1021
suring sebum secretion in the rats together with preputial gland weight and prostate and seminal vesicle weights as androgen primed organs. We measured the response to cimetidine in the intact and castrate rat with and without exogenous androgen. In the intact rat there was a decrease in prostate and seminal vesicle weights but no effect on cutaneous sebaceous glands and only a slight effect on preputial gland. There was a much, smaller effect in the castrate. When given with testesterone the cimetidine showed an androgenic action. The conclusion in my report to S.K.F. (we did not publish the work) was that the simplest explanation of these puzzling results was that cimetidine was a weak androgen which showed either an androgenic or antiandrogenic effect (by competition) which varied with the target organ and ambient concentration of androgen. More work was needed to establish this and exclude other mechanisms; moreover, in view of the species and tissue differences in sebaceous gland responsethe effect of cimetidine would be worth trying on the human sebaceous
gland.
Like S.K.F. we did not take our own advice, which explains how it is we took so long to show that the human sebaceous gland is inhibited by cimetidine. Of course cimetidine is an antiandrogen-though blockade of 5-HT suggested by Burton and Lovall does not greatly appeal as a mechanism because our own evidence is that 5-HT is irrelevant to human sebaceous function-but there remain other more interesting ideas, and we are now looking at the H2 receptor itself. It is too soon to be other than tentative about therapeutic possibilities but, like Burton and Lovall, we feel that it would be sensible to try a number of therapeutic tricks, including combination with antibiotic and other inhibitors of sebum production, especially if this were done by others who have more sympathy for, and expertise with, clinical trials. Department of Dermatology, The University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
occupations selected by Vianna and Polan, Lymphoma deaths are reported in Milham’s study. For reticulum cell sarcoma, none of the PMRs for these twelve occupations are in excess (greater than 100), for lymphosarcoma only one out of the twelve is in excess, while for Hodgkin’s disease, only the fourteen
three out of the twelve are in excess. I think if Vianna and Polan were to calculate PMRs, as Milham did, or recalculate rates as suggested above, they may find that the excess in mortality from lymphomas disappears. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,
U.S.A.
PHILIP E. ENTERLINE
DIETARY VITAMIN D
SiR,-The letter by D Rees (Oct. 6, p. 754), regretting the omission from the Ministry of Agriculture, Fisheries and Food publication Food Facts of any reference to vitamin D, is unfortunate in implying a role for dietary vitamin D in maintenance of vitamin D status. Rees appears to accept that the source of vitamin D is the action of sunlight on skin but not the corollary, that dietary vitamin D contributes an unimportant amount of the total body pool of this vitamin. Intakes several times greater than those currently prevailing are required to produce a response in plasma vitamin D levels similar to that achieved by sunlight.1-4 A lack of dietary vitamin D is not a cause of rickets or osteomalacia.S Low vitamin D states do occur, but the conditions under which these cause disease to develop are unknown. Low vitamin D states arise from a number of causes: for example, lack of exposure to sunlight may be the cause in the elderly6 but this is not so in Asians.7 Dunn Nutritional Laboratory, Cambridge CB4 1XJ
D. E. M. LAWSON
SAM SHUSTER
OVARIAN FAILURE IN GALACTOSÆMIA LYMPHOMAS AND BENZENE
SIR,-Vianna and Polan! have reported an excess in deathfrom major lymphomas among men in occupations where benzene or coal tar fractions are handled. The death-rates they present were developed by relating occupational information
rates
from the U.S. decennial census to occupational information appearing on death certificates. This procedure is likely to produce erroneous results since in the U.S. the census occupation is the current or last occupation while the death certificate calls for the usual occupation. For retired persons (65 and over), relating these two items seems hopeless, and mortality data are not ordinarily reported by occupation for this age group. Where mortality at other ages has been studied, a correction of population data has-been made to convert counts of current occupation to counts of usual occupation. Data presented by Vianna and Polan relate to all ages and apparently they did not attempt any correction. The excess in death rates they report are for occupations more likely to be usual than current (or last) and thus the excess may simply be an artefact. One solution to this problem is to look simply at proportionate mortality ratios (PMRs) which are based only on occupation as defined on the death certificate. Milham2 has calculated these ratios for the State of Washington. For twelve of 5. Archibald A, Shuster S. The measurement of sebum secretion in the rat. Br J Dermatol 1970; 82: 146. 6. Shuster S, Thody AJ. The control and measurement of sebum secretion. J Invest Dermatol 1974; 62: 172-90. 1. Vianna NJ, Polan A. Lymphomas and occupational benzene exposure. Lan-
cet 1979; i: 1394-95. 2. Milham S. Occupational mortality in Washington State 1950-71: N.I.O.S.H. research report, vols I, n, and III. U.S. Government Printing
Office, 1976.
