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Biomedical subjects

Y Samson

Publications and source records attributed to Y Samson.

At least 91 records · Page 5Linked to original sources

[Late neurologic complications of galactosemia: study of 3 cases].

Galactosemia is an autosomal recessive, inborn error of galactose metabolism due to the deficiency of galactose-I-phosphate uridyl transferase. Late-onset neurologic complications may develop despite Galactose restriction. Three adult patients are reported. They suffered from mental retardation. Two of them developed progressive cerebellar ataxia, spastic gait and postural tremor. The magnetic resonance imaging revealed moderate cortical atrophy, multifocal areas of increased signal in the periventricular white matter on T2-weighted images, and in one case, abnormal myelination. The Fluoro-2-deoxy-D-glucose position emission tomography showed different patterns of regional hypometabolism.

Adult↗

Movement- and task-related activations of motor cortical areas: a positron emission tomographic study.

Using repeated measurements of regional cerebral blood flow with positron emission tomography, we investigated the regional cortical activations induced in 10 normal subjects, by two different finger motor tasks, i.e., a repeated flexion-extension of all fingers and a repeated flexion-extension of the middle finger. The all-finger movement only activated the primary sensorimotor cortex (SM) and the supplementary motor area (SMA) contralateral to the movement. However, the activation of the SMA was clearly task related during this motor task, because it was only observed when the movement was triggered by an auditory cue but not when it was self-paced. The middle finger movement was performed during self-paced conditions. It induced a much more complex pattern of activation than the all-finger movement, characterized by a high degree of SM and SMA activation contralateral to the side of the movement, as well as a slight ipsilateral activation of these areas. We suggest that this pattern of cortical activation may reflect the process of individuating finger movement or the early stages of motor learning of this unusual and technically difficult movement. Our data also confirm that the SM activation is closely linked to the intrinsic parameters of the movement; while the SMA may be activated by different aspects of the movement realization and preparation.

Adult↗

Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon.

Several recent reports have suggested that foetal ventral mesencephalic transplants could alleviate motor symptoms in patients with Parkinson's disease. Expectations of future success must be clarified by precise analysis of the extent and limitation of recovery associated with an assessment of function of the graft using [18F]fluorodopa (18F-dopa) PET. Two patients with idiopathic Parkinson's disease, severely impaired despite optimal medication, have been followed 10 and 17 months after stereotaxic unilateral intrastriatal transplantation of neural cells dissociated from human foetal ventral mesencephalon. Analysis of the clinical evolution complied with the protocol established in the 'Core Assessment Program for Intracerebral Transplantation'. Both patients have benefited from the transplantation in their daily activities and in motor timed tests, although they still exhibit parkinsonian symptoms and require L-dopa therapy. This is associated with a gradual increase in 18F-dopa uptake at the site of grafting. There are two major clinical changes: (i) a bilateral motor improvement for the speed of movements (the quality of movements improved almost exclusively on the side contralateral to the graft); (ii) a change in the outcome of the L-dopa treatment as exemplified by a postoperative transient period of heavy dyskinesias and subsequent additive actions of the two treatments. These results confirm that neural transplantation may be useful for patients with Parkinson's disease. The improvement recorded on the side ipsilateral to the graft does not match that observed on the contralateral side and it is proposed that bilateral transplantation may be necessary. The existence of a transient postoperative period of heavy dyskinesias suggests that the patients may benefit from a controlled decrease of L-dopa intake after grafting.

Adult↗

Brain metabolism after recurrent insulin induced hypoglycaemic episodes: a PET study.

Neuropsychological testing was carried out and the rate of oxygen metabolism in the brain was measured by PET in 15 highly selected patients with type 1 diabetes. The aim was to investigate the impact on the brain of hypoglycaemic comas resulting from insulin treatment. No significant difference was found between nine patients with a history of more than 10 hypoglycaemic comas and six others who denied any history of such events. These data suggest that intensified insulin treatment, although increasing the frequency of hypoglycaemic coma, may not always be harmful for the brain. This may be explained by the limited duration of hypoglycaemic coma induced by conventional insulin treatment.

Adult↗

Rest tremor and extrapyramidal symptoms after midbrain haemorrhage: clinical and 18F-dopa PET evaluation.

