Search PubMed⌕ Search

Biomedical subjects

D Le Bars

Publications and source records attributed to D Le Bars.

At least 37 records · Page 2Linked to original sources
PubMed2000

Renal blood flow measurement by positron emission tomography using 15O-labeled water.

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Animals↗
PubMed2000

Rectal sensitivity assessed by a reflexologic technique: further evidence for two types of mechanoreceptors.

We previously showed that slow-ramp rectal distensions induce graded inhibitions of the somatic nociceptive RIII reflex recorded from the lower limb, which correlated with both distension volume and visceral sensation. In contrast, rapid phasic rectal distensions induced facilitatory or biphasic effects (i.e., facilitations followed by inhibitions) depending on the level of distension. To examine the role of mucosal and serosal rectal mechanoreceptors in these viscerosomatic interactions, we analyzed, in six healthy volunteers, the effects of both types of rectal distension on the RIII reflex after topical application of lidocaine or placebo administered in a double-blind and crossover fashion. Inhibitions of the RIII reflex induced by both slow-ramp and rapid distensions were strongly reduced after administration of lidocaine but not after placebo. In contrast, facilitations of the RIII reflex observed during the initial phase of rapid distensions were not modified after lidocaine or placebo applications. These results suggest that inhibitions, but not facilitations, of the nociceptive RIII reflex triggered by rectal distensions depend preferentially on the activation of superficial mucosal receptors. This reflexologic technique might thus represent an interesting tool for studying the role of the different rectal mechanoreceptors involved in visceral sensations.

Adult↗
PubMed1999

Transient and falsely lateralizing flumazenil-PET asymmetries in temporal lobe epilepsy.

We have observed a falsely lateralizing mesial temporal [11C]-flumazenil binding asymmetry in three patients who had temporal lobe epilepsy (TLE) with normal hippocampal volumes. This abnormality was not detected 3 months later in two of the patients who underwent a second PET study. We conclude that transient and falsely lateralizing changes of flumazenil binding might occur in patients with TLE and no hippocampal sclerosis.

Adult↗
PubMed1999

Ventromedial thalamic neurons convey nociceptive signals from the whole body surface to the dorsolateral neocortex.

The somatosensory properties of ventromedial (VM) thalamic neurons were investigated in anesthetized rats by examining their responses to calibrated cutaneous stimuli. A population of neurons within the lateral part of the ventromedial thalamus (VMl) showed two peaks of activation after percutaneous electrical stimuli, regardless of which part of the body was stimulated. The early and late peaks were elicited by Adelta- and C-fiber activities with mean conduction velocities of 12.9 +/- 0.9 and 1 +/- 0.2 m/sec, respectively. These responses were strongly depressed or blocked after microinjections within the medullary subnucleus reticularis dorsalis of xylocaine or the NMDA antagonist MK-801. None of the VMl neurons responded to innocuous cutaneous or proprioceptive stimuli. In contrast, all these neurons responded to noxious mechanical and thermal stimulation of the limbs and showed monotonic increases in their discharges to increasingly strong noxious cutaneous stimuli. In addition, some VMl neurons were antidromically activated by stimulation in layer I of the dorsolateral frontal cortex. These findings suggest that the rat VMl conveys and encodes cutaneous nociceptive inputs from any part of the body surface to layer I of the dorsolateral neocortex. This reticulo-thalamo-cortical network may allow any signal of pain to gain access to widespread areas of the neocortex and thus help prime the cortex for attentional reactions and/or the coordination of motor responses.

Animals↗
PubMed1999

Organization of cortical projections to the medullary subnucleus reticularis dorsalis: a retrograde and anterograde tracing study in the rat.

The distribution and organization of cortical projections to the subnucleus reticularis dorsalis (SRD), the neighboring cuneate nucleus (Cu), and trigeminal nucleus caudalis (Sp5C) were studied in the rat using microinjections of wheat germ agglutinin-apo horseradish peroxidase-gold and Biotin-Dextran. Cortical cells projecting to the caudal medulla were confined to the contralateral layer V with their descending axons crossing the midline at the level of pyramidal decussation. Cortical afferents to Sp5C originated from cells located mainly in the primary somatosensory cortex (S1) and the insular cortex, whereas cortical projections to the Cu originated mainly from the primary motor cortex (M1), the primary and secondary somatosensory cortex (S1 and S2). The SRD received dense cortical afferents from larger, widespread cortical areas: M1, M2, S1, S2, and the insular cortex. The existence of dense cortico-SRD connections supports the possibility of a pyramidal influence over SRD neurons, which might modify nociceptive information ascending to the cortex itself. This proposal is consistent with the fact that SRD efferents terminate densely in thalamic areas that influence sensorimotor cortical regions which in turn project to the SRD. Moreover, these corticofugal mechanisms could allow the cortex to select its own input by suppressing or augmenting transmission of signals through SRD-hindbrain/forebrain pathways or by coordinating activities in spino-SRD-spinal circuits and thus selecting the relevant information produced by the noxious stimulus.

