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RADIOACTIVE FOOD AND WATER
871 the correct diagnosis, large collections of pus could remain unrecognised and lead to death. Suppurative arthritis has been described by Mills et al.12 as a complication of steriod therapy; but only 2 of the 12 Manchester patients were receiving corticosteroid therapy at the time to
of onset. Intra-articular injection of hydrocortisone is another
potential
cause
of
suppurative arthritis,13 14 but such
infection is generally believed to be due to faulty technique.
Certainly repeated injections-and possibly systemic steroids-may predispose to the collapse of weight-bearing joints,15 16 but this is probably due to excessive movement of a diseased joint permitted by relief of pain (as in a Charcot joint) and not to infection. When careful asepsis is maintained, infection rarely complicates intra-articular injections. The outcome of acute suppurative arthritis in otherwise healthy people is today generally favourable. Poor endresults seem to be more closely related in delay in starting treatment than to any other single factor.10 17 An early diagnosis can be made only by joint aspiration, which should be undertaken as soon as the condition is suspected. Systemic administration of antibiotics effective against the particular organism usually suffices; but effusions should be repeatedly aspirated, and the opportunity can then be taken for local injection of antibiotics. Surgical drainage is rarely necessary. The joint should be immobilised in a splint until the infection has subsided, when active exercise will restore movement in a surprisingly short time.
RADIOACTIVE FOOD AND WATER
IN the investigation of man’s environment and its influence upon his health, natural radioactivity has attracted much less attention than the radioactive environment devised by man himself. Nevertheless, knowledge of natural environmental radioactivity has expanded rapidly, particularly in the direction of physical measurement of the various sources of radiation, but this progress has not been matched by parallel advances in biological observation and knowledge. Biologically, the most important natural terrestrial sources of radioactivity are the radium and thorium series. Decay by alpha-emission -in view of the high relative biological efficiency of alpha particles-is of the utmost importance when natural activity is ingested in food and water. Alpha activity in food varies tremendously : in Turner et al.’s samples," the most active food (Brazil nuts) had 20,000 times the alpha activity of the least active foods. The range extended from less than 0-1 µµC per 100 g. to 1690 I-LI-LC per 100 g. in the nuts. The same foods vary from area to area, and Marsden and Green 1B1 have demonstrated that changes in pH of the soil produced notable changes in the alpha activity of the same strain of wheat. Among the foods more regularly eaten in this country, breakfast cereals contain the most natural radioactivity, and milk products, fruit, and vegetables are low in the list. An adequate Western diet is unlikely to contain less than 5 uuC of alpha activity per day; and exotic nutty 12.
13. 14. 15. 16.
Mills, L. C., Boylston, B. F., Greene, J. A., Mayer, J. H. J. Amer. med. Ass. 1957, 164, 1310. Gowans, J. D. C., Granieri, P. A. New Engl. J. Med. 1959, 261, 502. Tondreau, R. L., Hodes, P. J., Schmidt, E. R. Amer. J. Roengenol. 1959, 82, 258. Chandler, G. N., Wright, V. Lancet, 1958, ii, 661. Sweetnam, D. R., Mason, R. M., Murray, R. O. Brit. med. J. 1960, i, 1392.
17. 18. 19.
Chartier, Y., Martin, W. J., Kelly, P. J. Ann. intern. Med. 1959, 50, 1462. Turner, R. C., Radley, J. M., Mayneord, W. V. Hlth Phys. 1958, 1, 268. Marsden, E., Green, E.
N.
Nature, Lond. 1961, 189, 326.
