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Biomedical subjects

O Blin

Publications and source records attributed to O Blin.

At least 73 records · Page 4Linked to original sources

Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy.

We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate:ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.

Adult↗

A single report of hemiplegic arm stretching related to yawning: further investigation using apomorphine administration.

We observed a stroke patient with an infarct of the internal capsule interrupting the pyramidal tract who stretched his hemiplegic arm during spontaneous and apomorphine-induced yawning. The putative mechanism by which yawning can induce the paradoxical motor response of the plegic arm in the patient might be the functional efficiency of a pathway projecting directly from the stimulated basal ganglia to lower motor systems in the brainstem.

Apomorphine↗

Low luminance contrast sensitivity: effects of training on psychophysical and optokinetic nystagmus thresholds in man.

We compared psychophysical contrast sensitivity function (psi-CSF) and optokinetic contrast sensitivity function (OKN-CSF) in man, for the combination of three spatial and three temporal frequencies. psi-CSF was defined as the inverse of the contrast threshold, that is the contrast value of a sinusoidal grating for which a subject was able to identify the width of a drifting grating. OKN-CSF was defined as the inverse of the contrast value of the grating which triggered an involuntary optokinetic nystagmus. In highly experienced subjects, OKN-CSF was overall higher than psi-CSF. More precisely, differences between both contrast sensitivity functions occurred mainly in the low spatio-temporal frequency range (below 4 c/deg and 9 Hz). In naive subjects, psi-CSF reached the level of OKN-CSF after two consecutive test sessions. OKN-CSF did not change with training. Similarly, high spatio-temporal frequency psychophysical thresholds did not change with training and, moreover, approximated OKN-CSF thresholds. Low spatio-temporal frequency psychophysical sensitivity was initially lower than corresponding OKN-CSF sensitivity; however, after only two training sessions, the two functions were indistinguishable due to a selective increase in psychophysical low spatio-temporal frequency sensitivity.

Adult↗

Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study.

We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five of the patients had conduction blocks. The study design was a double-blind, placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day injected for 5 consecutive days). We evaluated the patients before and 5, 28, and 56 days after drug administration using a computerized analyzer for muscle strength, the Norris scale for disability, motor nerve conduction velocities for patients with conduction blocks, and measurements of immunologic markers. Compared with placebo, IVIg induced a significant increase in muscle strength only in the patients with conduction blocks.

Adult↗

[Clinical aspects of depression in the psychotic patient].

In order to study clinical aspects of depression in psychotic patients, it is necessary to first differentiate between the following states, as a function of the currently accepted international classification of mental disorders: 1) depressions correlated with psychotic symptomatology (delirium, hallucinations); 2) psychotic disorders with depressive symptomatology; 3) schizo-affective disorders. The greatest interest is currently in the assessment of the second category, in particular study of depression in schizophrenics. This is due to a number of factors, including the relatively great frequency of the disorder, its differential significance as a function of the time in the natural history of the disease, as well as prognostic and therapeutic implications. Proper clinical evaluation is thus important. Until the last few years, this evaluation was based primarily upon use of depression scales or factorial scores, either from general psychopathology scales or specific schizophrenia scales. A number of empirical studies have recently cast some doubt upon validity of these scales for evaluation of depression in psychotic patients, and more specific instruments such as the Calgary Depression Scale (CDS) and the Psychotic Depression Scale (PDS) have been developed. The first validation studies with these scales open up an interesting perspective, in particular for the evaluation of the effects of neuroleptics.

Depressive Disorder↗

Pharmacological basis of immunotherapy in autoimmune diseases.

The clinical development of immunomodulatory agents for the treatment of autoimmune diseases is an arduous process. This can be explained by the fact that the true pathogenic mechanism of the disease(s) is unknown. Moreover, the properties and pharmacokinetic profile of these immunomodulatory agents are different from other classic therapeutic compounds. The aim of this brief review is to discuss a number of general aspects of the clinical pharmacology of i.v. immune globulin as well as more recent immunotherapeutic approaches such as anti-cytokine therapy, which are currently being applied in the immunotherapy for neurologic and rheumatic autoimmune disorders such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and rheumatoid arthritis. A better understanding of the interaction of the therapeutic compound and the host immune response, the knowledge of its kinetic profile, and the development of surrogate markers of clinical efficacy should help in designing randomized and blinded clinical trials that will ultimately determine the optimal therapeutic regimen.

Adjuvants, Immunologic↗

GABA-ergic control of visual perception in healthy volunteers: effects of midazolam, a benzodiazepine, on spatio-temporal contrast sensitivity.

