 1971, ii, 296. 6. Kimbrough, R. D. Archs environ. Hlth, 1971, 23, 119. 7. Gillespie, W. A., Simpson, K., Tozer, R. C. Lancet, 1958, ii, 1075. 1. 2.
385 Bristol Maternity Hospital. The routine care of the infants included sealing the umbilical cord stump with ’Octaflex’ when the cord was divided after birth. The whole trunk was then dusted with ster-zac powder (containing 0-33% hexachlorophane), taking care to apply it thoroughly to the umbilical area, groins, perineum, and axillx. The average of powder applied daily to each baby was less than 1-5 g. (less than 5 mg. hexachlorophane). Subsequently, while the infants remained in hospital the umbilical and amount
napkin areas were powdered every time a napkin was changed. Except for an initial cleaning with water on cottonwool, soon after birth, the infants were not bathed until the cord stumps separated. Two heparinised blood-samples were taken from each infant. The first (1-2 ml.) was from the umbilical cord immediately after birth, and the second (0-5-0-75 ml.) on the 8th day from a heel-prick that was also used to obtain blood for Guthrie tests. The risk of contamination of the capillary samples with hexachlorophane from the skin was reduced, though perhaps not entirely eliminated, by washing the feet with plain soap and water after every powder application and before collecting the blood. The risk of contamination might have been eliminated by venepuncture, but we did not think that this was justified. Despite care to avoid it, contamination was even more likely with cord samples. Ster-zac powder was applied to the perineums of most mothers during " dry shaving "; and in some cases the midwife who delivered the baby, and powdered it for the first time, subsequently collected blood from the cord attached to the placenta. Very little contamination from these sources might affect the results and probably explains one surprisingly high cord level,
described below.
Hexachlorophane in blood was measured at the Huntingdon Research Centre by the method of Porcaro et al.s modified for the Perkin Elmer Flgas/light chromatograph. The normal " background " of the method was equivalent to a hexachlorophane concentration between 0-01 and 0-02 ;j.g. per ml., but no adjustment was made for this in the results. The results (table i) showed a comparatively high concentration (1-88 g. per ml.) in the cord sample of TABLE I-HEXACHLOROPHANE CONCENTRATIONS IN
INFANTS’
BLOOD
not known whether any mothers used cosmetic preparations or vaginal sprays that may explain the presence of hexachlorophane in adult blood.5 The 8th-day capillaryblood samples of 13 infants contained slightly more hexachlorophane than the cord samples. But no capillary level exceeded one-half of the minimum concentration reported as toxic in rats that were fed with hexachlorophane for
much
longer periods.5 5 were roughly similar to those of Curley et awl. (table 11), though allowance must be made for differences in analytical technique and for the greater risk of contamination in our capillary samples than in Curley’s venous ones. Moreover, Curley’s samples were taken from infants between 1 and 11 days old, whereas ours were all taken on the 8th day. Our results
TABLE II-COMPARISON OF BLOOD-HEXACHLOROPHANE CONCENTRATIONS (ng. per ml.) IN TWO SERIES
’" hxcludmg
case
9.
Hexachlorophane, like other disinfectants, may be toxic if enough is absorbed by accidental ingestion or through burned skin. But from the available evidence it seems that the blood concentrations of hexachlorophane absorbed from either dusting-powder or solution applied to the skin in the 1st week of life are well below toxic levels and any that is absorbed is rapidly eliminated. No harm could be attributed to the use of ster-zac powder in 830 infants observed in a follow-up study for 6 months after birth, 9,10and none has been recorded in many thousands of babies that must have been treated in various centres of this country. Plueckhahn and Banks 11found no evidence of harm in a very thorough survey of 24,322 infants whose skin was treated with 3% hexachlorophane emulsion-a method that places much more hexachlorophane on the skin than when powder is used. On the other hand, hexachlorophane undoubtedly has prevented much staphylococcal sepsis in infants ?.s,10,12-14 and breast abscesses in mothers. 15, 16It would be foolish to avoid using a substance that is demonstrably valuable in preventing serious infectious disease and is evidently safe if correctly employed, under medical supervision. It need not be used after the first 7-10 days of life except perhaps when a baby stays longer in hospital. Already there are reports of increasing incidence of staphylococcal disease among infants in hospitals from which hexachlorophane has been withdrawn 18 We are grateful to Mr. C. Harris, of Hough, Hoseason and Co. Ltd., who arranged the blood analyses.
United Bristol
Hospitals,
Bristol 2. 9. *
Twin.
t Excluding
case
9 (see
text).
infant no. 9, a twin. This almost certainly was due to accidental contamination, since there was some difficulty in collecting the blood and the other twin (no. 10) had a low cord level. Some other cord samples also contained small amounts of hexachlorophane, owing either to plasental transfer from maternal blood or to contamination. It is 8.
