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Biomedical subjects

Jack L Lancaster

Publications and source records attributed to Jack L Lancaster.

29 records · Page 2Linked to original sources
PubMed2003

Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q.

We report on a 12-year-old boy who presented with delayed development and CNS dysmyelination. Genetic studies showed a normal 46,XY karyotype by routine cytogenetic analysis, and 46,XY.ish del(18)(q23)(D18Z1+, MBP-) by FISH using a locus-specific probe for the MBP gene (18q23). Though the patient appeared to have normal chromosome 18s by repeated high resolution banding analysis, his clinical features were suggestive of a deletion of 18q. These included hearing loss secondary to stenosis of the external auditory canals, abnormal facial features, and foot deformities. FISH studies with genomic probes from 18q22.3 to 18qter confirmed a cryptic deletion which encompassed the MBP gene. In an attempt to further characterize the deletion, whole genome screening was conducted using array based comparative genomic hybridization (array CGH) analysis. The array CGH data not only confirmed a cryptic deletion in the 18q22.3 to 18qter region of approximately 7 Mb, it also showed a previously undetected 3.7 Mb gain of 4q material. FISH studies demonstrated that the gained 4q material was translocated distal to the 18qter deletion breakpoint. The 18q deletion contains, in addition to MBP, other known genes including CYB5, ZNF236, GALR1, and NFATC1, while the gained 4q material includes the genes FACL1 and 2, KLKB1, F11 and MTNR1A. The use of these combined methodologies has resulted in the first reported case in which array CGH has been used to characterize a congenital chromosomal abnormality, highlighting the need for innovative molecular cytogenetic techniques in the diagnosis of patients with idiopathic neurological abnormalities.

Central Nervous System↗
PubMed2003

Asymmetry of the brain surface from deformation field analysis.

The detection of asymmetry of exposed brain surfaces is examined, and a new method, deformation-based asymmetry (DBA), is introduced. DBA is based on analysis of two high-resolution magnetic resonance brain images, each with features representative of the subject group from which they were derived. Warping of individual brain images to their group representative image using octree spatial normalization provides sets of displacement vectors that are used in estimating deformation variance. For DBA group-representative left and right hemisphere images are compared. Representative hemisphere images are warped to each other and asymmetry analyzed using standardized d-values calculated as the ratio of displacement vector magnitude to the estimated component of variance in the direction of the displacement vector for each surface voxel. D-values were calculated within hemispheres by dividing subjects into two equal groups and comparing left-to-left and right-to-right. D-values from this ipsilateral hemisphere grouping were pooled. D-values from contralateral hemispheres were compared with the pooled ipsilateral hemisphere data. The proportion of d-values above a fixed level was used to test for difference between the two groups. High-resolution magnetic resonance (MR) images from 20 young, right-handed males were studied using DBA. No significant differences were seen between sub-grouped ipsilateral d-values (P > 0.10). Highly significant asymmetries (P < 0.0001) were found between hemispheres, and in each lobe. Common right frontal and left occipital petalias were seen. The DBA method can theoretically be applied to any two groups of globally similar structures where analysis of dissimilarity of regional features is sought.

Adult↗
PubMed2003

Three-pool model of white matter.

PURPOSE: To investigate the use of a three-pool relaxation model to measure myelin, myelinated-axon, and mixed water-pool fractions in white matter (WM) during myelination. MATERIALS AND METHODS: MRI at 1.9 Tesla, and conventional spin-echo imaging were used to acquire T1 and T2 relaxation data in 15 normal children ranging in age from 3 months to 13 years 4 months. Three equations with three unknowns were solved to calculate three water-pool fractions for each child in a frontal association-fiber area and a frontal-parietal projection-fiber area. The temporal trend of the fractions was compared with a theoretical three-pool myelination model. RESULTS: The myelin level in the projection-fiber area rose earlier than in the association-fiber area following the standard caudal-to-rostral trend. The temporal trend of the three-pool fractions followed that predicted by the theoretical myelination model in both brain areas. The myelinated-axon and mixed pool sizes were significantly different in the two WM areas following early myelination, although their myelin pools were similar. T1 values correlated more highly with the myelinated-axon and mixed pool fractions than with the myelin pool fraction. CONCLUSION: The three-pool relaxation model provides measurements of water-pool fractions in WM that follow values predicted during myelination.

Adolescent↗
PubMed2003

Positron emission tomography scanning in essential blepharospasm.

