Biomedical subjects

Aileen Murphy

Publications and source records attributed to Aileen Murphy.

9 recordsLinked to original sources

PubMed2006

Sexual orientation, sexual abuse, and HIV-risk behaviors among adolescents in the Pacific Northwest.

OBJECTIVES: We explored HIV risk behaviors, sexual orientation, and sexual abuse among 5 school-based cohorts in Seattle, Wash (SEA95 and SEA99:N=7477 and N=6590), and British Columbia (BC92, BC98, and BC03 [weighted]: N=239975, N=281576, and N=265132). METHODS: An HIV risk scale of 7 items assessed risky sexual behaviors and injection drug use. Self-identified sexual orientation included heterosexual, bisexual, gay/lesbian, and, in British Columbia only, mostly heterosexual. Analyses of covariance were conducted separately by gender and were adjusted for age and sexual abuse when comparing means. RESULTS: Gay/lesbian and bisexual adolescents had higher mean age-adjusted risk scores compared with heterosexual and mostly heterosexual adolescents. After we controlled for sexual abuse history, mean scores were 2 to 4 times higher among abused students than among nonabused students in each sexual orientation group. Age/abuse-adjusted models better explained the variance in risk scores (R(2)=0.10-0.31), but sexual orientation remained an independent predictor. CONCLUSION: Sexual minority adolescents who attended school reported higher HIV risk behaviors, and higher prevalence of sexual victimization may partially explain these risks.

Adolescent↗

PubMed2005

Efficacy, safety, and treatment satisfaction of tadalafil versus placebo in patients with erectile dysfunction evaluated at tertiary-care academic centers.

OBJECTIVES: To determine the efficacy, safety, and treatment satisfaction of tadalafil 20 mg for erectile dysfunction (ED) in patients evaluated at tertiary-care academic centers. METHODS: In this randomized, double-blind, placebo-controlled trial, patients were randomly allocated to receive fixed-dose tadalafil 20 mg (n = 146) or placebo (n = 49) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ); patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and SEP; and safety by adverse events, laboratory values, and vital signs. RESULTS: Mean baseline IIEF erectile function (EF) domain was 12.98. Fifty-one percent of enrolled patients had severe baseline ED, and 82% had organic ED. Pre-existing, ED-associated comorbid conditions were common. When compared with patients treated with placebo, those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain (P <0.001), successful penetration attempts (SEP question 2; P <0.001), successful intercourse (SEP question 3; P <0.001), and all secondary efficacy outcomes (P <0.001). Patients and their sexual partners were also significantly more satisfied with tadalafil treatment (P <0.001), including overall satisfaction (P <0.001) and length of time the treatment worked (P <0.001). Mild or moderate headache, dyspepsia, and myalgia were the most frequent treatment-emergent adverse events reported. CONCLUSIONS: Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated. These results were observed in a tertiary-care, academic center population with a high incidence of severe, organic ED, and comorbid medical conditions, factors known to compromise erectile function and treatment outcome.

Aged↗

PubMed2005

Induction of human immunodeficiency virus type 1-specific T cells by a bluetongue virus tubule-vectored vaccine prime-recombinant modified virus Ankara boost regimen.

In the absence of strategies for reliable induction of antibodies broadly neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have shifted toward the induction of cell-mediated immunity. Here we describe the construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular structures spontaneously formed by protein NS1 of bluetongue virus. We demonstrated that NS1 tubules can accommodate a protein as large as 527 amino acids without losing their self-assembly capability. When injected into BALB/c mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major histocompatibility complex class I-restricted T cells. These could be boosted by modified virus Ankara expressing the same immunogen and generate a memory capable of gamma interferon (IFN-gamma) production, proliferation, and lysis of sensitized target cells. Induced memory T cells readily produced IFN-gamma 230 days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity and antigenic simplicity, the NS1 delivery system could serve as a priming agent for heterologous prime-boost vaccination regimens. Its usefulness in primates, including humans, remains to be determined.

Animals↗

PubMed2004

A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil.

