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PubMed1999

Phonological loop and central executive functioning in Alzheimer's disease.

The phonological loop and central executive functioning were examined in patients with Alzheimer's disease (AD) and in normal elderly subjects. AD patients showed abnormal functioning of the phonological loop and decreased performance on tasks assessing the central executive. However, when AD patients were separated into two groups on the basis of their span level, both groups showed deficits of the central executive but only patients with the lower span level presented a dysfunction of the phonological loop as well as impaired performance in tasks of phonological discrimination, articulation rate and speed of processing. These results are interpreted in terms of progression of the disease, with high-span level patients being less severely demented and displaying deficits only in higher-level cognitive functions (such as manipulation of information stored in working memory) whereas patients with a low span level have impairments encompassing a series of more basic processes.

Aged↗

PubMed2002

Reflexive gaze orienting induces the line-motion illusion.

When a static line is presented near a brief cue, participants report motion within the line from the cued end towards the uncued end. Attention may mediate this effect by speeding the processing of the attended end of the line; however, apparent motion mechanisms between the cue and the line may also contribute. This study uses a new type of attentional cue, reflexive gaze orienting (RGO), which recruits attention automatically but uses a cue presented remotely from the line. Thus, RGO rules out motion mechanisms that might be recruited by a cue appearing in the vicinity of the line, and allows one to evaluate the contribution of attention per se to the illusion. In three experiments, RGO induced the line-motion illusion, establishing attention as a source of the illusion. Although attention may accelerate processing at the attended location, alternative mechanisms by which attention could cause the line-motion illusion are considered.

Adolescent↗

PubMed2003

A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180 mg alone and with alcohol, with hydroxyzine hydrochloride 50 mg as a positive internal control, on aspects of cognitive and psychomotor function related to driving a car.

BACKGROUND: Antihistamines (H(1)-receptor antagonists) are the mainstay of symptomatic therapy for allergic disorders. Antihistamines are needed that cause no disruptive effects on cognitive and psychomotor function. It is essential that antihistamines maintain the integrity of the cognitive system, not only in ambulatory patients at increased risk of drug-induced traffic- or work-related accidents, but also in students and others whose cognitive or intellectual impairment may adversely affect their performance.Objective; The goal of this study was to investigate the acute effects of fexofenadine hydrochloride 180 mg, alone and with a "social" dose of alcohol, on subjective feelings of sedation and on a battery of objective measures related to driving a car. These measures included information processing, psychomotor speed, and reaction time in an on-the-road car-driving task. Hydroxyzine hydrochloride 50 mg was included in the study as a positive internal control to validate the sensitivity of the psychometri tests to nonspecific impairment. METHODS: In this randomized, double-blind, 6-way, crossover study conducted at the Human Psychopharmacology Research Unit, Medical Research Centre (University of Surrey, Guildford, United Kingdom), 18 healthy volunteers received fexofenadine 180 mg, hydroxyzine 50 mg, and placebo alone and with alcohol (0.3 g/kg body weight or approximately 0.43-0.50 g/L blood-alcohol concentration). Treatment periods were separated by a washout period of at least 6 days. Subjects performed tests of cognitive and psychomotor performance at 1, 3, and 5 and hours after dosing. The test battery included subjective ratings of sedation, critical flicker fusion (CFF), choice reaction time (including recognition reaction time [RRT], motor reaction time [MRT], total reaction time [TRT], and brake reaction time [BRT]. RESULTS: Eighteen healthy male volunteers (median age, 30.5 years [range, 23-44 years]) were entered into the study. Fexofenadine alone and with alcohol had no significant effect on performance compared with placebo and was not distinguishable from placebo in any of the objective or subjective tests at any point. However, impairment was evident following the administration of hydroxyzine. Hydroxyzine caused significant impairment in CFF (P < 0.05), RRT (P < 0.001), and TRT (P < 0.001) compared with placebo. Hydroxyzine with alcohol significantly disrupted performance on all of the above measures with respect to both placebo and fexofenadine (P < 0.05) as well as MRT (P < 0.001). No significant treatment effects on BRT were found. CONCLUSION: Fexofenadine 180 mg did not have disruptive effects on objective measures related to driving a car and aspects of psychomotor and cognitive function, even when combined with a dose of alcohol equivalent to 0.3 g/kg body weight, in a study in which the psychometric assessments were shown to be sensitive to impairment.