diets may go as high as 1000 µµC.20 No-one can yet say how many people are consuming diets of very high activity, and in view of the sparse information about tissue doses from absorbed alpha-emitters, and the very few metabolic balance studies that have been conducted, it would be easy to underestimate or even overlook the biological impact of such diets. Considering the large energy releases involved in tissue, it would be surprising if active foods had no effect at all. The natural radioactive content of drinking-waters also varies widely. Deep-well waters are fairly active (a longlived activity of about 0-6 µµC per litre, which is of the same order as the strontium-90 content observed in rivers and lakes in the first half of 1959 20); but much higher values have been recorded. Turner et al.21 examined spa waters that went as high as 48-5 µµC per litre, and some of their Cornish samples had as much long-lived alpha activity as 9-4 µµC per litre. Values for short-lived alpha activity (excess radon and daughters) may reach much greater levels (9000-10,000 µµC per litre in the water from St. Ives); but what this signifies biologically is again uncertain. The experiments which Meyer 22 described in 1929 still seem to be the best guide to the metabolism of radon and radium, and they suggest a mean time of residence in the body of the order of 1 hour for radon. Mayneord 20 remarks, in an appendix to the Medical Research Council report, that the energy deposited by the disintegration of radon with that of its daughters could be appreciable in people drinking spa or some Cornish waters. Turner et al. 21 also examined some specimens of West Devon water, and their findings accord with those of Abbatt et a1.23 Attention had been drawn to this area by Allen-Price’s suggestion 24 that there were unexpected variations in cancer incidence (such as the Registrar General’s figures have demonstrated in North Wales, particularly in Anglesey) and that a connection with water-supplies was possible. An intensive programme of further measurements (both of radioactivity and trace elements) is being conducted in West Devon, and integrated with a social survey, in an attempt to define a human population and individual exposure to radiation and to any other agents in the water. Lucas and his colleagues 25 at the Argonne National Laboratory are doing something similar in the Middle West. Certainly, the chief need for the immediate future is more information about doses received by human tissues from radioactive substances absorbed in water and food, and that involves knowing much more about what happens to these substances in all human tissues: this is primarily a question of biology and not of physics. To interpret these accumulating data it is necessary to relate them to living populations and particularly to individuals at every stage of life, and this can only be done by investigations on a wide and expensive scale. A great many small inquiries, carefully coordinated and fitted into a general overall plan, might be the most fruitful approach. Radiation is only one factor in man’s environment, and the mass of new physical details about natural radioactivity must not obscure the possible influences of other agents, such as trace elements. Indeed, the beautiful 20.
W. V. in Hazards to Man of Nuclear and Allied Radiations; A Second Report to the Medical Research Council. H.M. Stationery Office, 1960. Turner, R. C., Radley, J. M., Mayneord, W. V. Nature, Lond. 1961,189, 348. Meyer, S. Mitt. Inst. Radiumforsch. Wien. 1929, Nr. 238. Abbatt, J. D., Lakey, J. R. A., Mathias, D. J. Lancet, 1960, ii, 1272. Allen-Price, E. D. ibid. 1960, i, 1235. Lucas, H. F., Krause, D. P. Radiology, 1960, 74, 114.
Mayneord, p. 75.
21.
22. 23. 24. 25.
872
precision of physical measurements may mislead us by obscuring the present lack of balance created by deficiencies in parallel human biological and metabolic knowledge.
time of the difficult. It is too
calamity and thereafter, but this would ’::
dismiss possible unfortunate socn. of the large-scale discharge of chioc:: consequences patients, as feared by Professor Titmussl but some c the auguries are hopeful. soon to
CHILDREN OF PSYCHOTIC PARENTS
NEUROTIC and psychotic traits are believed to be inherited independently, and the study reported by Dr. Valerie Cowie to the Section of Psychiatry of the Royal Society of Medicine on April 11 was designed to measure neuroticism in the children of psychotic parents, and thus to throw a light on the environmental effect of the psychosis. Conducted at the Genetics Unit of the Institute of Psychiatry, London (later the M.R.C. Psychiatric Genetics Research Unit), the survey examined some 330 children of psychotic patients treated in the Bethlem Royal and Maudsley Hospitals and compared them with a similar number of control children of mentally healthy patients treated in general hospitals. Ages ranged from 2 to 55, and data were derived mainly from clinical interviews with the parents, but also from a special form of teacher’s report and, with older patients, a self-administered
McARDLE’S SYNDROME
