Biomedical subjects

D K Jones

Publications and source records attributed to D K Jones.

At least 19 recordsLinked to original sources

PubMed2006

Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI.

OBJECTIVE: To use diffusion tensor MRI to quantify and compare degeneration of the pons and cerebellar peduncles in multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Parkinson disease (PD) and to relate changes in diffusion measures to clinical features and localized atrophy. METHODS: We used a region-of-interest approach to measure changes in fractional anisotropy and mean diffusivity in the middle cerebellar peduncles, decussation of the superior cerebellar peduncles, and pons in 17 patients with MSA, 17 with PSP, 12 with PD, and 12 healthy volunteers. We also evaluated atrophy of the cerebellar peduncles and pons on T2-weighted magnetic resonance images in patients with MSA and PSP. RESULTS: In MSA, fractional anisotropy was markedly reduced in the middle cerebellar peduncles, and mean diffusivity increased both here and in the pons compared with other groups, whereas in PSP, mean diffusivity was strikingly increased in the decussation of superior cerebellar peduncles. Cerebellar ataxia was related to mean diffusivity in the middle cerebellar peduncles (r = 0.71, p = 0.001) and pons (r = 0.60, p = 0.01) in MSA. Diffusion measures were related to localized atrophy in both MSA and PSP. CONCLUSIONS: Diffusion tensor MRI can be used to quantify neurodegenerative processes in different brain stem and cerebellar structures in multiple system atrophy and progressive supranuclear palsy during life, and may have diagnostic value. Larger studies of early, undifferentiated parkinsonian syndromes are indicated to provide estimates of the relative diagnostic value of diffusion measures, atrophy measures, and visual assessment of scans.

Aged↗

PubMed2004

Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular dementia. Both discrete lacunar infarcts and more diffuse ischaemic changes, seen as confluent high signal (leukoaraiosis) on T2 weighted magnetic resonance imaging (MRI), occur. However, there is a weak correlation between T2 lesion load and cognitive impairment. Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage. OBJECTIVES: To determine whether DTI measures are correlated more strongly with cognitive performance than lesion load on T2 weighted images, and whether these correlations are independent of conventional MRI parameters. METHODS: 36 patients with ischaemic leukoaraiosis (leukoaraiosis plus a previous lacunar stroke) and 19 healthy volunteers underwent DTI, conventional MRI, and neuropsychological assessment. RESULTS: On DTI, diffusivity was increased both within lesions and in normal appearing white matter. Mean diffusivity of normal appearing white matter correlated with full scale IQ (r = -0.46, p = 0.009) and tests of executive function. These correlations remained significant after controlling for age, sex, brain volume, and T1/T2 lesion volumes. No significant correlation was identified between T2 lesion load and IQ or neuropsychological scores. Of conventional measures, brain volume correlated best with cognitive function. CONCLUSIONS: Diffusion tensor measurements correlate better with cognition than conventional MRI measures. They may be useful in monitoring disease progression and as a surrogate marker for treatment trials. The findings support the role of white matter damage and disruption of white matter connections in the pathogenesis of cognitive impairment in cerebral small vessel disease.

Aged↗

PubMed2001

Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study.

Ischemic leukoaraiosis is a consistent concomitant of vascular dementia. Conventional MRI provides little information about underlying white matter tract disruption and correlates poorly with cognitive dysfunction. Diffusion tensor MRI may provide better markers of tract integrity. Changes in the normal-appearing white matter were demonstrated in 30 patients with ischemic leukoaraiosis compared with 17 age-matched control subjects. These changes correlated with executive dysfunction assessed by the Wisconsin Card Sorting Test.

Aged↗

PubMed2001

Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline.

