Biomedical subjects

P Desmond

Publications and source records attributed to P Desmond.

At least 19 recordsLinked to original sources

PubMed2001

Selective bilateral hippocampal volume loss in chronic schizophrenia.

BACKGROUND: The hippocampus is implicated in the pathophysiology of schizophrenia; however, volumetric changes are subtle and have limited diagnostic specificity. It is possible that the shape of the hippocampus may be more characteristic of schizophrenia. METHODS: Forty-five patients with chronic schizophrenia and 139 healthy control subjects were scanned using magnetic resonance imaging. Hippocampi were traced manually, and two-dimensional shape information was analyzed. RESULTS: Two shape factors were found to be adequate to represent variance in the shape of the hippocampus. One of these factors, representing volume loss behind the head of the hippocampus, provided a degree of discrimination between patients with chronic schizophrenia and healthy control subjects; however, overall hippocampal volume following appropriate adjustment for brain volume showed a similar level of discrimination. Patients with chronic schizophrenia were best characterized using these two measures together, but diagnostic specificity was only moderate. CONCLUSIONS: This study identified that less of the hippocampus was distributed in its posterior two-thirds in patients with chronic schizophrenia, and specifically in the region just posterior to the hippocampal head. Group discrimination on the basis of hippocampal volume and shape measures was moderately good. A full three-dimensional analysis of hippocampal shape, based on large samples, would be a useful extension of the study.

Adolescent↗

PubMed2001

A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia.

Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.

Adolescent↗

PubMed2001

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Aged↗

PubMed2001

Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection.

Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C virus (HCV) infection is associated with advanced liver disease, including cirrhosis. The aims of this study were to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in HCV-infected patients and to determine the role of Fas in HCV-mediated apoptosis. Liver tissue from 44 HCV-infected patients with variable alcohol consumption, and 10 normal control subjects who did not consume alcohol was examined for hepatocyte apoptosis, proliferation and Fas expression. Alcohol consumption was assessed using the 'Lifetime Drinking History' alcohol questionnaire. HCV RNA, alanine aminotransferase (ALT) and ferritin were also assessed in addition to demographic data. Hepatocyte apoptosis was significantly greater in HCV-infected patients compared to controls. Expression of Fas (CD95) was found in HCV patients but not in controls. The degree of Fas expression correlated with hepatocyte apoptosis as detected by terminal UTP nick end labelling (TUNEL). Active ethanol consumption led to a significant increase in hepatocyte apoptosis. Fas expression correlated with fibrosis in HCV-infected patients who were not actively drinking ethanol. In summary, HCV leads to increased apoptotic cell death in hepatocytes. Programmed cell death can be further up-regulated by active ethanol consumption. The correlation between Fas expression and TUNEL supports the hypothesis that the Fas-Fas ligand interaction is the major mechanism for HCV-induced hepatocyte apoptosis.

Adult↗

PubMed2001

Liver toxicity. Could this be a drug reaction?

BACKGROUND: Adverse reaction to prescription medications, over the counter medications and complementary medicines, are an important cause of liver toxicity. OBJECTIVE: To highlight the importance of drug induced liver toxicity in patients presenting with abnormal liver function tests. DISCUSSION: In patients who present with symptoms of liver dysfunction such as anorexia, itch or Jaundice and in whom liver function tests are abnormal, the possibility of an adverse reaction to medications should be considered. A detailed history of all medications taken in the past few months, including complementary medicines, should be obtained. After exclusion of other causes of liver disease such a viral hepatitis or gallstones, the cessation of the offending medication and the normalisation of liver tests is usually sufficient to establish a diagnosis. Occasionally, referral to a specialist and liver biopsy may be required.

Adult↗

PubMed2000

Magnetic resonance spectroscopy and schizophrenia: what have we learnt?

OBJECTIVE: Magnetic resonance spectroscopy (MRS) has been increasingly used to investigate the in vivo biochemistry of particular regions of the brain in patients with schizophrenia. We review the literature and discuss the theoretical constructs that form the presumed impetus for these studies in light of the current methodological limitations. Future directions are noted. METHOD: The available published literature in English formed the basis for this review. RESULTS: The results of 31P-MRS have been interpreted as reflecting a relative increase in cell membrane degradation in prefrontal cortical regions at certain phases of schizophrenia. 1H-MRS studies, though less consistent, provide evidence suggestive of a decrease in neuronal cell mass in the hippocampal region, which supports the findings of volumetric studies. Both groups of MRS studies support a neuro-developmental hypothesis of brain dysfunction in schizophrenia. However, current methodological problems limit the reliable interpretation of MRS data. A clear understanding of the methodology and its reliable interpretation is yet to emerge. CONCLUSIONS: MRS remains a research instrument that is yet to be fully utilised in schizophrenia research. A few replicated findings are emerging, although the interpretation of these spectroscopic findings needs to be validated.

