Search PubMedSearch

Biomedical subjects

P Desmond

Publications and source records attributed to P Desmond.

At least 19 recordsLinked to original sources

Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study.

BACKGROUND: It has been proposed that the hippocampus is a potential site for a neurodevelopmental lesion in schizophrenia. While smaller hippocampal volumes have been described in chronic schizophrenia, there have been few magnetic resonance imaging studies in first-episode psychosis. Furthermore, no studies have examined the specificity of this finding to first-episode schizophrenia, compared with first-episode affective psychosis. METHODS: Hippocampal and whole-brain volumes were estimated using high-resolution magnetic resonance imaging in 140 controls, 46 patients with chronic schizophrenia, and 32 patients with first-episode psychosis. RESULTS: Patients with chronic schizophrenia and first-episode psychosis had significantly smaller hippocampal volumes as compared with controls. Within the first-episode group, both patients with schizophrenia/schizophreniform psychosis and those with affective psychosis had smaller left hippocampal volumes as compared with controls. Smaller right hippocampal volumes were associated with age and illness duration in patients with chronic schizophrenia. Hippocampal volumes were not correlated with age of illness onset or medication dosage in either patient group. CONCLUSIONS: These data show that smaller hippocampal volumes are present from the onset of illness. While these findings would support the neurodevelopmental model of schizophrenia, the finding of smaller left hippocampal volume in patients with first-episode schizophrenia and affective psychosis does not support the prediction that smaller hippocampi are specific to schizophrenia. The association of smaller right hippocampal volumes with increased illness duration in chronic schizophrenia suggests either that there is further neurodegeneration after illness onset or that bilateral small hippocampi predict chronicity.

Adult

Addressing adverse events through clinical indicators.

In an attempt to improve the reporting rate of adverse drug reactions the Adverse Drug Reaction Advisory Committee approached the Australian Council on Healthcare Standards Care Evaluation Program to develop a set of indicators to improve healthcare standards by heightening awareness amongst clinical staff of the morbidity, mortality and financial implications of adverse drug reactions. Ten clinical indicators addressing: (i) reporting of adverse drug reactions; (ii) adherence to treatment protocols for anaphylaxis; (iii) monitoring of warfarin; and (iv) monitoring of streptokinase, were field tested in ten Australian health-care organizations, to determine that the data were available, that the indicators were relevant to clinical practice and that the measures were achievable. Based on the results of this field test, six adverse drug reaction clinical indicators will be introduced into the Australian Council on Healthcare Standards Evaluation and Quality Improvement Program from January 1999.

Adverse Drug Reaction Reporting Systems

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

Clinical, magnetic resonance imaging and endocrinological differences between delusional and non-delusional depression in the elderly.

OBJECTIVE: To investigate neuroradiological, endocrinological and clinical differences between delusional and non-delusional depression. DESIGN: A cross-sectional study of depressed subjects. SETTING: Melbourne, Australia. PARTICIPANTS: Sixty-one subjects (inpatients) over the age of 55 meeting DSM-III-R criteria for major depression of whom 22 had delusional subtype of depression. MEASURES: Clinical assessment, including documentation of vascular risk factors. Cognitive assessment by the Cambridge Cognitive Examination (CAMCOG). Magnetic resonance imaging (MRI) scans were performed on a 0.3 Tesla scanner with temporal lobe atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) rated visually on 4-point scales. A standard 1 mg dexamethasone suppression test (DST) was performed. RESULTS: Subjects with delusional depression had significantly more vascular risk factors than those without delusions. There were no differences in measures of temporal lobe atrophy, PVL, DST results or cognitive test scores, though there was a non-significant trend for DWML to be more prevalent in those with delusions. Delusional depression was associated with a shorter duration of history and more frequent treatment with ECT. CONCLUSIONS: The increase in vascular risk factors and trend towards greater DWML on MRI suggests an organic contribution to delusional depression in the elderly. In contrast to some previous reports, we found no differences in cortical MRI appearance or neuroendocrine measures between groups.

Aged

Sequential increases in the intrahepatic expression of epidermal growth factor, basic fibroblast growth factor, and transforming growth factor beta in a bile duct ligated rat model of cirrhosis.

