- Email: [email protected]
A BIOLOGICAL BAROMETER
351
disturbance, and unless secondary bacterial infection ensues these disappear completely within a few weeks. Cowpox is now a rare disease, largely owing to the higher
nancy. In the latter case, serial cultivation may be carried through many generations with the, virus still present in the cultures,’ although cell growth may be less vigorous,
standards of modern dairy farming, but it may appear out of the blue ". Some epidemics have been traced to a milker who has acquired his infection in his previous
than in cultures of normal embryonic lungs.8 9 It is possible that rubella virus produces its teratogenic effect by acting upon the genetic apparatus of cells. The virus certainly produces chromosome breaks in some human embryo cells in’vitro. Is there any evidence that it also produces chromosome damage in vivo? First reports failed to show any clear chromosome effects in cultured leucocytes from infants born with congenital rubella 10 or in cultures from-tissues removed by surgical termination of pregnancy.:> - but more positive findings were later reported.9 11’Ì2 These findings are interesting, but they leave many questions unanswered. A number of viruses have been reported to produce chromosome breaks in leucocytes cultured from patients with virus infections, and the addition of rubella virus to this list is not remarkable in itself. Evidence of chromosome damage in cultures prepared directly from naturally infected embryos is more convincing, but here there is the problem that severely damaged cells may fail to undergo even a single cycle of cell division on cultivation in vitro. There is the further complication that chromosome breaks are not uncommonly found in spontaneous abortions not associated with rubella, so that it is not easy to know what should be taken as a normal baseline. The long-term persistence of rubella virus in human embryonic cells raises important questions about the eventual fate of a virus in the descendants of these cells. Is the infectivity of rubella virus lost for ever when attempts to recover the virus in post-natal life fail, or could it be reactivated by some later event in vivo or in response to some manipulation of cultured cells in vitro ? Rubella virus is probably the most important infectious agent producing a teratogenic effect in man, but it is almost certainly not alone in this respect.
"
employment. Pseudo-cowpox is commoner both in cows and man, but many human infections are too slight to be seen by a doctor. A recent account of a small epidemic in an enclosed community of nuns illustrates some of the usual features.3 Most of the 32 cows in milk belonging to the sisterhood had papular lesions on the udders. The dry cows were unaffected. The permanent herdswoman was not infected, but in all the 5 nuns being taught the art of milking small painless lumps developed on the fingers. None of them was ill, and all the lesions healed uneventfully except for one which became secondarily infected. It is common experience that pseudo-cowpox is limited to those who are fresh to milking, so it is a reasonable guess that one attack gives some immunity. Those who have seen the two diseases in man will not usually find the distinction difficult, and diagnosis can be confirmed simply and quickly by examination of the virus in the overlying scab under an electron microscope. The farmer may know both diseases by the same name but ought to be able to differentiate the mild eruption which spreads through his herd slowly from the more infectious variolar vaccinx veras which run through his herd like lightning and make a large hole in the milk
cheque.
CHROMOSOMES IN CONGENITAL RUBELLA
RUBELLA virus readily parasitises the developing human embryo, in some cases causing intrauterine death and abortion and in others producing cataract, deafness, heart-disease, and mental retardation in the newborn infant. Sometimes, however, the infection is confined to the placenta, and the infant is normal. Virus-isolation studies in pregnancies terminated by surgery suggest that the infection may die out in some pregnancies, whereas in others, virus can be recovered from many tissues and organs at birth and for several months thereafter.45 What determines the outcome in any particular pregnancy is still largely unknown. Embryonic age at the time of infection is clearly one factor, but there must be many others. Investigations in human embryonic cells cultivated in vitro are easier to control than in-vivo studies, and they may throw some light upon the problem. Rubella virus produces no clear cytopathic effect on normal human embryonic cells, but virus-infected culFibrotures behave differently from normal cultures. blasts from normal lungs or pituitary fail to grow when subcultivated after infection with rubella virus, whereas cells from normal embryonic skin and pharyngeal mucosa, when infected, continue to grow well after many serial subcultivations but remain infected with virus and show a high proportion of chromosome breaks. Clearly the cell type is important. Normal embryonic lung cells infected in vitro seem to behave differently from lung cells infected in vivo and cultured after surgical termination of preg3. 4. 5.