SiR,—Iread the letter by
Dr Kaufman and his colleagues 737) with considerable interest because I believe that clinicians looking after treated galactosxmic girls will be able to reinforce their clinical findings. I certainly have one such case; she is the eldest of the small number of affected girls under my care. However, the next two patients have had children of their own, and the fourth, now aged 12 years, seems to be a healthy young girl. My hunch is that galactose-1phosphate, the intermediary in galactosaemia which, however strict the diet, accumulates in body cells to some degree, interferes with the binding affinity of receptor sites for gonadotrophins.
(Oct. 6,
p.
2 18th
Century House, Oakley Park, Frilford Heath, Oxon.
Abingdon,
GEORGE KOMROWER
1. Poskitt EM, Cole T, Lawson DEM, Diet, sunlight and 25-hydroxyvitamin D in healthy children and adults. Br Med J 1979; i: 221. 2. Stamp TCB, Haddad JG, Twigg CA. Comparison of oral 25-hydroxycholecalciferol, vitamin D and ultraviolet light as determinants of circulating 25-hydroxyvitamin D. Lancet 1977; i: 1341. 3. Somerville PJ, Lien JWK, Kaye MJ. The calcium and vitamin D status in an elderly female population and their response to administered supplemental vitamin D3. Gerontology 1977; 32: 659. 4. Pietrek J, Windo J, Preece MA, O’Riordan JLH, Dunnigan MG, McIntosh WB, Ford JA. Prevention of vitamin D deficiency in Asians. Lancet 1976; i: 1145. 5. Pittet PG, Davie M, Lawson DEM, Role of nutrition in the development of osteomalacia in the elderly. Nutr Metab 1979; 23: 109. 6. Lawson DEM, Paul AA, Black AE, Cole TJ, Mandel AP, Davie M. Relative contributions of diet and sunlight to vitamin D state in the elderly. Br Med J 1979; ii: 303. 7. Dunnigan M. Asian rickets and osteomalacia in Britain. In: Child nutrition and its relation to mental and physical development. London: Kellogg Company of Great Britain Ltd: 43.
suring sebum secretion in the rats together with preputial gland weight and prostate and seminal vesicle weights as androgen primed organs. We measured the response to cimetidine in the intact and castrate rat with and without exogenous androgen. In the intact rat there was a decrease in prostate and seminal vesicle weights but no effect on cutaneous sebaceous glands and only a slight effect on preputial gland. There was a much, smaller effect in the castrate. When given with testesterone the cimetidine showed an androgenic action. The conclusion in my report to S.K.F. (we did not publish the work) was that the simplest explanation of these puzzling results was that cimetidine was a weak androgen which showed either an androgenic or antiandrogenic effect (by competition) which varied with the target organ and ambient concentration of androgen. More work was needed to establish this and exclude other mechanisms; moreover, in view of the species and tissue differences in sebaceous gland responsethe effect of cimetidine would be worth trying on the human sebaceous
gland.
Like S.K.F. we did not take our own advice, which explains how it is we took so long to show that the human sebaceous gland is inhibited by cimetidine. Of course cimetidine is an antiandrogen-though blockade of 5-HT suggested by Burton and Lovall does not greatly appeal as a mechanism because our own evidence is that 5-HT is irrelevant to human sebaceous function-but there remain other more interesting ideas, and we are now looking at the H2 receptor itself. It is too soon to be other than tentative about therapeutic possibilities but, like Burton and Lovall, we feel that it would be sensible to try a number of therapeutic tricks, including combination with antibiotic and other inhibitors of sebum production, especially if this were done by others who have more sympathy for, and expertise with, clinical trials. Department of Dermatology, The University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
occupations selected by Vianna and Polan, Lymphoma deaths are reported in Milham’s study. For reticulum cell sarcoma, none of the PMRs for these twelve occupations are in excess (greater than 100), for lymphosarcoma only one out of the twelve is in excess, while for Hodgkin’s disease, only the fourteen
three out of the twelve are in excess. I think if Vianna and Polan were to calculate PMRs, as Milham did, or recalculate rates as suggested above, they may find that the excess in mortality from lymphomas disappears. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,
U.S.A.