Chronic hepatic regeneration constitutes an important part of the cirrhotic process. The factors regulating chronic hepatic regeneration, however, remain unclear. We therefore analyzed the intrahepatic messenger RNA (mRNA) expression of growth factors (epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], hepatocyte growth factor [HGF], transforming growth factor [TGF]-alpha, and TGF-beta) at progressive time points (postoperative days 2, 7, 14, and 21) in a rat bile duct-ligated (BDL) model of cirrhosis versus sham controls. Intrahepatic growth factor mRNA expression was quantitatively assessed by polymerase chain reaction (PCR) using a dot-blot hybridization technique. Cirrhosis was associated with statistically significant (P < .05) progressive increases in the intrahepatic mRNA expression of bFGF (80-fold), EGF (25-fold), and TGF-beta (fourfold) in BDL animals versus controls. Furthermore, immunohistochemistry of hepatic sections showed a progressive up-regulation of bFGF protein in areas of bile duct proliferation. These areas also showed a dramatic increase in the number of hepatic stellate cells (HSC). In contrast, the intrahepatic expression of hepatocyte growth factor (HGF) mRNA was only significantly increased at postoperative days 7 and 14 in BDL animals before returning to control levels as cirrhosis developed. There were no significant differences found at any timepoint in the expression of TGF-alpha in BDL animals versus controls. In conclusion, the development of cirrhosis in this BDL rat model was associated with a progressive increase in the intrahepatic expression of EGF, bFGF, and TGF-beta. Early increased expression of HGF was not maintained in established cirrhosis. The findings suggest that these growth factors may play important roles in the pathogenesis of chronic hepatic regeneration in cirrhosis.

Animals

Degree of left hippocampal atrophy correlates with severity of neuropsychological deficits.

The relationship between the degree and distribution of hippocampal atrophy measured by volumetric magnetic resonance imaging and severity of memory deficits in 25 patients with temporal lobe epilepsy secondary to mesial temporal sclerosis was assessed. Hippocampal volumes were expressed as a ratio of smaller to larger, normal ratio greater than 0.95. Neuropsychology tests included: subtests of the WAIS-R, Rey Auditory Verbal Learning Task, Rey Figure and the Austin Maze. Degree of left hippocampal atrophy in patients with left temporal lobe epilepsy was associated with severity of verbal memory deficits as measured by RAVLT total recall (P < 0.05), delayed recall (P < 0.001), story recognition (P < 0.001), list recognition (P < 0.001) and final delayed recall (P < 0.001) and recall of the Rey Figure (P < 0.01). There was no association between degree of right hippocampal atrophy and any of the memory tests. Diffuse left hippocampal atrophy was associated with more severe verbal memory deficits than anterior atrophy. We conclude, the association between degree of left hippocampal atrophy and verbal memory provides further evidence of the predominant involvement of the left hippocampus in verbal memory. The finding of a relationship between degree of left hippocampal atrophy and measures of non-verbal function suggests these tests are dependent on verbal memory, or that mesial temporal sclerosis is a bilateral but asymmetrical condition.

Adolescent

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

Magnetic resonance imaging correlates of memory impairment in the healthy elderly: association with medial temporal lobe atrophy but not white matter lesions.

OBJECTIVE: To investigate the neuroradiological correlates of age-related cognitive decline in the elderly. DESIGN: A sample of healthy control subjects underwent magnetic resonance imaging (MRI) scanning and cognitive testing. SETTING: Melbourne, Australia. PARTICIPANTS: 40 volunteers over the age of 55 who were spouses of subjects seen in a hospital memory clinic, subjects from a register of normal volunteer subjects (not staff) kept for research purposes or residents of a retirement hostel. MEASURES: Hippocampal and amygdala (HA) atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: After controlling for age and education, lower scores on the memory subscale of the CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL. CONCLUSIONS: HA atrophy on MRI is associated with impaired memory performance in the healthy elderly, while PVL and DWML are not. Further study should determine whether HA atrophy is a risk factor for developing dementia.

Aged

Does hippocampal atrophy on MRI predict cognitive decline? A prospective follow-up study.

