Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.

Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling.

Influence of dietary mushroom Agaricus bisporus on intestinal morphology and microflora composition in broiler chickens.

In this study, we evaluated the intestinal morphology and bacteria populations in broiler chickens fed for six weeks diets that contained different amount of the mushroom Agaricus bisporus. Ninety day-old female chicks were randomly divided into three dietary treatments, each with three replicates kept in floor pens and fed a basal diet supplemented with the dried mushroom at levels of 0, 10 or 20 g/kg fresh feed. Feed and water were offered to birds ad libitum. The morphological examinations of the intestine were carried out on 1-cm long excised segments from duodenum, jejunum and ileum. The populations of total aerobes, total anaerobes, Lactobacilli spp., Bifidobacteria spp., Escherichiacoli, Bacteroides spp. and Enterococci were enumerated in ileum and caecum by conventional microbiological techniques using selective agar media. The results of the study showed that dietary mushroom supplementation did not significantly affect intestinal morphology at either level of inclusion. Morphometrical parameters of depth of duodenum, jejunum and ileum crypt and height of villi revealed no differences amongst dietary treatments. In the ileum, Lactobacilli spp. were higher in birds supplemented at the level of 20 g/kg compared to controls; however, other measurements of bacteria loads were similar amongst the three dietary treatments. In the caecum, Lactobacilli spp. and Bifidobacteria spp. loads were higher in birds supplemented at either level of inclusion compared to control birds, although these did not differ between the two levels of supplementation. In conclusion, dietary mushroom supplementation may beneficially affect intestinal health of broiler chickens.

Health motivation and emotional vigilance in genetic testing for prostate cancer risk.

Actual uptake of genetic testing for cancer susceptibility is generally lower than 50%, despite a high initial interest above 80%. As population-based genetic testing for cancer susceptibility becomes more widespread, there will be an increasing need to understand the relationship of patient-affective factors to test intention and actual uptake behavior. Using hypothetical genetic testing for prostate cancer susceptibility as an example, we used surveys of 400 men in the general population of Philadelphia to develop a Structural Equation Modeling diagram to reveal the influence of affective factors implicated in the intention to undergo genetic testing for prostate cancer risk. Results showed that most men want genetic testing for prostate cancer, believe strongly in its benefits, and are not deterred by negative affect. Our data suggest that high positive expectations, plus a high desire to comply with physician and family suggestions, result in an increased test intention. Informed consent assessment, therefore, requires an appreciation not only of patient risk, but awareness of patient motivation and affect as well.

The family covenant and genetic testing.

The physician-patient relationship has changed over the last several decades, requiring a systematic reevaluation of the competing demands of patients, physicians, and families. In the era of genetic testing, using a model of patient care known as the family covenant may prove effective in accounting for these demands. The family covenant articulates the roles of the physician, patient, and the family prior to genetic testing, as the participants consensually define them. The initial argument defines the boundaries of autonomy and benefit for all participating family members. The physician may then serve as a facilitator in the relationship, working with all parties in resolving potential conflicts regarding genetic information. The family covenant promotes a fuller discussion of the competing ethical claims that may come to bear after genetic test results are received.

How men view genetic testing for prostate cancer risk: findings from focus groups.

OBJECTIVE: To determine the values, beliefs, and attitudes that influence a man's intention to undergo or defer genetic testing for prostate cancer risk. DESIGN: Qualitative, using focus group interviews 12 focus groups were conducted to identify key values and beliefs about genetic testing for prostate cancer risk in anticipation of its future availability. SETTING: Medium-sized, mid-west, US city. PARTICIPANTS: Community sample of 90 lay men of diverse educational, ethnic, and age backgrounds. ANALYSIS: Descriptive statistics and immersion/crystallization to identify themes and sub-themes. RESULTS: The major areas of concern were distilled into the following. THEMES: beliefs about consequences, expectations, benefits for patients, beliefs about barriers, and susceptibility concerns. CONCLUSION: Identifying these men's values will help health professionals anticipate the informational and ethical needs of patients in the informed consent process. Men will need to understand how such testing may affect their planning regarding future prostate health, and how medical information is used outside of the physician patient relationship.

Family physicians' perspectives on genetics and the human genome project.

The objective of the study was to determine family physicians' attitudes and beliefs about human genetics research and the human genome project (HGP). The design of the study involved qualitative, semi-structured interviews. Primary variables of interest included family physicians' training; their attitudes about the HGP; requests for genetics counseling; and their approaches to counseling requests. The setting was a medium-sized, Midwest, US city. The participants were 16 university-affiliated, community-based family physicians. For contents analysis, we used a coding scheme to identify illustrative themes and subthemes. While most of the family physicians reported familiarity with genetics and the HGP, and experiences with counseling requests, nearly all (15) reported little training in genetics counseling. Four major themes were identified: 1) impact on clinical care; 2) educational issues relevant to genetics and the HGP; 3) ethical concerns; and 4) family medicine responsibilities. These family physicians do not perceive genetics as having a substantial impact on their practice, but do expect major clinical changes in the future. Many feel there have been inadequate educational opportunities to learn about genetics, and some indicate reluctance to invest in self-education until genetic problems become more clinically relevant. These practitioners envision a role for family medicine the specialty to shape priorities in genetics research.

Considering advance directives for oncology patients.

Communication is an important cornerstone to the physician-patient relationship when considering advance directives. Discussing advance directives with patients is a process best initiated in routine, well-adult care that can be made more daunting when the patient is critically ill; yet, when patients are afflicted with cancer, communication on advance directives can be optimized when the primary care physician and oncologist together work with the patient. The need to counsel patients on advance directives regardless of the venue (whether inpatient or outpatient) highlights that an ongoing alliance between the oncologist and the primary care physician can help facilitate consent to, and allow periodic review of, advance directives by cancer patients. This process ensures that the patient's preferences are respected at life's end.

