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Biomedical subjects

M C Gagnieu

Publications and source records attributed to M C Gagnieu.

14 recordsLinked to original sources

Lateralization of the effects of the benzodiazepine drug oxazepam on medial olivocochlear system activity in humans.

Benzodiazepines (Bzd) are known to interact with GABAergic inhibitory neurotransmission. Previous research on their effect on human auditory efferent pathways--through evoked otoacoustic emissions suppression by contralateral acoustic stimulation (CAS)--indicated a decrease in medial olivocochlear (MOC) efferent system inhibitory activity, after oral intake of oxazepam--representative of the Bzd drug class. To date, this pharmacological effect was only assessed in the right ear. Since a leftward asymmetry of Bzd receptors localization in human auditory cortex has been described recently, we explored in this study the hypothesis of an asymmetrical action of Bzd on MOC efferent functioning. The results revealed a significant difference of Bzd effect probing the right ear versus the left ear, with CAS-induced suppression being less effective in the right than left ear after oxazepam intake. This finding raises the question of possible neurochemical left-right asymmetry in the descending auditory pathways. The potential localization of this asymmetry is discussed.

Adult↗

Influence of benzodiazepines on auditory perception.

The aim of this study was to test for an influence of benzodiazepine (BZD) on various perceptual and/or cognitive auditory processes. Loudness, auditory selective attention, and the ability of subjects to form perceptual streams out of alternating tone sequences were tested. Nine subjects were tested before, 1, 3, 7, and 24 h after a single-dose oxazepam vs placebo administration in a crossover design. A sample of blood allows us to measure plasma oxazepam concentration. The results revealed a significant reduction in stream segregation expressed as d' scores 1 h after oxazepam intake in the test subjects. No significant change occurred across time in the same subjects when they were administrated a placebo in another session. Furthermore, oxazepam had no substantial and systematic influence either on auditory selective attention or on loudness perception. Altogether, these results suggest that the perceptual organization of sound sequences involves inhibitory neural mechanisms, which can be affected by BZDs. This outcome is consistent with existing models of auditory stream segregation and may be paralleled with earlier findings on the effect of BZDs on perceptual binding in the visual modality.

Acoustic Stimulation↗

Benzodiazepines alter cochleo-cochlear loop in humans.

By using otoacoustic emission, we looked for change in outer hair cell (OHC) motile activity and medial olivocochlear (MOC) system inhibition due to benzodiazepine administration, a drug that is known to produce a pharmacological effect by interacting with GABAergic inhibitory neurotransmission. No effect was observed on OHC motile activity, in contrast benzodiazepines decreased MOC system effectiveness suggesting the existence of GABAergic fibers projecting onto the MOC system.

Administration, Oral↗

Simple high-performance liquid chromatographic separation of oxazepam and its diastereoisomeric glucuronides in serum. Applications in a pharmacokinetic study in sheep.

This paper describes a highly specific and sensitive method for quantifying oxazepam and its diastereoisomeric glucuronides in serum. The method involves sample clean-up by solid-phase extraction on C18 cartridge followed by quantitation on a reversed-phase HPLC column. Diazepam is used as internal standard. Extraction recovery from serum proved to be more than 86%. Precision, expressed as C.V., was in the range 1.2-9.5%. The limits of quantification were 40, 400, and 200 nmol/l for oxazepam, S-(+)- and R-(-)-glucuronides, respectively. This method was applied to the determination of oxazepam and its diastereoisomeric glucuronides in serum collected during a pharmacokinetic study performed in sheep after oral administration of racemic oxazepam. S-(+)/R-(-) ratios were measured all along the sampling time collection and the pharmacokinetic parameters were determined.

Animals↗

[Value of the cytology of bronchoalveolar lavage in the early diagnosis of nosocomial lung infections in patients with thoracic injuries].

Mechanically ventilated patients, especially those with thorax trauma, suffer commonly from nosocomial pneumonia. In these patients, conventional diagnostic criteria for bacterial pneumonia may not be completely reliable, as an accurate interpretation of the chest radiograph is too difficult. The invasive means for the diagnosis of pneumonia (protected specimen brush, bronchoalveolar lavage), require 24-48 hours to obtain the results of cultures. Therefore no information is available to guide the initial choice of antimicrobial therapy. For some authors, the quantification of intracellular bacteria, present in cytocentrifuged preparations made from lavage fluid, may provide rapid identification of patients with pneumonia. We evaluated the benefit of this type of analysis in thorax trauma patients. In 36 patients, 48 samples were taken. With a threshold value of 10% of cells containing intracellular organisms, microscopic examination had a sensitivity and a specificity of 83%. We conclude that this technique may be useful for the early diagnosis of nosocomial pneumonia in ventilated thorax trauma patients.

