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Biomedical subjects

E Carlier

Publications and source records attributed to E Carlier.

At least 19 recordsLinked to original sources

Methylene blue administration in septic shock: a clinical trial.

OBJECTIVE: A release of nitric oxide has been incriminated in the cardiovascular alterations of septic shock. Since guanylate cyclase is the target enzyme in the endothelium-dependent relaxation mediated by nitric oxide, we studied the acute effects of methylene blue, a potent inhibitor of guanylate cyclase in patients with septic shock. DESIGN: Prospective clinical trial. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Fourteen patients with severe septic shock requiring adrenergic therapy. INTERVENTIONS: Short-term intravenous infusion of methylene blue. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were obtained at baseline, and 30, 60, and 90 mins after the infusion of 2 mg/kg of methylene blue. Methylene blue administration was followed by a progressive increase in mean arterial pressure (from 61.1 +/- 7.6 to 71.7 +/- 12.0 mm Hg at 60 mins, p < .01). Pulmonary arterial pressure, cardiac filling pressures, cardiac output oxygen delivery, and oxygen consumption were not significantly affected. Left ventricular stroke work increased from 42.5 +/- 17.9 to 48.9 +/- 14.5 g.m after 60 mins (p < .05). Arterial lactate concentration decreased from 3.4 +/- 1.4 to 2.7 +/- 1.3 mmol/L (p < .05). Since these effects were transient, a second dose of methylene blue was administered 90 mins later to six patients and was followed by a similar response. No adverse effect was observed. CONCLUSIONS: In septic shock patients, the administration of methylene blue results in a transient and reproducible increase in arterial pressure, associated with an improvement in cardiac function, but does not increase cellular oxygen availability. The significant reduction in blood lactate concentration is probably related to the reductor effect of methylene blue, rather than to an improvement in tissue oxygenation.

Adult

Sodium channel internalization in developing neurons.

Neurotoxin-induced activation of voltage-dependent Na+ channels provoked rapid (t1/2 = 15-20 min) channel down-regulation in cultured rat brain neurons, resulting in a 50%-70% decrease in [3H]saxitoxin and 125I-alpha-scorpion toxin binding capacities as well as a decrease in Na+ peak current. Experiments using 125I-alpha-scorpion toxin as both a Na+ channel activator and a surface channel probe showed that a fraction of the bound toxin was internalized, since it was not releasable by acidic washing. Internalization was inhibited by tetrodotoxin, abolished in Na(+)-free medium, and induced by amphotericin B, a Na+ ionophore. Moreover, down-regulation occurred only in immature neuronal tissue, either cultured fetal neurons or postnatal hippocampal slices, but was absent in adult brain. These observations indicate that Na+ channel internalization is triggered by Na+ influx into neurons and may be involved in the control of electrical activity during development.

Aging

Corticosterone effects on long-term potentiation in mouse hippocampal slices.

Corticosterone (CORT) can alter several electrophysiological properties in the hippocampus. Few studies have reported the effects of CORT on hippocampal long-term potentiation (LTP). In the CA1 region of the hippocampal slice, we studied the relative increase in population spike (PS) amplitude after inducing tetanus (PS-LTP) in control conditions and in the presence of CORT (0.5 nM or 5 microM). Two perifusion mediums were used which differed in calcium concentration (M1:Ca 2.5 mM; M2: Ca 3.1 mM). In the control slices, the PS-LTP amplitude was greater in the M1 medium. With the low CORT concentration (0.5 nM), the PS-LTP amplitude was greater than in control conditions in the M2 medium only. A similar PS-LTP amplitude increase was also observed in the M2 medium after application of 0.5 nM aldosterone (type I receptor analog). With the high CORT concentration (5 microM), PS-LTP amplitude decreased in the two conditions. This effect was reversed by co-application of RU486 (type II receptor antagonist). These results demonstrate that CORT can modulate PS-LTP via its two types of hippocampal CORT receptors, depending on the concentration applied. They also showed that the extracellular calcium concentration may contribute to the functional change induced by CORT.

Aldosterone

Nosocomial colonization and infection with multiresistant Acinetobacter baumannii: outbreak delineation using DNA macrorestriction analysis and PCR-fingerprinting.