Porcaro, B. J., Shubiak, P., Manowitz, M. J. pharm. Sci. 1969, 58, 251.
10. 11. 12. 13. 14. 15. 16. 17.
V. G. ALDER D. BURMAN BERYL D. CORNER W. A. GILLESPIE.
Simpson, K., Tozer, R. C., Gillespie, W. A. Br. med. J. 1960, i, 315. Baber, K. G., Corner, B. D., Duncan, E. H. L., Eades, S. M., Gillespie, W. A., Walker, S. C. B. J. Hyg., Camb. 1967, 65, 381. Plueckhahn, V. D., Banks, J. Med. J. Aust. 1972, i, 897. Plueckhahn, V. D., Banks, J. ibid. 1963, ii, 519. Farquharson, D. D., Penny, S. F., Edwards, H. E., Barr, E. Can. med. Ass. J. 1952, 67, 247. Gluck, L., Wood, H. F. New Engl. J. Med. 1961, 265, 1177. Comer, B. D., Crowther, S. T., Eades, S. M. Br. med. J. 1960, i, 1927. Plueckhahn, V. D., Banks, J. ibid. 1964, ii, 414. Ayliffe, G. A. J., Brightwell, K. M., Ball, P. M., Derrington, M. Personal communication.
18. Morbid. Mortal.
Wkly Rep. 1972, 21,
37.
SIR,—We
were
interested
to see
the letter
by Joseph
and
Netsky1 extending the studies which have been undertaken
this
in
laboratory
on
the motor
neuron
in muscular
They confirmed our finding in murine muscular dystrophy5 of no structural abnormality at the light microscopic level in the anterior-horn cells of the spinal cord, and similarly found no abnormality in the dystrophic hamster. Our recently completed ultrastructural study has also failed to show significant abnormalities in
dystrophy.2-5
dystrophic-mouse anterior-horn cells. Joseph and Netskyalso state that
no
abnormality
was
in the nerve-roots, and we wish to report that this is not so in our material. Both dorsal and ventral roots of the lumbar area, and the upper part of the sciatic-nerve plexus, show dramatic changes reminiscent of the appearances seen in developing fetal nerve. 6-8 There is a gross reduction in the number of Schwann cells and myelin sheaths, most of the axons lying packed in groups without intervening Schwann-cell cytoplasm. These non-myelinated axons range in diameter up to 6 {.L, which is much larger than in the normal (up to 1-5 (.L). This change is present at all ages. It appears that these dystrophic mice have an arrest of Schwann-cell division and myelination in the upper parts of the axons. It would be intriguing to know the physiological effects of this change. Would the extensive area of non-myelination of large axons produce conduction block Would the conduction as occurs in de-myelination ? velocity of these large non-myelinated axons be of the order of normal non-myelinated fibres as might be expected from the absence of a myelin sheath, or would it be of the order of normal myelinated fibres in keeping with their large axonal diameters ? We should emphasise that these findings of peripheralnerve abnormalities in murine muscular dystrophy do not prove the neuropathic theory of muscular dystrophy.2,3 Such changes have not been seen in human or hamster It seems more likely to us that, in the murine nerves. disease, the genetic lesion produces an abnormality of the peripheral nerves unrelated to the primary muscle disease, in the same way as the genetic lesion in Duchenne-type muscular dystrophy produces a cardiomyopathy also unrelated to the primarv muscle disease. seen
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE.
W. G. BRADLEY MARGARET JENKISON.
ADENOVIRUSES IN HUMAN CANCER SiR,-Dr. McAllister and his co-workerspresented data controverting the view that adenoviruses are probable xtiological agents in human cancer. They specifically mention our inability to provide serological evidence of neoplastic-adenovirus infection of human beings in mass sero-epidemiological studies. I wish to add that we have further looked for the presence of adenovirus-induced T (tumour) antigens in commonly occurring tumours of man. Specific adenovirus-tumour sera were tested using indirect fluorescent-antibody techniques versus tissuecultured and cryostat-sectioned human tumours. These 2very sensitive and preliminary results were reported. This study and further work have not been fruitful in demonstrating such antigens in human tumours with the sera we used. I would hasten to add, however, that studies using groupB adenovirus anti-tumour sera and sera directed against tumours and T-antigens induced by adenoviruses of non-human species seem to be in order.
specific
University of Connecticut School of Medicine, Farmington, Connecticut 06032,
M. J. CASEY.
U.S.A.
