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Biomedical subjects

G A Baker

Publications and source records attributed to G A Baker.

At least 37 records · Page 2Linked to original sources

Measuring the impact of multiple sclerosis on psychosocial functioning: the development of a new self-efficacy scale.

OBJECTIVE: To develop a scale to measure self-efficacy in neurologically impaired patients with multiple sclerosis and to assess the scale's psychometric properties. DESIGN: Cross-sectional questionnaire study in a clinical setting, the retest questionnaire returned by mail after completion at home. SETTING: Regional multiple sclerosis (MS) outpatient clinic or the Clinical Trials Unit (CTU) at a large neuroscience centre in the UK. SUBJECTS: One hundred persons with MS attending the Walton Centre for Neurology and Neurosurgery and Clatterbridge Hospital, Wirral, as outpatients. METHODS: Cognitively impaired patients were excluded at an initial clinic assessment. Patients were asked to provide demographic data and complete the self-efficacy scale along with the following validated scales: Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale, Impact, Stigma and Mastery and Rankin Scales. The Rankin Scale and Barthel Index were also assessed by the physician. RESULTS: A new 11-item self-efficacy scale was constructed consisting of two domains of control and personal agency. The validity of the scale was confirmed using Cronbach's alpha analysis of internal consistency (alpha = 0.81). The test-retest reliability of the scale over two weeks was acceptable with an intraclass correlation coefficient of 0.79. Construct validity was investigated using Pearson's product moment correlation coefficient resulting in significant correlations with depression (r= -0.52) anxiety (r =-0.50) and mastery (r= 0.73). Multiple regression analysis demonstrated that these factors accounted for 70% of the variance of scores on the self-efficacy scale, with scores on mastery, anxiety and perceived disability being independently significant. CONCLUSION: Assessment of the psychometric properties of this new self-efficacy scale suggest that it possesses good validity and reliability in patients with multiple sclerosis.

Adult↗

Molecular dynamics ensemble, equation of state, and ergodicity.

The variant of the NVE ensemble known as the molecular dynamics ensemble was recently redefined by Ray and Zhang [Phys. Rev. E 59, 4781 (1999)] to include the specification of a time invariant G (a function of phase and, explicitly, the time) in addition to the total linear momentum M. We reformulate this ensemble slightly as the NVEMR ensemble, in which R/N is the center-of-mass position, and consider the equation of state of the hard-sphere system in this ensemble through both the virial function and the Boltzmann entropy. We test the quasiergodic hypothesis by a comparison of old molecular dynamics and Monte Carlo results for the compressibility factor of the 12-particle, hard-disk systems. The virial approach, which had previously been found to support the hypothesis in the NVEM ensemble, remains unchanged in the NVEMR ensemble. The entropy S approach depends on whether S is defined through the phase integral over the energy sphere or the energy shell, the parameter straight theta being 0 or 1, respectively. The ergodic hypothesis is found to be supported for straight theta=0 but not for straight theta=1.

Journal Article↗

Linkage and redox isomerism in ruthenium complexes of catecholate, semiquinone, and o-acylphenolate ligands derived from 1,2-dihydroxy-9,10-anthracenedione (alizarin) and related species: syntheses, characterizations, and photophysics.

The complexes Ru(CO)2L2(AL-2H) (AL = alizarin; L = PPh3, PCyc3, PBu3, P(m-NaSO3C6H4)3), Ru(CO)(dppe)(PBu3)(AL-2H), and RuH(CO)L2(AL-H) (L = PPh3, PCyc3), and Ru(CO)2L2(AR-2H) (AR = anthrarobin; L = PBu3) were prepared by reactions of Ru3(CO)12, L, and AL, and the complexes RuH(CO)(PPh3)2(AL-H), RuH(CO)(PPh3)2(QN-H) (QN = quinizarin), and RuH(CO)(PPh3)2(LQN-H) (LQN = leucoquinizarin) are prepared by reactions of RuH2(CO)(PPh3)3 with AL or QN. The AL-2H and AR-2H ligands act as 1,2-catecholates, whereas the AL-H, QN-H, LQN-H ligands are 1,9-o-acylphenolate ligands. RuH(CO)(PPh3)2(AL-H) is characterized by X-ray crystallography. The electrochemistry of these complexes is examined, and the semiquinone complexes [Ru(CO)2L2(AL-2H)]+ (L = PPh3, PCyc3, PBu3) and [Ru(CO)(dppe)(PBu3)(AL-2H)]+ are generated by chemical oxidation and were characterized by EPR and IR spectroscopy. The photophysical properties are also reported.

