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BRAIN-COPPER CONCENTRATION IN MENKES' DISEASE
613 BRAIN-COPPER CONCENTRATION IN MENKES’ DISEASE
SIR,-Danks and his colleagueshave added very valuable information on the chemical pathology of Menkes’ disease by demonstrating a lack of copper in serum and liver. They also included figures on the copper concentration in brain in one of their patients. Unfortunately, however, no controls were referred to. To elucidate the possible role of copper deficiency in the pathogenesis of cerebral disease it is, of course, important to know whether the cerebral copper concentration is decreased
prescription pad we should help to swing our patients positive view of health so that they change their life style to include sufficient exercise. Was it Wilde who said the only thing to do with good advice is to pass it on ? But then perhaps I might be thought to have a vested interest. over to a more
31 Edwardes
We have just completed a neuropathological study on a of Menkes’ disease.2 Two formalin-fixed brain specimens were later submitted to copper analysis. One (Al) was taken from an area in the right temporal lobe with severe pathological changes, another (A2) from the border zone between the right parietal and occipital lobes with less severe changes. Two specimens from the same regions in each of two control patients of comparable age (4 and 6 months) were treated in the same way (Bl, B2, and Cl, C2). The copper concentrations were measured by atomic absorption after digestion with sulphuric acid and nitric acid.
Quadruple determinations were made in each case, and the copper content of all chemicals used in the procedure was determined and found
to
be
negligible.
The results are somewhat higher than the findings of Danks et al. but were of the same order of magnitude. No significant difference between copper concentrations in the diseased and normal brains can be demonstrated. This finding makes us somewhat hesitant to accept Danks’ view that the pathogenesis of cerebral changes can be explained as a simple lack of copper as a co-factor in the cytochrome-oxidase system of the brain. Department of Neuropathology, Aarhus Municipal Hospital, Aarhus University School of Medicine, DK-8000 Aarhus C, and EDITH RESKE-NIELSEN Department of Inorganic HANS OLAV CHRISTENSEN LOU Chemistry, PETER ANDERSEN University of Copenhagen, PER VAGN-HANSEN. Denmark.
VIGOROUS EXERCISE AND CORONARY HEART-DISEASE
SIR,- The excellent article (Feb. 17, p. 333) by Professor Morris and his colleagues is yet another pointer to the medical benefits of vigorous physical activity. I wonder whether doctors have a different standard when they readily prescribe new drugs, which are costly and whose benefit is by no means certain, and yet refrain from giving blunt advice which is free. There are now drugs which lower blood-lipid levels and may well reduce coronary heart-disease. The case is at least as good for the probable benefits of suitable exercise on coronary disease.3 Perhaps instead of reaching for the Danks, D. M., Campbell, P. E., Walker-Smith, J., Stevens, B. J., Gillespie, J. M., Blomfield, J., Turner, B. Lancet, 1972, ii, 1100. 2. Vagn-Hansen, P., Reske-Nielsen, E., Christensen Lou, H. O. Acta neuropath. (in the press). 3. Bannister, R. Br. med. J. 1972, ii, 711. 1.
ROGER BANNISTER.
CARDIOVASCULAR DISEASE IN HARD AND SOFT WATER AREAS
or not.
case
Square,
London W8.
SIR,-We should like to reply to the points raised by correspondents (Feb. 10, p. 321) on our paper (Jan. 20, p. 122). Mr Malpas has identified a major difficulty in the investigation of the relationship between local watersupplies and cardiovascular disease-that many of the towns with soft water have a " long tradition of heavy industry ". We have devoted considerable attention to this aspect since first learning of the " water story ", and the results have been published in detail.l-4 There is a considerable range of social, economic, and industrial conditions amongst the county boroughs of England and Wales with soft water and, likewise, in those having hard For example, in grading the twelve towns now water. studied being by an overall " social factor " score,3 Hull and Grimsby, which were included in our 6 hard-water towns, had scores quite similar to those of the soft-water towns in the north (Bradford, Halifax, Preston, and Salford). While there are small correlations between various socioeconomic indices and water composition, there is no indication that the explanation might lie here and that the correlations with water hardness are merely reflecting an association with a third such factor. Clarification of this situation may well come from " geographical pathology ": it should not be forgotten that the water story originated in an acute observation in Japan5 which correlated differences in cerebrovascular mortality with the acidity (softness) of the water-supplies. Our choice of towns from the extremes of the cardiovascular death-rate distribution was deliberate. Mrs. Lloyd and her colleagues have criticised the choice on the grounds that confusion may arise whether the findings are associated with variation in local water-supplies or merely with their differing death-rates. They have misunderstood the aim of our present studies. There is a 50% difference in mean death-rates from cardiovascular disease between the two groups of towns; our major concern is to investigate this difference in an attempt to assess the likelihood of a direct causal association between water components and disease. Our choice of towns was limited to those where the water-supply had not changed substantially over recent decades. The 6 soft-water towns have the characteristic high mortality-rates of such towns, and at the other end of the distribution there is no choice, since no hard-water town has an even moderately high death-rate. The study now reported is one of a series we are making in these towns to determine: (1) Whether there are any physical or behavioural differences between comparable groups of men in the towns which might indicate that they would subsequently experience the observed differences in mortality. (2) Whether there are differences in the presentation of heart-disease between the two sets of towns and, in parMorris, J. N., Crawford, M. D., Heady, J. A. Lancet, 1961, i, 860. Morris, J. N., Crawford, M. D., Heady, J. A. ibid. 1962, ii, 506. Crawford, M. D., Gardner, M. J., Morris, J. N. ibid. 1968, i, 827. Gardner, M. J., Crawford, M. D., Morris, J. N. Br. J. prev. soc. Med. 1969, 23, 133. 5. Kobayashi, J. Ber. Ohara Inst. 1957, 11, 12.
