- Email: [email protected]
APATHETICS ANONYMOUS
1026 from hospital: many mothers commented on the anxiety of first assuming responsibility for the child at home and the apparent lack of guidance at that time. The research committee’s recommendations are, for the most part, unexceptionable and unremarkable. They would have well-designed clinics, no stinting of outlay on their staff or premises, and effective appointment systems; more advertisement of antenatal instruction and more evening classes; encouragement of husbandly interest in the pregnancy and participation in classes; close liaison between those giving antenatal instruction and those conducting labour; and more support for the mother newly discharged home. The committee pleads, too, for more sex education in schools-but this more, apparently, on account of preconceptions than of any of their findings. The report rather suggests that, provided instruction is forthcoming when it is relevant, it need not be given before.
OROPHARYNGEAL CANCER IN INDIA
MANY of the poorer people in India chew tobacco, alone or mixed with lime, with betel leaf, or with nut and lime. As has long been known, oral and oropharyngeal cancer is common in that part of the world, and from 34 to 47% of patients attending special cancer hospitals have tumours in this region. In Agra,23 oropharyngeal cancer is exceeded in frequency only by female genital cancer; and breast and gastrointestinal cancer are relatively rare. Wahi et al.2 report their findings in 1916 patients with oral or oropharyngeal cancer. 52% arose on the buccal mucosa and 27% on the tongue, the anterior two-thirds of which was involved four times as often as the posterior third (this distribution is at variance with findings in other parts of India4 where these cancers are common). The male/female ratio was 2-3/1, and the peak age in both sexes was 50-54 years. The disease was often painless for some time, and, though most patients sought advice within six months of onset, 70% were in stage III or iv when first seen, and the prognosis was extremely poor because of early involvement of lymphnodes on one or both sides of the neck. Over 98% of these cancers were squamous cancers, and the degree of differentiation decreased progressively from lips to tonsil. Compared with other countries, the frequency of other oral tumours, especially tumours of the minor salivary glands, was also greater. But such salivary-gland tumours in the mouth are also familiar in other tropical countries where oral epidermoid cancers are not excessively common.
frequency of oropharyngeal cancer in India and the variations in the primary sites suggest local differences in environmental factors. In Agra, oral leukoplakia was found chiefly in the buccal mucosa and less often In patients with such leukoplakia the on the tongue. The
serum-vitamin-A levels were below those of normal controls, and patients with oral cancer had still lower levels of vitamin A. The consumption neither of alcohol nor of highly spiced foodstuffs seemed significant as a likely cause of oropharyngeal cancer; and syphilis did not seem relevant. The important influence in the 821 patients closely studied by Wahi et al. was tobacco, either chewed 1. 2.
Orr, I. M. Lancet, 1933, ii, 575. Wahi, P. N., Lahiri, B., Kehar, U., Arora, S. Br. J. Cancer, 1965, 19, 627.
3. 4.
Wahi, P. N., Kehar, U., Lahiri, B. ibid. p. 642. Khanolkar, V. R. Cancer Res. 1944, 4, 313.
or smoked. Tobacco-chewing was a habit of 86% of those with leukoplakia and of 73% of those with oral cancer, but only 12% of the control series used tobacco. All women with lip cancer chewed tobacco. In those who did not use tobacco the anterior region of the tongue was more often affected, and the buccal mucosa was rarely involved. Those who chewed tobacco usually smoked it too, and the quid was often held in the cheek for long periods. Dental hygiene in the populations was poor. The question is whether tobacco is directly responsible, as a factor in persons with poor dental hygiene and vitamin-A deficiency, which may increase keratinisation of the oral mucosa. Certainly the case implicating tobaccochewing as the chief cause of oropharyngeal cancer is strong. Curiously enough, however, Wahi et al. have not considered the role of betel or of lime, which have been investigated elsewhere 56 as possible co-carcinogens. Itmay be impossible to identify the effects of these separate factors in retrospective studies, since individuals vary in their habits during their life. Yet further evidence must be sought, for it would be hard to deny the Indian peasant the solace of tobacco-chewing if it could be made a safe habit. Hirayama has now reviewed the situation concerning oropharyngeal cancer in Central and South East Asia. He makes a strong case against tobacco-chewing, noting especially the close association between the site of the cancer and the place where the quid was usually lodged in the mouth. But he also pointed to the very high frequency in areas where tobacco was chewed with shell lime; to the comparative rarity of the disease in Kabull (Afganistan) and in Nigeria, where tobacco is chewed without lime; and to the high frequency in New Guinea, where betel and lime are chewed without tobacco. Very strong suspicion therefore attaches to lime as a cocarcinogen. The World Health Organisation now has a research project under way in the Mainpuri district of India to examine this possibility.
