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E Chiu

Publications and source records attributed to E Chiu.

At least 19 recordsLinked to original sources

Differential clinical and motor control function in a pair of monozygotic twins with Huntington's disease.

We report a pair of monozygotic Huntington's disease (HD) twins who, although sharing identical CAG repeat lengths, not only present with marked differences in clinical symptoms but also behavioral abilities as measured by our experimental procedures. Both HD twins and two healthy control subjects were tested twice over 2 years. Patient A was generally more impaired at a motor level, whereas Patient B showed greater attentional impairment; Patient B, however, showed more progressive deterioration. The control subjects' performance remained consistent over the 2-year interval. Patient A clinically had the more hyperkinetic hypotonic variant of the disease, whereas Patient B, who was the more impaired, presented with a more hypokinetic hypertonic (rigid) variant. The influences of epigenetic pre- and postnatal environmental factors should not be ignored.

Adult

Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study.

OBJECTIVE: To determine the difference in outcome among elderly people with major depression who do and do not have severe white matter lesions on magnetic resonance imaging. DESIGN: Follow up study. SETTING: Two psychiatric and two general hospitals in Melbourne, Australia. SUBJECTS: 60 depressed subjects aged over 55 referred to hospital psychiatric services with major depressive disorder meeting American Psychiatric Association (DSM-IIIR) criteria. MAIN OUTCOME MEASURE: Proportion with good outcome as determined by full recovery from initial illness and no evidence of depressive relapse or cognitive decline during follow up among those with and without lesions. RESULTS: Mean (SD) follow up was 31.9 (9.9) months. Survival analysis showed a significant effect of severe lesions on time to poor outcome (P=0.04), with median survival 136 days in those with severe lesions compared with 315 days in those without. CONCLUSION: Severe white matter change on magnetic resonance imaging is associated with poor outcome in elderly depressed subjects.

Aged

A study of the quality of life of the severely mentally ill.

As part of a larger study, the Lehman Quality of Life Interview (QOLI) was conducted a total of 85 times with 55 clients with serious mental illness. Results revealed widespread adverse objective circumstances (unemployment, poverty and social isolation) despite which most clients rated their satisfaction levels about average (about equally satisfied and dissatisfied). As expected, subjective quality of life indicators were generally better predictors of global well-being (GWB) (itself based on subjective ratings) than were objective indicators. Correlations between objective and subjective indicators were very low and insignificant. Moderate relationships were found between GWB and levels of personal functioning, and changes in levels of personal functioning, as rated by mental health workers. Retests showed that subjective quality of life was relatively stable over intervals of several months. The findings suggest that leisure and social relations would be suitable areas for interventions that might improve clients' quality of life.

Adaptation, Psychological

Is good clinical research practice for clinical trials good clinical practice?

This article presents results of monitoring of the recruitment process for a phase III study of a new antidepressant drug in elderly patients with depressive disorders, focusing on the peculiarities of recruitment posed by the presence of comorbidity and coadministration of medications. Data are derived from screening of 188 patients, the majority of whom lived at home, referred for trial inclusion. One hundred and seventy-one (91%) had Hamilton Rating Scale score in excess of 18 and met inclusion criteria. Only eight (4.2%) elderly depressed subjects could be recruited, after application of exclusion criteria. The trial data so obtained may be scientifically credible, but the conclusions reached by trials with very stringent exclusion criteria do not reflect the practice environment in which the product will be prescribed by clinicians. This raises questions of the relevance of good clinical research practice and good clinical practice guidelines to the reality of good clinical practice beyond the trial situation.

Aged

The relationship between two scales measuring aggressive behaviour among elderly nursing home residents.

Data from a large 6-month prospective study of aggressive behaviour in 11 nursing homes for the elderly are used to examine the relationship between two aggression scales (SOAS and RAGE). There was a strong and significant correlation between the SOAS and RAGE scales for the total and the subscale scores. Both these scales appear useful in measuring aggressive behaviour in nursing homes for the elderly and the nursing home staff can be trained in completing them effectively.

Aged

Impairments of movement kinematics in patients with Huntington's disease: a comparison with and without a concurrent task.

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movements profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially, with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand is its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Adrenergic Uptake Inhibitors

Temporal lobe magnetic resonance imaging can differentiate Alzheimer's disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment.

