Biomedical subjects

B Renaud

Publications and source records attributed to B Renaud.

At least 19 recordsLinked to original sources

PubMed1998

Coupling on-line brain microdialysis, precolumn derivatization and capillary electrophoresis for routine minute sampling of O-phosphoethanolamine and excitatory amino acids.

In previous papers, we described the analysis of excitatory amino acids (EAAs) and catecholamines in microdialysis samples using capillary electrophoresis with laser-induced fluorescence detection (CE-LIFD). In the present paper, we report that an automated analysis of such samples can be easily achieved by on-line coupling of the microdialysis probe with a continuous flow derivatization system and a commercially available CE-LIFD apparatus. Because of the short analysis time (less than 2 min) and high separation efficiency (100-200,000 theoretical plates), high temporal resolution of microdialysis (minute range) is preserved as compared to off-line systems, while both EAAs and O-phosphoethanolamine (PEA) can be simultaneously detected. This new method has been applied to the measurement of these compounds in microdialysis samples from hippocampal slice cultures and striatum of anesthetized rats. Extracellular concentrations of EAAs, but not PEA, increased during perfusion of a solution containing high K+ or a glutamate uptake inhibitor. However, after in vitro ischemia on hippocampal slices, both EAAs and PEA concentrations increased, but with different temporal patterns.

Animals↗

PubMed1998

Biological parameters in major depression: effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. Relation to early clinical outcome.

BACKGROUND: Clinical and pharmacologic studies report a relative or absolute serotonergic deficiency in major depression; however, the variability of clinical characteristics of illness has led to controversial results. In the present work, we looked for a possible relationship between i) biochemical values that indirectly reflect aminergic neurons activity and clinical characteristics and ii) their evolution and the early clinical outcome under antidepressive therapies (ATs). METHODS: Platelet serotonin content, platelet monoamine oxydase activity, and urinary biopterins were measured in 27 depressed patients before and during four different ATs (paroxetine, viloxazine, moclobemide, or electroconvulsive therapy). Depressive symptomatology and its evolution under ATs were quantified using three clinical rating scales. RESULTS: A severe symptomatology, high serotonin (5-HT) platelet content, and high or low urinary B could represent risk factors leading to a smaller or delayed response to an AT. Furthermore, the early improvement under ATs was negatively correlated to pretreatment 5-HT platelet content. CONCLUSIONS: Determination of 5-HT level could be useful in the choice of an AT.

Adrenergic Uptake Inhibitors↗

PubMed1998

Is the potent 5-HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in the rat brain?

The effects of the new methoxy-chroman 5-HT1A receptor agonist, alnespirone (S-20499), on the dopamine systems in the rat brain were assessed in vivo by means of electrophysiological and neurochemical techniques. Cumulative doses of alnespirone (0.032-4.1 mg kg(-1), i.v.) did not modify the spontaneous firing rate of dopamine neurons in the substantia nigra as well as in the ventral tegmental area. The local application of alnespirone (0.1-10 microM) by reverse microdialysis into the dorsal striatum did not affect the dopamine output but induced a moderate, although dose-independent, increase of 5-HT (5-hydroxytryptamine, serotonin) concentrations in the dialysate. As expected of a 5-HT1A receptor agonist, intraperitoneal (i.p.) administration of alnespirone at 2-32 mg kg(-1) markedly decreased 5-HT turnover in the striatum. Parallel measurements of dopamine turnover showed that alnespirone exerted no effect except at the highest dose (32 mg kg(-1), i.p.) for which a significant increase was observed. Interestingly, both alnespirone-induced reduction in 5-HT turnover and increase in dopamine turnover could be prevented by pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexa ne carboxamide). Altogether, these data indicate that alnespirone does not exert any direct influence on central dopamine systems. The enhanced dopamine turnover due to alnespirone at high dose appeared to result from 5-HT1A receptor stimulation, further supporting the idea that this receptor type may play a key role in 5-HT-dopamine interactions in brain.