IN 1951 McArdle2 described the case of a patient who had a hitherto unrecognised form of myopathy which was apparently due to a defect in muscle-glycogen breakdown, The patient’s principal complaints were of pain and stiffness in all the voluntary muscles following even moderate exertion. The symptoms had been present from early childhood, but by severely restricting his muscular activity the patient had learnt to live with his disability, A similar case was reported by Schmid and Mahler3 in 1959, but in this case the clinical manifestations became increasingly severe after adolescence; severe muscular cramps, often accompanied by transient myoglobinuria, were followed by weakness and wasting of muscles in the trunk and limbs. Biochemical investigations on specimens of muscle obtained by biopsy revealed that the glycogen Maudsley personality inventory. content of the muscle was greatly increased (though Plotting the incidence in time of neurotic symptoms glycogen could be synthesised from uridine diphosphate showed an excess during the two years after the onset of in vitro), that conversion of glycogen to lactate in the parental psychosis, and individual case-reports, too, glucose vitro was greatly reduced, and that all phosphorylase often showed a causal relationship. But the overall rating was absent. The activity of other glycogenolytic for neuroticism did not differ materially between proband activity Pearson4 has since described enzymes was normal. and control groups-a point which Dr. Cowie took to another case of the condition; the clinical history was indicate the transience of environmentally precipitated similar to that given by McArdle’s patient, in that childhood neuroses. Early onset, too, of affective disorder severe muscular pain, stiffness, and even local swelling in a parent was more harmful than such disorders of late followed moderate exertion. Graduated exercises on onset-further support for the environmental hypothesis. a treadmill revealed very poor exercise tolerance, but Of the various diagnostic groups, the small number of this could be greatly improved by continuous intravenous obsessive-compulsive parents (of either sex) produced infusion of glucose. In this case histochemical examinathe highest proportion of disturbed children-overtion of a biopsy specimen of muscle confirmed that all the dependent, faddy, and prone to tantrums, but generally muscle-fibres were loaded with glycogen and that not obsessional themselves. phosphorylases a and b were absent. Whereas each of the Regarding the age at which damage was greatest, cases hitherto reported has been sporadic, Schmid and parental psychosis when the child was under 2 seemed to Hammaker5 now describe three cases in a single sibship, produce no excess of neurotic features; and though in the and suggest that this disorder is probably genetically 3-5 group the incidence was higher, it did not reach determined and that it is due to an autosomal recessive significance. The sex of the parent mattered most with gene. They found that some symptomatic improvement schizophrenia, for while a schizophrenic father did little followed thrice-daily intramuscular injections of glycagon, damage, such mothers were associated with adverse Probably the condition, though rare, is commoner than circumstances more than any other group studied. It should be considered in all is generally realised. Perhaps the most important suggestion from this work patients complaining of generalised muscular pain and is that community care of the psychotic may be a lot less cramps following slight or moderate exercise, particularly harmful to others than one might expect-supporting, as if the symptoms date back to early childhood. Very Dr. A. A. Baker pointed out, a clinical impression many possibly some patients diagnosed as cases of myotonia had held. His unit for mothers and children had shown paradoxa6 and some with paroxysmal myoglobinuria; that even a mother in catatonic stupor or excitement could may have this syndrome, which appears to represent yet feed a baby on the breast; and discharged schizophrenics another type of glycogen-storage disease,s involving (who never, in his view, needed to be separated from their specifically the skeletal muscles. children) seemed to make rather better mothers than discharged neurotics. Mr. JULIAN TAYLOR,-consulting surgeon to Universe But Dr. Cowie and others (notably Dr. John Bowlby) College Hospital, London, and the National Hospital, Queer. pointed to some inevitable shortcomings in design: the Square, and a former professor of surgery at the Universi’.y d control group was not a random population, the age-range Khartoum, died on April 15 aged 72. of probands was very great, and the validity of much of 1. Titmuss, R. M. Address to annual meeting of National Association for Mental Health, March 10, 1961. See Lancet, March 18, 1961, p. 608. the data-particularly the retrospective data-could be 2. McArdle, B. Clin. Sci. 1951, 10, 13. questioned. Furthermore, the duration of the psychosis, 3. Schmid, R., Mahler, R. J. clin. Invest. 1959, 38, 2044. the degree of manifest disturbance, and the length of 4. Pearson, C. See Lancet, Feb. 4, 1961, p. 276. 5. Schmid, R., Hammaker, L. New Engl. J. Med. 1961, 264, 223. 6. Marshall, J. J. Neurol. Psychiat. 1952, 15, 206. contact between parent and child were not recorded. As Hed, R. Myoglobinuria in Man. Stockholm, 1955. Dr. Bowlby said, one really needs a careful study at the 7. 8. See Lancet, Jan. 28, 1961, p. 206.