APATHETICS ANONYMOUS
THE delay in building the new Chelsea group of special hospitalsis not unparalleled elsewhere, but it is particularly hard to accept for several reasons. The uncertainty about whether and when the site for the first phase will be available would have been resolved long ago had it not been for the lack of dynamism, amounting to apathy, of the Ministry of Health; the project team has produced a plan which has been generally accepted; the old hospitals which the new are to replace in the first phase of the plan are notably dilapidated and inconvenient; and these new hospitals are essential if London is to remain a centre for instruction and research in the
more
recondite clinical
specialties. It now seems that the site may not be fully cleared until 1971-72. Phase 1 is to include St. Mark’s Hospital (diseases of the rectum), St. John’s (skin), and the three small urological hospitals clustered round Covent Garden -namely, St. Peter’s, St. Paul’s, and St. Philip’s. At the existing St. John’s a 50-minute journey separates the inpatient from the outpatient department; and the three urological hospitals have, between them, only two X-ray departments, but a putative sixteen boilers with seven 5. Muir, C. S., Kirk, R. Br. J. Cancer, 1960, 14, 597. 6. Shanta, A., Krishnamurthi, S. ibid. 1963, 17, 8. 7. Hirayama, T. Bull. Wld Hlth Org. 1966, 34, 41. 8. See Lancet, Jan. 22, 1966, p. 189.
1027 hard put to it to keep up steam at night. According the present schedule, by the time the first phase is completed, these three buildings are unlikely to be fit for storing potatoes, let alone accommodating patients. While all these small special hospitals are becoming unsuitable for clinical care, they are also becoming unsuitable for teaching and research; yet the Ministry refuses to recognise, or anyhow to respond to, their particular and pressing claims. The inaction over the Chelsea plan is but one token of the continuing deterioration of British hospital buildings —a deterioration which annual juggling with the Hospital Plan cannot conceal for ever. One day the public will realise that in hospital construction this country not only has thirty years’ leeway to make good but is still losing ground. Then a crash programme may be instituted. Meanwhile the Government might be asked to explain how it defends deferring completion of the Chelsea plan - possibly until the 21st century.
boilermen who
NEMALINE MYOPATHY
are
to
NEW STYLE CAVEMEN
THERE seems no end to the variations on outlandish behaviour which teenagers can devise. Scarcely have we got used to the clashes of mods and rockers than we are confronted with the trogs.1 Coming mostly from the Midlands, Manchester, and Merseyside, they congregate in the caves and potholes near Matlock in Derbyshire where they live rough. Some are youngsters on the run from their homes, others are merely weekend visitors in pursuit of fun and kicks. Local residents not unexpectedly dislike their presence and complain of sexual promiscuity, More sinister reports drug-taking, and rowdiness. circulate of mock marriages between boys and often quite young girls, and even of black magic. All this (and the numbers of cave-dwellers, estimated by some at 1000 at a time) is no doubt greatly exaggerated. Nevertheless, the meaning of this kind of behaviour is worth considering. How far is it normal adolescent exhibitionism and rejection of the adult world, and how far does it reflect a deeper social malaise ? Is national publicity likely to inflate its adherents and increase its influence ? If it did, would that matter ? There are no easy answers to these questions. Adolescents nearly always need to form peer groups and to carry out their own kind of activities far from parental supervision. It is part of the growing-up process and has its benign aspect. Drug-taking and sexual promiscuity cannot be so easily dismissed, for such practice can spread and attract others to its deviant lure. But our best defence against the possible dangers arising from deviant youth cults is neither social ostracism, nor repressiveness, but determined support for inadequate home lives. The adult community must show that it regards youth, not as a social illness, but as a valuable stage in development and in social growth. This means, inter alia, lowering the age of legal majority, giving the franchise earlier, and allowing young citizens more control over their own affairs. It means giving them a worthwhile job to do and leaving them to get on with it, yet not abandoning them entirely to their own resources. Guidance and affection, lacking in many homes and neighbourhoods, can be given without patronage only in a truly caring community where all have a place and all are equally valued. 1. Times,
April
14 and
18, 1966.
