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Biomedical subjects

G Barrett

Publications and source records attributed to G Barrett.

At least 19 recordsLinked to original sources
PubMed2004

Differential effects on the laser evoked potential of selectively attending to pain localisation versus pain unpleasantness.

OBJECTIVE: To determine the effects on the laser evoked potential (LEP) of selectively attending to affective (unpleasantness) versus sensory-discriminative (localisation) components of pain. METHODS: LEPs, elicited by painful CO2 laser stimulation of two areas of the right forearm, were recorded from 62 electrodes in 21 healthy volunteers, during three tasks that were matched for generalised attention: Localisation (report stimulus location), Unpleasantness (report stimulus unpleasantness), Control (report pain detection). LEP components are named by polarity, latency, and electrode. RESULTS: N300-T7 peak amplitude was significantly greater during Localisation than Unpleasantness. The difference in N300-T7 amplitude between Localisation and Control approached significance, suggesting an increased amplitude in Localisation compared with Control, rather than a reduced amplitude in Unpleasantness. Peak amplitude, latency, and topography of N300-FCz, P450, P600-800 (early P3) and P800-1000 (late P3) did not differ significantly between tasks. CONCLUSIONS: These results suggest that the N300-T7 LEP peak reflects the activity of cerebral generators involved in the localisation of pain. The topography of N300-T7 is consistent with a source in contralateral secondary somatosensory cortex/insula and maybe primary somatosensory cortex. SIGNIFICANCE: This study confirms a role of the lateral pain system in the localisation of pain, and distinguishes it from stimulus novelty or attention.

Adult↗
PubMed2004

Conceptualisation, development, and evaluation of a measure of unplanned pregnancy.

STUDY OBJECTIVE: To develop a measure of unplanned pregnancy that is valid, reliable, and appropriate in the context of contemporary demographic trends and social mores and can be used in a variety of situations, including the production of population prevalence estimates. DESIGN: A two stage study design: qualitative (inductive) methods to delineate the construct of pregnancy planning, and quantitative/psychometric methods to establish the means of measurement. SETTING: Eight health service providers (comprising 14 clinics, including antenatal, abortion, and one general practitioner) across London, Edinburgh, Hertfordshire, Salisbury, and Southampton in the UK. PARTICIPANTS: Samples comprised a mixture of pregnant (continuing pregnancy and opting for abortion) and recently pregnant (post-abortion and postnatal) women. At the qualitative stage, 47 women took part in depth interviews (20 of whom were re-interviewed after the birth of their baby). Items were pre-tested with 26 women, and two psychometric field tests were carried out with, respectively, 390 and 651 women. MAIN RESULTS: A six item measure of unplanned pregnancy was produced. Psychometric testing demonstrated the measure's high reliability (Cronbach's alpha = 0.92; test-retest reliability = 0.97) and high face, content, and construct validity. Women's positions in relation to pregnancy planning are represented by the range of scores (0-12). CONCLUSIONS: A psychometric measure of unplanned pregnancy, the development of which was informed by lay views, is now available. The measure is suitable for use with any pregnancy regardless of outcome (that is, birth, abortion, miscarriage) and is highly acceptable to women.

Abortion, Induced↗
PubMed2001

Development of a fully integrated analysis system for ions based on ion-selective optodes and centrifugal microfluidics.

A fully integrated, miniaturized analysis system for ions based on a centrifugal microfluidics platform and ion-selective optode membranes is described. The microfluidic architecture is composed of channels, five solution reservoirs, a measuring chamber, and a waste reservoir manufactured onto a disk-shaped substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on device, onto a support layer and then immobilized on the disk. Fluid propulsion is achieved by the centrifugal force that results from spinning the disk, while a system of valves is built onto the disk to control flow. These valves operate based on fluid properties and fluid/substrate interactions and are controlled by the angular frequency of rotation. With this system, we have been able to deliver calibrant solutions, washing buffers, or "test" solutions to the measuring chamber where the optode membrane is located. An analysis system based on a potassium-selective optode has been characterized. Results indicate that optodes immobilized on the platform demonstrate theoretical responses in an absorbance mode of measurement. Samples of unknown concentration can be quantified to within 3% error by fitting the response function for a given optode membrane using an acid (for measuring the signal for a fully protonated chromoionophore), a base (for fully deprotonated chromoionophore), and two standard solutions. Further, the ability to measure ion concentrations by employing one standard solution in conjunction with acid and base and with two standards alone were studied to delineate whether the current architecture could be simplified. Finally, the efficacy of incorporating washing steps into the calibration protocol was investigated.

Calibration↗
PubMed2001

Systemic administration of antisense p75(NTR) oligodeoxynucleotides rescues axotomised spinal motor neurons.

