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G A Baker

Publications and source records attributed to G A Baker.

At least 55 records · Page 3Linked to original sources
PubMed1998

A parallel multiharmonic frequency-domain fluorometer for measuring excited-state decay kinetics following one-, two-, or three-photon excitation.

We report on the performance of a new, multiharmonic frequency-domain instrument that uses the high harmonic content of a passively mode-locked, pulse-picked femto-second Ti-sapphire laser as the excitation source for the determination of one-, two-, or three-photon excited time-resolved fluorescence anisotropy and intensity decay kinetics. In operation, the new instrument can provide a complete frequency-domain data set at 100 modulation frequencies in less than 1 min. The new instrument exhibits 5-10-ps measurement precision and it can rapidly and accurately recover complex excited-state fluorescence anisotropy and intensity decay kinetics under one-, two-, or three-photon excitation for dilute or optically dense samples that exhibit single or multiexponential decay kinetics. This latter aspect of the instrument is demonstrated by successfully determining the excited-state intensity decay kinetics for a dilute aqueous solution of rhodamine 6G dissolved in a high concentration of bromocresol green. This approach is extended by determining the excited-state fluorescence intensity decay kinetics of dilute fluorescein directly in undiluted, whole blood as a function of pH under two-photon excitation conditions. The high-speed capabilities of the new instrument are exploited by performing two-photon excited fluorescence anisotropy decay experiments on the fly for site-selectively labeled bovine serum albumin as it undergoes enzymatic digestion by trypsin.

Anisotropy↗
PubMed1998

Unfolding of acrylodan-labeled human serum albumin probed by steady-state and time-resolved fluorescence methods.

Steady-state and time-resolved fluorescence spectroscopy was used to follow the local and global changes in structure and dynamics during chemical and thermal denaturation of unlabeled human serum albumin (HSA) and HSA with an acrylodan moiety bound to Cys34. Acrylodan fluorescence was monitored to obtain information about unfolding processes in domain I, and the emission of the Trp residue at position 214 was used to examine domain II. In addition, Trp-to-acrylodan resonance energy transfer was examined to probe interdomain spatial relationships during unfolding. Increasing the temperature to less than 50 degrees C or adding less than 1.0 M GdHCl resulted in an initial, reversible separation of domains I and II. Denaturation by heating to 70 degrees C or by adding 2.0 M GdHCl resulted in irreversible unfolding of domain II. Further denaturation of HSA by either method resulted in irreversible unfolding of domain I. These results clearly demonstrate that HSA unfolds by a pathway involving at least three distinct steps. The low detection limits and high information content of dual probe fluorescence should allow this technique to be used to study the unfolding behavior of entrapped or immobilized HSA.

2-Naphthylamine↗
PubMed1998

Quality of life and epilepsy: the Liverpool experience.

The use of quality of life (QOL) measures in epilepsy research is relatively recent compared with that in other chronic conditions such as coronary heart disease and diabetes. However, in recent years much research has been undertaken to develop and validate QOL measures for use in various groups of people with epilepsy, including children, the elderly, and newly diagnosed patients. QOL measures are now available for use in both clinical trials and primary care. The Liverpool Group is one of the leading research teams in this field and is probably best known for developing the Liverpool Seizure Severity Scale. However, the group has also developed a number of other QOL measures, with an emphasis on keeping the measures appropriate, practical, and responsive, and always considering the burden to patients. This review describes some of the measures the Liverpool Group has developed, outlines their application in clinical trials of a number of aspects of antiepileptic drugs, and details the importance of some of the findings. The diversity of the group's approach and of its involvement in assessing the QOL of people with epilepsy are emphasized.

Adult↗
PubMed1998

The relationship between seizure frequency, seizure type and quality of life: findings from three European countries.

Understanding the relationship between seizure frequency, seizure type and scores obtained from quality of life (QOL) measures is important if the incorporation of QOL measures into epilepsy clinical trials is to become standard practice. There is also a need to consider cross-cultural differences obtained from QOL measures, particularly in the context of multicentre international trials. In this study, 300 patients recruited from UK, Germany and France completed the Functional Status Questionnaire (FSQ); information about patients' clinical and demographic status was also collected. Results from the study highlighted that seizure type and seizure frequency, as well as country of origin, were significant predictors of scores on the FSQ. It is important to measure the effect of seizure type, not just seizure frequency, on QOL when testing for differences between antiepileptic therapies in the context of clinical trials.

Cross-Cultural Comparison↗
PubMed1998

Liverpool Seizure Severity Scale revisited.