The prevalence of nosocomial acinetobacter colonization and infection in a university hospital was reviewed and multiresistant Acinetobacter baumannii infections in an intensive care unit (ICU) were investigated using epidemiological typing and a case-control study. Acinetobacter colonization at various body sites was found in 3.2 to 10.8 per 1000 patients. Acinetobacter infection accounted for 0.3% of endemic nosocomial infections in critically ill patients and for 1% of nosocomial bacteraemia hospitalwide. Over a three-week period, four ventilated patients developed colonization, followed by pneumonia in two patients, with A. baumannii resistant to multiple antimicrobials. Cultures of samples from respiratory equipment and ICU surfaces (n = 27) as well as from hands of personnel (n = 14) failed to yield A. baumannii, except for one sample of respiratory tubing. Antibiogram, biotype, chromosomal DNA macrorestriction profiles and polymerase chain reaction (PCR) mediated fingerprints of A. baumannii isolates (n = 31) indicated that this outbreak was caused by two strains, one of which later spread to another hospital where it caused a second outbreak. Both strains were clearly discriminated from control strains from cases of sporadic infection. Risk factors for cross-colonization that were identified by a case-control comparison were neurosurgery, mechanical ventilation and treatment with broad-spectrum antibiotics. Transmission was controlled by implementing contact isolation precautions and routine sterilization of ventilator tubing. Wider use of sensitive genotypic methods like DNA macrorestriction analysis and PCR-mediated fingerprinting for typing nosocomial pathogens should improve the detection of micro-epidemics amenable to early control.

Acinetobacter

Acute and chronic effects of lisinopril on renal and systemic hemodynamics in hypertension.

Acute and chronic effects of the converting enzyme inhibitor lisinopril on renal and systemic hemodynamics were studied in 12 patients with mild to moderate essential hypertension. After a washout period, cardiac output (measured by Doppler echography), renal plasma flow, and glomerular filtration rate (measured by isotopic techniques) were determined before and after oral administration of 20 mg lisinopril (visit 1). The same protocol was repeated after 3 months of lisinopril therapy 20 mg once daily (visit 2). Acute administration of lisinopril, both in untreated hypertensive patients (visit 1) and during long-term treatment (visit 2), decreased blood pressure (p < 0.05) and increased renal plasma flow (p < 0.05), while cardiac output and glomerular filtration rate were unchanged. Comparison of baseline parameters between visits 1 and 2 showed that chronic treatment with lisinopril decreased blood pressure and renal vascular resistance and that these effects were still significant 24-hours postdosage. We conclude that lisinopril is an effective antihypertensive agent with favorable renal hemodynamic effects.

Adult

Modulation of the in vitro electrophysiological effect of corticosterone by extracellular calcium in the hippocampus.

The electrophysiological effects of various concentrations of corticosterone (CORT) on the hippocampus were investigated using extracellular recordings from CA1 hippocampal slice preparations subjected to four different extracellular concentrations of calcium. In all cases, the CORT effect was manifested by a PS amplitude decrease without affecting the slope of either the input volley or the EPSP. Our results showed that, for the lowest extracellular calcium concentrations (1.3 and 2.5 mM), the inhibitory effect of CORT on the PS amplitude appeared only with the supra-physiological 10,000 nM CORT concentration, whereas for the highest ones (3.13 and 5.32 mM) this effect was observed, respectively, with 5 and 0.05 nM CORT concentrations. The antiglucocorticoid RU 486, used in combined application with CORT, blocked the electrophysiological effect of CORT. The possible involvement of calcium-dependent mechanisms at the CORT receptor level or in the final cellular response are discussed.

Animals

Prostaglandin E1 infusion for right ventricular failure after cardiac transplantation.