MEASUREMENT OF ARTERIAL BLOOD-PRESSURE
SIR,-In reply to Dr. Hull’s letter3 concerning the expression of the mean of several blood-pressure readings to one decimal place in our study of a and P adrenergic blockade,4 individual blood-pressures were recorded to the nearest 1 mm. Hg, using a cuff-deflation rate of around 1 mm. Hg per 2 seconds, with the arm at the level of the heart. We are surprised that Dr. Hull inferred that the individual pressures were read to 0-1 mm. Hg. It provides more information to express the mean of a series of whole numbers to a decimal place rather than rounding off to an integer, and it is standard statistical practice to do so. Furthermore, we were anxious that the data we presented should be suitable for further calculations by the reader. We imply no more in the use of the decimal point than does the Registrar-General when referring to an average family size of 2-8 children. Department of the Professor of Medicine, Radcliffe Infirmary,
Regius
L. J. BEILIN B. E. JUEL-JENSEN.
Oxford OX2 6HE.
STERILISATION
SIR,-Mr. Diggory and Mr. Craft (July 8, p. 87) ask if the exclusion of sperm on the examination of uncentrifuged semen is a satisfactory procedure from the legal point of view. The law requires that the surgeon should act in accordance with a practice adopted by a responsible body of surgeons with experience in the particular field, and, as is pointed out, many surgeons consider that microscopical examination of a slide made from an uncentrifuged ejaculate is adequate. Medical Defence Union, Tavistock House South, Tavistock Square, London W.C.1.
PHILIP H. ADDISON, Secretary.
Joseph, B. S., Netsky, M. G. Lancet, 1972, i, 1347. McComas, A. J., Sica, R. E. P. ibid. 1970, i, 119. McComas, A. J., Sica, R. E. P., Currie, S. Nature, 1970, 226, 1263. Bradley, W. G. Dvl. Med. Child Neurol. 1971, 13, 528. Papapetropoulos, T. A., Bradley, W. G. J. Neurol. Neurosurg. Psychiat. 1972, 35, 60. 6. Peters, A., Muir, A. R. Q. Jl exp. Physiol. 1959, 44, 117. 7. Gamble, H. J. J. Anat. 1966, 100, 487. 8. Ochoa, J. ibid. 1971, 108, 231.
1. 2. 3. 4. 5.
ABSORPTION OF HEXACHLOROPHANE FROM INFANTS’ SKIN 5
that small amounts of absorbed into the blood of infants whose skin was washed with hexachlorophane solution has aroused interest and some alarm in view of the toxic actions attributed to hexachlorophane.6There is no information about the absorption of hexachlorophane from powder (’ Ster-zac ’), which has been widely used in this country since its introduction about fifteen years ago in Bristol to prevent staphylococcal infection in infants.7 The matter was therefore investisated in 15 healthv infants in the
SIR,-The demonstration
hexachlorophane
are
McAllister, R. M., Gilden, R. V., Green, M. Lancet, 1972, i, 831. Casey, M. J. in Immunity and Tolerance in Oncogenesis (edited by L. Severi); p. 147. Perugia, Italy, 1970. 3. Lancet, 1972, i, p. 1399. 4. ibid. p. 979. 5. Curley, A., Hawk, R. E., Kimbrough, R. D., Nathenson, G., Finberg, L. ibid. 1971, ii, 296. 6. Kimbrough, R. D. Archs environ. Hlth, 1971, 23, 119. 7. Gillespie, W. A., Simpson, K., Tozer, R. C. Lancet, 1958, ii, 1075. 1. 2.
385 Bristol Maternity Hospital. The routine care of the infants included sealing the umbilical cord stump with ’Octaflex’ when the cord was divided after birth. The whole trunk was then dusted with ster-zac powder (containing 0-33% hexachlorophane), taking care to apply it thoroughly to the umbilical area, groins, perineum, and axillx. The average of powder applied daily to each baby was less than 1-5 g. (less than 5 mg. hexachlorophane). Subsequently, while the infants remained in hospital the umbilical and amount
napkin areas were powdered every time a napkin was changed. Except for an initial cleaning with water on cottonwool, soon after birth, the infants were not bathed until the cord stumps separated. Two heparinised blood-samples were taken from each infant. The first (1-2 ml.) was from the umbilical cord immediately after birth, and the second (0-5-0-75 ml.) on the 8th day from a heel-prick that was also used to obtain blood for Guthrie tests. The risk of contamination of the capillary samples with hexachlorophane from the skin was reduced, though perhaps not entirely eliminated, by washing the feet with plain soap and water after every powder application and before collecting the blood. The risk of contamination might have been eliminated by venepuncture, but we did not think that this was justified. Despite care to avoid it, contamination was even more likely with cord samples. Ster-zac powder was applied to the perineums of most mothers during " dry shaving "; and in some cases the midwife who delivered the baby, and powdered it for the first time, subsequently collected blood from the cord attached to the placenta. Very little contamination from these sources might affect the results and probably explains one surprisingly high cord level,
described below.