5-Hydroxytryptophan↗

PubMed1998

Assessment of pharmacodynamic and pharmacokinetic characteristics of drugs using microdialysis sampling and capillary electrophoresis.

Microdialysis sampling combined with capillary electrophoresis is emerging as a new approach in drug studies. It allows the continuous monitoring, in vivo or in vitro, of changes in free endogenous compounds as well as in drug substances, following the administration of pharmacological agents. The low volume requirement of capillary electrophoresis for injection allows the collection of dialysates during short sampling times, leading to a precise temporal description of drug-induced biochemical changes or pharmacokinetics. Various protocols can be used for analyzing endogenous compounds and drug substances in microdialysis samples. Capillary electrophoresis with laser-induced fluorescence detection often affords the high sensitivity level which is needed in most studies. Furthermore, the direct on-line coupling of microdialysis, derivatization of samples, and electrophoretic analysis now brings a separation-based biosensor, allowing a real-time description of chemical events with a high molecular specificity. Microdialysis sampling combined with capillary electrophoresis has recently been used to assess pharmacodynamic and pharmacokinetic characteristics of various drugs in animal studies; it may also represent a new approach in clinical pharmacology in the near future.

Animals↗

PubMed1998

Differential effects of neurotensin on dopamine release in the caudal and rostral nucleus accumbens: a combined in vivo electrochemical and electrophysiological study.

The time-course of variations in extracellular dopamine concentration following local pressure ejection of 10(-7) to 10(-3) M neurotensin into the ventral tegmental area of the rat was determined in the minute range in the nucleus accumbens by means of differential normal pulse voltammetry associated with carbon fibre electrodes. The effects of neurotensin ejection into the ventral tegmental area were further investigated on the firing activity of the corresponding dopaminergic neurons. The lowest concentration of neurotensin (10(-7) M) enhanced the extracellular dopamine concentration throughout the nucleus accumbens and stimulated the discharge activity of ventral tegmental area dopaminergic neurons. The two highest concentrations of neurotensin (10(-5) M and 10(-3) M) evoked two patterns of responses on the extracellular dopamine concentration and on the discharge activity of dopaminergic neurons. The extracellular dopamine concentration was increased above basal levels in the caudal part of the nucleus accumbens. In the rostral part, the evoked changes exhibited a multiphasic time-course characterized by a decreasing phase below baseline. The firing rate of dopaminergic neurons was either increased or decreased, depending on the neuron being tested. In fact, neurotensin ejection was always followed by an exacerbation of bursting activity, the resulting effect on the mean firing rate being related to the duration of the interburst intervals. Indeed, short interburst intervals permitted an increase in mean firing rate whereas long interburst intervals, indicative of excessive depolarization, led to a decrease in mean firing rate. These results suggest that variations in extracellular dopamine concentration evoked by neurotensin administration into the ventral tegmental area are the result of neurotensin-evoked changes in dopaminergic activity. Moreover, the differential effects evoked by high concentrations of neurotensin could be attributable to two subpopulations of ventral tegmental area dopaminergic neurons which could project differentially to the caudal and the rostral parts of the nucleus accumbens.

Action Potentials↗

PubMed1998

Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis.

