Improving the post-transcriptional aspects of lentiviral vectors.
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Animals↗
Biomedical subjects
T Hope
Publications and source records attributed to T Hope.
Psychiatric, demographic and personality characteristics of elderly sex offenders.
BACKGROUND: Psychiatric disorders are purported to play a role in the aetiology of violent crime, but evidence for their role in sexual offending is less clear. The authors investigated the prevalence of psychiatric morbidity and personality disorders in elderly incarcerated sex offenders compared with elderly non-sex offenders. METHOD: One hundred and one sex offenders and 102 non-sex offenders aged over 59 years wereinterviewed using standardized semi-structured interviews for psychiatric illness (the Geriatric Mental State) and the personality disorder (Structured Clinical Interview for DSM-IV personality disorders). Data on demographic, offence and victim characteristics were collected. RESULTS: Six per cent of the elderly sex offenders had a psychotic illness, 7% a DSM-IV major depressive episode and 33% a personality disorder; and 1% had dementia. These prevalence figures were not different from the elderly non-sex offenders interviewed in this study. Differences emerged at the level of personality traits with sex offenders having more schizoid, obsessive-compulsive, and avoidant traits, and fewer antisocial traits compared with non-sex offenders. CONCLUSIONS: Elderly sex offenders and non-sex-offenders have similar prevalence rates of mental illness. However, elderly sex offenders have increased schizoid, obsessive-compulsive, and avoidant personality traits, supporting the view that sex offending in the elderly is associated more with personality factors than mental illness or organic brain disease.
Aged↗
Assessment of dynamic cerebral autoregulation based on spontaneous fluctuations in arterial blood pressure and intracranial pressure.
Assessments of dynamic cerebral autoregulation usually measure the cerebral blood flow velocity (CBFV) response to changes in arterial blood pressure (ABP). We studied the effect of substituting ABP by cerebral perfusion pressure (CPP), expressed as the difference between ABP and intracranial pressure (ICP), in estimates of dynamic autoregulation obtained by transfer function analysis. CBFV, ABP and ICP were recorded during periods of physiological stability in 30 patients with severe head injury. Transfer function analysis was performed using the following combinations of input-output variables: ABP-CBFV, CPP-CBFV and CBFV-ICP. Frequency and time-domain (step response) functions were averaged for recordings with mean ICP < 20 mmHg (group A) and mean ICP > or = 20 mmHg (group B). The ABP-CBFV transfer function parameters and step response for group A were similar to previous studies in normal subjects, but group B showed deterioration of dynamic autoregulation. Radically different step responses were obtained from both groups for the CPP-CBFV transfer function and the coherence was not significantly improved. The CBFV-ICP transfer function had the highest values of coherence and indicates that changes in CBFV are the cause of spontaneous fluctuations in ICP. Furthermore, the ICP step response plateau was significantly higher for group B than for group A. An alternative calculation of the CBFV step response to changes in CPP resembled the corresponding responses for the ABP input. For spontaneous fluctuations in ABP, ICP and CBFV, it is not possible to calculate the CPP-CBFV transfer function directly due to the high positive correlation between ICP and CBFV, but an alternative estimate can be obtained by using the CBFV-ICP transfer function. The latter could also be useful as a method to assess intracranial compliance in head injury patients.
Adult↗
Estimating the relationship between disease progression and cost of care in dementia.
BACKGROUND: Previous studies have shown a positive relationship between disease severity and cost. AIMS: To explore the factors affecting time to institutionalisation and estimate the relationship between the costs of care and disease progression. METHOD: Retrospective analysis of a longitudinal data-set for a cohort of 100 patients diagnosed with Alzheimer's disease or vascular dementia. RESULTS: Changes in both Mini-Mental State Examination (MMSE) and Barthel scores have independent and significant marginal effects on costs. Each one-point decline in the MMSE score is associated with a pound sterling 56 increase in the four-monthly costs, whereas each one-point fall in the Barthel index is associated with a pound sterling 586 increase in costs. CONCLUSIONS: It may be inappropriate for economic models of disease progression in dementia to be based solely on measures of cognitive change. MMSE and the Barthel index are independent significant predictors of time to institutionalisation and cost of care, but changes in the Barthel index are particularly important in predicting costs outside institutional care.
Age Factors↗
Psychosis of Alzheimer's disease is associated with elevated muscarinic M2 binding in the cortex.