Neale, E. J. E., Calvert, H. T. Br. J. Derm. 1967, 79, 318. Monif, G., Avery, S. B., Korones, S. B., Sever, J. L. Lancet, 1965, i, 723. Sever, J. L. in Advances in Teratology (edited by D. H. M. Woollam); vol. II, p. 127. London, 1967. 6. Plotkin, S. A., Boué, A., Boué, J. G. Am. J. Epidemiol. 1965, 81, 71.
-
A BIOLOGICAL BAROMETER
FOR millions of children malnutrition means a poor in life, and for some it means death. With a health problem of this magnitude there is need for a cheap, easy, and accurate method of assessing nutritional status in large population surveys. The late Dr. B. T. Squires, of Bulawayo, devised a simple test 13 which seems to fit the bill. In 1963 14 he described characteristic changes in the appearance of cells from the buccal mucosa (due apparently to increased keratinisation) in malnourished children and in young animals kept on a low-proteincalorie diet, and after experimenting with various staining methods he found one that gave a reliable indication of keratinisation. The stain he used was acid-fuchsin with light-green (fall),15 which, unexpectedly, produces a bluestart
7. 8. 9.
10. 11. 12.
13. 14. 15.
Kay, H. E. M., Peppercorn, M. E., Porterfield, J. S., McCarthy, K., Taylor-Robinson, C. H. Br. med. J. 1964, ii, 166. Rawls, W. E., Melnick, J. L. J. exp. Med. 1966, 123, 795. Chang, T. H., Moorhead, P. S., Boué, J. G., Plotkin, S. A., Hoskins, J. M. Proc. Soc. exp. Biol. Med. 1966, 122, 236. Mellman, W. J., Plotkin, S. A., Moorhead, P. S., Hartnett, E. M. Am. J. Dis. Child. 1965, 110, 473. Nusbacher, J., Hirschhorn, K., Cooper, L. Z. New Engl. J. Med. 1967, 276, 1409. Kuroki, Y., Makino, S., Aya, T., Nagayama, T. Jap. J. hum. Genet. 1966, 11, 17. Squires, B. T. Cent. Afr. J. Med. 1966, 12, 223. Squires, B. T. Br. J. Nutr. 1963, 17, 303. MacConail, M. A., Gurr, E. Ir. J. med. Sci. April, 1960, p. 182.
352 mauve-red range in the stained tissue, young non-cornified cells staining blue or violet, older cornified cells becoming red or mauve. Buccal smears from healthy puppies and piglets showed a high proportion (70-90%) of blue cells, and the number fell sharply (to less than 40%) within a few days of changing to a protein-calorie-deficient diet. These results were confirmed in healthy and malnourished children, but hopes that the test might be used as a specific indicator of nutritional status proved overoptimistic, for mild infections, such as the common cold, can reduce the blue-cell count to about 30%, in two or three days, and serious infections like rheumatic carditis and trypanosomiasis can depress it to around 10%. Nevertheless, it is useful in screening for excluding healthy children before more detailed investigations. For a precise result at least 500 cells should be counted, but this is seldom needed for screening purposes-a predominant blue or red colour can easily be seen by holding the slide up to the light, and only in the mauve overlap range (40-60% blue or violet cells, any count below 50% being regarded as abnormal) is a count needed.
Despite its shortcomings, this test is a useful barometer of health, and it has the added advantage that the patient’s cooperation is not essential-even the most unwilling child will open his mouth sooner or later, if only to cry.