PURPOSE: To assess patient preference for erectile dysfunction treatment between either sildenafil or tadalafil, each administered with their respective dosing instructions, and to evaluate preference for either sildenafil or tadalafil dosing instructions during tadalafil therapy. METHODS: We conducted a randomized, double-blind, crossover study consisting of four treatment arms. Because the dosing instructions for sildenafil and tadalafil are different, a unique methodology using sham placebo arms was employed to maintain the blind. To assess drug preference, 219 patients were randomized to either sildenafil 50 mg or tadalafil 20 mg, with dosing instructions reflecting their respective product profiles. To assess dosing instruction preference during tadalafil therapy, 46 patients were randomized to tadalafil 20 mg with either tadalafil or sildenafil dosing instructions. After 12 weeks, patients were crossed-over. After 4 weeks of each treatment, all patients following sildenafil dosing instructions were offered the opportunity for an upward dose titration. In a double-blind fashion, all patients who requested an upward titration received additional capsules. To mimic the pattern of dose usage observed in clinical practice, the number of patients who received additional double-blind active medication was limited to 35% of patients taking sildenafil in each treatment period in each country. Following the crossover treatment period, patients chose their preferred double-blind treatment with dosing instructions to receive in the 12-week extension period. RESULTS: In the drug preference assessment, 132 of 181 (73%) evaluable patients chose to receive tadalafil (p < 0.001) during the extension period. In the dosing instruction preference assessment, 24 of 36 (67%) evaluable patients preferred tadalafil with tadalafil dosing instructions (p = 0.046). Sildenafil and tadalafil were well tolerated. CONCLUSIONS: In the doses utilized in this study, 73% of patients preferred tadalafil with tadalafil dosing instructions for the treatment of their erectile dysfunction over sildenafil with sildenafil dosing instructions. During tadalafil therapy, 67% of patients preferred tadalafil dosing instructions over sildenafil dosing instructions.

Adult↗

PubMed2004

Measuring sexual orientation in adolescent health surveys: evaluation of eight school-based surveys.

PURPOSE: To examine the performance of various items measuring sexual orientation within 8 school-based adolescent health surveys in the United States and Canada from 1986 through 1999. METHODS: Analyses examined nonresponse and unsure responses to sexual orientation items compared with other survey items, demographic differences in responses, tests for response set bias, and congruence of responses to multiple orientation items; analytical methods included frequencies, contingency tables with Chi-square, and ANOVA with least significant differences (LSD)post hoc tests; all analyses were conducted separately by gender. RESULTS: In all surveys, nonresponse rates for orientation questions were similar to other sexual questions, but not higher; younger students, immigrants, and students with learning disabilities were more likely to skip items or select "unsure." Sexual behavior items had the lowest nonresponse, but fewer than half of all students reported sexual behavior, limiting its usefulness for indicating orientation. Item placement in the survey, wording, and response set bias all appeared to influence nonresponse and unsure rates. CONCLUSIONS: Specific recommendations include standardizing wording across future surveys, and pilot testing items with diverse ages and ethnic groups of teens before use. All three dimensions of orientation should be assessed where possible; when limited to single items, sexual attraction may be the best choice. Specific wording suggestions are offered for future surveys.

Adolescent↗

PubMed2004

Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial.

PURPOSE: We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP). MATERIALS AND METHODS: This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater "yes" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion. RESULTS: Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p <0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events. CONCLUSIONS: Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.

Carbolines↗

PubMed2003

Switching patients with erectile dysfunction from sildenafil citrate to tadalafil: results of a European multicenter, open-label study of patient preference.

