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Cognition and health-related quality of life in a well-defined subgroup of patients with partial epilepsy.

To investigate the extent and nature of the objective and subjective cognitive deficits and health-related quality of life (HRQOL) in adult outpatients with relatively well-controlled partial epilepsy without symptomatic aetiology, who were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of the epilepsy history and medication on various cognitive functions and the HRQOL. 56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy were compared with 56 age-, gender-, and education-matched healthy controls. Patients were tested on attention, memory, speed of information processing, and executive functioning. Questionnaires aimed at measuring self-perceived cognitive functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were used to compare the two groups. Linear regression analysis was performed to identify the epilepsy and medication-related factors that are associated with cognitive functioning and HRQOL. Patients scored lower on measures of attention (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00). Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical functioning was unaffected. These patients also expressed reductions in mental functioning as indicated by a low self-perceived cognitive functioning (P = 0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency, localisation, years on CBZ, and CBZ dosage were not related to cognitive functioning or HRQOL. Patients with partial epilepsy, even when able to maintain regular jobs, have impaired cognition and HRQOL that cannot be attributed to their epilepsy history or CBZ dosage or years of CBZ intake. Therefore, physicians should be more aware of their cognition and HRQOL, in addition to the antiepileptic drug regime.

Adolescent↗

Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system and cognitive impairment are consistent findings in depression. This study examines the associations between HPA system regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. METHODS: The HPA system dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. RESULTS: Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. CONCLUSIONS: Our data support the assumption that psychopathological symptoms and the HPA system dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.

Adult↗

Elevation of core temperature and mental functioning.

The purpose of this study was to investigate whether raised core temperature due to gradually increased amounts of exercise affects concentration and speed of information processing, 20 paid men, separated into groups of high (> 56 ml/kg/min.) and low fitness (< 46 ml/kg/min.) according to their maximal oxygen uptake (VO2max), participated in two experimental conditions (exercise and control). Concentration was measured by the Random Number Generation test of attentional deployment given every 10 min. of cycling at workloads calculated as 40, 50, 60, 70, and 80% of individual VO2max values and 10 min. after exercise cessation (exhaustion). Speed of information processing was estimated by an eight-choice reaction time/movement time task given before and after exercise and 15 min. after exercise cessation. Core temperature was recorded at the same time individuals were administered the psychological tests. Analyses indicated that core temperatures increased significantly as a function of exercise intensity for high and low fitness groups. Correlations among the psychophysiological factors indicated that increases in core temperature were not associated with mental functioning. However, at certain core temperatures, core temperature and average choice reaction time/movement time were associated with participants' fitness.

Adult↗

Evaluating neuropsychological impairment in chronic fatigue syndrome.

This study was designed to provide an estimate of the prevalence of neuropsychological impairment in chronic fatigue syndrome (CFS), to evaluate the concordance between impairment found on standardized tests and self-reported neuropsychological problems, and to study the relationship between neuropsychological functioning and fatigue severity and psychological processes. We adopted an individual approach to determine neuropsychological impairment as contrasted with the group-comparisons approach used in previous studies. Also, correction for premorbid functioning and confounders was done on an individual basis. The results show that a minority of participants were impaired in neuropsychological functioning. There was no relationship between neuropsychological impairment on standardized tests and self-reported memory and concentration problems. Neuropsychological functioning was not related to fatigue or depression. Slowed speed of information processing and motor speed were related to low levels of physical activity.

Adult↗

Sleep, vigilance and cognition in postmenopausal women: placebo-controlled studies with 2 mg estradiol valerate, with and without 3 mg dienogest.

OBJECTIVE: To determine the effects in postmenopausal women with insomnia of hormone replacement therapy (HRT) with 2 mg estradiol valerate (E2V) alone, or in combination with 3 mg dienogest (DNG), in the context of the introduction of the novel preparation Climodien (2 mg E2V/2 mg DNG) (Schering AG, Berlin, Germany). METHODS: Parallel groups of women with insomnia related to the postmenopausal syndrome were randomized to 2 months' treatment with 2 mg E2V, 2 mg E2V/3 mg DNG or placebo (respectively, n = 17, 16, 16). Patients were then studied with techniques for assessing sleep quality, vigilance and cognition. Sleep quality was determined subjectively by means of the questionnaire-based sleep and awakening quality scale (SSA), and objectively with polysomnography. Sleep-related breathing disorders were evaluated by means of the apnea/hypopnea index. Vigilance was measured using quantitative electroencephalography with statistical probability mapping. Cognition (speed of information processing, cognition processing capacity and perceptual processing resources) was studied using the techniques of auditory event-related potentials (P300 latency and amplitude). RESULTS AND CONCLUSIONS: Treatment with 2 mg E2V and 2 mg E2V/3 mg DNG significantly improved subjective sleep quality and showed trends towards improvements in objective sleep quality. The combination of 2 mg E2V/3 mg DNG also improved the apnea/hypopnea index. Vigilance was slightly improved by treatment with 2 mg E2V and markedly with 2 mg E2V/3 mg DNG. Speed of information processing was improved with 2 mg EV2 and 2 mg E2V/3 mg DNG, whilst the latter also improved cognitive processing capacity and perceptual processing resources. The study provides evidence that HRT can improve sleep quality and mental functioning in postmenopausal women and that E2V/DNG combinations, such as 2 mg E2V/2 mg DNG, should be considered for this indication and also for the treatment of sleep-related breathing disorders in the menopause. The addition of dienogest to estradiol valerate did not antagonize the benefits of estradiol valerate in terms of sleep quality but rather potentiated estradiol valerate-related improvements in vigilance and some aspects of cognition.