CARE IN TERMINAL CANCER
catalogue of virtues that society expects from its doctors, none is more demanding of their spirit and humanity than the care of their patients in the terminal stages of cancer. At a symposiumheld early this year at the Royal College of Surgeons of England, Dr. Cicely Saunders, with the background of her experience at St. Joseph’s Hospice, spoke with wisdom and compassion on this aspect of treatment. We must emphasise treatment "; for all too readily, when every resource of active treatment has been exhausted and when our impotence to influence events becomes increasingly distressful and embarrassing, the temptation to tiptoe away from the patient may be strong. " It seems so strange, no one seemed to want to look at me," said one woman. We do not realise how much we can do simply by going to see the patient. " The short visit which can be relied on is often of more value than the infrequent longer call ... patients watch us as we watch them. They want to see what we are thinking and they will wait until they believe we will listen to what they have to say. They ask for our awareness of them as people." One could argue that this applies to all treatment and not only to the treatment of the dying cancer patient. But this is the testing time of the patient, the family, and, above all, the doctor. This is when the plusquality emerges. In the case of the patient, this goes without saying. But the stress lies heavily on the family as well. Often, as Dr. Saunders remarks, when home care is no longer possible and the patient is transferred to an institution, they are obsessed with a feeling of guilt. They need reassurance, and the care of the family comes within the responsibility of the doctor. Thoughtfulness and humanity in this last phase can bring rewards of their own to the doctor. "When we look back," Dr. Saunders said, " we remember not what death has IN the
"
1. Ann. R. Coll.
Surg. 1967, 41,
162.
done to them, but what about it."
they
have done
to our
thoughts
NAPALM
NAPALM bombing of Japanese cities during the last months of the 1939-45 war caused many more deaths than the atomic attacks on Hiroshima and Nagasaki. In the Korean war, napalm was described as the mainstay of the American Forces: current production runs at 50 million lb. a month. The casualties caused by these incendiary bombs are described by Reich and Side1.1 Burns are the major injuries; heat-stroke, carbon-monoxide poisoning, and nephropathy are among the lethal side-effects. Napalm burns are usually third-degree burns, and early skingrafting is often impracticable. When the napalm is coritaminated with white phosphorus (used in the ignition of napalm bombs and land-mines) wounds may continue to smoulder long after the original injury. Napalm gel is easily prepared by adding the aluminium soaps of naphthenic and oleic acids in varying amounts to ordinary petrol. The heat of a napalm flame can reach that of burning petrol, 2060 C. Petrol is volatile, and the flame is transient, but napalm gel contains the flame and prolongs the burning-time. A canister containing 165 gallons, dropped from a low-flying plane, can spread napalm over an area of about 2500 sq. yards, and incendiary raids of this description may be beyond the capacity of rescue teams and hospitals to cope with the casualties.
CLEAN AIR
IT was always possible to clean Manchester Cathedral -that it has proved sensible to do so is a measure of some confidence in the industrial provisions of the Clean Air Act 1956. But in other respects (e.g., in the issue of smoke-control orders 2) progress has been slow, owing, in part, to dilatoriness by some local authorities but also to technical difficulties in measurement and control. Some of these problems are illustrated by the latest advice to local authorities given in Whitehall’s interpretation3 of a working-party report 4 on the emission of grit and dust. The working-party was appointed three years ago, but it has not undertaken any practical work: thus for furnaces, the lack of sufficient data " to be able to judge what standards are reasonable and practicable " remains. But even when levels of emission have been worked out they must seem, at least to an outsider, not ungenerous. A coal-fired boiler producing 100,000 lb. of steam an hour could, were it to operate continuously for a year, emit up to 250 tons of debris, and still comply with standards which are, in any case, unenforceable. The figure for an oil-fired boiler would be about a third of this, though why any standard of cleanliness should be referred to the type of fuel is not immediately clear. In any event, local f authorities have had to wait ten years to hear of the intention5 of the Minister of Housing and Local Government to empower them to require the measurement of furnace emissions.
t
1. Reich, P., Sidel, V. W. New Engl. J. Med. 1967, 277, 86. 2. See Lancet, 1966, i, 257. 3. Grit and Dust. H.M. Stationery Office, 1967. 3s. 4. Report of the Working Party on Grit and Dust Emissions. H.M. Stationery Office, 1967. Pp. 27. 3s. 5. Ministry of Housing and Local Government and Welsh Office joint circular. H.M. Stationery Office, 1967. 5d.