OBJECTIVE: To evaluate the incidence and risk factors for catheter-related central vein thrombosis in ICU patients. DESIGN: Observational prospective multicenter study. SETTING: An 8-bed surgical ICU, a 10-bed surgical cardiovascular ICU, and a 10-bed medical-surgical ICU. PATIENTS: During an 18-month period, 265 internaljugular or subclavian catheters were included. Veins were explored by duplex scanning performed just before or < 24 h after catheter removal. Suspected risk factors of catheter-related central vein thrombosis were recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-seven catheters were excluded from the analysis. Therefore 208 catheters were analyzed. Mean age of patients was 64+/-15 years, simplified acute physiologic score was 12+/-5, organ system failure score at insertion was 1+/-1, and mean duration of catheterization was 9+/-5 days. A catheter-related internal jugular or subclavian vein thrombosis occurred in 33% of the cases (42% [95% confidence interval (CI), 34 to 49%] and 10% [95% CI, 3 to 18%], respectively). Thrombosis was limited in 8%, large in 22%, and occlusive in 3% of the cases. Internal jugular route (relative risk [RR], 4.13; 95% CI, 1.72 to 9.95), therapeutic heparinization (RR 0.47; 95% CI, 0.23 to 0.99), and age >64 years (RR, 2.44; 95% CI, 2.05 to 3.19) were independently associated with catheter-related thrombosis. Moreover, the risk of catheter-related sepsis was 2.62-fold higher when thrombosis occurred (p=0.011). CONCLUSIONS: Catheter-related central vein thrombosis is a frequent complication of central venous catheterization in ICU patients and is closely associated with catheter-related sepsis.

APACHE↗

PubMed1997

Microdialysis monitoring of extracellular glutamate combined with the simultaneous recording of evoked field potentials in hippocampal organotypic slice cultures.

These experiments combined extracellular electrophysiological multirecordings from hippocampal organotypic slice cultures with application of drugs to and sampling of extracellular fluid from a restricted region of the slice using a microdialysis probe. Glutamate (Glu) concentrations were monitored in 0.5 or 2 min microdialysis samples, while evoked field potentials responses (EvFPR) in the CA1 region of the hippocampus (stimulation in the CA3 area) were simultaneously recorded using a multi-electrodes array (Physiocard). Glu was assayed by capillary electrophoresis with laser-induced fluorescence detection combined with a continuous flow derivatization of dialysates. The performance of this combined approach was demonstrated by monitoring extracellular Glu concentrations and EvFPR after K+ induced depolarisation, Glu uptake blockade by trans-pyrrolidine-2,4-dicarboxylic acid (PDC), and electrical stimulation. Such an approach allows a global monitoring of the neuronal functioning with a fine time resolution (up to 30 s) on a simple in vitro brain slice model, to be used as a complement to conventional in vivo microdialysis studies.

Animals↗

PubMed1997

Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO synthase inhibitors.

A porphyrinic microsensor combined with in vivo voltammetry was used to monitor extracellular nitric oxide (NO) in the locus coeruleus (LC) of anaesthetized rats. Administration of N omega-nitro-L-arginine p-nitro-anilide (100 mg/kg, i.p) or 7-nitro indazole (30 mg/kg, i.p.), which both inhibit preferentially neuronal NO synthase (NOS), induced a marked decrease in the NO oxidation peak height. On the other hand, N omega-nitro-L-arginine methyl ester (L-NAME) (200 mg/kg, i.p.), a less selective NOS inhibitor, failed to decrease the NO signal. Moreover, intra LC administration of NMDA, known to activate LC noradrenergic neurones, increased the NO signal. This study demonstrates the usefulness of in vivo voltammetry to monitor basal levels of NO and their changes in the LC. Differential effects of NOS inhibitors show that their central activity need to be assessed through in situ measurement of NO before using these inhibitors as neuropharmacological tools.

Anilides↗

PubMed1997

On the involvement of a tonic dopamine D2-autoinhibition in the regulation of pulse-to-pulse-evoked dopamine release in the rat striatum in vivo.

The dopamine overflow evoked by trains of electrical stimulation pulses applied to the ascending dopaminergic pathway was measured with continuous amperometry in the striatum of anesthetised rats. As previously observed in in vitro studies, a pulse by pulse analysis showed a fall in dopamine overflow evoked by pulses 2 to 6, compared to the response evoked by pulse 1. However, in contrast with in vitro findings, the present in vivo data showed that the dopamine receptor antagonist haloperidol i) completely reverses the fall in dopamine overflow between pulse 1 and subsequent pulses, ii) enhances the dopamine overflow elicited by pulse 1. These results suggest that in vivo, both basal and pulse-evoked dopamine overflow results in stimulation of dopamine D2-type autoreceptors and therefore in regulation of dopamine release.

