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Objective: The pharmacokinetics of ropivacaine 0.2% were evaluated during a 48-hour continuous extrapleural infusion with 2 different infusion rates in patients undergoing cardiovascular surgery. The hypotheses that no toxic plasma concentrations of ropivacaine would be reached and that proportionality exists among plasma concentrations and dosage used were tested. Design: A prospective, randomized, nonblinded study. Setting: The investigation was performed as a single-center study in the Division of Cardiovascular Anesthesia, University Hospital of Zurich, in Switzerland. Participants: Seventeen consenting adults scheduled for elective cardiovascular surgery, with or without extracorporeal bypass, via the lateral thoracotomy approach were enrolled. Interventions: For postoperative pain relief, patients were randomly assigned to receive continuous extrapleural infusion of ropivacaine 0.2% at a rate of either 6 or 9 mL/h over 48 hours. Measurements and Main Results: Plasma concentrations of ropivacaine reached toxic levels (>2.2 mg/L) in 25% of cases. No proportionality of plasma concentrations of ropivacaine existed when the 2 dosing regimens were compared. Conclusions: Plasma concentrations of ropivacaine, administered at the given dose and rates during continuous extrapleural infusion, are unpredictable and may reach toxic levels in patients undergoing major cardiothoracic surgery. [Copyright &y& Elsevier]

Abstract: Objective: To establish an in vitro model for measurement of the excitability properties of cutaneous sensory axons. Methods: We used a saphenous skin–nerve preparation from adult rat in combination with computerized threshold tracking. We measured strength–duration time constant, the recovery of excitability after a supramaximal stimulus and the accommodation to conditioning subthreshold polarizing stimuli (threshold electrotonus, current–threshold relationship) and compared these with previously published recordings from sensory axons in human median nerve. Results: Threshold electrotonus and the amplitude of superexcitability were indistinguishable between human median nerve in vivo and rat saphenous nerve in vitro, but several excitability parameters were significantly different in the rat: strength–duration time constant was significantly shorter (0.19±0.01 vs. 0.53±0.02ms); the refractory period was shorter (1.9±1.1ms vs. 3.5±1.0ms) and late subexcitability was smaller (6.3±0.3% vs. 11.3±0.5%); thirdly, during recording of current–threshold relationship, rat nerves displayed more inward rectification to strong hyperpolarizing currents. Parameters were stable over more than 3h. Conclusions: Excitability changes of sensory Aβ-fibres can be reliably studied in the rat in vitro and are qualitatively similar to humans. Significance: This rat model will facilitate pharmacological studies of nerve excitability and work on models of neuropathy. [Copyright &y& Elsevier]

The validity and reliability of using psychological autopsies to diagnose a psychiatric disorder is a critical issue. Therefore, interrater and test–retest reliability of the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders and the usefulness of these instruments for the psychological autopsy method were investigated. Diagnoses by informant''s interview were compared with diagnoses generated by a personal interview of 35 persons. Interrater reliability and test–retest reliability were assessed in 33 and 29 persons, respectively. Chi-square analysis, kappa and intraclass correlation coefficients, and Kendall''s tau were used to determine agreement of diagnoses. Kappa coefficients were above 0.84 for substance-related disorders, mood disorders, and anxiety and adjustment disorders, and above 0.65 for Axis II disorders for interrater and test–retest reliability. Agreement by personal and relative''s interview generated kappa coefficients above 0.79 for most Axis I and above 0.65 for most personality disorder diagnoses; Kendall''s tau for dimensional individual personality disorder scores ranged from 0.22 to 0.72. Despite of a small number of psychiatric disorders in the selected population, the present results provide support for the validity of most diagnoses obtained through the best-estimate method using the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders. This instrument can be recommended as a tool for the psychological autopsy procedure in post-mortem research. [Copyright &y& Elsevier]

We tested the effects of variation of stimulus onset asynchrony (SOA) on visual working memory (WM) performance across different load levels and the underlying brain activation patterns using functional magnetic resonance imaging (fMRI) in 48 healthy participants. Participants were instructed to memorise arrays of coloured squares and had to perform a match/non-match judgement on a probe stimulus after a jittered delay. We presented visual pattern masks at four SOAs after the offset of the memory array (100 ms, 200 ms, 400 ms, and 800 ms). Memory performance decreased with increased load and shortened SOA. Brain activation data showed significant effects of load (during encoding and retrieval), SOA (retrieval) and an interaction of load by SOA (encoding), mainly in frontal and parietal areas. There was also a direct relationship between successfully stored items and activation in the right inferior parietal lobule and the left middle frontal gyrus. The neurobehavioral results suggest that the frontal regions, together with the inferior parietal lobe, are associated with successful WM performance, especially under the most challenging conditions of high load and short SOAs. [ABSTRACT FROM AUTHOR]