! I
’ ’
of onset. Intra-articular injection of hydrocortisone is another
potential
cause
of
suppurative arthritis,13 14 but such
infection is generally believed to be due to faulty technique.
Certainly repeated injections-and possibly systemic steroids-may predispose to the collapse of weight-bearing joints,15 16 but this is probably due to excessive movement of a diseased joint permitted by relief of pain (as in a Charcot joint) and not to infection. When careful asepsis is maintained, infection rarely complicates intra-articular injections. The outcome of acute suppurative arthritis in otherwise healthy people is today generally favourable. Poor endresults seem to be more closely related in delay in starting treatment than to any other single factor.10 17 An early diagnosis can be made only by joint aspiration, which should be undertaken as soon as the condition is suspected. Systemic administration of antibiotics effective against the particular organism usually suffices; but effusions should be repeatedly aspirated, and the opportunity can then be taken for local injection of antibiotics. Surgical drainage is rarely necessary. The joint should be immobilised in a splint until the infection has subsided, when active exercise will restore movement in a surprisingly short time.
RADIOACTIVE FOOD AND WATER
IN the investigation of man’s environment and its influence upon his health, natural radioactivity has attracted much less attention than the radioactive environment devised by man himself. Nevertheless, knowledge of natural environmental radioactivity has expanded rapidly, particularly in the direction of physical measurement of the various sources of radiation, but this progress has not been matched by parallel advances in biological observation and knowledge. Biologically, the most important natural terrestrial sources of radioactivity are the radium and thorium series. Decay by alpha-emission -in view of the high relative biological efficiency of alpha particles-is of the utmost importance when natural activity is ingested in food and water. Alpha activity in food varies tremendously : in Turner et al.’s samples," the most active food (Brazil nuts) had 20,000 times the alpha activity of the least active foods. The range extended from less than 0-1 µµC per 100 g. to 1690 I-LI-LC per 100 g. in the nuts. The same foods vary from area to area, and Marsden and Green 1B1 have demonstrated that changes in pH of the soil produced notable changes in the alpha activity of the same strain of wheat. Among the foods more regularly eaten in this country, breakfast cereals contain the most natural radioactivity, and milk products, fruit, and vegetables are low in the list. An adequate Western diet is unlikely to contain less than 5 uuC of alpha activity per day; and exotic nutty 12.
13. 14. 15. 16.
Mills, L. C., Boylston, B. F., Greene, J. A., Mayer, J. H. J. Amer. med. Ass. 1957, 164, 1310. Gowans, J. D. C., Granieri, P. A. New Engl. J. Med. 1959, 261, 502. Tondreau, R. L., Hodes, P. J., Schmidt, E. R. Amer. J. Roengenol. 1959, 82, 258. Chandler, G. N., Wright, V. Lancet, 1958, ii, 661. Sweetnam, D. R., Mason, R. M., Murray, R. O. Brit. med. J. 1960, i, 1392.
17. 18. 19.
Chartier, Y., Martin, W. J., Kelly, P. J. Ann. intern. Med. 1959, 50, 1462. Turner, R. C., Radley, J. M., Mayneord, W. V. Hlth Phys. 1958, 1, 268. Marsden, E., Green, E.
N.
Nature, Lond. 1961, 189, 326.