BACKGROUND: Normal aging is accompanied by a decline of cognitive abilities, and executive skills may be affected selectively, but the underlying mechanisms remain obscure and preventive strategies are lacking. It has been suggested that cortical "disconnection" due to the loss of white matter fibers may play an important role. But, to date, there has been no direct demonstration of structural disconnection in humans in vivo. METHODS: The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal conventional MRI scans, and a group of 10 younger controls. The older group also underwent neuropsychological assessment. RESULTS: Diffusional anisotropy, a marker of white matter tract integrity, was reduced in the white matter of older subjects and fell linearly with increasing age in the older group. Mean diffusivity was higher in the older group and increased with age. These changes were maximal in anterior white matter. In the older group, anterior mean diffusivity correlated with executive function assessed by the Trail Making Test. CONCLUSIONS: These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consistent with the cortical disconnection hypothesis of age-related cognitive decline. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at preventing cognitive decline.

Adult↗

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.

Aged↗

PubMed2000

Investigation of the haem-nicotinate interaction in leghaemoglobin. Role of hydrogen bonding.

A strategic assessment of the contributions of two active-site hydrogen bonds in the binding of nicotinate to recombinant ferric soybean leghaemoglobin a (rLb) was carried out by mutagenic replacement of the hydrogen-bonding residues (H61A and Y30A variants) and by complementary chemical substitution of the carboxylate functionality on the nicotinate ligand. Dissociation constants, Kd (pH 5.5, mu = 0.10 M, 25.0 +/- 0.1 degrees C), for binding of nicotinate to ferric rLb, H61A and Y30A were 1.4 +/- 0.3 microM, 19 +/- 1 microM and 11 +/- 1 microM, respectively; dissociation constants for binding of nicotinamide were, respectively, 38 +/- 1 mM, 50 +/- 2 mM and 12 +/- 1 mM, and for binding of pyridine were 260 +/- 50 microM, 4.5 +/- 0.5 microM and 66 +/- 8 microM, respectively. Binding of cyanide and azide to the H61A and Y30A variants was unaffected by the mutations. The pH-dependence of nicotinate binding for rLb and Y30A was consistent with a single titration process (pKa values 6.9 +/- 0.1 and 6.7 +/- 0.2, respectively); binding of nicotinate to H61A was independent of pH. Reduction potentials for the rLb and rLb-nicotinate derivatives were 29 +/- 2 mV (pH 5.40, 25.0 degrees C, mu = 0.10 M) and - 65 +/- 2 mV (pH 5.42, 25.0 degrees C, mu = 0.10 M), respectively. The experiments provide a quantitative assessment of the role of individual hydrogen bonds in the binding process, together with a definitive determination of the pKa of His61 and unambiguous evidence that titration of His61 controls binding in the neutral to alkaline region.

Base Sequence↗

PubMed2000

Extracorporeal shock wave therapy in the management of Peyronie's disease: initial experience.

OBJECTIVE: To evaluate prospectively the efficacy of extracorporeal shock wave therapy (ESWT) as a conservative treatment for Peyronie's disease. PATIENTS AND METHODS: After obtaining ethical committee approval, 37 patients with Peyronie's disease were treated using ESWT. Before treatment the degree of angulation was assessed by artificially inducing an erection with a vacuum device. The severity of pain on erection was assessed using a visual analogue scale (0-5). Each patient was treated with a minimum of three sessions of ESWT (3000 shock waves at an energy density of 0.11-0.17 mJ/mm2) at 3-week intervals. The results were analysed using the Wilcoxon signed-rank test. RESULTS: Of the 37 patients, 34 completed the protocol; the mean (range) duration of the disease was 19.43 (4-60) months and the mean follow-up 7.5 (5-11) months. Almost half (47%) of the patients reported an improvement in angulation, with a mean reduction of 29.3 degrees (10 degrees -60 degrees ) (P < 0.001); 12 of the 20 (60%) patients with pain on erection reported immediate relief, the mean reduction being 2.3 (1-4) on the visual analogue scale (P < 0.001). There was only minimal bruising at the site of treatment and no major side-effects were reported. CONCLUSION: ESWT is an effective and safe treatment for Peyronie's disease; the long-term follow-up and results are awaited.

Adult↗

PubMed2000

Cluster analysis of diffusion tensor magnetic resonance images in human head injury.

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.

Adolescent↗

PubMed2000

Analysis of position and isometric joysticks for powered wheelchair driving.