Adult↗

PubMed2000

Anion- and pH-linked conformational transition in horseradish peroxidase.

In a previous study we have shown that bringing horseradish peroxidase to pH 3.0 induces a spectroscopic transition (G. Smulevich et al., Biochemistry 36 (1997) 640). We have extended the investigation on this pH-linked conformational change to different experimental conditions, such as (i) in phosphate alone, (ii) in HCl alone and (iii) in phosphate + NaCl. The data obtained allow a number of conclusions to be drawn, namely: (a) the exposure to pH 3.0 under all conditions brings about an alteration of the distal portion of the heme pocket, leading to the rapid formation of a hexa-coordinated species; (b) only in the presence of phosphate is the hexa-coordination followed by a slow cleavage (or severe weakening) of the proximal Fe-His bond, and (c) the rate of this second process is speeded up in the presence of Cl- ions. Such observations underline the presence of a communication pathway between the two opposite sides of the heme pocket, such that any alteration of the structural arrangement on one side of the heme cavity is transmitted to the other, inducing a corresponding conformational change.

Anions↗

PubMed2001

Biodegradable fibres spun from poly(lactide) generated by reactive extrusion.

Poly(lactide) (PLA) was spun both in a high speed spinning process with take-up velocities of 1000-5000 m min(-1) and in a spin drawing process at draw ratios of 4-6. The effect of the melt spinning conditions on the development of the structural hierarchy in the fibres and the relations to the textile physical properties were investigated. The PLA fibres were characterised with regard to the degree of crystallinity by DSC and WAXS, the orientation by WAXS and birefringence, and the stress-strain behaviour. The maximum physical break stress and the E-modulus observed in the spin drawn fibres were about 490 MPa and 6.3 GPa, respectively, at an elongation at break of 30%. The PLA was a copolymer of L-lactide (92 wt.%) and meso-lactide (8 wt.%) and was generated by reactive extrusion polymerisation. The PLA virgin pellets were analysed regarding their degradation during the spinning processes. Their thermal and rheological properties were determined by DSC and dynamic rheological measurements, respectively, to derive suitable parameters for the melt spinning processes.

Biodegradation, Environmental↗

PubMed2002

Discourse in different voices: reconciling N = 1 and N = many.

When groups are convened to discuss the making of policy, people are chosen to represent particular interests because they have relevant experience. Different stakeholders, however, may use differing discourses, and particular discourses may be privileged in particular contexts. This means that important contributions to the discussion may not be reflected in final reports. Discursive incommensurability is particularly seen when individual, personal experience is presented in meetings where quantification or "numbers talk" is privileged. While pooled personal experience may carry some weight in such a context, individual anecdote does not. The inclusion of 'consumers' in policy making groups may result in their dysempowerment. Their presence promises that they will have influence, but their voices disappear from the final document. The promise of empowerment is not realised. Dysempowerment may translate into empowerment with time, as it has done with feminism and the HIV/AIDS lobby. In order to speed the process, we suggest some practical means whereby mixed discourses may be generated and monitored. For constructive interchange, each party to the discourse needs to express the interests and arguments relevant to the group he or she represents. Supporting this principle of representation are principles of implicature and radical respect. Implicature is the act of implying what is relevant to others involved in the discourse. Radical respect is a fundamental and foundational respect for others in their roles as representatives of stakeholders with legitimate interests in the topic of the discourse.

Australia↗

PubMed2000

Accurate diagnosis of Helicobacter pylori. Culture, including transport.

