Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.

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Abstract. Mass concentrations of carbonaceous and inorganic components of submicron (aerodynamic diameters < 0.6 gm) aerosol particles were measured at Cape San Juan, a coastal site located on the extreme northeastern tip of Puerto Rico. Additionally, carbonaceous aerosols and condensation nuclei (CN) were measured offshore during a limited shipboard sampling experiment at an Atlantic Ocean site away from the coast. Both sites were exposed to trade winds during the sampling periods. Under these conditions no obvious upwind anthropogenic sources should impact the sites.

Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.

Highly active antiretroviral therapy (HAART) is the standard treatment for infection with human immunodeficiency virus (HIV).The most common HAART regimen consists of the combination of at least one protease inhibitor (PI) with two nucleoside reverse transcriptase inhibitors (NRTIs). Contrary to PIs, NRTIs require intracellular activation from the parent compound of their triphosphate moiety to suppress HIV replication. Simultaneous intracellular determination of two NRTI triphosphates is difficult to accomplish due to their relatively small concentrations in peripheral blood mononuclear cells (PBMCs), requiring large amounts of blood from HIV-positive patients. Recently, we described a method to determine intracellular zidovudine triphosphate (ZDV-TP) concentrations in HIV-infected patients by using solid-phase extraction and tandem mass spectrometry. The limit of quantitation (LOQ) for ZDV-TP was 0.10 pmol, and the method was successfully used for the determination of ZDV-TP in HIV-positive patients. In this study, we enhanced the aforementioned method by the simultaneous quantitation of ZDV-TP and lamivudine triphosphate (3TC-TP) in PBMCs from HIV-infected patients. The LOQ for 3TC-TP was 4.0 pmol, with an interassay coefficient of variation and an accuracy of 7 and 12%, respectively. This method was successfully applied to the simultaneous in vivo determination of the ZDV-TP and 3TC-TP pharmacokinetic profiles from HIV-infected patients receiving HAART.Highly active antiretroviral therapy (HAART) has been used successfully for treatment of human immunodeficiency virus (HIV) since the discovery of protease inhibitors (PIs) (3,4,20). HAART treatment includes a broad category of antiretroviral drug combinations with the goals of decreasing plasma HIV-1 RNA levels below the limit of detection, limiting disease progression, and delaying the appearance of resistant mutants (12). The most common HAART regimen consists of the combination of one PI with two nucleoside reverse transcriptase inhibitors (NRTIs). This triple drug combination has shown dramatic improvements in viral suppression over the combination of the two nucleosides zidovudine and lamivudine (ZDV and 3TC, respectively) (8-10).Contrary to PIs, NRTIs require intracellular activation from the parent compound of their triphosphate (TP) moiety to suppress HIV replication. ZDV and 3TC are not active against HIV; they need to be metabolized to 5Ј-ZDV-TP (ZDV-TP) and 5Ј-3TC-TP (3TC-TP) to act as competitive inhibitors of HIV reverse transcriptase or be incorporated into the viral genome (2,7,11,23). Studies conducted with HIV-infected populations have not established any relationship between ZDV or 3TC concentrations in plasma and the efficacy of these agents (19). On the other hand, a recent study showed a linear relationship between ZDV-TP intracellular concentrations and an increase in the percent change in CD4 ϩ cells from baseline in HIV-infected adults (5). Furthermore, several stud- Several approaches have been reported for the individual determinatio...