The infusion of prostaglandin E1, a vasodilating substance with predominant effects on the pulmonary vasculature, has been found effective in the management of pulmonary hypertension associated with various diseases. The reported experience with prostaglandin E1 after cardiac transplantation is, however, limited. We used prostaglandin E1 in 18 patients in whom acute right ventricular failure developed after orthotopic cardiac transplantation. The infusion was started within 24 hours after operation in 16 patients and was continued for up to 7 days. Maximal doses of prostaglandin E1, administered via a central venous catheter, ranged from 30 to 120 ng/kg/min. Norepinephrine was simultaneously infused via a left atrial catheter in 10 patients to prevent a reduction in systemic arterial pressure. The prostaglandin E1 infusion resulted in significant reductions in mean arterial pressure and pulmonary vascular resistance and simultaneous increases in cardiac index and stroke index. Mean arterial pressure was stable and left ventricular stroke work increased. The alveolar oxygen tension/forced inspiratory oxygen index tended to decrease during the infusion. Three patients died, two of right heart failure and one of multiple organ failure associated with cardiac allograft rejection. In patients in whom right ventricular failure associated with pulmonary hypertension develops after cardiac transplantation, prostaglandin E1, combined with norepinephrine whenever the arterial pressure declines, can effectively reduce pulmonary artery pressures and improve global cardiac function without compromising systemic perfusion.

Adult

[In vitro functional differentiation of hippocampal corticosterone receptors by mineralo- and glucocorticoids].

Modulation of CA1 evoked electrophysiological properties (amplitude, latency, paired-pulse facilitation) by different concentrations of aldosterone (ALDO), spironolactone (SPI), and corticosterone (CT) was studied in hippocampal slice preparation from BALB/c mice. ALDO (5 nM) induced a prolonged increase of the population spike (PS) amplitude with a decrease of its latency and of the paired pulse facilitation. The same effect was observed with a solution of CT (0.5 nM) alone or combined with ALDO (0.5 nM), but no effect was observed with a solution of combined CT (0.5 nM) and SPI (500 nM). Implication of corticosteroid receptors in this response was discussed.

Aldosterone

Effects of RU 486 on hippocampal slice electrophysiology in normal and adrenalectomized BALB/c mice.

Modulation of the electrophysiological properties (amplitude, latency, paired-pulse facilitation) of the CA1 hippocampal field by different concentrations of RU 486 was studied in hippocampal slice preparations from normal (sham) and adrenalectomized BALB/c mice. In the sham group as well as in the adrenalectomized group, RU 486 had no effect with the lower concentrations used (0.05 and 0.5 nM), but produced a decrease in the population spike amplitude for the higher concentrations used (5 and 50 nM). This decrease was delayed and sustained. Combined application of RU 486 at 5 nM and corticosterone at 0.5 or 5 nM displayed an excitatory effect, but no inhibitory effect. Combined application of RU 486 and dexamethasone showed no significant effect. These results are related to the antagonist and agonist properties of RU 486 and to the different steroid receptor systems in the hippocampus.

Adrenalectomy

Administration of enoximone in cardiogenic shock.

Thirteen patients in severe cardiogenic shock, persisting despite the use of adrenergic agents, were treated with enoximone, a recently available phosphodiesterase inhibitor. Cardiogenic shock was characterized by low cardiac output (less than 2.5 liter.min-1.m-2), elevated pulmonary artery balloon-occluded pressure (greater than or equal to 15 mm Hg), decreased urine output (less than 20 ml.hour-1) and increased blood lactate (greater than or equal to 2.0 mEq.liter-1). Ten patients were mechanically ventilated. A short-term intravenous infusion of 0.5 mg.kg-1 in 20 minutes of enoximone resulted in significant increases in cardiac index (from 1.8 +/- 0.3 to 2.9 +/- 0.3 liter.min-1.m-2, p less than 0.001) and stroke index (from 17.8 +/- 3.3 to 21.9 +/- 5.1 ml.m-2, p less than 0.001) and significant decrease in pulmonary artery balloon-occluded pressure (from 21.7 +/- 5.8 to 19.8 +/- 6.0 mm Hg, p less than 0.01) without a consistent change in mean arterial pressure (from 79 +/- 8 to 76 +/- 9 mm Hg, difference not significant). Enoximone administration decreased arterial oxygen tension (from 108 +/- 42 to 94 +/- 36 mm Hg, p less than 0.01) and increased venous admixture (from 12.8 +/- 6.5 to 16.0 +/- 8.0%, p less than 0.01). In 8 patients, a second infusion of 0.5 mg.kg-1 immediately thereafter amplified these changes. All patients but one survived the episode of cardiogenic shock and 5 patients left the hospital alive. These results indicate that the addition of enoximone to adrenergic agents in the treatment of cardiogenic shock can markedly increase cardiac output and stroke volume without substantial effects on arterial pressure.