Aged↗

Effect of two doses of ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects.

The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms. The dual-coding phenomenon (a break point between coding verbal material and images) was demonstrated in all the tests. After placebo, the break point was observed at 960 ms and dual coding beginning at 1920 ms. After each dose of the ginkgo extract, the break point (at 480 ms) and dual coding (at 960 ms) were significantly shifted toward a shorter presentation time, indicating an improvement in the speed of information processing.

Aged↗

A case-based consiliarius for therapy recommendation (ICONS): computer-based advice for calculated antibiotic therapy in intensive care medicine.

We report here on the system ICONS which utilizes case-based reasoning for medical decision support. As an application domain we have chosen the medical field of 'calculated antibiotic therapy' in an intensive care medicine setting. The system ICONS which runs on a personal computer suggests adequate antibiotic therapy regimen satisfying medical and economic conditions. To speed up the process of finding an adequate antibiotic therapy for a current patient, case-based reasoning is used for finding previously documented similar cases and for modifying them according to the requirements of the current patient. To reduce the memory capacity for the documentation of cases, collections of similar cases are clustered to prototypes. Medical knowledge is represented within a hierarchy of such prototypes and cases and an additional context-sensitive background knowledge-base. A knowledge acquisition tool was programmed that allows revisions of the background medical knowledge-base by simple and comprehensive methods. In addition to the advantage of producing site-specific and time-dependent knowledge, case-based reasoning is a practical method for speeding-up the process of generating and evaluating hypotheses in medical classification tasks.

Anti-Bacterial Agents↗

[The effects of phenytoin and carbamazepine on the cognitive function of epileptic patients].

We made a comparative study of the cognitive function of 60 epileptic patients before and after the use of phenytoin (DPH) and carbamazepine (CBZ). Five types of neuropsychological tests were adopted. Although both DPH and CBZ affected cognitive function, the degrees of their effects were not the same. DPH affected cognitive function in a broad field, including concentration, remembrance, psychological motor speed and mental processing, whereas CBZ had only slight effect on perception and motor speed. It is stressed that cognitive function disorder caused by antiepileptic drugs should be early detected by synchronous examinations of the level of antiepileptic drugs and the neuropsychological functions.

Attention↗

Effects of the nicotinic antagonist mecamylamine on inspection time.

RATIONALE: Several lines of evidence suggest that nicotinic acetylcholine receptors (nAchRs) are involved in speed of information processing, and inspection time appears to be particularly sensitive to nicotinic manipulation. OBJECTIVE: The present study sought to examine the effects of the nAchR antagonist mecamylamine on inspection time. Furthermore, the extent to which the anticholinesterase donepezil would reverse the effects of mecamylamine on inspection time was also examined. METHODS: A double-blind, repeated measures design was employed. Subjects (n = 6) received placebo, mecamylamine (20 mg PO) or mecamylamine (20 mg PO) and donepezil (5 mg PO). Inspection time and physiological measures were then assessed. RESULTS: The mecamylamine condition and the mecamylamine and donepezil condition were associated with an increase in heart rate, when compared to the placebo condition. There was a significant slowing of inspection time in the mecamylamine condition; compared to placebo, which was partly reversed by donepezil. CONCLUSIONS: The slowing of inspection time following mecamylamine is consistent with the role of nAchRs in speed of information processing, and add to the evidence that IT may in part index nAchR system integrity.

Adolescent↗

Dissociable effects in reaction time performance after unilateral cerebral infarction: a comparison between the left and right frontal cortices in rats.

