Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Body habitus as a predictor of injury pattern after blunt trauma.

The records of obese and nonobese victims of blunt trauma were compared to determine if obese individuals are predisposed to a specific injury pattern. Prospectively collected data on 6368 adults admitted to a level I trauma center over a 4-year period were analyzed. Twelve percent (743 patients) met Body Mass Index (weight/height2) criteria for obesity (greater than or equal to 30 kg/m2). The obese group was older (p less than 0.01) and had lower ISSs (p less than 0.05) and higher GCS scores (p less than 0.01). More obese patients were injured in vehicular crashes (62.7% vs. 54.1% [p less than 0.01]). The obese victims were more likely to have rib fractures, pulmonary contusions, pelvic fractures, and extremity fractures and less likely to have incurred head trauma and liver injuries (p less than 0.05). Obese people injured in vehicular crashes had a similar injury pattern with no difference in seating position, direction of impact, seat belt use, and ejection.     

Differential cytokeratin expression in normal, hyperplastic and malignant epithelial cells from human prostate.

Studies were undertaken to define the expression of cytokeratins in normal, hyperplastic and malignant epithelial cells from human prostate. Cytokeratin (CK) polypeptides, separated by two-dimensional electrophoresis, were identified by immunoblotting with CK-specific monoclonal antibodies. CK polypeptides 5, 7, 8, 15, 18 and 19 were identified in fresh normal and hyperplastic prostate. Expression of CK 15 has not been previously reported in human prostate. Analysis of central and peripheral zone tissues from human prostate did not reveal qualitative differences in CK expression between these areas. Epithelial cells harvested from fresh BPH tissue by percoll gradient centrifugation and propagated in vitro using selective culture techniques showed alterations in CK expression compared to intact human prostate. Specifically, CKs 6, 14, 16 and 17 were noted in cultured BPH epithelial cells but not fresh normal prostate or BPH tissue. Immunoblot analysis of the established prostate cancer cell lines PC3, DU145 and LNCAP showed expression of CKs 8 and 18 but not CKs 5, 7 and 15 which were observed in benign prostate. These studies further characterize CK expression in benign and malignant human prostate and provide insights which may be useful in differentiating normal, hyperplastic and malignant epithelial cells in the human prostate gland.     

The association of non-insulin-dependent diabetes mellitus with perceived quality of life in a biethnic population: the San Luis Valley Diabetes Study.

OBJECTIVES: This study evaluated the association between quality of life and non-insulin-dependent diabetes mellitus (NIDDM) status, and whether this association differs between Hispanics and non-Hispanic Whites. METHODS: Between 1986 and 1989, cross-sectional data on perceived quality of life (PQOL) were collected from 223 persons with NIDDM and 753 non-diabetic subjects. RESULTS: After adjustment, persons with NIDDM rated their PQOL significantly lower than did control subjects. The relationship of diabetes and PQOL did not differ by ethnicity. The number of complications of diabetes was not associated with lower PQOL scores. CONCLUSIONS: Control and treatment strategies should reflect an understanding of the impact that diabetes has on social functioning, leisure activities, and physical and mental health.     

Effects of Positive and Negative Mood on Sexual Arousal in Sexually Functional Males

Effects of positive and negative musical mood induction on subjective and objective sexual arousal were examined in a group of sexually functional males (N = 24). Subjects evidenced significantly greater objective and subjective sexual response in the positive mood induction condition relative to both baseline and a neutral control condition. In contrast, the negative mood induction condition yielded significantly less objective sexual arousal than baseline and a neutral control condition. Data provide additional empirical support for the hypothesized impact of mood on sexual arousal.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.