JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001
Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia
PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source]

Visual event-related potentials in children with phenylketonuria

ACTA PAEDIATRICA, Issue 1 2000
RM Henderson
Visual event-related potentials (ERPs) were examined in 16 children (aged 5,14 y) with phenylketonuria (PKU) and 16 age- and sex-matched controls. Lifetime median measures of phenylalanine (Phe) were 230-460 ,mol/l. The most recent Phe levels were 56,624 ,mol/l. ERPs were recorded whilst the children performed a discrimination task. All stimuli were square wave gratings degree, which appeared for 33 ms. A response to an infrequent grating that differed in orientation or spatial frequency was required. The older children with PKU had a delay in the first peak (P1) of the ERP, and age-related changes in the amplitude of P1. There was attenuation of the second peak across age groups in PKU. There was no evidence of reduced response accuracy or longer reaction times in children with PKU. Latencies of the cognitive P3 were not delayed in PKU. The delayed early peaks are consistent with previous studies that have shown delayed visual evoked potentials in PKU. The lack of differences in reaction time and P3 may be due to relatively good Phe control in children with PKU, or to the simplicity of the task. Suggestions are made for future ERP studies of PKU. [source]

Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal Syndrome

ALCOHOLISM, Issue 9 2006
Karl-Jürgen Bär
Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n=20, no treatment required) and in patients with moderate to severe AW syndrome (n=20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Results: Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. Conclusions: We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies. [source]

Mechanisms of face perception in humans: A magneto- and electro-encephalographic study

NEUROPATHOLOGY, Issue 1 2005
Shoko Watanabe
We have been studying the underlying mechanisms of face perception in humans using magneto- (MEG) and electro-encephalography (EEG) including (1) perception by viewing the static face, (2) differences in perception by viewing the eyes and whole face, (3) the face inversion effect, (4) the effect of gaze direction, (5) perception of eye motion, (6) perception of mouth motion, and (7) the interaction between auditory and visual stimuli related to the vowel sounds. In this review article, we mainly summarize our results obtained on 3, 5, and 6 above. With the presentation of both upright and inverted unfamiliar faces, the inferior temporal cortex (IT) centered on the fusiform gyrus, and the lateral temporal cortex (LT) near the superior temporal sulcus were activated simultaneously, but independently, between 140 and 200 ms post-stimulus. The right hemisphere IT and LT were both active in all subjects, and those in the left hemisphere in half of the subjects. Latencies with inverted faces relative to those with upright faces were longer in the right hemisphere, and shorter in the left hemisphere. Since the activated regions under upright and those under inverted face stimuli did not show a significant difference, we consider that differences in processing upright versus inverted faces are attributable to temporal processing differences rather than to processing of information by different brain regions. When viewing the motion of the mouth and eyes, a large clear MEG component, 1M (mean peak latency of approximately 160 ms), was elicited to both mouth and eye movement, and was generated mainly in the occipito-temporal border, at human MT/V5. The 1M to mouth movement and the 1M to eye movement showed no significant difference in amplitude or generator location. Therefore, our results indicate that human MT/V5 is active in the perception of both mouth and eye motion, and that the perception of movement of facial parts is probably processed similarly. [source]

Two-Timing: Politics and Response Latencies in a Bilingual Survey

POLITICAL PSYCHOLOGY, Issue 1 2000
Joseph F. Fletcher
Through the recording of response times in a national four-wave bilingual panel survey, this study reports improvements in the prediction of vote choice up to 1 year in advance of a federal election. These results were achieved with conventional computer-assisted telephone interviewing (CATI) software, indicating that the immediate use of response time measures isboth practical and attractive for commercial as well as academic survey units. Even so, response latencies were found to be sensitive to political circumstance, such that timings should be analyzed separately for minority and majority populations. Moreover, a broad analytic focus, beyond timing only vote intention and partisan commitment, is recommended because latency data on core questions of identity and allegiance reveal a great deal about the contours ofpolitical context. [source]

