9. Delisle MB, Gorce P, Hirsh E, et al. Motor neuron disease, parkinsonism and dementia. Report of a case with diffuse Lewy body-like intracytoplasmic inclusions. Acta Neuropathol 1987; 75: 104-08. 10. Byrne EJ, Lennox G, Lowe J, Godwin-Austen RB. Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry
1989; 52: 709-17. 11. Gibb WRG, Mountjoy CQ, Mann DMA, Lees AJ. A pathological study of the association between Lewy body disease and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1989; 52: 701-08. 12. Hansen L, Salmon D, Galasko D, et al. The Lewy body variant of
Alzheimer’s disease: a clinical and pathological entity. Neurology 1990; 40: 1-7. 13. Neary D, Snowden JS, Northen B, Goulding P. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 1988; 51: 353-61. 14. Neary D, Snowden JS, Mann DMA, Northen B, Goulding PJ, McDermott N. Frontal lobe dementia and motor neuron disease. JH Neurol Neurosurg Psychiatry 1990; 53: 23-32. 15. Lowe J, Blanchard A, Morrell K, et al. Ubiquitin is a component of intermediate filament inclusion bodies of diverse type in man, including those of Parkinson’s disease, Pick’s disease, and Alzheimer’s disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle and Mallory bodies in alcoholic liver disease. J Pathol 1988; 155: 9-15. 16. Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y. Lewy bodies are ubiquitinated: a light and electronmicroscopy immunocytochemical study. Acta Neuropathol 1988; 75: 345-53. 17. Goldman JE, Yen S-H, Chiu F-C, Peress NS. Lewy bodies of Parkinson’s disease contain neurofilament antigen. Science 1983; 221: 1082-84. 18. Leigh PN, Anderton BH, Dodson A, Gallo J-M, Swash M, Power DM. Ubiquitin deposits in anterior horn cells in motor neurone disease. Neurosci Lett 1988; 93: 197-203. 19. Murayama S, Mori H, Ihara Y, Bouldin TW, Suzuki K, Tomonaga M. Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann Neurol 1990; 27: 137-48. 20. Kono C, Matsubara M, Inagaki T. Idiopathic orthostatic hypotension with numerous Lewy bodies in the sympathetic ganglia. Neurol Med Japan 1976; 4: 568-70. 21. Kosaka K, Oyanagi S, Matsushita M, et al. Presenile dementia with Alzheimer-, Pick-, and Lewy body changes. Acta Neuropathol 1976; 36: 221-33. 22. Colmant H-J. Die myatrophische Lateralsklerose. In: Lubarsch O, Henke F, Rössle R, eds. Handbuch der speziellen pathologischen Anatomie und Histologie. Vol 13/2B. Berlin: Springer, 1958: 2624-92. 23. Bonduelle M. Amyotrophic lateral sclerosis. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. Vol 22. Amsterdam: North Holland, 1975: 281-338. 24. Kurland LT, Mulder DW. Epidemiological investigations of amyotrophic lateral sclerosis. 1, Neurology 1954; 4: 355-78. 25. Schenk VWD. Re-examination of a family with Pick’s disease. Ann Hum Genet 1959; 23: 325-33. 26. Spencer PS, Nunn PB, Hugon J, et al. Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 1987; 237: 517-22. 27. Sjögren T, Sjögren H, Lingren A. Morbus Alzheimer and morbus Pick. Genetic chemical and patho-anatomical study. Acta Psychiatr Neurol Scand 1952; 1 (suppl): 82. 28. Salazar AM, Masters CL, Gajdusek DC, Gibbs CJ. Syndromes of amyotrophic lateral sclerosis and dementia: relation to transmissible Creutzfeldt-Jakob disease. Ann Neurol 1983; 14: 17-26. 29. Connolly JH, Allen IV, Dermott E. Transmissible agent in the amyotrophic form of Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 1988; 51: 1459-60. 30. Esquirol E. Des maladies mentales. Brussels: Librairie Médicale et Scientifique de J. B. Tircher, 1838: 201-18.