Bacteriology laboratories are interested in culturing H. pylori for several reasons: (1) to investigate its growth requirements and metabolism; (2) for diagnostic purposes; (3) to establish the antibiotic susceptibility of isolates; (4) to identify potential virulence factors; and (5) to investigate microbial host-cell interactions. Despite the reasons listed, culture of H. pylori from gastric biopsy specimens is becoming less popular among clinical laboratories and physicians. The main reason is that it has become generally accepted that culture techniques are too demanding with many factors that must be controlled, in addition to simple and less expensive methods now available. Some of the disadvantages of culture include (1) special conditions for specimen transportation, (2) speed in processing of the sample to increase the probability of recovering the organism, (3) the use of expensive and complicated media with special conditions for maintenance, (4) the need for special incubation conditions, and (5) the length of time necessary to obtain a result for establishing treatment options in the patient. This article reviews aspects of H. pylori culture that could explain use being relegated to only a few clinical laboratories, some regional laboratories, and reference centers. There are several misconceptions in relation to culture techniques, such as transport and the processing of biopsy specimens. This article has mentioned simple and clear points that optimize the recovery rates of H. pylori by culture.

Bacteriological Techniques↗

PubMed1997

The hydrocortisone-induced transcriptional down-regulation of beta-galactoside alpha2,6-sialyltransferase in the small intestine of suckling rats is suppressed by mifepristone (RU-38.486).

The progressive loss of sialic acids of the brush-border membrane glycoproteins is one of the major biochemical changes which occur in the rat small intestine during the transition from suckling to weaning, and this process is speeded up by an injection of glucocorticoids to the suckling animals. We used the rat liver beta-galactoside alpha2,6-sialyltransferase (ST6(N), EC 2.4.99.1) cDNA as a probe to examine the mRNA level of this enzyme in the small intestine of both suckling (13-day-old) and weaned (25-day-old) rats. In the ileum of suckling rats, the ST6(N) mRNA level was about four times higher than in the jejunum, whereas the membrane-bound enzyme activity was less than two times higher. In comparison with the controls, hydrocortisone treatment significantly decreased the level of this transcript and of the corresponding enzyme activity in both segments of the small intestine of suckling rats. Additionally, the antiglucocorticoid mifepristone (RU-38.486) suppressed the effect of hydrocortisone. The expression of ST6(N) mRNA in the small intestine of weaned (25-day-old) rats was several times lower than that in suckling (13-day-old) rats, and was unresponsive to hydrocortisone as well as to mifepristone. These results indicate that the glucocorticoid-induced transcriptional down-regulation of ST6(N) expression in the small intestine of suckling rats is mediated via the glucocorticoid receptor pathway, and support the notion that alterations in sialylation of brush-border membrane glycoconjugates occurring upon weaning are the result of a lower expression of ST6(N).

Animals↗

PubMed2000

Activities of daily living among heart transplant candidates: neuropsychological and cardiac function predictors.

BACKGROUND: The ability of patients to perform day-to-day tasks (e.g., medication management, dietary regulation) is an important concern of transplant teams. METHODS: We studied a clinical series of 75 heart transplant candidates and 38 controls to examine the predictive validity of demographic, neuropsychologic, and cardiac function variables to a performance-based measure of instrumental activities of daily living (IADL) capacity (i.e., Everyday Problems Test, EPT). RESULTS: Multiple regression analyses, controlling for education and race, indicated that neuropsychologic tests accounted for between 34% and 67% of the variance across IADL domains (e.g., cooking, household chores, medication management). The IADL capacity was most consistently predicted by long-standing verbal ability (Shipley Institute of Living Scale-Vocabulary, SILS-VOC) and psychomotor speed and mental flexibility (Trail Making Test-Part B, TMT-B). Similarly, SILS-VOC and TMT-B also tended to show the best operating characteristics (i.e., sensitivity, specificity, positive predictive power, negative predictive power) for detection of dependence across IADL domains. In contrast, cardiac function measures (e.g., cardiac output, mean atrial pressure) were largely unrelated to the patient's performance on the paper-and-pencil EPT task. CONCLUSIONS: Long-standing intellectual ability, and a measure of speeded information processing and mental flexibility are the best predictors of IADL capacity.