PURPOSE: To localize in the brain using positron emission tomography neuroimaging with (18)fluorodeoxyglucose [PET ((18)FDG)] differences in glucose metabolism between patients with essential blepharospasm (EB) and controls. DESIGN: Prospective case-control study. METHODS: Positron emission tomography neuroimaging with (18)fluorodeoxyglucose was performed in 11 patients with EB and 11 controls matched for age and gender. Global analysis of images was used to localize differences in glucose metabolism between groups. RESULTS: Multiple cortical and subcortical abnormalities were observed in EB patients in comparison with controls. Cortical areas with the largest and most significant clusters of increased glucose uptake were the inferior frontal gyri, right posterior cingulate gyrus, left middle occipital gyrus, fusiform gyrus of the right temporal lobe, and left anterior cingulate gyrus. Cortical areas with the largest and most significant clusters of decreased glucose uptake were the inferior frontal gyri, ventral to the area of increased glucose metabolism. Subcortical abnormalities, consisting of increased glucose uptake, involved the right caudate and consisting of decreased glucose uptake, involved the left inferior cerebellar hemisphere and thalamus. CONCLUSIONS: Global analysis of positron emission tomography neuroimaging with (18)fluorodeoxyglucose neuroimaging in EB patients in comparison with controls demonstrates a pattern of abnormalities involving several cortical and subcortical areas that control blinking, including the inferior frontal lobe, caudate, thalamus, and cerebellum.

Adult↗
PubMed2003

Estimation of the local statistical noise in positron emission tomography revisited: practical implementation.

The purpose of this report is to implement novel modifications to overcome the limitations of an existing algorithm for estimating the local statistical noise in a positron emission tomography (PET) image without performing repeated measures. The original algorithm is based on a modification of the filtered back-projection algorithm that allows the variance to be estimated using only a single sinogram. In addition, the effects of photon absorption, random coincidences, radioactive decay, and detector nonuniformity are taken into account. However, there are some limitations when applying this method with modern scanners. In particular, it is common practice to interleave the projections in the sinogram (to increase the sampling rate along each projection) and to perform an interpolation when actually back-projecting to reconstruct the images. Both of these procedures introduce covariance among the elements of the projections, which is cumbersome and impractical to deal with using the existing technique for creating a variance image. An alternative image reconstruction scheme that is shown to be equivalent to image reconstruction using traditional filtered back-projection greatly simplifies the estimation of the variance image. The proposed methods were tested by Monte Carlo simulations and by using repeated scans of a uniform phantom filled with F-18. Results demonstrate that the proposed methods are very rigorous and stable when compared to calculations of the local variance using either repeated measures with a large number of measurements, or region-of-interest estimates of the variance, assuming homogeneous variance structure. In addition, strategies for extending the proposed technique are discussed that would permit the estimation of the variance due to measurement error of a pixel in a brain map from both single subjects and pooled group data.

Algorithms↗
PubMed2003

Attention deficit hyperactivity disorder and neurocognitive correlates after childhood stroke.

We investigated the frequency and neurocognitive correlates of attention deficit hyperactivity disorder and traits of this disorder (ADHD/Traits) after childhood stroke and orthopedic diagnosis in medical controls. Twenty-nine children with focal stroke lesions and individually matched children with clubfoot or scoliosis were studied with standardized psychiatric, intellectual, academic, adaptive, executive, and motivation function assessments. Lifetime ADHD/Traits were significantly more common in stroke participants with no prestroke ADHD than in orthopedic controls (16/28 vs. 7/29; Fisher's Exact p < .02). Lifetime ADHD/Traits in the orthopedic controls occurred exclusively in males with clubfoot (7/13; 54%). Participants with current ADHD/Traits functioned significantly worse (p < .005) than participants without current ADHD/Traits on all outcome measures. Within the stroke group, current ADHD/Traits was associated with significantly lower verbal IQ and arithmetic achievement (p < .04), more nonperseverative errors (p < .005), and lower motivation (p < .004). A principal components analysis of selected outcome variables significantly associated with current ADHD/Traits revealed "impaired neurocognition" and "inattention-apathy" factors. The latter factor was a more consistent predictor of current ADHD/Traits in regression analyses. These findings suggest that inattention and apathy are core features of ADHD/Traits after childhood stroke. This association may provide clues towards the understanding of mechanisms underlying the syndrome.

