- Email: [email protected]
The Water Story
1012
The Water
Story
farction. This is, as they concede, pure speculation, but a similar suggestion arose from a pathological a softinquiry in the U.K. in which cardiac lesions in 9 water and a hard-water area were compared.9 It was found that men who had died suddenly from ischaemic heart-disease in the soft-water area had less extensive coronary atheroma and lower scores for lumen stenosis, age for age, than those who had died suddenly in the hard-water area. This seemed to indicate a causal factor affecting the myocardium over and above those involved in the arterial disease, and it was suggested that there was an increased susceptibility of the myocardium in the soft-water area. These suggestions focus attention on how little is known about the relative importance of the various factors or " causes " of these sudden deaths. Sudden " deaths (differently defined according to the data being analysed) at present constitute the major part of the problem of ischaemic heart-disease. We do not know, for example, what proportions are in fact due to arrhythmias, have limited coronary-artery disease, or "
Kobyashi, J. Ber. Ohara Inst. land. Forsch. 1957, 11, 12. Schroeder, H. A. J. Am. med. Ass. 1960, 172, 1902. Schroeder, H. A. J. chron. Dis. 1960, 12, 586. Morris, J. N., Crawford, M. D., Heady, J. A. Lancet, 1961, i, 860. Crawford, M. D., Gardner, M. J., Morris, J. N. ibid. 1968, i, 827. Biorck, G., Bostrom, H., Widstrom, A. Acta med. scand. 1965, 178, 239. Mulahy, R. Lancet, 1968, i, 975. Anderson, T. W., Le Riche, W. H., MacKay, J. S. New Engl. J. Med. 1969, 280, 805. 9. Crawford, T., Crawford, M. D. Lancet, 1967, i, 229.
1. 2. 3. 4. 5. 6. 7. 8.
CRAWFORD 10 found fewer occluded and less recent thrombosis in 100 men arteries coronary who had died suddenly from ischaemic heart-disease (coroner’s cases) than in 100 men who had died of ischaemic heart-disease after varying periods in hospital. Epidemiologically, some of the known risk factors in is chaemic heart-disease (for example, physical inactivity 11 and smoking 12) are more closely associated with the sudden deaths than with the other forms of presentation of ischsemic heart-disease. A W.H.O. working party is exploring the possibility of establishing registers of ischxmic heart-disease by notification and surveillance, and it is hoped to gain more information about these deaths. If it is confirmed that the association between ischaemic heart-disease and water hardness is due entirely to the " sudden " deaths, the possible importance of water minerals in the mechanism must be considered. It is important to emphasise, however, that the water factor is associated with all cardiovascular disease, including cerebrovascular disease, and not with ischaemic heart-disease only; hypertension could be the are
AN association between cardiovascular mortality and indices of water hardness is now well established: the softer, or more acid, the drinking-water the higher the death-rate. This association has been found in several very different countries-Japan, 1 U.S.A.,23 U.K.,45 Sweden, Ireland 7-and although different components of cardiovascular mortality seem to be more closely involved in some of these countries than in others disease in Japan and (for example, cerebrovascular " " in myocardial degeneration Sweden), the similarity of the findings in the two largest studies (in the U.S.A. and in the U.K.) is remarkable. In these countries all main groups-cerebrovascular disease, coronary heart-disease, and " other " heart-disease-showed highly significant correlations with water hardness. Recently the existence of this " water factor " has been demonstrated in yet another area; ANDERSON et al.8 have shown that, in Ontario, the standardised deathrates for ischaemic heart-disease (I.C.D. 420) for men and women aged 35-74, based on the deaths in 1967, decline from 416 per 100,000 in soft-water areas to 365 per 100,000 in hard-water areas, while death-rates from " other " disease show no such trend. Further, when the deaths were divided into " sudden " and " non-sudden " (on the basis of whether or not the death certificate was signed by a coroner) the higher death-rate in the soft-water area was found to be due entirely to an excess of " sudden " deaths. ANDERSON et al. postulate that the higher deathrate in the soft-water area might be the result of increased susceptibility to the fatal cardiac arrhythmias which may arise in the first few hours after myocardial in-
hypertensive.
