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  • 1
    Electronic Resource
    Electronic Resource
    Typical and Atypical Neuroleptics Induce Alteration in Blood-Brain Barrier and Brain 59FeCl3 Uptake (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Long-term neuroleptic medication of schizophrenic patients induces extrapyramidal motor side effects, of which tardive dyskinesia (TD) is the most severe. The etiology of TD is still obscure. Recently, it was suggested that abnormal iron metabolism may play a crucial role in neuroleptic-induced dopamine D2 receptor super-sensitivity. The apparent relationship between neuroleptics and iron is further supported by the increase of iron in the basal ganglia of patients with TD. We now report on the ability of neuroleptics to alter the blood-brain barrier in the rat and to potentiate the normally limited iron transport into the brain. Thus, chronic treatment of rats with chlorpromazine and haloperidol facilitated 59Fe3+ uptake into brain cells. In contrast, clozapine, an atypical antipsychotic neuroleptic with little extrapyramidal motor side effects, caused iron sedimentation in brain blood vessels with no sign of detectable iron in the cells. Moreover, chronic treatment with chlorpromazine and haloperidol caused a 43% and 24% reduction, respectively, in liver nonheme iron, whereas clozapine induced an 81% increase. The apparent different potentials of chlorpromazine, haloperidol, and clozapine to increase iron transport into the brain from its peripheral stores may be linked to the severity of extrapyramidal motor side effects they induce and to the pathophysiology of TD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62031112.x
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  • 2
    Electronic Resource
    Electronic Resource
    Changes in reward-induced brain activation in opiate addicts (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 14 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H215O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01753.x
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  • 3
    Electronic Resource
    Electronic Resource
    How does the human brain deal with a spinal cord injury? (1998)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The primary sensorimotor cortex of the adult brain is capable of significant reorganization of topographic maps after deafferentation and de-efferentation. Here we show that patients with spinal cord injury exhibit extensive changes in the activation of cortical and subcortical brain areas during hand movements, irrespective of normal (paraplegic) or impaired (tetraplegic patients) hand function. Positron emission tomography ([15O]-H2O-PET) revealed not only an expansion of the cortical ‘hand area' towards the cortical ‘leg area', but also an enhanced bilateral activation of the thalamus and cerebellum. The areas of the brain which were activated were qualitatively the same in both paraplegic and tetraplegic patients, but differed quantitatively as a function of the level of their spinal cord injury. We postulate that the changes in brain activation following spinal cord injury may reflect an adaptation of hand movement to a new body reference scheme secondary to a reduced and altered spino-thalamic and spino-cerebellar input.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1998.00454.x
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  • 4
    Electronic Resource
    Electronic Resource
    Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers (2003)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 18 (2003), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study investigated the processing of increasing monetary reward in nonsmoking and smoking subjects. The choice of the subject populations has been motivated by the observation of differences between nonsmokers and smokers in response to rewarding stimuli in a previous study. Subjects performed a pattern recognition task with delayed response, while rCBF was measured with [\mathrm{H}^{15}_{2}O] PET. Correct responses to the task were reinforced with three different amounts of monetary reward. The subjects received the sum of the rewards at the end of the experiment. The results show that a cortico-subcortical loop, including the dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus and the thalamus is involved in processing increasing monetary reward. Furthermore, the striatal response differentiates nonsmokers from smokers. Thus, we found significant correlations between rCBF increases in striatum and increasing monetary reward and between striatal rCBF increases and mood in nonsmokers, but not in smokers. Moreover, no significant mood changes among the different monetary rewards could be observed in smokers. We infer that the response of the striatum to reward is related to changes in subjective feelings. The differences between smokers and nonsmokers confirm our previous conclusions that the association between blood flow, performance, mood and amount of reward is more direct in nonsmokers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2003.02791.x
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  • 5
    Electronic Resource
    Electronic Resource
    Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET) (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 135-140 
    Details
    ISSN: 1432-1041
    Keywords: Savoxepine ; Neuroleptic drug ; dopamine D2 receptor antagonist ; positron emission tomography ; striatal receptor binding ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50–60% after 24–36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3–7 h after administration and amounted to 40 to 75% at the peak time (20–29 h). This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315470
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  • 6
    Electronic Resource
    Electronic Resource
    Somatosensory discrimination of shape: prediction of success in normal volunteers and parkinsonian patients (1998)
    Springer
    Experimental brain research 120 (1998), S. 104-108 
    Details
    ISSN: 1432-1106
