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G S Wasserman

Publications and source records attributed to G S Wasserman.

At least 19 recordsLinked to original sources
PubMed2001

Dissociating sensory and cognitive contributions to visual persistence II. Photoreceptor integration of flash pairs as a function of interflash interval, intensity, integration site, and candidate code.

Perceived duration can be assessed behaviorally by adjusting the interval between two flashes so that an observer just perceives a certain relation between them. In such studies, the cognitive characteristics of the required relation necessarily interact with the sensory characteristics of the responses evoked by the two flashes. To dissociate the contributions of these two factors, we executed a physiological study which yielded more complete information on the role of each factor in two paradigms which have been used to characterize perceived duration behaviorally, namely the persistence-of-form design and the successive field design. The effect of sensory manipulations have yielded particularly problematic results in these two paradigms because opposite trends were found when intensity was varied. Intracellular recordings were therefore taken from photoreceptor cells exposed to procedural manipulations which match the sensory and cognitive variations employed in behavioral paradigms. The sensory variables of flash intensity, state of adaptation, and flash interval were explored with some completeness. Cognitive factors were assessed in two ways. First, the contribution of the neural site of sensory integration was determined by making a clear distinction between data collected when all stimuli affect the same receptors versus data collected when different stimuli affect different receptors. Second, the consequences of arbitrary choices of candidate code and dependent variable were also explored. When so organized, the physiological data provide a coherent basis for harmonizing apparently contradictory behavioral results because they qualitatively paralleled the behavioral data's complex dependence on intensity and interval. In particular, both direct and inverse dependencies of response duration on intensity exist in both physiology and behavior with the exact nature of the trend depending as much on the cognitive analysis of the neural responses as on their dynamics and energetics. Further, large quantitative differences were found which also were an expression of the different ways in which the two behavioral paradigms affect receptor potentials.

Adaptation, Ocular↗
PubMed2001

Dissociating sensory and cognitive contributions to visual persistence I. Photoreceptor response duration as a function of flash intensity, adaptation state, and candidate code.

Numerous careful behavioral studies of visual persistence have reported a variety of apparently contradictory effects. Variation of flash intensity has particularly been found to have both direct and inverse effects on subjective duration. This conflict has been addressed by theories which contain both sensory and cognitive components. Depending on the weight given to these components, one obtains theories which emphasize intensity dependence or task dependence. Few comparably detailed physiological studies of persistence exist. To clarify the issues raised by these theories, we examined the responses evoked in the model photoreceptor of the Limulus lateral eye. To explore the role of sensory variables, we manipulated adaptation state and flash intensity. To explore cognitive variables, the durations of the photoreceptor potentials (RPs) evoked in this model system were assessed by a mutually complementary and complete set of candidate sensory codes. Accordingly, sharp microelectrodes were used to record RPs intracellularly from single photoreceptor cells in response to 40-ms flashes whose intensity was varied over at least 3.6 log units. Two light adaptation states were used which differed in sensitivity by 3.5 log units. This model system made it possible to employ stringent objective assessments of data quality which ensured that only cells which had remained stable for several hours contributed to the present data. A variety of code-dependent trends were found: direct, inverse, invariant, and U-shaped trends related flash intensity to RP duration, while adaptation state interacted with some of these trends. Only some of the expectations which had generated this research were qualitatively corroborated and numerous quantitative discrepancies were found between data and theory. While caution is necessary when generalizing from neural responses to perception, these data indicate that two major gaps now exist in this field. First, both task and stimulus variables need to be exhaustively explored in more complete behavioral experiments. The present data make it more likely that sensory models and cognitive models simply address different aspects of the same phenomenon. Second, similarly detailed questions need to be posed to more central neural loci, particularly to those in the various visual cortices.

Adaptation, Ocular↗
PubMed2001

Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents.