Animals↗

PubMed1997

Monoamine metabolism in the locus coeruleus measured concurrently with behavior during opiate withdrawal: an in vivo microdialysis study in freely moving rats.

Using microdialysis, changes in monoamine metabolism were monitored in the locus coeruleus of freely moving rats during opiate withdrawal concomitantly with behavioral symptoms. Rats were infused with morphine (2 mg/kg/h, s.c.) or saline for 5 days and challenged with naltrexone (100 mg/kg, s.c.) on day 6. Following naltrexone challenge, the classic behavioral symptoms of morphine withdrawal were observed in rats treated with morphine but not in saline-infused rats. In morphine-dependent rats, naltrexone induced a marked increase (280%) in dialysate concentrations of 3,4-dihydroxyphenylacetic acid, an index of the functional activity of the noradrenergic neurons in the locus coeruleus. The local concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were also increased (70%) during morphine withdrawal. Taken together, these results (a) confirm in unanesthetized rats the hypothesis of an activation by opiate withdrawal of noradrenergic neurons in the locus coeruleus and (b) suggest an increase in serotonergic transmission in the same nucleus during morphine withdrawal.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

[Contribution of air mycological control for the prevention of invasive nosocomial aspergillosis].

This study analyses the results of systematic air sampling during 11 months in hospital areas where patients are particularly exposed to Invasive Nosocomial Aspergillosis (INA). The results demonstrate that isolement of Aspergillus fumigatus is occasional and allows the control and validation of cleaning, disinfection and filtration measures. The efficiency of this protocol suggests its prophylactic value in INA.

Air Microbiology↗

PubMed1996

In vivo monitoring of extracellular noradrenaline and glutamate from rat brain cortex with 2-min microdialysis sampling using capillary electrophoresis with laser-induced fluorescence detection.

The measurement of neurotransmitters by capillary electrophoresis (CE) has emerged as a reliable and sensitive method for microdialysis sample analysis. This paper describes a method which employs laser-induced fluorescence detection (LIFD) of catecholamines and excitatory amino acid derivatives formed after reaction with naphthalene-2,3-dicarboxaldehyde. On-line derivatization of very small volumes of microdialysis samples (500 nl) is developed before two off-line analyses (total run time of less than 10 min) are performed to detect derivatives of catecholamines and excitatory amino acids formed in each sample. High microdialysis temporal resolution is reached (2-min fractions) for the simultaneous monitoring of noradrenaline (NA) and glutamate concentrations from rat brain cortex microdialysates. The system performance is evaluated and pharmacological characterization of the determination of NA in cortical dialysates by CE-LIFD is reported.

Animals↗

PubMed1996

Enhanced temporal resolution for the microdialysis monitoring of catecholamines and excitatory amino acids using capillary electrophoresis with laser-induced fluorescence detection. Analytical developments and in vitro validations.

This paper reports the development of a method based on capillary electrophoresis with laser-induced fluorescence detection for the simultaneous determination of catecholamines and excitatory amino acids on submicroliter microdialysis samples, with short analysis times (3 min or less), high sensitivity (nanomolar range, i.e., attomoles detected) and high separation efficiency (up to 1.10(6) theoretical plates). A continuous flow derivatization of small volumes of microdialysate (500 nl) using naphthalene-2,3-dicarboxaldehyde as derivatizing reagent is described. Thereafter, two subsequent off-line analyses are performed on each of the 30-s dialysates to determine catecholamines and amino acids. The performances of the present method are demonstrated in vitro by monitoring rapid fluctuations in the concentration of catecholamines and amino acids in the external microdialysis medium.

