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VIRUSES OF ACUTE HÆMORRHAGIC CONJUNCTIVITIS
545 treated with topical sodium fusidate (’ Fucidin ’ ointment). In contrast, a mean healing-time of 10-5 days was recorded in a control group of 836 patients treated with simple dressings or other topical antibiotics, such as neomycin or framycetin. This 25% reduction in mean healing-time with fucidin ointment was statistically significant. The number of patients given systemic antibiotics in either group was almost identical. In treating incised subcutaneous abscesses, one is faced with the practical problem of ensuring intimate contact between local antibiotic and infecting organisms. It was decided therefore to investigate4 the value of injecting fusidic-acid gel (’ Fucidin Caviject ’) on one occasion only into the abscess cavity after incision, drainage, and careful curettage. A control group of incised abscesses were treated by repeated applications of a superficial dressing impregnated with sodium fusidate. There was a striking reduction in healing-time brought about by the intracavity use of fusidic-acid gel; healing-times were reduced by about one half (P= 0°001). The overall number of patients given systemic antibiotics was much reduced compared with the previous investigation, but again the use in either group was statistically similar. Injecting fusidic-acid gel allows the use of much smaller incisions and consequently produces an improved cosmetic effect. It also obviates " steam-age " procedures, such as wicks and the sewing-in of drains, both of which are excruciatingly painful (I have had personal experience!). That it is a once-only technique should be an additional benefit in those patients who fail to return for follow-up. The use of sodium fusidate as a topical antibiotic might be criticised on the grounds that if a patient had a hypersensitivity reaction the future use of this valuable systemic drug would be precluded in that patient. However, I have used sodium fusidate topically in an estimated 12,000 patients over the past nine years without any evidence whatsoever of adverse reactions. Having placed greater reliance on topical antibiotics, I have now largely abandoned the use of systemic antibiotics for pyogenic subcutaneous infections, except where there is evidence of infection spread. Leeds (St. James’) University Hospital, Leeds.
I. C. RITCHIE.
PAY OFFER TO N.H.S. HOSPITAL STAFF
SIR,-I would be grateful if you would publish the following motion passed at a meeting of the residents’ mess at East Birmingham Hospital on Feb. 20. "The
recent pay offer by the Government to the hospital staff is derisory when seen in relation to the essential contribution that they make to patient care, and in view of their low pay and the rapidly rising cost of living. Accordingly this meeting votes to support the ancillary workers in their claim and recommends doctors to consult with the ancillary unions and report back."
ancillary
It is important that the National Health Service does not suffer because of the economic problems of the present Government. We must be prepared to pay a decent living wage to the ancillary workers. Our neglect of these workers is symptomatic of the financially parlous state in which our Health Service now finds itself, reflected in crumbling hospitals and chronic nursing shortages. Industrial action will cause more or less hardship for everyone, including the strikers. However, in the long term if the ancillary staff’s wages are not increased it will be the Health Service, in which most of us work, which will suffer. It is to be hoped that the ancillary workers will gain 4.
Ritchie, I. C. Br. med. J. 1972, ii, 381.
support from other hospital groups. This should include doctors, who in the past were only too willing to threaten withdrawal from the Health Service when their pay negotiations were not going well. Cooperation with the ancillary unions by not strike-breaking will also be vitally important if the situation is not to be exacerbated and the Health Service to degenerate into bitter antagonism between different groups of workers. 10 Bull
Birmingham
Street, B17 0HH.