SOME remarkable abnormalities of skeletal muscle have been discovered by histological examination of musclebiopsy samples from children with benign and apparently non-progressive myopathies. In 1956 Shy and Magee1 reported that, in a group of conditions of this type in a single family, most of the muscle-fibres were found to contain a non-functioning central core; the cores had different staining characteristics from the peripheral parts of the muscle-fibres, which seemed to be normal in structure and enzyme activity. This entity has become known as " central core disease " and many other cases have now been recorded. In 1963 Shy and his colleagues2 described a 4-year-old girl with a familial, congenital, non-progressive weakness of proximal limb muscles. Biopsy revealed collections of unique rod-like or threadlike structures in otherwise normal muscle-cells. Under the electron microscope these peculiar structures looked like fibrils-an appearance accentuated by regular transverse bands with a reported periodic spacing of 145 A. This condition was given the name " nemaline myopathy " because of the rod or thread (Greek nesra) configuration of these bodies, and similar cases have since been described.3-5 Shy and Gonatas 6 described enormously enlarged and abnormal mitochondria in the muscle of patients with a similar benign and non-progressive myopathy, and they named this condition " megaconial myopathy "; but the specificity of this finding is still in doubt. Nemaline myopathy, on the other hand, is now widely accepted as a histopathological entity, though clinically it is almost impossible to distinguish from the other forms of benign congenital myopathy, or indeed from some cases of socalled " benign congenital hypotonia " in which the muscles are histologically normal.’7
Many workers have been interested in the origin of the rod-like bodies, and two reports 8now strongly suggest that this material arises from an abnormality of the Z band of the muscle-fibre. Examination of muscle from these cases under the electron microscope shows a characteristic hypertrophy and morphological abnormality of the Z bands. Even the rods lying free under the sarcolemma, showing no apparent continuity with the Z band of surviving muscle-fibres, have the same transverse striations and the same periodicity as those in the normal Z band. Some sections have also shown rods formed from what seem to be normal Z bands. The rods, like the Z bands, probably contain mainly tropomyosin B, and hence the histological appearances are likely to arise from formation of excess protein in the Z band, which then results in hypertrophy and in the eventual budding-off of the characteristic rods. Gonatas et al. suggest that if native tropomyosin or a similar protein is crystallised along the Z band, this may obstruct an interaction between active sites of the actin of the I band and the myosin of the A band, thus accounting for mild muscular weakness. 1. 2.
Shy, G. M., Magee, K. R. Brain, 1956, 79, 610. Shy, G. M., Engel, W. K., Somers, J. E., Wanko, T. ibid. 1963, 86,
3.
Conen, P. E., Murphy, E. G., Donohue, W. L. Can. med. Ass. J. 1963, 89, 983. Engel, W. K., Wanko, T., Fenichel, G. M. Archs Neurol. Psychiat., Chicago. 1964, 11, 22. Spiro, A. J., Kennedy, C. ibid. 1965, 13, 155. Shy, G. M., Gonatas, N. K. Science, N.Y. 1964, 145, 493. Walton, J. N. J. Neurol. Neurosurg. Psychiat. 1957, 20, 144. Gonatas, N. K., Shy, G. M., Godfrey, E. H. New Engl. J. Med. 1966, 274, 535. Price, H. M., Gordon, G. B., Pearson, C. M., Munsat, T. L., Blumberg, J. M. Proc. natn. Acad. Sci. U.S.A. 1965, 54, 1398.