1. We studied the effects of midazolam (MDZ), a benzodiazepine, on spatio-temporal contrast sensitivity, choice reaction time, and mood visual analogue scales in healthy volunteers. 2. Eight extensively trained, healthy volunteers were included in a placebo-controlled cross-over double-blind trial of MDZ (0.15 mg kg-1). Treatments were injected intramuscularly and evaluations were performed before and 0.5, 1, 2, 3 and 4 h after drug administration. Spatio-temporal contrast sensitivity was measured using a micro-computer with appropriate software. Stimuli were vertical gratings with adjustable contrast, with spatial frequencies of 0.25, 1 and 4 cpd. Four conditions of temporal modulation were used: the grating was either static or drifting laterally with temporal frequencies of 1, 3 and 9 Hz. 3. An analysis of variance was performed on the data. As compared with placebo, MDZ induced an increase in choice reaction time and sedation (as assessed on visual analogue scales). From 0.5-4 h after the injection, MDZ produced an overall decrease in visual sensitivity, as compared with placebo. More specifically, MDZ preferentially affected medium to high spatial frequencies and low temporal frequencies. Several non-exclusive hypotheses may account for the results: 1) an increase in the size of the receptive fields, 2) a preferential effect on the visual parvocellular pathways which mediate the sensitivity to high spatial and low temporal frequencies.

Adult↗

Dopaminergic modulation of visual sensitivity in man.

A large body of experimental evidence supports the hypothesis that dopamine is a functional neuromodulator at many levels of the visual system. Intrinsic dopaminergic neurons were characterized in most mammalian retina, including man. These neurons give rise to a dendritic plexus covering the retina. Thus, dopamine seems to be involved in the organization of the ganglion cell and the bipolar cell receptive fields and modulates physiological activity of photoreceptors, both processes which underlie sensitivity and spatial selectivity of visual processing in the early stage of the visual system. Moreover, few data are now available concerning the functional significance of dopaminergic modulation of visual sensitivity in man. Parkinson's disease is a specific disorder of central dopaminergic systems. Abnormalities in the pattern-evoked potentials and electroretinogram have been found in parkinsonian patients. Contrast sensitivity, a useful tool for measuring visual spatio-temporal sensitivity in man, has also been shown to be modified due to this affection. Dynamic contrast sensitivity is primarily decreased in these patients, distinguishing them from the normal aging process. Because these modifications in shape of the contrast sensitivity function are reversed by L-Dopa, and that neuroleptic administration could reproduce them in schizophrenia patients, it was suggested that dopamine might tune the contrast sensitivity function in man. We have recently shown that subcutaneous apomorphine induces changes in contrast sensitivity in healthy volunteers, which preferentially affect motion sensitivity. These dopaminergic sensitive modifications in the shape of the contrast sensitivity function might reflect a change in the range of sensitivity of the visual system, both in dynamic and spatial properties. This could be explained by a modification in the spatial and dynamic properties of the ganglion cell responses in the retina. Moreover, we suggest both from our results and from the review of the literature that human psychophysical data confirm the hypothesis that dopamine may be involved in light retinal adaptation, as light-induced and dopamine-induced modifications in the shape in the contrast sensitivity function are quite similar.

Contrast Sensitivity↗

Regression of allopurinol-induced peripheral neuropathy after drug withdrawal.

A patient experienced an axonomyelinic peripheral neuropathy during a long-term allopurinol treatment. The symptoms and signs regressed after drug withdrawal, and the nerve conduction velocities and distal latencies improved. The incidence of allopurinol-induced peripheral neuropathy is very low. Thus, facilitatory factors have to be sought.

Allopurinol↗

[New methods of analysis of gait in the evaluation of the action of anti-inflammatory drugs. Apropos of naproxen].

Two nontraumatizing and reproducible tools for quantitative gait analysis as part of the objective evaluation of nonsteroidal antiinflammatory drugs are reported. The Bessou gait analyzer is a simple mechanical device which measures spatiotemporal and kinematic parameters (stride length; duration of stride, weight-bearing, and forward swing; speed and peak speed of swing; and overall speed of walking). The ELITE system is a considerably more complex instrument for analyzing three-dimensional motions through high-speed shape recognition. Computerized data management allows not only to determine the spatiotemporal parameters listed above but also to study displacements of selected landmarks in several planes and to derive joint angles and angular speeds. Coupling of the ELITE system to a force platform and to telemetric transmission surface electromyography substantially expands the range of data provided. The mechanical gait analyzer was used to evaluate the effects of naproxen in 11 patients with osteoarthritis of the knee; another similar study in 13 patients with osteoarthritis of the hip is ongoing. Gait was recorded before and after daily administration of naproxen for seven days. After treatment, walking speed was significantly increased as a result of increased stride length and decreased stride duration. Durations of monopodal and bipodal weight-bearing decreased concomitantly with the increase in speed, whereas duration of forward swing remained unchanged. These data demonstrating improved kinematic gait parameters show that naproxen is effective in reducing the adverse mechanical effects of pain. This study also demonstrates the usefulness of gait analysis for evaluating drugs.

