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Biomedical subjects

O Rascol

Publications and source records attributed to O Rascol.

At least 127 records · Page 7Linked to original sources
PubMed1993

Lack of yohimbine effect on ambulatory blood pressure recording: a double-blind cross-over trial in parkinsonians with orthostatic hypotension.

Yohimbine is an alpha 2-adrenergic antagonist which has been proposed for the treatment of orthostatic hypotension (OH). We investigated in a double-blind placebo-controlled crossover trial the effects of yohimbine (2 mg tid) on blood pressure (BP) and heart rate (HR) using ambulatory monitoring of blood pressure (AMBP) in 17 patients (69 +/- 5 years) with Parkinson's disease (PD) suffering from non drug-induced OH. At the end of each sequence of 4 weeks, mean systolic (SBP) and diastolic (DBP) BP and HR (+/- SD), BP variability (coefficient of variation of the mean) and nychtemeral rhythm were calculated for day-time (09:00-19:00 h) and night-time (23:00-06:00 h). OH related to PD was characterized by: i) loss of the nychtemeral rhythm of BP (night/day ratio: 1.18 +/- 0.14) but not of HR (night/day ratio: 0.87 +/- 0.04), ii) high variability of BP during day-time and iii) post-prandial hypotension (12 out of 17 patients). There was no significant difference in AMBP parameters between baseline, yohimbine and placebo periods. This study shows that AMBP is a simple and reproducible method to assess the effects of drugs used in the management of OH on BP parameters (mean values and variability) and that yohimbine is not effective to correct OH of PD. Future studies must investigate other more selective alpha 2-adrenergic antagonists.

Aged↗
PubMed1993

[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↗
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↗
PubMed1992

Supplementary and primary sensory motor area activity in Parkinson's disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine.

We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs.

Aged↗
PubMed1992

Parkinson's disease and weight loss: a study with anthropometric and nutritional assessment.

In order to investigate a putative weight loss in patients with Parkinson's disease, an anthropometric and biochemical study was undertaken. We compared body weight and indexes of fat [body mass index (BMI), tricipital skinfold] and lean [midarm muscle area (MMA), calf circumference] mass in men and women suffering from idiopathic Parkinson's disease with normal controls. We found that women suffering from Parkinson's disease exhibited a significant weight loss (-8.5%) and decreased calf circumference when compared with controls. A decrease (-4.3%) in total body weight was also found in men with Parkinson's disease but the difference did not reach the level of significance. Protein biochemical markers of nutritional status (albumin, prealbumin, retinol binding protein, transferrin) were normal in Parkinson's disease patients. The present study demonstrates the occurrence of weight loss in a large population of patients with Parkinson's disease. The putative mechanisms involved in the weight loss are discussed.

Aged↗
PubMed1992

Alterations in the properties of hippocampal pyramidal neurons in the aged rat.

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.

Acetylcholine↗
PubMed1992

Naloxone or haloperidol but not yohimbine reverse apomorphine-induced respiratory depression.

Intravenous injection of low doses of naloxone was found to reverse the respiratory depression induced by apomorphine in chloralose-anesthesized dogs. Similar results were obtained with haloperidol, whereas yohimbine remained ineffective. These data suggest that apomorphine depresses respiratory rate through a mechanism involving both dopamine and opiate mechanisms but not alpha 2-adrenoceptors. Respiratory arrest induced by overdosages of apomorphine can be treated with naloxone.

Animals↗
PubMed1992

Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content?

The contribution of neuromelanin (NM) to the pathogenesis of Parkinson's disease (PD) has long been suspected. In particular, a correlation has been reported between the estimated cell loss in the mesencephalic dopaminergic cell groups and the percentage of NM-pigmented neurons in these cell groups. To test whether the amount of pigment per cell is a critical factor or whether the presence of NM within a neuron is sufficient to account for the degeneration of dopaminergic neurons, the NM content was measured in each neuron from representative sections throughout the ventral mesencephalon of four controls subjects and four patients with PD. Intraneuronal NM was quantified by a densitometric method, using known amounts of synthetic melanin as standards. In control brains, the distribution of melanized neurons in the nigral complex showed a high proportion of lightly melanized neurons in the ventral tegmental area and the pars alpha and gamma of the substantia nigra (SN), whereas heavily melanized neurons were mostly located in the pars beta and lateralis of the SN. An inverse relationship was observed between the percentage of surviving neurons in PD compared with controls and the amount of NM they contain, suggesting that the vulnerability of the dopaminergic neurons is related to their NM content. Factors other than NM may be involved in the differential vulnerability of catecholaminergic neurons in PD. In particular, the constant topography of the cell loss suggests that cell position within the nigral complex is a key factor.

Aged↗
PubMed1991

Bereitschaftspotential in a simple movement or in a motor sequence starting with the same simple movement.

The Bereitschaftspotential (BP) recorded from 3 derivations (vertex, left and right precentral areas) in 20 right-handed, normal young subjects was compared in 2 kinds of motor task: a simple movement (task A) and a motor sequence (task B) starting with the simple movement (A). Differences in the onset time and amplitude of the BP were observed: the onset was earlier and the amplitude was larger in the sequential motor task (B) than in the simple one (A). These differences were more important at the vertex (Cz) and in the right precentral area (C4) than in the left contralateral precentral area (C3). These results suggest that the preparatory processes involved in a motor sequence do not exclusively concern the initial movement but also the remainder of the motor task and that the BP is dependent upon the duration or the complexity of the motor task to be executed. The BP seems on temporal grounds to be a global and not a partial expression of a motor task. The changes in the onset time and amplitude of the BP are maximal at the vertex and this could be related to a greater and perhaps earlier activation of SMA in complex sequential motor tasks.

