The use of second-generation antipsychotics and the changes in physical growth in children and adolescents with perinatally acquired HIV.

Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3-18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1-3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection.

Lifetime changes in body mass index and risk of breast cancer in minority women

Introduction: Obesity is an epidemic in the United States, especially among Hispanics and African-Americans. Studies of obesity and breast cancer risk and subtype have been conducted primarily in non-Hispanic whites. Obesity is inversely associated with premenopausal breast cancer, but both obesity and weight gain increase the risk of postmenopausal disease. Obesity has been associated with breast cancer subtype in many studies. Methods: To assess the association between changes in body mass index (BMI) over the lifetime, weight gain, and breast cancer in Mexican-American women, we conducted a case-control study using 149 cases and 330 age-matched controls. In a second study, we identified 212 African-American and 167 Mexican-American women with breast cancer in the ongoing ELLA Bi-National Breast Cancer Study, abstracted medical charts to classify tumors as ER+/PR+, HER2+, or ER-/PR-/HER2-, and assessed the association between lifetime changes in body mass index, weight gain, and breast cancer subtype. In both studies, growth mixture modeling was use to identify trajectories of change in BMI over the lifetime, and these trajectories were used as exposures in a logistic regression model to calculate odds ratios (OR). Results: There was no association between trajectories of change in BMI and breast cancer risk in Mexican-American women. In addition, BMI at ages 15 and 30 and at diagnosis was not associated with breast cancer. However, adult weight gain was inversely associated with breast cancer risk (per 5kg, OR=0.92, 95% CI: 0.85-0.99). The case-only analysis found no association between obesity at ages 15 and 30 and at diagnosis and breast cancer subtype. Further, there was no association between adult weight gain (defined as weight change from age 15 to time of diagnosis) and breast cancer subtype. Conclusions: Obesity was not associated with breast cancer risk in Mexican-American women, while adult weight gain reduced the risk independently of menopausal status. These results are contradictory of those in non-Hispanic white women and suggest that the etiology of breast cancer may differ by race/ethnicity. Further, obesity was not associated with breast cancer subtype in African-American and Mexican-American women, contrary to results in non-Hispanic white women. ^

Development of combined micro -preparation, separation, and mass spectrometry methods and application in the microdialysis study of neuropeptide metabolism

Two sets of mass spectrometry-based methods were developed specifically for the in vivo study of extracellular neuropeptide biochemistry. First, an integrated micro-concentration/desalting/matrix-addition device was constructed for matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) to achieve attomole sensitivity for microdialysis samples. Second, capillary electrophoresis (CE) was incorporated into the above micro-liquid chromatography (LC) and MALDI MS system to provide two-dimensional separation and identification (i.e. electrophoretic mobility and molecular mass) for the analysis of complex mixtures. The latter technique includes two parts of instrumentation: (1) the coupling of a preconcentration LC column to the inlet of a CE capillary, and (2) the utilization of a matrix-precoated membrane target for continuous CE effluent deposition and for automatic MALDI MS analysis (imaging) of the CE track.^ Initial in vivo data reveals a carboxypeptidase A (CPA) activity in rat brain involved in extracellular neurotensin metabolism. Benzylsuccinic acid, a CPA inhibitor, inhibited neurotensin metabolite NT1-12 formation by 70%, while inhibitors of other major extracellular peptide metabolizing enzymes increased NT1-12 formation. CPA activity has not been observed in previous in vitro experiments. Next, the validity of the methodology was demonstrated in the detection and structural elucidation of an endogenous neuropeptide, (L)VV-hemorphin-7, in rat brain upon ATP stimulation. Finally, the combined micro-LC/CE/MALDI MS was used in the in vivo metabolic study of peptide E, a mu-selective opioid peptide with 25 amino acid residues. Profiles of 88 metabolites were obtained, their identity being determined by their mass-to-charge ratio and electrophoretic mobility. The results indicate that there are several primary cleavage sites in vivo for peptide E in the release of its enkephalin-containing fragments. ^