BSE IN PERSPECTIVE On
Siamese cat was destroyed by Bristol University. The animal had had features of a nervous system illness, including an unsteady gait, and had not responded to treatment. revealed features of Necropsy spongiform encephalopathy-the first time that such changes had been noted in domestic cats, according to Mr Keith Meldrum, the Govenment’s chief veterinary officer. When the
Fisheries and Food (MAFF) disclosed this information on May 10, Mr John Bower, president of the British Veterinary Association, said "it is tempting but purely speculative to link this with BSE [bovine spongiform encephalopathy], the disease in cattle". Curiosity may not have killed the cat but media speculation has almost pole-axed the beef industry in Britain. Passions about BSE were duly aroused yet again; there were calls for the slaughter of complete herds in which the disease has presented; and the Government’s response showed how few lessons they had learnt from the salmonella and eggs saga-Agriculture Minister John Gummer fed a hamburger to his young daughter and seemed to think all would be well. Meanwhile, Prof Ivor H. Mills, in a letter to The Times (May 17), is not alone in believing that "it is not good enough to say the chances of harm [to human beings], we think, are very small".
Ministry of Agriculture,
of eliminating infected herds is entirely for controlling conventional contagious infections such as foot and mouth disease, which spread rapidly within exposed populations of cattle, but BSE is different. This is the fifth year of the BSE outbreak and the eighth or ninth since the first exposure of cattle to putatively infectious bone and meat meal (lower sterilisation temperatures for preparation of cattle feed were introduced by MAFF some years ago) but there is still no evidence of cattle-to-cattle contagion-the affected animals are index cases in a common-source extended epidemic. MAFF is monitoring the health of more than 300 progeny from cows with BSE, but it is too early to say that maternal transmission will not occur. In the two ruminant species susceptible to natural scrapie, ewe-to-lamb transmission is much more common than lateral spread in sheep, but in goats there is no good evidence that infection is passed from mother to offspring. Neither route operates in unnatural hosts such as hamsters or mice when scrapie is introduced experimentally. Similarly, although there is some confusion as to whether the scrapie-like disease, transmissible mink encephalopathy, is caused by feeding infected bovine or ovine tissue, neither lateral nor vertical transmission occurs. Because BSE is also an artificially-introduced form of scrapie, the Southwood Committee, its 1989 report to the Department of Health and MAFF, thought that cattle too are likely to be "dead-end" hosts. A decade ago it seemed as if scrapie could not be transferred experimentally to cattle. However, follow-up observations on the brains of inoculated cattle, reported on p 1275, now suggest that transmission did occur. The "downer cow" may after all be the US equivalent of the "mad cows" of the UK. A
The feline spongiform encephalopathy (confirmed in a second cat and now suspected in a third) cannot be ignored,
but nothing is known about the aetiology or transmissibility of the cat condition and there is no known connection with BSE. It could be regarded as the first example of rare and unsuspected encephalopathies in cats or other species brought to light by the increased surveillance suggested by the Southwood Committee; increasing capacity to detect such cases does not necessarily implicate BSE or signal a human health hazard. Similarly, it will not be surprising if the reporting rate for Creutzfeldt-Jakob disease (CJD, a human spongiform encephalopathy known to have been transmitted by growth hormone extracted from cadaver pituitary glands and by corneal transplantation) increases in the UK through the greater surveillance which is being introduced.
When the Southwood Committee reported, its view was that BSE is extremely unlikely to constitute a risk to human health because it is simply scrapie in cattle. Numerous studies had failed to show any association between CJD and dietary or occupational exposure to sheep tissue, and the occurrence of CJD in Australia and New Zealand, where scrapie is absent, was believed to be reassuring. Nothing has altered the fundamental factors on which the Southwood conclusion was based, and the Government has gone further than Southwood recommended by introducing a ban on offal as well as nervous tissue for human consumption (offal contains intestinal and lymphoid tissue, likely sites of replication of the BSE agent during the long incubation period of the disease). Nevertheless, public confidence in the safety of beef is understandably at a low ebb and a House of Commons Select Committee is to mount an immediate investigation into whether BSE poses a threat to human health. Since they are unlikely to have any more scientific evidence at their disposal, at the very least they should recommend better inspection and policing of abattoir practice and a sales ban on bovine offal products prepared from animals under six months old (current regulations exclude young calves).
