BackgroundAcetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.MethodsSamples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.ResultsTrial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.ConclusionsLower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.

Electrophysiological work in nonhuman primates has established the existence of multiple types of signals in the temporal lobe that contribute to recognition memory, including information regarding a stimulus's relative novelty, familiarity, and recency of occurrence. We used high-density event-related potentials (ERPs) to examine whether young infants represent these distinct types of information about previously experienced items. Twenty-four different highly familiar and initially novel items were each repeated exactly once either immediately (Experiment 1), or following one intervening item (Experiment 2). A late slow wave (LSW) component of the ERP exhibited neural responses consistent with recency signals over right-central leads, but only when there were no intervening stimuli between repetitions. The LSW also exhibited responses consistent with familiarity signals over anterior-temporal leads, but only when there were intervening stimuli between repetitions. A mid-latency negative component (i.e., the Nc) also distinguished familiar from novel items, but did not exhibit a pattern of responding consistent with familiarity signals. These findings suggest that infants encode information about a variety of objects from their natural environments into long-term memory, and can discriminate between familiar and unfamiliar items, and between recently seen and new items, very quickly (within 1 sec). They also suggest that infants represent information about not only whether a stimulus is familiar or unfamiliar but also whether it has been seen recently.Correspondence should be sent to Kelly A. Snyder,

Certain baseline characteristics identified a subset of women seen in an STD clinic that were associated with future unintended pregnancy. Targeted interventions addressing these factors are needed.