1. 2. 3. 4.
SIR,-Danks and his colleagueshave added very valuable information on the chemical pathology of Menkes’ disease by demonstrating a lack of copper in serum and liver. They also included figures on the copper concentration in brain in one of their patients. Unfortunately, however, no controls were referred to. To elucidate the possible role of copper deficiency in the pathogenesis of cerebral disease it is, of course, important to know whether the cerebral copper concentration is decreased
prescription pad we should help to swing our patients positive view of health so that they change their life style to include sufficient exercise. Was it Wilde who said the only thing to do with good advice is to pass it on ? But then perhaps I might be thought to have a vested interest. over to a more
31 Edwardes
We have just completed a neuropathological study on a of Menkes’ disease.2 Two formalin-fixed brain specimens were later submitted to copper analysis. One (Al) was taken from an area in the right temporal lobe with severe pathological changes, another (A2) from the border zone between the right parietal and occipital lobes with less severe changes. Two specimens from the same regions in each of two control patients of comparable age (4 and 6 months) were treated in the same way (Bl, B2, and Cl, C2). The copper concentrations were measured by atomic absorption after digestion with sulphuric acid and nitric acid.
Quadruple determinations were made in each case, and the copper content of all chemicals used in the procedure was determined and found
to
be
negligible.
The results are somewhat higher than the findings of Danks et al. but were of the same order of magnitude. No significant difference between copper concentrations in the diseased and normal brains can be demonstrated. This finding makes us somewhat hesitant to accept Danks’ view that the pathogenesis of cerebral changes can be explained as a simple lack of copper as a co-factor in the cytochrome-oxidase system of the brain. Department of Neuropathology, Aarhus Municipal Hospital, Aarhus University School of Medicine, DK-8000 Aarhus C, and EDITH RESKE-NIELSEN Department of Inorganic HANS OLAV CHRISTENSEN LOU Chemistry, PETER ANDERSEN University of Copenhagen, PER VAGN-HANSEN. Denmark.
VIGOROUS EXERCISE AND CORONARY HEART-DISEASE
SIR,- The excellent article (Feb. 17, p. 333) by Professor Morris and his colleagues is yet another pointer to the medical benefits of vigorous physical activity. I wonder whether doctors have a different standard when they readily prescribe new drugs, which are costly and whose benefit is by no means certain, and yet refrain from giving blunt advice which is free. There are now drugs which lower blood-lipid levels and may well reduce coronary heart-disease. The case is at least as good for the probable benefits of suitable exercise on coronary disease.3 Perhaps instead of reaching for the Danks, D. M., Campbell, P. E., Walker-Smith, J., Stevens, B. J., Gillespie, J. M., Blomfield, J., Turner, B. Lancet, 1972, ii, 1100. 2. Vagn-Hansen, P., Reske-Nielsen, E., Christensen Lou, H. O. Acta neuropath. (in the press). 3. Bannister, R. Br. med. J. 1972, ii, 711. 1.
ROGER BANNISTER.
CARDIOVASCULAR DISEASE IN HARD AND SOFT WATER AREAS
or not.
case
Square,
London W8.
SIR,-We should like to reply to the points raised by correspondents (Feb. 10, p. 321) on our paper (Jan. 20, p. 122). Mr Malpas has identified a major difficulty in the investigation of the relationship between local watersupplies and cardiovascular disease-that many of the towns with soft water have a " long tradition of heavy industry ". We have devoted considerable attention to this aspect since first learning of the " water story ", and the results have been published in detail.l-4 There is a considerable range of social, economic, and industrial conditions amongst the county boroughs of England and Wales with soft water and, likewise, in those having hard For example, in grading the twelve towns now water. studied being by an overall " social factor " score,3 Hull and Grimsby, which were included in our 6 hard-water towns, had scores quite similar to those of the soft-water towns in the north (Bradford, Halifax, Preston, and Salford). While there are small correlations between various socioeconomic indices and water composition, there is no indication that the explanation might lie here and that the correlations with water hardness are merely reflecting an association with a third such factor. Clarification of this situation may well come from " geographical pathology ": it should not be forgotten that the water story originated in an acute observation in Japan5 which correlated differences in cerebrovascular mortality with the acidity (softness) of the water-supplies. Our choice of towns from the extremes of the cardiovascular death-rate distribution was deliberate. Mrs. Lloyd and her colleagues have criticised the choice on the grounds that confusion may arise whether the findings are associated with variation in local water-supplies or merely with their differing death-rates. They have misunderstood the aim of our present studies. There is a 50% difference in mean death-rates from cardiovascular disease between the two groups of towns; our major concern is to investigate this difference in an attempt to assess the likelihood of a direct causal association between water components and disease. Our choice of towns was limited to those where the water-supply had not changed substantially over recent decades. The 6 soft-water towns have the characteristic high mortality-rates of such towns, and at the other end of the distribution there is no choice, since no hard-water town has an even moderately high death-rate. The study now reported is one of a series we are making in these towns to determine: (1) Whether there are any physical or behavioural differences between comparable groups of men in the towns which might indicate that they would subsequently experience the observed differences in mortality. (2) Whether there are differences in the presentation of heart-disease between the two sets of towns and, in parMorris, J. N., Crawford, M. D., Heady, J. A. Lancet, 1961, i, 860. Morris, J. N., Crawford, M. D., Heady, J. A. ibid. 1962, ii, 506. Crawford, M. D., Gardner, M. J., Morris, J. N. ibid. 1968, i, 827. Gardner, M. J., Crawford, M. D., Morris, J. N. Br. J. prev. soc. Med. 1969, 23, 133. 5. Kobayashi, J. Ber. Ohara Inst. 1957, 11, 12.
1. 2. 3. 4.