OBJECTIVES: Results from recent drug trials suggest a role for the cholinergic system in the manifestation of neuropsychiatric symptoms in AD. To date, the status of muscarinic acetylcholine receptor subtypes in AD in relation to accompanying behavioral disturbances is unknown. This study aimed to measure alterations of muscarinic M(1) and M(2) receptor binding in the frontal and temporal cortex of AD and to correlate the neurochemical findings with clinical features. METHODS: The cognitive and behavioral features of 26 patients with AD were assessed prospectively using standardized tests. Together with 14 matched controls, the status of muscarinic M(1) and M(2) receptors in the postmortem frontal and temporal cortex of these patients were measured by radioligand binding assays and were correlated with clinical data. RESULTS: Compared with controls, M(2) receptor density was reduced only in the frontal cortex of AD, whereas M(1) was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M(2) receptor density was increased in the frontal and temporal cortex of patients with AD with psychotic symptoms compared with those without these symptoms. CONCLUSIONS: This study suggests a role for M(2) receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M(2) antagonists.
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Psychiatric disorder and personality factors associated with suicide in older people: a descriptive and case-control study.
OBJECTIVE: To determine the rates of psychiatric disorder and personality variables in a sample of older people who had committed suicide and to compare the rates in a subgroup of this sample with those in a control group of people who died from natural causes. DESIGN: Descriptive psychological autopsy study, including interviews with informants, of psychiatric and personality factors in 100 suicides in older people. Case-control study using subgroup of 54 cases and matched control group. SETTING: Four counties and one large urban area in central England, UK. SUBJECTS: Individuals 60 years old and over at the time of death who had died between 1 January 1995 and 1 May 1998, and whose deaths had received a coroner's verdict of suicide (or an open or accidental verdict, where the circumstances of death indicated probable suicide). The control group was an age-and sex-matched sample of people dying through natural causes in the same time period. MAIN OUTCOME MEASURES: ICD-10 psychiatric disorder, personality disorder and trait accentuation. MAIN RESULTS: Seventy-seven per cent of the suicide sample had a psychiatric disorder at the time of death, most often depression (63%). Personality disorder or personality trait accentuation was present in 44%, with anankastic or anxious traits the most frequent. Depression, personality disorder, and personality trait accentuation emerged as predictors of suicide in the case-control analysis. CONCLUSION: Personality factors, as well as depression, are important risk factors for suicide in older people.
Aged↗
Death and dementia.
OBJECTIVE: To investigate the last phase of dementia and the causes of death; comparing autopsy and death certificate diagnoses. DESIGN: Prospective, 11-year, longitudinal study of behavioural and psychological changes in dementia, with autopsy follow-up. SETTING: Participants with dementia, living at home with a carer. All lived in Oxfordshire, UK. PARTICIPANTS: Ninety-one people with dementia (Alzheimer's disease and/or vascular dementia) who died during the course of the study. MEASURES: At four-monthly intervals, carers were interviewed about the participants' behaviour using the Present Behavioural Examination. Participants were also assessed cognitively. Causes of death were established from death certificates and, where possible, from post-mortem examination. RESULTS: The main immediate cause of death recorded at autopsy was pneumonia (57%), followed by cardiovascular disease (16%) and pulmonary embolus (14%). This agreed with the immediate cause of death on 53% of death certificates. Pulmonary embolism and bronchopneumonia were under-reported on death certificates. Dementia was mentioned on 73% of death certificates. The dementing illness lasted for a mean of 8.5 years with 58% dying in a debilitated state associated with severe dementia. In the period before death, 35% were unable to walk, 58% were hypophagic, 73% were incontinent of urine, 21% incontinent of faeces and 76% entered an institution permanently for a mean period of 18 months. CONCLUSION: Family and professional carers of people with dementia can be given some information about prognosis to help them plan for the likely outcome of dementia.
Aged↗
Wandering in dementia: a longitudinal study.