Reaction time performance reflects the speed of information processing, both in humans and lower vertebrates like the rat. The present study compared reaction time performance in rats following unilateral infarction to the frontal cortex. The objective was to model cognitive impairment as it is seen in humans after stroke. Rats were trained in a reaction time paradigm, after which unilateral cortical infarction was induced photochemically. Reaction time performance was differentially affected after unilateral infarction to either the left or right frontal cortex, whereas sham operation did not result in a significant alteration in reactivity. An overall increase in reaction time of about 10% was present at 4 weeks after frontal infarction. In addition, a lateralized reaction time deficit occurred very early after right frontal infarction as an increase of 10-15% in trials directed towards the contralesional side. Additional analyses showed that these reaction time deficits can be explained differently: the former as a gradual and general decrease in the speed of information processing, whereas the latter shows specific impairment to initiate a contralateral motor response. The former matches well with the mental slowing observed in stroke patients, whereas the latter resembles a neglect phenomenon. We conclude that measuring reaction time performance after frontal cortical infarction in rats could offer a useful tool to model particular human cognitive impairments following cerebral infarction.

Animals↗

Hemispheric differences in the rates of information processing for simple non-verbal stimuli.

An inspection time task, used to gauge differences in speed of information processing between the hemispheres, was administered to 22 normal subjects. It was found that the left visual field-right hemisphere (LVF-RH) exhibited an inferior performance relative to the right visual field-left hemisphere (RVF-LH). These results were consistent with other studies which have found an RVF-LH advantage for the processing of temporal/serial information. The possible ramifications of these results for models of asymmetry which do and do not attribute the left hemisphere's preferential capacity for language to these fundamental processes are then discussed.

Adult↗

Proposal of a computerized algorithm for continuous wave CO2 laser on-line control during orthopaedic surgery. Phase II: simplified algorithm version (LCA-s) and helmet-mounted data access device solution.

This paper is the continuation of the Phase I report published in 1992 by Canestri. It contains recent findings on how to speed-up the process of sublimated volume forecasting for a TEM11* CO2 laserbeam in CW mode following an original model proposed by the author--called LCA--here presented in a simplified version (LCA-s) on PMMA (polymethylmethacrilate) samples. Other interesting parameters, such as the time required to create the minimal injury vb along with its physical interpretations, are reported and explained. TEM11*, TEM01* and TEM00 beams profiles are also compared and discussed for LCA-s. The results of both Phase I and Phase II of this investigation can be integrated in one single solution package for the end-user, combining fast decisions making and operational features. The final part of this paper describes the 'helmet-mounted' data recall visor methodology which allows the surgeon to access to a data base for information retrieval during the course of an operation without interrupting the surgical case itself. This particularly interesting application allows the surgeon to consult a centrally-located data base which contains important information regarding similar clinical cases, choice of laserbeam profiles and focal lengths, simulation of beam behaviours, performances and other data. The on-line and direct access to the data base supports him in all those borderline situations in the O.R. in which the laser device type and configuration/calibration play a device role in the success of the operation. Also, the helmet-mounted display frees surgeon's hands in order to allow him to continue the operation while consulting the data base on-line, thus speeding up decision processes regarding changes of laser set-up, general calibration optimization and remote clinical consultancy.

Algorithms↗

Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial.

Attention deficits after traumatic brain injury (TBI) are common and disabling. Many pharmacologic agents have been used to ameliorate attention deficits, and considerable interest has focused on methylphenidate (MP) because of its documented efficacy in attention deficit disorder. However, clinical studies of MP in subjects with TBI have yielded mixed results. We examined the effects of MP on attentional function in individuals with TBI referred specifically for attentional assessment and treatment. Subjects were studied in a double-blind, placebo-controlled, repeated crossover design, using five different tasks designed to measure various facets of attentional function. MP produced a significant improvement in the speed of mental processing. Orienting to distractions, most aspects of sustained attention, and measures of motor speed were unaffected. These results suggest that MP may be a useful treatment in TBI but is primarily useful for symptoms that can be attributed to slowed mental processing.

Adolescent↗

Tickling expectations: neural processing in anticipation of a sensory stimulus.

Predictions of the near future can optimize the accuracy and speed of sensory processing as well as of behavioral responses. Previous experience and contextual cues are essential elements in the generation of a subjective prediction. Using a blocked fMRI paradigm, we investigated the pattern of neural activation in anticipation of a sensory stimulus and during the processing of the somatosensory stimulus itself. Tickling was chosen as the somatosensory stimulus rather than simple touch in order to increase the probability to get a high degree of anticipation. The location and nature of the stimulus were well defined to the subject. The state of anticipation was initiated by attributing an uncertainty regarding the time of stimulus onset. The network of activation and deactivation during anticipation of the expected stimulus was similar to that engaged during the actual sensory stimulation. The areas that were activated during both states included the contralateral primary sensory cortex, bilateral areas in the inferior parietal lobules, the putative area SII, the right anterior cingulate cortex and areas in the right prefrontal cortex. Similarly, common decreases were observed in areas of sensorimotor cortex located outside the area representing the target of stimulus, i.e., areas that process information which is irrelevant to the attended process. The overlapping pattern of change, during the somatosensory stimulation and the anticipation, furthers the idea that predictions are subserved by a neuronal network similar to that which subserves the processing of actual sensory input. Moreover, this study indicates that activation of primary somatosensory cortex can be obtained without intra-modal sensory input. These findings suggest that anticipation may invoke a tonic top-down regulation of neural activity.

