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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Epidemiological survey of central nervous system germ cell tumors in Canadian children.

OBJECTIVES: To determine the incidence and characteristics of pediatric patients with central nervous system (CNS) germ cell tumors (GCT) in Canada. METHOD: A national retrospective review of hospital charts was done on all patients with CNS GCT diagnosed between 1990 and 2004. Patients had to be under age 18 years at the time of diagnosis of a CNS germ cell tumor and be a resident of Canada. Information extracted included age and year of diagnosis, pathological diagnosis, location of tumor, evidence of disseminated disease at time of diagnosis and biological markers. RESULTS: One hundred and twenty-one cases were identified (83 germinoma; 38 non-germinoma germ cell tumor). The mean annual incidence of CNS GCT was 1.06 per million children (0.7 per million for germinoma; 0.3 per million for NGGCT). Though yearly incidences varied, there was no clear trend to increased incidence. Male predominance was noted (2.4:1 for germinoma; 11:1 for NGGCT). The primary locations were the pineal and suprasellar regions. At the time of diagnosis, disseminated disease was not uncommon (22% germinoma; 32% NGGCT). Beta human gonadotrophin was elevated in the serum, cerebrospinal fluid (CSF) or both in 7% of patients with germinoma and 36% of patients with NGGCT. Elevation of alpha-fetoprotein in serum, CSF or both was seen in 34% of patients with NGGCT. CONCLUSION: The incidence of CNS germ cell tumors in Canadian children is similar to that observed in other Western countries.

Adolescent↗
PubMed2005

Retinotopy within rat primary visual cortex using optical imaging.

The purpose of this study was to determine the retinotopic organization of rat primary visual cortex (area 17) using optical imaging technology. Stimulating discrete regions of visual space resulted in localised changes in the remitted light during optical imaging of visual cortex in rat. From these localised changes, our results confirm previous electrophysiological studies on the location, size and organization of rat primary visual cortex. Small differences in the cortical magnification factor (CMF) were found between visual field areas with the highest CMF confined to the upper nasal region. No significant CMF differences were found within the horizontal and vertical visual field axes. No secondary visual areas were activated either anterior or medial to area 17 with the pattern stimuli used in the current study. However, there was evidence of activity to upper nasal stimulation on the posterior lateral extrastriate area. The location of area 17 from optical imaging activity was confirmed anatomically using conventional immunohistochemical techniques. This study shows the retinotopic organization of rat primary visual cortex and serves as a precursor before examining animal models of retinal degeneration and the effectiveness of potential therapies to stem retinal disease.

Animals↗
PubMed2005

Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli.

Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 mum intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans.

Animals↗
PubMed2005

Neurovascular coupling investigated with two-dimensional optical imaging spectroscopy in rat whisker barrel cortex.

Optical imaging slit spectroscopy is a powerful method for estimating quantitative changes in cerebral haemodynamics, such as deoxyhaemoglobin, oxyhaemoglobin and blood volume (Hbr, HbO2 and Hbt, respectively). Its disadvantage is that there is a large loss of spatial data as one image dimension is used to encode spectral wavelength information. Single wavelength optical imaging, on the other hand, produces high-resolution spatiotemporal maps of brain activity, but yields only indirect measures of Hbr, HbO2 and Hbt. In this study we perform two-dimensional optical imaging spectroscopy (2D-OIS) in rat barrel cortex during contralateral whisker stimulation to obtain two-dimensional maps over time of Hbr, HbO2 and Hbt. The 2D-OIS was performed by illuminating the cortex with four wavelengths of light (575, 559, 495 and 587 nm), which were presented sequentially at a high frame rate (32 Hz). The contralateral whisker pad was stimulated using two different durations: 1 and 16 s (5 Hz, 1.2 mA). Control experiments used a hypercapnic (5% CO2) challenge to manipulate baseline blood flow and volume in the absence of corresponding neural activation. The 2D-OIS method allowed separation of artery, vein and parenchyma regions. The magnitude of the haemodynamic response elicited varied considerably between different vascular compartments; the largest responses in Hbt were in the arteries and the smallest in the veins. Phase lags in the HbO2 response between arteries and veins suggest that a process of upstream signalling maybe responsible for dilating the arteries. There was also a consistent increase in Hbr from arterial regions after whisker stimulation.

Algorithms↗
PubMed2004

Integration of neural responses originating from different regions of the cortical somatosensory map.