The 75 kD low-affinity neurotrophin receptor (p75(NTR)) is expressed in developing and axotomised spinal motor neurons. There is now convincing evidence that p75(NTR) can, under some circumstances, become cytotoxic and promote neuronal cell death. We report here that a single application of antisense p75(NTR) oligodeoxynucleotides to the proximal nerve stumps of neonatal rats significantly reduces the loss of axotomised motor neurons compared to controls treated with nonsense oligodeoxynucleotides or phosphate-buffered saline. Our investigations also show that daily systemic intraperitoneal injections of antisense p75(NTR) oligodeoxynucleotides for 14 days significantly reduce the loss of axotomised motor neurons compared to controls. Furthermore, we found that systemic delivery over a similar period continues to be effective following axotomy when intraperitoneal injections were 1) administered after a delay of 24 hr, 2) limited to the first 7 days, or 3) administered every third day. In addition, p75(NTR) protein levels were reduced in spinal motor neurons following treatment with antisense p75(NTR) oligodeoxynucleotides. There were also no obvious side effects associated with antisense p75(NTR) oligodeoxynucleotide treatments as determined by behavioural observations and postnatal weight gain. Our findings indicate that antisense-based strategies could be a novel approach for the prevention of motor neuron degeneration associated with injuries or disease.

Animals↗
PubMed2001

Influence of hypoglycaemia, with or without caffeine ingestion, on visual sensation and performance.

Full-field visual evoked potentials and visual information processing were measured in 16 normal, healthy subjects during a hyperinsulinaemic clamp. A randomized cross-over design was used across three conditions: hypoglycaemia and caffeine; hypoglycaemia and placebo; and euglycaemia and caffeine. The latency of the P100 component of the pattern-reversal visual evoked potential increased significantly from rest to hypoglycaemia, but no effect of caffeine was found. Subjects were subsequently divided into two median groups based on the increase in P100 latency in the placebo condition (Group 1, +0.5 ms; Group 2, +5.6 ms). In the absence of caffeine, an inverse correlation between the increase in P100 latency from rest and a deterioration in visual movement detection was found for Group 2, but not for Group 1. Caffeine ingestion resulted in a further increase in P100 latency, from rest to hypoglycaemia, for subjects in Group 2. Hypoglycaemia in the absence of caffeine produces changes in visual sensation from rest to hypoglycaemia. In those subjects most sensitive to the effects of hypoglycaemia (Group 2), the increase in P100 latency was associated with poorer performance in tests of visual information processing. Caffeine ingestion produced further increases in P100 latency in these subjects.

Adult↗
PubMed2001

Attention and cognition in bradykinetic-rigid syndromes: an event-related potential study.

Bradykinetic-rigid syndromes are often accompanied by cognitive impairment. Because prominent motor involvement in these disorders may interfere with neuropsychological testing, we used event-related potentials (ERPs) for the assessment of cognition and attention in 41 patients with various bradykinetic-rigid syndromes of less than 5 years duration: idiopathic Parkinson's disease corticobasal degeneration, Steele-Richardson-Olszewski syndrome (SRO), and multiple system atrophy. Patients were compared with matched normals. ERP abnormalities in the auditory "oddball" paradigm were found only in corticobasal degeneration and SRO. ERP abnormalities in selective attention tasks were present in all patient groups, changes in SRO being the most prevalent. Abnormalities in corticobasal degeneration were present under "less-attention-demanding" conditions and suggested involvement of posterior parts of the brain. Multiple system atrophy and idiopathic Parkinson's disease patient groups had minimal ERP abnormalities. However, reaction times in MSA were longer in all paradigms. The results of the study support the view that bradykinetic-rigid syndromes involve some attentional deficits, but also have distinct reaction time and ERP characteristics, which may be helpful in differential diagnosis.

Acoustic Stimulation↗
PubMed2000

Chemical grafting of molecularly imprinted homopolymers to the surface of microplates. Application of artificial adrenergic receptor in enzyme-linked assay for beta-agonists determination.

A technique for coating of microplate wells with a molecularly imprinted polymer (MIP), specific for epinephrine, is presented. 3-Aminophenylboronic acid was polymerized in the presence of epinephrine using oxidation of the monomer by ammonium persulfate. This process resulted in the grafting of a thin polymer layer onto the polystyrene surface of the microplates. The polymer affinity was determined by an enzyme-linked assay using a conjugate of horseradish peroxidase and norepinephrine (HRP-N). It was found that imprinting resulted in increased affinity of the polymer toward HRP-N and epinephrine. Influence of the buffer pH and concentration on the polymer affinity was analyzed. It was shown that the MIP-coated microplates could be used for assay development and drug screening. The high stability of the polymers and good reproducibility of the measurements make MIP coating an attractive alternative to traditional antibodies or receptors, used in ELISA.