Abstract: Non-pharmacological approaches such as mirror therapy and graded motor imagery often provide amelioration of amputees'' phantom limb pain (PLP), but elimination has proved difficult to achieve. Proprioception of the amputated limb has been noted in studies to be defective and/or distorted in the presence of PLP, but has not, apparently, been researched for various stages of amelioration up to the absence of PLP. Previous studies using functional magnetic resonance imaging (fMRI) suggested that pathological cortical reorganisation after amputation may be the underlying neurobiological correlate of PLP. We report two cases of permanent elimination of PLP after application of imaginative resonance training. The patients, 69years and 84years old, reported freedom from PLP together with in-depth achievement of proprioception of a restored limb at the end of the treatment, which may thus be taken as an indication of permanence. Pre/post fMRI for the first case showed, against a group of healthy controls, analogous changes of activation in the sensorimotor cortex. [Copyright &y& Elsevier]

Abstract: Aims: The aim of this present study was to investigate the changes of peripheral sensory nerve excitability produced by propofol. Main methods: In a recently described in vitro model of rodent saphenous nerve we used the technique of threshold tracking (QTRAC®) to measure changes of axonal nerve excitability of Aβ-fibres caused by propofol. Concentrations of 10μMol, 100μMol and 1000μMol were tested. Latency, peak response, strength-duration time constant (τSD) and recovery cycle of the sensory neuronal action potential (SNAP) were recorded. Key findings: Our results have shown that propofol decreases nerve excitability of rat primary sensory afferents in vitro. Latency increased with increasing concentrations (0μMol: 0.96±0.07ms; 1000μMol 1.10±0.06ms, P <0.01). Also, propofol prolonged the relative refractory period (0μMol: 1.79±1.13ms; 100μMol: 2.53±1.38ms, P <0.01), and reduced superexcitability (0 μMol: −14.0±4.0%; 100μMol: −9.5±5.5%) and subexcitability (0μMol: 7.5±1.2%; 1000μMol: 3.6±1.2) significantly during the recovery cycle (P <0.01). Significance: Our results have shown that propofol decreases nerve excitability of primary sensory afferents. The technique of threshold tracking revealed that axonal voltage-gated ion channels are significantly affected by propofol and therefore might be at least partially responsible for earlier described analgesic effects. [Copyright &y& Elsevier]

Abstract: Suicide is a public health problem all around the world. Family studies showed a strong heritability but, to date, few genetic data are available. Thus, in the present study we investigated whether a panel of single nucleotide polymorphisms (SNPs) in neuronal cell adhesion molecule 1 (NCAM) 1 was associated with suicidal behaviour as well as specific traits related to suicide. A total of two hundred and fifty-nine individuals with a positive history of suicidal behaviour and 312 healthy subjects were enrolled in the study. Rs2301228, rs1884, rs1245113, rs1369816, rs2196456 and rs584427 in NCAM1 were genotyped. No marker was significantly associated with suicidal behaviour vs. controls or with sub-types of attempted vs. completed, violent vs. non-violent, impulsive vs. non-impulsive suicide. Nonetheless rs1884 and rs2196456 SNPs were both marginally associated with the trait “inhibition of aggressiveness” in suicide attempters. Even though the investigated SNPs in NCAM1 do not seem to be directly associated with suicidal behaviour, our results could suggest that SNP variants in NCAM1 may impact on related traits, particularly by mediating inhibition of aggressiveness. However, independent studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Abstract: Structural brain changes in schizophrenia are well documented in the neuroimaging literature. The classical morphometric analyses of magnetic resonance imaging (MRI) data have recently been supplemented by diffusion tensor imaging (DTI), which mainly assesses changes in white matter (WM). DTI increasingly provides evidence for abnormal anatomical connectivity in schizophrenia, most often using fractional anisotropy (FA) as an indicator of the integrity of WM tracts. To better understand the clinical significance of such anatomical changes, we studied FA values in a whole-brain analysis comparing paranoid schizophrenic patients with a history of auditory hallucinations and matched healthy controls. The relationship of WM changes to psychopathology was assessed by correlating FA values with PANSS scores (positive symptoms and severity of auditory hallucinations) and with illness duration. Schizophrenic patients showed FA reductions indicating WM integrity disturbance in the prefrontal regions, external capsule, pyramidal tract, occipitofrontal fasciculus, superior and inferior longitudinal fasciculi, and corpus callosum. The arcuate fasciculus was the only tract which showed increased FA values in patients. Increased FA values in this region correlated with increased severity of auditory hallucinations and length of illness. Our results suggest that local changes in anatomical integrity of WM tracts in schizophrenia may be related to patients'' clinical presentation. [Copyright &y& Elsevier]

