hprt mutant frequencies, nonpulmonary malignancies, and domestic radon exposure: "postmortem" analysis of an interesting hypothesis.

The hypothesis that exposure to domestic radon raises the risk for leukemia and other nonpulmonary cancers has been proposed and tested in a number of epidemiologic studies over the past decade. During this period, interest in this hypothesis was heightened by evidence of increased frequencies of mutations at the hypoxanthine guanine phosphoribosyl transferase (hprt) gene in persons exposed to domestic radon (Bridges BA et al. [1991]: Lancet 337:1187-1189). An extension of this study (Cole J et al. [lsqb[1996]: Radiat Res 145:61-69) and two independent studies (Albering HJ et al. [1992[: Lancet 340:739; Albering HJ et al. [1994[: Lancet 344:750-751) found that hprt mutant frequency was not correlated with domestic radon exposure, and two well-designed epidemiologic studies showed no evidence of a relation between radon exposure and leukemia in children or adults. In this report, we present additional data from a study of Colorado high school students showing no correlation between domestic radon exposure and hprt mutant frequency. We use reanalyses of previous studies of radon and hprt mutant frequency to identify problems with this assay as a biomarker for domestic radon exposure and to illustrate difficulties in interpreting the statistical data. We also show with analyses of combined data sets that there is no support for the hypothesis that domestic radon exposure elevates hprt mutant frequency. Taken together, the scientific evidence provides a useful example of the problems associated with analyzing and interpreting data that link environmental exposures, biomarkers, and diseases in epidemiologic studies.

Vascular damage after photodynamic therapy of solid tumors: a view and comparison of effect in pre-clinical and clinical models at the University of Louisville.

Microvascular damage that results in blood flow stasis is a frequent consequence of photodynamic therapy. The magnitude of this response is dependent on the type of photosensitizer employed for treatment, the amount of drug and light used in therapy and the time period between drug injection and treatment. This review highlights the mechanisms that lead to blood flow stasis in tumor and normal tissues and discusses methods to increase the selectivity of vascular response.

An animal model for mania: preliminary results.

1. In human bipolar patients mania and bipolar depression are both characterized by decreased membrane Na,K-AtPase activity. Additionally, digoxin neurotoxicity in patients frequently presents with symptoms of mania or depression. 2. These findings suggest that central nervous system Na,K-ATPase inhibition may play a pathophysiologic role in bipolar illness. 3. The authors tested this hypothesis by administering intracerebroventricular (i.c.v.) ouabain to rats at sublethal doses. The authors then measured behavioral activity as total square crossings in an open field. 4. Motoric activity was significantly increased by i.c.v. administration of 5 microliters of ouabain at 10(-3) M. This preliminary study suggests that i.c.v. ouabain administration may provide a useful animal model of mania that is based on observed biochemical changes in humans.