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This study examined relationships between timing of gay-related developmental milestones, early abuse, and emergence of poor health outcomes in adulthood among 1,383 gay/bisexual men in the Urban Men's Health Study. Latent Profile Analysis grouped participants as developing early, middle or late based on the achievement of four phenomena including age of first awareness of same-sex sexual attractions and disclosure of sexual orientation. Participants who developed early were more likely, compared to others, to experience forced sex and gay-related harassment before adulthood. They were more likely to be HIV seropositive and experience gay-related victimization, partner abuse and depression during adulthood. Early forced-sex, gay-related harassment and physical abuse were associated with several negative health outcomes in adulthood including HIV infection, partner abuse, and depression. This analysis suggests that the experience of homophobic attacks against young gay/bisexual male youth helps to explain heightened rates of serious health problems among adult gay men.

In general, patterns of use are shaped by age, education, gender, and illness severity. Larger, more supportive networks decrease the use of patterns of care that include formal health care providers, and decrease direct entry into the mental health sector. These results are in line with NEM's predictions for lower class populations and help clarify inconsistencies in previous research on social networks. The implications of this perspective for health services research and treatment are discussed.

Sex researchers and mental health clinicians have long recognized that the stigma surrounding homosexuality plays an important role in shaping the social psychological adjustment of gay, lesbian, and bisexual (g/l/b) people. In recent years, researchers have suggested that sexual identity- related distress may influence the physical health status of g/l/b people, primarily because of the ways these self-related feelings and beliefs impact patterns of health-related behavior. This study examines the influence of sexual identity distress and social support on g/l/b youth's drug and alcohol use, psychological distress, and risky sexual behavior. The data come from a services research demonstration program conducted at the Indiana Youth Group, Inc., a g/l/b youth development agency based in Indianapolis, Indiana. Results indicate that sexual identity distress is strongly associated with psychological distress, less frequent use of alcohol, and using fewer types of illegal drugs. Being out to more people in one's support network, however, attenuates the severity of youth's sexual identity-related distress. Youth who report more support ties to g/l/b people indicate engaging in more frequent risky sexual behavior. The implications of these findings for theories of g/l/b youth's sexual identity development are discussed.

This research explores the experiences of mental illness stigma in 24 youth (58.3% male, 13-24 years, 75% Latino) in psychiatric outpatient treatment. Using Link and Phelan’s (2001) model of stigmatization, we conducted thematic analysis of the interview texts, examining experiences of stigma at individual and structural levels, in addition to the youths’ social-psychological processes. Youth in psychiatric treatment acknowledged that their larger cultural context holds pejorative viewpoints toward those with mental illness and reported experiences of stigma within their families and social networks. Our results also offer insight into the social-psychological processes of stigma, highlighting how labeling may influence their self-concept and the strategies in which youth engage to manage a stigmatized identity. We discuss differences in stigma experiences by gender, age, and diagnosis. Findings provide new information on the stigma experiences of youth in psychiatric treatment and suggest that a multilevel approach to reduce stigma is warranted.

Cyclophosphamide (CPA) is an anticancer prodrug that is dependent on cytochrome P450 (CYP) metabolism for its therapeutic effectiveness. In spite of the use of CPA in the clinic for over 50 years, little is known about the relationship between its toxicokinetics and therapeutic response. We have employed a powerful new model, the Hepatic Cytochrome P450 Reductase Null (HRN) mouse, which has almost no hepatic cytochrome P450 activity, to study the toxicokinetics of CPA and to establish in vivo the role of hepatic P450 metabolism in its pharmacokinetics. In HRN mice the in vitro metabolism and intrinsic clearance of CPA was over 6-fold lower than in wild-type animals. This change in CPA metabolism was also reflected in vivo, with a profound difference in the pharmacokinetics of both CPA and its metabolites. At a CPA dose of 100 mg/kg, the C max , plasma area under the curve (AUC) and half-life were increased by 2.6-, 6.2-, and 3.2-fold, respectively, in the HRN mice. Similar changes were also observed at a dose of 300 mg/kg. These data confirm that hepatic metabolism is the major route of CPA elimination and disposition. The primary metabolites of CPA, 4-hydroxycyclophosphamide (4-OH-CPA) and 3-dechloroethylcyclophosphamide, were still formed, but at altered rates in the HRN mice. At 100 mg/kg the t 1/2 for 4-OH-CPA was increased 1.8-fold, the C max reduced 1.7-fold, and the AUC remained unchanged. This latter finding shows that P450-mediated oxidative metabolism is essential for the clearance of this compound. Toxicokinetic analysis of CPA-induced myelosuppression and granulocytopenia showed that at high doses (z z100 mg/kg) there was no difference in myelotoxicity between the wild-type and HRN mice. However, at lower doses (V V70 mg/kg) a significant difference was observed, with little toxicity seen in HRN mice but at least a 45% reduction in the bone marrow granulocyte population in wild-type mice. Meta-analysis of the toxicity experiments showed the myelotoxicity of CPA was found to be closely correlated with the C max of 4-OH-CPA (r 2 = 0.80, P = 0.002). As the therapeutic effectiveness of CPA has been linked to the AUC for 4-OH-CPA, the finding that 4-OH-CPA C max may determine its level of myelotoxicity indicates that the therapeutic index could be altered by changing the method of CPA administration.

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