504

close collaboration of the obstetrician experienced inamniocentesis, the paediatrician, the geneticist, andthe biochemist.A note of caution is necessary. Though it would

seem that amniocentesis, in experienced hands, withprevious placental localisation by sonography, is a

comparatively straightforward procedure, it is not

without risk to the fetus and possibly also to themother. Quite apart from the possible dangers oftrauma to the fetus, of haemorrhage, and of infection,there is the risk of isoimmunisation if a transplacentalhaemorrhage occurs. For this reason it has beenrecommended that unimmunised rhesus-negativewomen subjected to amniocentesis should be given aprophylactic dose of Rh immunoglobulin. 2 TheMedical Research Council in Britain has in factmounted a multicentre collaborative study in orderto determine the possible risks of amniocentesiscarried out in early pregnancy for genetic reasons. Afurther complication is that the laboratory proceduresthemselves are not without their difficulties, and forthis reason amniocentesis should be offered onlywhen the laboratory concerned has had adequateexperience in the particular cytogenetic or biochemicalstudies indicated. By collaborative studies such asthose being encouraged by the Medical ResearchCouncils of Canada and Britain, a great deal morewill undoubtedly be learned of the possible risks ofamniocentesis. At the same time new techniquesfor antenatal diagnosis must be pursued. After all,in families at high risk of having a child with a seriousgenetic disorder, antenatal diagnosis with selectiveabortion of affected fetuses seems the only path opento people who want children but are unwilling toaccept the risk of having an affected child.

LEADS IN OESOPHAGEAL CANCER

INCIDENCE-RATES for oesophageal cancer can varyenormously between communities or between geo-graphical areas which are quite close at hand.1-3 In

trans-Saharan, south, eastern, but not generally inwestern Africa it has become very common. High-incidence areas are seen also in the Caribbean islandsand in a vast belt from the Middle East to northernChina.45 5 A number of environmental factors havecome under suspicion, but so far there is not enoughevidence definitely to incriminate any. Heavy metals,alcohol, some contaminant of alcohol,6 iron deficiency,tobacco, alkalis, hot drinks, viruses, and nitrosamines 7are all possible candidates. Cook 2 suggested, for

Africa, an association between maize cultivation (andpresumed consumption as a staple or in fermentedbeer or distilled drinks) and cesophageal cancer. Pure

alcohol, though, seems to be excluded experimentally. 8Known contaminants of drinks include heavy metals(e.g., zinc and copper) and nitrosamines, and so

widely different are the methods of fermentation and

1. Doll, W. R. Br. J. Cancer, 1969, 23, 1.2. Cook, P. ibid. 1971, 25, 853.3. Jayant, K., Balakrishnan, V., Senghvi, L. D. ibid. p. 611.4. Kmet, J., Mahboubi, E. Science, 1972, 175, 864.5. Lancet, 1973, ii, 1365.6. Clemmesen, J. J. natn. Cancer Inst. 1951, 12, 1.

7. Magee, P., Barnes, J. M. Br. J. Cancer, 1956, 10, 114.8. Drill, V. A. Pharmac. Rev. 1952, 4, 1.

distillation that the possibilities are legion. Mc-Glashan 9 suggested that dimethylnitrosamine mightbe formed when wild yeasts acted in any nitrogen-richfermenting beverage, and nitrosamines have beenfound in the mixture of raisins, pomegranate seeds,and peppercorns eaten by the Turkoman women ofnorthern Iran.9 9 Nitrosamines cannot be disregardedwherever food and drink contain nitrates (nitrates canaccumulate in plants grown in molybdenum-poorsoils 10). Perhaps the latest possible factor to beadded to the list is mould. People do not usually eatmouldy cereals, but these may be used for makingfermented foods and alcoholic drinks. In Russia,during the 1939-45 war, it was recognised thatoverwintered grain contaminated with toxic speciesof Fusarium mould caused " alimentary toxicaleukia ",11 and extracts of Fusarium isolates producea similar disease in cats.12 Schoental and Joffe 12have found that rats given crude extracts of Fusariumcultures in high doses show depletion of lymphoidtissues and subsequent infections, suggesting an

immunosuppressive action. In the oesophagus andstomach there is ulceration followed by regenerationand basal-cell hyperplasia. The liver is unaffected.

Immunosuppression and induction of hyperplasiasuggest that Fusarium extracts may contain carcino-genic substances," and ingestion of metabolites ofthis and other moulds may perhaps play a part in thecausation of digestive-tract cancers.

SULPHASALAZINE-INDUCED LUNG DISEASE

DESPITE its side-effects, which include nausea, vomit-ing, headache, rashes, febrile reactions, arthralgia,and less commonly agranulocytosis, hasmolytic anxmia,jaundice, and neurotoxicity,1s-15 sulphasalazine(’ Salazopyrin ’) has for thirty years been a populartreatment for ulcerative colitis. Another side-effectcan now be added to the list : information is availableon six patients with suspected sulphasalazine-inducedlung damage. 16-21 1 Two have been women and four

men, aged between 35 and 58 years. The dose of oralsulphasalazine was 4 g. daily in four patients, and theother two received 1-5-3 g. and 6-8 g. daily, respec-tively. The duration of sulphasalazine treatment

before the onset of respiratory symptoms was 2 monthsin three patients, 4 months in two, and 5 monthsin one. Dyspnoea was the dominant symptom in

every case. Three had cough and unexplained weight-loss, but sputum, wheeze, and a history of allergyto either aspirin or sulphonamides were present in

individual patients only. No patient was a known

9. McGlashan, N. D. Medical Geography; p. 247. London, 1973.10. DuPlessis, L. N., Nunn, J. R., Roach, W. A. Nature, 1969, 222, 1198,11. Schoental, R., Joffe, A. Z. J. Path. 1974, 112, 37.12. Joffe, A. Z. in Microbial Toxins (edited by S. Kadis, A. Ciegler,

and S. J. Ajl); p. 139. New York, 1971.13. Passmore, R., Robson, J. S. (editors) A Companion to Medical

Studies; vol. 2. Oxford, 1970.14. Beeson, P. B., McDermott, W. (editors) Cecil-Loeb Textbook of

Medicine. Philadelphia, 1971.15. Wallace, I. W. Practitioner, 1970, 204, 850.16. Jones, G. R., Malone, D. N. S. Thorax, 1972, 27, 713.17. Thomas, P., Seaton, A., Edwards, J. Clin. Allergy, 1974, 4, 41.18. Collins, J. R., Sth. med. J. 1968, 61, 354.19. Davies, D., MacFarlane, A. Gut, 1974, 15, 185.20. Hutton, W. N. Unpublished.21. Mahler, R. F. Unpublished.