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J Blin

Publications and source records attributed to J Blin.

34 records · Page 2Linked to original sources
PubMed1991

Regional cerebral glucose metabolism compared in rodents and humans.

In order to compare regional brain glucose metabolism in rats and humans, this parameter was measured using Sokoloff's deoxyglucose method in rats, and positron emission tomography with magnetic resonance imaging in humans. An atlas of cerebral regions of interest common to both species was developed to facilitate the evaluation of the relationship in regional values. We found among the regions studied a significant positive correlation in their metabolic values (r = 0.72, P less than 0.001) and coefficients of variation (r = 0.59, P less than 0.01) suggesting that regional brain glucose consumption is comparable between rat and human. Results of this study support the view that rat and human brain may be phylogenetically linked functionally as well as anatomically.

Aged↗
PubMed1991

PET studies of [18F]methyl-MK-801, a potential NMDA receptor complex radioligand.

Using positron emission tomography (PET), the potential of 18F-labelled fluoro-methyl-MK-801([18F]FMM) as a radioligand for in vivo studies of the NMDA receptor complex was investigated in baboons. In baseline conditions, there was a slight differential retention of [18F]FMM in cerebral cortex and striatum relative to cerebellum, compatible with specific binding. However, neither pretreatment with pharmacological doses of MK-801 or phencyclidine, nor severe, transient brain hypoxia, were able to clearly alter [18]FMM brain regional kinetics, indicating limited usefulness of this radioligand for in vivo PET investigations of the NMDA receptor.

Animals↗
PubMed1991

Somatostatin replacement therapy for Alzheimer dementia.

Somatostatin is consistently diminished in brains of patients with Alzheimer's disease. To evaluate whether pharmacological restoration of this transmitter deficit has therapeutic value, the synthetic analogue octreotide was administered intravenously to 14 Alzheimer patients under double-blind, placebo-controlled conditions. At the highest dose administered, spinal fluid concentrations approximated those found in brains of experimental animals receiving behaviorally effective amounts of the drug. Neuropsychological testing, however, showed no clinically significant improvement. Coadministration of octreotide and physostigmine to 1 patient also failed to improve cognition. Positron emission tomographic studies in 6 patients revealed a generalized decrease in glucose metabolism as a result of octreotide infusion. These findings suggest that stimulation of the somatostatin system has no value in the symptomatic treatment of Alzheimer dementia.

Aged↗
PubMed1991

PET studies of cortical diaschisis in patients with motor hemi-neglect.

Six patients presenting with multimodal, predominantly motor hemi-neglect, were investigated by 15O2 or 18F-DG and PET to study the local cerebral metabolism in intact regions. All had suffered from an acute right-sided (n = 5) or left-sided (n = 1) focal hemispheric lesion (cortico-subcortical and purely subcortical in three patients each). Frontal and parietal cortices on the side of the lesion were significantly hypometabolic relative to the other side in each case, presumably as a result of diaschisis, whereas thalamic hypometabolism was significant in only 4 patients. Compared to absolute metabolic rates for controls, the uninjured hemisphere showed a trend towards hypometabolism. Hence, true hyperactivity of the contralateral hemisphere with respect to the ipsilateral cerebral cortex was not associated with motor hemineglect in this series. On the contrary, hemineglect was associated with a widespread hypometabolism of the entire ipsilateral cerebral cortex in the context of a moderately reduced metabolism of the ipsilateral thalamus and contralateral cerebral cortex. These findings are consistent with the implication of a cortico-subcortical network serving attention.

Aged↗
PubMed1991

Does ageing aggravate parkinsonian disability?