factor. Interest is increasing in the possibility that trace elements may be concerned in cardiovascular disease. On present evidence, cadmium and lead are the two most likely to be incriminated. As SCHROEDER 13 has shown, cadmium causes hypertension in animals, it accumulates in the human kidney with age, and higher concentrations are found in hypertensive kidneys. Cadmium is usually present as an impurity with zinc and could contaminate drinking-water from galvanised pipes; however, its concentration in drinking-water was recently found to be well below conventional safety limits in the U.S.A.14 and the U.K.5 Evidence has lately been presented that lead may still be being picked up from pipes in some soft-water areas in the U.K.15; and plumbosolvency has certainly been a problem in the past. The lead content of bones was found to be greater in people who had died in a soft-water area than in a hard-water area.16 Trace elements in post-mortem tissue from soft-water and hard-water areas need further common
investigation. The possible importance of the bulk elements in drinking-water-calcium, magnesium, and sodium-9
also be examined. CRAWFORD and CRAWFORD found that tissue levels of calcium and magnesium were lower in a soft-water area than a hard-water area, and work in the U.S.A. has shown that serum levels of calcium and magnesium were significantly lower in men in a soft-water town than in a similar group in a hard-water town.17 These findings have to be confirmed and extended to see whether the-differences are reflected in the ionised fraction of serum calcium and magnesium. must
10. 11. 12.
Crawford, T., Crawford, M. D. Evolution of the Atheromatous Plaque; p. 279. Chicago, 1964. Morris, J. N. Uses of Epidemiology. Edinburgh, 1967. U.S. Public Health Service. Framingham Heart Study. U.S. Public Service Publications no. 1515, 1966.
13. 14. 15. 16. 17.
Schroeder, H. A. J. chron. Dis. 1965, 18, 647. Schroeder, H. A. J. Am. med. Ass. 1966, 195, 81. Crawford, M. D., Morris, J. N. Lancet, 1967, ii, 1087. Crawford, M. D., Crawford, T. ibid. 1969, i, 699. Bierenbaum, M. L., Fleischman, A. I., Dunn, J. P., Belk, H. D., Storter, B. M. Proceedings of Asian-Pacific Congress of Cardiology, 1968.
1013
of calcium has been largely but there are indications that the difference in intake due to the water contribution may be sizeable 18 19; if absorption factors are taken into account it may be even more important. Ideas concerning calcium homoeostasis are changing 20: it is no longer thought to depend on bone as a depot but to be much more a matter of absorption and excretion, with the kidneys playing a major role.21 Water calcium, being mainly in ionised form, may be of special importance. There are many questions here which need ad-hoc investigation. Clearly, the elucidation of the whole " water story " is important because of the large number of deaths concerned and because clues may be found to the pathogenesis of some aspects of cardiovascular disease in general.
Drinking-water as a ignored in the past
source
18. Widdowson, E. M. Br. med. Bull. 1944, 10, 219. 19. Report of the Government Chemist. H.M. Stationery Office, 1963. 20. see Lancet, 1968, ii, 1379. 21. Peacock, M., Robertson, W. G., Nordin, B. E. C. Lancet, Feb. 22, 1969,
p. 384.