793.
4.
5. 6. 7. 8. 9.
OROPHARYNGEAL CANCER IN INDIA
MANY of the poorer people in India chew tobacco, alone or mixed with lime, with betel leaf, or with nut and lime. As has long been known, oral and oropharyngeal cancer is common in that part of the world, and from 34 to 47% of patients attending special cancer hospitals have tumours in this region. In Agra,23 oropharyngeal cancer is exceeded in frequency only by female genital cancer; and breast and gastrointestinal cancer are relatively rare. Wahi et al.2 report their findings in 1916 patients with oral or oropharyngeal cancer. 52% arose on the buccal mucosa and 27% on the tongue, the anterior two-thirds of which was involved four times as often as the posterior third (this distribution is at variance with findings in other parts of India4 where these cancers are common). The male/female ratio was 2-3/1, and the peak age in both sexes was 50-54 years. The disease was often painless for some time, and, though most patients sought advice within six months of onset, 70% were in stage III or iv when first seen, and the prognosis was extremely poor because of early involvement of lymphnodes on one or both sides of the neck. Over 98% of these cancers were squamous cancers, and the degree of differentiation decreased progressively from lips to tonsil. Compared with other countries, the frequency of other oral tumours, especially tumours of the minor salivary glands, was also greater. But such salivary-gland tumours in the mouth are also familiar in other tropical countries where oral epidermoid cancers are not excessively common.
frequency of oropharyngeal cancer in India and the variations in the primary sites suggest local differences in environmental factors. In Agra, oral leukoplakia was found chiefly in the buccal mucosa and less often In patients with such leukoplakia the on the tongue. The
serum-vitamin-A levels were below those of normal controls, and patients with oral cancer had still lower levels of vitamin A. The consumption neither of alcohol nor of highly spiced foodstuffs seemed significant as a likely cause of oropharyngeal cancer; and syphilis did not seem relevant. The important influence in the 821 patients closely studied by Wahi et al. was tobacco, either chewed 1. 2.
Orr, I. M. Lancet, 1933, ii, 575. Wahi, P. N., Lahiri, B., Kehar, U., Arora, S. Br. J. Cancer, 1965, 19, 627.
3. 4.
Wahi, P. N., Kehar, U., Lahiri, B. ibid. p. 642. Khanolkar, V. R. Cancer Res. 1944, 4, 313.
or smoked. Tobacco-chewing was a habit of 86% of those with leukoplakia and of 73% of those with oral cancer, but only 12% of the control series used tobacco. All women with lip cancer chewed tobacco. In those who did not use tobacco the anterior region of the tongue was more often affected, and the buccal mucosa was rarely involved. Those who chewed tobacco usually smoked it too, and the quid was often held in the cheek for long periods. Dental hygiene in the populations was poor. The question is whether tobacco is directly responsible, as a factor in persons with poor dental hygiene and vitamin-A deficiency, which may increase keratinisation of the oral mucosa. Certainly the case implicating tobaccochewing as the chief cause of oropharyngeal cancer is strong. Curiously enough, however, Wahi et al. have not considered the role of betel or of lime, which have been investigated elsewhere 56 as possible co-carcinogens. Itmay be impossible to identify the effects of these separate factors in retrospective studies, since individuals vary in their habits during their life. Yet further evidence must be sought, for it would be hard to deny the Indian peasant the solace of tobacco-chewing if it could be made a safe habit. Hirayama has now reviewed the situation concerning oropharyngeal cancer in Central and South East Asia. He makes a strong case against tobacco-chewing, noting especially the close association between the site of the cancer and the place where the quid was usually lodged in the mouth. But he also pointed to the very high frequency in areas where tobacco was chewed with shell lime; to the comparative rarity of the disease in Kabull (Afganistan) and in Nigeria, where tobacco is chewed without lime; and to the high frequency in New Guinea, where betel and lime are chewed without tobacco. Very strong suspicion therefore attaches to lime as a cocarcinogen. The World Health Organisation now has a research project under way in the Mainpuri district of India to examine this possibility.
