Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distracter stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distracters, the slow potentials generated by memory trials showed further enhancement of negativity whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction. © 1997 by the Massachusetts Institute of Technology

Working memory in schizophrenia and mania: Acute and subacute phases

Baekground: Patients with schizophrenia tend to have impaired performance on tests of working memory (WM). Neurocognitive models have linked WM to certain symptoms of schizophrenia. This study aimed to assess WM in schizophrenia and mania in the acute and subacute phases of the illness and explore correlations between WM and symptom clusters. Methods: A visuo-spatial delayed response task was used to assess WM in schizophrenia (n=20), mania (n= 14) and well controls (n=20). Patients were tested during the first week of an acute admission, and subjects were retested after four weeks. WM, symptoms (PANSS, TLC) and executive ability (COWAT, Stroop, Trail Making) were assessed at both time points. Results: When assessed for overall WM errors (both sensory and memory), there was a significant group difference (F- 11.53, df 2, 40; p

Improved one-step solid-phase extraction method for morphine, morphine-3-glucuronide, and morphine-6-glucuronide from plasma and quantitation using high-performance liquid chromatography with electrochemical detection

This communication describes an improved one-step solid-phase extraction method for the recovery of morphine (M), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) from human plasma with reduced coextraction of endogenous plasma constituents, compared to that of the authors' previously reported method. The magnitude of the peak caused by endogenous plasma components in the chromatogram that eluted immediately before the retention time of M3G has been reduced (similar to 80%) significantly (p < 0.01) while achieving high extraction efficiencies for the compounds of interest, viz morphine, M6G, and M3G (93.8 +/- 2.5, 91.7 +/- 1.7, and 93.1 +/- 2.2%, respectively). Furthermore, when the improved solid-phase extraction method was used, the extraction cartridge-derived late-eluting peak (retention time 90 to 100 minutes) reported in our previous method, was no longer present in the plasma extracts. Therefore the combined effect of reducing the recovery of the endogenous components of plasma that chromatographed just before the retention time of M3G and the removal of the late-eluting, extraction cartridge-derived peak has resulted in a decrease in the chromatographic run-time to 20 minutes, thereby increasing the sample throughput by up to 100%.

Hydromorphone-3-glucuronide: Biochemical synthesis and preliminary pharmacological evaluation

Hydromorphone-3-glucuronide (H3G) was synthesized biochemically using rat liver microsomes, uridine-5'-diphosphoglucuronic acid (UDPGA) and the substrate, hydromorphone. Initially, the crude putative H3G product was purified by ethyl acetate precipitation and washing with acetonitrile, Final purification was achieved using semi-preparative high-performance-liquid-chromatography (HPLC) with ultraviolet (UV) detection. The purity of the final H3G product was shown by HPLC with electrochemical and ultraviolet detection to be > 99.9% and it was produced in a yield of approximate to 60% (on a molar basis). The chemical structure of the putative H3G was confirmed by enzymatic hydrolysis of the glucuronide moiety using P-glucuronidase, producing a hydrolysis product with the same HPLC retention time as the hydromorphone reference standard. Using HPLC with tandem mass spectrometry (HPLC-MS-MS) in the positive ionization mode, the molecular mass (M+1) was found to be 462 g/mol, in agreement with H3G's expected molecular weight of 461 g/mol. Importantly, proton-NMR indicated that the glucuronide moiety was attached at the 3-phenolic position of hydromorphone. A preliminary evaluation of H3G's intrinsic pharmacological effects revealed that following icy administration to adult male Sprague-Dawley rats in a dose of 5 mu g, H3G evoked a range of excitatory behavioural effects.including chewing, rearing, myoclonus, ataxia and tonic-clonic convulsions, in a manner similar to that reported previously for the glucuronide metabolites of morphine, morphine-3-glucuronide and normorphine-3-glucuronide.

Solid-phase extraction method with high-performance liquid chromatography and electrochemical detection for the quantitative analysis of oxycodone in human plasma

A sensitive and reproducible solid-phase extraction (SPE) method for the quantification of oxycodone in human plasma was developed. Varian Certify SPE cartridges containing both C-8 and benzoic acid functional groups were the most suitable for the extraction of oxycodone and codeine (internal standard), with consistently high (greater than or equal to 80%) and reproducible recoveries. The elution mobile phase consisted of 1.2 ml of butyl chloride-isopropanol (80:20, v/v) containing 2% ammonia. The quantification limit for oxycodone was 5.3 pmol on-column. Within-day and inter-day coefficients of variation were 1.2% and 6.8% respectively for 284 nM oxycodone and 9.5% and 6.2% respectively for 28.4 nM oxycodone using 0.5-ml plasma aliquots. (C) 1998 Elsevier Science BN. All rights reserved.