The influence of age of onset of Parkinson's disease on the severity and the pattern of motor symptoms was investigated by comparing the motor scores with and without levodopa therapy in two groups of patients divided according to age of onset (early less than 50, late greater than 60 years) and matched for disease duration (n = 69 in each group, Study I). The baseline score, that is, the motor disability of patients when off levodopa, was similar in the early- and late- onset groups. In contrast, the residual motor score, assessed when the effect of levodopa treatment was maximum and stable, was significantly higher in the late onset group. When the two groups of patients were matched, in addition, for their residual motor score, (n = 54 in each group, Study II), no difference was observed between the early and late onset groups, except for gait disorder which was more severe in older patients. These results suggest that age of onset mainly affects the response to levodopa therapy, because it may increase the prevalence of non-dopaminergic lesions of the brain, including those responsible for gait disorders.

Age Factors↗
PubMed1991

Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam.

The cognitive-enhancing effects of pramiracetam in animal models of learning and memory are characterized by an inverted U-shaped dose-response curve. We evaluated antidementia efficacy of this drug in 10 patients with probable Alzheimer's disease employing a 2-phase, placebo-controlled, enrichment-type trial design. Eight patients evidenced a best dose in the dose-finding phase, but in the subsequent replication phase only two again improved to a similar degree. PETs with fluorodeoxyglucose obtained in two individuals showed no definite change. Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.

Aged↗
PubMed1990

Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations.

In 41 patients with progressive supranuclear palsy (PSP) that was diagnosed on the basis of eight clinical criteria (25 patients with all eight criteria [probable PSP] and 16 with six or seven criteria [possible PSP]), we studied cerebral energy metabolism by using positron emission tomography and the fludeoxyglucose F 18 or the oxygen 15 method. Compared with age-matched controls, each of the cortical and subcortical metabolic values was significantly reduced, with a predominance in the frontal cortex, in both groups of patients with probable and possible PSP, without a difference between these two groups, suggesting similar underlying disease. The frontal metabolic value decreased with disease duration, but the relative frontal hypometabolism (expressed as the fronto-occipital metabolic ratio) was apparently already present in the early stages of the disease. The parkinsonian motor score was correlated with the caudate and thalamic metabolic values. The intellectual deterioration index was significantly correlated with both the frontal and the nonfrontal metabolic values. Finally, the frontal neuropsychological score was significantly correlated with only the fronto-occipital metabolic ratio. Hence, in PSP, a degenerative brain disease with subcortical lesions, the prominent frontal lobe-like syndrome essentially depends on the relative hypometabolism of the frontal cortex.

Aged↗
PubMed1990

A method for the in vivo investigation of the serotonergic 5-HT2 receptors in the human cerebral cortex using positron emission tomography and 18F-labeled setoperone.

Following previous validation in baboons, we have studied the characteristics of [18F]setoperone as a radioligand for investigating serotonergic 5-hydroxytryptamine2 (5-HT2) receptors in the normal, unmedicated human brain with positron emission tomography (PET); subjects orally pretreated with therapeutic amounts of ketanserin, sulpiride, or prazosin were also studied to evaluate the specificity and sensitivity of [18F]setoperone brain specific binding. In controls (n = 10), the tracer showed a clear-cut retention in both frontal cortex and striatum (known to contain a high density of 5-HT2 receptors) relative to cerebellum (known to be devoid of 5-HT2 receptors). In the seven young controls (20-39 years old), the frontal cortex/cerebellum and striatum/cerebellum ratios increased during the first hour to reach similar values of 2.53 +/- 0.12 and 2.38 +/- 0.11 (mean +/- SEM), respectively, and were essentially stable during the second hour. Pretreatment with ketanserin (a 5-HT2 blocker) significantly reduced the frontal cortex/cerebellum ratio to 0.7-1.0 at 65 min, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. During sulpiride treatment (a D2 blocker), the frontal cortex/cerebellum ratio was not altered, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. With prazosin pretreatment (an alpha 1-adrenergic blocker), neither the frontal cortex/cerebellum nor the striatum/cerebellum ratio was modified. These data in humans with PET demonstrate that [18F]setoperone labels with high sensitivity and selectivity 5-HT2 receptors in the frontal cortex; in striata, however, binding is to both 5-HT2 and D2 receptors. The deproteinated-to-whole plasma radio-activity concentration ratio increased with time following injection. The mean percentage of intact [18F]setoperone, in deproteinated plasma, was 82, 74, 53, 45, 30, and 22% at 5, 10, 20, 30, 60, and 110 min following injection, respectively. These data indicate that [18F]setoperone (a) is significantly bound to plasma proteins and (b) is significantly metabolized into several labeled metabolites that are much more hydrophilic than setoperone and, hence, presumably do not cross the blood-brain barrier. These results suggest the suitability of [18F]setoperone data for modeling of 5-HT2 receptor binding in brain.