Status 5 Years after Bilateral Hand Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006
S. Schneeberger
Graft survival and function early after hand transplantation is good. It remains unknown, however, whether long-term survival is limited by chronic rejection. We here describe the clinical course and the status 5 years after bilateral hand transplantation with emphasis on immunosuppression (IS), function, morphology and graft vascular changes. Clinical observation, evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, CT angiography, electrophysiologic studies including compound motor and sensory action potentials (CMAP, CSAP) and somatosensory evoked potentials were performed and results recorded at regular intervals. Following reduction of IS one mild (grade II) rejection episode occurred at 4 years. Subsequently, skin histology remained normal and without signs of chronic rejection. Hand function continuously improved during the first 3 years and remained stable with minor improvement thereafter. CMAP and CSAP progressively increased during the observation period. Latencies of the cortical responses were prolonged but amplitudes were within normal range. Investigation of hand vessels revealed no signs of occlusion but showed revascularization of a primarily occluded right radialis artery. Motor and sensory function improved profoundly between years 1 and 5 after hand transplantation. No signs whatsoever of chronic rejection have been observed. [source]

Effect of fixation tasks on multifocal visual evoked potentials

CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2005
Alessandra Martins MB BS
Abstract Purpose:, This study investigated the effects of cognitive influence on the multifocal visual evoked potential (mVEP) at different levels of eccentricity. Three different foveal fixation conditions were utilized involving varying levels of task complexity. A more complex visual fixation task has been known to suppress peripheral signals in subjective testing. Methods:, Twenty normal subjects had monocular mVEPs recorded using the AccuMap objective perimeter. This allowed simultaneous stimulation of 58 segments of the visual field to an eccentricity of 24°. The mVEP was recorded using three different fixation conditions in random order. During task 1 the subject passively viewed the central fixation area. For task 2 alternating numbers were displayed within the fixation area; the subject on viewing the number ,3' in the central fixation area indicated recognition by pressing a button. Throughout task 3, numbers were displayed as in task 2. The subject had the cognitive task of summating all the numbers. Results:, Analysis revealed that the increased attention and concentration demanded by tasks 2 and 3 in comparison with task 1 resulted in significantly enhanced central amplitudes of 9.41% (Mann,Whitney P = 0.0002) and 13.45% (P = 0.0002), respectively. These amplitudes became reduced in the periphery and approached those of task 1, resulting in no significant difference between the three tasks. Latencies demonstrated no significant difference between each task nor at any eccentricity (P > 0.05). As the complexity of each task increased the amount of alpha rhythm was significantly reduced. Conclusions:, Our findings indicate that task 1 required a minimal demand of cognition and was associated with the greatest amount of alpha rhythm. It was also the most difficult to perform because of loss of interest. The other two tasks required a greater demand of higher order cognitive skills resulting in significantly enhanced amplitudes centrally and the attenuation of alpha rhythm. Therefore, amplitudes are increased around the area of attention. [source]

Modeling Network Latency and Parallel Processing in Distributed Database Design

DECISION SCIENCES, Issue 4 2003
Jesper M. Johansson
ABSTRACT The design of responsive distributed database systems is a key concern for information systems managers. In high bandwidth networks latency and local processing are the most significant factors in query and update response time. Parallel processing can be used to minimize their effects, particularly if it is considered at design time. It is the judicious replication and placement of data within a network that enable parallelism to be effectively used. However, latency and parallel processing have largely been ignored in previous distributed database design approaches. We present a comprehensive approach to distributed database design that develops efficient combinations of data allocation and query processing strategies that take full advantage of parallelism. We use a genetic algorithm to enable the simultaneous optimization of data allocation and query processing strategies. We demonstrate that ignoring the effects of latency and parallelism at design time can result in the selection of unresponsive distributed database designs. [source]

Latency and outcome of prophylaxis in bipolar disorder: role of severity as a confounding variable?

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2004
To the editor:
No abstract is available for this article. [source]

Cooling Abolishes Neuronal Network Synchronization in Rat Hippocampal Slices

EPILEPSIA, Issue 6 2002
Sam P. Javedan
Summary: ,Purpose: We sought to determine whether cooling brain tissue from 34 to 21°C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. Methods: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450,500 ,m) from Sprague,Dawley male rats, maintained in an air,fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34°C, reduced to 21°C within 20 min. Results: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a ,-aminobutyric acid (GABA)A -receptor antagonist. Cooling from 34 to 21°C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse,evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. Conclusions: Tetany-induced neuronal network synchronization by GABAA -sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity. [source]

Parasitized Salamanders are Inferior Competitors for Territories and Food Resources