An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation

Objective: To investigate a proposed model in which manipulative therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect by activating a descending pain inhibitory system. The a priori hypothesis tested was that manipulative therapy produces mechanical hypoalgesia and sympatho-excitation beyond that produced by placebo or control. Furthermore, these effects would be correlated, thus supporting the proposed model. Design: A randomized, double-blind, placebo-controlled, repeated-measures study of the initial effect of treatment. Setting: Clinical neurophysiology laboratory. Subjects: Twenty-four subjects (13 women and 11 men; mean age, 49 yr) with chronic lateral epicondylalgia (average duration, 6.2 months). Intervention: Cervical spine lateral glide oscillatory manipulation, placebo and control. Outcome Measures: Pressure pain threshold, thermal pain threshold, pain-free grip strength test, upper limb tension test 2b, skin conductance, pileous and glabrous skin temperature and blood flux. Results: Treatment produced hypoalgesic and sympathoexcitatory changes significantly grater than those of placebo and control (p < .03). Confirmatory factor-analysis modeling, which was performed on the pain-related measures and the indicators of sympathetic nervous system function, demonstrated a significant correlation (r = .82) between the latencies of manipulation-induced hypoalgesia and sympathoexcitation. The Lagrange Multiplier test and Wald test indicated that the two latent factors parsimoniously and appropriately represented their observed variables. Conclusions: Manual therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect beyond that of placebo or control. The strong correlation between hypoalgesic and sympathoexcitatory effects suggests that a central control mechanism might be activated by manipulative therapy.

Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management

Twenty-three patients treated with intracerebroventricular (ICV) morphine in this study not only obtained excellent pain relief without rapid increases in dose, but also experienced a reduction in morphine-related side effects. By 24 h after initiation of ICV morphine, the mean trough cerebrospinal fluid (CSF) morphine concentration (approximately 20 mu M) was 50-fold higher than the baseline concentration (approximately 0.4 mu M), and the CSF concentration of morphine-6-glucuronide (M6G) was undetectable (

The genus Deretrema Linton, 1910 (Digenea : Zoogonidae) from southern Great Barrier Reef fishes, with a description of Deretrema woolcockae n. sp.

Two species of Deretrema (Zoogonidae) are reported from labrid fishes from the Great Barrier Reef. D. nahaense Yamaguti, 1942 is recorded from the gall-bladders of the labrids Thalassoma hardwicke (Bennett), T. jansenii (Bleeker), T. lunare (Linnaeus) and T. lutescens (Lay & Bennett). This species is recognised, despite having been formerly synonymised with D. pacificum Yamaguti, 1942. In addition to morphological distinction, D. nahaense appears to have strict host-specificity for the genus Thalassoma. D. woolcockae n.sp. is described from the gall-bladder of Hemigymnus fasciatus (Bloch). The new species is close to D. acutum Pritchard, 1963 and D. plotosi Yamaguti, 1940, but differs slightly in the distribution of the vitelline follicles, the sucker-ratio and the position of the cirrus-sac. In addition, this species also appears to have a distinct host-specificity, being restricted to one labrid species.

Systemic coadministration of chloramphenicol with intravenous but not intracerebroventricular morphine markedly increases morphine antinociception and delays development of antinociceptive tolerance in rats

Chloramphenicol, an in vitro inhibitor of the glucuronidation of morphine to its putative antianalgesic metabolite, morphine-3-glucuronide (M3G), was coadministered with morphine in adult male Sprague-Dawley rats to determine whether it inhibited the in vivo metabolism of morphine to M3G, thereby enhancing morphine antinociception and/or delaying the development of antinociceptive tolerance. Parenteral chloramphenicol was given acutely (3-h studies) or chronically (48-h studies). Morphine was administered by the i.v. or i.c.v. route. Control rats received chloramphenicol and/or vehicle. Antinociception was quantified using the hotplate latency test. Coadministration of chloramphenicol with i.v. but not i.cv. morphine increased the extent and duration of morphine antinociception by approximate to 5.5-fold relative to rats that received i.v. morphine alone. Thus, the mechanism through which chloramphenicol enhances i.v. morphine antinociception in the rat does not directly involve supraspinal opioid receptors. Acutely, parenteral coadministration of chloramphenicol and morphine resulted in an approximate to 75% increase in the mean area under the serum morphine concentration-time curve but for chronic dosing there was no significant change in this curve, indicating that factors other than morphine concentrations contribute significantly to antinociception. Antinociceptive tolerance to morphine developed more slowly in rats coadministered chloramphenicol, consistent with our proposal that in vivo inhibition of M3G formation would result in increased antinociception and delayed development of tolerance. However, our data also indicate that chloramphenicol inhibited the biliary secretion of M3G. Whether chloramphenicol altered the passage of M3G and morphine across the blood-brain barrier remains to be investigated.