ACADEMIC VIRTUE IN THE BRAVE NEW BRITAIN
day brings fresh evidence that a new broom is sweeping vigorously through the medical faculties of British universities. Academic heads have been brought down from the clouds and the former thoughtful gaze has been replaced by the hard stare of the entrepreneur as the remorseless search for profitability is pursued. From the high flyers of industry on the newly formed University Funding Council Each
the grassroots workers in academe, the word "value" has lost all meanings but one. In what is widely seen as a battle for survival, universities and their faculties clamber over each other for access to the goldmine of industrial support and the UFC accolades that this will bring. Some medical academics, who have for some time discretely achieved commercial success, now find that their skills have become fashionable. Misgivings have to be suppressed-they are seen as a failure to adapt to the brave new academic world of the Thatcher dream. Oxford started early and their Department of Pharmacology has literally been built on industrial support.11 This month’s prize goes to St George’s Hospital Medical School in London. It is reportedthat the biotechnology group Porton International is to invest a minimum of k 10 million over 20 years towards development costs of new drugs and treatments. In exchange for royalty payments to St George’s, Porton will own all patents, although St George’s will be able to collaborate with other commercial groups in areas where Porton is not interested. It is reassuring to know that the Dean of St George’s has emphasised the need to maintain the "virginity of academe". No-one will blame a medical school for acting in the spirit of the age, perhaps from realism rather than principle. Protective clauses have no doubt been built into the contract-how far they operate in practice is more questionable. Porton’s interest—eg, in preventive medicine or in lifestyle modifications that enable patients to reduce drug usage-is likely to be less than all-consuming. How much free communication of data is allowed before patents have been established, or how far promising developments to
by the industrial member of the partnership guessed, although these matters have caused serious difficulties elsewhere.3 It seems likely that the University of London and Porton International will be wrestling with these issues over the next two decades. This is no temporary aberration. It is a response by the universities and medical schools to the sort of question that has persistently been asked by ministers. It is a question that the Prime Minister is believed to have peremptorily addressed to a delegation from the Medical Research Council which visited her early in her ministry. Cutting their pleas short, she demanded that they tell her what the are
returns had been on the millions invested in the MRC over the years. It is not thought likely that she was requesting information on citation ratings or Nobel prizes. The same broom, of course, has been sweeping-other areas. Revenue raising is the order of the day in the health service, and the Secretary of State wishes to see "wealth creation" incorporated in the curriculum of schools responsible for their own budgets. All will contribute to the economic prosperity of the country. The only flies in the political ointment are an economy in deep trouble, a demoralised teaching profession with plummetting recruitment, and a health service in disarray from the introduction of "market principles" on top of reduced returns from land sales as property values fall. Only the higher reaches of Government can fail to be impressed by the curiously mixed nature of the blessings that the enterprise society has produced. By coincidence, the clinical research community passed its own verdict on the revolutionised academic environment in the same week as the report of the St George’s contract. The MRC announced its disappointment that only half the places in its imaginative 7-year fellowship programme for clinical research had been filled. Why should the brightest and most able enter academic medicine when a real business career offers materially greater rewards?
1. Editorial. Privatised pharmacology. Lancet 1987; ii: 1439-40. 2. Wittstock M. Porton links with St George’s. The Times, May 8, 1990. 3. Kenney M. Biotechnology: the university-industrial complex. New Haven: Yale University Press, 1986.
GROWTH AND NUTRITION IN CHILDREN WITH CEREBRAL PALSY Cerebral
is the commonest cause of physical Most affected children are small, for reasons not disability.1 fully understood;2 the effect of low birthweight may be a factor. The degree of neurological impairment is more important. Children with mild celebral palsy who can walk are usually below average height, but are not malnourished. However, very dependent disabled children are short, underweight for stature, with wasted muscles and reduced skinfold thickness. Abnormal muscle tone and activity are associated with dwarfing of limbs; it is possible that a trophic influence from the brain is disrupted. Children with severe cerebral palsy have difficulty achieving an adequate food intake for several reasons. Disabled children cannot forage for food in the kitchen or buy snacks at the sweetshop as readily as ablebodied children. Those with communication difficulties may not easily be able to ask for food or express their preferences. Many have poor hand function and are unable to feed themselves. Children with cerebral palsy involving the head