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Biomedical subjects

A Simmons

Publications and source records attributed to A Simmons.

At least 109 records · Page 6Linked to original sources
PubMed1997

Functional magnetic resonance imaging of the acute effect of intravenous heroin administration on visual activation in long-term heroin addicts: results from a feasibility study.

This preliminary report is the first demonstration of the acute effects of diacetylmorphine (heroin) administration on functional activation in the human brain using functional magnetic resonance imaging (fMRI). Four opiate addicts who received regular prescriptions for heroin, underwent fMRI using a visual activation paradigm before and after a dose of 30 mg heroin. All four showed a decrease after the heroin dose in the extent of significant activation. This method shows promise for sequential scanning to determine brain activity in response to different drugs and routes of drug administration.

Acute Disease↗
PubMed1997

Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement.

Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.

Echo-Planar Imaging↗
PubMed1997

Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach.

We report a novel method to identify brain regions generically activated by periodic experimental design in functional magnetic resonance imaging data. This involves: 1) registering each of N individual functional magnetic resonance imaging datasets in a standard space; 2) computing the median standardised power of response to the experimental design; 3) testing median standardised power at each voxel against its nonparametrically ascertained distribution under the null hypothesis of no experimental effect; and 4) constructing a generic brain activation map. The method is validated by analysis of 6 null images, acquired under conditions when the null hypothesis was known to be true; 8 images acquired during periodic auditory-verbal stimulation; and 6 images acquired during periodic performance of a covert verbal fluency task.

Acoustic Stimulation↗
PubMed1997

Retention of herpes simplex virus DNA sequences in the nuclei of mouse footpad keratinocytes after recovery from primary infection.

Persistence of herpes simplex virus (HSV) DNA in mouse footpad keratinocytes was studied by non-isotopic in situ hybridization. HSV DNA was retained in keratinocyte nuclei for more than 2 weeks after disappearance of infectious virus and viral antigens. The anatomical location of viral DNA became more superficial with increasing time post-infection, reflecting the migration of cells from the basal layer of the epidermis towards the stratum granulosum. Latency-associated transcripts (LATs) were not detected in footpad cells at any of the times studied. In contrast, LATs were detected readily in the nuclei of lumbar ganglionic neurons innervating HSV DNA positive footpads. It was concluded that, after termination of productive infection in the skin, HSV DNA persists transiently in keratinocyte nuclei, in the absence of abundant latency-associated transcription. An implication of these data is that detection of HSV DNA in the skin may reflect recent, but not necessarily current, cutaneous virus replication.

Animals↗
PubMed1997

Functional MR imaging during odor stimulation: preliminary data.

PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, cerebellar, and occipital activation. Activation with combined trigeminal and olfactory system odors increased more than sixfold with repeated testing. CONCLUSION: Olfactory nerve-mediated and combined olfactory and trigeminal nerve-mediated odorants activate different regions of the brain. Orbitofrontal stimulation spreads to all parts of the brain when a trigeminal component is added. Habituation (deactivation) occurs with repeated testing of olfactory nerve-mediated odorants, while, paradoxically, activation increases with repeated exposure to odors that also stimulate the trigeminal nerve.

Adult↗
PubMed1997

An open-label study conducted to evaluate the efficacy of Betadine cold sore paint.

An open-label, randomised, parallel-group efficacy study was designed to compare Betadine cold sore paint and Stoxil topical ointment for the prevention of shedding of herpes simplex virus (HSV) from cold sores. Seventy-two patients aged 18-61 years (mean 32.2 years), with symptoms indicating recent onset of herpes labialis, were entered into the study. Patients were randomised to receive Betadine cold sore paint, Stoxil topical ointment or no treatment. To detect infectious virus, swabs were taken for virus culture before and 2 h after treatment. The no-treatment control group was included to monitor the efficiency of the swabbing technique. The primary measure of efficacy was the proportion of patients in each group returning a swab positive for HSV prior to treatment application and negative for HSV 2 h after treatment application. All 72 patients completed the study. HSV clearance rates were 0.636 for the Betadine treatment group and 0.092 for the Stoxil treatment group (p = 0.00056). It was concluded that recovery of infectious HSV from the lips of patients who applied Betadine cold sore paint to their lesions was significantly lower than from patients who applied Stoxil topical ointment.