Activities of Daily Living↗

PubMed2001

Neuropsychological profile of a 9-year-old child with subcortical band heterotopia or 'double cortex'.

Subcortical band heterotopia (SBH) or 'double cortex', is a congenital brain abnormality that results from aberrant migration of neurons during development of the cortex. MRI shows a continuous band of heterotopic grey matter located between the cortex and ventricular walls, separated from them by a thin layer of white matter. The condition is quite rare, found predominantly in females, and is occasionally familial with an X-linked dominant inheritance. Current research has focused on genetic and neurological correlates, with cognitive assessment restricted to a global measure of general intellectual functioning. This paper describes in detail the results of a neuropsychological assessment of a 9-year-old female recently diagnosed with SBH. Predominant features were a significantly reduced speed of processing for visuomotor and oral output and reduced immediate registration of information. This difficulty has functional implications affecting skill acquisition, learning in the classroom, and social interaction.

Attention↗

PubMed1987

Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel.

The long-term, in vivo effects of a single, subcurative dose (200 mg/kg body weight of mouse) of praziquantel on the structure of adult Schistosoma mansoni and on the process and speed of tegumental repair are described. In both male and female worms praziquantel caused often extensive damage to the tegument, in the form of surface blebbings, swellings and lesions, and vacuolization and disruption of the subtegumental tissues. Repair of the drug-induced tegumental damage occurred slowly with partial and, more rarely, complete repair only being seen after 65 days post-treatment (p.t.), although signs of damage were still observed, particularly in male worms, at 100 days p.t. In contrast, repair of damage to the subtegumental/parenchymal tissues including the tegumental perikarya occurred relatively quickly, with the majority of worms examined appearing normal by 8-12 days p.t. The possible role(s) of the host immune response in relation to the speed of tegumental repair in vivo is discussed.

Animals↗

PubMed1995

Trichuris trichiura infection and cognition in children: results of a randomized clinical trial.

The effects of mild to moderate infections of Trichuris trichiura on cognitive functions were investigated in Jamaican children aged 7 to 10 years. In all, 189 infected children and 100 uninfected classmates were studied. The infected children were randomly assigned to receive treatment (albendazole) or a placebo. All children were given cognitive tests on enrolment and 14 weeks later. These included verbal fluency (generation of ideas), digit span (working memory), number choice (speed of processing of visual stimuli), visual search (sustained attention) and a French Vocabulary test (paired-associate learning). At baseline, the infected children had lower scores than the uninfected ones in fluency (P = 0.01), search (P = 0.02) and French (P = 0.01). Treatment effects were examined among infected children and there was no significant treatment effect for any of the tests. However, there was a significant treatment by weight-for-age interaction in fluency (P < 0.05). The children with low weight-for-age (Z-score < -1) improved with treatment while there was no improvement with treatment among the other children. We concluded that treatment of children with mild to moderate T. trichiura infections using albendazole produces little benefit in cognition if they are adequately nourished; however, undernourished children are more likely to benefit.

Age Factors↗

PubMed2001

Acute tryptophan depletion in schizophrenia.

BACKGROUND: Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients. METHODS: Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink. RESULTS: The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores. CONCLUSIONS: Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders.

Administration, Oral↗

PubMed2004

Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injury.

