Gamma-glutamyl transpeptidase activity during carcinogenesis of hamster buccal pouch epithelium

Gamma-glutamyl transpeptidase (GGT) activity has been demonstratedhistochemically in a number of experimentally induced neoplasmsand has been suggested as a label for potential precursors forthe development of squamous cell carcinomas. This study exploresthe kinetics of GGT-stained cell populations, their correlationwith the hypothesized initiated cells and evidence of malignanttransformation of epithelium in hamster buccal pouch by a 15-weekregime of tri-weekly topical application of 7,12-dimethylbenz[a]anthracene(DMBA) in mineral oil. GGT-positive foci were detected histochemicallyin tissue sections as early as 1 week after application of thecarcinogen, when there was no morphological evidence of dysplasia.The average number of the GGT-positive foci in each experimentalperiod was found to increase with time. Even though the majorityof the foci were small, consisting of only a single cell ora small group of cells, a few larger GGT-positive lesions werenoted, particularly in the later period of the experiment. Atotal of 66 grossly visible neoplasms were found. Thirty-sevenof these were submitted for GGT staining. Thirty-two (86.5%)of these showed patchy GGT activity, primarily in the superficialepithelial cells and/or the keratin. In the non-neoplastic epithelium,the GGT staining could involve any or all layers of cells. GGTactivity was not detected in untreated or mineral oil-treatedmucosa. The results of this study support the hypothesis thatGGT activity may label potential precursors for the developmentof squamous cell carcinomas.     

Nonspecific mitochondrial disease with epilepsy in children: diagnostic approaches and epileptic phenotypes

OBJECTIVES: This study sought to characterize epileptic phenotypes in children with nonspecific mitochondrial disease (MD) and to evaluate MD diagnostic approaches. METHODS: A retrospective analysis of the medical, electroencephalogram, and laboratory records of 142 patients with epilepsy was performed. The patients were evaluated for MD, and 124 patients were included in the final cohort. The MD criteria used included an oral glucose lactate stimulation test (OGLST) and urine organic acid/plasma amino acid (UOA/PAA) assays as metabolic indicators of modified Walker criteria, as suggested by Bernier et al. (Neurology 59:1406-1411, 2002). RESULTS: Twenty-two patients were classified as having definite MD (9), probable MD (5), possible MD (6), or pyruvate dehydrogenase (PDH) deficiency (3), including one patient which showed a respiratory chain (RC) defect and PDH deficiency. Seven out of eight patients in whom significant RC defects were observed showed complex I defects. In 14 patients, epileptic seizures start at infantile ages. Of 17 patients who substantially presented generalized seizures, 4 patients started with partial seizures. Five patients consistently presented only partial seizures. The OGLST and UOA/PAA assays were useful for a more precise diagnosis of MD, although low positive predictive value of the OGLST was regrettable. No patient was classified as definite MD by Walker's original criteria, but the use of our revised MD criteria resulted in the classification of nine additional patients as definite MD. CONCLUSIONS: MD manifested considerable diverse epileptic phenotypes and should be considered in the differential diagnosis of epilepsy in children with unexplained encephalomyopathy and progressive and fluctuating clinical courses.     

HIPDM single photon emission computed tomography brain imaging in partial onset secondarily generalized tonic-clonic seizures

HIPDM-Single photon emission computed tomography brain imaging was performed during interictal and ictal stages in three patients with complex partial seizures and secondarily generalized tonic-clonic seizures. In all three patients, interictal studies demonstrated decreased regional cerebral perfusion (rCP) and ictal studies showed increased rCP in the epileptogenic region. The demonstration of focal hyperperfusion by SPECT performed during secondarily generalized tonic-clonic seizures suggests that rCP in the epileptic focus remains higher than in other cerebral regions during immediate postictal stages, even in secondarily generalized seizures.