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J B Chalk

Publications and source records attributed to J B Chalk.

At least 19 recordsLinked to original sources
PubMed2002

The Cys282Tyr polymorphism in the HFE gene in Australian Parkinson's disease patients.

Iron homeostasis is altered in Parkinson's disease (PD). The HFE protein is an important regulator of cellular iron homeostasis and variations within this gene can result in iron overload and the disorder known as hereditary haemochromatosis. We studied the Cys282Tyr single nucleotide polymorphism as a genetic risk factor for PD in two distinct and separately collected cohorts of Australian PD patients and controls. In the combined cohort comprising 438 PD patients and 485 control subjects, we revealed an odds ratio for possession of the 282Tyr allele of 0.61 (95% confidence interval, CI=0.42-0.90, P=0.011) from univariate chi-squared and 0.59 (95% CI=0.39-0.90, P=0.014) after logistic regression analyses (correcting for potential confounding factors). These results suggest that possession of the 282Tyr allele may offer some protection against the development of PD.

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PubMed2001

4D deformation modeling of cortical disease progression in Alzheimer's dementia.

This work describes the development of a model of cerebral atrophic changes associated with the progression of Alzheimer's disease (AD). Linear registration, region-of-interest analysis, and voxel-based morphometry methods have all been employed to elucidate the changes observed at discrete intervals during a disease process. In addition to describing the nature of the changes, modeling disease-related changes via deformations can also provide information on temporal characteristics. In order to continuously model changes associated with AD, deformation maps from 21 patients were averaged across a novel z-score disease progression dimension based on Mini Mental State Examination (MMSE) scores. The resulting deformation maps are presented via three metrics: local volume loss (atrophy), volume (CSF) increase, and translation (interpreted as representing collapse of cortical structures). Inspection of the maps revealed significant perturbations in the deformation fields corresponding to the entorhinal cortex (EC) and hippocampus, orbitofrontal and parietal cortex, and regions surrounding the sulci and ventricular spaces, with earlier changes predominantly lateralized to the left hemisphere. These changes are consistent with results from post-mortem studies of AD.

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PubMed2001

Ischaemic preconditioning in the rat brain: a longitudinal magnetic resonance imaging (MRI) study.

Ischaemic preconditioning in rats was studied using MRI. Ischaemic preconditioning was induced, using an intraluminal filament method, by 30 min middle cerebral artery occlusion (MCAO), and imaged 24 h later. The secondary insult of 100 min MCAO was induced 3 days following preconditioning and imaged 24 and 72 h later. Twenty-four hours following ischaemic preconditioning most rats showed small sub-cortical hyperintense regions not seen in sham-preconditioned rats. Twenty-four hours and 72 h following the secondary insult preconditioned animals showed significantly smaller lesions (24 h = 112 +/- 31 mm(3), mean +/- standard error; 72 h = 80 +/- 35 mm(3)), which were confined to the striatum, than controls (24 h = 234 +/- 32 mm(3), p = 0.026; 72 h = 275 +/- 37 mm(3), p = 0.003). In addition during lesion maturation from 24 to 72 h post-secondary MCAO, preconditioned rats displayed an average reduction in lesion size as measured by MRI whereas sham-preconditioned rats displayed increases in lesion size; this is the first report of such differential lesion volume evolution in cerebral ischaemic preconditioning.

Animals↗
PubMed2001

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.

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PubMed2000

Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy.

We wish to report the detection of dimethyl sulfone (methylsulfonylmethane, C2H6O2S) in the brain of a normal 62-year-old male using in vivo proton magnetic resonance spectroscopy. The presence of this exogenous metabolite resulted from ingestion of a dietary supplement containing dimethyl sulfone. The concentration of this compound in the brain was measured to be 2.4 mmol, with a washout "half life" of approximately 7.5 days. The in vivo T1 and T2 relaxation times of dimethyl sulfone were measured to be 2180 ms and 385 ms, respectively. The concentration of major brain metabolites, namely N-acetylaspartate, total Creatine and Choline, and myo-Inositol were within normal limits.

Brain↗
PubMed2000

Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging.

A novel MRI method--diffusion tensor imaging--was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.