Autopsy studies were undertaken in a 47-year-old college-educated male patient who, 7 months prior to an unexpected death, had sustained a mild traumatic brain injury (TBI) as manifested by brief loss of consciousness and an initial Glasgow Coma Scale score of 14. The patient died from cardiac arrest secondary to an undiagnosed and unknown arteriosclerotic cardiovascular disease as assessed by the coroners office at the time of autopsy. Gross inspection of the brain at autopsy was normal; however, microscopic analysis demonstrated what were considered trauma findings of hemosiderin-laden macrophages in the perivascular space and macrophages in the white matter, particularly the section taken from the frontal lobe. The patient had partially returned to work at the time of death, but had encountered problems with diminished cognitive performance in his work as an appraiser. Neuropsychological studies were generally within normal limits although several tests of either speed of processing or short-term memory showed lower than expected performance. This case demonstrates the presence of subtle neuropathological changes in the brain of a patient who sustained a mild TBI and was still symptomatic for the residual effects of the injury 7 months post injury when he unexpectedly died.

Attention↗

PubMed2005

A prospective study of the recovery of attention from acute to 2 years following pediatric traumatic brain injury.

Limited research has investigated specific attentional sequelae following pediatric traumatic brain injury (TBI), such as sustained, selective, and shifting attention, as well as speed of processing. Little is known about the pattern of recovery of these skills or their interaction with ongoing development. The present study examined attentional abilities at acute, 6-, 12-, and 24-month time points postinjury in a group of 71 children who had sustained a mild, moderate, or severe TBI. Results indicated that children who sustained a severe TBI generally performed poorest, but showed most recovery over time. The pattern of recovery was dependent on the attentional component being measured. Specifically, deficits were most evident on more complex and timed tasks. While a number of areas showed recovery over time, for some attentional components, difficulties persisted to 24 months postinjury.

Adaptation, Psychological↗

PubMed1999

A prospective analysis of the recovery of attention following pediatric head injury.

Little is known about specific attentional sequelae following a closed head injury, their pattern of recovery or their interaction with ongoing development. The present study examined attentional abilities in a group of children who had sustained a mild, moderate, or severe head injury. Results showed that the severe head injury group exhibited greater deficits on a number of attentional measures at acute and 6 months postinjury phases, in comparison to children in the mild and moderate head injury groups. Specifically, deficits were most evident on timed tasks where speed of processing was an integral component. Difficulties persisted to at least 6 months postinjury and so may lead to cumulative deficits over time.

Attention↗

PubMedDate not supplied

Rapid identification of substrates for novel proteases using a combinatorial peptide library.

Fluorogenic substrates for assaying novel proteolytic enzymes could be rapidly identified using an easy, solid-phase combinatorial assay technology. The methodology was validated with leader peptidase of Escherichia coli using a subset of an intramolecularly quenched fluorogenic peptide library. The technique was extended toward the discovery of substrates for a new aspartic protease of pharmaceutical relevance (human napsin A). We demonstrated for the first time known to us that potent fluorogenic substrates can be discovered using extracts of cells expressing recombinant enzyme to screen the peptide library. The straightforward and rapid optimization of protease substrates greatly facilitates the drug discovery process by speeding up the development of high throughput screening assays and thus helps more effective exploitation of the enormous body of information and chemical structures emerging from genomics and combinatorial chemistry technologies.

Amino Acid Sequence↗

PubMed2004

Graphoepitaxial deposition of cationic polymer micelles on patterned SiO2 surfaces.

We have studied the deposition of polymer micelles formed from poly(styrene)-block-poly(2-vinylpyridine) (PS-PVPH+) from room-temperature aqueous solutions at pH 1 onto a hydrophilic Si/SiO2 surface with a relief pattern 100 nm deep with variable widths. It has been found that the micelle density is substantially higher and the ordering of the micelles is improved for micelles that adsorb in the 100 nm depressions in the width range of ca. 500-5000 nm. We ascribe these effects to capillary forces that pull the aqueous solution into the canyons where the micelles can be trapped. While the ordering of the micelles can be substantial, they do not form a perfect hexagonal crystal. If the surface is chemically modified by a Au coating, the micelle-surface interaction is strengthened and the degree of ordering is diminished. These results demonstrate that a combination of graphoepitaxy and processing conditions (speed of substrate withdrawal or evaporation of solvent) can be used to make fairly ordered polymer micelle arrays over a space of (at least) several millimeters.

Journal Article↗