disturbance, and unless secondary bacterial infection ensues these disappear completely within a few weeks. Cowpox is now a rare disease, largely owing to the higher
nancy. In the latter case, serial cultivation may be carried through many generations with the, virus still present in the cultures,’ although cell growth may be less vigorous,
standards of modern dairy farming, but it may appear out of the blue ". Some epidemics have been traced to a milker who has acquired his infection in his previous
than in cultures of normal embryonic lungs.8 9 It is possible that rubella virus produces its teratogenic effect by acting upon the genetic apparatus of cells. The virus certainly produces chromosome breaks in some human embryo cells in’vitro. Is there any evidence that it also produces chromosome damage in vivo? First reports failed to show any clear chromosome effects in cultured leucocytes from infants born with congenital rubella 10 or in cultures from-tissues removed by surgical termination of pregnancy.:> - but more positive findings were later reported.9 11’Ì2 These findings are interesting, but they leave many questions unanswered. A number of viruses have been reported to produce chromosome breaks in leucocytes cultured from patients with virus infections, and the addition of rubella virus to this list is not remarkable in itself. Evidence of chromosome damage in cultures prepared directly from naturally infected embryos is more convincing, but here there is the problem that severely damaged cells may fail to undergo even a single cycle of cell division on cultivation in vitro. There is the further complication that chromosome breaks are not uncommonly found in spontaneous abortions not associated with rubella, so that it is not easy to know what should be taken as a normal baseline. The long-term persistence of rubella virus in human embryonic cells raises important questions about the eventual fate of a virus in the descendants of these cells. Is the infectivity of rubella virus lost for ever when attempts to recover the virus in post-natal life fail, or could it be reactivated by some later event in vivo or in response to some manipulation of cultured cells in vitro ? Rubella virus is probably the most important infectious agent producing a teratogenic effect in man, but it is almost certainly not alone in this respect.
"
employment. Pseudo-cowpox is commoner both in cows and man, but many human infections are too slight to be seen by a doctor. A recent account of a small epidemic in an enclosed community of nuns illustrates some of the usual features.3 Most of the 32 cows in milk belonging to the sisterhood had papular lesions on the udders. The dry cows were unaffected. The permanent herdswoman was not infected, but in all the 5 nuns being taught the art of milking small painless lumps developed on the fingers. None of them was ill, and all the lesions healed uneventfully except for one which became secondarily infected. It is common experience that pseudo-cowpox is limited to those who are fresh to milking, so it is a reasonable guess that one attack gives some immunity. Those who have seen the two diseases in man will not usually find the distinction difficult, and diagnosis can be confirmed simply and quickly by examination of the virus in the overlying scab under an electron microscope. The farmer may know both diseases by the same name but ought to be able to differentiate the mild eruption which spreads through his herd slowly from the more infectious variolar vaccinx veras which run through his herd like lightning and make a large hole in the milk
cheque.
CHROMOSOMES IN CONGENITAL RUBELLA
RUBELLA virus readily parasitises the developing human embryo, in some cases causing intrauterine death and abortion and in others producing cataract, deafness, heart-disease, and mental retardation in the newborn infant. Sometimes, however, the infection is confined to the placenta, and the infant is normal. Virus-isolation studies in pregnancies terminated by surgery suggest that the infection may die out in some pregnancies, whereas in others, virus can be recovered from many tissues and organs at birth and for several months thereafter.45 What determines the outcome in any particular pregnancy is still largely unknown. Embryonic age at the time of infection is clearly one factor, but there must be many others. Investigations in human embryonic cells cultivated in vitro are easier to control than in-vivo studies, and they may throw some light upon the problem. Rubella virus produces no clear cytopathic effect on normal human embryonic cells, but virus-infected culFibrotures behave differently from normal cultures. blasts from normal lungs or pituitary fail to grow when subcultivated after infection with rubella virus, whereas cells from normal embryonic skin and pharyngeal mucosa, when infected, continue to grow well after many serial subcultivations but remain infected with virus and show a high proportion of chromosome breaks. Clearly the cell type is important. Normal embryonic lung cells infected in vitro seem to behave differently from lung cells infected in vivo and cultured after surgical termination of preg3. 4. 5.