Adult↗

[Normal and pathological cognitive aging].

The relation of age associated changes of cognitive functions to those of dementia diseases is not well investigated for very old age. Because aging as well as dementia diseases are associated with cognitive deficits, this leads to differential diagnostic problems in very old age. Relevant with respect to this differentiation are on the one hand the concepts of cognitive ageing, the dementia syndrome and dementia diseases, and on the other hand empirical findings with respect to 1. the neuropsychological crossectional pattern, 2. the premorbid intelligence or adult intelligence level, 3. the speed of decline. ad 1. The speed of cognitive processes shows a considerable reduction in normal aging. However, the reduction of learning and orientation as well as pronounced word-finding problems seem to be characteristic of the development of a dementia syndrome. ad 2. The importance of the level of adult intelligence is demonstrated by the possibility that a very old person with low adult intelligence level is diagnosed as demented without suffering from one of the dementia diseases. In the opposite case of a slowly progressive dementia disease in a person with a superior level of adult intelligence a diagnosis of dementia according the standard criteria can be given only in an advanced stage of the disease. ad 3. The importance of the speed of decline of cognitive performance for the diagnosis of dementia is discussed (e.g. < 1 point of the MMSE vs > 3 MMSE points per year). An optimization of the time course criterion (change-sensitive tests and an empirically determined cut-off) could improve the early dementia diagnosis, which relies up to now mostly on crossectional features. The more precise assessment of the deterioration speed would be an opportunity to investigate the factors or processes which determine the deterioration speed, knowledge of which in turn would be a starting point for development of therapy.

Adult↗

Cold extrusion as a continuous single-step granulation and tabletting process.

The potential of cold extrusion as a continuous granulation/tabletting technique was investigated. Extrudates (X, 9 mm) were produced using twin-screw extrusion, cut manually into tablets (thickness, 4 mm) and dried at 25 degrees C for 20 h. alpha-Lactose monohydrate (200 M) was used as an excipient, PVP (Kollidon K30) and water as binders, and hydrochlorothiazide as the model drug. The influence of formulation (water content, PVP addition, drug incorporation) and process (total input rate and screw speed) parameters on the process (torque, die pressure, visual evaluation of tablets) and on the tablet properties (tensile strength, friability, disintegration time, porosity) was evaluated. Formulation, as well as process parameters, affected the process feasibility, but had only a minor effect on the tablet properties at conditions that allowed continuous tablet production. All alpha-lactose monohydrate tablets formulated without and with PVP and produced at optimum conditions showed tensile strengths above 0.7 and 1.5 MPa, friabilities below 1.0 and 0.9%, and disintegration times below 1 and 8 min, respectively. This technique allows single-step granulation/tabletting of pure alpha-lactose monohydrate, indicating that cold extrusion could be used as alternative tablet production technique for ingredients with poor compaction properties. As the tablets prepared by extrusion have a much higher porosity compared with conventional tablets, this technique could also be useful for tablet production of formulations with poor disintegrating properties.

Chemistry, Pharmaceutical↗

Structure prediction of protein complexes by an NMR-based protein docking algorithm.

Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential structures. In this paper, we are discussing a variant of the protein-protein docking problem, where the input consists of the tertiary structures of proteins A and B plus an unassigned one-dimensional 1H-NMR spectrum of the complex AB. We present a new scoring function for evaluating and ranking potential complex structures produced by a docking algorithm. The scoring function computes a 'theoretical' 1H-NMR spectrum for each tentative complex structure and subtracts the calculated spectrum from the experimental one. The absolute areas of the difference spectra are then used to rank the potential complex structures. In contrast to formerly published approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530-2537]) we do not use distance constraints (intermolecular NOE constraints). We have tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank (Bernstein et al., 1977) and whose 1H-NMR shift assignments are available from the BMRB database. The best result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfect separation between good approximations of the true complex structure and false positives.

Algorithms↗

Video image processing greatly enhances contrast, quality, and speed in polarization-based microscopy.

Video cameras with contrast and black level controls can yield polarized light and differential interference contrast microscope images with unprecedented image quality, resolution, and recording speed. The theoretical basis and practical aspects of video polarization and differential interference contrast microscopy are discussed and several applications in cell biology are illustrated. These include: birefringence of cortical structures and beating cilia in Stentor, birefringence of rotating flagella on a single bacterium, growth and morphogenesis of echinoderm skeletal spicules in culture, ciliary and electrical activity in a balancing organ of a nudibranch snail, and acrosomal reaction in activated sperm.

Acrosome↗