diets may go as high as 1000 µµC.20 No-one can yet say how many people are consuming diets of very high activity, and in view of the sparse information about tissue doses from absorbed alpha-emitters, and the very few metabolic balance studies that have been conducted, it would be easy to underestimate or even overlook the biological impact of such diets. Considering the large energy releases involved in tissue, it would be surprising if active foods had no effect at all. The natural radioactive content of drinking-waters also varies widely. Deep-well waters are fairly active (a longlived activity of about 0-6 µµC per litre, which is of the same order as the strontium-90 content observed in rivers and lakes in the first half of 1959 20); but much higher values have been recorded. Turner et al.21 examined spa waters that went as high as 48-5 µµC per litre, and some of their Cornish samples had as much long-lived alpha activity as 9-4 µµC per litre. Values for short-lived alpha activity (excess radon and daughters) may reach much greater levels (9000-10,000 µµC per litre in the water from St. Ives); but what this signifies biologically is again uncertain. The experiments which Meyer 22 described in 1929 still seem to be the best guide to the metabolism of radon and radium, and they suggest a mean time of residence in the body of the order of 1 hour for radon. Mayneord 20 remarks, in an appendix to the Medical Research Council report, that the energy deposited by the disintegration of radon with that of its daughters could be appreciable in people drinking spa or some Cornish waters. Turner et al. 21 also examined some specimens of West Devon water, and their findings accord with those of Abbatt et a1.23 Attention had been drawn to this area by Allen-Price’s suggestion 24 that there were unexpected variations in cancer incidence (such as the Registrar General’s figures have demonstrated in North Wales, particularly in Anglesey) and that a connection with water-supplies was possible. An intensive programme of further measurements (both of radioactivity and trace elements) is being conducted in West Devon, and integrated with a social survey, in an attempt to define a human population and individual exposure to radiation and to any other agents in the water. Lucas and his colleagues 25 at the Argonne National Laboratory are doing something similar in the Middle West. Certainly, the chief need for the immediate future is more information about doses received by human tissues from radioactive substances absorbed in water and food, and that involves knowing much more about what happens to these substances in all human tissues: this is primarily a question of biology and not of physics. To interpret these accumulating data it is necessary to relate them to living populations and particularly to individuals at every stage of life, and this can only be done by investigations on a wide and expensive scale. A great many small inquiries, carefully coordinated and fitted into a general overall plan, might be the most fruitful approach. Radiation is only one factor in man’s environment, and the mass of new physical details about natural radioactivity must not obscure the possible influences of other agents, such as trace elements. Indeed, the beautiful 20.
W. V. in Hazards to Man of Nuclear and Allied Radiations; A Second Report to the Medical Research Council. H.M. Stationery Office, 1960. Turner, R. C., Radley, J. M., Mayneord, W. V. Nature, Lond. 1961,189, 348. Meyer, S. Mitt. Inst. Radiumforsch. Wien. 1929, Nr. 238. Abbatt, J. D., Lakey, J. R. A., Mathias, D. J. Lancet, 1960, ii, 1272. Allen-Price, E. D. ibid. 1960, i, 1235. Lucas, H. F., Krause, D. P. Radiology, 1960, 74, 114.
Mayneord, p. 75.
21.
22. 23. 24. 25.
872
precision of physical measurements may mislead us by obscuring the present lack of balance created by deficiencies in parallel human biological and metabolic knowledge.
time of the difficult. It is too
calamity and thereafter, but this would ’::
dismiss possible unfortunate socn. of the large-scale discharge of chioc:: consequences patients, as feared by Professor Titmussl but some c the auguries are hopeful. soon to
CHILDREN OF PSYCHOTIC PARENTS
NEUROTIC and psychotic traits are believed to be inherited independently, and the study reported by Dr. Valerie Cowie to the Section of Psychiatry of the Royal Society of Medicine on April 11 was designed to measure neuroticism in the children of psychotic parents, and thus to throw a light on the environmental effect of the psychosis. Conducted at the Genetics Unit of the Institute of Psychiatry, London (later the M.R.C. Psychiatric Genetics Research Unit), the survey examined some 330 children of psychotic patients treated in the Bethlem Royal and Maudsley Hospitals and compared them with a similar number of control children of mentally healthy patients treated in general hospitals. Ages ranged from 2 to 55, and data were derived mainly from clinical interviews with the parents, but also from a special form of teacher’s report and, with older patients, a self-administered
McARDLE’S SYNDROME