The control interface is one of the most critical components of the electric-powered wheelchair (EPW). The control interface must accommodate the user's limitations and maximize the user's abilities. This study extended Fitts' Law for target-acquisition to a continuously updated target. The extended Fitts' Law was used to examine EPW driving with a standard position sensing joystick and a prototype isometric joystick (IJ). The extended Fitts' Law provides insight into the difficulty of performing target-acquisition tasks with an EPW. The test results showed significant differences (p < 0.05) among the two types of joysticks for selected measures of information processing capacity, movement time, root-mean-square-error, and average velocity while performing turning maneuvers. The mean values indicate that the IJ may provide superior turning performance.

Algorithms↗

PubMed1999

Diffusion tensor MRI assesses corticospinal tract damage in ALS.

BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI. OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI. METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS-11 with limb onset (mean age 54.5 +/- 10.7 years) and 11 with bulbar onset (mean age 49.6 +/- 11.7 years)-and compared them with 20 healthy, age-matched controls (mean age 46.0 +/- 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated. RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration. CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.

Adult↗

PubMed1999

Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI.

A technique for assessing in vivo fiber connectivity in the human brain is presented. The method utilizes a novel connectivity algorithm that operates in three spatial dimensions and uses estimates of fiber tract orientation and tissue anisotropy, obtained from diffusion tensor magnetic resonance imaging, to establish the pathways of fiber tracts. Sample in vivo connectivity images from healthy human brain are presented that demonstrate connections in the white matter tracts. White matter connectivity information is potentially of interest in the study of a range of neurological, psychiatric, and developmental disorders and shows promise for following the natural history of disease.

Algorithms↗

PubMed1999

A modified technique of atriofemoral bypass for visceral and distal aortic perfusion in thoracoabdominal aortic surgery.

Modified atriofemoral bypass (AFB) was used for repair of thoracoabdominal aortic aneurysms (TAAA). The primary circuit consisted of a centrifugal pump and heat exchanger to perfuse and warm the systemic circulation. A parallel secondary circuit with a second heat exchanger perfused the viscera with cold blood. A progressive sequential cross-clamping technique was used. This technique offers theoretical hemodynamic and metabolic advantages and may prove to be useful in preventing ischemic and reperfusion injury to the spinal cord and kidneys.

Aged↗

PubMed1999

Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI.

BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

Adult↗

PubMed1999

Echoplanar MRI in patients with an acute stroke syndrome.

An increasing number of patients with an acute stroke syndrome are being admitted to hospitals with on-site echoplanar MRI scanners. In this pictorial review, we describe our experience of an MRI protocol in the first 150 such patients scanned in our hospital. We illustrate some of the advantages of using echoplanar MRI. Diffusion and susceptibility weighted acquisitions may supplement conventional MR sequences by providing useful additional information about the age and location of the lesion, together with a high sensitivity to the presence of blood breakdown products.

Acute Disease↗

PubMed1999

Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging.

The optimization of acquisition parameters for precise measurement of diffusion in anisotropic systems is described. First, an algorithm is presented that minimizes the bias inherent in making measurements with a fixed set of gradient vector directions by spreading out measurements in 3-dimensional gradient vector space. Next, it is shown how the set of b-matrices and echo time can be optimized for estimating the diffusion tensor and its scalar invariants. The standard deviation in the estimate of the tensor trace in a water phantom was reduced by more than 40% and the artefactual anisotropy was reduced by more than 60% when using the optimized scheme compared with a more conventional scheme for the same scan time, and marked improvements are demonstrated in the human brain with the optimized sequences. Use of these optimal schemes results in reduced scan times, increased precision, or improved resolution in diffusion tensor images. Magn Reson Med 42:515-525, 1999.

Adult↗

PubMed1998

Class I heme peroxidases: characterization of soybean ascorbate peroxidase.