BACKGROUND: Three inhibitors of phosphodiesterase 5 (PDE5) are now available for the treatment of erectile dysfunction (ED): sildenafil citrate, vardenafil, and tadalafil. Pharmacologic differences between these compounds may result in patient preferences for one over another and may influence treatment decisions made by the physician and patient. Therefore, clinical research is needed to investigate whether individual properties of the PDE5 inhibitors play a role in shaping patient preference. OBJECTIVES: The goal of this study was to determine what proportion of ED patients currently taking sildenafil would, after a period of treatment with tadalafil, elect to resume treatment with sildenafil at the customary dose and what proportion would elect a switch to tadalafil 20 mg for a longer period. The tolerability of both treatments was also investigated. METHODS: This was a short-term, multicenter, open-label, 1-way crossover trial conducted in Sweden and Italy. Eligible patients included men aged >or=18 years with a minimum 3-month history of ED who had been taking sildenafil at stable fixed doses of 25, 50, or 100 mg as needed for at least 6 weeks and up to 24 weeks. The study consisted of 6 phases: a 1-week screening phase, a 3-week sildenafil assessment phase, a 1-week washout phase, a 6-week tadalafil initiation phase, a 3-week tadalafil assessment phase, and a 6-month extension phase, during which patients received their treatment of choice free of charge. The primary outcome measure was the proportion of patients electing to take sildenafil or tadalafil during the extension phase. RESULTS: Of 155 men enrolled, 147 (97.8%) completed the assessment phases of the trial. Of these 147 men, 133 (90.5%) elected to receive tadalafil in the 6-month extension phase and 14 (9.5%) elected to receive sildenafil (P < 0.001). The proportions preferring tadalafil to sildenafil were similar irrespective of age group (>or=50 years, 92%; <50 years, 90%), severity of ED (mild, 95%; moderate, 88%; severe, 96%), etiology of ED (psychogenic, 94%; organic, 91%; mixed, 87%), and sildenafil dose at study entry (50 mg, 90%; 100 mg, 89%). Both medications were well tolerated. The most common treatment-emergent adverse events occurring in >or=2% of patients during the tadalafil assessment phase included headache (4.8%), nasal congestion (4.1%), dyspepsia (3.4%), flushing (2.7%), back pain (2.0%), diarrhea (2.0%), and nausea (2.0%); the most common treatment-emergent adverse events during the sildenafil assessment phase were flusing (7.1%), nasal congestion (6.5%), headache (4.5%), and nasopharyngitis (3.2%). CONCLUSIONS: In this short-term, open-label study, patients who were currently taking sildenafil for ED and then received tadalafil preferred to continue oral therapy with tadalafil over sildenafil by a ratio of approximately 9:1. Although the study sought to mimic the experience of actual patients receiving treatment for ED, the results are subject to potential limitations due to the design of the study, which included differences in dosing instructions and dosages for sildenafil and tadalafil. Both sildenafil and tadalafil were well tolerated.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

Induction of HLA-A2-restricted CTL responses by a tubular structure carrying human melanoma epitopes.

Epitope-based vaccination strategies designed to induce strong tumor-specific CD8(+) T cell responses are being widely considered for cancer immunotherapy. Here, two recombinant tubular structures, NS1-Mela 1 and NS1-Mela 2, carrying, respectively two HLA-A2 epitopes derived from human melanoma antigens were constructed and their capability to induce CTL responses in vivo were studied in HLA-A2 transgenic mice. Strong CTL responses specific for GnT-V/NA 17-A and gp100 (154-162) epitopes were generated in HLA-A2 transgenic mice immunized by the construct NS1-Mela l carrying these two epitopes. The second construct NS1-Mela 2 carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice. Thus, recombinant tubular structures containing multiple tumoral epitopes may lead to new strategies for the induction of strong tumor-specific CTL responses in cancer patients.

Amino Acid Sequence↗

PubMedDate not supplied

Hazards of stigma: the sexual and physical abuse of gay, lesbian, and bisexual adolescents in the United States and Canada.

Some studies suggest lesbian, gay, and bisexual (LGB) teens are at higher risk than peers for violence at home, in school, and in the community. That can bring them into the child welfare system or services for runaway and homeless teens. This study compared self-reported experiences of sexual and physical abuse based on sexual orientation and gender in seven population-based surveys of youth. The authors used c2 and age-adjusted odds of abuse to compare bisexual to heterosexual, mostly heterosexual, and gay and lesbian students. They also provide case studies to illustrate the experiences of such youth.

Adolescent↗