Hexachlorophane in blood was measured at the Huntingdon Research Centre by the method of Porcaro et al.s modified for the Perkin Elmer Flgas/light chromatograph. The normal " background " of the method was equivalent to a hexachlorophane concentration between 0-01 and 0-02 ;j.g. per ml., but no adjustment was made for this in the results. The results (table i) showed a comparatively high concentration (1-88 g. per ml.) in the cord sample of TABLE I-HEXACHLOROPHANE CONCENTRATIONS IN
INFANTS’
BLOOD
not known whether any mothers used cosmetic preparations or vaginal sprays that may explain the presence of hexachlorophane in adult blood.5 The 8th-day capillaryblood samples of 13 infants contained slightly more hexachlorophane than the cord samples. But no capillary level exceeded one-half of the minimum concentration reported as toxic in rats that were fed with hexachlorophane for
much
longer periods.5 5 were roughly similar to those of Curley et awl. (table 11), though allowance must be made for differences in analytical technique and for the greater risk of contamination in our capillary samples than in Curley’s venous ones. Moreover, Curley’s samples were taken from infants between 1 and 11 days old, whereas ours were all taken on the 8th day. Our results
TABLE II-COMPARISON OF BLOOD-HEXACHLOROPHANE CONCENTRATIONS (ng. per ml.) IN TWO SERIES
’" hxcludmg
case
9.
Hexachlorophane, like other disinfectants, may be toxic if enough is absorbed by accidental ingestion or through burned skin. But from the available evidence it seems that the blood concentrations of hexachlorophane absorbed from either dusting-powder or solution applied to the skin in the 1st week of life are well below toxic levels and any that is absorbed is rapidly eliminated. No harm could be attributed to the use of ster-zac powder in 830 infants observed in a follow-up study for 6 months after birth, 9,10and none has been recorded in many thousands of babies that must have been treated in various centres of this country. Plueckhahn and Banks 11found no evidence of harm in a very thorough survey of 24,322 infants whose skin was treated with 3% hexachlorophane emulsion-a method that places much more hexachlorophane on the skin than when powder is used. On the other hand, hexachlorophane undoubtedly has prevented much staphylococcal sepsis in infants ?.s,10,12-14 and breast abscesses in mothers. 15, 16It would be foolish to avoid using a substance that is demonstrably valuable in preventing serious infectious disease and is evidently safe if correctly employed, under medical supervision. It need not be used after the first 7-10 days of life except perhaps when a baby stays longer in hospital. Already there are reports of increasing incidence of staphylococcal disease among infants in hospitals from which hexachlorophane has been withdrawn 18 We are grateful to Mr. C. Harris, of Hough, Hoseason and Co. Ltd., who arranged the blood analyses.
United Bristol
Hospitals,
Bristol 2. 9. *
Twin.
t Excluding
case
9 (see
text).
infant no. 9, a twin. This almost certainly was due to accidental contamination, since there was some difficulty in collecting the blood and the other twin (no. 10) had a low cord level. Some other cord samples also contained small amounts of hexachlorophane, owing either to plasental transfer from maternal blood or to contamination. It is 8.
Porcaro, B. J., Shubiak, P., Manowitz, M. J. pharm. Sci. 1969, 58, 251.
10. 11. 12. 13. 14. 15. 16. 17.
V. G. ALDER D. BURMAN BERYL D. CORNER W. A. GILLESPIE.
Simpson, K., Tozer, R. C., Gillespie, W. A. Br. med. J. 1960, i, 315. Baber, K. G., Corner, B. D., Duncan, E. H. L., Eades, S. M., Gillespie, W. A., Walker, S. C. B. J. Hyg., Camb. 1967, 65, 381. Plueckhahn, V. D., Banks, J. Med. J. Aust. 1972, i, 897. Plueckhahn, V. D., Banks, J. ibid. 1963, ii, 519. Farquharson, D. D., Penny, S. F., Edwards, H. E., Barr, E. Can. med. Ass. J. 1952, 67, 247. Gluck, L., Wood, H. F. New Engl. J. Med. 1961, 265, 1177. Comer, B. D., Crowther, S. T., Eades, S. M. Br. med. J. 1960, i, 1927. Plueckhahn, V. D., Banks, J. ibid. 1964, ii, 414. Ayliffe, G. A. J., Brightwell, K. M., Ball, P. M., Derrington, M. Personal communication.
18. Morbid. Mortal.
Wkly Rep. 1972, 21,
37.