Adult↗
PubMed1989

Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels.

The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.

Adult↗
PubMed1989

Striatal dopamine D2 receptors in tardive dyskinesia: PET study.

The dopamine D2 receptors were investigated in vivo in eight neuroleptic-free patients with persistent tardive dyskinesia using positron emission tomography and 76Br-bromospiperone. The striatal receptor density, estimated by the striatum/cerebellum radioligand concentration ratio, was not elevated in patients as compared with age-matched controls but was positively correlated with the severity of orofacial dyskinesia assessed with the Abnormal Involuntary Movement Rating Scale. These results indicate that tardive dyskinesia is associated with normal levels of striatal D2 receptors but the severity of orofacial movements may depend on the relative density of striatal D2 receptors.

Aged↗
PubMed1988

[18F]setoperone: a new high-affinity ligand for positron emission tomography study of the serotonin-2 receptors in baboon brain in vivo.

The potential usefulness of 18F-labelled setoperone, a high-affinity antagonist of the serotonin-2 (S2) receptors, to study the S2 receptors in vivo with positron emission tomography (PET) was investigated in four baboons. In the control state, there was a rapid wash-out of intravenously injected tracer from the cerebellum, a structure essentially devoid of S2, receptors, and marked retention in both the cerebral cortex and the striatum (region/cerebellum ratios up to 3 and 3.5 after 60 min in cortex and striatum, respectively). The retention of radioligand in the cerebral cortex was abolished after pretreatment with spiperone or ketanserin at saturating doses. In striatum, however, radioligand retention was fully prevented by spiperone but only partly by ketanserin. These results demonstrate that [18F]setoperone was bound to the S2 receptors in the cerebral cortex, whereas the radioligand was bound to both the S2 and the dopamine D2 receptors in the striatum. The high cortex/cerebellum ratio achieved indicates that [18F]setoperone should be a useful radiotracer for PET studies of the S2 receptors.

Animals↗
PubMed1988

D1 and D2-type dopamine receptors in patients with Parkinson's disease and progressive supranuclear palsy.

The densities of D1- and D2-type dopamine receptors were measured with [3H]SCH23390 and [3H]spiperone, in the caudate nucleus and putamen of a large series of patients with Parkinson's disease or progressive supranuclear palsy, in relation to markers of dopaminergic and cholinergic innervation of the striatum ([3H]dihydrotetrabenazine binding and choline acetyltransferase activity). Correlations were sought between these parameters and clinical characteristics of the patients (abnormal involuntary movements, dementia, confusional syndrome or treatment). In Parkinson's disease, the densities of both types of receptors were unchanged, whereas in PSP, the density of D2, but not D1-type dopamine receptors, was decreased in the caudate nucleus and the putamen. No correlations between the biochemical and clinical data were found.

Adenylyl Cyclases↗
PubMed1988

Does levodopa aggravate Parkinson's disease?

We studied the possible deleterious effect of levodopa therapy on 185 patients with Parkinson's disease and concluded that the time when levodopa is introduced, the daily dose, and the duration of treatment do not aggravate Parkinson's disease. We also studied 72 parkinsonian patients with levodopa-induced abnormal involuntary movements to see whether early initiation of levodopa therapy affected the time of onset of abnormal involuntary movements. The results suggested that it did not, and that levodopa was started early in these patients because of the severity of their motor disability.

Female↗
PubMed1987

Nerve cell death in degenerative diseases of the central nervous system: clinical aspects.

The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms.

Adult↗