The purpose of the study was to examine the psychometric properties of the revised Liverpool Seizure Severity Scale. The scale has been adapted to increase its content validity and its potential for detecting change attributable to antiepileptic drug treatment. Ninety-seven patients completed the revised scale of which 32 completed it for both major and minor seizures. Reliability of the revised scale was conducted using assessment of internal consistency and test-retest. T-tests were conducted to assess the ability of patients to differentiate between major and minor seizures on scores of the seizure-severity scale. The psychometric properties of the scale were not adversely affected by either the increase in the number of items or the additional response scores. Patients completing the two scales of major and minor seizures were able to reliably differentiate between the two. We have attempted to improve the Liverpool Seizure Severity Scale in order to enhance its reliability, validity and sensitivity to change. The amendments we have made have not adversely affected its psychometric properties and we hope that it will make it more acceptable for use in clinical trials of new antiepileptic drug treatment. The revised scale is currently being applied to a number of clinical trials.

Adolescent↗
PubMed1998

Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards.

PURPOSE: To systematically review the methodology and use of neuropsychological tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: Trial reports were found by searching Medline 1966-1996 and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and neuropsychological test data was extracted by using a proforma. RESULTS: 43 reports met our inclusion criteria, representing 40 RCTs. as three RCTs had generated two reports. Twenty-two were actively controlled, and 18 were placebo-controlled studies. Reporting of basic methods such as randomization method was poor. There has been no uniform approach to the use of neuropsychological tests, and a total of 87 has been used. The Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at 13 times each, but were not used or reported in a uniform manner. CONCLUSIONS: Poor reporting of methods and the use of a plethora of neuropsychological tests create great difficulties for anyone wishing to make sense of currently available data. If we are better to understand the neuropsychological effects of AEDs, a more rational approach is needed, for which recommendations are made.

Adult↗
PubMed1998

Simulating a memory impairment: can amnesics implicitly outperform simulators?

OBJECTIVES: The purpose of this study was to examine the effectiveness of a variety of tests in differentiating simulating test performances from genuine memory-impaired and normal (control) test performances. DESIGN: A simulation design was implemented, based on an analogue design in which normal participants were given experimental instructions to feign a mental impairment and are compared to (a) other normal participants with instructions to perform honestly, and (b) a comparison group, for example, acquired brain-injured persons, with similar instructions. METHOD: Forty individuals comprised the simulating and control group and all participants were randomly assigned to the simulating and control groups. Twenty memory-impaired patients, all of whom had been diagnosed as suffering from a memory impairment following acquired brain damage, participated as the memory-impaired control group. The simulation group was directed to imitate a person with a memory impairment. The primary outcome measure involved identifying those tests, if any, where simulators were significantly different from normal and memory-impaired participants. RESULTS: On 5 of the 15 tasks administered, simulators performed significantly differently from normal and memory-impaired participants. Of these 5 tasks, the coin-in-the-hand, when administered in conjunction with the autobiographical interview, identified 95 per cent of the simulators without misclassifying any of the memory-impaired or normal participants. CONCLUSION: It is suggested that these two tests, when administered jointly, might be of use in clinical settings to assist in the detection of malingerers.

Adult↗
PubMed1997

The Neurotoxicity Scale--II. Results of a patient-based scale assessing neurotoxicity in patients with epilepsy.

The Neurotoxicity Scale was devised as a patient-based report scale to assess the adverse effects of antiepileptic drugs on cognitive function. In a previous report we reported the clinical validity of the scale, tested in a double-blind randomized study, using a benzodiazepine in normal volunteers. In the present study, the clinical sensitivity, construct validity and reliability of the scale was tested in patients with epilepsy. Patients (n = 189), selected from both participating centres, representative for the patients with chronic epilepsy were included in the study. Reliability was tested with Cronbachs alpha and yields an almost maximal score (.95). Clinical sensitivity was compared with the previous normal volunteer study and was evaluated as satisfactory. Construct validity showed a five-factor structure, explaining 66.5% of the variance, with 'fatigue and slowing' as the dominant factor. In line with the assumptions for this scale and with the results obtained in normal volunteers, the scale appears to be unsuitable for differential assessment of type or severity of drug-induced impairment. The most valid primary outcome measure is the overall score that renders a global ('all or nothing') evaluation indicating that a subject experiences cognitive impairment and associates this with the antiepileptic treatment. Other factors that may impair cognitive function, such as seizure frequency do not influence this score. The scale has therefore maximal applicability as a screening instrument in outpatient practice and in early (phase II, IIIa) drug trials.

Adult↗
PubMed1997

Non-epileptic attack disorder: a psychological perspective.

