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Biomedical subjects

N Fabre

Publications and source records attributed to N Fabre.

At least 19 recordsLinked to original sources
PubMed1999

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease.

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

Aged↗
PubMed1999

[Fast visual categorization and speed of processing in migraine].

It has been suggested that the visual cortex of migraine sufferers is hypersensitive. To test this hypothesis, we compared the speed of visual processing in eight migraine patients (including three with aura) and nine controls performing two categorisation tasks of different complexity. In the complex task developed by Thorpe et al. (1996), subjects had to detect the presence of animals in briefly presented photographs (20 ms). The speed of visual processing was measured by the latency of the differential cerebral activity that appears around 150 ms between target and non-target trials. In the simple task, subjects performed a square/circle categorisation. All subjects were faster (445 ms/497 ms) with a higher rate of success (97%/91%) in the simple task. But in both tasks, the behavioural performance and the associated evoked potentials did not show any difference suggesting a cortical hypersensitivity in migraine sufferers.

Adolescent↗
PubMed1998

Normal frontal perfusion in patients with frozen gait.

We have studied the frontal perfusion in the resting condition of two groups of patients with frozen gait: 10 patients with the syndrome of "isolated gait ignition failure" (IGIF) and 8 patients with idiopathic Parkinson's disease (PD) and severe "off" freezing. These patients were compared with two other groups: one including 20 age-matched volunteers as normal control subjects and the other one including 12 patients with progressive supranuclear palsy (PSP) as a positive control with expected frontal hypoperfusion. Frontal perfusion was assessed using single photon emission computed tomography (SPECT) regional cerebral blood flow measurement with intravenous 133Xenon. A significant frontal hypoperfusion was only present in the PSP group but not in the three others. These results do not support the hypothesis that start hesitations and freezing when walking are related to a frontal lobe dysfunction. However, it is possible that frontal neuronal dysfunction occurs without measurable cerebral blood flow changes in the resting condition.

Aged↗
PubMed1998

Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia.

We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop.

Aged↗
PubMed1997

[Parkinson "plus"].

"Parkinson plus" is a group of sporadic degenerative disorders associating Parkinsonism, poorly sensitive to L-dopa, to other neurological syndromes. Thus, progressive supranuclear palsy includes Parkinson's disease, vertical gaze paralysis, nuchal dystonia and dementia; multisystem atrophies associate to different degrees Parkinson's disease (striatonigral degeneration), a cerebellar syndrome (olivopontocerebellar atrophy), dysautonomia (Shy-Drager syndrome), pyramidal syndrome, etc. Other diseases (corticobasal degeneration, diffuse Lewy body disease) also belong to the Parkinson "plus" group. Clinical differentiation between Parkinson "plus" and idiopathic Parkinson's disease is difficult. Their prognosis and treatment are substantially different. Certain diagnosis is based solely upon anatomical observations.

Antiparkinson Agents↗
PubMed1997

The ipsilateral cerebellar hemisphere is overactive during hand movements in akinetic parkinsonian patients.

We compared the rCBF changes induced by the execution of a finger-to-thumb opposition motor task in the cerebellar hemispheres of 12 normal subjects, 12 parkinsonian patients whose medication had been withheld for at least 18 h and 16 parkinsonian patients on medication using single photon emission tomography and i.v. 133Xe. The normal subjects and parkinsonian patients on medication exhibited the same pattern of response, with a significant increase in rCBF in the contralateral primary motor cortex and in the supplementary motor areas. No significant rCBF change was detected in the cerebellum of these two groups; this finding was expected since our technique cannot detect cerebellar activation when the motor task is executed at a relatively low rate and small amplitude as it was in this study. The parkinsonian patients off medication exhibited a markedly different pattern of activation characterized by a significant overactivation in the ipsilateral cerebellar hemisphere and a significant underactivation in the supplementary motor areas. These results suggest that parkinsonian patients off medication may try to compensate for their basal ganglia-cortical loop's dysfunction using other motor pathways involving cerebellar relays.