Supporting assisted suicide. How do the public and physicians feel about aiding in death?

In January 1997, the Michigan State Medical Society began a series of interdisciplinary forums to discuss guidelines and safeguards for physician-assisted suicide as part of its ongoing analysis of that vexing issue. The forums derive from the minority statement in the MSMS official position, from physicians who would approve of assisting suicide in a limited number of cases, but only upon the patient's voluntary request and as a last resort. Is it possible to develop guidelines which would succeed in limiting the practice of physician-assisted suicide to that small group of patients? Or, as opponents charge, would guidelines predictably fail to contain the practice and lead to the feared slippery slope?

Black/white differences in attitudes toward physician-assisted suicide.

In 1994, as the Michigan legislature considered whether to continue a law banning physician-assisted suicide, we conducted a series of surveys on this topic. One of these surveys, conducted in Detroit, was designed to measure the attitudes of a largely black population toward physician-assisted suicide. Questionnaires were mailed to 500 residents of Detroit. The questionnaire described a plan for legalizing physician-assisted suicide, called Plan A, that incorporated eligibility standards and safeguards to minimize abuse. Attitudes on three issues were investigated: 1) Should physician-assisted suicide be banned or legalized? 2) Should voluntary euthanasia also be permitted? 3) Might respondents request legalized physician-assisted suicide for themselves? Majorities of both whites and blacks supported Plan A; however, support was much lower among blacks than whites. Blacks were also less likely to support voluntary euthanasia or to envision asking for physician-assisted suicide themselves. Our analysis indicates that when age and sex are held constant, strength of religious commitment may account for much of the black-white difference in attitudes. We also consider alternative explanations based on cultural attitudes and degree of trust in the medical system.

A preventive ethics approach to counseling patients about clinical futility in the primary care setting.

Given the current themes of futility and managed care in medicine and bioethics, the primary care setting needs to account for how to address futility. We argue for applying the concept of clinical futility to primary care medicine. A preventive ethics approach directs the primary care physician to explain and counsel against futile interventions, with a negotiation strategy for circumstances of disagreement. These efforts will require primary care physicians to concentrate their efforts on education, negotiation, and enhanced trust in their patient relationships. Using a preventive ethics approach in these circumstances, the physician can better protect the interests of the patient by avoiding nonbeneficial interventions, especially those that also are potentially harmful.

Attitudes of Michigan physicians and the public toward legalizing physician-assisted suicide and voluntary euthanasia.

BACKGROUND: There has been a continuing public debate about assisted suicide and the proper role, if any, of physicians in this practice. Legislative bans and various forms of legalization have been proposed. METHODS: We mailed questionnaires to three stratified random samples of Michigan physicians in specialties likely to involve the care of terminally ill patients: 500 in the spring of 1994, 500 in the summer of 1994, and 600 in the spring of 1995. Similar questionnaires were mailed to stratified random samples of Michigan adults: 449 in the spring of 1994 and 899 in the summer of 1994. Several different questionnaire forms were used, all of which included questions about whether physician-assisted suicide should be banned in Michigan or legalized under certain conditions. RESULTS: Usable questionnaires were returned by 1119 of 1518 physicians eligible for the study (74 percent), and 998 of 1307 eligible adults in the sample of the general public (76 percent). Asked to choose between legalization of physician-assisted suicide and an explicit ban, 56 percent of physicians and 66 percent of the public support legalization, 37 percent of physicians and 26 percent of the public preferred a ban, and 8 percent of each group were uncertain. When the physicians were given a wider range of choices, 40 percent preferred legalization, 37 percent preferred "no law" (i.e., no government regulation), 17 percent favored prohibition, and 5 percent were uncertain. If physician-assisted suicide were legal, 35 percent of physicians said they might participate if requested--22 percent would participate in either assisted suicide or voluntary euthanasia, and 13 percent would participate only in assisted suicide. Support for physician-assisted suicide was lowest among the strongly religious. CONCLUSIONS: Most Michigan physicians prefer either the legalization of physician-assisted suicide or no law at all; fewer than one fifth prefer a complete ban on the practice. Given a choice between legalization and a ban, two thirds of the Michigan public prefer legalization and one quarter prefer a ban.

Attitudes and behaviors on physician-assisted death: a study of Michigan oncologists.

PURPOSE: To ascertain the attitudes of oncologists toward physician-assisted death, ie, physician-assisted suicide and active euthanasia, as well as their experiences with these activities and their opinions toward their legalization. METHODS: A survey was mailed to all practicing 250 oncologists in the state of Michigan, with subsequent development of psychometric scales and their correlation with self-reported behaviors in physician-assisted death. RESULTS: Analysis revealed five distinct, meaningful factors regarding approval or disapproval of physician-assisted death. These factors reflected global attitudes toward physician-assisted death, passive euthanasia, philosophical prohibitions toward physician-assisted death, concerns of legal consequences with physician-assisted death, and attitudes that physician-assisted death could be avoided with better end-of-life care (alpha = .94, .74, .76, .87, and .84, respectively). High levels of therapy withdrawal were reported (81%), with significant reservations toward assisted suicide and active euthanasia, although reported participation in such actions was noteworthy (18% and 4%, respectively). The scales reflecting global and philosophical attitudes correlated with several attitudes and behaviors toward physician-assisted death (P < .001). Legislation that would allow physician-assisted death was favored by 20.8% of respondents. CONCLUSION: Although they have reservations about physician-assisted death, significant numbers of oncologists are willing to consider such actions should they become legal. Given the substantial number of physicians who report that they have already participated in physician-assisted death, these findings may help better understand the attitudes that motivate physician behaviors toward assisted death.