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PubMed1999

A 1H MRS study of probable Alzheimer's disease and normal aging: implications for longitudinal monitoring of dementia progression.

In order to evaluate the capability of 1H MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N-acetylaspartylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mI, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mI and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel.

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PubMed1999

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia.

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event.

Anisotropy↗
PubMed1998

Prefrontal cortex involvement in selective letter generation: a functional magnetic resonance imaging study.

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Adult↗
PubMed1998

The Modified Card Sorting Test: test-retest stability and relationships with demographic variables in a healthy older adult sample.

OBJECTIVES: To investigate the test-retest stability of a standardized version of Nelson's (1976) Modified Card Sorting Test (MCST) and its relationships with demographic variables in a sample of healthy older adults. DESIGN: A standard card order and administration were devised for the MCST and administered to participants at an initial assessment, and again at a second session conducted a minimum of six months later in order to examine its test-retest stability. Participants were also administered the WAIS-R at initial assessment in order to provide a measure of psychometric intelligence. METHODS: Thirty-six (24 female, 12 male) healthy older adults aged 52 to 77 years with mean education 12.42 years (SD = 3.53) completed the MCST on two occasions approximately 7.5 months (SD = 1.61) apart. Stability coefficients and test-retest differences were calculated for the range of scores. The effect of gender on MCST performance was examined. Correlations between MCST scores and age, education and WAIS-R IQs were also determined. RESULTS: Stability coefficients ranged from .26 for the percent perseverative errors measures to .49 for the failure to maintain set measure. Several measures were significantly correlated with age, education and WAIS-R IQs, although no effect of gender on MCST performance was found. CONCLUSIONS: None of the stability coefficients reached the level required for clinical decision making. The results indicate that participants' age, education, and intelligence need to be considered when interpreting MCST performance. Normative studies of MCST performance as well as further studies with patients with executive dysfunction are needed.

Adult↗
PubMed1997

Deficits on self ordered tasks associated with hyperostosis frontalis interna.

A 74 year old patient, EW, with dorsolateral frontal cortical compression due to hyperostosis frontalis interna, in the absence of the Morgagni or Stewart-Morel syndromes, is described. In addition to conventional neuropsychological measures EW was administered one nonspatial and two spatial self ordered working memory tasks, as well as a standard measure of fluid intelligence or g. She showed impaired performance on all three self ordered working memory tasks compared with a normal control group of 10 subjects matched for age, education, sex, and IQ. By contrast, her performance on the fluid intelligence test was comparable with that of the controls. It is concluded that the compression of dorsolateral frontal cortex accompanying hyperostosis frontalis interna may produce selective cognitive impairment.

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PubMed1996

Localized 1H NMR spectroscopy of rat spinal cord in vivo.

A movable, actively decoupled surface coil has been employed to obtain a localized 1H NMR spectrum from the lumbosacral spinal cord of a live Lewis rat. A volume selective 'VOSY' normally spelled out as 'volume selective spectroscopy' spectroscopy pulse sequence that incorporates 'phase ramped' selective RF pulses, has been used to minimize random phase jitter in the NMR signal as a result of the large frequency shifts required to locate the voxel in the center of the cord while using intense gradient pulses. Spectra from 13-microliters voxels in healthy rats and in rats inoculated with guinea pig spinal cord and complete Freund's adjuvant, resulting in experimental autoimmune encephalomyelitis, are shown.

Animals↗
PubMed1995

Restoration of conduction in the spinal roots correlates with clinical recovery from experimental autoimmune encephalomyelitis.

In the Lewis rat, acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants is characterized by tail and hindlimb weakness that resolves spontaneously after several days. In rats with neurological signs of this form of EAE (MBP-EAE) we have previously demonstrated demyelination and nerve conduction block in the proximal peripheral nervous system (PNS) and in the central nervous system (CNS). The present study was performed to assess conduction in the PNS and CNS, after recovery from acute MBP-EAE, using direct recordings from surgically exposed spinal roots and spinal cord dorsal columns. The study revealed that 1-2 weeks after clinical recovery from tail paralysis there was almost complete restoration of conduction in the sacral spinal roots but persistent severe conduction abnormalities in the dorsal columns. Significant restoration of conduction through the dorsal columns occurred over the following 2 weeks. These findings indicate that PNS conduction block due to a demyelinating polyradiculitis is a major cause of the neurological signs of acute MBP-EAE in the Lewis rat.