The neural pathways responsible for detecting peripheral tactile stimuli are well known; however, the interactions between different somatosensory regions have been less well investigated. This study demonstrates how the contralateral sensory response of rat barrel cortex to whisker stimulation is affected by stimulation of contralateral forepaw and ipsilateral whisker and forepaw. The barrel cortex in the right hemisphere was located using optical imaging. A 16-channel multielectrode was used to measure field potentials evoked by contralateral electrical stimulation of the whisker pad. A standard response in the right barrel cortex to single pulse electrical stimulation of the contralateral whisker pad was modulated by applying conditioning stimulation to one of three other regions of the body (the ipsilateral whisker pad, the ipsilateral or contralateral forepaws). In conditions where the standard contralateral whisker stimulus preceded the conditioning pulse, the size of response was identical to when it was stimulated alone. However, when the ipsilateral whisker and contralateral forepaw conditioning stimuli preceded the contralateral whisker pad stimulation, up to a 35% reduction in the contralateral whisker response was observed. These results confirm and extend previous studies [Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 11026-11031; J. Neurosci. 21 (2001) 5251-5261], which show bilateral integration of neural activity within the rat somatosensory system. Furthermore, the longer latency of the inhibition following stimulation of the contralateral forepaw suggests the possible involvement of extracortical circuitry.

Animals↗
PubMed2004

Increased leucine turnover in women during the third trimester of uncomplicated pregnancy.

Plasma amino acid concentrations decrease in pregnancy despite increased requirements for both maternal and fetal protein accretion. There are few published data on changes in amino acid turnover in pregnancy. The aim of this study is to test the hypotheses that (1) whole body nonoxidative leucine disposal (NOLD) is higher and (2) whole body oxidative leucine disposal (OLD) is lower in the third trimester of pregnancy than in the nonpregnant state. After an overnight fast 8 pregnant women between 33 and 35 weeks gestation had a primed infusion of labeled [1-(13)C] leucine and a prime dose of NaH(13)CO(3). Carbon dioxide production was measured using indirect calorimetry. Gas chromatography-mass spectrometry was used to determine (13)CO(2) enrichment of expired air and oxidative and nonoxidative leucine turnover by measuring (13)C keto-isocaproate plasma enrichment, which reflects intracellular leucine enrichment. Women acted as their own controls after the puerperium. Whole body leucine turnover expressed per unit body weight was increased in pregnancy (median [interquartile range or IQR]: pregnant = 103.1 [14.9] v nonpregnant = 90.1 [10.9] micromol/kg/h). The mean (+/-SD) of the differences was 11.4 +/- 5.6 micromol/kg/h, P =.0006. NOLD was increased in pregnancy (pregnant = 86.8 [10.1] v nonpregnant = 73.3 [9.5] micromol/kg/h). The mean (+/-SD) of the differences was 10.6 +/- 5.4 micromol/kg/h, P =.0008. OLD was not significantly altered in pregnancy (pregnant = 17.3 [4.5] v nonpregnant = 15.91 [2.4] micromol/kg/h). The mean (+/-SD) of the differences was 0.84 +/- 1.94 micromol/kg/h, P =.26. In conclusion, women have significantly higher NOLD in the third trimester of pregnancy than when not pregnant but there are no significant changes in OLD.

Adult↗
PubMed2004

Haemodynamic responses to sensory stimulation are enhanced following acute cocaine administration.

Cocaine enhances neural activity in response to sensory stimulation, an effect that may play a role in the development of drug craving. However, cocaine-induced sensory enhancement may be difficult to study in humans using neuroimaging if the global increases in baseline haemodynamic parameters, which cocaine produces, interfere with the ability of enhanced sensory-related neural activity to lead to enhanced haemodynamic responses. To investigate the effect of cocaine-induced baseline haemodynamic changes on sensory-related haemodynamic (and electrophysiological) responses, field potential (FP) and haemodynamic responses (obtained using optical imaging spectroscopy and laser-Doppler flowmetry) in the barrel cortex of the anaesthetised rat were measured during mechanical whisker stimulation following cocaine (0.5 mg/kg) or saline administration. During cocaine infusion, the relationship between blood flow and volume transiently decoupled. Following this, cocaine caused large baseline increases in blood flow (133%) and volume (33%), which peaked after approximately 6 min and approached normal levels again after 25 min. During the peak baseline increases, FP responses to whisker stimulation were similar to saline whereas several haemodynamic response parameters were slightly reduced. After the peak, significant increases in FP responses were observed, accompanied by significantly enhanced haemodynamic responses, even though the haemodynamic baselines remained elevated. Hence, the haemodynamic response to sensory stimulation is transiently reduced in the presence of large increases in baseline but, after the baseline peak, enhanced neural responses are faithfully accompanied by enhanced haemodynamic responses. The findings suggest that any cocaine-induced enhancement of sensory-related neural activity in humans is likely to be detectable by neuroimaging.