BACKGROUND: Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined. METHODS: We studied 222 subjects using T1 weighted MRI with 5.1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N = 40); DSM-III-R major depression (N = 61); NINCDS/ADRDA DAT (N = 77) and OTHER (N = 44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of 'memory complainers'). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0-3 scale by two experienced neuroradiologists blind to clinical diagnosis. RESULTS: Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history. CONCLUSIONS: Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

Age Factors

Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma.

Primary nasal T or NK cell lymphoma is rarely seen in the Western population but is more common in the Orientals. Although it often presents with localized disease, the prognosis is generally poor. Long-term remission is seen in only 50% of patients with stage I disease despite aggressive treatment with chemotherapy and radiotherapy, and is invariably fatal if disseminated. Conventional chemotherapy for relapsed disease is usually not successful. Since 1992, three patients with relapsed primary nasal T/NK cell lymphoma have received high-dose chemotherapy with autologous bone marrow rescue at Queen Mary Hospital, Hong Kong. High-dose cyclophosphamide, BCNU and etoposide were used for conditioning. Two of them had a favourable response and remained in complete remission at 12 and 44 months post-transplant. The third patient unfortunately had a systemic relapse 6 months after the transplant. It appears from this experience that, like other aggressive non-Hodgkin's lymphomas, high-dose chemotherapy and autologous bone marrow rescue is an effective treatment for relapsed primary nasal lymphoma following failure of conventional chemotherapy and radiotherapy.

Adult

Effect of directed attention in Huntington's disease.

This experiment sought to ascertain whether overt gaze (i.e., directed attention) would influence attentional performance in Huntington's disease (HD), via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Subjects looked (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Patients with HD showed performance advantages when directing attention (i.e., gaze) at the responding hand, especially for expected events. Patients with HD, however, were not sensitive to distributions of event probability in the uncrossed arm posture, nor when looking away from the responding hand. With the crossed arm posture, and when directing attention at the expected side, patients with HD became more sensitive to distributions of event probability. In HD, there may be a disruption of fronto-striatal circuitry on both cortical and subcortical levels which may account for impairments both in holding and shifting attention.

Adult

The assessment of clinically significant change using the Life Skills Profile.

OBJECTIVE: In the context of the need to develop practical outcome measures, the present study aimed to assess the sensitivity of the Life Skills Profile (LSP) in terms of differences between hospital-based and community-based clients, and to assess the sensitivity of the LSP to changes over time. In this way, criteria could be established whereby the LSP could be used to determine appropriate changes in locus of care, both in terms of the "cut-off' for hospital-based and community-based tenure, and the level of "clinically significant change' in functioning. METHOD: The LSP was administered at 3-monthly intervals to 200 clients of an area public mental health service with serious mental illness over a 21-month period. Locus of care (hospital or community) was noted at each administration. RESULTS: Clients in the community scored significantly better than those in hospital, however there was a great deal of overlap. Using hospital or community tenure as the variable of interest, a measure of reliable and clinically significant change over a 3-month period based on the LSP was developed. A total LSP score of 116.5 or above best discriminated clients in the community from those in hospital, and a difference of 18 points or more in two LSP obtained 3 months apart was unlikely to have arisen by chance. A simple, two-part criterion of significant change based on these results showed 89% accuracy in matching transition (or lack of transition) between hospital and community with changes in LSP scores. CONCLUSIONS: The results need to be understood within the methodological limitations of the present study. The findings provide users of the LSP with guidelines for the interpretation of repeat assessments. This may encourage more services to use formal reassessment methods to monitor the progress of their clients.

Humans

Magnetic resonance imaging of trabecular bone structure in the distal radius: relationship with X-ray tomographic microscopy and biomechanics.

The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 microns isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156 x 156 x 300 microns). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (approximately 3 times), trabecular width (approximately 3 times), fractal dimension (approximately 1.4 times) and first Betti number/ volume (approximately 10 times), and an underestimation of trabecular spacing (approximately 1.6 times) in the MR images compared with the 18-microns XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.

Absorptiometry, Photon

The effect of Huntington's disease and Gilles de la Tourette's syndrome on the ability to hold and shift attention.