P. R. GULLY.
VIRUSES OF ACUTE HÆMORRHAGIC
CONJUNCTIVITIS Sirread with interest the articles
on acute
hsemor-
rhagic conjunctivitis (Jan. 13, pp. 61 and 86). 1 note that the relationship of the Singapore epidemic conjunctivitis virus (1970) 1-5 to the viruses subsequently isolated in Hong Kong (1971),s Japan (1971),7 and Singapore (1971)8 has not been established. May I present a summary of our findings in a study carried out on two strains of Singapore epidemic conjunctivitis virus (s.E.c. 24/1970 and S.E.C. 146/1971), two strains of Hong Kong conjunctivitis virus (HK 3454/1971 and HK 3751/1971) obtained from Dr W. K. Chang, Department of Microbiology, University of Hong Kong, and two strains of Japanese acute haemorrhagic conjunctivitis virus (Jap. A.H.C. 648/1971 and Jap. A.H.C. 670/1971) from Dr R. Kono, National Institute of Health, Tokyo ? All six viruses resemble the enteroviruses in size, resistance to ether acid pH 3-0, and reaction to acridineorange stain, but they were not neutralised by 13 serumpools containing antisera to poliovirus types 1, 2, 3, echovirus types 1 to 7, 9, 11 to 27, and 29 to 33, coxsackievirus types A7, A9, A16, and B1 to B6. The s.E.c. 24/1970 and HK 3751/1971 viruses were non-cytopathogenic in monkeykidney cell cultures, while the remaining 1971 viruses produced cytopathogenic effects in this cell line. The HK 3751/1971 virus alone was pathogenic for suckling mice. With regard to their antigenic relationship, monkey immune serum to s.E.c. 24/1970 virus neutralised HK 3751/1971 and Jap. A.H.C. 670/1971 viruses at low (1/20) serum dilution, but not the remaining 1971 viruses. A sample of low-titre (1/20) monkey immune serum to HK 3751/1971 virus supplied by Dr Chang neutralised S.E.c. 24/1970 virus at 1/20 serum dilution and not the remaining 1971 viruses. However, a batch of high-titre ( > 1/1280) monkey immune serum to HK 3751/1971 virus produced in this laboratory neutralised s.E.C. 24/1970 virus at 1/640 and the remaining viruses at 1/5 to 1/10 serum dilutions. The titre and neutralisability of immune serum used for comparative study obviously play an important role in the test. The S.E.C. 146/1971, HK 3454/ 1971, Jap. A.H.c. 648/1971, and Jap. A.H.C. 670/1971 viruses are antigenically similar in that immune sera to these viruses neutralised each of these viruses at high serum dilutions (1/160 to > 1/1280), but not the S.E.C. These antigenic 24/1970 and HK 3751/1971 viruses. similarities were substantiated by serological tests on patients’ sera collected during the 1970 and 1971 outbreaks in Singapore. 1. 2. 3.
4. 5. 6. 7. 8.
Lim, K. H., Yin-Murphy, M. Singapore med. J. 1971, 12, 247. Lim, K. H., Yin-Murphy, M. Proceedings of the 6th SingaporeMalaysia Congress of Medicine, 1971; p. 310. Lim, K. H., Yin-Murphy, M. Fourth Congress, Asia-Pacific Academy of Ophthalmology, Auckland, New Zealand, April 13, 1972 (in the press). Yin-Murphy, M. S.E. Asian J. trop. Med. publ. Hlth, 1972, 3, 303. Yin-Murphy, M., Lim, K. H. Lancet, 1972, ii, 857. Chang, W. K. Personal communication. Kono, R., et al. Lancet, 1972, i, 1191. Yin-Murphy, M. S.E. Asian J. trop. Med. publ. Hlth (in the press).
546 It is possible that the first picornavirus of epidemic conjunctivitis isolated in Singapore in 1970 had undergone antigenic changes to give rise to variants or subtypes as exemplified by viruses (HK 3751/1971 and Jap. 670/1971) isolated in the following year. However, although antigenically related, more than one type of picornavirus could have been involved in the pandemic outbreak in Southeast Asia during 1970 and 1971. These viruses of epidemic conjunctivitis may represent new variants of an established enterovirus or a new enterovirus-type. Alternatively, they may be classified as a third subgroup of the picornaviruses distinct from the subgroups enteroviruses and rhinoviruses on the basis of the distinctly different syndrome associated with them. University of Singapore, Department of Bacteriology, Faculty of Medicine, Singapore 3.
(2) Among healthy, premenopausal Caucasian women a wide range of urinary oestriol excretion-rates, far exceeding the 10-15% mean variation between menstrualcycle phases or between successive cycles of an individual.
there is
Review of data from many laboratories confirms that 2025% of healthy premenopausal women aged 19+ excrete
urinary oestriol/cestrone+ significantly reduced (P<0-01) 17p-cestradiol. They also may have considerably reduced plasma clearance-rates for cestrone and 17[3-oestradio!.