Animals↗
PubMed2003

Relation between insulin kinetics and insulin sensitivity in pregnancy.

BACKGROUND: Different time-concentration profiles of plasma insulin following insulin modification of a frequently sampled intravenous glucose-tolerance-test (FSIVGTT) were observed in a study investigating maternal metabolism and fetal macrosomia. We aimed to investigate whether these differences were related to the volume of distribution of insulin, insulin clearance, or both. DESIGN: Forty-four women were studied between 33 and 35 weeks' gestation using an insulin-modified FSIVGTT. Specific insulin was assayed with an enzyme-linked immunosorbent assay. Insulin sensitivity was calculated using the minimal model and the homeostasis model assessment (HOMA). The volume of distribution and clearance of insulin were calculated from measurements between 2 and 155 min after insulin modification using a one-compartment model. RESULTS: In accordance with the method for deriving the volume of distribution, there was a significant negative correlation between the increment in insulin concentration and the volume of distribution (rho=-0.92, P<0.0001). The insulin increment was also related negatively to the clearance of insulin (rho=-0.88, P<0.0001). There was a significant correlation between the volume of distribution and both the insulin sensitivity index (rho=0.56, P<0.0001) and HOMA-%S (rho=0.30, P=0.048), and between the clearance of insulin and both the insulin sensitivity index (rho=0.83, P<0.0001)) and HOMA-%S (rho=0.34, P=0.025). CONCLUSION: The different time-concentration profiles of plasma insulin resulted from differences in the volume of distribution and clearance of insulin. There was a correlation between insulin kinetics and the insulin sensitivity index. Further research is required to investigate possible mechanisms by which insulin kinetics may be related to insulin sensitivity.

Enzyme-Linked Immunosorbent Assay↗
PubMed2003

Distance-dependent modifiable threshold for action potential back-propagation in hippocampal dendrites.

In hippocampal CA1 pyramidal neurons, action potentials generated in the axon back-propagate in a decremental fashion into the dendritic tree where they affect synaptic integration and synaptic plasticity. The amplitude of back-propagating action potentials (b-APs) is controlled by various biological factors, including membrane potential (Vm). We report that, at any dendritic location (x), the transition from weak (small-amplitude b-APs) to strong (large-amplitude b-APs) back-propagation occurs when Vm crosses a threshold potential, x. When Vm > x, back-propagation is strong (mostly active). Conversely, when Vm < x, back-propagation is weak (mostly passive). x varies linearly with the distance (x) from the soma. Close to the soma, x << resting membrane potential (RMP) and a strong hyperpolarization of the membrane is necessary to switch back-propagation from strong to weak. In the distal dendrites, x >> RMP and a strong depolarization is necessary to switch back-propagation from weak to strong. At approximately 260 micrometer from the soma, 260 approximately RMP, suggesting that in this dendritic region back-propagation starts to switch from strong to weak. x depends on the availability or state of Na+ and K+ channels. Partial blockade or phosphorylation of K+ channels decreases x and thereby increases the portion of the dendritic tree experiencing strong back-propagation. Partial blockade or inactivation of Na+ channels has the opposite effect. We conclude that x is a parameter that captures the onset of the transition from weak to strong back-propagation. Its modification may alter dendritic function under physiological and pathological conditions by changing how far large action potentials back-propagate in the dendritic tree.

Action Potentials↗
PubMed2002

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Adult↗
PubMed2002

Wealth condensation in pareto macroeconomies.

We discuss a Pareto macroeconomy (a) in a closed system with fixed total wealth and (b) in an open system with average mean wealth, and compare our results to a similar analysis in a super-open system (c) with unbounded wealth [J.-P. Bouchaud and M. Mézard, Physica A 282, 536 (2000)]. Wealth condensation takes place in the social phase for closed and open economies, while it occurs in the liberal phase for super-open economies. In the first two cases, the condensation is related to a mechanism known from the balls-in-boxes model, while in the last case, to the nonintegrable tails of the Pareto distribution. For a closed macroeconomy in the social phase, we point to the emergence of a "corruption" phenomenon: a sizeable fraction of the total wealth is always amassed by a single individual.

Journal Article↗
PubMed2002

Irish X-ray departments demonstrate varying levels of adherence to European guidelines on good radiographic technique.

