Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

Rhinebothrium pearsoni, sp nov., is described from Banks' shovelnosed ray, Aptychotrema banksii (Muller & Henle). PhyNobothrium orectolobi, sp. nov., is described from the wobbegong, Orectolobus maculatus (Bonnaterre). Anthobothrium amuleturn, sp nov., is described from the common shovel- nosed ray, Rhinobatos armatus (Gray). Pedibothrium ottleyi, sp. nov., is described from the zebra shark, Stegostoma tigrinum (Pennant), and the genus Pedibothrium Linton, 1909, is emended. Calliobothrium creeveyae, sp. nov., is described from the school shark, Galeorhinus australis (Macleay). Polypocephalus moretonensis, sp nov., is described from the estuary stingray, Dasyatis fluviorum Ogilby. Tylocephalum carnpanulatum, sp. nov., is described from the shark ray, Rhina ancylostomus Bloch & Schneider. Also described are a species of Balanobothrium Hornell, 1912, from S. tigrinum; a species of Cathetocephalus Dailey & Overstreet, 1973, and a species of Discocephalum Linton, 1890, from the black-tip shark, Carcharhinus spallanzani (Le Sueur), and Hornellobothrium cobraformis Shipley & Hornell, 1906, from the spotted eagle-ray, Aetobatis narinari (Euphrasen).

Summary Nitro-L-arginine inhibits the production of nitric oxide and can thereby cause vasoconstriction in vivo. One consequence of this is that nitro-L-arginine can increase hypoxia in a range of transplantable and spontaneous murine solid tumours. Bioreductive drugs such as RB6145 are more active under hypoxic conditions, and the combination of RB6145 with nitro-L-arginine in vivo shows greater anti-tumour activity than either agent individually. In mice given nitro-L-arginine at 10 mg kg-' i.p. up to 1 h before or after 300 mg kg-' i.p. RB6145, survival of KHT tumour cells was reduced by 3-4 logs when assessed by clonogenic assay 24 h after treatment. RB6145 or nitro-L-arginine alone caused no more than 20% cell kill. Similar effects were found in SCCVII tumours. The tumour response to the drug combination was tumour size dependent, with increased tumour cell sensitivity occurring when the tumour volume at the time of treatment was increased. Further, the response of KHT tumours to the combination of RB6145 and nitro-L-arginine was also dependent on the time interval between treatment and on when tumours were excised for determination of survival in vitro. The relative surviving fraction was about 0.3 for intervals less than 4 h but was reduced to 0.01 at 12 h and 0.001 at 24 h. These results were supported by histological examination of tumours, when necrosis at 2 h after treatment was less than 5% but increased to greater than 90% at 24 h. RB6145-induced normal tissue damage, as measured by CFU-A survival, was not altered by combining with nitro-L-arginine. Hence, this drug combination may provide therapeutic benefit. It is likely that the substantial anti-tumour effects are due to enhancement of bioreductive toxicity through increased tumour hypoxia, although additional mechanism(s) may also contribute to the overall response.

In ecosystems where large-scale disturbances are infrequent, the mode of succession may be difficult to discern and floristic surveys alone cannot be used determine the underlying processes causing vegetation change. To determine the causes of vegetation change in response to a large-scale fire event, we combined traditional floristic survey data, plant functional traits and environmental variables in a model-based solution to the fourth-corner problem. This approach allowed us to describe the trait-environment relationship and provides an intuitive matrix of environment by trait interaction coefficients. We could then quantify the strength and direction of associations between plant traits, species life-forms and environmental factors in two alpine plant communities over nine years post-fire. Initially, the fire drastically reduced vegetation cover and species density to very low levels. The fourth-corner analysis interaction coefficients indicated that over the course of the nine-year study a high abundance of graminoids, a low abundance of shrubs, tall species and those with high leaf dry matter content had the strongest associations with the two plant communities. We also found evidence for functional homogenisation between these two communities using this novel technique. Analysing plant traits and species responses post-fire in this manner can be used to infer the ecological processes driving shifts in vegetation.