Animals↗
PubMed1999

Alteration of descending modulation of nociception during the course of monoarthritis in the rat.

Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures and modulate the transmission of nociceptive signals, were investigated at different stages during the development of adjuvant-induced monoarthritis in the rat. After behavioral evaluation, recordings of trigeminal convergent neurons were performed in anesthetized animals with acute (24-48 hr) or chronic (3-4 weeks) monoarthritis of the ankle. Inhibitions of C-fiber-evoked neuronal responses during and after the application of noxious conditioning stimuli to the ankle were measured to evaluate DNIC. The conditioning stimuli consisted of mechanical (maximal flexion and graded pressures) and graded thermal stimuli and were applied alternately to normal and arthritic ankles. Behaviorally, the two groups of animals exhibited a similar increased sensitivity to mechanical stimuli applied to the arthritic joint (i.e., an increased ankle-bend score and a decreased vocalization threshold to pressure stimuli). However, they showed different electrophysiological profiles. In the animals with acute monoarthritis, the DNIC-induced inhibitions produced by mechanical or thermal stimulation of the arthritic joint were significantly increased at all intensities compared with the normal joint. In contrast, in the chronic stage of monoarthritis, the DNIC-induced inhibitions triggered by thermal or pressure stimuli were similar for both ankles, except with the most intense mechanical stimuli. This discrepancy between the behavioral and electrophysiological findings suggests that inputs activated during chronic monoarthritis may fail to recruit DNIC and may thus be functionally different from those activated in the acute stage of inflammation.

Animals↗
PubMed1999

Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study.

Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results.

Adult↗
PubMed1999

[Neurophysiological bases of the counterirritation phenomenon:diffuse control inhibitors induced by nociceptive stimulation].

To define the counterirritation phenomenon, we might refer to the Hippocratic aphorism: 'If two sufferings take place at the same time, but at different points, the stronger one makes the weaker silent'. On the basis of this clinically common observation, often used advantageously by the patients themselves, a number of therapeutic methods have been developed which are grouped under the terms counterirritation or counterstimulation. This phenomenon has not been scientifically analysed until recent years. Experimental results gathered during the last decade have shown that counterirritation phenomena have a well-defined neural substrate both in animals and in man. In particular, they have proved not to rely on segmental mechanisms, but rather imply spino-bulbo-spinal loops involving ascending pathways in the anterolateral spinal columns, integration in the lower brain stem, and descending influences reaching dorsal horn neurons via the dorsolateral quadrant. The results also suggest that the study of counterirritation is essential for accessing the physiology of nociception and pain control. The very existence of the counterirritation phenomenon is the easiest demonstrable index of a specific system for pain modulation in man. Besides its scientific interest, the elucidation of its neurophysiological bases has clinical importance, in as much as it may ameliorate our understanding of certain pain syndromes and contribute to the development of new investigative and therapeutic procedures.

Animals↗
PubMed1999

Neuroanatomical correlates of visually evoked sexual arousal in human males.

Brain areas activated in human male sexual behavior have not been characterized precisely. For the first time, positron emission tomography (PET) was used to identify the brain areas activated in healthy males experiencing visually evoked sexual arousal. Eight male subjects underwent six measurements of regional brain activity following the administration of [15O]H2O as they viewed three categories of film clips: sexually explicit clips, emotionally neutral control clips, and humorous control clips inducing positive but nonsexual emotions. Statistical Parametric Mapping was used to identify brain regions demonstrating an increased activity associated with the sexual response to the visual stimulus. Visually evoked sexual arousal was characterized by a threefold pattern of activation: the bilateral activation of the inferior temporal cortex, a visual association area; the activation of the right insula and right inferior frontal cortex, which are two paralimbic areas relating highly processed sensory information with motivational states; and the activation of the left anterior cingulate cortex, another paralimbic area known to control autonomic and neuroendocrine functions. Activation of some of these areas was positively correlated with plasma testosterone levels. Although this study should be considered preliminary, it identified brain regions whose activation was correlated with visually evoked sexual arousal in males.

Adult↗
PubMed1999

Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.

BACKGROUND: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. METHODS: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. CONCLUSIONS: Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.

Analgesics, Opioid↗
PubMed1999

Functional anatomy of perceptual and semantic processing for odors.

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.

Adult↗
PubMed1998

The influence of temporal summation on a C-fibre reflex in the rat: effects of lesions in the rostral ventromedial medulla (RVM).