IN 1951 McArdle2 described the case of a patient who had a hitherto unrecognised form of myopathy which was apparently due to a defect in muscle-glycogen breakdown, The patient’s principal complaints were of pain and stiffness in all the voluntary muscles following even moderate exertion. The symptoms had been present from early childhood, but by severely restricting his muscular activity the patient had learnt to live with his disability, A similar case was reported by Schmid and Mahler3 in 1959, but in this case the clinical manifestations became increasingly severe after adolescence; severe muscular cramps, often accompanied by transient myoglobinuria, were followed by weakness and wasting of muscles in the trunk and limbs. Biochemical investigations on specimens of muscle obtained by biopsy revealed that the glycogen Maudsley personality inventory. content of the muscle was greatly increased (though Plotting the incidence in time of neurotic symptoms glycogen could be synthesised from uridine diphosphate showed an excess during the two years after the onset of in vitro), that conversion of glycogen to lactate in the parental psychosis, and individual case-reports, too, glucose vitro was greatly reduced, and that all phosphorylase often showed a causal relationship. But the overall rating was absent. The activity of other glycogenolytic for neuroticism did not differ materially between proband activity Pearson4 has since described enzymes was normal. and control groups-a point which Dr. Cowie took to another case of the condition; the clinical history was indicate the transience of environmentally precipitated similar to that given by McArdle’s patient, in that childhood neuroses. Early onset, too, of affective disorder severe muscular pain, stiffness, and even local swelling in a parent was more harmful than such disorders of late followed moderate exertion. Graduated exercises on onset-further support for the environmental hypothesis. a treadmill revealed very poor exercise tolerance, but Of the various diagnostic groups, the small number of this could be greatly improved by continuous intravenous obsessive-compulsive parents (of either sex) produced infusion of glucose. In this case histochemical examinathe highest proportion of disturbed children-overtion of a biopsy specimen of muscle confirmed that all the dependent, faddy, and prone to tantrums, but generally muscle-fibres were loaded with glycogen and that not obsessional themselves. phosphorylases a and b were absent. Whereas each of the Regarding the age at which damage was greatest, cases hitherto reported has been sporadic, Schmid and parental psychosis when the child was under 2 seemed to Hammaker5 now describe three cases in a single sibship, produce no excess of neurotic features; and though in the and suggest that this disorder is probably genetically 3-5 group the incidence was higher, it did not reach determined and that it is due to an autosomal recessive significance. The sex of the parent mattered most with gene. They found that some symptomatic improvement schizophrenia, for while a schizophrenic father did little followed thrice-daily intramuscular injections of glycagon, damage, such mothers were associated with adverse Probably the condition, though rare, is commoner than circumstances more than any other group studied. It should be considered in all is generally realised. Perhaps the most important suggestion from this work patients complaining of generalised muscular pain and is that community care of the psychotic may be a lot less cramps following slight or moderate exercise, particularly harmful to others than one might expect-supporting, as if the symptoms date back to early childhood. Very Dr. A. A. Baker pointed out, a clinical impression many possibly some patients diagnosed as cases of myotonia had held. His unit for mothers and children had shown paradoxa6 and some with paroxysmal myoglobinuria; that even a mother in catatonic stupor or excitement could may have this syndrome, which appears to represent yet feed a baby on the breast; and discharged schizophrenics another type of glycogen-storage disease,s involving (who never, in his view, needed to be separated from their specifically the skeletal muscles. children) seemed to make rather better mothers than discharged neurotics. Mr. JULIAN TAYLOR,-consulting surgeon to Universe But Dr. Cowie and others (notably Dr. John Bowlby) College Hospital, London, and the National Hospital, Queer. pointed to some inevitable shortcomings in design: the Square, and a former professor of surgery at the Universi’.y d control group was not a random population, the age-range Khartoum, died on April 15 aged 72. of probands was very great, and the validity of much of 1. Titmuss, R. M. Address to annual meeting of National Association for Mental Health, March 10, 1961. See Lancet, March 18, 1961, p. 608. the data-particularly the retrospective data-could be 2. McArdle, B. Clin. Sci. 1951, 10, 13. questioned. Furthermore, the duration of the psychosis, 3. Schmid, R., Mahler, R. J. clin. Invest. 1959, 38, 2044. the degree of manifest disturbance, and the length of 4. Pearson, C. See Lancet, Feb. 4, 1961, p. 276. 5. Schmid, R., Hammaker, L. New Engl. J. Med. 1961, 264, 223. 6. Marshall, J. J. Neurol. Psychiat. 1952, 15, 206. contact between parent and child were not recorded. As Hed, R. Myoglobinuria in Man. Stockholm, 1955. Dr. Bowlby said, one really needs a careful study at the 7. 8. See Lancet, Jan. 28, 1961, p. 206.
! I
’ ’