The Commission of European Communities (CEC) publication "European Guidelines on Quality Criteria for Diagnostic Radiographic Images" includes examples of good radiographic technique for a number of common X-ray examinations. If these guidelines are followed, compliance with dose and image quality criteria as specified in the CEC document should be demonstrated. Studies in England, Germany and Greece have shown that a number of X-ray departments are not using optimum techniques. The aim of this study is to demonstrate the level of adherence to CEC guidelines in Irish hospitals 3-4 years following publication of the above document. 16 hospitals were randomly chosen and the following details on technique and equipment were recorded for chest, abdomen, pelvis and lumbar spine examinations of standard sized patients: tube potential, focus-to-film distance, automatic exposure control (AEC), film-screen combination, X-ray tube filtration and secondary radiation grid. Varying levels of adherence to the guidelines were evident depending on the parameter being investigated, with no hospital demonstrating 100% compliance and no hospital demonstrating 100% non-compliance. For all parameters, with the exception of AEC use, the majority of hospitals exhibited non-adherence for at least one projection. The results suggest that if hospitals in Ireland observe the straightforward examples of good radiographic technique described in the CEC publication, significant reductions in collective dose can be achieved.

European Union↗
PubMed2001

Tensionless structure of a glassy phase.

We study a class of homogeneous finite-dimensional Ising models which were recently shown to exhibit glassy properties. Monte Carlo simulations of a particular three-dimensional model in this class show that the glassy phase obtained under slow cooling is dominated by large-scale excitations whose energy E(l) scales with their size l as E(l) approximately l(Theta) with Theta approximately 1.33(20). Simulations suggest that in another model of this class, namely the four-spin model, energy is concentrated mainly in linear defects, making the domain walls tensionless in this case also. Two-dimensional variants of these models are trivial and most likely the energy of excitations scales with the exponent Theta=1.

Journal Article↗
PubMed2001

Crystallization of a supercooled liquid and of a glass: Ising model approach.

Using Monte Carlo simulations we study crystallization in the three-dimensional Ising model with four-spin interaction. We monitor the morphology of crystals which grow after placing crystallization seeds in a supercooled liquid. Defects in such crystals constitute an intricate and very stable network that separates various domains by tensionless domain walls. We also show that the crystallization which occurs during the continuous heating of the glassy phase takes place at a heating-rate-dependent temperature.

Journal Article↗
PubMed2001

Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome 16 involved in progression of bladder cancer from occult preneoplastic conditions to invasive disease.

Histologic and genetic mapping with 30 hypervariable markers mapped to chromosome 16 were performed on 234 DNA samples of five cystectomy specimens from patients with invasive bladder cancer. Allelic losses of individual markers were related to microscopically identified precursor conditions in the entire bladder mucosa and invasive cancer. Their significance for the development and progression of neoplasia from in situ preneoplastic conditions to invasive disease was analysed by the nearest neighbor algorithm and binomial maximum likelihood analysis. Using this approach we identified five distinct regions of allelic losses defined by their flanking markers and predicted size as follows. p13.3(D16S418-D16S406, 1.2 cM), p13.1(D16S748-D16S287, 12.9 cM), q12 1(D16S409-D16S514, 24.0 cM), q22.1 (D16S496-D16S515, 5.4 cM), and q24 (D16S507-D16S511, 5.9 cM and D16S402-D16S413, 17.4 cM). The regions mapping to p13.1 and q24 were involved in early intraurothelial phases of bladder neoplasia such as mild to moderate dysplasia. On the other hand the deleted region mapping to p13.3 was involved in progression of severe dysplasia/carcinoma in situ to invasive bladder cancer. Testing of markers that exhibited statistically significant LOH in relation to progression of neoplasia from precursor conditions to invasive cancer on 28 tumors and voided urine samples from 25 patients with bladder cancer revealed that q12.1 showed LOH in 46.4% of tumor and 32.0% of voided urine samples. The LOH of a single marker D16S541 could be detected in approximately 28% of tumors and 20% of voided urine samples of patients with bladder cancer. These data imply that the deleted region centered around marker D16S541 spanning approximately 10 cM and flanked by D16S409 and D16S415 contains a novel putative tumor suppressor gene or genes playing an important role in the development of human bladder cancer. To facilitate more precise positional mapping and identification of pathogenetically relevant genes, we analysed of human genome contig and sequence databases spanning the deleted regions. Multiple known candidate genes and several smaller gene-rich areas mapping to the target regions of chromosome 16 were identified.

Aged↗