Brain↗

PubMed2000

Where does treatment fit into the strategy to control hepatitis C?

The prevalence of hepatitis C varies greatly between countries of the Asia-Pacific region. The incidence of new cases is also markedly different between countries, particularly related to the prevalence of injecting drug use. Overall, the currently available treatments for hepatitis C are unlikely to have a major impact in the control of the infection from a population perspective while success rates are relatively low (20-45% sustained antiviral response) and treatment costs are high. There are some specific situations, such as reducing the incidence of mother-to-baby transmission or sexual transmission, where antiviral treatment can be used as a strategy to prevent further infection. The major aims of prevention of hepatitis C infection should lie with public health measures to prevent new infections, particularly amongst injecting drug users, and ultimately the development of an effective vaccine..

Asia↗

PubMed2000

A randomized, placebo-controlled study to evaluate the efficacy of 12-month famciclovir treatment in patients with chronic hepatitis B e antigen-positive hepatitis B.

We conducted a randomized, placebo-controlled clinical study evaluating famciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months post-treatment follow-up) in patients with chronic hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV) infection. The study was conducted in 80 centers in North America, Europe, and Australia/New Zealand. A total of 417 patients with histologically documented chronic hepatitis B (histologic activity index [HAI] 9.5-11.0) received famciclovir (500 mg 3 times daily or 1.5 g once daily) or placebo. Famciclovir 500 mg 3 times daily significantly reduced HBV DNA and median HAI scores versus placebo. By week 8, median HBV DNA decreased from 1,645 to 283 MEq/mL (famciclovir 500 mg 3 times daily) and from 1,147 to 304 MEq/mL (famciclovir 1.5 g once daily), while increasing for placebo (1,617 to 1,685 MEq/mL). Median change in HBV DNA at the end of therapy was -76% (famciclovir 500 mg 3 times daily; P <.01) and -60% (famciclovir 1.5 g once daily; P =.25) versus -37% for placebo. Median change in HAI was -1.5 points (famciclovir 500 mg 3 times daily; P =.02) and -1.0 point (famciclovir 1.5 g once daily; P =.35) and zero for placebo. Fifty percent of patients receiving famciclovir 500 mg 3 times daily (P =.07) and 43% receiving 1.5 g once daily (P =.41) experienced >/=2 points improvement in HAI versus 37% for placebo. Nine percent of patients treated with famciclovir 500 mg 3 times daily underwent anti-HBeAg seroconversion with undetectable HBV DNA at end of follow-up versus 3% in the placebo group (P =.05). Famciclovir was well tolerated; the incidence of post-treatment alanine transaminase (ALT) elevations was comparable with placebo. In conclusion, famciclovir 500 mg 3 times daily gave modest suppression of viral replication, but translated into significant histologic improvement in median HAI score at 1 year.

2-Aminopurine↗

PubMed2000

Echoplanar magnetic resonance imaging in acute stroke.

Echoplanar magnetic resonance imaging (EPI) enables rapid, non-invasive imaging and analysis of cerebral pathophysiology in acute stroke. It represents an important clinical advance over computed tomography (CT) and conventional magnetic resonance (MR) scanning. It can rapidly delineate infarcted cerebral tissue and distinguish acute from chronic stroke. In addition, EPI has the potential to quickly determine the presence and degree of potentially viable brain tissue in the ischaemic penumbra. Thrombolysis is thought to reperfuse the penumbra and hence reduce infarct size. The thrombolytic agent tissue plasminogen activator (t-PA) improves outcome in ischaemic stroke when administered within the first 3 hours of onset. However, there is a significant risk of haemorrhage, and the time window for benefit may well exceed 3 hours in some patients. Hence, by facilitating diagnosis of 'at-risk' tissue in the ischaemic penumbra, a major clinical role of EPI may well become the rational selection of patients for acute interventional stroke therapy.

Brain↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