Anthraquinones↗

Extending the reach of immunoassays to optically dense specimens by using two-photon excited fluorescence polarization.

Fluorescence anisotropy/polarization measurements represent a powerful tool for quantifying biomolecule/ligand complexation. These types of measurements are also at the heart of a wide variety of commercial homogeneous fluoroimmunoassays. In this note, we demonstrate the power of two-photon excited fluorescence anisotropy (2-PEFA) measurements as a tool for quantifying hapten/antibody association in the presence of a strongly absorbing, nonfluorescent dye. The results of these experiments show that 2-PEFA measurements are intrinsically more sensitive when compared to traditional one-photon excited fluorescence anisotropy (1-PEFA) strategies and 2-PEFA-based measurements allow one to perform accurate hapten/antibody binding measurements in strongly absorbing samples directly under conditions where 1-PEFA measurements fail completely. Overall, the 2-PEFA approach offers significant advantages when compared to traditional 1-PEFA methods especially in strongly absorbing samples. 2-PEFA also opens the door to perform more rapid and reliable polarization/anisotropy-based measurements with minimal sample preparation.

Fluorescence Polarization Immunoassay↗

Effects of ethanol volume percent on fluorescein-labeled spinach apo- and holocalmodulin.

We report the effects of EtOH volume percent (0-70%) on spinach apo- and holocalmodulin that have been site-selectively labeled with fluorescein (F). In these experiments, calmodulin (CaM) has one F reporter group attached to Cys-26, and this site is located immediately adjacent to one of the four primary Ca(2+)-binding sites (EF hands). The optimum analytical CaM-F sensitivity to Ca2+ occurs between approximately 10 and 30% EtOH. Our results also show that added EtOH causes changes in CaM and these changes are surprisingly different for apo- and holo-CaM. Apo-CaM-F appears to lose one of its two waters of hydration at approximately 20% EtOH and retains one water of hydration between approximately 20 and 70% EtOH. In apo-CaM-F, the semiangle that describes the range over which the fluorescein reporter group can precess remains essentially constant (42 +/- 2 degrees) between 0 and 70% EtOH. This shows that the fluorescein reporter group precessional freedom in apo-CaM-F is not affected significantly by EtOH. Holo-CaM-F also appears to lose one water of hydration at approximately 20-30% EtOH but then appears to denature as the EtOH volume percent increases. The fluorescein reporter group semiangle within holo-CaM-F decreases from 43 +/- 1 degrees in neat aqueous buffer to 36 +/- 1 degrees at 70% EtOH. This shows that holo-CaM-F is less nativelike and the EF hand "closes down" about the fluorescein reporter group in holo-CaM-F as the EtOH volume percent increases.

Apoproteins↗

Lamotrigine add-on for drug-resistant partial epilepsy.

BACKGROUND: Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. OBJECTIVES: To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). SELECTION CRITERIA: Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. MAIN RESULTS: We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available preclude any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. REVIEWER'S CONCLUSIONS: Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

Anticonvulsants↗

Effects of temperature on calcium-sensitive fluorescent probes.

The effect of temperature on the binding equilibria of calcium-sensing dyes has been extensively studied, but there are also important temperature-related changes in the photophysics of the dyes that have been largely ignored. We conducted a systematic study of thermal effects on five calcium-sensing dyes under calcium-saturated and calcium-free conditions. Quin-2, chlortetracycline, calcium green dextran, Indo-1, and Fura-2 all show temperature-dependent effects on fluorescence in all or part of the range tested (5-40 degrees C). Specifically, the intensity of the single-wavelength dyes increased at low temperature. The ratiometric dyes, because of variable effects at the two wavelengths, showed, in general, a reduction in the fluorescence ratio as temperature decreased. Changes in viscosity, pH, oxygen quenching, or fluorescence maxima could not fully explain the effects of temperature on fluorescence. The excited-state lifetimes of the dyes were determined, in both the presence and absence of calcium, using multifrequency phase-modulation fluorimetry. In most cases, low temperature led to prolonged fluorescence lifetimes. The increase in lifetimes at reduced temperature is probably largely responsible for the effects of temperature on the physical properties of the calcium-sensing dyes. Clearly, these temperature effects can influence reported calcium concentrations and must therefore be taken into consideration during any investigation involving variable temperatures.

Aminoquinolines↗

Quality-of-life and behavioral outcome measures in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards.