APATHETICS ANONYMOUS
THE delay in building the new Chelsea group of special hospitalsis not unparalleled elsewhere, but it is particularly hard to accept for several reasons. The uncertainty about whether and when the site for the first phase will be available would have been resolved long ago had it not been for the lack of dynamism, amounting to apathy, of the Ministry of Health; the project team has produced a plan which has been generally accepted; the old hospitals which the new are to replace in the first phase of the plan are notably dilapidated and inconvenient; and these new hospitals are essential if London is to remain a centre for instruction and research in the
more
recondite clinical
specialties. It now seems that the site may not be fully cleared until 1971-72. Phase 1 is to include St. Mark’s Hospital (diseases of the rectum), St. John’s (skin), and the three small urological hospitals clustered round Covent Garden -namely, St. Peter’s, St. Paul’s, and St. Philip’s. At the existing St. John’s a 50-minute journey separates the inpatient from the outpatient department; and the three urological hospitals have, between them, only two X-ray departments, but a putative sixteen boilers with seven 5. Muir, C. S., Kirk, R. Br. J. Cancer, 1960, 14, 597. 6. Shanta, A., Krishnamurthi, S. ibid. 1963, 17, 8. 7. Hirayama, T. Bull. Wld Hlth Org. 1966, 34, 41. 8. See Lancet, Jan. 22, 1966, p. 189.
1027 hard put to it to keep up steam at night. According the present schedule, by the time the first phase is completed, these three buildings are unlikely to be fit for storing potatoes, let alone accommodating patients. While all these small special hospitals are becoming unsuitable for clinical care, they are also becoming unsuitable for teaching and research; yet the Ministry refuses to recognise, or anyhow to respond to, their particular and pressing claims. The inaction over the Chelsea plan is but one token of the continuing deterioration of British hospital buildings —a deterioration which annual juggling with the Hospital Plan cannot conceal for ever. One day the public will realise that in hospital construction this country not only has thirty years’ leeway to make good but is still losing ground. Then a crash programme may be instituted. Meanwhile the Government might be asked to explain how it defends deferring completion of the Chelsea plan - possibly until the 21st century.
boilermen who
NEMALINE MYOPATHY
are
to
NEW STYLE CAVEMEN
THERE seems no end to the variations on outlandish behaviour which teenagers can devise. Scarcely have we got used to the clashes of mods and rockers than we are confronted with the trogs.1 Coming mostly from the Midlands, Manchester, and Merseyside, they congregate in the caves and potholes near Matlock in Derbyshire where they live rough. Some are youngsters on the run from their homes, others are merely weekend visitors in pursuit of fun and kicks. Local residents not unexpectedly dislike their presence and complain of sexual promiscuity, More sinister reports drug-taking, and rowdiness. circulate of mock marriages between boys and often quite young girls, and even of black magic. All this (and the numbers of cave-dwellers, estimated by some at 1000 at a time) is no doubt greatly exaggerated. Nevertheless, the meaning of this kind of behaviour is worth considering. How far is it normal adolescent exhibitionism and rejection of the adult world, and how far does it reflect a deeper social malaise ? Is national publicity likely to inflate its adherents and increase its influence ? If it did, would that matter ? There are no easy answers to these questions. Adolescents nearly always need to form peer groups and to carry out their own kind of activities far from parental supervision. It is part of the growing-up process and has its benign aspect. Drug-taking and sexual promiscuity cannot be so easily dismissed, for such practice can spread and attract others to its deviant lure. But our best defence against the possible dangers arising from deviant youth cults is neither social ostracism, nor repressiveness, but determined support for inadequate home lives. The adult community must show that it regards youth, not as a social illness, but as a valuable stage in development and in social growth. This means, inter alia, lowering the age of legal majority, giving the franchise earlier, and allowing young citizens more control over their own affairs. It means giving them a worthwhile job to do and leaving them to get on with it, yet not abandoning them entirely to their own resources. Guidance and affection, lacking in many homes and neighbourhoods, can be given without patronage only in a truly caring community where all have a place and all are equally valued. 1. Times,
April
14 and
18, 1966.