An autosomal mutant recessive genotype limited to Caucasians with a gene frequency ±50% may account for impaired cestrone and oestradiol hydroxylation to cestriol.6 While aestrone and 17p-oestradiol are known mammary carcinogens, oestriol appears to be less carcinogenic.2 PREVENTION
M. YIN-MURPHY.
OF
INDUCED
MAMMARY
CARCINOMA AND ADENOMA
BY CESTROGENS
(results recorded
as
number of
tumour-bearing rats/total survivors)
ENDOCRINE PROFILES AND BREAST CANCER
SIR,-In the paper by Dr Argiielles and others (Jan. 27, 165), we question certain aspects of their methods and conclusions. The use of only 18 controls for 115 patients is surprising; furthermore, their ages, parity, and age-atfirst-pregnancy are not presented. We would also feel easier if we were certain that at least a portion of the oestrogen determinations had been done in duplicate, to demonstrate laboratory reliability. Even if one accepts the results presented, the data do not seriously weaken xtiological hypotheses concerning the importance of the oestriol ratio, especially its influence before age 30. In spite of the authors’ attempt to minimise its importance, the effect of the tumour upon cestrogen levels is still uncertain, though of considerable importance. Furthermore, some would question the apparent assumption p.
that oestrogen levels in older women with disease reflect the levels in younger women free of disease. This assumption would be necessary to relate the current levels to an
xtiological
process. Department of Preventive Medicine, School of Hygiene, University of Toronto.
ROBERT W. MORGAN D. V. VAKIL.
ŒSTRIOL AND PREVENTION OF BREAST CANCER
SIR,-Breast cancer remains the commonest cause of death in middle-aged women in Great Britain and in the United States. Since Professor MacMahon and Professor Cole1 among others have evinced interest in the anticarcinogenic activity of oestriol which we first proposed 2-4 (based on subnormal " oestriol excretion in 62%of untreated breast-cancer patients, compared with 21 °,o of age-matched controls), we should like to call attention to confirmatory work. (1) Premenopausal, healthy, non-pregnant Asiatic women, in whom breast-cancer risk is slight compared with Caucasians, have uniformly high rates of urinary oestriol excretion,5.6 largely derived from the oxidation of cestrone and 17-cestradiol by aryl hydroxylases of the liver and gut.’ "
1. 2.
3. 4. 5. 6. 7.
MacMahon, B., Cole, P. Lancet, 1970, ii, 153. Lemon, H. M., Wotiz, H. H., Parsons, L., Mozden, P. J. J. Am. med. Ass. 1966, 196, 1128. Lemon, H. M. Cancer, 1969, 23, 781. Lemon, H. M. ibid. 1970, 25, 423. MacMahon, B., Cole, P., Brown, J. B., Aoki, K., Tong Ming Lin, Morgan, R. W., Ngai-Chen Woo. Lancet, 1971, ii, 900. Lemon, H. M. J. surg. Oncol. 1972, 3, 255. Lemon, H. M. Proc. cent. Soc. clin. Res. 1972, 20, 796.
* Difference from carcinogen-treated
significant,
P <
0’001
by X’.
Recessive mutant genotypes with maximum impairment of oestrogen hydroxylation would also be expected to have reduced androgen hydroxylation and hence reduced 17oxosteroid excretion in many instances.The observations of Bacigalupo and Schubert of low cestriol excretion in premenopausal German women with fibrocystic breast disease,9 who resembled their German breast-cancer patients,10 need to be confirmed in view of the heightened breast-cancer risk in this group. (3) After more than 500 rat-years’ observation of the antibreast-cancer effects of cestrogens implanted in intact Sprague-Dawley female rats, oestriol is found to be the most active protective cestrogen yet tested against neoplasms induced by 20 mg. oral 7,12-dimethyl-benzanthracene (D.M.B.A.) 11 or by 50 mg. procarbazine (P.c.) administered at 50-55 days of age (see table).12 In these experiments, the oestrogen-NaCI pellet was implanted subcutaneously in the nuchal region 24-48 hours before oral carcinogen administration. Animals were examined weekly and all growing tumours exceeding 5 mm. were examined by biopsy; if positive for adenoma or carcinoma, the animal All non-tumour-bearing animals were was sacrificed. observed until death, when they were examined by necropsy. The superior protective action of cestriol may be partly related to its greater solubility in plasma and decreased
binding to plasma-albumin, compared to cestrone or 17 (3-aestradiol. Dehydroepiandrosterone, testosterone, 16-keto-17j3cestradiol, 2-OH-oestradiol, and 17 a-aestradiol similarly 8.