In intact rats, an inhibitory mechanism counteracts the increase in excitability of a flexor reflex seen in spinal animals following high-intensity, repetitive stimulation of C-fibres. We tested the hypothesis that the rostral ventromedial medulla (RVM) is involved in these processes. Electromyographic responses elicited by electrical stimulation of the sural nerve, were recorded from the ipsilateral biceps femoris in halothane-anaesthetised, sham-operated or RVM-lesioned rats. There were no significant differences between the C-fibre reflexes in the two groups in terms of their thresholds, latencies, durations or mean recruitment curves. The excitability of the C-fibre reflex was tested following 20 s of high-intensity homotopic electrical conditioning stimuli at 1 Hz. During the conditioning period, the EMG responses first increased in both groups (the wind-up phenomenon), but then decreased in the sham-operated rats and plateaued in the RVM-lesioned rats. These effects were followed by inhibitions that were very much smaller in the RVM-lesioned rats, both in terms of their magnitudes and their durations. It is concluded that the RVM is involved in inhibitory feedback mechanisms elicited by temporal summation of C-fibre afferents that both counteract the wind-up phenomenon and trigger long periods of inhibition.

Animals↗
PubMed1998

An electrophysiological investigation into the monosynaptic H-reflex in the rat.

In order to set up a non-invasive, reliable and reproducible model for investigating alpha-motoneuronal activity, we studied the electrophysiological features of a monosynaptic H-reflex in anaesthetised intact rats, anaesthetised and non-anaesthetised rats transected at the level of the obex. Electrical stimulation of the tibial nerve at the ankle elicited an H-reflex, an F-wave and a direct motor (M) response in the plantaris muscles of all preparations. The H-reflex and F-wave exhibited very similar latencies. The H-reflex had a low threshold and a constant latency. Its amplitude increased as a function of stimulus intensity to reach a maximum value but then decreased when the stimulus intensity was further increased. It could follow high rates of stimulation without any change in shape or latency. The F-wave had a lower amplitude which together with its latency varied from one stimulus to the next. It appeared with intensities of stimulation that elicited an almost maximal M-response and did not decrease when the stimulation was increased. It did not appear systematically from one stimulus to the next. The H-reflex, but neither the F-wave nor the direct motor M-response, was depressed both by vibratory stimuli applied on the Achilles' tendon and following nociceptive stimulation of the flexor reflex afferents. This model could be used for assessing any potential direct effect on motoneurones of a physiological or pharmacological conditioning procedure.

Achilles Tendon↗
PubMed1998

Organization of diencephalic projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a retrograde and anterograde tracer study in the rat.

The distribution and organization of diencephalic projections from the subnucleus reticularis dorsalis (SRD) and the neighbouring cuneate nucleus (Cu) were studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin in SRD and Cu and wheat germ agglutinin-apo horseradish peroxidase-gold in some selected thalamic areas. As previously reported, the efferent projections from the Cu were essentially contralateral and terminated mainly in the ventroposterolateral thalamic nucleus. Less dense terminals from the Cu were also observed in the posterior thalamic group, the ventral aspect of the zona incerta and the caudal and dorsal portion of the reuniens area. Retrograde tracer injections in the medial ventroposterolateral thalamic nucleus labeled numerous cells in the contralateral Cu, with a smaller number in the gracile nucleus. From the SRD, terminals were observed in the lateral aspect of the ventromedial thalamic nucleus, the lateral parafascicular area and, to a lesser extent, in the ventral aspect of the zona incerta and the core of the reuniens area. Retrograde tracer injections in the lateral part of the ventromedial thalamic nucleus labeled cells in the caudal medulla, many of which were located in the dorsal-most aspect of the SRD throughout its caudo-rostral extent. The existence of SRD-thalamic connections reinforces the idea that the caudal reticular formation is an important nociceptive relay to the thalamus. Our data shed new light on old hypotheses suggesting that, in addition to spino-thalamic pathways, spino-reticulo-thalamic pathways may play an important role in distributing pain signals to the forebrain.

Animals↗
PubMed1998

Effect of analgesics on audible and ultrasonic pain-induced vocalization in the rat.

Brief electrical pulses applied to the rat tail elicit a complex vocal response which includes audible (peeps, chatters) and ultrasonic (USV) components. Aspirin and amitriptyline had no effect on the vocal responses. Morphine showed a dose-dependent and naloxone reversible antinociceptive effect on the 1st and 2nd audible peeps by decreasing their intensity (evaluated by their envelopes which correspond to the outer bounds of the soundwave amplitude plotted as a function of time), with ED50 values of 1.96 mg/kg and 0.36 mg/kg i.v. respectively. Paracetamol significantly reduced only the intensity of the second peep at the dose of 200 mg/kg iv. Chatter intensity was decreased by doses of 1 and 3 mg/kg i.v. of morphine which would suggest an effect on emotional components of pain. The intensity of USV was affected by morphine injection although the variations observed were non-significant. These data clearly implicate a specific role for the opioid analgesics in modifying the vocal pain related behaviors.

Amitriptyline↗
PubMed1998

High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635.

No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis. Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand.

Animals↗
PubMed1998

Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients.

We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery.

Brain↗