Administration, Cutaneous↗
PubMed1997

Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.

Adult↗
PubMed1996

Simulation of MRI cluster plots and application to neurological segmentation.

The advent of magnetic resonance imaging has provided new opportunities for volume measurement of tissues, with applications increasing dramatically in recent years. Cluster classification techniques have proved the most popular for volume measurement, yet little attention has been paid to how the choice of images for analysis affects the quality and ease of segmentation. To address this issue, we have developed a system to simulate MRI cluster plots using multicompartmental anthropomorphic software models of anatomy, and components for image contrast, signal-to-noise ratio, image nonuniformity, tissue heterogeneity, imager field strength, the partial volume effect, correlation between proton density, T1 and T2, and a variety of data preprocessing techniques. The effect of these components on tissue cluster size, shape, orientation, and separation is demonstrated. The simulation allows an informed choice of pulse sequence, acquisition parameters, and data preprocessing for cluster classification to be made as well as providing an aid to interpretation of acquired data cluster plots and a valuable educational tool. The system has been used to choose suitable images for neurological segmentation of grey matter, white matter, CSF, and multiple sclerosis lesions using spin-echo, inversion recovery, and gradient-echo pulse sequences. Constraints on image selection are discussed.

Brain↗
PubMed1996

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome.

Two subjects with narcoleptic syndrome and three healthy volunteers underwent functional magnetic resonance imaging during the simultaneous presentation of periodic auditory and visual stimuli both before and after administration of amphetamine. The effect of amphetamine in control subjects was a small reduction in the extent of sensory-induced activation. In the narcoleptic subjects, amphetamine led to an increase in the extent of induced activation within primary and association sensory cortex.

Acoustic Stimulation↗
PubMed1996

Assessment of changes in dual-energy X-ray absorptiometry performance following a system upgrade.

System upgrades are a constant feature of many highly technical specialties and are normally assumed to have a negligible effect on patient data. We report on the assessment of an upgrade made to a Norland XR-26 dual-energy X-ray absorptiometry (DXA) system. The upgraded version (2.3) consisted of new hip positioning aids, hip image analysis software and updates to the normal ranges. Measurements of femoral neck and trochanteric bone mineral density correlated well between versions (r = 0.969 and r = 0.971), those for femoral neck and trochanteric bone mineral content less well (r = 0.956 and r = 0.911), and Ward's triangle values and femoral neck area measurements were poorly correlated (r = 0.719-0.881). The upgrade was claimed to improve precision while reducing analysis and imaging time. Improved precision was not demonstrated, with good precision found both before and after the upgrade. Correlation between femoral neck Z-scores were good for the European normal range (r = 0.970), but unacceptable for the UK range (r = 0.769). These correlations were not close enough to allow patients scanned with the old version to be followed up with scans using the upgrade. The upgrade was, however, preferred for new attenders because of the improved speed and automation of hip analysis, without loss of precision. The most important implication in terms of patient management was the change made to the UK normal range, which had a very large effect on the number of patients deemed to be at risk from osteoporosis. It is essential that any upgrade introduced to an existing DXA system is carefully evaluated, since it may affect system performance and patient results.

Absorptiometry, Photon↗
PubMed1995

Neural correlates of working memory in a visual letter monitoring task: an fMRI study.

Complex mental operations rely on the coordinated activity of widely distributed brain regions constituting neurocognitive networks. Using multislice echoplanar functional magnetic resonance imaging (fMRI) we have contrasted regional brain activity during a control and an experimental condition which differed with respect to the demands placed on verbal working memory. Subjects were seven right-handed healthy male volunteers. Analysis of group and individual data revealed activation in the anterior and posterior parasagittal cortex in all subjects, left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five subjects). These results suggest that verbal working memory is subserved by a neurocognitive network comprising cortical regions involved in attention, executive function and short term mnemonic processes.

Adult↗
PubMed1995

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.