Is there an association between normal cognitive functioning and trinucleotide repeat expansion at loci involved in neurodegenerative disorders?

Recent reports have shown neurodegenerative disorders to be associated with abnormal expansions of a CAG trinucleotide repeat allele at various autosomal loci. While normal chromosomes have 14 to 44 repeats, disease chromosomes may have 60 to 84 repeats. The number of CAG repeats on mutant chromosomes correlates with increasing severity of disease or decreasing age at onset of symptoms. Since we are interested in identifying the many quantitative trait loci (QTL) influencing brain functioning, we examined the possibility that the number of CAG repeats in the normal size range at these loci are relevant to "normal" neural functioning. We have used 150 pairs of adolescent (aged 16 years) twins and their parents to examine allele size at the MJD, SCA1, and DRPLA loci in heterozygous normal individuals. These are part of a large ongoing project using cognitive and physiological measures to investigate the genetie influences on cognition, and an extensive protocol of tests is employed to assess some of the key components of intellectual functioning. This study selected to examine full-scale psychometric IQ (FSIQ) and a measure of information processing (choice reaction time) and working memory (slow wave amplitude). CAG repeat size was determined on an ABI Genescan system following multiplex PCR amplification. Quantitative genetic analyses were performed to determine QTL effects of MJD, SCA1, and DRPLA on cognitive functioning. Analyses are in progress and will be discussed.

The glass ceiling hypothesis - A comparative study of the United States, Sweden, and Australia

The general-care glass ceiling hypothesis states that not only is it more difficult for women than for men to be promoted up levels of authority hierarchies within workplaces but also that the obstacles women face relative to men become greater as they move rtp the hierarchy. Gender-based discrimination in promotions is not simply present across levels of hierarchy but is more intense at higher levels. Empirically, this implies that the relative rates of women being promoted to higher levels compared to men should decline with the level of the hierarchy. This article explores this hypothesis with data from three countries: the United States, Australia, and Sweden. The basic conclusion is that while there is strong evidence for a general gender gap in authority-the odds of women having authority are less than those of men-there is no evidence for systematic glass ceiling effects in the United States and only weak evidence for such effects in the other two countries.

An extragalactic HI cloud with no optical counterpart?

We report the discovery, from the H I Parkes All-Sky Survey (HIPASS), of an isolated cloud of neutral hydrogen, which we believe to be extragalactic. The H I mass of the cloud (HIPASS J1712-64) is very low, 1.7 x 10(7) M-circle dot, using an estimated distance of similar to 3.2 Mpc. Most significantly, we have found no optical companion to this object to very faint limits [mu(B) similar to 27 mag arcsec(-2)]. HIPASS J1712-64 appears to be a binary system similar to, but much less massive than, H I 1225 + 01 (the Virgo H. I cloud) and has a size of at least 15 kpc. The mean velocity dispersion measured with the Australia Telescope Compact Array (ATCA) is only 4 km s(-1) for the main component and, because of the weak or nonexistent star formation, possibly reflects the thermal line width (T < 2000 K) rather than bulk motion or turbulence. The peak column density for HIPASS J1712-64, from the combined Parkes and ATCA data, is only 3.5 x 1019 cm(-2), which is estimated to be a factor of 2 below the critical threshold for star formation. Apart from its significantly higher velocity, the properties of HIPASS J1712-64 are similar to the recently recognized class of compact high-velocity clouds. We therefore consider the evidence for a Local Group or Galactic origin, although a more plausible alternative is that HIPASS J1712-64 was ejected from the interacting Magellanic Cloud-Galaxy system at perigalacticon similar to 2 x 10(8) yr ago.