Annotations MORE EFFECTS OF CIGARETTES
publicised dangers of smoking are bronchial chronic bronchitis and cardiovascular disease. carcinoma, There are many other possibilities, however, which are receiving increasing attention. The habituating effects of nicotineare associated with its actions on the central nervous system; and, though much is known about these effects in animals, comparatively little is known about the central action of nicotine in man. Evidence has come to light, however, which indicates that these effects are strong and could be important. Webster2 reported that cigarette smoking caused a dramatic but transient reduction in skeletal muscle tone in spastic patients. Domino and von Baumgarten3 have now examined the effects on the patella reflex of 115 young men of smoking cigarettes of differing nicotine content. The reflex was elicited automatically by a reflex hammer attached to a solenoid and recorded by a strain-gauge transducer and electromyogram of the ipsilateral quadriceps femoris muscle. Negligible depression of the reflex was produced by smoking a nicotine-free lettuce cigarette. A low-nicotine tobacco cigarette produced approximately 45% depression within five minutes and a high-nicotine cigarette 67% depression. A second cigarette smoked 25 minutes after the first produced a similar depression. No significant differences were found between smokers and non-smokers. No conclusions could be drawn concerning the site of action of nicotine in producing patella-reflex depression, but these observations are of importance from many aspects; for example, patella responses during clinical examinations may be influenced by a recently smoked cigarette. The implications as far as motor function in general is concerned must also be considered. Welch et al. describe placentas obtained after childbirth from 17 non-smoking and 17 smoking women. They measured the activity of enzymes which hydroxyTHE best
late
3, 4 benzpyrene and N-demethylate 3-methyl-4-
monomethylamino-azobenzene. No activity was detected in the placentas from non-smoking women, but these enzymes were detected in varying concentrations in placentas from smokers. Welch et al. conclude that the induction of these enzymes is probably caused by systemic absorption of polycyclic hydrocarbons in cigarette smoke and by their transport to the placenta. Once again, the implications of this work are many and important. The effects of cigarette smoking on enzyme induction not only in the placenta but also in other organs will require further study. We must also inquire whether carcinogenic polycyclic hydrocarbons can pass from the placenta into the human fetus, and, if so, what action they may have.
OVERSEAS MEDICAL STUDENTS IN BRITAIN
STATISTICIANS of higher education have lately adopted definition for "overseas student". As a result about 1 student in every 10 under the old system no longer counts as overseas. The latest (new definition) figures issued by the Association of Commonwealth Universities1 show that at the beginning of the academic year 1967-68, 16,045 men and women from overseas were enrolled for full-time study or research in British universities. 1727 were studying medicine, dentistry, or other subjects directly related to health. 1085 were studying medicine, 740 at the postgraduate level. Of 525 part-time students in the medicine, dentistry, and health category, all but 26 were doing postgraduate work. a new
AN ABC OF MEDICAL GENETICS
About 2% of all liveborn children carry a chromosome abnormality or mutant gene which significantly affects their health. As more and more diseases caused by infection and other environmental influences are being brought under control, so are genetically determined disorders becoming relatively more prominent. The apparent paradox of the maintenance of both human diversity and family likeness in successive generations has intrigued men for centuries; for the medical practitioner, however, human heredity is no longer a matter for idle speculation. On p. 1014 this week, Dr. C. 0. Carter begins a series of seven articles in which he will examine the mechanical, chemical, and arithmetical
bases of inheritance in man, the way in which successful treatment of some inherited conditions is changing the frequency of mutant genes in the population, and the objectives of genetic counselling and the assessment of risk. The seven articles, together with some additional material, will be published as a book later this year.
HARDLY AN EXPERIMENT
Having reached this
page,
inquiring readers
may
begin
to wonder whether The Lancet is conducting a small experiment with new type faces. That is not so. These words were set in type in Worcester, Massachusetts, where we will continue to produce the journal (though, inevitably, it
will be smaller than usual) until normal work sumed at our printers in Watford, England.
can
be
re-
1. See
Lancet, 1968, i, 579. Webster, D. D. Clin. Pharmac. Ther. 1964, 5, 900. 3. Domino, E. F., von Baumgarten, A. M. ibid. 1969, 10, 72. 4. Welch, R. M. et al. ibid. p. 100. 2.
1. Students from Other Countries in Universities in Britain
Obtainable from the Association of 36 Gordon Square, London W.C.1.
Commonwealth
1967-68.
