Primary progressive aphasia, left anterior atrophy, and neurofibrillary hippocampal pathology: observations in an unusual case.

A 71-year-old, right-handed woman experienced onset of a slowly progressive, nonfluent language disorder. She maintained normal cognitive abilities until age 80 and developed a mild spastic right hemiparesis the following year. By age 82, she had become severely demented, mute, and akinetic. Postmortem brain examination showed moderate asymmetric atrophy (wt = 1000 g), which was most prominent in the left perisylvian and posterior frontal regions, with disproportionate enlargement of the left lateral ventricle. Microscopically, a high density of neurofibrillary tangles was present in the hippocampal pyramidal cell layer and entorhinal cortex (up to 45/400 x field, R > L). Gliosis and patchy neuronal loss were symmetrically present in the frontal and parietal lobes including speech areas, but neurofibrillary tangles and neuritic plaques were present in only small numbers (0-1/400 x field). In this case of primary progressive aphasia, pathologic changes associated with Alzheimer's disease occurred in allocortex but not in neocortex. These clinical and neuropathologic findings expand on those previously reported in primary progressive aphasia and suggest a need for further study of this syndrome.

Effect of storage conditions on nitrosated, acylated, and oxidized pyridine alkaloid derivatives in smokeless tobacco products.

Very large concentration increases in nitrite (34-fold), nitrosated pyridine alkaloids, and related 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (14- to 33-fold) occurred in moist snuff during storage at 24 degrees C for 52 weeks, whereas, decreases in all parent and some acylated pyridine alkaloids were observed in the same material. Nitrite concentrations in dry snuff decreased up to 90% during storage; increased contents of nitrosated alkaloids and NNK of 30 to 80% were also observed. Storage effects on chewing tobacco included a 75% increase in nitrite and small increases of nitrosated alkaloids and NNK. Sums of parent alkaloids in moist snuff decreased 24 and 54% after storage for 24 weeks at 24 and 32 degrees C, respectively, while sums of alkaloid derivatives increased, up to 36-fold for nitrosated alkaloids and NNK, 92% for acylated, and 133% for oxidized components. Levels of N'-nitrosonornicotine, NNK, and N'-nitrosoanatabine after 52 weeks' storage at 24 degrees C were 547, 41, and 296% higher, respectively, in ambient air-exposed moist snuff than in the nonexposed counterpart. A mathematical model was evaluated and used to calibrate nonlinear gas chromatography alkali bead detector response to the individual components. This permitted the use of a single analysis for all required individual compounds over a wide concentration range.

Effects of air-curing environment on alkaloid-derived nitrosamines in burley tobacco.

Levels of nitrite and pyridine alkaloid-derived total tobacco-specific nitrosamines (TSNA) were significantly higher in tobacco leaf (normal or late harvest) air-cured at 32 degrees C/83% relative humidity (RH) than in more moderate environments, i.e., 15 degrees C/50% RH and 24 degrees C/70% RH. These constituents increased appreciably from day 10 to day 21 of the cure. The near-concurrent appearances of maximal total contents of TSNA [sum of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone) (NNK)] and nitrite supports the concept that nitrite is a limiting and proximal precursor of total TSNA during the curing of tobacco. During a long curing period (50 days) at 32 degrees C/83% RH, nicotine and anatabine contents decreased, but TSNA contents increased in leaves of all harvest dates and stalk positions. These results support the view that nicotine and anatabine are precursors of TSNA. Measurement of nitrite and individual alkaloids during post-harvest processing of tobacco leaf may provide an index of the potential accumulation of alkaloid-derived nitrosamines.

Cholinergic enhancement and REM sleep latency in the aged: lecithin does not reproduce physostigmine effect.

The administration of lecithin has failed to improve memory in aged or demented individuals. We studied the effect of lecithin on another cholinergic function, REM sleep latency. Intravenous doses of physostigmine shortened the latency to the first REM sleep period, but oral lecithin did not. In contrast to physostigmine, brain cholinergic function may not be enhanced by lecithin, which may explain why lecithin does not improve cognitive function.