Neale, E. J. E., Calvert, H. T. Br. J. Derm. 1967, 79, 318. Monif, G., Avery, S. B., Korones, S. B., Sever, J. L. Lancet, 1965, i, 723. Sever, J. L. in Advances in Teratology (edited by D. H. M. Woollam); vol. II, p. 127. London, 1967. 6. Plotkin, S. A., Boué, A., Boué, J. G. Am. J. Epidemiol. 1965, 81, 71.
-
A BIOLOGICAL BAROMETER
FOR millions of children malnutrition means a poor in life, and for some it means death. With a health problem of this magnitude there is need for a cheap, easy, and accurate method of assessing nutritional status in large population surveys. The late Dr. B. T. Squires, of Bulawayo, devised a simple test 13 which seems to fit the bill. In 1963 14 he described characteristic changes in the appearance of cells from the buccal mucosa (due apparently to increased keratinisation) in malnourished children and in young animals kept on a low-proteincalorie diet, and after experimenting with various staining methods he found one that gave a reliable indication of keratinisation. The stain he used was acid-fuchsin with light-green (fall),15 which, unexpectedly, produces a bluestart
7. 8. 9.
10. 11. 12.
13. 14. 15.
Kay, H. E. M., Peppercorn, M. E., Porterfield, J. S., McCarthy, K., Taylor-Robinson, C. H. Br. med. J. 1964, ii, 166. Rawls, W. E., Melnick, J. L. J. exp. Med. 1966, 123, 795. Chang, T. H., Moorhead, P. S., Boué, J. G., Plotkin, S. A., Hoskins, J. M. Proc. Soc. exp. Biol. Med. 1966, 122, 236. Mellman, W. J., Plotkin, S. A., Moorhead, P. S., Hartnett, E. M. Am. J. Dis. Child. 1965, 110, 473. Nusbacher, J., Hirschhorn, K., Cooper, L. Z. New Engl. J. Med. 1967, 276, 1409. Kuroki, Y., Makino, S., Aya, T., Nagayama, T. Jap. J. hum. Genet. 1966, 11, 17. Squires, B. T. Cent. Afr. J. Med. 1966, 12, 223. Squires, B. T. Br. J. Nutr. 1963, 17, 303. MacConail, M. A., Gurr, E. Ir. J. med. Sci. April, 1960, p. 182.
352 mauve-red range in the stained tissue, young non-cornified cells staining blue or violet, older cornified cells becoming red or mauve. Buccal smears from healthy puppies and piglets showed a high proportion (70-90%) of blue cells, and the number fell sharply (to less than 40%) within a few days of changing to a protein-calorie-deficient diet. These results were confirmed in healthy and malnourished children, but hopes that the test might be used as a specific indicator of nutritional status proved overoptimistic, for mild infections, such as the common cold, can reduce the blue-cell count to about 30%, in two or three days, and serious infections like rheumatic carditis and trypanosomiasis can depress it to around 10%. Nevertheless, it is useful in screening for excluding healthy children before more detailed investigations. For a precise result at least 500 cells should be counted, but this is seldom needed for screening purposes-a predominant blue or red colour can easily be seen by holding the slide up to the light, and only in the mauve overlap range (40-60% blue or violet cells, any count below 50% being regarded as abnormal) is a count needed.
Despite its shortcomings, this test is a useful barometer of health, and it has the added advantage that the patient’s cooperation is not essential-even the most unwilling child will open his mouth sooner or later, if only to cry.
