drug of choice for women of child-bearing potential. 12 This comforting assertion has now been challenged.13,14 In 1989, Jones and his colleagues,13 in a largely anectodal study, found an impressive frequency of craniofacial defects (11%), fingernail hypoplasia (26%), and developmental delay (20%) in 35 liveborn children exposed prenatally to CBZ as monotherapy. Rosa14 reported a retrospective study of all pregnant Medicaid recipients in Michigan who had delivered between 1980 and 1988 and who were taking anti epileptic drugs. 4 babies with spina bifida were born to 1490 women; in 3 of these, the mother received CBZ in combination with valproate, phenytoin, or a barbiturate. Pooling his data with those from similar studies, Rosa concluded that "exposure to CBZ in without concurrent exposure to VPA [valproate], carries a 1% risk of spina bifida". This is about 13-7 times the expected rate. What can one conclude from these and other studies? Anectodal evidence clearly indicates that CBZ is a minor teratogen. The drug is metabolised in the liver, partly in the form of a pharmacologically active epoxide (CBZ-E), a chemical species that is highly mutagenic.ls Production of CBZ-E is increased by concomitant treatment with other enzymeinducing antiepileptic drugs such as phenytoin and phenobarbitone, and its breakdown is inhibited by valproate.16 That epoxide hydralase activity in fetal liver is much lower than that in adult liver may indicate a failure to detoxify CBZ-E in susceptible infants .17 It is easy to be influenced by the flow of negative case-reports. A malformed infant exposed in utero to an antiepileptic drug will undoubtedly come to medical attention whereas an uncomplicated pregnancy and delivery is more likely to go unnoticed. Despite mounting evidence, the case remains to be proven against CBZ (and perhaps also against valproate18) by large, prospective, multicentre and ideally international investigations based on pregnancy registers. The outlook for the pregnant woman with epilepsy is less serious than was thought previously; seizures pose a greater overall risk to such women than do antiepileptic drugs used properly.19 Despite the concerns about teratogenesis, treated epilepsy should not preclude a woman from childbearing. More than 90 % of such pregnancies will be uneventful and will result in a healthy baby. utero,
1. Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet 1968; ii: 1296. 2. Brodie MJ. Management of epilepsy during pregnancy and lactation. Lancet 1991; 336: 426-27. 3. Nakane Y, Okuma T, Takahashi R, et al. Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan. Epilepsia 1980; 21: 663-80. 4. Lindhout D, Hoppener RJEA, Meinardi H. Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine). Epilepsia 1984; 25: 77-83. 5. Hanson JW, Smith DW. The fetal hydantoin syndrome. JPediatr 1975;
Meldrum BS, eds. Recent advances in epilepsy 4. Edinburgh: Churchill Livingstone, 1988: 93-107.
E, Löfkvist E, Mauguiere F. Valproate and spina bifida. Lancet 1984; ii: 1392. 8. Lindhout D, Schmidt D. In-utero exposure to valproate and neural tube defects. Lancet 1986; i: 1392-93. 9. Di Liberti JH, Farndon PA, Dennis NR, Curry CJR. The fetal valproate syndrome. Am J Med Genet 1984; 19: 473-81. 10. Rudd NL, Freedom RM. A possible primidone embryopathy. J Pediatr 1979; 94: 835-37. 11. Editorial. Carbamazepine update. Lancet 1989; ii: 595-97. 12. Hopkins A. Prescribing in pregnancy: epilepsy and anticonvulsant drugs. Br Med J 1987; 294: 497-501. 13. Jones ICJ, Lacro RV, Johnson KA, Adams J. Pattern of malformations in 7. Robert
children of women treated with carbamazepine during pregnancy. N Engl J Med 1989; 320: 1661-66. 14. Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991; 324: 674-77. 15. Shum S, Jensen NM, Nebert DW. The Ah locus: in utero toxicity and teratogenesis associated with genetic differences in B(a) P metabolism. Teratology 1979; 20: 365-76. 16. Johnson FN, Brodie MJ. Pharmacokinetics of carbamazepine: implications for clinical use. Rev Contemp Pharmacother 1990; 1: 85-98. 17. Pacifici M, Colizzi C, Giuliani L, Rane A. Cytosolic epoxide hydrolase in fetal and adult human liver. Arch Toxicol 1983; 54: 331. 18. Editorial. Valproate, spina bifida, and birth defect registries. Lancet 1988; ii: 1404-05. 19. Yerby MS, Lepak I. Epilepsy and the outcomes of pregnancy. J Epilepsy
1990; 3: 193-99.