9. 10. 11. 12.
Bulbrook, R. D., Hayward, J. L., Spicer, C. C. Lancet, 1971, ii, 395. Bacigalupo, G., Schubert, K. Klin. Wschr. 1960, 38, 804. Bacigalupo, G., Schubert, K. Eur. J. Cancer, 1966, 2, 75. Lemon, H. M. Proc. Am. Ass. Cancer Res. 1972, 13, 4. Lemon, H. M. ibid. (in the press).
I. C. RITCHIE.
PAY OFFER TO N.H.S. HOSPITAL STAFF
SIR,-I would be grateful if you would publish the following motion passed at a meeting of the residents’ mess at East Birmingham Hospital on Feb. 20. "The
recent pay offer by the Government to the hospital staff is derisory when seen in relation to the essential contribution that they make to patient care, and in view of their low pay and the rapidly rising cost of living. Accordingly this meeting votes to support the ancillary workers in their claim and recommends doctors to consult with the ancillary unions and report back."
ancillary
It is important that the National Health Service does not suffer because of the economic problems of the present Government. We must be prepared to pay a decent living wage to the ancillary workers. Our neglect of these workers is symptomatic of the financially parlous state in which our Health Service now finds itself, reflected in crumbling hospitals and chronic nursing shortages. Industrial action will cause more or less hardship for everyone, including the strikers. However, in the long term if the ancillary staff’s wages are not increased it will be the Health Service, in which most of us work, which will suffer. It is to be hoped that the ancillary workers will gain 4.
Ritchie, I. C. Br. med. J. 1972, ii, 381.
support from other hospital groups. This should include doctors, who in the past were only too willing to threaten withdrawal from the Health Service when their pay negotiations were not going well. Cooperation with the ancillary unions by not strike-breaking will also be vitally important if the situation is not to be exacerbated and the Health Service to degenerate into bitter antagonism between different groups of workers. 10 Bull
Birmingham
Street, B17 0HH.
P. R. GULLY.
VIRUSES OF ACUTE HÆMORRHAGIC
CONJUNCTIVITIS Sirread with interest the articles
on acute
hsemor-
rhagic conjunctivitis (Jan. 13, pp. 61 and 86). 1 note that the relationship of the Singapore epidemic conjunctivitis virus (1970) 1-5 to the viruses subsequently isolated in Hong Kong (1971),s Japan (1971),7 and Singapore (1971)8 has not been established. May I present a summary of our findings in a study carried out on two strains of Singapore epidemic conjunctivitis virus (s.E.c. 24/1970 and S.E.C. 146/1971), two strains of Hong Kong conjunctivitis virus (HK 3454/1971 and HK 3751/1971) obtained from Dr W. K. Chang, Department of Microbiology, University of Hong Kong, and two strains of Japanese acute haemorrhagic conjunctivitis virus (Jap. A.H.C. 648/1971 and Jap. A.H.C. 670/1971) from Dr R. Kono, National Institute of Health, Tokyo ? All six viruses resemble the enteroviruses in size, resistance to ether acid pH 3-0, and reaction to acridineorange stain, but they were not neutralised by 13 serumpools containing antisera to poliovirus types 1, 2, 3, echovirus types 1 to 7, 9, 11 to 27, and 29 to 33, coxsackievirus types A7, A9, A16, and B1 to B6. The s.E.c. 24/1970 and HK 3751/1971 viruses were non-cytopathogenic in monkeykidney cell cultures, while the remaining 1971 viruses produced cytopathogenic effects in this cell line. The HK 3751/1971 virus alone was pathogenic for suckling mice. With regard to their antigenic relationship, monkey immune serum to s.E.c. 24/1970 virus neutralised HK 3751/1971 and Jap. A.H.C. 670/1971 viruses at low (1/20) serum dilution, but not the remaining 1971 viruses. A sample of low-titre (1/20) monkey immune serum to HK 3751/1971 virus supplied by Dr Chang neutralised S.E.c. 24/1970 virus at 1/20 serum dilution and not the remaining 1971 viruses. However, a batch of high-titre ( > 1/1280) monkey immune serum to HK 3751/1971 virus produced in this laboratory neutralised s.E.C. 24/1970 virus at 1/640 and the remaining viruses at 1/5 to 1/10 serum dilutions. The titre and neutralisability of immune serum used for comparative study obviously play an important role in the test. The S.E.C. 146/1971, HK 3454/ 1971, Jap. A.H.c. 648/1971, and Jap. A.H.C. 670/1971 viruses are antigenically similar in that immune sera to these viruses neutralised each of these viruses at high serum dilutions (1/160 to > 1/1280), but not the S.E.C. These antigenic 24/1970 and HK 3751/1971 viruses. similarities were substantiated by serological tests on patients’ sera collected during the 1970 and 1971 outbreaks in Singapore. 1. 2. 3.