BACKGROUND: Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin-associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity. METHODS: Serum levels of tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, and interleukin 10 were measured by ELISA in children and adolescents (n = 35) with acetaminophen overdose. Peak cytokine levels were examined relative to biochemical evidence of hepatocellular injury, nomogram risk assessment, and prothrombin time. RESULTS: Five patients had aspartate aminotransferase or alanine aminotransferase levels >1000 IU/L, and 4 patients had aspartate aminotransferase or alanine aminotransferase levels > or =100 IU/L and < or =1000 IU/L. No elevations of tumor necrosis factor alpha or interleukin 1beta were detected. Peak interleukin 8, but not interleukin 6 or interleukin 10, correlated with hepatotoxicity (Mann-Whitney exact test, P <.001). The peak interleukin 8 level was greater in patients at high risk by the nomogram combined with those presenting at >15 hours, as compared with other patients (Mann-Whitney U test, P <.01). The interleukin 8 level peaked before aspartate aminotransferase or alanine aminotransferase in 5 of the 9 patients with hepatotoxicity. In addition, interleukin 8 concentrations of >20 pg/mL were associated with peak prothrombin time values (Mann-Whitney exact test, P <.015). CONCLUSIONS: Interleukin 8 elevation in patients with acetaminophen hepatotoxicity corresponds with other common clinical measures that are predictive of hepatocellular injury. Further study is warranted to evaluate possible mechanistic relationships between inflammatory cytokines and acetaminophen hepatotoxicity in children and adults.

Acetaminophen↗
PubMed2001

Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses. .

Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1,000 IU/L), and 6 subjects had transaminase elevation of 100 to 1,000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6,000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury.

Acetaminophen↗
PubMed2000

Acetaminophen intoxication during treatment: what you don't know can hurt you.

For over two decades, pediatricians have been made aware of the potential risk associated with the acute ingestion of large single and/or multiple doses of acetaminophen (APAP). Clearly, APAP-induced hepatotoxicity remains as a recognized medical emergency which, when treated promptly with appropriate gastrointestinal decontamination and when indicated, with the antidote N-acetylcysteine, has a uniformly good clinical outcome. Recently, the hepatotoxic potential associated with "therapeutic" APAP administration has been brought to the attention of the pediatric community. This review explores the issue of APAP toxicity with therapeutic intent by examining both the clinical literature and also, relevant information concerning the basic pharmacology and toxicology of this old and widely used nonprescription drug. A "risk profile" is developed with regard to factors that may predispose infants and children to this iatrogenic form of toxicity so that the awareness of physicians and other caregivers (including parents) can be heightened and preventative education administered. As is true for most all potentially beneficial medicines used in pediatrics, awareness of the actual amount of drug received from all sources and caution to not exceed the age-appropriate dosing guidelines (i.e., both amount and duration) contained in the approved labeling for all products containing APAP will insure safe and effective therapy.

Acetaminophen↗
PubMed1996

Receiver operating characteristic (ROC) analysis of neural code efficacies. I. Graded photoreceptor potentials and data quality.

Nerve cell signals are different in form from the stimuli that evoke them and they exhibit complex spatio-temporal characteristics. This defines a neural coding problem which is addressed by two current theories: Multiple Meaning Theory holds that neural signals contain patterns that make statements about combinations of stimulus properties; the Task Dependence Hypothesis suggests that different features of identical neural signals mediate performance in different behavioral tasks. These coding issues were addressed by investigating the representation of sensory information in the distal nervous system after transduction of visual stimuli into bio-electric signals. The objects of study were light-evoked neural responses which had been intracellularly recorded from single retinula (photoreceptor) cells in Limulus lateral eyes. The efficacies with which sensory information was represented by various candidate neural codes were calculated using receiver operating characteristic (ROC) analyses to provide objective indices. The specific visual problem under investigation was discrimination between light flashes whose intensities differed by a very small amount. A wide range of light adaptation states and relative stimulus intensities were explored. Extremely stringent data quality standards were applied which restricted the investigation to cells whose potentials did not exhibit any statistically significant drift during the hours required for data collection. Seven cellular characterizations were simultaneously monitored to detect drift in a given cell's potentials; these characterizations included the value of the membrane potential and the values of six candidate codes. These codes were: the area under the light-evoked receptor potential (RP), the mean value of the RP, the peak height of the RP, the slope of the onset of the RP, the duration required for the RP to drop from its peak by a given amount, and the duration required for the RP to end. The results were: (1) Light adaptation increases efficacy. (2) Thus, light adaptation trades sensitivity for acuity (as characterized by ROC discriminations). (3) Increasing relative light flash intensity also increases efficacy. (4) The efficacies of the various codes are significantly different and fall in the following order: area > or = peak = mean > or = duration-end = slope = duration-drop. These findings further demonstrate that arbitrary characterizations of stimulus-response relationships are very likely to be incomplete. They particularly indicate that many commonly used and quite conventional neural analysis strategies may substantially under-estimate system performance.

Adaptation, Ocular↗
PubMed1996

Receiver operating characteristic (ROC) analysis of neural code efficacies. II. Optic nerve action potentials and neural transmission.