Universities,
The Water
Story
farction. This is, as they concede, pure speculation, but a similar suggestion arose from a pathological a softinquiry in the U.K. in which cardiac lesions in 9 water and a hard-water area were compared.9 It was found that men who had died suddenly from ischaemic heart-disease in the soft-water area had less extensive coronary atheroma and lower scores for lumen stenosis, age for age, than those who had died suddenly in the hard-water area. This seemed to indicate a causal factor affecting the myocardium over and above those involved in the arterial disease, and it was suggested that there was an increased susceptibility of the myocardium in the soft-water area. These suggestions focus attention on how little is known about the relative importance of the various factors or " causes " of these sudden deaths. Sudden " deaths (differently defined according to the data being analysed) at present constitute the major part of the problem of ischaemic heart-disease. We do not know, for example, what proportions are in fact due to arrhythmias, have limited coronary-artery disease, or "
Kobyashi, J. Ber. Ohara Inst. land. Forsch. 1957, 11, 12. Schroeder, H. A. J. Am. med. Ass. 1960, 172, 1902. Schroeder, H. A. J. chron. Dis. 1960, 12, 586. Morris, J. N., Crawford, M. D., Heady, J. A. Lancet, 1961, i, 860. Crawford, M. D., Gardner, M. J., Morris, J. N. ibid. 1968, i, 827. Biorck, G., Bostrom, H., Widstrom, A. Acta med. scand. 1965, 178, 239. Mulahy, R. Lancet, 1968, i, 975. Anderson, T. W., Le Riche, W. H., MacKay, J. S. New Engl. J. Med. 1969, 280, 805. 9. Crawford, T., Crawford, M. D. Lancet, 1967, i, 229.
1. 2. 3. 4. 5. 6. 7. 8.
CRAWFORD 10 found fewer occluded and less recent thrombosis in 100 men arteries coronary who had died suddenly from ischaemic heart-disease (coroner’s cases) than in 100 men who had died of ischaemic heart-disease after varying periods in hospital. Epidemiologically, some of the known risk factors in is chaemic heart-disease (for example, physical inactivity 11 and smoking 12) are more closely associated with the sudden deaths than with the other forms of presentation of ischsemic heart-disease. A W.H.O. working party is exploring the possibility of establishing registers of ischxmic heart-disease by notification and surveillance, and it is hoped to gain more information about these deaths. If it is confirmed that the association between ischaemic heart-disease and water hardness is due entirely to the " sudden " deaths, the possible importance of water minerals in the mechanism must be considered. It is important to emphasise, however, that the water factor is associated with all cardiovascular disease, including cerebrovascular disease, and not with ischaemic heart-disease only; hypertension could be the are
AN association between cardiovascular mortality and indices of water hardness is now well established: the softer, or more acid, the drinking-water the higher the death-rate. This association has been found in several very different countries-Japan, 1 U.S.A.,23 U.K.,45 Sweden, Ireland 7-and although different components of cardiovascular mortality seem to be more closely involved in some of these countries than in others disease in Japan and (for example, cerebrovascular " " in myocardial degeneration Sweden), the similarity of the findings in the two largest studies (in the U.S.A. and in the U.K.) is remarkable. In these countries all main groups-cerebrovascular disease, coronary heart-disease, and " other " heart-disease-showed highly significant correlations with water hardness. Recently the existence of this " water factor " has been demonstrated in yet another area; ANDERSON et al.8 have shown that, in Ontario, the standardised deathrates for ischaemic heart-disease (I.C.D. 420) for men and women aged 35-74, based on the deaths in 1967, decline from 416 per 100,000 in soft-water areas to 365 per 100,000 in hard-water areas, while death-rates from " other " disease show no such trend. Further, when the deaths were divided into " sudden " and " non-sudden " (on the basis of whether or not the death certificate was signed by a coroner) the higher death-rate in the soft-water area was found to be due entirely to an excess of " sudden " deaths. ANDERSON et al. postulate that the higher deathrate in the soft-water area might be the result of increased susceptibility to the fatal cardiac arrhythmias which may arise in the first few hours after myocardial in-
hypertensive.