PURPOSE: To review the methodology and use of quality-of-life and behavioral measures used in randomized controlled trials (RCTs) of antiepileptic drugs in patients with epilepsy. METHODS: Trial reports were found by searching a previously developed comprehensive database of epilepsy RCTs and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and quality-of-life and behavioral measure data were extracted. RESULTS: There were 52 different measures used in 46 trials, with the Profile of Mood States, the Minnesota Multiphasic Personality Inventory, and the Washington Psychosocial Seizure Inventory being applied the most frequently. Overall, evidence of the reliability, validity, and sensitivity of measures used in populations of people with epilepsy was sparse. There was also little information on the clinical interpretation of the results. CONCLUSION: Our results highlight a consistent failure to apply quality-of-life and behavioral measures in RCTs in a systematic way. We found repeated evidence of researchers' failure to review the use of previous measures and selection of measures without evidence of their appropriateness for use in a population with epilepsy. We recommend the use of quality-of-life and behavioral measures in RCTs with proven psychometric properties in a population with epilepsy.

Adult↗

Patient-based assessments of quality of life in newly diagnosed epilepsy patients: validation of the NEWQOL.

PURPOSE: In epilepsy, patient-based assessments are increasingly used as outcome measures in clinical trials of novel therapies alongside the traditional clinical measures of efficacy. The objective of this study was to validate psychometrically a quality of life (QOL) measure developed for use with recently diagnosed epilepsy patients. METHODS: The NEWQOL (Quality of Life in Newly Diagnosed Epilepsy Instrument) is a 93-item self-administered battery designed to assess QOL in patients with new-onset epilepsy. NEWQOL consists of eight multi-item scales (13 subscales) measuring several health parameters: Anxiety, Depression, Social Activities, Symptoms, Locus of Control/ Mastery, Neuropsychological Problems (includes the following subscales: Fatigue, Memory, Concentration, Motor Skills, and Reading), Social Stigma, Worry, Work Limitations, and several single-item measures (General Health, Number of Seizures, Social Limitations, Social Support, Self Concept, Ambition Limitations, Health Transition, and General Limitations). The NEWQOL was collected at baseline and 1 week post-baseline from 108 patients in the U.K. and U.S. RESULTS: All of the multi-item scales had high item discriminant validity, good test-retest reliability, and acceptable levels of internal consistency reliability; all but the Reading and Stigma subscales had negligible floor and ceiling effects. General linear models were used to examine the known groups validity of NEWQOL. Significant differences were observed in the Worry, Symptoms, Summary Neuropsychological Scales, and all Neuropsychological subscales (Memory, Fatigue, Concentration, Motor Skills, and Reading), indicating poorer functioning in the more frequent or severe seizure groups. CONCLUSIONS: Results from this study offer supportive evidence that NEWQOL has good validity and reliability and can discriminate between patient groups, particularly in relation to symptoms and psychological problems. We conclude that NEWQOL represents a useful measure for future studies in this patient population.

Adolescent↗

The stigma of epilepsy: a European perspective.

PURPOSE: To study the stigma of epilepsy in a European sample. METHODS: Clinical and demographic details and information about patient-perceived stigma was collected by using self-completed questionnaires mailed to members of epilepsy support groups. RESULTS: Stigma data were collected from >5,000 patients living in 15 countries in Europe. Fifty-one percent reported feeling stigmatised, with 18% reporting feeling highly stigmatised. High scores were correlated with worry, negative feelings about life, long-term health problems, injuries, and reported side effects of antiepileptic drugs (AEDs). Cross-cultural comparisons revealed significant differences between countries. A multivariate analysis identified impact of epilepsy, age of onset, country of origin, feelings about life, and injuries associated with epilepsy as significant contributors on scores on the stigma scale. CONCLUSIONS: This study confirms the findings of previous studies that have identified the importance of both clinical and nonclinical factors in understanding the stigma of epilepsy. The results of cross-cultural differences require further explanation, and much more research should be conducted to reduce the stigma associated with epilepsy.

Adolescent↗

Kinetics and thermodynamics of free flavins and the flavin-based redox active site within glucose oxidase dissolved in solution or sequestered within a sol-gel-derived glass.

