Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin-Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium-deficient diet for two generations (Se؊). In Se؊ rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair-fed selenium-adequate rats (Se؉). Weight and tail length were reduced by 31% and 13% in the Se؊ rats, respectively (p < 0.001). The Se؊ diet was associated with a 68% reduction of pituitary growth hormone (GH; p ‫؍‬ 0.01) and a 50% reduction of plasma insulin-like growth factor I (IGF-I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se؊ rats. This group had a 2-fold increase in parathyroid hormone (

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The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of normal mucosa and 331 transitional bladder carcinomas, including 293 superficial (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means of eight parameters relating to densitometric, run-length distribution, and co-occurrence matrix features. The results show that the chromatin texture of the superficial lesions was markedly different from that of the invasive tumours, which exhibited a distinctly more dense and heterogeneous chromatin pattern. The data also show that the increasing level of malignancy, as revealed by the increasing clinical stage, was accompanied by an increase in the overall chromatin condensation level. Only some areas of the nucleus actually increased in density; other pale areas appeared concomitantly with these increasingly denser chromatin areas. This chromatin density increase corresponded to a marked increase in the frequency of small dense chromatin clumps; these joined together into very large dense chromatin clumps, which were distributed more and more heterogeneously in the nucleus as the clinical stage of the tumour increased.

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Tumor growth represents the ratio between cell gain (number of mitoses per unit of time, ie, proliferative activity) and cell loss (number of cell deaths during the same unit of time). While in adults, proliferative activity parallels the level of malignancy in astrocytic tumors and therefore represents a useful diagnostic marker, cell loss has never been concomitantly assessed in tumors of this type. We hypothesize that cell density assessable on histologic slides represents the ratio between cell gain and cell loss. This hypothesis concerns only the diffuse type of astrocytic tumors. Proliferative activity (assessed by MIB1 antigen immunostain) and cell density were thus quantitatively assessed by means of a cell image processor in a series of 54 supratentorial astrocytic tumors of adult patients, which included 15 astrocytomas (ASTs), 18 anaplastic astrocytomas (ANAs), and 21 glioblastomas (GBMs). The results show that proliferative activity and cell density were highly correlated (P=.003) and that both correlated with histopathologic grade. The patients with a high-grade astrocytic tumor (ie, ANA or GBM) that exhibited a low level of In adults, astrocytic tumors represent the most common primary tumors of the central nervous system and include low-grade tumors, ie, astrocytomas M a n u s c r i p t received June 25, 1996; revision accepted September 27,1996.Address reprint requests to Dr Kiss: Laboratory of Histology, Faculty of Medicine, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium.proliferative activity but high cell density survived for significantly shorter periods than did patients with a tumor that exhibited low proliferative activity and low cell density (P=.002). The patients with a high-grade astrocytic tumor that exhibited high proliferative activity and high cell density survived for significantly less time than did the patients with a tumor that exhibited high proliferative activity but low cell density (P<.05). A marked difference in survival periods was observed between the patients with a high-grade astrocytic tumor that exhibited a low level of proliferative activity and low cell density and the patients with a tumor that exhibited a high level of proliferative activity and high cell density (P<.001). The concomitant determination of proliferative activity and cell density seems likely to enable determination of the few adult patients who have high-grade astrocytic tumors and who will survive for a considerable period (several years).

High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.