OBJECTIVE: This article analyzes the natural history of wandering behavior throughout the course of dementia. DESIGN: Prospective, 10-year, longitudinal study of wandering behavior in dementia, with autopsy follow-up. SETTING: Participants with dementia, living at home with a carer. All lived in Oxfordshire, UK. PARTICIPANTS: Eighty-six people with dementia who were living at home with a carer and who were able to walk unaided at entry to study. MEASURES: At 4-monthly intervals, the carers were interviewed using the Present Behavioural Examination to assess wandering behavior in detail; participants with dementia were assessed cognitively. Nine types of "wandering" behavior were distinguished. RESULTS: Changes in wandering behavior were not generally related to gender, age, or time since onset of dementia. Onset of different types of wandering behavior showed some relationship with cognitive state. Various forms of increased walking first appeared during moderate dementia, each type typically persisting for 1 to 2 years. Late dementia was characterized by decreased walking and immobility. CONCLUSIONS: Wandering behavior in dementia can cause great problems for carers. There are different causes for such changes, some of which are related to cognitive ability, for example increased confusion results in ineffectual "pottering" and getting lost. Increased walking at night corresponds with disruption of diurnal rhythm.
Activity Cycles↗
Health of elderly male prisoners: worse than the general population, worse than younger prisoners.
BACKGROUND: Assessment of the health of men aged 60 and over in English and Welsh prisons. METHODS: 203 men were interviewed from 15 prisons, comprising one-fifth of all sentenced men in this age group in England and Wales. Assessment included semi-structured interviews covering chronic and acute health problems, and recording of major illnesses from the medical notes and prison reception health screen. RESULTS: 85% of the elderly prisoners had one or more major illnesses reported in their medical records, and 83% reported at least one chronic illness on interview. The most common illnesses were psychiatric, cardiovascular, musculoskeletal and respiratory. CONCLUSION: The rates of illness in elderly prisoners are higher than those reported in other studies of younger prisoners and surveys of the general population of a similar age. The increasing number of elderly people in prison poses specific health challenges for prison health-care services.
Adult↗
Synaptic pathology in prefrontal cortex is present only with severe dementia in Alzheimer disease.
Synaptic pathology is proposed to be integral to the clinical expression of Alzheimer disease (AD). Most studies have assessed only the vesicle protein synaptophysin as a measure of synaptic integrity. The interrelationships of synaptophysin, other presynaptic proteins, the cholinergic system, and severity of dementia in AD remain unclear. We studied the presynaptic proteins synaptophysin, syntaxin and SNAP-25, along with choline acetyltransferase (ChAT) activity in prefrontal cortex (BA 46) samples from 18 subjects with AD and 16 controls. Mean values of presynaptic protein immunoreactivities were significantly reduced, by 21%-28%, and ChAT activity was reduced by 41% in the AD groups. Synaptic protein immunoreactivity and ChAT activity were correlated with Mini-Mental State Examination scores obtained 1 yr prior to death. When AD cases were subgrouped into mild/moderate and severe illness at time of death, all differences in presynaptic proteins and ChAT activity were significant between controls and severe cases. However, no significant differences were detected in BA 46 between controls and mild/moderate cases. Considerable synaptic reserve or plasticity remains in BA 46 until the late stages of AD. Synaptophysin and ChAT appear to be more vulnerable in severe AD than are syntaxin or SNAP-25.
Aged↗
The pharmacokinetics of epidural ropivacaine in infants and young children.
UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.
Algorithms↗
Simultaneous measurement of plasma ropivacaine and bupivacaine concentrations by HPLC with UV detection.
The authors developed a high-performance liquid chromatography (HPLC) assay for the simultaneous determination of plasma ropivacaine and bupivacaine concentrations using ultraviolet (UV) detection and a simple solid-phase extraction procedure. The absolute retention times of ropivacaine, bupivacaine, and the internal standard pentycaine were 1.9, 3.0, and 5.6 minutes, respectively. The assay had a linearity of 2000 ng/mL, a sensitivity of 5 ng/mL, an average recovery of 98%, and an average day-to-day imprecision of <10% for both drugs. A patient correlation study (n = 23) using this HPLC method and an established gas chromatographic assay revealed a slope of 1.01, an intercept of -10.6 ng/mL, and a correlation coefficient of 0.99 for ropivacaine; and a slope of 0.96, an intercept of 14.7 ng/mL, and a correlation coefficient of 0.99 for bupivacaine. Of the 60 different drugs tested, only quinidine and lidocaine extracted but did not interfere with the measurement of the drugs of interest. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of plasma ropivacaine and bupivacaine concentrations.
Amides↗
Rationing and life-saving treatments: should identifiable patients have higher priority?
