Place of death: U.S. trends since 1980.

Place of death is one indicator of the state of end-of-life care. We examine trends in national death certificate data on place of death from 1980 to 1998. During these years the percentage of Americans dying as hospital inpatients decreased from approximately 54 percent to 41 percent.

Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region.

It was reported recently that exposure to an adverse rearing environment lowers central nervous system (CNS) serotonergic activity in a nonhuman primate (rhesus monkeys), but only among animals having the shorter variant of a functional, biallelic repeat polymorphism in the regulatory region of the serotonin transporter (5-HTT) gene. Because repeat variants of the same core sequence affect transcriptional efficiency of the 5-HTT gene in humans, we examined whether biallelic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) acts analogously to modulate a previously described association between socio-economic status (SES) and CNS serotonergic function. The 5-HTTLPR was genotyped in 139 adult men and women (n = 75 and 64) who were administered a standard neuroendocrine challenge to assess central serotonergic responsivity (plasma prolactin (PRL) response to the serotonin releasing agent, fenfluramine).

A comparison of d, l-fenfluramine and citalopram challenges in healthy adults.

Dimensional personality characteristics (e.g. impulsivity) and related behaviors and psychiatric disorders are linked to abnormalities of central nervous system (CNS) serotonergic functioning.

Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity.

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity.

Neurobiologic function and temperament in subjects with personality disorders.

Background: Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects.

Methods: A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria) participated in these studies.

Central nervous system serotonergic responsivity and aggressive disposition in men.

To determine whether normative variability in aggressive behavior correlates negatively with central nervous system (CNS) serotonergic function among men, plasma prolactin (PRL) responses to a standard fenfluramine challenge (administered to assess central serotonergic responsivity) were examined in relation to interview-assessed aggression histories among 118 adult males derived from a nonpatient, community sample. Fenfluramine-induced, peak PRL rises were smaller in subjects whose 'aggression' scores fell above the sample median, compared to their less aggressive counterparts (P<.002).

Short-term suppression of ovarian function and immune measures in healthy women.

Ovarian function was suppressed to postmenopausal levels with a GnRH agonist for four months in healthy, premenopausal women to examine the effect of short-term alterations in sex steroid exposure on immune measures at rest and in response to standardized laboratory stressors. Twenty-two women were assessed at three times: (a) during the early follicular phase of the menstrual cycle; (b) after ovarian function had been suppressed by a GnRH agonist; and (c) either in the early follicular phase after the resumption of regular menstrual cycling (group labeled Cycle), or when women received estradiol transdermally in conjunction with a GnRH agonist (group labeled Patch). A third group of 11 women was assessed at similar time points, but in a different order of pharmacologic intervention to evaluate the effects of ovarian function suppression that were not confounded by habituation to the laboratory stressors (group labeled Hormone Control).

Retest reliability of prolactin response to dl-fenfluramine challenge in adults.

Neuropharmacologic probes to assess central nervous system (CNS) serotonergic responsivity (e.g., dl-fenfluramine) stimulate serotonergic neurotransmission, thereby causing proportional release of pituitary-derived hormones into the circulation.

Influence of estrogen replacement therapy on cardiovascular responses to stress of healthy postmenopausal women.

Two experiments were conducted to understand the influence of estrogen exposure on cardiovascular responses to acute stress measured by impedance cardiography. Study I compared stress responses of 29 postmenopausal women who used postmenopausal hormone replacement therapy (HRT) and 29 who did not use HRT. Women who did not use HRT had higher systolic blood pressure and pulse pressure responses to the tasks relative to HRT users.

Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults.

The apolipoprotein E genotype (APOE) is an established risk factor for Alzheimer disease, with the age-at-onset occurring earlier in individuals having at least one APOE epsilon 4 allele, relative to the APOE epsilon 3 or APOE epsilon 2 isoforms. Moreover, nondemented older adults with the APOE epsilon 4 allele also show diminished cognitive performance, particularly on tests of learning and memory, and an accelerated decline in memory performance with increasing age. The current investigation extends the study of the APOE epsilon 4 allele and cognitive performance to healthy, middle-aged adults.

Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme.

The oleoresin secreted by grand fir (Abies grandis) is composed of resin acids derived largely from the abietane family of diterpene olefins as precursors which undergo subsequent oxidation of the C18-methyl group to a carboxyl function, for example, in the conversion of abieta-7,13-diene to abietic acid. A cDNA encoding abietadiene synthase has been isolated from grand fir and the heterologously expressed bifunctional enzyme shown to catalyze both the protonation-initiated cyclization of geranylgeranyl diphosphate to the intermediate (+)-copalyl diphosphate and the ionization-dependent cyclization of (+)-copalyl diphosphate, via a pimarenyl intermediate, to the olefin end products. Abietadiene synthase is translated as a preprotein bearing an N-terminal plastidial targeting sequence, and this form of the recombinant protein expressed in Escherichia coli proved to be unsuitable for detailed structure-function studies.

Effects of behavioural family management on family communication and patient outcomes in schizophrenia.

Background: Family interventions for schizophrenia have proved to be highly effective in preventing relapse, but it is not clear how they work or how they should be structured.

Aims: To examine the effects of a behavioural family intervention and a family support programme on communication, problem solving and outcome in order to determine the impact of structured communication training.

Method: Patients and family members participating in the Treatment Strategies in Schizophrenia study were videotaped engaging in 10-minute problem-solving conversations at baseline and after the conclusion of the family intervention.

A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.

This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride).

Do the daily experiences of healthy men and women vary according to occupational prestige and work strain?

Objective: This study evaluated the influence of occupational prestige and work strain on mood, the occurrence of interpersonal conflict, and ambulatory blood pressure and heart rate.

Methods: Participants were 50 men and 50 women matched for occupational prestige who were healthy and middle-aged and who completed measures of mood and conflict simultaneously with measures of ambulatory blood pressure and heart rate recorded every 30 minutes during waking hours of two workdays and one nonworkday; at the end of each day, overall ratings were made. Work strain was assessed by the Work Section of the Self-Evaluation and Social Support Interview Schedule.

Stereochemistry of the cyclization-rearrangement of (+)-copalyl diphosphate to (-)-abietadiene catalyzed by recombinant abietadiene synthase from Abies grandis.

[reaction: see text] Syntheses and enzymatic cyclizations of 8alpha-hydroxy-17-nor copalyl diphosphate (8a), (15R)-[15-2H1] 8b, and (15R,17E)-[15-3H1,17-2H1] copalyl diphosphate ([2H,3H] 2) catalyzed by recombinant abietadiene synthase (rAS) gave 17-nor manoyl oxide (9a), (16E)-[16-2H1] 9b, and (15S,16R)-[16-2H1,16-3H1] abietadiene ([2H1,3H1] 4), respectively. These and other results indicate that conversion of CPP (2) to abietadiene (4) occurs by anti S(N)' cyclization to a sandaracopimar-15-en-8-yl carbocation intermediate (13+, 13beta-methyl) followed by hydrogen transfer and methyl migration suprafacially on the si face of the vinyl group.

Effects of lovastatin on cognitive function and psychological well-being.

Purpose: Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function, mood, and behavior, but few clinical trials have studied these effects.

Subjects And Methods: In this double-blind investigation, 209 generally healthy adults with a serum low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Assessments of neuropsychological performance, depression, hostility, and quality of life were conducted at baseline and at the end of the treatment period.

Does socioeconomic status relate to central serotonergic responsivity in healthy adults?

Objective: We tested whether low SES was associated with reduced central serotonergic responsivity in a community sample of adult men and women and the extent to which standardized measures of aggression and impulsivity mediate the association.

Methods: A total of 270 adults who were enrolled in a clinical trial on the neurobehavioral effects of lipid lowering were given a neuropharmacologic challenge (plasma prolactin response to orally administered fenfluramine) to measure serotonergic responsivity. Measures of family income and educational attainment were standardized and summed to derive an overall index of SES.