factor. Interest is increasing in the possibility that trace elements may be concerned in cardiovascular disease. On present evidence, cadmium and lead are the two most likely to be incriminated. As SCHROEDER 13 has shown, cadmium causes hypertension in animals, it accumulates in the human kidney with age, and higher concentrations are found in hypertensive kidneys. Cadmium is usually present as an impurity with zinc and could contaminate drinking-water from galvanised pipes; however, its concentration in drinking-water was recently found to be well below conventional safety limits in the U.S.A.14 and the U.K.5 Evidence has lately been presented that lead may still be being picked up from pipes in some soft-water areas in the U.K.15; and plumbosolvency has certainly been a problem in the past. The lead content of bones was found to be greater in people who had died in a soft-water area than in a hard-water area.16 Trace elements in post-mortem tissue from soft-water and hard-water areas need further common
investigation. The possible importance of the bulk elements in drinking-water-calcium, magnesium, and sodium-9
also be examined. CRAWFORD and CRAWFORD found that tissue levels of calcium and magnesium were lower in a soft-water area than a hard-water area, and work in the U.S.A. has shown that serum levels of calcium and magnesium were significantly lower in men in a soft-water town than in a similar group in a hard-water town.17 These findings have to be confirmed and extended to see whether the-differences are reflected in the ionised fraction of serum calcium and magnesium. must
10. 11. 12.
Crawford, T., Crawford, M. D. Evolution of the Atheromatous Plaque; p. 279. Chicago, 1964. Morris, J. N. Uses of Epidemiology. Edinburgh, 1967. U.S. Public Health Service. Framingham Heart Study. U.S. Public Service Publications no. 1515, 1966.
13. 14. 15. 16. 17.
Schroeder, H. A. J. chron. Dis. 1965, 18, 647. Schroeder, H. A. J. Am. med. Ass. 1966, 195, 81. Crawford, M. D., Morris, J. N. Lancet, 1967, ii, 1087. Crawford, M. D., Crawford, T. ibid. 1969, i, 699. Bierenbaum, M. L., Fleischman, A. I., Dunn, J. P., Belk, H. D., Storter, B. M. Proceedings of Asian-Pacific Congress of Cardiology, 1968.
1013
of calcium has been largely but there are indications that the difference in intake due to the water contribution may be sizeable 18 19; if absorption factors are taken into account it may be even more important. Ideas concerning calcium homoeostasis are changing 20: it is no longer thought to depend on bone as a depot but to be much more a matter of absorption and excretion, with the kidneys playing a major role.21 Water calcium, being mainly in ionised form, may be of special importance. There are many questions here which need ad-hoc investigation. Clearly, the elucidation of the whole " water story " is important because of the large number of deaths concerned and because clues may be found to the pathogenesis of some aspects of cardiovascular disease in general.
Drinking-water as a ignored in the past
source
18. Widdowson, E. M. Br. med. Bull. 1944, 10, 219. 19. Report of the Government Chemist. H.M. Stationery Office, 1963. 20. see Lancet, 1968, ii, 1379. 21. Peacock, M., Robertson, W. G., Nordin, B. E. C. Lancet, Feb. 22, 1969,
p. 384.