4. 5. 6. 7. 8.
Lim, K. H., Yin-Murphy, M. Singapore med. J. 1971, 12, 247. Lim, K. H., Yin-Murphy, M. Proceedings of the 6th SingaporeMalaysia Congress of Medicine, 1971; p. 310. Lim, K. H., Yin-Murphy, M. Fourth Congress, Asia-Pacific Academy of Ophthalmology, Auckland, New Zealand, April 13, 1972 (in the press). Yin-Murphy, M. S.E. Asian J. trop. Med. publ. Hlth, 1972, 3, 303. Yin-Murphy, M., Lim, K. H. Lancet, 1972, ii, 857. Chang, W. K. Personal communication. Kono, R., et al. Lancet, 1972, i, 1191. Yin-Murphy, M. S.E. Asian J. trop. Med. publ. Hlth (in the press).
546 It is possible that the first picornavirus of epidemic conjunctivitis isolated in Singapore in 1970 had undergone antigenic changes to give rise to variants or subtypes as exemplified by viruses (HK 3751/1971 and Jap. 670/1971) isolated in the following year. However, although antigenically related, more than one type of picornavirus could have been involved in the pandemic outbreak in Southeast Asia during 1970 and 1971. These viruses of epidemic conjunctivitis may represent new variants of an established enterovirus or a new enterovirus-type. Alternatively, they may be classified as a third subgroup of the picornaviruses distinct from the subgroups enteroviruses and rhinoviruses on the basis of the distinctly different syndrome associated with them. University of Singapore, Department of Bacteriology, Faculty of Medicine, Singapore 3.
(2) Among healthy, premenopausal Caucasian women a wide range of urinary oestriol excretion-rates, far exceeding the 10-15% mean variation between menstrualcycle phases or between successive cycles of an individual.
there is
Review of data from many laboratories confirms that 2025% of healthy premenopausal women aged 19+ excrete
urinary oestriol/cestrone+ significantly reduced (P<0-01) 17p-cestradiol. They also may have considerably reduced plasma clearance-rates for cestrone and 17[3-oestradio!.
An autosomal mutant recessive genotype limited to Caucasians with a gene frequency ±50% may account for impaired cestrone and oestradiol hydroxylation to cestriol.6 While aestrone and 17p-oestradiol are known mammary carcinogens, oestriol appears to be less carcinogenic.2 PREVENTION
M. YIN-MURPHY.
OF
INDUCED
MAMMARY
CARCINOMA AND ADENOMA
BY CESTROGENS
(results recorded
as
number of
tumour-bearing rats/total survivors)
ENDOCRINE PROFILES AND BREAST CANCER
SIR,-In the paper by Dr Argiielles and others (Jan. 27, 165), we question certain aspects of their methods and conclusions. The use of only 18 controls for 115 patients is surprising; furthermore, their ages, parity, and age-atfirst-pregnancy are not presented. We would also feel easier if we were certain that at least a portion of the oestrogen determinations had been done in duplicate, to demonstrate laboratory reliability. Even if one accepts the results presented, the data do not seriously weaken xtiological hypotheses concerning the importance of the oestriol ratio, especially its influence before age 30. In spite of the authors’ attempt to minimise its importance, the effect of the tumour upon cestrogen levels is still uncertain, though of considerable importance. Furthermore, some would question the apparent assumption p.
that oestrogen levels in older women with disease reflect the levels in younger women free of disease. This assumption would be necessary to relate the current levels to an
xtiological
process. Department of Preventive Medicine, School of Hygiene, University of Toronto.