Action Potentials↗
PubMed1994

Clinical and histological findings in proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Distribution of demyelination differs from that in EAE induced by other antigens.

Proteolipid protein (PLP) is the major protein of central nervous system (CNS) myelin. In some species, intradermal inoculation with PLP and adjuvants causes experimental autoimmune encephalomyelitis (PLP-EAE) characterized by neurological signs of tail and limb weakness and by inflammation and demyelination in the CNS. A previous study found that inoculation of Lewis rats with 100 micrograms of PLP causes PLP-EAE with a low incidence of neurological signs and a highly variable clinical course. In the present study we assessed PLP-EAE produced by inoculation with 1000 micrograms of PLP per rat. Fifty-one of 59 (86%) Lewis rats developed neurological signs 8 to 20 days (mean = 12.0 +/- 2.0) after inoculation with 1000 micrograms of PLP. In such rats, mononuclear cell infiltrates were present in the brain and spinal cord while primary demyelination occurred mainly in the subpial regions of the spinal cord, especially in the dorsal root entry and ventral root exit zones. The histological findings were compared with those in acute EAE induced in the Lewis rat by inoculation with whole CNS tissue or with myelin basic protein: in PLP-EAE, in contrast to these other models, the disease was essentially restricted to the CNS. This form of EAE should be useful in future studies of the consequences of autoimmunity to PLP.

Animals↗
PubMed1994

Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) and can be induced by inoculation of animals with homogenized CNS tissue or highly purified myelin proteins such as myelin basic protein (MBP) or proteolipid protein (PLP). It is widely studied as a possible animal model of multiple sclerosis. We performed the present neurophysiological study to define the location of nerve conduction abnormalities in EAE induced by immunization with PLP (PLP-EAE) and in EAE induced by immunization with MBP (MBP-EAE) in the Lewis rat. In rats with tail weakness due to acute PLP-EAE, conduction was normal in the spinal nerve roots and peripheral nerves but there was evidence of conduction block in a high proportion of the fibres in the dorsal columns of the lumbosacral spinal cord. In contrast, in acute MBP-EAE, there was conduction block in a high proportion of fibres in the sacral dorsal and ventral roots of the peripheral nervous system (PNS) and in the dorsal columns of the lumbosacral spinal cord. The distribution of nerve conduction abnormalities is consistent with previous histological studies showing that inflammation and primary demyelination are restricted to the CNS in PLP-EAE, but are present in the CNS and in the spinal roots of the PNS in MBP-EAE. The restriction of functional abnormalities to the CNS in PLP-EAE but not in MBP-EAE may have implications for the human inflammatory demyelinating diseases, including multiple sclerosis.

Action Potentials↗
PubMed1992

Spasticity and white matter abnormalities in adult phenylketonuria.

A 19 year old male with phenylketonuria (PKU) developed a spastic paparesis 8 months after stopping his restricted phenylalanine diet. CT and MRI showed abnormalities of the deep cerebral white matter, and visual evoked response latencies were prolonged. The spasticity gradually improved over several months after resuming the PKU diet. A repeat MRI scan was unchanged. His brother also had PKU and ceased dietary restrictions, but his only neurological abnormality was a slight increase in the deep tendon reflexes of the lower limbs. CT and MRI of his brain was normal. DNA analysis showed that both brothers were homozygous for the same PKU mutation. These patients demonstrate that reversible neurological signs may develop in patients with classic PKU after ceasing dietary restrictions and that these may be associated with abnormalities seen on neuro-imaging.

Adult↗
PubMed1991

Sensorimotor peripheral neuropathy in rheumatoid arthritis.

We describe 3 patients with severe sensorimotor neuropathy complicating rheumatoid arthritis. Two patients had evidence of vasculitis and an axonal neuropathy. These patients were unusual in that the neuropathy occurred early in the course of rheumatoid arthritis. The third patient had a demyelinating neuropathy with a high cerebrospinal fluid protein level, and is a probable example of a chronic inflammatory neuropathy occurring in rheumatoid arthritis. All patients improved or were stabilized with corticosteroid therapy.

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