Colleen Millan

Seminal lead concentrations negatively affect outcomes of artificial insemination

OBJECTIVE To determine the relationships among seminal lead levels, acrosome status, and artificial insemination cycle fecundity (AI f) in semen donors. DESIGN Longitudinal analysis of seminal lead levels, sperm function testing, and fecundity. SETTING University medical center andrology and research laboratories. PATIENT(S) Semen donors (n = 15) participating in a therapeutic donor insemination program. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Seminal plasma lead levels, acrosome sensitivity to progesterone (P) and voltage-gated potassium channel inhibitors (e.g., charybdotoxin [CBTx]), and AI f. RESULT(S) Seminal plasma lead levels and AI f were strongly negatively correlated. Semen donors were divided into three groups by acrosome response to P: normal (CBTx sensitive [Rs] or CBTx resistant [Rr]: responders) and reduced (nonresponders [NR]) (Rs > Rr >> NR). Seminal lead differed among the three groups (NR > Rr > Rs). Comparison of 330 artificial insemination cycles from four Rs, four Rr, and two NR demonstrated that cycle AI f also differed significantly between groups (Rs >Rr >>NR). CONCLUSION(S) Measurements of seminal plasma lead, P-stimulated acrosome loss, and sensitivity to CBTx may provide prognostic information on the fertility status of potential donors as well as male infertility patients. Such evaluations may assist in donor acceptance, or in the case of patients, in selection of the appropriate treatment regimen.

Reverse transcriptase genotype and antiretroviral susceptibility of human immunodeficiency virus isolates from patients with advanced disease treated with didanosine: Correlation with virologic response and survival

To identify correlates of virologic response and survival, the reverse transcriptase (RT) genotype and in vitro antiviral susceptibility of human immunodeficiency virus (HIV) isolates from 20 patients treated with didanosine were studied. Patients had advanced HIV disease and were intolerant to or had failed zidovudine. Neither RT genotype nor antiviral susceptibility testing, as determined by a peripheral blood mononuclear cell‐based assay, correlated with a virologic response to didanosine, as determined previously by quantitative serum culture. Only one (8%) of 12 isolates obtained after 6–12 months of treatment showed mutation at codon 74 conferring didanosine resistance. Reversions were seen in three of five patients with pre‐treatment zidovudine resistance mutations at codons 70, but in none of eight with mutations at codon 215. Pre‐treatment isolates encoding mutations at RT codon 215 or encoding codon 123 asp were associated with both significantly greater CD4 lymphocyte depletion and shorter survival. In this cohort of patients with advanced HIV disease, neither rapid emergence of didanosine resistance nor rapid reversion of zidovudine resistance was observed. To better understand the relationship between virologic response and in vitro susceptibility to didanosine, more precise tools may be needed.