ETHOLOGY, Issue 4 2000
Daria S. Maksimowich
Parasites have been shown to impair the behaviour of their hosts, compromising the host's ability to exploit and compete for resources. We conducted two experiments to determine whether infestation with an ectoparasitic mite (Hannemania eltoni) was associated with changes in aggressive and foraging behaviour in the Ozark zigzag salamander, Plethodon angusticlavius. In a first experiment, male salamanders with high parasite loads were less aggressive overall than males with low parasite loads during territorial disputes. In addition, males with high parasite loads were more aggressive toward opponents with high parasite loads (symmetric contests) than toward opponents with low parasite loads (asymmetric contests). In contrast, males with low parasite loads did not adjust their level of aggression according to the parasite load of the opponent. In a second experiment, foraging behaviour of females was tested in response to ,familiar' (Drosophila) prey and ,novel' (termite) prey. Latency to first capture was significantly longer for parasitized than non-parasitized females when tested with ,familiar' prey, but not for ,novel' prey. Our results suggest that parasite-mediated effects may have profound influences on individual fitness in nature. [source]

The role of P300 in the recovery of post-stroke global aphasia

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2006
G. Nolfe
Seventeen right-handed patients suffering from global aphasia caused by a recent stroke in the left-hemisphere were studied. Passive P300 auditory event related potential paradigm was applied every months for 6 months. Aachen subtests were used for evaluating comprehension. Only a minority of the patients displayed the P300 at the baseline. Those patients had the best outcome at the Aachen comprehension subtest. Latency and amplitude changed over time in an unpredictable way. The number of patients presenting with the P300 also fluctuated, since some patients could regain the potential, whereas some other patients could lose that from month to month. Passive P300 is a monitor of recovery following global aphasia. A single passive P300 recording is useful for prognostic purposes. Repairing mechanisms in the first 6 months have a non-linear trend. [source]

Violent phenotype in SAL mice is inflexible and fixed in adulthood

AGGRESSIVE BEHAVIOR, Issue 5 2009
Deepa Natarajan
Abstract Violence was shown to be qualitatively different from functional hyper-aggression in mice selected for high aggression namely Short Attack Latency (SAL), Turku Aggressive (TA) and North Carolina (NC900) strains. This study aimed at investigating whether this adulthood violent phenotype as seen previously in the SAL mice is fixed and hence behaviorally inflexible right from day 1 of the experiment or consequential, i.e., subject to gradual change from functional aggression to violence. The functionally hyper-aggressive strains namely TA and NC900 strains served as controls for the study. Methodologically, behavioral (in)flexibility was studied using the overall sequential structure of agonistic behavior. In particular, intra-individual variations in the overall agonistic behavior as well as offensive, pre- and post-offensive behavior transitions, directly related to the resident,intruder interactions were investigated. The SAL mice showed the least intra-individual variation in their overall sequential agonistic structure as well as a fixed offense-oriented agonistic behavior of highest magnitude when compared with the other strains. Additionally, the pre- and post- offensive transitions were most salient in the functionally hyper-aggressive TA and NC900 strains, whereas virtually absent in the SAL mice. Thus, the violent behavior of the adult SAL mice is behaviorally inflexible or fixed, whereas the functionally hyper-aggressive behavior of the adult TA and NC900 mice is behaviorally flexible and constantly adaptive to the opponent behavior, over 3 days of repeated resident,intruder interaction. Aggr. Behav. 35:430,436, 2009. © 2009 Wiley-Liss, Inc. [source]

Use of a rodent model to show that varicella-zoster virus ORF61 is dispensable for establishment of latency,

JOURNAL OF MEDICAL VIROLOGY, Issue S1 2003
Hitoshi Sato
Abstract Varicella-zoster virus (VZV) results in a latent infection in humans after primary infection. Latency has also been established in guinea pigs and rats after inoculation with the virus. It was found that infection of cotton rats with the Oka vaccine strain of VZV results in a latent infection. To begin to identify which genes are required for latency, we infected cotton rats with VZV strain Oka that is deleted for ORF61. ORF61 protein transactivates certain VZV promoters and enhances the infectivity of viral DNA in transient transfections. Deletion of ORF61 results in abnormal syncytia and impairs the growth of VZV in vitro. Inoculation of cotton rats with ORF61-deleted Oka virus resulted in latent VZV infection in the nervous system similar to that seen for animals infected with parental virus. Thus, the cotton rat can be used to study the ability of mutants in the Oka vaccine strain of VZV to establish latent infection. J. Med. Virol. 70:S79,S81, 2003. © 2003 Wiley-Liss, Inc. [source]

Novel Polysaccharide-derived hydrogel prevents perineural adhesions in a rat model of sciatic nerve adhesion