sprout from Brussels
Many a head in European ministries of health must be shaking in wonder if not despair over a directive issued by the Council of the European Communities1 about the minimum safety and health requirements for work with display screen equipment. Among the many whereases to adorn the obligatory preamble one claims that "this Directive is a practical contribution towards creating the social dimension of the internal market". It is not clear whether this is some subtle irony sneaked into the text by one of the member states, much as some wits try to get a joke in their entry past the editor of Who’s Who. But before we dissect the corpse let us glance at it. The pathology of visual display units has a long history. It started by threatening eyesight, continued with dermatological risks, was followed by obstetric complications, and has completed the circle with the cachet of European legalisation. There is no dispute that some users have experienced difficulties in those spheres, although unimpeachable correlations are hard to come by. It is also true that some types of display work are demanding and stressful and may consequently cause well-documented symptoms. Nevertheless, there are many less comfortable occupations than those involving display units, and no one seems to be concerned with their ergonomics. The use of microscopes springs to mind (although this has become an issue in Soviet industrial medicine). Articles 1 and 2 of the Directive cover exclusions and definitions while Articles 3-8 contain instructions to employers regarding the ergonomics of workstations, emphasise the need for information on health and safety matters to be imparted to employees, advise on employees’ daily work routines, and prescribe consultations with, and participation by, employees in matters covered by this Directive. Medical aspects are considered in Article 9 on the protection of workers’
eyesight. It gives workers the entitlement to an appropriate eye and eyesight test to be carried out by a person with the necessary capabilities. Such a test is to be applied before the start of display screen work (when this takes place on a regular and habitual basis), at regular intervals subsequently, and ad hoc if the eyes and
difficulties. An forms of the ophthalmological investigation part entitlement if the preceding test indicates it. "Corrective appliances appropriate for the work concerned" have to be provided at no cost to the worker if the preceding examinations have found this necessary and "normal corrective appliances cannot be used". This brief summary should indicate that Brussels has provided a seed-bed for legal, medical, and social complications for all the pious hope of having made a practical contribution to the social dimension. In Britain, it is a Common Law requirement that no one shall hire himself out for work that he cannot do. Use of visual display units is becoming more and more widespread, and whether or not such a unit is going to be used in a particular job is ascertainable at a first interview. The putative need for the first test proposed by the Directive therefore conflicts with British law and may similarly conflict with prevailing laws of other EC member states. Although Article 2 contains definitions there is no defmition of an eye test. It has not so far been an employer’s task to work
provide an ophthalmological screening service. Not only has it transpired in the past that screening tests--eg, for glaucoma-are not cost-effective, it is also plain that if Parliament, even the European Parliament, wanted such tests to be made available they would say so. Alternatively, we are owed an explanation as to why tests are unnecessary for the rest of us, and why users of display screens should be privileged. In any case, since such tests are essentially preventive and relate to public health, it can be argued that they are the concern of national health systems; the Directive admits as much in an afterthought. Eyesight tests that do not involve refraction are not very demanding, and, given suitable prompted automated equipment, can be self-administered. Their installation should not break the bank; small establishments could share facilities. So far so good. But what sort of eye tests does the Council envisage? A glance at the external eye? A peep inside with an ophthalmoscope? An examination with a slit-lamp or perhaps an ultrasonic scan? To be followed by an electroretinogram, an electro-oculogram, and visual evoked potentials? Or will the test be confined to measurement of the intraocular pressure followed by checks on the visual fields? The point is not only that doctors are not interested when there is nothing to be interested in, but also where are all the required personnel to be found, no matter what testing of eyes is to be done?. In Britain, the number of display units in use will be in six or seven figures. Some are shared, but the number
pairs of eyes that will need "regular" (how frequent?) tests, probably quite unnecessarily, is going to be large. There is not an unlimited number of eye specialists and opticians to be tapped in any country.
The Council has ensured that market forces-the care of the pocket rather than the care of the patient-shall prevail. For the easy and comparatively remunerative work done on healthy eyes will delay the attention that should be given to those who need it. As a practical contribution to the formation of a social fabric the
Council’s prescription seems unimpressive. However, long before the Council will have come to see, let alone acknowledge, the error of their ways, their Directive will have to be made to work by the Members of the Community. Is it possible that the Directive contains its own salvation? Although the document vouchsafes entitlements to workers who habitually use display screen units, at no point does it say that it is concerned with all of them. Thus it may be possible to make a stab at rationalisation by suggesting that the Directive shall apply essentially to workers at some risk, perhaps to those aged 55 years and over. Medical notes would contain information about conditions liable to run in families, lead to eye tests on the basis of commonsense preventive medicine rather than on a bureaucratic edict, and so fulfil the laudable spirit of the Directive. Whatever the views ultimately to be enshrined in our laws, prudence seems to counsel that ministers in various EC countries should harmonise their policies. In this way 90/270/EEC might benefit the populace and not prove to be a social albatross around member states’ necks. 1. Council Directive of May 29, 1990. L 156/14-18.
90/270/EEC. Official J Eur Commun
Radiotherapy or surgery for squamous cell oesophageal carcinoma? The optimum management of oesophageal cancer remains controversial for several reasons. First, oesophageal cancer is not a single disease. In strict pathological terms it comprises the relatively more common squamous cell carcinoma and the much less common adenocarcinoma; the latter arises in metaplastic (Barrett’s) epithelium or, occasionally, de novo in mucus-secreting glands. However, in practice adenocarcinoma of the gastric cardia with involvement of the lower oesophagus has become at least as frequent as a cause of malignant oesophageal obstruction and poses a very similar therapeutic challenge. Second, management largely depends on the apparent stage of the disease at presentation. Although subtle symptoms may develop before the tumour has penetrated into the muscular wall of the
oesophagus,1 presentation is usually delayed until the onset of dysphagia, by which time the tumour is often at a very late stage of its natural history when