Due to the serious medical consequences in failing to recognize non-epileptic attack disorder (NEAD), and the frequency with which neurologists come into contact with such patients, clearly NEAD constitutes a major concern for clinicians in the field of epilepsy. This article presents the psychological characteristics of 185 patients with NEAD. Psychological factors that were identified as being important in the understanding of the development and maintenance of NEAD included: anxiety or stress; physical abuse; significant bereavement; family dysfunctioning; relationship problems; depression; sexual abuse. An absence of relevant psychological factors was found in only 5% of patients. From patients' descriptions of their attacks, it appears that many symptoms are related to anxiety. Our findings are largely supported by previous studies and their relevance to effective management and treatment of NEAD patients is discussed.

Adolescent↗
PubMed1997

Factors influencing compliance with antiepileptic drug regimes.

Failure to comply with drug regimes is prevalent amongst patients with epilepsy and the consequence of this is often an increased risk of further seizures. This paper describes the level of, and influences upon, non-compliance with antiepileptic drug (AED) treatment. A postal questionnaire was sent to an unselected, community-based population of patients with epilepsy. This instrument included questions about patients' AED treatment, any related side-effects, and AED-taking behaviour. Univariate analysis showed that factors associated with compliance were patient age, how important patients felt it was to take drugs as prescribed, whether patients reported feelings of stigma, whether on mono- or polytherapy, whether they were experiencing any side-effects because of AEDs, whether patients had a regular arrangement to see their GP about epilepsy and how easy they found their GP to talk to. Multivariate analysis showed that the strongest predictors of non-compliance were feeling it was not very or not at all important to take AEDs as prescribed, being a teenager, being aged under 60 and being on monotherapy. Further implementation of educational programmes for people with epilepsy would help to improve levels of compliance thereby reducing the risk of unnecessary seizures.

Adaptation, Psychological↗
PubMed1997

Psychometric properties and factor structure of the Wechsler Memory Scale-Revised in a sample of persons with intractable epilepsy.

The Wechsler Memory Scale-Revised (WMS-R) is used routinely as a presurgical assessment of memory for clients considering elective resection of the temporal lobe and/or hippocampus for the relief of intractable temporal lobe epilepsy. This research investigated the psychometric properties of the WMS-R in a population of people with epilepsy. The sample consisted of 181 patients with a diagnosis of epilepsy who underwent a complete neuropsychological examination as a routine part of their investigation. The results confirm that the WMS-R has acceptable levels of reliability as measured by internal consistency. A factor analysis revealed a consistent three-factor structure: Visual Memory, Verbal Memory, and Attention/ Concentration factors. Multiple regression analysis, however, indicated that the Visual Memory index was susceptible to a number of influences, throwing into question whether it is a pure measure of nonverbal memory functioning.

Adolescent↗
PubMed1997

Quality of life of people with epilepsy: a European study.

PURPOSE: To study the impact of epilepsy and its treatment on people with epilepsy in Europe. We therefore aimed to collect data from as many countries as possible. METHODS: Clinical and demographic details and information about psychosocial functioning was collected using self-completed questionnaires mailed to members of epilepsy support groups. RESULTS: Quality of life data was collected from >5,000 patients living in 15 countries in Europe. Over a third of all respondents had frequent seizures, and a fifth believed that their seizures were not well enough controlled by antiepileptic medication. Reported levels of side effects from medication were high. A significant number of respondents reported changing their medication because of side effects or poor control. Respondents reported that epilepsy and its treatment had a significant impact on a number of different aspects of their daily lives. Half of all respondents felt stigmatised by their epilepsy. There were significant differences by seizure type and frequency in the way respondents scored on measures of the perceived impact of their condition, the stigma associated with it and their health status as measured by a generic scale, the SF36. CONCLUSIONS: This study confirms the findings of previous smaller-scale studies that reducing side effects and achieving better control of seizures are key to improving the quality of life of people with epilepsy, as is reducing the stigma and handicap associated with it.

Age of Onset↗
PubMed1997

Patients' experiences of injury as a result of epilepsy.

PURPOSE: The increased risk of mortality among people with epilepsy is well documented; people with epilepsy are more likely than the general population to die as a result of an accident. Data about incidence of nonfatal accidents and associated factors are not so readily available, even though such accidents are more common than fatal injuries. We report the proportion of people who sustain various injuries during a seizure and the key variables predicting injury. METHODS: Questionnaires were mailed to an unselected, community-based population of patients with epilepsy. The questionnaire included clinical and demographic details, previously validated scales of psychosocial well-being, and questions about seizure-related injuries. RESULTS: Of patients who had had at least one seizure during the previous year, 24% sustained at least one head injury, 16% sustained a burn or scald, 10% a dental injury, and 6% some other fracture. Seizure type, seizure severity, and seizure frequency were key predictors of having sustained at least one of these four seizure-related injuries. Key predictors of burn/scald were seizure severity, seizure frequency and sex; those of head injury were seizure severity and type; that of dental injury was seizure severity; and those of some other fracture were seizure severity, duration of epilepsy, and three or more drug-related adverse effects. CONCLUSIONS: These data help identify significant risk factors associated with seizure-related injuries and so facilitate sensible patient counseling about how the risks of such injuries can be minimized.