Abstract: The purpose of the present study was to longitudinally track changes of metabolite markers detectable by magnetic resonance spectroscopy (MRS) in subjects with mild cognitive impairment (MCI) and to analyze these changes with respect to the rate of cognitive decline and clinical disease progression. Fifteen subjects with MCI and 12 healthy elderly controls were investigated longitudinally (average follow-up period: 3.4 years) using absolute quantification of metabolites within the mid-parietal grey matter and the parietal white matter [N-acetylaspartate (NAA), myo-inositol, choline, creatine, glutamine)] Our main findings include that a longitudinal decline in cognitive function (particularly in memory function) within the MCI group was predicted by a decline in absolute concentrations of the metabolic markers NAA and creatine. This effect was mainly explained by a significant decrease of NAA and creatine in those MCI subjects who converted to Alzheimer''s dementia (AD) during the follow-up period. No differences were found at baseline between MCI converters and stable subjects, indicating that at least in the present study MRS did provide a predictive discrimination between converters and stable subjects. Our findings support the use of MRS as a tool for objectively monitoring disease progression even during the earliest stages of AD. [Copyright &y& Elsevier]

Abstract: We investigated the vividness of mental imagery and its possible relationship with the predisposition towards hallucinations in 52 schizophrenia (SZ) patients, 44 of their first-degree relatives (R) and two healthy control groups (high-schizotypy [CHS; n =24]; low-schizotypy [CLS; n =24]). We investigated phenomenological and cognitive trait markers of schizophrenia, including cognitive correlates of hallucinations and vividness of mental imagery, and the influence of individual psychopathology. Overall, scores on the mental imagery questionnaire (QMI [Sheehan, P.W., 1967. Reliability of a short test of imagery. Perceptual and Motor Skills 25, 744.]) suggested higher mental imagery vividness in first-degree relatives, high-schizotypy controls and patients, than in low-schizotypy controls. However, vividness of mental imagery was independent of predisposition towards hallucinations and cognitive test performance scores. These results suggest that vividness of mental imagery may be a trait marker across the schizophrenia spectrum. In addition we propose that imagery proneness is relatively independent of the individual psychopathology. [Copyright &y& Elsevier]

Abstract: Estrogen is thought to be involved in the pathophysiology of depression and suicidal behaviors. We studied gene variants of estrogen receptor alpha (rs827421, rs1913474, rs1801132, rs722207, rs974276 and rs910416) in 167 German suicide attempters (affective spectrum n =107, schizophrenia spectrum n =35, borderline personality disorder n =25), 92 German individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. These were also not associated with related features, such as violence or impulsivity of suicide attempt, State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the hypothesis that estrogen receptor alpha gene variants are major contributors to suicide or to anger- or aggression-related behaviors. [Copyright &y& Elsevier]

Abstract: We investigated a 27-year old patient with paranoid schizophrenia. Brain activity related to visual hallucinations was found in higher visual areas corresponding to the content of the hallucinations (faces, bodies, scenes) and the hippocampus. We assume that the hippocampal activity is related to the retrieval of visual images from memory and that sensory cortex activity is related to the vividness of the perceptual experience. [Copyright &y& Elsevier]

Abstract: With life expectancy increasing continuously, the effects of neurodegeneration on brain function are a topic of ever increasing importance. Thus there is a need for tools and models that probe both the functional consequences of neurodegenerative processes and compensatory mechanisms that might occur. As neurodegenerative burden and compensatory mechanisms may change over time, these tools will ideally be applied multiple times over the lifespan. Specifically, in order to elucidate whether brain-activation patterns in Alzheimer''s disease (AD) and in healthy aging follow general rules in the context of degeneration and compensation, it is necessary to compare functional brain-activation patterns during different states of neurodegeneration. This article integrates the findings of functional activation studies at different stages of neurodegeneration: in healthy aging, in subjects at high risk of developing dementia, in subjects with mild cognitive impairment (MCI), and in patients suffering from AD. We review existing theoretical models that aim to explain the underlying mechanisms of functional activation changes in aging and dementia, and we propose an integrative account, which allows for different neural response patterns depending on the amount of neuronal damage and the recruitment of compensatory pathways. [Copyright &y& Elsevier]

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer''s disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification. [Copyright &y& Elsevier]

In recent years various approaches to the application of computerized assessment in psychiatry have been reported. Patients’ acceptance is important for reliability and validity of results. Comparisons with conventional paper-and-pencil tests are missing.The present study aimed to investigate the acceptance of computerized assessment, particularly compared to conventional paper-and-pencil techniques, in seriously impaired psychiatric inpatients.For this purpose a questionnaire (OPQ) was developed by the authors and evaluated in 135 psychiatric inpatients. Seventy-eight of these patients completed a set of neuropsychological and psychopathological assessments two times, once using the conventional approach and additionally using a computer version. Their OPQ results were analyzed, in the total sample as well as in diagnostic subgroups.Although the psychiatric patients had some problems in dealing with the computer, computerized assessment was convincingly well accepted and even superior to conventional paper-and-pencil techniques. Overall only few differences were found between diagnostic subgroups, indicating a higher relevance of computer attitude in depressive disorders. General skepticism concerning the feasibility of computerized assessment in psychiatric inpatients appears to be unjustified. [Copyright &y& Elsevier]