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.     

Parental influences on young girls' fruit and vegetable, micronutrient, and fat intakes.

OBJECTIVE: To evaluate parents' fruit and vegetable intake and their use of pressure to eat in child feeding as predictors of their 5-year-old daughters' fruit and vegetable, micronutrient, and fat intakes. SUBJECTS: Data were obtained from 191 non-Hispanic white families with 5-year-old girls. DESIGN: Parent data included reports of pressure in child feeding and their own fruit and vegetable intake. Girls' intakes of fruits and vegetables, selected micronutrients, and fat were the main outcomes of interest. STATISTICAL ANALYSIS: Structural equation modeling was used to test a model describing relationships among parents' fruit and vegetable intake, parents' use of pressure in child feeding, and daughters' fruit and vegetable, micronutrient, and fat intakes. RESULTS: The model provided a good fit to the data, revealing that girls' fruit and vegetable intake was positively related to their parents' reported fruit and vegetable intake. Parents who consumed fewer fruits and vegetables tended to report greater pressure in child feeding and had daughters who consumed fewer fruits and vegetables. Girls' reported fruit and vegetable intakes were positively related to their micronutrient intakes and negatively associated with fat intake. APPLICATIONS/CONCLUSIONS: This research demonstrates that parents' own fruit and vegetable intake may encourage fruit and vegetable intake in their daughters, leading to higher micronutrient intakes and lower dietary fat intakes. Conversely, pressure to eat may discourage fruit and vegetable intake among young girls.     

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.     

Prosthetic graft infection: limitations of indium white blood cell scanning

The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results. (ABSTRACT TRUNCATED AT 250 WORDS)