The present study measured the occurrence, distribution, and bioaccumulation of fluoxetine in samples of water, polar organic chemical integrative sampler (POCIS), sediment, and caged freshwater mussels at stream sites near a municipal wastewater treatment facility effluent discharge. We assessed the relation of the environmental concentrations to reproductive endpoints in mussels in acute laboratory tests. Concentrations of fluoxetine in water and POCIS samples were similar (<20% difference) within each site and were greatest in the effluent channel (104-119 ng/L), and decreased at 50 m and 100 m downstream. Likewise, concentrations of fluoxetine in sediment and mussel (Elliptio complanata) tissue were greatest in the effluent channel (17.4 ng/g wet wt for sediment and 79.1 ng/g wet wt for mussels). In 96-h lab tests, fluoxetine significantly induced parturition of nonviable larvae from female E. complanata exposed to 300 microg/L (p = 0.0118) and 3,000 microg/L (p < 0.0001) compared to controls. Fluoxetine exposure at 300 microg/L (p = 0.0075) and 3,000 microg/L (p = 0.0001) also resulted in stimulation of lure display behavior in female Lampsilis fasciola and Lampsilis cardium, respectively. In male E. complanata, 3,000 microg fluoxetine/L significantly induced release of spermatozeugmata during a 48-h exposure. These results suggest that fluoxetine accumulates in mussel tissue and has the potential to disrupt several aspects of reproduction in freshwater mussels, a faunal group recognized as one of the most imperiled in the world. Despite the disparity between measured environmental concentrations of fluoxetine and effects concentrations in our short-term tests with these long-lived animals, additional tests are warranted to evaluate the effects of long-term exposure to environmentally relevant concentrations and critical lifestages (e.g., juveniles).

Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure.

A clinical study was conducted to compare the use of oral fluid to urine for compliance monitoring of pain patients. Patients (n = 133) undergoing treatment for chronic pain at four clinics participated in the study and provided paired oral fluid and urine specimens. Oral fluid specimens were collected with Quantisal(TM) saliva collection devices immediately following urine collection. Oral fluid specimens were analyzed for 42 drugs and/or metabolites by validated liquid chromatography-tandem mass spectrometry procedures. Accompanying urine specimens were initially screened by immunoassay and non-negative results were confirmed. Of the 1544 paired tests, 329 (21.3%) drug analytes were positive, and 984 (63.7%) were negative for both specimens resulting in an overall agreement of 85%. There were 83 (5.4%) analyte results that were positive in oral fluid and negative in urine, and 148 (9.6%) were negative in oral fluid and positive in urine for an overall disagreement of 15%. Cohen's Kappa value was 0.64, indicating "substantial" agreement. The primary exceptions to agreement were the lower detection rates for hydromorphone, oxymorphone, and benzodiazepines in oral fluid compared to urine. The authors conclude that, overall, oral fluid tests produced comparable results to urine tests with some minor differences in detection rates for different drug classes.

Objective To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. Design Prospective cohort study. Setting Medical and surgical ICUs in a large tertiary care hospital in the United States. Patients Patients with acute respiratory failure and/or shock who received fentanyl during the first five days of their ICU stay. Measurements and Main Results We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to five days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 µg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance (CL), intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 (95% confidence interval: 32 to 39) L/hr, 55 (42 to 68) L/hr, 203 (140 to 266) L, and 523 (428 to 618) L, respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart disease were included. Conclusions In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients.

As concerns mount over the human health risks associated with consumption of fish contaminated with persistent organic pollutants, there exists a need to better evaluate fish body burdens without lethally sampling many of the important commercial and sport species of interest. The aim of this study was to investigate two novel methods for estimating organic contaminants in fish that are a concern for both fish and human health. The removal of fish adipose fins, commonly done in mark-recapture studies with salmonid species, was evaluated as a nonlethal sampling technique to estimate concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in flathead catfish (Pylodictis olivaris), relative to those found in muscle fillets of the same fish. We also assessed the efficacy of using poly(dimethylsiloxane) (PDMS) as a mobile passive sampling device (PSD) attached directly to wild flathead catfish for assessing location-specific exposure of the fish to waterborne contaminants. The results of this study have demonstrated for the first time that organic contaminant concentrations in adipose fin were highly correlated (R2 = 0.87) with muscle fillet concentrations, indicating that the adipose fin of certain fishes may be used to accurately estimate tissue concentrations without the need for lethal sampling. Moreover, mobile PSDs attached directly to fish and used here for the first time accurately estimated ultratrace concentrations of waterborne PCBs and OCPs without any apparent harm to the fish, indicating that there are no practical or physical barriers to the use of mobile passive samplers attached to aquatic organisms. Among the many practical implications of this research, two potential priority items include the analysis of organic contaminants in farm-raised and sport fish intended for human consumption, without the economic and population losses associated with lethally sampling fish to obtain tissues, and identifying specific areas where fish may be accumulating large portions of their contaminant burden.