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010
Michiro Yamamoto
Abstract We investigated the effects of a novel carboxymethylcellulose (CMC)-derived hydrogel, in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC, for preventing perineural adhesion after extensive internal neurolysis of rat sciatic nerve. Sciatic nerves were randomly assigned to one of the following groups: the Control group, operated but no treatment; the HA group, operated and treated with 1% hyaluronan; the CMC,PE(L) group, operated and treated with low-viscosity CMC,PE hydrogel; and the CMC,PE(H) group, operated and treated with high-viscosity CMC,PE hydrogel. Perineural adhesions were evaluated at 6 weeks. Nerves were also subjected to biomechanical testing to assess ultimate breaking strength. Electrophysiological and wet muscle weight measurements were performed. Breaking strengths were significantly lower for the CMC,PE(L) group than for the Control and HA groups. Latency was significantly longer for the Control group than for the CMC,PE(L) group at 20 days. The mean percentage of wet muscle weight to body weight was significantly lower for the Control group than for the CMC,PE(L) group at 6 weeks. Low-viscosity CMC,PE hydrogel appears to prevent perineural adhesions and allow early restoration of nerve function. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:284,288, 2010 [source]

Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to rats

JOURNAL OF PINEAL RESEARCH, Issue 4 2004
Leila Bikjdaouene
Abstract:, We have previously proven that some synthetic kynurenines behave as antagonists of the N-methyl- d -aspartate receptor inhibiting neuronal subtype of nitric oxide synthase activity. We now investigate the anticonvulsant activity of four of these kynurenines in pentylenetetrazole (PTZ)-treated rats. The rats were treated with each kynurenine (10,160 mg/kg, s.c.) 30 min before PTZ administration (100 mg/kg, s.c.). Then, latency, duration and intensity of the first seizure and the percent animal survival were noted. PTZ-induced death was counteracted by high doses of kynurenines. Latency of the first seizure was significantly increased and its intensity reduced at the same doses, whereas the duration of the first seizure significantly decreased with doses of 20 mg/kg in most of the kynurenines tested. Three hours after PTZ administration, the surviving animals were sacrificed and the levels of brain amino acids and nitrite were measured. PTZ administration increased glutamate, glutamine, serine and taurine levels in different brain areas. High doses of kynurenines generally counteracted the effects of PTZ on excitatory amino acids, but they also reduced inhibitory aminoacids. However, the most consistent effect of kynurenines was the dose-dependent reduction of brain nitrite levels induced by PTZ. These results reveal a new family of anticonvulsant drugs that affect mainly to nitric oxide production in the brain. [source]

High-Alcohol Preferring Mice Are More Impulsive Than Low-Alcohol Preferring Mice as Measured in the Delay Discounting Task

ALCOHOLISM, Issue 7 2009
B. G. Oberlin
Background:, Repeated studies have shown that high impulsivity, when defined as the tendency to choose small immediate rewards over larger delayed rewards, is more prevalent in drug addicts and alcoholics when compared with nonaddicts. Assessing whether impulsivity precedes and potentially causes addiction disorders is difficult in humans because they all share a history of drug use. In this study, we address this question by testing alcohol-naïve mice from lines showing heritable differences in alcohol intake. Methods:, Replicated selected lines of outbred high-alcohol preferring (HAP) mice were compared to a low-alcohol preferring (LAP) line as well as the low-drinking progenitor line (HS/Ibg) on an adjusting amount delay discounting (DD) task. The DD task employs 2 levers to present subjects with a choice between a small, immediate and a large, delayed saccharin reward. By adjusting the quantity of the immediate reward up and down based on choice behavior, the task allows an estimate of how the subjective value of the delayed reinforcer decreases as delays increase. Latency to respond was also measured for each trial. Results:, Both HAP2 and HAP1 lines of mice were more impulsive than the LAP2 and HS/Ibg lines, respectively. Hyperbolic curve-fitting confirmed steeper discounting in the high-alcohol drinking lines. In addition, the high-alcohol drinking lines demonstrated greater within-session increases in reaction times relative to the low-alcohol drinking lines. No other differences (consumption of saccharin, total trials completed) consistently mapped onto genetic differences in alcohol drinking. Conclusions:, Alcohol-naïve outbred mice selected for high-alcohol drinking were more impulsive with saccharin reinforcers than low-alcohol drinkers. These data are consistent with results seen using inbred strain descendents of high-alcohol drinking and low-alcohol drinking rat lines, and suggest that impulsivity is a heritable difference that precedes alcoholism. [source]