CARE IN TERMINAL CANCER
catalogue of virtues that society expects from its doctors, none is more demanding of their spirit and humanity than the care of their patients in the terminal stages of cancer. At a symposiumheld early this year at the Royal College of Surgeons of England, Dr. Cicely Saunders, with the background of her experience at St. Joseph’s Hospice, spoke with wisdom and compassion on this aspect of treatment. We must emphasise treatment "; for all too readily, when every resource of active treatment has been exhausted and when our impotence to influence events becomes increasingly distressful and embarrassing, the temptation to tiptoe away from the patient may be strong. " It seems so strange, no one seemed to want to look at me," said one woman. We do not realise how much we can do simply by going to see the patient. " The short visit which can be relied on is often of more value than the infrequent longer call ... patients watch us as we watch them. They want to see what we are thinking and they will wait until they believe we will listen to what they have to say. They ask for our awareness of them as people." One could argue that this applies to all treatment and not only to the treatment of the dying cancer patient. But this is the testing time of the patient, the family, and, above all, the doctor. This is when the plusquality emerges. In the case of the patient, this goes without saying. But the stress lies heavily on the family as well. Often, as Dr. Saunders remarks, when home care is no longer possible and the patient is transferred to an institution, they are obsessed with a feeling of guilt. They need reassurance, and the care of the family comes within the responsibility of the doctor. Thoughtfulness and humanity in this last phase can bring rewards of their own to the doctor. "When we look back," Dr. Saunders said, " we remember not what death has IN the
"
1. Ann. R. Coll.
Surg. 1967, 41,
162.
done to them, but what about it."
they
have done
to our
thoughts
NAPALM
NAPALM bombing of Japanese cities during the last months of the 1939-45 war caused many more deaths than the atomic attacks on Hiroshima and Nagasaki. In the Korean war, napalm was described as the mainstay of the American Forces: current production runs at 50 million lb. a month. The casualties caused by these incendiary bombs are described by Reich and Side1.1 Burns are the major injuries; heat-stroke, carbon-monoxide poisoning, and nephropathy are among the lethal side-effects. Napalm burns are usually third-degree burns, and early skingrafting is often impracticable. When the napalm is coritaminated with white phosphorus (used in the ignition of napalm bombs and land-mines) wounds may continue to smoulder long after the original injury. Napalm gel is easily prepared by adding the aluminium soaps of naphthenic and oleic acids in varying amounts to ordinary petrol. The heat of a napalm flame can reach that of burning petrol, 2060 C. Petrol is volatile, and the flame is transient, but napalm gel contains the flame and prolongs the burning-time. A canister containing 165 gallons, dropped from a low-flying plane, can spread napalm over an area of about 2500 sq. yards, and incendiary raids of this description may be beyond the capacity of rescue teams and hospitals to cope with the casualties.
CLEAN AIR
IT was always possible to clean Manchester Cathedral -that it has proved sensible to do so is a measure of some confidence in the industrial provisions of the Clean Air Act 1956. But in other respects (e.g., in the issue of smoke-control orders 2) progress has been slow, owing, in part, to dilatoriness by some local authorities but also to technical difficulties in measurement and control. Some of these problems are illustrated by the latest advice to local authorities given in Whitehall’s interpretation3 of a working-party report 4 on the emission of grit and dust. The working-party was appointed three years ago, but it has not undertaken any practical work: thus for furnaces, the lack of sufficient data " to be able to judge what standards are reasonable and practicable " remains. But even when levels of emission have been worked out they must seem, at least to an outsider, not ungenerous. A coal-fired boiler producing 100,000 lb. of steam an hour could, were it to operate continuously for a year, emit up to 250 tons of debris, and still comply with standards which are, in any case, unenforceable. The figure for an oil-fired boiler would be about a third of this, though why any standard of cleanliness should be referred to the type of fuel is not immediately clear. In any event, local f authorities have had to wait ten years to hear of the intention5 of the Minister of Housing and Local Government to empower them to require the measurement of furnace emissions.
t
1. Reich, P., Sidel, V. W. New Engl. J. Med. 1967, 277, 86. 2. See Lancet, 1966, i, 257. 3. Grit and Dust. H.M. Stationery Office, 1967. 3s. 4. Report of the Working Party on Grit and Dust Emissions. H.M. Stationery Office, 1967. Pp. 27. 3s. 5. Ministry of Housing and Local Government and Welsh Office joint circular. H.M. Stationery Office, 1967. 5d.