Brain Mapping↗
PubMed1995

Abnormal vestibuloocular reflex cancellation in multiple system atrophy and progressive supranuclear palsy but not in Parkinson's disease.

We have measured the gain of the vestibuloocular reflex (VOR) in darkness and its cancellation by fixation in 37 patients with Parkinson's disease (PD), 26 patients with multiple system atrophy (MSA), 11 patients with progressive supranuclear palsy (PSP), and 19 normal volunteers. The capacity to cancel the VOR by fixation (VOR cancellation) was significantly reduced in the MSA and PSP patients compared with the PD and normal subjects (p < 10(-4)). A VOR cancellation < 90% (i.e., the mean VOR cancellation of the normals--2 SD) was present in four PD patients, 23 MSA patients, and 11 PSP patients. This criteria distinguished PD and MSA with a 89% sensitivity and a 89% specificity. Our results demonstrate that the VOR cancellation is impaired in most patients with MSA and PSP but not with PD. In MSA patients, the abnormal VOR cancellation is probably not related to the nigrostriatal dopaminergic deficit and more likely reflects a cerebellar dysfunction. Impaired VOR cancellation is a clinical criteria to differentiate MSA and PSP from PD.

Age Factors↗
PubMed1994

Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells.

Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. Considering that heat shock proteins (hsp) and specifically the small hsps have been increasingly linked to growth regulation, we sought to determine whether the mammalian small hsp (hsp28) is a growth-regulatory candidate during hematopoietic cell differentiation. Because of its effects on cell growth and differentiation and its increasing clinical use as a differentiating agent, we examined the effect of retinoic acid (RA) on hsp28 during differentiation of the human leukemic HL-60 cell line. Although hsp28 was constitutively expressed at low levels in untreated HL-60 cells, steady state hsp28 protein increased transiently, concomitant with the onset of G1 cell cycle arrest. Furthermore, hsp28 phosphorylation transiently increased within one hour following treatment with RA. Interestingly, in contrast to other differentiating agents the induction of hsp28 by RA was post-transcriptionally mediated with hsp28 protein and mRNA being discordantly regulated. These observations underscore the complex regulation of hsp28 by RA during granulocytic differentiation of human leukemic cells and indicate hsp28 as an intermediary in the pathway through which retinoids exert their growth and differentiative effects.

Cell Cycle↗
PubMed1994

Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinson's disease.

One month of adjunct treatment with naltrexone (100 mg/day) was compared with placebo in a double-blind, randomized, cross-over design in two groups of patients with Parkinson's disease. The first group was composed of 10 patients with a moderate motor impairment insufficiently controlled by monotherapy with bromocriptine. The second group was composed of eight patients with L-dopa-induced peak-dose dyskinesia. Naltrexone as compared with placebo did not demonstrate any significant change in motor function in either group. These negative clinical results do not support a significant role of endogenous opioid systems in the pathophysiology of motor impairment in Parkinson's disease.

Aged↗
PubMed1994

Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa.

Regional cerebral blood flow (rCBF) changes in cortical motor areas were measured during a movement of the dominant right hand in 15 patients with Parkinson's disease deprived of their usual levodopa treatment, in 11 patients with Parkinson's disease undergoing long-term treatment with levodopa, and in 15 normal volunteers. The supplementary motor areas were significantly activated in the normal subjects and in the patients receiving levodopa but not in the patients deprived of levodopa. The contralateral primary sensory motor area was significantly activated in all three groups. The ipsilateral primary sensory motor cortex was not activated in the normal subjects and the non-treated patients but was in the patients treated with levodopa. It is concluded that the supplementary motor area hypoactivation which is observed in akinetic non-treated patients with Parkinson's disease is not present in patients undergoing long-term treatment with levodopa. This result suggests that (a) levodopa improves the functional activity of supplementary motor areas in Parkinson's disease and (b) there is no pharmacological tolerance to this effect. The ipsilateral primary motor cortex activation observed in the patients treated with levodopa could be related to levodopa-induced abnormal involuntary movements.