How Do Young Children Process Beliefs About Beliefs?: Evidence from Response Latency

MIND & LANGUAGE, Issue 3 2007
HARUO KIKUNO
Conceptual change theory posits a change in the form of reasoning from 3 to 4 years old while bias theory posits that processing factors are responsible for errors among younger children. The results from three experiments showed that children who failed a test of false belief took as long to respond as those who passed, and both groups of children took longer to respond to belief questions than to questions about prior states of reality. These results seem to support the bias theory. [source]

The Effect of Topical Epinephrine on Peripheral Nerve Conduction,,§

THE LARYNGOSCOPE, Issue 10 2002
Quintessa Miller MD
Abstract Objective/Hypothesis The aim of the study was to determine the effect of direct application of epinephrine solution on peripheral nerve conduction latency and amplitude. It was hypothesized that epinephrine does not cause neurapraxia when a standard (1:10,000) solution is applied topically. Study Design Eleven animals were divided into two groups of five and six. Group I had their left sciatic nerves and group II had their right sciatic nerves treated with epinephrine-soaked patties. The contralateral nerves of each group served as controls. Methods Nerve conduction studies were performed at baseline and immediately, at 1 minute, and at 5 minutes after patty application. Results Latency was found to increase above baseline immediately after patty application (P = .003) for the epinephrine-treated and saline-treated groups. Furthermore, the amplitude at 5 minutes after patty application increased from baseline (P = .009) for both groups. These observed differences were below what is considered to be clinically significant. Conclusion Topical epinephrine at a standard solution (1:10,000) does not lead to clinically significant nerve conduction abnormalities. [source]

The influence of various graphical and numeric trend display formats on the detection of simulated changes,

ANAESTHESIA, Issue 11 2009
R. R. Kennedy
Summary Integration of a large amount of information is important in anaesthesia but there is little research to guide the development of data displays. Anaesthetists from two hospitals participated in five related screen based simulation studies comparing various formats for display of historical or ,trend' data. Participants were asked to indicate when they first noticed a change in each displayed variable. Accuracy and latency (i.e. delay) in detection of changes were recorded. Latency was shorter with a graphic display of historical data than with a numeric display. Increasing number of variables or reduction of y -axis height increased the latency of detection. If the same number of data points were included, there was no difference between graphical and numerical displays of historical data. There was no difference in accuracy between graphical or numerical displays. These results suggest that the way trend data is presented can influence the speed of detection of changes. [source]

Epstein-Barr virus persistence and reactivation in myasthenia gravis thymus

ANNALS OF NEUROLOGY, Issue 6 2010
Paola Cavalcante PhD
Objective Increasing evidence supports a link between Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic human herpesvirus, and common B-cell,related autoimmune diseases. We sought evidence of EBV infection in thymuses from patients with myasthenia gravis (MG), an autoimmune disease characterized by intrathymic B-cell activation. Methods Seventeen MG thymuses (6 follicular hyperplastic, 6 diffuse hyperplastic, 5 involuted) and 6 control thymuses were analyzed using in situ hybridization for EBV-encoded small RNAs (EBERs), immunohistochemistry for EBV latent and lytic proteins, and polymerase chain reaction for EBV DNA and mRNA. Results All 17 MG thymuses showed evidence of active EBV infection, whereas none of the control thymuses were infected. Cells expressing EBERs (12 of 17) and EBV latency proteins (EBNA2, LMP1, and LMP2A) (16 of 17) were detected in medullary infiltrates and in germinal centers. Cells expressing early (BFRF1, BMRF1) and late (p160, gp350/220) lytic phase EBV proteins were present in 16 MG thymuses. Latency (EBNA1, LMP2A) or lytic (BZLF1) transcripts (often both) were present in all MG thymuses, and EBV DNA (LMP1 gene) was detected in 13 MG thymuses. We also found CD8+ T cells, CD56 + CD3-natural killer cells, and BDCA-2+ plasmacytoid dendritic cells in immune infiltrates of MG thymuses, but not germinal centers, suggesting an attempt of the immune system to counteract EBV infection. Interpretation Dysregulated EBV infection in the pathological thymus appears common in MG and may contribute to the immunological alterations initiating and/or perpetuating the disease. ANN NEUROL 2010;67:726,738 [source]

