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This qualitative study identified four life trajectories that influenced the decision in young women to have genetic testing for mutations in BRCA1/2 and subsequent risk reduction decisions after receiving a positive mutation result. Fifty nine women between the ages of 18-39 years were interviewed in this grounded theory study, 44 of those tested were found to have a mutation in either BRCA1 or BRCA2. Of those with a mutation, 23 had no history of cancer and 21 had a breast cancer diagnosis. Analysis of the 44 participants tested found that risk reducing decisions were related to the life trajectories that preceded genetic testing. These life trajectories included: 1) Long-standing awareness of breast cancer in the family, 2) Loss of one's mother to breast cancer at a young age, 3) Expression of concern by a health care provider, and 4) Personal diagnosis of breast cancer. Understanding possible influences behind decision making for genetic testing and risk reduction in young women may assist health care providers in offering age appropriate guidance and support.

Purpose: Depression is a highly prevalent condition in primary care settings. In our previously reported work, we investigated the processes and conditions that influence primary care clinicians' recognition of depression. Three conditions influence the recognition of depression: familiarity with the patient, time available, and clinical experience. This article further describes the role of clinical experience in depression care., Methods: The grounded theory method was used to guide data collection and analysis. In-depth, in-person interviews were conducted with a purposeful sample of 8 clinicians. All interviews were audiotaped and transcribed., Results: We identified 3 areas that comprise clinical experience relevant to depression care: (1) knowing one's professional role, (2) knowing oneself, and (3) knowing one's patients. In knowing one's professional role, 4 subdimensions were identified: (1) becoming familiar with illness patterns and clinical skills, (2) learning what works in the real world, (3) understanding what being a doctor is about, and (4) thinking of the whole person. The analysis indicated that clinical experience results from professional and personal growth during interactions with patients. The outcome of this developmental process was the achievement of comfort with depression care, a critical mediating variable that influenced primary care clinicians' recognition of depression., Conclusions: The developmental process of attaining comfort in managing depression warrants further exploration. Developing interventions to speed this process offers another approach to enhancing care for the management of depression.

A constitutive null mutation of the neural-specific isotype of protein kinase C (gamma-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that gamma-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of gamma-PKC gene deletion also may be due to altered gene expression. To examine alterations in gene expression, microarray analyses were performed on striatal tissue from wild types and mutants. A total of 143 genes and ESTs were identified as potential candidates related to differences between null mutants and wild types. Confirmation studies using qRT-PCR indicated that the expression of transthyretin was increased about 8-fold in striatum of naïve mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because gamma-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naïve and control-diet treated mutants, but did not affect transthyretin expression in wild types.

Neuroadaptive changes that occur in the development of ethanol tolerance may be the result of alterations in gene expression. We have shown that PKCgamma wild-type mice develop tolerance to the sedative-hypnotic effects of ethanol after chronic ethanol treatment; whereas, mutant mice do not, making these genotypes a suitable model for identifying changes in gene expression related to tolerance development. Using a two-stage process, several genes were initially identified using microarray analyses of cerebellar tissue from ethanol-treated PKCgamma mutant and wild-type mice. Subsequent confirmation of a subset of these genes using quantitative real time reverse transcriptase polymerase chain reactions (qRT-PCR) was done to verify gene expression changes. A total of 109 genes from different functional classifications were identified in these groups on the microarrays. Eight genes were selected for verification as follows: three, Twik-1, Plp, and Adk2, were chosen as genes related to tolerance; another three, Hsp70.2, Bdnf, and Th, were chosen as genes related to resistance to tolerance; and two genes, JunB and Nur77, were selected as candidate genes sensitive to chronic ethanol. The results from the verification experiments indicated that Twik-1, which codes for a potassium channel, was associated with tolerance and appeared to be dependent on the presence of PKCgamma. No genes were confirmed to be related to resistance to tolerance; however, expression of two of these, Hsp70.2 and Th, were found to be sensitive to chronic ethanol and were added to the transcription factors, JunB and Nur77, confirmed by qRT-PCR, as a subset of genes that respond to chronic ethanol.