Adult↗
PubMed1991

Sublingual apomorphine in Parkinson's disease: a clinical and pharmacokinetic study.

The clinical response and the pharmacokinetic parameters of 3 mg subcutaneous (SC) and 30 mg sublingual (SL) apomorphine were compared in nine patients with Parkinson's disease. The magnitude of the motor responses (evaluated by tapping and walking tests and the Webster scale) was similar for SC and SL apomorphine. However, the onset to action was delayed after SL when compared with SC apomorphine. No significant difference was found in bioavailability (area under the curve: AUC) or peak plasma concentration (Cmax) between SC and SL apomorphine, whereas time to peak plasma concentration (Tmax) was shorter after SC apomorphine. Eight other patients were treated for a mean time of 4 months with SL apomorphine with a significant reduction in daily "off" hours. However, four of these eight patients developed stomatitis after some weeks of treatment. These results indicated that (a) pharmacokinetics parallel the clinical response to SL apomorphine, (b) SL apomorphine can reduce severe off periods in parkinsonian patients when used chronically, and (c) its long-term use is limited by a severe side effect (stomatitis).

Administration, Sublingual↗
PubMed1991

Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms.

1. We have measured regional cerebral blood flow (rCBF) and motor function before and after the subcutaneous (s.c.) injection of apomorphine in parkinsonian patients deprived of their usual treatment for at least 48 h. 2. Nineteen patients, pretreated with domperidone (20 mg three times daily for 48 h), received a mean dose of 5.8 mg s.c. apomorphine. All patients switched 'on'. The mean motor score was significantly improved (-65%, P less than 0.01) but no significant change in rCBF was observed. 3. Seven other patients, not pretreated with domperidone, received a lower dose (0.3 mg) of s.c. apomorphine. No change in motor score was observed while the mean rCBF significantly increased (+12%, P less than 0.05). 4. We conclude that s.c. apomorphine increases rCBF in parkinsonian patients. This effect is independent of the central therapeutic effects of the drug. It is mediated by the stimulation of dopaminergic receptors of the cerebral vessels. These receptors are located outside the cerebral blood brain barrier and can be considered as 'peripheral' ones.

Aged↗
PubMed1991

Effects of calcium channel agonist and antagonists on calcium-dependent events in CA1 hippocampal neurons.

The effects of a variety of calcium channel modulators on different calcium-dependent events in CA1 pyramidal hippocampal neurons were analysed using intracellular recordings in an in vitro slice preparation. The following substances were tested: the dihydropyridine calcium agonist BAY K 8644, the dihydropyridine calcium antagonist nimodipine, the phenylalkylamine verapamil and the snail toxin omega-conotoxin GVIA (omega-CgTx). BAY K 8644 increased the repolarization time of the after hyperpolarization (AHP) following a spike burst. This effect was antagonized by nimodipine. BAY K 8644 also prolonged the calcium spike and, in some cases, increased the size of the synaptic events resulting from activation of the Schaffer collateral/commissural system. Nimodipine decreased the size of the AHP in some neurons but had no consistent effect on synaptic events. Verapamil at low concentrations (1-10 microM) had no significant effects on the calcium-dependent events in the hippocampus. Increasing the concentration (up to 100 microM) led to a progressive suppression of the AHP and of the slow inhibitory postsynaptic potential (IPSP), probably via an action on potassium conductances. In addition, the baclofen-induced hyperpolarization was blocked by verapamil. Interestingly, at this higher concentration, verapamil could suppress the AHP without depressing the calcium spike. omega-CgTx selectively blocked the synaptic events (especially the IPSPs) but had no effect on non-synaptic events. This last compound exhibits a high degree of selectivity, acting on N-type calcium channels which are involved in neurotransmitter release. Our results provide evidence that different classes of agents which act on calcium channels can be used to discriminate between different calcium-dependent responses in CA1 hippocampal neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Square wave jerks in parkinsonian syndromes.

The frequency of square wave jerks (SWJ) was compared in eight patients with progressive supranuclear palsy (PSP), 25 patients with multiple system atrophy or Parkinson's disease plus (MSA/PP), 85 patients with idiopathic Parkinson's disease (PD) and 20 age-matched normal volunteers. In the control group, the mean (SD) SWJ frequency (SWJ larger than 1 degree amplitude) was 2.3 (2.4)/min. Abnormal ocular fixation (SWJ frequency greater than 10/min) was observed in a large proportion of PSP patients (7/8) and of MSA/PP patients (16/25) but in few PD patients (13/85). In the group of PD patients with abnormal ocular fixation, freezing of gait, falls and instability were more severe than in the group of PD patients with normal fixation. The study of ocular fixation may help to differentiate PD clinically from other Parkinsonian syndromes. SWJ are probably not related to the central degeneration of the dopaminergic nigrostriatal pathway observed in PD.

Aged↗
PubMed1991

Cognition and cerebral blood flow in lateralised parkinsonism: lack of functional lateral asymmetries.

Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.

Aged↗