ROBERT W. MORGAN D. V. VAKIL.
ŒSTRIOL AND PREVENTION OF BREAST CANCER
SIR,-Breast cancer remains the commonest cause of death in middle-aged women in Great Britain and in the United States. Since Professor MacMahon and Professor Cole1 among others have evinced interest in the anticarcinogenic activity of oestriol which we first proposed 2-4 (based on subnormal " oestriol excretion in 62%of untreated breast-cancer patients, compared with 21 °,o of age-matched controls), we should like to call attention to confirmatory work. (1) Premenopausal, healthy, non-pregnant Asiatic women, in whom breast-cancer risk is slight compared with Caucasians, have uniformly high rates of urinary oestriol excretion,5.6 largely derived from the oxidation of cestrone and 17-cestradiol by aryl hydroxylases of the liver and gut.’ "
1. 2.
3. 4. 5. 6. 7.
MacMahon, B., Cole, P. Lancet, 1970, ii, 153. Lemon, H. M., Wotiz, H. H., Parsons, L., Mozden, P. J. J. Am. med. Ass. 1966, 196, 1128. Lemon, H. M. Cancer, 1969, 23, 781. Lemon, H. M. ibid. 1970, 25, 423. MacMahon, B., Cole, P., Brown, J. B., Aoki, K., Tong Ming Lin, Morgan, R. W., Ngai-Chen Woo. Lancet, 1971, ii, 900. Lemon, H. M. J. surg. Oncol. 1972, 3, 255. Lemon, H. M. Proc. cent. Soc. clin. Res. 1972, 20, 796.
* Difference from carcinogen-treated
significant,
P <
0’001
by X’.
Recessive mutant genotypes with maximum impairment of oestrogen hydroxylation would also be expected to have reduced androgen hydroxylation and hence reduced 17oxosteroid excretion in many instances.The observations of Bacigalupo and Schubert of low cestriol excretion in premenopausal German women with fibrocystic breast disease,9 who resembled their German breast-cancer patients,10 need to be confirmed in view of the heightened breast-cancer risk in this group. (3) After more than 500 rat-years’ observation of the antibreast-cancer effects of cestrogens implanted in intact Sprague-Dawley female rats, oestriol is found to be the most active protective cestrogen yet tested against neoplasms induced by 20 mg. oral 7,12-dimethyl-benzanthracene (D.M.B.A.) 11 or by 50 mg. procarbazine (P.c.) administered at 50-55 days of age (see table).12 In these experiments, the oestrogen-NaCI pellet was implanted subcutaneously in the nuchal region 24-48 hours before oral carcinogen administration. Animals were examined weekly and all growing tumours exceeding 5 mm. were examined by biopsy; if positive for adenoma or carcinoma, the animal All non-tumour-bearing animals were was sacrificed. observed until death, when they were examined by necropsy. The superior protective action of cestriol may be partly related to its greater solubility in plasma and decreased
binding to plasma-albumin, compared to cestrone or 17 (3-aestradiol. Dehydroepiandrosterone, testosterone, 16-keto-17j3cestradiol, 2-OH-oestradiol, and 17 a-aestradiol similarly 8.
9. 10. 11. 12.
Bulbrook, R. D., Hayward, J. L., Spicer, C. C. Lancet, 1971, ii, 395. Bacigalupo, G., Schubert, K. Klin. Wschr. 1960, 38, 804. Bacigalupo, G., Schubert, K. Eur. J. Cancer, 1966, 2, 75. Lemon, H. M. Proc. Am. Ass. Cancer Res. 1972, 13, 4. Lemon, H. M. ibid. (in the press).