A 25 year old man had an acute subarachnoid haemorrhage due to the rupture of a right peduncular subthalamic arteriovenous malformation. Seven months later he developed a left rest tremor associated with mild bilateral extrapyramidal symptoms and responsive to levodopa treatment. Surface EMG recording showed synchronous activity of agonist and antagonist muscles in the left limbs. A PET 18F-dopa study showed a large decrease of the Ki value in the right striatum. One year after the stroke a persistent postural component developed in the tremor.

Adult↗

[Cerebral ischemia. Value of measurement of cerebral blood velocity and of oxygen consumption in positron emission tomography].

Simultaneous PET measurement of the regional cerebral blood flow (CBF), oxygen extraction (EO2) and cerebral oxygen consumption (CMRO2) demonstrated two important points for the therapeutic management of cerebral ischaemic accidents (CIA): very rapid alterations of the haemodynamic state (CBF and EO2) and the tissue consequences (CMRO2) to the acute phase of CIA and the considerable pathophysiological heterogeneity of these consequences. These two points explain the difficulties encountered in the development of anti-ischaemic treatments. They show the necessity of developing simple techniques which would allow real-time monitoring of cerebral haemodynamics and the development of lesions following CIA. PET also allowed the direct evaluation of the haemodynamic repercussions of carotid artery occlusion, which are much more severe than suggested by classical data and it is therefore possible that the real frequency of CIA of "haemodynamic" origin is severely underestimated.

Blood Flow Velocity↗

Theoretical aspects of the study of benzodiazepine receptors in infantile autism.

This paper is part of a special section on 'psychopharmacotherapy in children' and focuses on benzodiazepine receptors in autism. Infantile autism in an early and pervasive developmental disorder described by Kanner in 1943. Anatomical, pathological and magnetic resonance imaging studies have indicated changes in the cerebellum and hippocampus of autistic subjects. Given the numerical importance and diffuse benzodiazepine receptors, their study by functional brain imaging methods in vivo could be value in cases of infantile autism as a gauge of neuronal potentiality. The main data concerning benzodiazepine complex are presented. The relations between these data and the neurophysiological hypotheses of autism are discussed.

Adolescent↗

[Positron-emission tomographic study of the dopaminergic system in a case of secondary unilateral tremor after mesencephalic hematoma].

A 30 year-old woman developed a postural and rest tremor of the left hand following a right peduncular post-traumatic hematoma. Two years later, positron emission tomography showed a marked decrease in [18F] fluorodopa uptake contrasting with a normal [76Br] bromolisuride uptake in the right striatum. This suggests that: 1) chronic unilateral dopaminergic striatal denervation may occur without persistent D2 dopaminergic receptor upregulation in humans; and 2) symptomatic mesencephalic tremor may be, at least in part, related to dopaminergic striatal denervation.

Adult↗

Regional cerebral blood flow in childhood autism: a SPECT study.

OBJECTIVE: The authors investigated a possible cortical brain dysfunction associated with infantile autism. METHOD: They measured regional cerebral blood flow with single photon emission computed tomography (SPECT) and xenon-133 in 21 children with primary autism (according to DSM-III-R criteria). Five cortical brain areas including frontal, temporal, and sensory association cortices were examined in order to test the recent hypothesis of cerebral dysfunction in primary autism. Anatomical references for each subject were obtained with computerized tomography or magnetic resonance imaging and were used to delimit the regions of interest for SPECT analysis. RESULTS: When the results from the group with primary autism were compared with an age-matched group of nonautistic children with slight to moderate language disorders (N = 14), no cortical regional abnormalities were found. CONCLUSIONS: It appears that there is no regional cortical dysfunction in primary autism; however, in light of methodological limitations, one cannot exclude the possibility of more localized or subcortical brain dysfunctions in autism.

Autistic Disorder↗

Decreased cerebral glucose utilization in myotonic dystrophy.

To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease.

Adult↗

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates.

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

Acetylcarnitine↗

Loss of hippocampal acetylcholinesterase staining after fornix lesion in the monkey.

Cholinergic denervation of the hippocampal formation has been extensively studied in rodents but not in primates. Therefore we studied the changes in acetylcholinesterase histochemical staining of the hippocampus occurring after bilateral transection of the fornices in the cynomolgus monkey. Animals were sacrificed 1.5, 6, 13, and 23 weeks after surgery. We found a 40-50% reduction in the density of acetylcholinesterase-positive fibers in the four analyzed regions (dentate gyrus, CA3, CA1, and subiculum) 1.5 week after surgery and a 60-80% reduction at longer time intervals. The characteristic diffuse AChE staining found in hippocampi from control animals disappeared after fornix lesion, except in the inner third of the molecular layer of the dentate gyrus. We did not find any evidence of spontaneous cholinergic reinnervation over the 6-month period. Thus, as in rats, fornix lesion produces dramatic changes in hippocampal AChE staining, presumably caused by a massive cholinergic denervation. However, in contrast to rodents, spontaneous reinnervation does not seem to occur in the months following the lesion in primates.