Adaptation, Psychological↗
PubMed2003

MR imaging volumetry of subcortical structures and cerebellar hemispheres in normal persons.

BACKGROUND AND PURPOSE: Volume changes in subcortical structures and cerebella have been associated with localization-related epilepsy and psychiatric illnesses. This study evaluated the effect of handedness and sex on the volumes of selected subcortical structures and cerebellar hemispheres in normal persons. METHODS: Volumetric measurements were performed of the caudate heads, thalami, and cerebellar hemispheres in 34 (20 right- and 14 left-handed, 19 female and 15 male) normal persons. Amygdalar and hippocampal volumes were reported previously for these persons. All study participants completed a 10-item handedness questionnaire. The MR imaging sequence was a 3D T1-weighted gradient-echo acquisition of the whole brain (24/6 [TR/TE]; flip angle, 25 degrees). MR images were spatially normalized, and volumes were painted with a 1.0 mm(3) resolution cursor on an SGI workstation. The effects of handedness and sex on standardized volumes and right-to-left volume ratios were calculated, and volumes were compared between right and left sides for each structure. RESULTS: Handedness did not affect standardized volumes or asymmetries of the caudate heads, thalami, or cerebellar hemispheres. The volumes of subcortical structures were bilaterally larger in women than in men. Right-to-left asymmetries were significant for the caudate head and cerebellum but not for the thalamus. CONCLUSION: These findings show that women have significantly larger subcortical structures than do men after spatial normalization to account for differences in brain size. Sex-specific normal ranges may be needed for evaluating volume changes related to epilepsy or other disease processes.

Adult↗
PubMed2002

Psychiatric disorders after childhood stroke.

OBJECTIVES: To determine the rate, types, and correlates of psychiatric disorder (PD) following stroke and orthopedic disorders in children and adolescents. METHOD: Children aged 5 to 19 were assessed. The study used a cross-sectional design that compared 29 stroke subjects with 29 congenital clubfoot or scoliosis subjects. Assessments of psychiatric status; cognitive, adaptive, academic, and family functioning; family psychiatric history; neuroimaging; and neurological status were conducted. The main outcome measure was a current PD not present before the stroke or orthopedic disorder. RESULTS: Poststroke PD occurred significantly more often than postorthopedic diagnosis PD (17/29 [59%] versus 4/29 [14%], p < or =.001). Subjects with ongoing poststroke PD had significantly more impaired intellectual and adaptive functioning, higher intensity family psychiatric history scores, and tended toward higher neurological severity index scores, but they were not different regarding lesion volume or family functioning compared with stroke subjects without PD. Regression analyses showed that neurological severity and family psychiatric history independently contributed significantly to predicting PD. CONCLUSIONS: The data suggest that there are significant biopsychosocial correlates of PD in children with focal neurological lesions. These include a relatively abnormal neurological exam, lower IQ, and increased family psychopathology.

Adolescent↗
PubMed2002

Putamen lesions and the development of attention-deficit/hyperactivity symptomatology.

OBJECTIVE: To investigate the association between focal stroke lesions of the putamen and either attention-deficit/hyperactivity disorder or traits of the disorder (ADHD/Traits). METHOD: Twenty-five children with focal stroke lesions were studied with standardized psychiatric assessments and anatomic brain magnetic resonance imaging. The pattern of lesion overlap in subjects with ADHD/Traits was determined. RESULTS: Fifteen of 25 subjects had ADHD/Traits. The densest area of overlapping lesions (n = 7) in subjects with ADHD/Traits included the posterior ventral putamen. The median lesion volume was 9.7 cm3, and the distribution was highly skewed. Lesion volume was not associated with ADHD/Traits. Therefore the following analyses focused on the 13 subjects with lesions < 10 cm3: ADHD/Traits were exhibited in 6/7 subjects with putamen lesionsversus 2/6 with no putamen lesions (Fisherexacttestp= .1). Half (4/8) of the subjects with ADHD/Traits had overlapping lesions encompassing the posterior ventral putamen. None of the 5 subjects without ADHD/Traits had lesions in this empirically derived region of interest (Fisher exact test p = .1). CONCLUSIONS: Lesions within the dopamine-rich ventral putamen, which is part of the ventral or limbic striatum, tended to increase the risk of ADHD/Traits. ADHD/Traits may therefore be a disinhibition syndrome associated with dysfunction in this cortical-striato-thalamocortical loop.

Adolescent↗