Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings

A 55 year old female receiving gemcitabine for stage IV non-small cell carcinoma of the lung developed the clinical-radiologic syndrome of posterior reversible encephalopathy syndrome (PRES). She had clinical manifestations of headaches, increasing somnolence and tonic-clonic seizures. The fluid-attentuated inversion recovery (FLAIR) MR imaging sequence conspicuously showed bihemispheric, symmetrical cortical and subcortical white matter hyperintensities that preponderantly involved the parietal and occipital lobes. Diffusion-weighted imaging (DWI) sequence reflected the preponderant existence of vasogenic edema in the involved areas. MR spectroscopy showed no significant N-acetyl aspartate (NAA) depletion or lactate elevation prospectively, indicating the absence of significant neuronal loss and reversibility of the brain parenchymal changes. The clinical and radiologic manifestations essentially resolved completely with discontinuation of the drug.     

SINGLET OXYGEN INDUCES FRANK STRAND BREAKS AS WELL AS ALKALI- AND PIPERIDINE-LABILE SITES IN SUPERCOILED PLASMID DNA

A covalently closed, circular, supercoiled plasmid was exposed to singlet oxygen by a separated-surface sensitizer. For each exposure, the quantity of single oxygen entering the DNA target solution was estimated by its oxidation of histidine. After singlet oxygen exposure, some DNA samples were treated to disclose occult lesions. Agarose gel electrophoresis was then used to resolve the unrelaxed supercoils from the relaxed circular and linear species, and all bands were quantitated fluorometrically. Exposure of supercoiled plasmid DNA to singlet oxygen induced frank DNA strand breaks, alkali-labile sites (pH 12.5, 90 degrees C, 30 min), and piperidine-labile sites (0.4 M, 60 degrees C, 30 min), all in a dose-dependent manner. Yields of alkali-labile and piperidine-labile sites ranged from one to four times the frank strand break yield. Replacement of buffered H2O by buffered D2O as the DNA solvent for singlet oxygen exposures increased DNA lesion yields by a factor of 2.6 (averaged over lesion classes). Our data for the detection of frank strand breaks is at variance with published results from studies in which singlet oxygen was derived from a thermolabile endoperoxide dissolved in the DNA solution.