Blood Gas Analysis

Effects of corticosterone on hippocampal slice electrophysiology in normal and adrenalectomized BALB/c mice.

Modulation of CA1 electrophysiological properties (amplitude, latency, paired-pulse facilitation) by different concentrations of corticosterone (CT) was studied in hippocampal slice preparations from normal (sham) and adrenalectomized (ADX) BALB/c mice. In the sham group, CT effects on the population spike (PS) amplitude were biphasic: at a low dose (200 pM) CT induced a delayed increase; at a moderate dose (2,000 pM), a rapid and partially reversible decrease was observed, and at higher doses (5,000 and 10,000 pM) this decrease was more pronounced after 30 min of washout. Diminution of latency and paired-pulse facilitation were obtained for the CT concentration inducing an increase of the PS amplitude. In the ADX group, similar CT effects were observed for lower doses: a decrease of the PS amplitude was observed for 40 and 100 pM and an increase for 5 pM, but variations of the PS amplitude were weaker than in the sham group. The role of the different CT receptor systems in this neuromodulatory effect is discussed.

Adrenalectomy

[Effects of adrenalectomy on in vitro evoked electrophysiological activity of the hippocampus in BALB/c mice].

The physiological properties of hippocampal slices from intact or adrenalectomized (ADX) BALB/c mice were studied in vitro. Mouse hippocampal slices displayed features similar to those observed in other species in terms of postsynaptic characteristics of response to stratum radiatum stimulation. In adrenalectomized mouse, the amplitude of population spike was reduced whereas the latency of population spike and cell responses to paired stimuli volleys were unchanged. The role of the endocrine status in this modification is discussed.

Adrenalectomy

A study of spontaneous and evoked activity in the rat hippocampus under helium-oxygen high pressure.

High pressures affect the physiology of the central nervous system. For a better understanding of this effect, we examined the hippocampal activity in the rat under high pressures (91 bars) of helium-oxygen. Effects of high pressure on hippocampal physiology are: an abnormally sustained 5-8 Hz pattern of spontaneous activity, followed, in some cases, by seizures; a marked decrease in the responses of CA1 pyramidal cells to stimulation of their commissural afferents; and a 50% decrease in the afterdischarge threshold. On the basis of the relatively well understood hippocampal physiology in normobaric conditions, our observations suggest that high pressures induce hypoexcitability of afferents and/or target cells.

Animals

[Effects of central administration of glucocorticoids on evoked electric activity of the hippocampus in mice].

The effect of central intraventricular administration (1 microgram) of corticosterone or dexamethasone on evoked electrical activity of dorsal hippocampus was analyzed in anaesthetized BALB/c mice. Corticosterone produced an important decrease in amplitude of the population spike activity elicited in CA1 field through commissural stimulation as well as through stimulation of the perforant path. In the same conditions, dexamethasone produced only a slight and brief effect.

Adrenal Cortex Hormones

Sectioning the efferent bundle decreases cochlear frequency selectivity.

Cochlear frequency selectivity was tested in rats and cats before and after sectioning the vestibular nerve which carries the efferent bundle to the cochlea. Compound action potential tuning curve were obtained by a simultaneous masking procedure. Transection of the efferent bundle resulted, in all group of animals, in an enlargement of the tip segment of the tuning curve. The Q10 dB value decreased by about 30% without any significant threshold change. These results taken together with previous developmental findings, suggest that efferents to outer hair cells could play a role in sharpening the frequency selectivity of the cochlea.

Animals

[Cellular detection of the in vivo incorporation of tritiated 2-deoxyglucose. Radioautographic study in the inner ear].

Inner ear injection of (3H) deoxyglucose was followed by in situ glutaraldehyde fixation and, after removal, by traditional preparation of the tissue for electron microscopy. Radioautography of semi-thin sections revealed preferential tracer accumulation in metabolically active structures such as the cochlear stria vascularis and the dark cells surrounding the basis of the vestibular cristae. Furthermore, in the vestibule, the perikaryon of some sensory cells was intensely labelled. These results show that an in vivo injection of deoxyglucose, followed by conventional histological processing can be used to mark active cells at both cellular and subcellular levels.

Animals