An efficient expression system [D. A. Dalton et al. Arch. Biochem. Biophys. 328, 1-8, 1996) for soybean nodule ascorbate peroxidase (APX) has, for the first time, been used to generate enzyme in large enough quantities for detailed biophysical analysis. The recombinant APX has been characterized by electronic absorption, EPR, NMR and circular dichroism spectroscopies, and by electrochemistry. Electronic, EPR, and NMR spectra are consistent with a high-spin ferric resting state for the enzyme at 298 K. Low-temperature EPR (7 K) and electronic absorption (77 K) experiments indicate formation of a low-spin heme derivative at these temperatures. The midpoint reduction potential for the Fe(III)/Fe(II) redox couple, determined by spectroelectrochemistry, is -159 +/- 2 mV vs SHE (pH 7.0, 25.0 degrees C, mu = 0.10 M). Circular dichroism spectra of pea and soybean APXs are very similar, indicating common structural features for the two enzymes. The melting temperature of soybean APX, as monitored by circular dichroism spectroscopy, is 49 degrees C. These results represent the first detailed spectroscopic and electrochemical analysis of soybean ascorbate peroxidase and are discussed in the broader context of other class I peroxidases.

Amino Acid Sequence↗

PubMed1998

Bacterial expression and spectroscopic characterization of soybean leghaemoglobin a.

A gene encoding leghaemoglobin a from soybean has been constructed and the soluble recombinant protein expressed in E. coli. The integrity of the recombinant protein has been assessed by a range of spectroscopic techniques. Electrospray mass spectrometry of the protein indicates that the molecular mass of the protein corresponds to the predicted amino acid sequence. Circular dichroism spectra of the ferric derivative and UV-visible spectra of various ferric and ferrous derivatives (pH 6.99, mu = 0.10 M, 25.0 degrees C) are consistent with published data for the wild-type protein. For the ferric derivative, UV-visible (298 and 77 K) and EPR (10 K) spectra indicate the existence of a thermal equilibrium between high- and low-spin forms. Titration of the protein (0.10 M NaCl, mu = 0.10 M, 25.0 degrees C) between pHs 6.68 and 10.35 indicate formation (pKa = 8.3+/-0.03) of a 6-coordinate, hydroxide-bound form of the protein at high pH. All of the above data are consistent with the behaviour of the wild-type protein.

Amino Acid Sequence↗

PubMed1998

Braking electric-powered wheelchairs: effect of braking method, seatbelt, and legrests.

OBJECTIVE: To examine the influence of three electric-powered wheelchair braking conditions and four wheelchair seating conditions on electric-powered wheelchair motion and Hybrid II test dummy motion. This study provides quantitative information related to assessing the safety of electric-powered wheelchair driving. DESIGN: Rehabilitation engineering comparison and ANSI/ RESNA standards testing. Convenience sample of eight different electric-powered wheelchairs. Within-chair comparisons were conducted. INTERVENTION: Electric-powered wheelchairs were compared under three braking scenarios (joystick release, joystick reverse, power-off) and four seating conditions (seatbelt and legrests, seatbelt and no legrests, no seatbelt but legrests, no seatbelt and no legrests). SETTING: A rehabilitation engineering center. MAIN OUTCOME MEASURES: The braking distance, braking time, and braking accelerations for electric-powered wheelchairs during three braking scenarios; trunk motion, head motion, and trunk angular acceleration during three braking scenarios and four seating conditions; and number of falls from the wheelchairs for three braking scenarios and four seating conditions. RESULTS: Significant differences (p < .05) were found in braking distance, braking time, and braking acceleration when comparing the joystick release and joystick reverse scenarios with the power-off scenario. The mean braking distance was shortest with the power-off braking scenario (.89m), whereas it was longest when the joystick was released (1.66m). Significant differences (p < .05) in head displacement and trunk angular displacement were observed among braking conditions and between seating conditions. There were also significant differences (p = .0011) among braking conditions for maximum trunk angular acceleration. The Hybrid II test dummy fell from the wheelchairs with highest frequency when there were no legrests and no seatbelt used. CONCLUSION: The results of this study indicate that use of a seatbelt when driving an electric-powered wheelchair reduces the risk of falling from a wheelchair. Furthermore, the use of legrests can reduce the risk of injury to the wheelchair driver. This study shows that the most abrupt braking occurs when deactivating the power switch.

Accidental Falls↗