Catecholamines↗

PubMed1996

Microdialysis monitoring of variations in extracellular levels of serotonin, GABA and excitatory amino acids in the frontal cortex of awake rats in response to a single peripheral or central administration of dexfenfluramine.

The effects of a single dexfenfluramine (D-fen) administration on the release of endogenous serotonin (5-hydroxytryptamine, 5-HT), excitatory (glutamate, Glu, aspartate, Asp) and inhibitory (gamma-aminobutyric acid, GABA) amino acids from the frontal cortex were studied by using in vivo microdialysis in freely-moving rats. Extracellular levels of these neurotransmitters were measured with HPLC coupled to electrochemical detection or with capillary electrophoresis coupled to laser-induced fluoresence detection (CE-LIFD). In a first study, single intraperitoneal administration of D-fen (0.5, 1.3, 5 and 10 mg/kg) increased extracellular 5-HT levels in a dose-dependent manner (maximal increase by 982% over baseline for the highest dose) while changes in Glu, Asp or GABA never reached statistical significance. In a second study, 73 nM of D-fen applied locally through the frontocortical dialysis probe, at a flow rate of 1.5 microliters/min in 30 microliters of perfusion fluid for 20 min, increased extracellular 5-HT and Asp levels [the maximal increases were to 1804% and 280% of the respective basal values (100%)] without altering extracellular levels of Glu and GABA. Thus, the order of magnitude of the changes induced by systemic administration or local infusion of D-fen on frontocortical extracellular levels of several neurotransmitters (5-HT > > Asp > GABA = Glu) demonstrate that D-fen, an indirect serotoninergic agonist, mainly increases 5-HT release while producing slight (Asp) or no (Glu, GABA) short-term in vivo variations in amino acid extracellular levels in the rat frontal cortex.

Animals↗

PubMed1996

High-speed separation of subnanomolar concentrations of noradrenaline and dopamine using capillary zone electrophoresis with laser-induced fluorescence detection.

Capillary zone electrophoresis with laser-induced fluorescence detection has been shown to give rapid separations with high resolution and sensitivity. These advantages are documented for catecholamines analysis in the present work, which shows that separation of subnanomolar concentrations of dopamine and noradrenaline (detection limits of 8.6 x 10(-11) M, corresponding to a detected amount of 143 zeptomoles of each catecholamine) can be performed in 82 s with an efficiency of several million theoretical plates.

Dopamine↗

PubMed1996

A randomized cross-over comparison of the hemodynamic response to intermittent hemodialysis and continuous hemofiltration in ICU patients with acute renal failure.

OBJECTIVE: To compare the hemodynamic response of ICU patients with acute renal failure of a 24-h continuous arteriovenous hemofiltration (CAVH) and that of patients with a 4-h intermittent hemodialysis (HD). DESIGN: Cross-over randomized clinical trial. The two periods to be compared were a 24-h CAVH and the 24-h encompassing a 4-h HD. These two periods were separated by a 24-h wash-out period. SETTING: Ten bed medicosurgical ICU of a tertiary care center in Paris, France. PATIENTS: Inclusion criterion was the requirement of replacement therapy for acute renal failure in patients already submitted to mechanical ventilation. INTERVENTIONS: CAVH was performed with Ringers' lactate used for restitution and infused before the hemofilter. The ultrafiltrate output was maintained at around 15 ml/min. HD was performed with a bicarbonate-buffered dialysate. MEAN OUTCOME MEASURES: Mean arterial pressure (MAP), use of adrenergic drugs, and change in body weight during each period. RESULTS: Twenty-seven consecutive patients were included, 15 CAVH-HD and 12HD-CAVH. CAVH and HD allowed the same metabolic efficacy. No hemodynamic parameter (MAP, amount of adrenergic drugs, change in body weight) differed between the two methods. CONCLUSIONS: CAVH is equivalent to HD in terms of MAP and the use of vasopressive drugs and fluids. Establishing the superiority of CAVH would require carefully controlled studies assessing either outcome or changes in tissue oxygenation.