A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.

Amino Acid Sequence↗
PubMed1995

Computerized brain tissue classification of magnetic resonance images: a new approach to the problem of partial volume artifact.

Due to the finite spatial resolution of digital magnetic resonance images of the brain, and the complexity of anatomical interfaces between brain regions of different tissue type, it is inevitable that some voxels will represent a mixture of two or three different tissue types. Outright assignment of such "bipartial" or "tripartial" voxels to one class or another is more problematic and less reliable than assignment of "full-volume" voxels, wholly representative of a single tissue type. We have developed a computerized system for brain tissue classification of dual echo MR data, which uses a polychotomous logistic model for discriminant analysis, combined with a Bayes allocation rule incorporating differential prior probabilities, and spatial connectivity tests, to assign each voxel in the image to one of four possible classes: gray matter, white matter, cerebrospinal fluid, or unclassified. The system supports automated volumetric analysis of segmented images, has low operational overheads, and compares favorably with previous multivariate or "multispectral" approaches to brain MR image segmentation in terms of both validity (bootstrap misclassification rate = 3.3%) and interoperator reliability (intra-class correlation coefficients for all three tissue classes > 0.9). We argue that these improvements in performance stem from better methodological management of the related problems of non-Normality of MR signal intensity values and partial volume artifact.

Artifacts↗
PubMed1995

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging.

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically "run" and "frozen" during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.

Echo-Planar Imaging↗
PubMed1995

Effect of gamma-irradiation on the effector function of T lymphocytes in microbial control.

A chlamydial-specific T cell clone, capable of inhibiting the growth of infectious Chlamydia in vivo and in vitro, was employed to investigate the effect of gamma-irradiation on the ability of effector T cells to control infections. Clone 2.14-0 (CD4+), specific for the Chlamydia trachomatis biovar agent of mouse pneumonitis (MoPn), was irradiated with varying doses (0, 2.5, 5.0, 10.0, 20.0 and 40.0 Gy) and its biological functions and ability to inhibit the intraepithelial growth of MoPn were assessed. The results revealed that although gamma-irradiation drastically reduced the proliferative response of the clone to antigen, it did not affect the phenotype and the effector function of inhibiting chlamydial growth. The preservation of anti-chlamydial function after gamma-irradiation correlated with the retention of IFN-gamma and TNF-alpha secretion in response to antigenic stimulation. We conclude that the biologic functions of T cells requiring proliferation and differentiation are more likely to be adversely affected by gamma-irradiation on the short-term, but the effector functions, possibly associated with cytokines and cytolysis, may be preserved among persisting effector T cells in an irradiated individual.

Animals↗
PubMed1995

A survey of dual-energy X-ray absorptiometry (DEXA) normal reference ranges used within the UK and their effect on patient classification.

Differences between dual-energy X-ray absorptiometry (DEXA) normal ranges can lead to patients being characterized as osteoporotic using one range and normal using another. To investigate the diversity of normal ranges used within the UK, a survey of all DEXA sites was carried out with a 60.6% response rate. The effect of the different ranges was evaluated by translating each range to an equivalent range for a Norland XR-26 system and applying the ranges to stratify a representative sample of over 1000 patients into grades of bone density based on percentages of age-matched mean BMD, Z-scores and T-scores. The effect of femoral neck and P/A spine L2-L4 regions was considered both separately and jointly. Large differences between the normal ranges were apparent, which resulted in the classification of the number of patients with a Z-score of less than -2.0 varying by a factor of more than 20 for the femoral neck and more than 3 for the spine. The number of patients defined as osteoporotic by a T-score less than -2.5 varied from none to over one-third of patients for the hip and by a factor of almost 3 for the spine. The exclusion criteria used for construction of the normal ranges varied markedly with none constructed using population-based sampling. Smoothing of normal ranges was carried out by DEXA manufacturers, while local normal ranges made use of raw unprocessed data. There is reason to question the validity of such processing. We recommend the construction of a unified UK normal range applicable to all UK DEXA systems in order to harmonize patient management and care.

Absorptiometry, Photon↗