The major difference between cisplatin-based chemotherapy doublets for advanced non-small cell lung cancer (NSCLC) is not in the outcomes of their use--rather, it is in the side effects and toxicities that they cause. The degree to which oncologists involve lung cancer patients in discussions regarding the selection of chemotherapy is unknown. A questionnaire regarding patient concerns about chemotherapy and physician discussions was sent to patients registered in the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE) database from 2000--2002. About three-quarters of the respondents reported that if they were given the option, they would consider side effects important in choosing a particular regimen--and nausea was the most important side effect that would influence that decision. Female patients were more likely to worry about infection and hair loss resulting from therapy than were men. Further, about two-thirds of patients reported that they had discussed differences in chemotherapy side effects with their physicians, particularly if the physicians were female, although less than half of those patients recalled discussing the selection of a particular regimen based upon its side-effect profile. Different chemotherapy regimens with varied side-effect profiles have been developed, but medical oncologists do not present options for chemotherapy uniformly to their patients based on possible or probable adverse reactions. Better communication between physician and patient about the likelihood of side effects may reduce chemotherapy-related stress for patients.

Background: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric alpha7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used alpha7 gene knockout (null mutant) mice to evaluate the potential role of alpha7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol., Methods: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (alpha7(-/-)) and wild-type (alpha7(-/-)) mice., Results: Relative to alpha7(+/+) mice, alpha7(-/-) mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the alpha7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism., Conclusions: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the alpha7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.

Purpose: To describe the experiences of disclosing genetic test results to biological family members among people tested for Huntington's disease (HD) or hereditary breast and ovarian cancer (HBOC)., Design: Grounded theory methodology., Methods: Open-ended, tape-recorded interviews were conducted with 29 participants-24 who had received genetic test results and 5 who had decided not to be tested. The participants were from three countries, including 15 U.S. states. Interviews occurred from 2 months to 4 years after receiving test results. Tapes were transcribed and analyzed for conceptual categories to describe the experience of disclosing genetic test results., Findings: Participants described the effects and meaning of disclosing test results to their various family members, and they selectively disclosed results to family members. The timing of disclosure was influenced by the particular disease and the person's perceived need to prepare. Disclosure of genetic test results brought the risk of HD and HBOC to the foreground, not only for the person tested but for family members as well., Conclusions: This study elucidated the perspective of the "discloser" and the consequences they anticipated and experienced.

Ethanol intoxication results partly from actions of ethanol at specific ligand-gated ion channels. One such channel is the GABA(A) receptor complex, although ethanol's effects on GABA(A) receptors are variable. For example, we found that hippocampal neurons from selectively bred mice and rats with high hypnotic sensitivity to ethanol have increased GABA(A) receptor-mediated synaptic responses during acute ethanol treatment compared with mice and rats that display low behavioral sensitivity to ethanol. Here we investigate whether specific protein kinase C (PKC) isozymes modulate hypnotic and GABA(A) receptor sensitivity to ethanol. We examined acute effects of ethanol on GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in mice lacking either PKCgamma (PKCgamma(-/-)) or PKCepsilon (PKCepsilon(-/-)) isozymes and compared the results to those from corresponding wild-type littermates (PKCgamma(+/+) and PKCepsilon(+/+)). GABA(A) receptor-mediated IPSCs were evoked in CA1 pyramidal neurons by electrical stimulation in stratum pyramidale, and the responses were recorded in voltage-clamp mode using whole-cell patch recording techniques. Ethanol (80 mM) enhanced the IPSC response amplitude and area in PKCgamma(+/+) mice, but not in the PKCgamma(-/-) mice. In contrast, ethanol markedly potentiated IPSCs in the PKCepsilon(-/-) mice, but not in PKCepsilon(+/+) littermates. There was a positive correlation between ethanol potentiation of IPSCs and the ethanol-induced loss of righting reflex such that mice with larger ethanol-induced increases in GABA(A) receptor-mediated IPSCs also had higher hypnotic sensitivity to ethanol. These results suggest that PKCgamma and PKCepsilon signaling pathways reciprocally modulate both ethanol enhancement of GABA(A) receptor function and hypnotic sensitivity to ethanol.