PHILIP E. ENTERLINE
DIETARY VITAMIN D
SiR,-The letter by D Rees (Oct. 6, p. 754), regretting the omission from the Ministry of Agriculture, Fisheries and Food publication Food Facts of any reference to vitamin D, is unfortunate in implying a role for dietary vitamin D in maintenance of vitamin D status. Rees appears to accept that the source of vitamin D is the action of sunlight on skin but not the corollary, that dietary vitamin D contributes an unimportant amount of the total body pool of this vitamin. Intakes several times greater than those currently prevailing are required to produce a response in plasma vitamin D levels similar to that achieved by sunlight.1-4 A lack of dietary vitamin D is not a cause of rickets or osteomalacia.S Low vitamin D states do occur, but the conditions under which these cause disease to develop are unknown. Low vitamin D states arise from a number of causes: for example, lack of exposure to sunlight may be the cause in the elderly6 but this is not so in Asians.7 Dunn Nutritional Laboratory, Cambridge CB4 1XJ
D. E. M. LAWSON
SAM SHUSTER
OVARIAN FAILURE IN GALACTOSÆMIA LYMPHOMAS AND BENZENE
SIR,-Vianna and Polan! have reported an excess in deathfrom major lymphomas among men in occupations where benzene or coal tar fractions are handled. The death-rates they present were developed by relating occupational information
rates
from the U.S. decennial census to occupational information appearing on death certificates. This procedure is likely to produce erroneous results since in the U.S. the census occupation is the current or last occupation while the death certificate calls for the usual occupation. For retired persons (65 and over), relating these two items seems hopeless, and mortality data are not ordinarily reported by occupation for this age group. Where mortality at other ages has been studied, a correction of population data has-been made to convert counts of current occupation to counts of usual occupation. Data presented by Vianna and Polan relate to all ages and apparently they did not attempt any correction. The excess in death rates they report are for occupations more likely to be usual than current (or last) and thus the excess may simply be an artefact. One solution to this problem is to look simply at proportionate mortality ratios (PMRs) which are based only on occupation as defined on the death certificate. Milham2 has calculated these ratios for the State of Washington. For twelve of 5. Archibald A, Shuster S. The measurement of sebum secretion in the rat. Br J Dermatol 1970; 82: 146. 6. Shuster S, Thody AJ. The control and measurement of sebum secretion. J Invest Dermatol 1974; 62: 172-90. 1. Vianna NJ, Polan A. Lymphomas and occupational benzene exposure. Lan-
cet 1979; i: 1394-95. 2. Milham S. Occupational mortality in Washington State 1950-71: N.I.O.S.H. research report, vols I, n, and III. U.S. Government Printing
Office, 1976.
SiR,—Iread the letter by
Dr Kaufman and his colleagues 737) with considerable interest because I believe that clinicians looking after treated galactosxmic girls will be able to reinforce their clinical findings. I certainly have one such case; she is the eldest of the small number of affected girls under my care. However, the next two patients have had children of their own, and the fourth, now aged 12 years, seems to be a healthy young girl. My hunch is that galactose-1phosphate, the intermediary in galactosaemia which, however strict the diet, accumulates in body cells to some degree, interferes with the binding affinity of receptor sites for gonadotrophins.
(Oct. 6,
p.
2 18th
Century House, Oakley Park, Frilford Heath, Oxon.
Abingdon,
GEORGE KOMROWER
1. Poskitt EM, Cole T, Lawson DEM, Diet, sunlight and 25-hydroxyvitamin D in healthy children and adults. Br Med J 1979; i: 221. 2. Stamp TCB, Haddad JG, Twigg CA. Comparison of oral 25-hydroxycholecalciferol, vitamin D and ultraviolet light as determinants of circulating 25-hydroxyvitamin D. Lancet 1977; i: 1341. 3. Somerville PJ, Lien JWK, Kaye MJ. The calcium and vitamin D status in an elderly female population and their response to administered supplemental vitamin D3. Gerontology 1977; 32: 659. 4. Pietrek J, Windo J, Preece MA, O’Riordan JLH, Dunnigan MG, McIntosh WB, Ford JA. Prevention of vitamin D deficiency in Asians. Lancet 1976; i: 1145. 5. Pittet PG, Davie M, Lawson DEM, Role of nutrition in the development of osteomalacia in the elderly. Nutr Metab 1979; 23: 109. 6. Lawson DEM, Paul AA, Black AE, Cole TJ, Mandel AP, Davie M. Relative contributions of diet and sunlight to vitamin D state in the elderly. Br Med J 1979; ii: 303. 7. Dunnigan M. Asian rickets and osteomalacia in Britain. In: Child nutrition and its relation to mental and physical development. London: Kellogg Company of Great Britain Ltd: 43.