Health care systems across the world are unable to afford the best treatment for all patients in all situations. Choices have to be made. One key ethical issue that arises for health authorities is whether the principle of the "rule of rescue" should be adopted or rejected. According to this principle more funding should be available in order to save lives of identifiable, compared with unidentifiable, individuals. Six reasons for giving such priority to identifiable individuals are considered. All are rejected. It is concluded that the principle of the rule of rescue should not be used in determining the allocation of health resources.
Decision Making↗
Clinical ethics committees: a worldwide development.
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Ethics Committees, Clinical↗
Clinical ethics support services in the UK: an investigation of the current provision of ethics support to health professionals in the UK.
OBJECTIVE: To identify and describe the current state of clinical ethics support services in the UK. DESIGN: A series of questionnaire surveys of key individuals in National Health Service (NHS) trusts, health authorities, health boards, local research ethics committees and health professional organisations. Interviews with chairmen/women of clinical ethics committees identified in the surveys. SETTING: The UK National Health Service. RESULTS: Responses to the questionnaires were received from all but one NHS trust and all but one health authority/board. A variety of models of clinical ethics support were identified including twenty formal clinical ethics committees (CECs). A further twenty NHS trusts expressed an intention to establish a CEC within the next twelve months. Most CECs in the UK have been in existence less than five years and are still defining their role. The chairmen identified education of committee members and contact with other ethics committees as important requirements for committee development. Problems were identified around lack of support for the committee and with raising the profile of the committee within the institution. There has been little evaluation of clinical ethics support services either in the UK or in other countries with longer established services. What evaluation has occurred has focused on process rather than outcome measures. CONCLUSIONS: Clinical ethics support services are developing in the UK. A number of issues have been identified that need to be addressed if such support services are to develop effectively.
Attitude of Health Personnel↗
Hidden psychiatric morbidity in elderly prisoners.
BACKGROUND: The number of elderly prisoners has increased significantly in Western countries over the past decade. Little is known about the psychiatric morbidity of this population. AIMS: To determine the prevalence of psychiatric morbidity in elderly sentenced prisoners. METHOD: A stratified sample of 203 male sentenced prisoners aged over 59 years, from 15 prisons in England and Wales, representing one in five men in this age group, was interviewed using semistructured standardised instruments for psychiatric illness and personality disorder. RESULTS: More than half of the elderly prisoners had a psychiatric diagnosis. The most common diagnoses were personality disorder and depressive illness. CONCLUSIONS: The prevalence of depressive illness was five times greater than that found in other studies of younger adult prisoners and elderly people in the community. Underdetected, undertreated depressive illness in elderly prisoners is an increasing public health problem.
Aged↗
Cholinergic deficits contribute to behavioral disturbance in patients with dementia.
BACKGROUND: Noncognitive behavioral changes such as depression, aggressive behavior, psychosis, and overactivity occur frequently in patients with dementia, in addition to cognitive impairment, and often determine the need for institutionalization. The biochemical basis of such changes is poorly understood. Clinical trial data indicate that cholinomimetics improve noncognitive behaviors. This study investigated the relationship between markers of the cholinergic and dopaminergic neurotransmitter systems and noncognitive behavioral symptoms assessed during the course of dementing illness. METHOD: Brains from 46 patients with dementia (36 with AD and 10 with mixed or other dementias using Consortium to Establish a Registry for AD criteria) were examined together with 32 normal controls. The patients with dementia had been evaluated every 4 months, often over several years, for cognitive performance (Mini-Mental State Examination) and behavior (Present Behavioral Examination). Concentrations of dopamine (DA) and major metabolites, choline acetyltransferase activity (ChAT), and density (Bmax) of DA D1 receptors in frontal and temporal cortex were studied by radioligand binding protocols. None of the patients was receiving cholinomimetic drugs. RESULTS: ChAT activity, but no other neurochemical markers, was reduced in AD compared with controls. Loss of ChAT activity correlated with cognitive impairment. Lowered ChAT activity also correlated with increasing overactivity in patients with dementia in both frontal and temporal cortex whereas ChAT:DA and ChAT:D1 ratios in temporal cortex correlated negatively with aggressive behavior. CONCLUSIONS: Disturbance of the cholinergic system may underlie both cognitive and some noncognitive behavioral changes in dementia, providing a basis for rational therapy.-1467
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Clinical ethics committees.
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Ethics Committees↗