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OBJECTIVES To investigate the possible role of hypoxia‐inducible factor 1α (HIF‐1α, a transcription factor important in regulating O2 homeostasis and physiological responses to oxygen deprivation) in the recurrence and progression of superficial urothelial bladder cancer, and to examine its expression in relation to proliferation status, apoptotic activity and intratumoral angiogenesis. PATIENTS AND METHODS Paraffin wax‐embedded tissue from 140 patients with superficial primary urothelial bladder carcinoma was immunostained for HIF‐1α, Ki‐67, single‐stranded DNA antibody for apoptotic cells, p53, bcl‐2, vascular endothelial growth factor and CD31 antigen. We calculated the proliferative rate, the apoptotic index and the microvessel density (MVD). The mean (sem) follow‐up was 46 (3.5) months, within which 86 patients relapsed while 18 progressed to a higher tumour stage and/or grade. RESULTS HIF‐1α expression was more common in high‐grade superficial urothelial carcinomas. The positivity was related to increased proliferative activity (P = 0.012), apoptotic rate (P = 0.006) and MVD (P < 0.001). HIF‐1α overexpression had a marginal adverse influence on progression‐free survival (P = 0.058; univariate analysis), but when combined with p53 overexpression, the unfavourable impact was statistically important (P = 0.028). In multivariate analysis, only grade and the high Ki‐67 labelling index were significant predictors of recurrence‐free survival, while T‐stage and the HIF‐1α+/p53+ phenotype emerged as the only independent variables of adverse prognostic significance for time to progression. CONCLUSIONS HIF‐1α overexpression combined with aberrant mutant p53 nuclear protein accumulation seem to indicate an aggressive phenotype, suggesting a potential biological model predictive of future risk of disease progression in patients with superficial urothelial bladder carcinoma. These indicators may be helpful in clinical practice to discriminate superficial bladder cancer worth a more intensive follow‐up, or more aggressive treatment.

Hypoxic-ischemic brain injury is a very important neurological problem of the perinatal period and a major cause of chronic disability later in childhood. The subsequent neurological deficits are a variety of motor defects-especially spasticity but also choreoathetosis, dystonia and ataxia, often grouped together as "cerebral palsy," mental retardation, and seizures. The gestational age determines the neuropathology of the brain injury. One of the patterns of hypoxic-ischemic encephalopathy, typically affecting full-term infants, consists of parasagittal lesions and ulegyria. The aim of this study is to describe the magnetic resonance imaging (MRI) features and discuss the "suggested" pathogenetic mechanisms of this pattern, which affects the cortex and the white matter in a mainly parasagittal distribution; in this type of brain injury, the damage usually involves the deeper sulcal portion while sparing the apex, thus resulting in the so-called mushroom gyri characteristic ulegyric pattern. We discuss the MRI findings of parasagittal lesions and ulegyria in the brain examinations of 14 patients with a clinical history of perinatal hypoxia/anoxia presenting with mental retardation, seizures, and cerebral palsy. Differential diagnosis from polymicrogyria is discussed.

HIF-1alpha and VEGF may play an important predictive and prognostic role in patients with LARC.

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