Adrenergic beta-Agonists↗
PubMed2000

Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor.

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB.

Animals↗
PubMed2000

Expression, purification, and characterization of the human receptor activator of NF-kappaB ligand (RANKL) extracellular domain.

Receptor activator of NF-kappaB ligand (RANKL) is a type II transmembrane protein found on osteoblasts which functions as a major determinant of osteoclast differentiation and activation. RANKL mediates bone homeostasis through binding to the cognate ligand on osteoclasts, RANK, and a soluble decoy receptor, osteoprotegerin (OPG). We designed a construct encoding the extracellular domain of human RANKL that conformed to reports of native processing. To encourage folding and posttranslational modification of a normally membrane-inserted moiety, we expressed the RANKL truncate as a secreted protein using the signal sequence from OPG in a Trichoplusia ni cell line using a baculovirus expression vector. RANKL was purified by a three-step process including an OPG-Fc affinity column. SDS-PAGE and mass spectral analysis indicated that the protein was >99% pure and glycosylated. Circular dichroism spectra revealed that the protein exhibited structural elements similar to tumor necrosis factor-alpha. By BIAcore analysis, RANKL bound to OPG with an affinity of 6.7 nM. Sedimentation equilibrium analytical ultracentrifugation analyses established that our protein existed as a trimer. We conclude that our expressed human RANKL truncate is folded, is functional, and exhibits self-association consistent with other family members.

Amino Acid Sequence↗
PubMed2000

Clinical application of event-related potentials in dementing illness: issues and problems.

Many of the problems associated with the clinical application of event-related potentials (ERPs) are well recognized. These include the broad inter-subject variability of peak latencies and amplitudes in control groups, as well as the apparent non-specificity of some ERP tests. In addition, it is often the case that the same test yields a different proportion of 'hits' (in terms of identification of abnormality in patients classified by other means as having dementia) when used by different research groups. This is almost certainly due to differences in the disease state of the patients being tested. The difference between hit rates identifies another important factor which is not often considered in the application of ERP tests in clinical medicine. This is that although an ERP test may identify abnormality in the later stages of disease, the true task for the test is to identify abnormality in early disease when evidence of cognitive dysfunction will be different and less frank than in later stages of the disorder. It is therefore, necessary to identify the cognitive deficits associated with the early stages of dementia and devise appropriate ERP tests to detect these deficits. A recent paper by Fox et al. (Fox, N.C., Warrington, E.K., Seiffer, A.L., Agnew, S.K., Rossor, M.N., 1998. Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's disease. A longitudinal prospective study. Brain 121, 1631-1639.) suggests that ERP tests of verbal memory function may be the most sensitive for detecting the early stages of Alzheimer's disease.

Cognition Disorders↗
PubMed2000

Women's sexual health after childbirth.

OBJECTIVE: To investigate the impact of childbirth on the sexual health of primiparous women and identify factors associated with dyspareunia. DESIGN: Cross-sectional study using obstetric records, and postal survey six months after delivery. SETTING: Department of Obstetrics and Gynaecology, St George's Hospital, London. POPULATION: All primiparous women (n = 796) delivered of a live birth in a six month period. METHODS: Quantitative analysis of obstetric and survey data. MAIN OUTCOME MEASURES: Self reported sexual behaviour and sexual problems (e.g. vaginal dryness, painful penetration, pain during sexual intercourse, pain on orgasm, vaginal tightness, vaginal looseness, bleeding/irritation after sex, and loss of sexual desire); consultation for postnatal sexual problems. RESULTS: Of the 484 respondents (61% response rate), 89% had resumed sexual activity within six months of the birth. Sexual morbidity increased significantly after the birth: in the first three months after delivery 83% of women experienced sexual problems, declining to 64% at six months, although not reaching pre-pregnancy levels of 38% . Dyspareunia in the first three months after delivery was, after adjustment, significantly associated with vaginal deliveries (P = 0 x 01) and previous experience of dyspareunia (P = 0 x 03). At six months the association with type of delivery was not significant (P = 0 x 4); only experience of dyspareunia before pregnancy (P < 0 x 0001) and current breastfeeding were significant (P = 0 x 0006). Only 15% of women who had a postnatal sexual problem reported discussing it with a health professional. CONCLUSIONS: Sexual health problems were very common after childbirth, suggesting potentially high levels of unmet need.

Adolescent↗
PubMed1999

Women's sexuality after childbirth: a pilot study.