Acetylcholinesterase↗

PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report.

The utility of the peripheral type benzodiazepine site ligand 11C-PK 11195, for imaging human glioma in conjunction with Positron Emission Tomography, relies on a high specific binding of the tracer to tumoral peripheral type benzodiazepines sites. In a patient with glioblastoma, we found that 11C-PK 11195 binding was two-fold higher in the tumor than in normal gray matter and that 30% of tumoral binding could be displaced by a large excess of unlabeled drug. These findings suggest that tumoral retention of the ligand is due, in part, to specific binding.

Aged↗

Catecholaminergic innervation of the hippocampus in the cynomolgus monkey.

We studied the immunocytochemical distribution of catecholaminergic fibers in the hippocampal formation from two cynomolgus monkeys by using phenylethanolamine-N-methyltransferase, dopamine-beta-hydroxylase, and tyrosine-hydroxylase antibodies. There were no phenylethanolamine-N-methyltransferase immunoreactive fibers suggesting the lack of epinephrine containing fibers. In order to compare the distributions of tyrosine-hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers, we counted fibers in four hippocampal regions, the dentate gyrus, CA3, CA1, and the subiculum at three different rostrocaudal levels. The distributions of dopamine-beta-hydroxylase and tyrosine-hydroxylase immunoreactive fibers were overlapping but clearly different, suggesting that the hippocampus receives both noradrenergic and dopaminergic inputs in primates. Dopamine-beta-hydroxylase-immunoreactive fibers were present in moderate density and roughly evenly distributed throughout the hippocampus. Tyrosine-hydroxylase immunoreactive fibers were found in high density in the dentate gyrus, in the stratum lacunosum-moleculare, and in the molecular layer of the subiculum. There were only minor side-side and rostrocaudal differences in the distribution of tyrosine-hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers. The identification of a putative dopaminergic projection to primate hippocampus, which is more dense and widely distributed than in the rodent, parallels similar increases in dopaminergic projections reported for primate cerebral neocortex.

Animals↗

Positron emission tomography study of brain benzodiazepine receptors in Friedreich's ataxia.

Central type benzodiazepine receptors were studied in 9 patients with Friedreich's ataxia and 12 healthy subjects using positron emission tomography (PET) and [11C]Ro 15-1788, a specific antagonist of the central type benzodiazepine receptors, as radioligand. A standard PET procedure was used in 5 patients and 8 controls to obtain brain kinetics of the total binding of the radioligand. The remaining subjects were intravenously injected with a saturating dose of unlabeled Ro 15-1788, 30 minutes after the tracer injection, to determine the nondisplaceable binding of [11C]Ro 15-1788. A semi-quantitative method was used to quantify the [11C]Ro 15-1788 data. None of the quantification indices in the cerebellar hemispheres, or in the other brain areas investigated, was significantly modified in patients with Friedreich's ataxia. These findings suggest that brain benzodiazepine receptors are unaffected in Friedreich's ataxia.

Adult↗

Regional specific binding of [11C]RO 15 1788 to central type benzodiazepine receptors in human brain: quantitative evaluation by PET.

The central type benzodiazepine receptors were studied in 17 healthy human subjects with 11C-RO 15 1788 and positron emission tomography (PET). The brain regional distribution of the tracer in eight control studies performed after injection of trace doses of 11C-RO 15 1788 was consistent with that of benzodiazepine receptors. Saturation studies with co-injected cold RO 15 1788 in the remaining subjects showed a dose-dependent decrease of brain radiotracer until full inhibition of specific binding was achieved with doses above 0.1 mg/kg (four studies). Based on the results, a simple method to estimate the specifically bound 11C-RO 15 1788 regionally in a single PET study is proposed, using the data from the full-saturation studies as a stable estimate of the nondisplaceable radioligand concentration. Using this method, it was found that quasiequilibrium between the estimated specifically bound and nondisplaceable components was achieved at times equal to or longer than 20 min after tracer administration. The validity of this method was partly supported by further results, showing a good agreement between the regional specific binding so calculated and postmortem data of receptor density.

Adult↗