We report on the steady-state and time-resolved fluorescence from the redox active site flavine adenine dinucleotides (FADs) that are bound to glucose oxidase (GOx) when this enzyme is dissolved in aqueous solution or sequestered within a sol-gel-derived glass. To the best of our knowledge, this represents the first report on the actual dynamics of an enzyme active site when the enzyme is part of a sol-gel-derived glass. The results from these experiments show that the "free" FAD intramolecular folding/unfolding kinetics are slowed 3-10-fold within the glass vs solution. The intramolecular exciplex formation event (i.e., excited-state FAD residue folding/unfolding) is completely arrested for the GOx-bound FAD if the enzyme is sequestered within a glass in the absence of glucose. This is significantly different from the behavior of GOx dissolved in solution. However, despite this difference in behavior, the GOx molecules that are sequestered within the glasses continue to function somewhat like GOx dissolved in aqueous solution if they are challenged with glucose. We also found that the GOx molecules do not leach from the glass and they exhibit rotational mobility that is only 2-fold less than GOx dissolved in aqueous solution at 20 degrees C. In aqueous solution or within these glasses, the enzyme pocket that hosts the FAD redox sites opens up by 25-30% when GOx is challenged with glucose. Finally, we present preliminary analytical results for film-based sol-gel-derived biosensors that contain GOx, L-amino acid oxidase or cholesterol oxidase wherein the intrinsic FAD fluorescence produces the analytical signal.

Binding Sites↗

Stress and avoidance in Pseudoseizures: testing the assumptions.

Twenty women and 10 men with Pseudoseizures were matched by age and gender with an epilepsy- and a healthy-control group. In response to clinical and research evidence of a relationship between Pseudoseizures and the experience of stress, it was hypothesised that people with Pseudoseizures would perceive their ongoing lives as more stressful, and use more avoidant and distancing coping, and less problem-focused coping, than people in the two control groups. Using the Perceived Stress Scale (Cohen et al., J. Health Soc. Behav. 24, 1983, 385-396) and the Ways of Coping, revised version (Folkman and Lazarus, Manual for Ways of Coping Questionnaire, Consulting Psychologist Press, Paola Alto, CA, 1988) the study found that people with Pseudoseizures: (1) perceived their ongoing lives as significantly more stressful; (2) were significantly more likely to use a maladaptive (escape-avoidant) coping strategy; and (3) were significantly less likely to use an adaptive (planful problem solving) approach to coping than healthy controls. The study findings indicate that people with Pseudoseizures experience lives as stressful as do people with epilepsy, and are likely to employ maladaptive coping responses. Implications for diagnosis, intervention and future research are discussed.

Adaptation, Psychological↗

The association of sexual and physical abuse with somatization: characteristics of patients presenting with irritable bowel syndrome and non-epileptic attack disorder.

BACKGROUND: Physical symptoms are commonly presented for treatment in the absence of physical pathology. This study tests predictions arising from the theory that childhood sexual abuse leads to emotional distress, illness orientation and social dysfunction as adults and that one or more of these effects, in turn, leads to presentation of functional (i.e. unexplained) symptoms. METHODS: Two groups of patients with physical symptoms in the absence of organic disease (non-epileptic attack disorder or irritable bowel syndrome) were contrasted with organically diseased groups with comparable symptoms (epilepsy and Crohn's disease, respectively). RESULTS: Despite their contrasting clinical presentation, irritable bowel and non-epileptic attack groups were similar in recalling more sexual and physical abuse, as both children and adults, than their comparison groups. They were also similar in being more emotionally and socially disturbed and illness-orientated, but these putative mediating variables could not account for the relationship of abuse with presentation of functional symptoms. CONCLUSIONS: Adults presenting functional neurological and abdominal symptoms are characterized by history of abuse. The current focus on childhood sexual abuse should be broadened to include sexual, and particularly physical, abuse in adulthood as well as childhood. The intervening processes that link abuse to somatization remain to be identified but are unlikely to include adult emotional and social disturbance or general illness-orientation.

Adult↗

The SF-36 as a health status measure for epilepsy: a psychometric assessment.

A considerable literature is now available on the applications and psychometric properties of the MOS SF-36 Health Survey. In epilepsy, the SF-36 has been used as a health status measure in its own right and as the stem for two condition-specific measures. This paper replicates for epilepsy previous work to support use of the SF-36 across a range of clinical conditions. Data were obtained from a European-wide descriptive study of quality of life of adults with epilepsy; analysis of responses on the SF-36 is based on 4,929 subjects in eight countries. Missing value rates for all SF-36 items were low; percentages for whom complete information available for subscales ranged from 95.7% to 98.6%. All subscales passed tests for item-internal consistency and item-discriminant validity. Reliability coefficients exceeded the standard recommended for group comparisons across all subscales. Floor effects were negligible for all but the two role disability subscales; there were substantial ceiling effects for five of the SF-36 subscales. We conclude that the SF-36 is a valid and reliable health status measure for descriptive studies of people with epilepsy, but ceiling effects may limit its usefulness as an outcome measure in the assessment of new treatments.