Accidents↗
PubMed1997

Current issues in the management of epilepsy: the impact of frequent seizures on cost of illness, quality of life, and mortality.

Cost of illness, quality of life (QOL), and sudden unexpected death in epilepsy are disease-related issues that have become increasingly prominent. Because new treatments for epilepsy are now becoming widely available, it is useful to attempt to determine the clinical factors most closely correlated with high disease management costs, excess mortality, and reduced QOL as a basis for considering whether new antiepileptic drugs (AEDs) or AED regimens may favorably influence these aspects of the chronic condition. Findings of recent studies in these diverse areas of epilepsy research indicate that a common clinical factor, seizure frequency, is closely associated with poorer outcomes with respect to cost of illness, QOL, and mortality. To the extent that newer AEDs can provide clinically significant reductions in seizure frequency among patients currently not optimally controlled with AEDs, a meaningful incremental benefit in each of these areas is a reasonable hypothesis. Prospective studies to assess the impact of better seizure control on these important outcomes are warranted.

Adolescent↗
PubMed1997

Quality of life after epilepsy surgery.

OBJECTIVE: To assess the relation between seizure status and quality of life after surgery for drug resistant epilepsy, using a previously validated quality of life model developed for use in epilepsy. METHODS: A retrospective postal survey was made on 94 patients who underwent surgery for epilepsy between 1986 and 1994, and 36 patients who after investigation during the same period were found to be unsuitable for surgery. A health related quality of life model was used containing validated measures of anxiety, depression, self esteem, mastery, impact of epilepsy, affect balance, stigma, overall health status, and overall quality of life, to examine the relation between postoperative seizure status and quality of life. RESULTS: Overall 47.9% of patients were seizure free after surgery. On all measures seizure free patients scored significantly better than either patients deemed unsuitable for surgery or those having more than 10 seizures per year after surgery. Patients having less than 10 seizures per year obtained intermediate scores. There was no difference between the groups unsuitable for surgery or having more than 10 seizures per year postoperatively. Employment rates were significantly different between groups, 80% of seizure free and 53% of patients having less than 10 seizures per year in gainful employment postoperatively, compared with 28% and 27% of patients having greater than 10 seizures per year or those who were unsuitable for surgery. CONCLUSIONS: Within broad categories, postoperative quality of life is clearly related to seizure outcome, but the study emphasises the importance of long term follow up in defining the tangible psychosocial effects of freedom from seizures.

Amygdala↗
PubMed1997

Behavioral and cognitive effects of lamotrigine.

Lamotrigine is a new antiepileptic drug that may possess unique cognitive and behavioral characteristics. Although lamotrigine can produce neurobehavioral toxicity, it is generally well tolerated. In one study directly comparing lamotrigine to placebo as add-on therapy in patients with intractable epilepsy, no objective cognitive effects were observed in a limited neuropsychological battery. Several studies have demonstrated favorable effects of lamotrigine on psychological well-being that were not explained by simple effects on seizure frequency and severity. In direct comparisons with carbamazepine and phenytoin, lamotrigine has been reported to produce positive effects on quality of life scales of patient perception. In addition, positive behavioral effects have also been observed in two blinded studies and several open trials for patients with severe mental disability and refractory epilepsy. Future studies with more extensive neuropsychological assessments are needed to delineate the differential cognitive and behavioral effects of lamotrigine in epilepsy and psychiatric disorders.

Adult↗
PubMed1996

The associations of psychopathology in epilepsy: a community study.

There is a plethora of studies documenting the association between psychosocial disadvantage and epilepsy but a paucity of studies explaining the precise nature of that relationship. Previous studies have been hampered by methodological problems including small sample size and selection bias. This study examined the aetiology of psychopathology in epilepsy in a cross-sectional community study. A significant proportion of patients were anxious and depressed and many reported side effects of their medication. Stepwise multiple regression techniques were employed to examine the relationship between clinical, demographic and psychosocial variables. Results indicated that psychosocial variables were the best predictors of each other but when these were taken into account, patient perceived seizure severity was an important predictor variable in understanding the relationship between epilepsy and psychosocial functioning.

Adult↗