Bronchoalveolar Lavage Fluid↗

[Intra-macrophage lipid particles collected by bronchoalveolar lavage: incidence and diagnostic value].

This study aimed to determine the incidence and diagnostic value of fat-laden alveolar macrophages obtained by bronchoalveolar lavage (BAL). In 128 patients, including 66 patients admitted for multiple trauma, 158 BAL were carried out. However, 41 BAL from 32 patients were excluded because of poor quality of samples (not enough macrophages, too many ciliated cells, or haemorrhage). All the patients were intubated and mechanically ventilated, having pulmonary infiltrates on the chest film. BAL samples were examined after staining with oil-red-O. They were considered to be positive when more than 5% of alveolar macrophages contained fat droplets. Among them 14 out of 47 patients (30%) without multiple trauma were positive; 7/14 had never been given any intravenous lipid infusion, and 5/14 had aspiration pneumonia (as opposed to 3/32 patients with negative BAL). Further 27 patients out of the 49 (55%) with multiple trauma were positive. Among them 10/49 had clinical evidence of fat embolism, however, only 7/10 had positive samples. All these last ten patients had been given intravenous lipid infusions. The rate of positive alveolar macrophages was correlated neither with the plasma triglyceride concentration, nor the Fracture Index Score, nor the delay between the end of the lipid infusion and the BAL. There was no significant difference in PaO2/FIO2 ratio between the patients with positive and negative BAL. Positive BAL was significantly associated with lipid infusions. The data therefore suggest that the presence of fat-laden alveolar macrophages are associated with various pathological pulmonary conditions, particularly aspiration pneumonia and lipid infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bronchoalveolar lavage in trauma patients for diagnosis of fat embolism syndrome.

Fat embolism syndrome (FES) is a rare but serious complication occurring after long bone fractures. Presence of fat droplets in cells obtained by bronchoalveolar lavage has been proposed as a specific tool for FES diagnosis in trauma patients. We evaluated this technique over a 15-month period in 85 patients. Twenty-eight patients were excluded. The remaining 57 patients were divided into three groups: group 1, 26 patients without trauma as control; group 2, 22 patients with trauma but without evidence of FES; and group 3, nine patients with trauma and evidence of FES. Six of 26 patients in group 1 and nine of 22 patients in group 2 exhibited fat droplets in alveolar macrophages, whereas three of nine patients of group 3 had not. This study suggests that (1) presence of fat droplets in alveolar macrophages is not a reliable method for diagnosis of FES after long bone trauma, and (2) many conditions are associated with fat droplets in alveolar macrophages.

Adult↗

Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease.

We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance.

Adult↗

Liquid chromatographic determination of homovanillic acid, 5-hydroxyindoleacetic acid and probenecid levels in human cerebrospinal fluid during probenecid test.

Homovanillic acid and 5-hydroxyindoleacetic acid, respectively the major metabolites of the central neurotransmitters dopamine and serotonin, are present in human lumbar cerebrospinal fluid, and their determination during the probenecid test is used to study brain monoamine abnormalities in man. We developed a high performance liquid chromatographic technique coupled with electrochemical detection which allows the simultaneous determination of homovanillic acid and 5-hydroxyindoleacetic acid on 10 microliter of human lumbar cerebrospinal fluid. Another liquid chromatographic technique coupled with ultra-violet detection was applied to the measurement of probenecid after injection of 10 microliter of native cerebrospinal fluid. The main advantages of these two techniques are their simplicity, sensitivity, rapidity (five cerebrospinal fluid samples are analysed within one hour) and their good day-to-day reproducibility . These methods were applied to probenecid tests performed in several neurological patients.

Adolescent↗

[Redox status in HIV+ patients under HAART].

Oxidative stress decreases immune defences and is also suggested to participate in the activation of HIV virus replication. That is why we decided to explore some biomarkers of oxidative stress (reduced glutathione, lipoperoxides, true malondialdehyde and vitamin C) in 20 HIV positive patients whose HIV replication was determined by measurement of RNA viral load. Reduced glutathione is decreased in HIV positive patients, without correlation with the viral load. The patients mean content of lipoperoxides is twice that of controls but with such a large range that there is no statistical difference.

Adult↗