Huntington's disease (HD) and Tourette's syndrome (TS) are two basal ganglia (BG) disorders, associated not simply with hyperkinetic movements but also with attentional impairments. The purpose of this experiment was to evaluate the attention deficits reported in HD and TS via the use of a vibrotactile choice reaction time (CRT) procedure involving biased probabilities of event occurrence. We attempted to ascertain whether HD and TS patients are impaired in their ability to shift their attention to an unexpected location, or when they have to hold attention to an expected location. The results demonstrate that HD patients, as compared to controls, experience difficulties in shifting their attention from expected to unexpected spatial locations; this effect was exacerbated with the adoption of a crossed arm configuration. On the other hand, TS patients' performance, although slower overall, was not qualitatively greatly different from that of the controls. We had previously found, with a similar paradigm, that Parkinson's disease patients instead manifest problems in holding or maintaining attention to an expected locus. We conclude that HD patients experience considerable difficulties in allocating attentional resources between expected and unexpected event occurrences. Perhaps due to pervasive subcortical damage and dysfunction in the circuits linking the frontal lobes with the BG. In TS, a similar if milder functional rather than structural deficit may be reflected in a pattern of responses which resembles a weaker version of the HD response pattern.

Adult

Bradykinesia and movement precision in Huntington's disease.

To determine whether bradykinesia in patients with Huntington's disease (HD) reflects impaired force production or an increased requirement for terminal visual guidance, 11 HD patients and matched controls performed drawing movements with varying precision requirements. Participants used an electronic pen upon a WACOM SD420 graphics tablet to join targets of either 10 or 20 mm diameter which were separated by a distance of 62.5 or 125 mm. While HD patients had slower movements, exhibiting more cycles of acceleration and deceleration, patients were not disproportionately affected by variations in target size or separation. Bradykinesia did not seem to be a product of impaired force production or increased reliance upon terminal visual guidance, since neither accelerative or decelerative phases were specifically affected by HD. However, movements of HD patients were of less consistent duration, implying variability associated with internal cues regulating movement.

Adult

Subcortical dysfunction in schizophrenia: a comparison with Parkinson's disease and Huntington's disease.

Neuropsychological performance in 20 chronic schizophrenic patients was contrasted to 25 Parkinson's disease, 12 Huntington's disease patients and 26 normal controls on measures shown to be sensitive to subcortical dysfunction. Some overlap was observed in the performance of the schizophrenic and basal ganglia groups on tasks of executive and mnestic function, but the general pattern indicated significant differences in performance. Notably, in contrast to the two basal ganglia groups, there was no evidence of slowed thinking, or impaired motor function in schizophrenia, which are considered hallmarks of subcortical grey matter disease. An association was observed between poor performance on the tests of executive function and the severity of negative symptoms. Our findings suggest that schizophrenia is not associated with primary subcortical impairment, but is more likely to reflect frontotemporal dysfunction. We consider that the similarities between this disorder and subcortical degenerative syndromes may be due to a difficulty in generating action in schizophrenia, perhaps arising from dorsolateral prefrontal disconnection.

Adult

Reliance on advance information and movement sequencing in Huntington's disease.

To identify the focus of impairment in the performance of sequential movements in Huntington's disease (HD) patients, the extent of their reliance on external advance information was examined. Twelve patients with HD and their age-matched controls performed a series of button-presses at sequential choice points along a response board. A sequential pathway was designated, and with each successive button press, advance visual information was systematically reduced to various extents in advance of each move. HD patients, like previously studied parkinsonian patients, were particularly disadvantaged with high levels of reduction in advance information, and as a consequence, both their initiation and execution of movements progressively slowed with each successive element in the response sequence. The pattern of results was not affected whether or not patients were taking neuroleptic medication, nor did performance on a variety of cognitive measures correlate with motor performance. Control subjects' performance, on the other hand, remained constant in terms of both initiation and execution with each of the three levels of reduction in advance information. We conclude that HD patients, like parkinsonian patients, who also suffer from a basal ganglia (BG) disorder, require external visual cues to sequence motor programs effectively. Our findings suggest that with HD there may be abnormalities in a central mechanism that controls switching between movement segments within an overall motor plan. The BG, which provide internal cues necessary for component sequencing, may be disrupted, thereby impairing the ability to use such internally generated cues to guide movement.

Adult