Axonal loss and myelin in early ON loss in postacute optic neuritis

ANNALS OF NEUROLOGY, Issue 3 2008
Alexander Klistorner PhD
Objective To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis. Method Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging. Results Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = ,0.66). Interpretation Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss. Ann Neurol 2008 [source]

Effects of Oral L-Arginine on the Foetal Condition and Neonatal Outcome in Preeclampsia: A Preliminary Report

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2006
Krzysztof Rytlewski
Randomized, placebo-controlled, double-blind, clinical trial. Oral therapy with 3 g of L-arginine daily or placebo as a supplement to standard therapy. Eighty-three preeclamptic women, randomly assigned to the L-arginine (n=42) or placebo (n=41) groups; [n=30 (L-arginine) and n=31 (placebo) ended the study, respectively]. Foetal gain chances due to ultrasound biometry, biophysical profile, Doppler velocimetry of pulsatility indices of umbilical and middle cerebral arteries, cerebro-placental ratio, as well as differences in duration of pregnancy and clinical data of newborn. L-arginine treatment transitory accelerated foetal gain and improved biophysical profile. Starting from 3rd week of therapy, the umbilical artery pulsatility indices values were significantly lower in L-arginine than in placebo group. Moreover, treatment with L-arginine caused significant increase of middle cerebral artery pulsatility indices and cerbro-placental ratio values. Latency was longer in L-arginine group. Neonates delivered in the L-arginine group revealed higher Apgar score. Supplementary treatment with oral L-arginine seems to be promising in improving foetal well-being and neonatal outcome as well as in prolonging pregnancy complicated with preeclampsia. However, these benefits require confirmation in more-powered, larger studies. [source]

Clindamycin and taste disorders

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2007
Mark C. H. De Groot
What is already known about this subject. ,,The antibiotic clindamycin has a bitter taste when it is used orally. What this study adds ,,A case series on oral as well as i.v. use of clindamycin associated with taste disorders is presented. ,,After corrections in a case-by-case analysis for several possible confounders such as indication, clindamycin is disproportionally associated with taste disorders. ,,Serum and hence saliva and sputum clindamycin levels seem to be responsible for this reversible adverse drug reaction. Aims Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin-induced taste disorders and to analyse the factors involved. Methods The adverse drug reaction database of the Netherlands Pharmacovigilance Centre was searched for reports concerning taste disorders with antibiotics. Clinical review of the cases and statistical analysis with logistic regression were performed. Characteristics of patients who reported taste disorders were compared for age, gender and formulation in clindamycin vs. other antibiotic users. Results Taste disorders were reported in seven (18%) of the clindamycin cases. In five reports an oral formulation was involved, in one report intravenous (i.v.) administration and in one report both formulations were used. Latency was <1 day after start and in one case taste disorders were present repeatedly at 10 min after every i.v. application. The adjusted reporting odds ratio was 7.0 (95% confidence interval 2.8, 17.3) and supports a possible causal relationship. Conclusions The association of clindamycin and taste disorders is supported by disproportionality analysis and seems to be independent of possible confounders such as age, gender and infections. The case reports suggest a role for clindamycin concentrations excreted in body fluids like saliva. [source]

Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitro

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2008
M Aulí
Background and purpose: To characterize the in vitro motor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon. Experimental approach: Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors. Key results: Strips developed weak spontaneous rhythmic contractions (3.67±0.49 g, 2.54±0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 ,M). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1,100 ,M) inhibited spontaneous contractions. Latency of off-contractions and nicotine responses were reduced by NG -nitro- L -arginine (1 mM) and blocked after further addition of apamin (1 ,M) or the P2Y1 receptor antagonist MRS 2179 (10 ,M) and were unaffected by the P2X antagonist NF279 (10 ,M) or ,-chymotrypsin (10 U mL,1). Amplitude of on- and off-contractions was reduced by atropine (1 ,M) and the selective NK2 receptor antagonist Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1 ,M). MRS 2179 reduced the amplitude of EFS on- and off-contractions without altering direct muscular contractions induced by ACh (1 nM,1 mM) or substance P (1 nM,10 ,M). Conclusions and implications: Latency of EFS-induced off-contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y1 receptors through apamin-sensitive K+ channels. EFS-induced on- and off-contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK2 receptors. Prejunctional P2Y1 receptors might modulate the activity of excitatory EMNs. P2Y1 and NK2 receptors might be therapeutic targets for colonic motor disorders. British Journal of Pharmacology (2008) 155, 1043,1055; doi:10.1038/bjp.2008.332; published online 1 September 2008 [source]

