Several observations suggest that tumour necrosis factor (TNF) plays a role in demyelination, although direct evidence for this is lacking. We have examined ultrastructurally rat sciatic nerves injected with TNF-alpha or TNF-beta: the effects of the two cytokines were found to be qualitatively similar. One day after injection nerves were oedematous and contained many inflammatory cells. Leucocytes were adherent to the walls of endoneurial vessels and sometimes were packed into the sub-endothelial layer apparently occluding the vascular lumen. Occasional myelinated axons were associated with macrophages and showed signs of myelin damage. By 3 days the inflammatory changes had diminished: some axons were degenerating or demyelinating. By 6-7 days, the vascular changes had resolved, and the endoneurium contained significant numbers of demyelinating and degenerating axons. Control nerves, which received injections of vehicle, showed no vascular changes and either no, or significantly fewer, degenerating or demyelinating axons. We conclude that the intraneural injection of TNF produces inflammatory vascular changes within the endoneurium, together with demyelination and axonal degeneration. We have also observed demyelination and degeneration in a preliminary study of the effects of TNF-alpha in mice. These findings may be relevant to the pathogenesis of demyelinating diseases such as Guillain-Barré syndrome.

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million women screened in the British breast cancer screening programme in 1991-2 and that 1465 of the cancers were invasive and < 10 mm in diameter.' Subsequently Yeoman et al reported that 39% of the cancers were palpable, leading to the conclusion that the balance, 39% (100-39-22), were non-invasive and impalpable.2 Now Joan Austoker reports that ductal carcinoma in situ made up 17-6% of the cancers.3 In view of its rarity, lobular carcinoma in situ seems unlikely to have accounted for the other 21-4% of minimal lesions. We are left wondering where the discrepancy lies. In any event, such a large number of non-invasive cancers presents a practical and ethical problem since there is no consensus among surgeons about how to treat them.4 It is recognised that an appreciable proportion do not become life threatening.We also note that figure 3 of Austoker's paper shows reduced mortality, with a relative risk of 0 5 among women aged 40-49 screened in the Malmo trial. This scarcely equates to a 29% increase in mortality among women under 55 screened in that trial5; this error would also affect the size of the cumulative reduction in mortality among the seven trials cited.Austoker reports that "primary care teams have an important part to play in encouraging women to attend for screening and in providing information and advice, and reassurance at all stages of the screening process." She subsequently lists the benefits (three) and disadvantages (seven). It Selfexamination oftestes is ofvalue EDITOR,-As Joan Austoker states, 120 deaths from testicular cancer a year do not justify population screening for this disease.' The question of education of young men about testicular cancer in general, and about self examination of the testes in particular, raises some different questions; it will indeed be difficult to evaluate education about self examination of the testes in terms of its effect on mortality from the disease and the proportion of patients requiring chemotherapy. I take issue, however, with Austoker's statement, based on anecdotal reports, that widespread application "might lead to a substantial increase in investigation of non-malignant conditions with its associated anxiety." Colleagues and I have reported the effect of distributing a leaflet about self examination of the testes. A study of a population of male students indicated that around 500 saw a copy of the leaflet.2 Shortly after they did so there were seven consultations at the student health service for scrotal complaints. After the interviews that were conducted to evaluate the effect of the leaflet a further six consultations took place. Such consultations were monitored throughout the investigation, which lasted seven months. From this it seems that publicity about self examination of the testes will, over a short period, provoke inquiries from around 1% of the people who are affected by the publicity. There is no evidence of any longer term anxiety that would appreciably affect the demand on health services.

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