Action potentials (APs) were intracellularly recorded from eccentric cells (which give rise to optic nerve fibers) in Limulus lateral eyes and their neural coding efficacies were determined over a wide range of light adaptation states and relative stimulus intensities. Extremely stringent data quality procedures were followed to ensure that the results are based on stable preparations. Waveforms which could be compared with those of comparable receptor potentials (RPs) were obtained by constructing plots of the reciprocals of successive interspike intervals, creating instantaneous spike frequency waveforms (ISFWs). Six candidate codes were then measured. They were: the area under the light-evoked ISFW, the mean value of the ISFW, the peak height of the ISFW, the slope of the onset of the ISFW, the duration required for the ISFW to drop from its peak by a given amount, and the duration required for the ISFW to end. Receiver operating characteristic (ROC) analyses were then applied to these coded ISFW values to provide objective indices of AP efficacies in the form of detectability (d') measurements. Several reliable findings were obtained: (1) Both adaptation state and relative intensity affect efficacy. More specifically, the d' values of all codes approach zero, representing chance detectability, when relatively weak flashes are presented in dark-adapted states. (2) Light adaptation produces a sensitivity-acuity tradeoff: as sensitivity decreases in more light-adapted states, detectabilities increase, indicating that ROC-characterized discrimination acuity increases. (3) The AP code efficacy order is similar to but not identical with the efficacy order previously found in photoreceptors: area = peak > or = mean > or = slope = duration-end = duration-drop. The previously measured photoreceptor RP efficacies were quantitatively compared with the present AP data from the optic nerve fiber level, with the following results: (1) All efficacies tend to decline at the more proximal neural level. (2) The decline is code dependent and transmission efficacy falls in this order: peak > area > mean > slope = duration-end = duration-drop. (3) The code which transmits best between photoreceptors and optic nerve fibers (i.e., the peak) differs from the code which has the highest efficacy at the photoreceptor level (i.e., the area); at the more proximal level, these two codes have indistinguishable efficacies. These findings support two conclusions: (1) They further demonstrate that arbitrary characterizations of stimulus-response relationships are very likely to be incomplete. This would be particularly important when, as is often the case in brain research, the mean code alone (i.e., the average firing rate) is used to characterize spike potentials. The present data show that the use of that code would have substantially underestimated detectability had it been used alone. (2) The fact that the code which most completely transmits information between cells is not the code which most completely represents information within a cell leads directly to a possible physiological basis for the existence of multiple neural codes. It particularly leads to the following extension of the Task Dependence Hypothesis of neural coding: Different codes may mediate performance in different behavioral tasks because different codes best serve different neural functions.

Action Potentials↗
PubMed1993

Two-week-old infant with isopropanol intoxication.

Isopropyl alcohol continues to be a frequent toxicologic exposure. However, no cases involving the newborn period have been described. A 14-day-old male infant presented to the emergency department (ED) with the mother's chief complaint that "He is not himself." Physical examination observed the infant to be lethargic and hypotonic. Laboratory evaluation revealed a positive urine drug screen for isopropanol and acetone. Elevated serum levels (in mg/dl) of isopropanol/acetone at 2:45, 4:15, 11:10, and 29:53 hours postpresentation were 101/136, 81/149, 20/155, and 5/72, respectively. Overall, this patient did remarkably well with minimal supportive care and was noted to have a normal neurologic examination within 10 hours of presentation despite rising serum acetone levels. This case brings into question the hypothesis that acetone, a metabolite of isopropanol, prolongs central nervous system depression in acute isopropyl alcohol intoxication. The importance of urine drug screens in children who present to the ED with unusual neurologic examinations is appreciated.

1-Propanol↗
PubMed1991

Lomotil overdose.

Explore the source record for details and available documents.

Atropine↗
PubMed1990

Chloroquine poisoning in a child.

Chloroquine poisoning in children, although infrequent, is extremely dangerous because of the narrow margin between therapeutic and toxic doses. Children clinically present with apnea, seizures, and cardiac arrhythmias. We present the case of a 12-month-old infant, the second-youngest patient reported in the US literature to die from chloroquine poisoning. A serum level of 4.4 mg/L (13.64 mumol/L) was obtained after the infant ingested only one tablet (300 mg). This establishes a new minimal lethal dose/blood level for children. Although some pediatric and adult pharmacokinetic and clinical similarities exist, the outcome is different. Pediatric mortality is 80%, whereas adult mortality is only 10%. Pediatric ingestion cases are primarily unintentional, and most adult cases are suicide attempts. Current treatment in adults includes a protocol of diazepam and epinephrine. Further studies involving children and these medications and other modalities are needed to improve survival.

Apnea↗