Adolescent↗

Cross-cultural differences in health-related quality of life of people with epilepsy: findings from a European study.

PURPOSE: To examine between-country differences in health-related quality of life (HRQOL) of adults with epilepsy across a large number of European countries. METHODS: Self-completion postal questionnaire sent to large sample of adults with epilepsy, recruited from epilepsy support groups or epilepsy outpatient clinics. The questionnaire was developed in English and translated. Back-translations from each language were checked for accuracy. The questionnaire sought information on clinical and socio-demographic details, and contained a number of previously validated scales of psychosocial well-being (the SF-36, the perceived impact of epilepsy scale, and a feelings of stigma scale). RESULTS: Controlling for socio-demographic and clinical characteristics, significant between-country differences were found in scores on the perceived impact of epilepsy scale, on seven of the eight SF-36 domains, and on the feelings of stigma scale. Respondents in Spain and the Netherlands fared consistently better, whilst those in France fared poorest, compared to those in other countries in terms of the various HRQOL measures used. CONCLUSION: Several possible reasons for the cross-cultural differences in HRQOL are proposed. Clearly, there is no single explanation and there may also be reasons which we have overlooked. This study emphasises the need for further comprehensive research in order that the position of people with epilepsy in different countries be more thoroughly understood in the social context.

Adolescent↗

Non-epileptic attack disorder (NEAD): a comprehensive review.

Non-epileptic attack disorder (NEAD) represents a well-recognized clinical problem with a reported incidence among individuals with a diagnosis of intractable epilepsy as high as 36%. A failure to identify this disorder may lead to certain risks for the patient including polypharmacy, anticonvulsant toxicity, hazardous intervention, social and economic demands and a lack of recognition or neglect of any underlying psychological distress. This review provides a description of NEAD in an historic and societal context and discusses the variety of terminology which has been applied to this psychophysiological phenomenon. Epidemiology and associated methodological limitations; and diagnostic and classification issues related to NEAD in comparison to epilepsy are considered. The problems of failure to recognize NEAD in comparison to epilepsy are considered. The problems of failure to recognize NEAD are outlined, and theoretical and empirical aetiological issues are discussed.

Culture↗

Detecting the faking of amnesia: a comparison of the effectiveness of three different techniques for distinguishing simulators from patients with amnesia.

This paper compared the effectiveness of three different procedures that have been put forward as possible ways of distinguishing patients with genuine memory problems from those who are attempting to simulate amnesia. The performance of 20 patients with amnesia was compared with the performance of 20 normal control individuals and 20 normal individuals who had been asked to simulate amnesia on the distraction/no distraction test (Baker, Hanley, Kimmance, & Slade, 1993), the coin-in-the-hand test (Kapur, 1994) and word fragment completion (Horton, Smith, Barghout, & Connolly, 1992). The distraction/no distraction test and the coin-in-the-hand test both proved successful in distinguishing patients with amnesia from simulators (p < .01). Excellent performance by virtually all patients with amnesia coupled with chance or below chance performance by 19/20 simulators on the coin-in-the-hand test was particularly striking. Consistent with the results of Horton et al. ( 1992), the word fragment completion test successfully discriminated between the performance of simulators and controls (p < .01). However, the fragment completion test proved incapable of distinguishing between the performance of patients with amnesia and simulators (p > .05). It is argued that there may be problems inherent in the use of tests designed to investigate implicit memory in attempts to detect malingering.

Adult↗

Patients' understanding of and adjustment to epilepsy: interim findings from a European survey.

The purpose of the study was to discover how much European patients with epilepsy and their carers understand about epilepsy. This article reports the interim results for the first four European countries recruited to the study and includes data collected from 1,920 people with epilepsy and 2,136 carers. Clinical and demographic details and data on understanding of epilepsy were collected using self-completed questionnaires mailed to members of epilepsy support groups. There were no significant differences between people with epilepsy and carers for scores on the Epilepsy Knowledge Questionnaire, although people with epilepsy were more likely to score in the higher ranges. Higher scorers on the questionnaire were more likely to be better educated, to have lower scores on the impact of epilepsy scales, to have higher scores on the adjustment to epilepsy scale, and were less likely to report feeling stigmatized. The study confirms the findings of previous studies that people with epilepsy are reasonably well informed, although some gaps in their knowledge were evident. A comparison of country differences will be made and multivariate statistical analysis will allow a better understanding of the contribution of knowledge to people's overall adjustment to their condition.

Adaptation, Psychological↗