SOME remarkable abnormalities of skeletal muscle have been discovered by histological examination of musclebiopsy samples from children with benign and apparently non-progressive myopathies. In 1956 Shy and Magee1 reported that, in a group of conditions of this type in a single family, most of the muscle-fibres were found to contain a non-functioning central core; the cores had different staining characteristics from the peripheral parts of the muscle-fibres, which seemed to be normal in structure and enzyme activity. This entity has become known as " central core disease " and many other cases have now been recorded. In 1963 Shy and his colleagues2 described a 4-year-old girl with a familial, congenital, non-progressive weakness of proximal limb muscles. Biopsy revealed collections of unique rod-like or threadlike structures in otherwise normal muscle-cells. Under the electron microscope these peculiar structures looked like fibrils-an appearance accentuated by regular transverse bands with a reported periodic spacing of 145 A. This condition was given the name " nemaline myopathy " because of the rod or thread (Greek nesra) configuration of these bodies, and similar cases have since been described.3-5 Shy and Gonatas 6 described enormously enlarged and abnormal mitochondria in the muscle of patients with a similar benign and non-progressive myopathy, and they named this condition " megaconial myopathy "; but the specificity of this finding is still in doubt. Nemaline myopathy, on the other hand, is now widely accepted as a histopathological entity, though clinically it is almost impossible to distinguish from the other forms of benign congenital myopathy, or indeed from some cases of socalled " benign congenital hypotonia " in which the muscles are histologically normal.’7
Many workers have been interested in the origin of the rod-like bodies, and two reports 8now strongly suggest that this material arises from an abnormality of the Z band of the muscle-fibre. Examination of muscle from these cases under the electron microscope shows a characteristic hypertrophy and morphological abnormality of the Z bands. Even the rods lying free under the sarcolemma, showing no apparent continuity with the Z band of surviving muscle-fibres, have the same transverse striations and the same periodicity as those in the normal Z band. Some sections have also shown rods formed from what seem to be normal Z bands. The rods, like the Z bands, probably contain mainly tropomyosin B, and hence the histological appearances are likely to arise from formation of excess protein in the Z band, which then results in hypertrophy and in the eventual budding-off of the characteristic rods. Gonatas et al. suggest that if native tropomyosin or a similar protein is crystallised along the Z band, this may obstruct an interaction between active sites of the actin of the I band and the myosin of the A band, thus accounting for mild muscular weakness. 1. 2.
Shy, G. M., Magee, K. R. Brain, 1956, 79, 610. Shy, G. M., Engel, W. K., Somers, J. E., Wanko, T. ibid. 1963, 86,
3.
Conen, P. E., Murphy, E. G., Donohue, W. L. Can. med. Ass. J. 1963, 89, 983. Engel, W. K., Wanko, T., Fenichel, G. M. Archs Neurol. Psychiat., Chicago. 1964, 11, 22. Spiro, A. J., Kennedy, C. ibid. 1965, 13, 155. Shy, G. M., Gonatas, N. K. Science, N.Y. 1964, 145, 493. Walton, J. N. J. Neurol. Neurosurg. Psychiat. 1957, 20, 144. Gonatas, N. K., Shy, G. M., Godfrey, E. H. New Engl. J. Med. 1966, 274, 535. Price, H. M., Gordon, G. B., Pearson, C. M., Munsat, T. L., Blumberg, J. M. Proc. natn. Acad. Sci. U.S.A. 1965, 54, 1398.
793.
4.
5. 6. 7. 8. 9.