Adult↗
PubMed1993

Analysis of the resistance to heat and hydrogen peroxide stresses in COS cells transiently expressing wild type or deletion mutants of the Drosophila 27-kDa heat-shock protein.

The Drosophila melanogaster small heat-shock protein, hsp27 (Dhsp27) belongs to a family of polypeptides which shares a sequence related to alpha-crystallin and which protect cell against heat shock. Dhsp27 accumulates following heat shock and, in absence of stress, in the central nervous system, imaginal discs and the gonads of the developing fly. Two internal and adjacent deletion mutants in the conserved alpha-crystallin domain of Dhsp27 were constructed. Expression vectors containing either the coding sequence of Dhsp27 or that of the two deletion mutants linked to the Simian-Virus-40 late promoter were used to transfect monkey COS cells. The transient expression of Dhsp27 was found to decrease the sensitivity of COS cells to heat and hydrogen-peroxide stresses as judged by Trypan-blue staining and indirect immunofluorescence analysis. Using this rapid test, we observed that a deletion of 62 amino acids, which lies at the 5' end of the conserved alpha-crystallin domain and covers the first 41 amino acids of this region had only a weak effect on the protective activity of Dhsp27. This suggests that the N-terminal half of the conserved alpha-crystallin domain may not be essential for the protective activity of the small hsp. In contrast, Dhsp27 was no more active when the last 42 amino acids of the alpha-crystallin domain were deleted. Biochemical fractionation and indirect immunofluorescence analysis indicated that the protective function of Dhsp27 was localized at the level of the nucleus.

Animals↗
PubMed1993

DNA analysis of haemophilia A families from southern France. Experience of a hospital laboratory.

A sample of 101 individuals from 19 unrelated families from Southern France affected with haemophilia A was studied in our laboratory from 1990 to 1992. The aim of the analysis was to define the carrier status of women related to a haemophiliac, or to find an informative DNA marker for further prenatal diagnosis in obligate carriers. Three intragenic (BclT/intron 18, XbaI/intron 22, AlwNI/intron x7) and two extragenic polymorphisms (TaqI/St14, BglII/DX13) were used for this study. The tested population exhibited some original characteristics, including a lower rate of heterozygosity for the FVIII BclI polymorphism and a number of specificities for the St14 RFLP. We also compared the different methodologies available for each RFLP in a routine diagnostic service, and determined a strategy for linkage analysis in our population.

Adult↗
PubMed1993

[Creutzfeldt-Jakob disease after treatment with human extracted growth hormone. A clinicopathological study].

This report describes the pathological changes observed in the brain of a 18-year-old patient who died with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Clinically, the disease began at age 17 with a rapidly progressive cerebellar syndrome, associated with myoclonus and mental deterioration. Cranial CT scan and MRI showed minor abnormalities. EEG demonstrated non specific changes. The patient became progressively demented, bedridden and died 10 months after the onset. Nine years earlier, he had been operated upon for craniopharyngioma and subsequently treated with cadaver-derived human growth hormone. Post-mortem examination of the brain revealed mild diffuse atrophy. Histology showed congophilic amyloid plaques found in both gray and white matters of the cerebrum and cerebellum, associated with spongiosis, mainly in the basal ganglia and cerebellum, and gliosis. They were immunostained with antiprion protein antibody using the immunoperoxidase method on paraffin embedded sections. The clinical findings in this case were similar to those of other cases of human growth hormone-associated CJD. However, this case is unusual because of the great number of amyloid plaques, which have been only rarely found in previous reports.

Amyloid↗
PubMed1993

Alopecia: an adverse effect of bromocriptine.

We report the cases of two patients who experienced a poorly known adverse effect of bromocriptine-alopecia. The first patient was an infertile 34-year-old woman treated with 2.5 mg of bromocriptine per day. The second patient was a 45-year-old woman with Parkinson's disease treated with 40 mg of bromocriptine per day. In both cases there was no preexisting hair loss. Hair loss ceased when bromocriptine was withdrawn and was not attributed to another etiology. Pathophysiological mechanisms are unknown.

Adult↗