Aged↗

[Iatrogenic axonal neuropathy and erythroderma induced by piroxicam. Manifestations of hypersensitivity?].

A case of peripheral neuropathy following treatment with piroxicam is reported. The patient developed muscle pain and asymmetrical sensory distal neuropathy of the lower limbs a few months after the onset of the treatment. Piroxicam was withdrawn and full recovery was achieved within one year. The simultaneous appearance in the same patient of erythroderma with microvasculitis on nerve and skin biopsies suggests a common type III hypersensitivity mechanism in the pathogenesis of these two side-effects of piroxicam.

Aged↗

Nociceptive threshold in hypothyroid patients.

The purpose of this study was to measure the nociceptive threshold in hypothyroid patients by determining when the nociceptive flexion reflex of the lower limb occurs under percutaneous electrical stimulation of the sural nerve, given that this threshold is well correlated with pain sensation. Twelve hypothyroid patients and twelve control subjects participated in the study. In the case of the hypothyroid patients, the nociceptive flexion reflex (or RIII reflex) was measured before and six weeks after the onset of substitution treatment. The results clearly indicate that the nociceptive threshold of the patients with hypothyroidism was significantly higher than that of the control subjects. After six weeks of substitution treatment, the RII threshold return to normal. The analgesia observed in the hypothyroid patients in this study do not appear to be correlated with the blood TSH level. The possible mechanisms of these analgesic effects are discussed.

Aged↗

A double-blind placebo-controlled trial of L-threonine in amyotrophic lateral sclerosis.

Fifteen patients with the unequivocal diagnosis of amyotrophic lateral sclerosis (ALS) completed a 1-year randomized double-blind placebo-controlled trial of L-threonine (2 g daily). During the study, patients in the placebo group showed a decline in functional status consistent with the natural history of ALS, which was not statistically different from outcome in the patients in the L-threonine group.

Aged↗

Influence of food on the tyramine pressor effect during chronic moclobemide treatment of healthy volunteers.

An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150...mg until an increase in SBP > or = 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal neurochemical markers in the rat, with special reference to the dopamine, choline, GABA and glutamate synaptosomal high affinity uptake systems.

Riluzole, a new compound with anticonvulsant properties, was found to induce a dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate into striatal synaptosomes when added to the incubation medium or after in vivo administration, whereas an inhibition of 3H-choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H-glutamate uptake differentially since 3H-dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake competitively and 3H-glutamate uptake non-competitively, which further suggests that the action of the compound is selective. After in vivo injection, riluzole did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate, aspartate or GABA contents. Since this compound was previously reported to induce a decrease in the spontaneous release of glutamate, serotonin, dopamine and possibly acetylcholine, the hypothesis is put forward that riluzole may, at least at high concentrations, have general effects on the striatal nerve terminals affecting both the uptake and release processes. This action may be correlated with the recently identified blocking properties of the compound on the sodium channels, as previously shown for local anaesthetics.

3,4-Dihydroxyphenylacetic Acid↗

Analgesic effect of indomethacin shown using the nociceptive flexion reflex in humans.

This study investigated whether indomethacin has an analgesic effect on the central nervous system. As analgesics which affect the central nervous system produce a correlated decrease in the subjective sensation of pain and in the nociceptive reflex in humans, the amplitude of the nociceptive flexion of the biceps femoris was studied. Eight patients (six men, two women) aged 35-70 years (mean 51) with rheumatic diseases were included in the study. Each patient was his or her own control and was given a single intramuscular injection of either 50 mg of indomethacin or a placebo. A placebo controlled, double blind experimental design was used. Patients were evaluated before and 30, 60, and 75 minutes after the injection. Seventy five minutes after injection, indomethacin gave a 54% decrease in the amplitude of the nociceptive reflex, whereas the placebo produced a decrease of only 12%. This suggests that indomethacin exerts a depressive effect on the amplitude of the nociceptive reflex and affects the central nervous system as part of its analgesic action.

Adult↗

Contrast sensitivity is increased in a case of nonparkinsonian freezing gait.

We measured spatiotemporal contrast sensitivity and gait variables in a 60-year-old man who had spontaneous episodes of freezing gait without any sign of rigidity or tremor. One major factor triggering freezing was the characteristics of visual space, as freezing episodes occurred during spontaneous walking and passing through apertures and never during walking with eyes closed. Initiation and maintenance of locomotion were greatly facilitated when transverse stripes with optimal intervals were placed on the ground in front of the patient. On the other hand, contrast sensitivity to low-to-intermediate spatiotemporal frequencies was increased in this patient when compared with that of elderly controls. These data suggest that hypersensitivity to visual stimulation and to modifications of the visual environment, associated with abnormal ocular motor behavior, can be one factor leading to the freezing gait phenomenon, which could be called "hypersensitivity braking" and be considered as a sensorimotor disorder.

Aged↗