    Keywords: Key words Somatosensory discrimination ; Tactile exploration ; Macrogeometric objects ; Information processing ; Perception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tactile discrimination of macrogeometric objects in a two-alternative forced-choice procedure represents a complex task including somatosensory and higher-order cognitive processing. The objects for somatosensory discrimination were rectangular parallelepipeds that differed in oblongness only. They were presented in sequential pairs to 12 normal volunteers and 13 parkinsonian patients. Owing to the dichotomy of the task, we calculated estimates of the probability of a correct answer by a binomial approach. The probability of a correct answer could be calculated on the basis of a logistic model ensuring that the probability values lie in the interval [0, 1]. The relationship between the probability of a correct answer and the difference in oblongness of the objects could be described solely by one coefficient determined by logistic regression. This coefficient summarized the effectiveness of the simultaneous and consecutive operations inherent in the task and allowed characterization of performances in groups and individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050382
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  • 7
    Electronic Resource
    Electronic Resource
    A Positron Emission Tomography Analysis of Glucose Metabolism in Alzheimer's Disease Brain Using [18F] Fluorodeoxyglucose: A Parallel Study with Elemental Concentrations (2000)
    Springer
    Journal of radioanalytical and nuclear chemistry 244 (2000), S. 179-184 
    Details
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Alzheimer's disease (AD) is a debilitating form of dementia which leads to impaired memory, thinking and behavior. This work examines elemental concentrations between "normal" and AD subjects as well as the hemispherical differences within the brain. Tissue samples from both hemispheres of the frontal lobe in both AD and normal subjects were examined for their trace element concentrations using PIXE and RBS analyses. Elemental concentrations were seen to differ between AD and normal brain tissue samples. While in the normal group concentrations were found to be significantly higher in the right hemisphere than in the left the converse was true in AD. A change in elemental concentrations may indicate possible alterations in the function of the blood brain barrier. This was examined by determining regional cerebral metabolic rates of glucose (rCMRGlu) using the in vivo technique of positron emission tomography (PET). Again variations between both hemispheres and between AD and normal were found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006792905118
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  • 8
    Electronic Resource
    Electronic Resource
    PET: Blood flow and oxygen consumption in brain tumors (1994)
    Springer
    Journal of neuro-oncology 22 (1994), S. 269-273 
    Details
    ISSN: 1573-7373
    Keywords: positron emission tomography ; brain tumors ; blood flow ; oxygen consumption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue perfusion and cerebral energy metabolism in brain tumor patients are regionally abnormal, and certain patterns of pathological changes may be demonstrated in and around tumor tissue. Tumor CBF may vary widely between subjects, whereas oxygen extraction is almost always markedly reduced. This is in apparent contradiction with the tumor tissue oxygen tension data (see previous chapter): since these are low, an increase of OER would be expected. Still, as discussed above, oxygen consumption calculated from oxygen tension or PET data yield the same relative decreases (0.3) of tumor oxygen utilization compared to normal brain. This suggests that the characteristic pathological changes of tumor cell energy metabolism have diminished oxygen demand and changed the level of coupling between CBF and OER. Since all published data on OER in tumor patients have been obtained by the steady state method, possibly resulting in an underestimation of OER, it will be mandatory to apply dynamic oxygen uptake measurements to circumvent this methodological problem and e.g. to make use of distribution volume of water to correct for tissue composition as has been reported in one paper studying patients with breast tumors. Because of the conspicuous regional changes in tumor oxygen metabolism it is expected that effectivity of chemotherapeutic measures is directly reflected by characteristical adaptations of metabolism. Systematic studies in this context have not been reported to date. Whether oxygen metabolism changes would be more sensitive than just CBF measurements as indicator of treatment effectivity remains to be seen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01052932
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  • 9
    Electronic Resource
    Electronic Resource
    Brain tumor iron uptake measured with positron emission tomography and 52Fe-citrate (1996)
    Springer
    Journal of neuro-oncology 29 (1996), S. 157-165 
    Details
    ISSN: 1573-7373
    Keywords: brain tumor ; iron-transferrin ; positron emission tomography ; blood-brain barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Iron and transferrin are required for DNA synthesis and cell division. Cellular iron uptake is mediated by transferrin receptors. In order to investigate whether iron uptake in brain tumors is associated with their histological grade, we studied 24 patients (5 astrocytoma, 11 glioblastoma, 8 meningioma) using positron emission tomography and 12 Fe-citrate. Tracer uptake from blood into brain and tumor tissue was assessed 1. using multiple time graphical analysis yielding a measure for unidirectional net tracer uptake (Ki and 2.) testing a one- and two-tissue kinetic compartment model, where K1 denotes tracer uptake from blood into tissue, k2 efflux from tissue into plasma, and 0 specific tracer binding. In the plasma, 52Fe was bound to a 80 kD protein (transferrin). Ki (in units of 10−5/min) was higher in glioblastomas (Ki mean ± SD 13.6 ± 6.1) compared with astrocytomas (4.8 ± 3.5, Mann Whitney p = 0.015) and contralateral brain (2.2 ± 0.9, Mann Whitney p = 0.009). Highest values were found in meningiomas (no blood-brain barrier (BBB); Ki 33.4 ± 16.5, Mann Whitney p = 0.008 compared with glioblastomas). Among the compartment models, fitting with Kl1 and regional plasma volume explained the data best (one-tissue model), data fits were not significantly improved by addition of a k2 or k3 parameter. K1 and Ki values were significantly correlated (Spearman Rank, p = 0.0006). We conclude that 52Fe accumulation in tumors is governed by tracer uptake at the BBB, and does not reflect number of transferrin receptors at the level of tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00182139
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  • 10
    Electronic Resource
    Electronic Resource
    Introduction (1994)
    Springer
    Journal of neuro-oncology 22 (1994), S. 237-237 
    Details
    ISSN: 1573-7373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01052926
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