Acute Kidney Injury↗

PubMed1996

Mortality of nosocomial pneumonia in ventilated patients: influence of diagnostic tools.

The overmortality induced by nosocomial infections, especially pneumonia in ventilated patients (VNP), is still a matter of controversy because it is difficult to know precisely the respective effects of VNP per se and both the underlying illness and the severity of the disease that indicates ICU stay. During a 3-yr period, for each patient mechanically ventilated for more than 48 h we recorded underlying illness, reason for mechanical ventilation, clinical and therapeutic data collected during the first 48 h of ventilation, and death in the ICU. Patients with suspicion of VNP (S-VNP) according to clinical, radiologic, and biologic criteria underwent bronchoscopy with protected specimen brush (PSB) and bronchoalveolar lavage culture (BAL-C). VNP was confirmed (C-VNP) if PSB > or = 10(3) cfu/ml and/or BAL-C > or = 10(4) cfu/ml. Prognostic multivariate analysis was performed introducing S-VNP and C-VNP as time-dependent covariates. Of the 387 studied patients, 112 S-VNP and 56 C-VNP were observed with overall mortality of 43% (168 patients). MacCabe, APACHE II score, shock, use of sedatives and absence of enteral nutrition were additively associated with an increased mortality as well as C-VNP (relative risk [RR]: 1.8, p = 0.007). Nevertheless, when S-VNP and C-VNP were simultaneously introduced in the Cox model, only S-VNP remained associated with increased mortality. In patients suspected of VNP, confirmation of VNP using PSB and/or BAL-C adds no prognostic information. Whether this could be explained by the lack of sensitivity of protected distal samples or the severity of underlying conditions of S-VNP patients is still an open issue. A multivariate analysis based on follow-up data during the ICU course of ventilated patients will be initiated in the near future.

Aged↗

PubMed1996

Usefulness of airway visualization in the diagnosis of nosocomial pneumonia in ventilated patients.

UNLABELLED: Clinical diagnosis of nosocomial pneumonia in ventilated patients remains a challenge in the ICU as none of the clinical biological and radiologic parameters can predict its diagnosis. To our knowledge, however, the accuracy of direct visualization of the bronchial tree has never been investigated. PURPOSE: To evaluate the interest of airway visualization and to select independent parameters that predict nosocomial pneumonia in ventilated patients. SETTING: A ten-bed medical-surgical ICU. METHODS: All consecutive patients suspected of having nosocomial pneumonia who underwent bronchoscopy with protected specimen brush, culture examination of BAL, and direct examination of BAL were studied. Clinical and biological data and airways findings were recorded prospectively. Patients were classified as having pneumonia or not according to the results of distal bacteriologic samples, follow-up, and histologic study. Respective accuracies of each variable were calculated using univariate analysis and stepwise logistic regression. RESULTS: Ninety-one patients with suspected nosocomial pneumonia were studied. Patients were randomly assigned to a construction group (n = 46) and a validation group (n = 45). Using multivariate analysis, 3 factors were associated with pneumonia (a decrease in PaO2/fraction of inspired oxygen ratio > or = 50 mm Hg, odds ratio [OR] = 9.97, p = 0.026; the presence of distal purulent secretions, OR = 7.46, p = 0.044; the persistence of distal secretions surging from distal bronchi during exhalation, OR = 12.25, p = 0.013). These three factors remained associated with pneumonia in the validation group. Interobserver repeatability of the bronchoscopic parameters was good. Having 2 or more of these 3 independent factors was able to predict pneumonia with a 94% sensitivity and a 89% specificity in the construction group and with a 78% sensitivity and a 89% specificity in the validation group. CONCLUSION: We conclude that direct visualization of the bronchial tree can immediately and accurately predict nosocomial pneumonia in ventilated patients before obtaining definite results of protected samples.

Aged↗