A pilot study was carried out investigating women's sexual health in the postnatal period. Postal questionnaires were sent to a cohort of 158 primiparous women approximately 7 months after delivery. Women who had resumed sexual intercourse were asked a detailed set of questions about problems experienced, sexual practices, frequency of intercourse, satisfaction with sex life, and consultation for postnatal sexual problems. All women were asked about the information they received on postnatal health prior to the birth and any information or help and advice they received from health professionals on the subject after the birth. Ninety-eight women (62%) responded. Women experienced significant levels of morbidity in the postnatal period; 3 months after delivery 58% experienced dyspareunia, 39% experienced vaginal dryness, and 44% suffered loss of sexual desire. These figures had reduced to 26, 22, and 35%, respectively, by the time of answering the questionnaire (approximately 8 to 9 months after delivery). Compared to before pregnancy, there was a decrease in frequency and satisfaction with sexual intercourse, although sexual practices changed little. Of the 67 women who reported a postnatal sexual problem, only 19% discussed this with a health professional. Conversations with health professionals in routine postnatal health contacts were mainly about contraception, and only rarely discussed problems with intercourse.

Adolescent↗
PubMed1999

Dietary exposures to nitrate in the UK.

Dietary exposures to nitrate have been estimated for two different groups of UK consumers. The daily dietary exposure of the general population was estimated from the UK 1997 Total Diet study to be 52 mg/day. Vegetables contributed approximately 70% to this total dietary exposure. Dietary exposure estimates for adult consumers of vegetables commonly eaten in the UK were 93 mg/day and 140 mg/day for mean and 97.5th percentile consumers, respectively. Dietary exposures to nitrate of UK consumers are similar to those in other European countries and are less than the Acceptable Daily Intake (ADI) for nitrate set by the European Commission's Scientific Committee for Food.

Adult↗
PubMed1999

Possible roles for mismatch negativity in neuropsychiatry.

OBJECTIVE: This article reviews research on the main characteristics of mismatch negativity (MMN) and its applications in neuropsychiatry. BACKGROUND: Event-related potentials (ERPs) have been used to study many aspects of information processing. Mismatch negativity is an early auditory ERP that has been identified as an index of an automatic (preconscious) alerting mechanism stimulating an individual to attend to unexpected environmental events. Disturbances of MMN may relate to abnormalities of auditory information processing contributing to the pathophysiology of neuropsychiatric conditions. METHOD: The authors review (1) studies that have evaluated the electrophysiological aspects of MMN and (2) studies that have investigated the different applications of MMN in neuropsychiatry. RESULTS: The first part of this article describes the characteristics of MMN, its cerebral origins, and electrophysiological parameters. We then discuss the role of "echoic memory" as well as that of attention and vigilance. In the second part of the article, disturbances in MMN associated with schizophrenia, depressive illness, dementing processes, and other neuropsychiatric states are discussed. CONCLUSIONS: MMN is a preconscious cognitive ERP, the main generators and functions of which are well defined. Observations relating to the origins of MMN and its role in early auditory information processing together with its possible behavioral significance, combined with observations of MMN aberrations in psychiatric conditions, may provide novel insights into the pathophysiology of neuropsychiatric states.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Comparative study of event-related potentials and positron emission tomography activation during a paired-associate memory paradigm.

Event-related potentials (ERP) and regional cerebral blood flow (rCBF) activation using 15O-labeled water associated with retrieval and retention of episodic memory were studied during a visual paired-association task with delayed response in eight healthy subjects. In both studies, the subjects memorized four pairs of figures during the learning period. They were presented with each cue (S1) and asked to judge whether the following figure (S2) formed one of the memorized pairs. In an attempt to identify brain activity related to memory function, a choice reaction task with delay was used as a behavioral control. The ERP study showed a posterior positive component in the difference waveform, which was obtained by subtracting responses in the choice reaction task from those in the paired association task, between 300 and 850 ms after S1 presentation. It was maximal at the parietal midline electrode and distributed predominantly over the left posterior quadrant of the scalp. The rCBF activation study showed a greater increase in rCBF in the right dorsolateral prefrontal cortex (Brodmann's area 46), left inferior frontal cortex (Brodmann's area 44/45), left thalamus, and bilateral cerebellar hemisphere during the paired association task as compared to the choice reaction task, which suggests a possible involvement of cerebello-thalamo-cortical circuit in the memory processing. Additionally, it is suggested that the scalp distribution of the ERP component may not necessarily represent regional cortical activation below the electrodes where such a component is observed and could indirectly represent activation in remote areas such as subcortical regions. It seems that ERP and rCBF activation may provide information about different aspects of higher brain function.

Adolescent↗