Developmental Changes in Endogenous Control of Attention: The Role of Target Familiarity on Infants' Distraction Latency

CHILD DEVELOPMENT, Issue 6 2002
Lisa M. Oakes
This study evaluated the interactive effects of endogenous and exogenous influences on infants' attention allocation by assessing the role of target familiarity on distraction latency during object exploration. In Experiment 1 (N= 54), infants' distraction latencies as they investigated both familiar toys (ones they previously had seen in a familiarization procedure) and novel toys (ones they had not seen in the familiarization procedure) were assessed longitudinally at 6.5 and 9 months of age. In Experiment 2 (N= 32), infants' distraction latencies were assessed at either 6.5 or 10 months as they investigated either familiar or novel targets. In both experiments, older infants, but not younger infants, exhibited longer latencies as they investigated novel toys as compared with their latencies as they investigated familiar toys. These results are discussed in terms of developmental changes in the interactive effects of endogenous and exogenous factors controlling attention allocation. [source]

Design and implementation of a high-performance CCA event service,

CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 9 2009
Ian Gorton
Abstract Event services based on publish,subscribe architectures are well-established components of distributed computing applications. Recently, an event service has been proposed as part of the common component architecture (CCA) for high-performance computing (HPC) applications. In this paper we describe our implementation, experimental evaluation, and initial experience with a high-performance CCA event service that exploits efficient communications mechanisms commonly used on HPC platforms. We describe the CCA event service model and briefly discuss the possible implementation strategies of the model. We then present the design and implementation of the event service using the aggregate remote memory copy interface as an underlying communication layer for this mechanism. Two alternative implementations are presented and evaluated on a Cray XD-1 platform. The performance results demonstrate that event delivery latencies are low and that the event service is able to achieve high-throughput levels. Finally, we describe the use of the event service in an application for high-speed processing of data from a mass spectrometer and conclude by discussing some possible extensions to the event service for other HPC applications. Published in 2009 by John Wiley & Sons, Ltd. [source]

Pattern-reversal visual evoked potentials in infants: gender differences during early visual maturation

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2002
CA Malcolm BScN RN RGN
This paper investigates gender differences in the peak latency and amplitude of the P1 component of the pattern-reversal visual evoked potential (pattern-reversal VEP) recorded in healthy term infants. Pattern-reversal VEPs in response to a series of high contrast black and white checks (check widths 120,, 60,, 30,, 24,, 12,, 6,) were recorded in 50 infants (20 males, 30 females) at 50 weeks post-conceptional age (PCA) and in 49 infants (22 males, 27 females) at 66 weeks PCA. Peak latency of the major component, P1, was considerably shorter in female compared with male infants. Differences in head circumference do not entirely account for the gender differences in peak latency reported here. A gender difference in P1 amplitude was not detected. These findings stress the importance of considering gender norms as well as age-matched norms when utilizing the pattern-reversal VEP in clinical investigations. Studies including a wider range of ages are clearly necessary in order to establish whether the earlier peak latencies in female infants represents a difference in the onset or rate of visual maturation. [source]

Learning large-scale spatial relationships in a maze and effects of MK-801 on retrieval in the rhesus monkey

DEVELOPMENTAL NEUROBIOLOGY, Issue 13 2007
Jian Hong Wang
Abstract Monkeys have strong abilities to remember the visual properties of potential food sources for survival in the nature. The present study demonstrated the first observations of rhesus monkeys learning to solve complex spatial mazes in which routes were guided by visual cues. Three monkeys were trained in a maze (6 m × 6 m) included of four different mazes. We recorded the cue and cup errors, latencies, and pathway for each trial. The data showed that monkeys learned the target place after three days in the first maze and spent a shorter time in learning the following mazes. The maze was an efficient method to measure the ability and proceeding of spatial memory in monkeys. Moreover, working memory can also be tested by using the maze. MK-801 at 0.02 mg/kg but not at 0.005 mg/kg impaired monkeys' retrieval of spatial memory after they learned all four mazes. The present maze may provide an efficient method to help bridging the gap in cognition between nonhuman primates and humans, and in particular to gain insight into human cognitive function and dysfunction. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source]

Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006
Timothy H. Moran
Abstract Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin,1 (CCK1) receptor. This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior. Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger, preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 360,367, 2006. [source]