Annotations MORE EFFECTS OF CIGARETTES
publicised dangers of smoking are bronchial chronic bronchitis and cardiovascular disease. carcinoma, There are many other possibilities, however, which are receiving increasing attention. The habituating effects of nicotineare associated with its actions on the central nervous system; and, though much is known about these effects in animals, comparatively little is known about the central action of nicotine in man. Evidence has come to light, however, which indicates that these effects are strong and could be important. Webster2 reported that cigarette smoking caused a dramatic but transient reduction in skeletal muscle tone in spastic patients. Domino and von Baumgarten3 have now examined the effects on the patella reflex of 115 young men of smoking cigarettes of differing nicotine content. The reflex was elicited automatically by a reflex hammer attached to a solenoid and recorded by a strain-gauge transducer and electromyogram of the ipsilateral quadriceps femoris muscle. Negligible depression of the reflex was produced by smoking a nicotine-free lettuce cigarette. A low-nicotine tobacco cigarette produced approximately 45% depression within five minutes and a high-nicotine cigarette 67% depression. A second cigarette smoked 25 minutes after the first produced a similar depression. No significant differences were found between smokers and non-smokers. No conclusions could be drawn concerning the site of action of nicotine in producing patella-reflex depression, but these observations are of importance from many aspects; for example, patella responses during clinical examinations may be influenced by a recently smoked cigarette. The implications as far as motor function in general is concerned must also be considered. Welch et al. describe placentas obtained after childbirth from 17 non-smoking and 17 smoking women. They measured the activity of enzymes which hydroxyTHE best
late
3, 4 benzpyrene and N-demethylate 3-methyl-4-
monomethylamino-azobenzene. No activity was detected in the placentas from non-smoking women, but these enzymes were detected in varying concentrations in placentas from smokers. Welch et al. conclude that the induction of these enzymes is probably caused by systemic absorption of polycyclic hydrocarbons in cigarette smoke and by their transport to the placenta. Once again, the implications of this work are many and important. The effects of cigarette smoking on enzyme induction not only in the placenta but also in other organs will require further study. We must also inquire whether carcinogenic polycyclic hydrocarbons can pass from the placenta into the human fetus, and, if so, what action they may have.
OVERSEAS MEDICAL STUDENTS IN BRITAIN
STATISTICIANS of higher education have lately adopted definition for "overseas student". As a result about 1 student in every 10 under the old system no longer counts as overseas. The latest (new definition) figures issued by the Association of Commonwealth Universities1 show that at the beginning of the academic year 1967-68, 16,045 men and women from overseas were enrolled for full-time study or research in British universities. 1727 were studying medicine, dentistry, or other subjects directly related to health. 1085 were studying medicine, 740 at the postgraduate level. Of 525 part-time students in the medicine, dentistry, and health category, all but 26 were doing postgraduate work. a new
AN ABC OF MEDICAL GENETICS
About 2% of all liveborn children carry a chromosome abnormality or mutant gene which significantly affects their health. As more and more diseases caused by infection and other environmental influences are being brought under control, so are genetically determined disorders becoming relatively more prominent. The apparent paradox of the maintenance of both human diversity and family likeness in successive generations has intrigued men for centuries; for the medical practitioner, however, human heredity is no longer a matter for idle speculation. On p. 1014 this week, Dr. C. 0. Carter begins a series of seven articles in which he will examine the mechanical, chemical, and arithmetical
bases of inheritance in man, the way in which successful treatment of some inherited conditions is changing the frequency of mutant genes in the population, and the objectives of genetic counselling and the assessment of risk. The seven articles, together with some additional material, will be published as a book later this year.
HARDLY AN EXPERIMENT
Having reached this
page,
inquiring readers
may
begin
to wonder whether The Lancet is conducting a small experiment with new type faces. That is not so. These words were set in type in Worcester, Massachusetts, where we will continue to produce the journal (though, inevitably, it
will be smaller than usual) until normal work sumed at our printers in Watford, England.
can
be
re-
1. See
Lancet, 1968, i, 579. Webster, D. D. Clin. Pharmac. Ther. 1964, 5, 900. 3. Domino, E. F., von Baumgarten, A. M. ibid. 1969, 10, 72. 4. Welch, R. M. et al. ibid. p. 100. 2.
1. Students from Other Countries in Universities in Britain
Obtainable from the Association of 36 Gordon Square, London W.C.1.
Commonwealth
1967-68.
Universities,