TOXIC FACTORS IN VENO‐OCCLUSIVE DISEASE

Veno-occlusive disease (V.O.D. ) has; since it was first described as such (Bras et al., 1954), remained an important disease in Jamaica. Jelliffe et al., 1954, and Stuart and Bras, 1957, 1959, presented the clinical aspects of this disease. Recently, Bras et nl., 1961, stated that 30 per cent of all cases of cirrhosis seen at autopsy in the University College Hospital, Jamaica were the end result of V.O.D. It had long been susected ( McFarlane and Branday, 1945; Royes, 1948) that bush-teas* may be the cause, although any unknown disease in this country has, at some time or other, been ascribed to these herbal concoctions. Morphological study of the lesions in the liver showed us that there was a remarkable resemblance with disease following Senecio poisoning as, for example, described by Wilmot and Robertson, 1920, and Selzer and Parker, 1951, for humans, and by Theiler, 1919, 1920, and Vanek, 1958, for animals, and produced by Davidson, 1935, in experimental rats. Moreover, intensive investigation into the habits of the Jamaican population soon revealed that both Senecio and Crotnlnrin species have been brewed as “bush-tea” and drunk by both adults and children. Attempts to reproduce the veno-occlusive changes in the liver of laboratory animals were successful with Crotalaria given by mouth when COWS and sheep were used (Bras et al., 1957). However, in our earlier experiments, rats, although developing hepatotoxic changes and cirrhosis, produced effects unlike V.O.D. in humans. When large single doses were given by mouth, acute necrosis resulted, as described from our laboratory (for instance, by Stirling and Urquhart, 1962), a development analogous to that described earlier by several authors ( e . g . , Henderson et al., 1951, and Bull et al., 1958). There was no V.O.D. in these rats, which died in the first 48 hours. When Crotalarin fulzja (and Senecio cliscolor) were given by mouth in small repeated dosages, rats gradually developed a fibrosis, starting in periportal location and proceeding to a severe cirrhosis in 30 to 50 days ( Gyijrgy, Goldblatt, and Bras, unpublished data). Again, these rats had no V.O.D. Recently, however, a chance observation led us to modify our experiments: rats were dosed with intermediate amounts of Crotalnrin extract (single dose by mouth) aiming to cause death of a substantial number of the animals somewhere between the fifth or the tenth day. It was then found that under such conditions the animals seemed to die in two waves (FIGURE 1) : ‘ Thc Jamaican population prcyares “bush-tea’’ by boiling leaves (of a variety of plants) in water. Many of these are taken for their alleged medicinal effect.