OBJECTIVES: To investigate whether the presence of hippocampal atrophy (HCA) on MRI in Alzheimer's disease (AD) leads to a more rapid decline in cognitive function. To investigate whether cognitively unimpaired controls and depressed subjects with HCA are at higher risk than those without HCA of developing dementia. DESIGN: A prospective follow-up of subjects from a previously reported MRI study. SETTING: Melbourne, Australia. PARTICIPANTS: Five controls with HCA and five age-matched controls without HCA, seven depressed subjects with HCA and seven without HCA, and 12 subjects with clinically diagnosed probable AD with HCA and 12 without HCA were studied. They were followed up at approximately 2 years with repeat cognitive testing, blind to initial diagnosis and MRI result. MEASURES: HCA was rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: No significant differences in rate of cognitive decline, mortality or progression to dementia were found between subjects with or without HCA. CONCLUSIONS: HCA was not found to be a predictor of subsequent cognitive decline in this series.

Aged

Mandibular invasion by squamous cell carcinoma: a computed tomographic and histological study.

Our knowledge of the entry and spread of oral cell carcinoma (SCC) into the mandible is increasing, making an impact on surgical planning. Fourteen resection specimens of mandibular bone and adjacent SCC were radiographically (CT) and histologically investigated. In six cases there was no involvement of mandibular bone; a continuous periosteal layer separated the tumour from bone. The remaining eight specimens showed bony involvement with good correlation between corresponding CT and histological slices in the five edentate cases. The site of entry of the tumour into the bone was usually through the alveolar crest with additional spread through the lingual cortex in tumours that lay lingual to the mandible. Although limited, our data shows that the main site of entry of SCC is through the alveolar crest. It also highlights the usefulness of CT in the identification of bone involvement in edentate cases. This information may assist in the planning of operations to preserve as much bone as is consistent with complete excision of the tumour.

Alveolar Process

Neuropsychological and structural brain changes in anorexia nervosa before and after refeeding.

The neuropsychological performance and Magnetic Resonance Imaging (MRI) brain appearance of a consecutive series of 46 in-patients with anorexia nervosa (AN) was compared with that of 41 normal-weight controls. The groups were matched for sex, age, estimated pre-morbid intelligence and education. AN patients who had gained at least 10% of their body weight were retested and rescanned. Controls were retested after a similar interval. The AN group performed significantly worse than the controls on tasks measuring attention, visuospatial ability and memory. On tasks assessing flexibility and learning, no group differences were evident although an examination of deficits in individuals revealed that more anorexics were impaired on both. Following treatment, the AN group improved relative to the control group only on those tasks assessing attention. Comparison of MRI measures showed a significant proportion of anorexics had enlarged lateral ventricles and dilated sulci on both cortical and cerebellar surfaces, but no dilatation was evident for the third and fourth ventricular measures. Improvements were found after treatment on some of the radiological measures but many differences remained. Relationships between morphological brain changes and cognitive impairments were weak. Lower weight, but not duration of illness, was associated with poorer performance on tasks assessing flexibility/inhibition and memory, and with greater MRI ventricular size.

Adult

A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease.

BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.

Aged

Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease.

BACKGROUND: An age-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. METHOD: To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. RESULTS: Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI. CONCLUSION: An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

Aged

Malignant granular cell tumour of the sciatic nerve.

A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated isodensity with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis.

Aged

The differentiation of depression from dementia by temporal lobe magnetic resonance imaging.

Temporal lobe Magnetic Resonance Imaging (MRI) was performed in 43 patients with NINCDS/ADRDA Alzheimer's disease (AD) (33 probable, 7 possible, 3 definite) and 32 subjects with DSM-III-R Major Depression (DEP) matched for age, sex and level of education. Hippocampus (anterior and posterior, right and left), amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated for atrophy on a 4-point scale. Good discrimination between groups could be achieved using a cut-off of 2 or more on anterior hippocampal atrophy rating (sensitivity 93%; specificity 84%; 89% cases correctly grouped overall). Even among a subgroup of 9 mild AD subjects and 10 cognitively impaired DEP subjects (matched on mini-mental state score), the same cut-off correctly grouped 84% (16/19) cases. Hippocampal atrophy increased with age in both AD and DEP subjects leading to a reduction in specificity (but not sensitivity) for those aged over 75. Within the AD group a significant correlation was observed between length of history and atrophy of the entorhinal cortex (r = 0.39, P = 0.009). We conclude that temporal lobe atrophy on MRI can provide good discrimination between AD and DEP subjects, including those DEP patients with cognitive impairment apparent on screening tests of cognitive function.

Aged