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Biomedical subjects

M Lamy

Publications and source records attributed to M Lamy.

At least 55 records · Page 3Linked to original sources

Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results.

We studied the effects of intravenous ephedrine on the onset time and the intubating conditions 2 min after a bolus dose of cisatracurium (0.15 mg kg-1). Thirty patients anaesthetized with sufentanil and propofol were randomly divided in 2 groups to receive either ephedrine (70 micrograms.kg-1) or saline, 5 s before propofol. Cisatracurium was administered after loss of consciousness. Neuromuscular block was assessed at the adductor pollicis using accelography. Tracheal intubation was performed 2 min after cisatracurium injection and rated as excellent, good, poor or bad. At intubation, neuromuscular block (% height of control T1) was greater in patients receiving ephedrine (36.1 +/- 25.8% vs 57.9 +/- 25.1%) (mean +/- SD). The frequency of excellent intubating conditions was higher after ephedrine (86.6%) than after saline (40.0%). The onset time of cisatracurium was shorter after ephedrine (167 +/- 64.8 s vs 234.9 +/- 63.1 s). Thus, a low dose of ephedrine given before induction of anaesthesia improves the intubating conditions 2 min after 0.15 mg kg-1 cisatracurium and this effect likely relates to a quicker onset of neuromuscular block.

Adult↗

Effects of mild hypothermic cardiopulmonary bypass on EEG bispectral index.

We studied the effect of mild hypothermic cardiopulmonary bypass (30 degrees C) on the EEG Bispectral Index in 10 patients undergoing elective CABG. BIS was recorded at 11 event-related time points during the procedure. After a significant decrease at the induction of anaesthesia, BIS was not further modified during the procedure. BIS was neither affected by surgical stimulation nor by CPB and mild hypothermia. We conclude that we did not find any reason to preclude the use of BIS to assess the hypnotic effects of anaesthetics during normothermic or mild hypothermic CPB.

Aged↗

Oxidation sensitivity may be a useful tool for the detection of the hematotoxic potential of newly developed molecules: application to antipsychotic drugs.

Some antipsychotic agents have been found to produce agranulocytosis and aplastic anemia. The oxidation phenomena and/or the formation of free radicals has been suggested to be causally related to various hematological disorders, e.g., agranulocytosis. Using five experimental conditions, we tested the oxidative potential of compounds with and without a history of hematological side effects, e.g., agranulocytosis and aplastic anemia. A statistical analysis was undertaken for each experimental condition and a multivariate analysis combining all results was performed. Two peroxidase-induced free radical models did not successfully discriminate between drugs with and without a history of causing hematologic problems (<70%). The lipid peroxidation system provided even less satisfactory discrimination, with only 56.25% correct classification. However, an 87.5% correct classification was obtained when using the oxidation potentials of these drugs determined at pH 4.7 and at pH 7.4. A multivariate analysis taking into account the five variables provided 87.5% success in classification. The two clusters were better discriminated in terms of a "distance coefficient." In a second analysis, the putative antipsychotic pyridobenzodiazepine analogues (JL5, JL8, JL18, and JL25) were classified in the cluster of toxic compounds, while the oxa- and thiazepine analogues (JL2, JL3, and JL13) were classified as nontoxic compounds. On the other hand, a few metabolites of clozapine and fluperlapine were classified in the toxic compound group. The procedure described herein is, to our knowledge, the first which classifies molecules of different structures as well as different pharmacological profiles according to their hematotoxic potential. Such a procedure could be used to predict drug-induced hematological side effects.

Agranulocytosis↗

Peroxynitrite reacts with biological nitrogen-containing cyclic molecules by a radical pathway, as demonstrated by ultraweak luminescence coupled with ESR technique.

Ultraweak luminescence (uwCL) was coupled with electron spin resonance to study the reactions of 3 heterocyclic compounds (tryptophan, serotonin and imidazole) with peroxynitrite at pH 8.7. Tryptophan and serotonin reacted with emission of a flash peak of light (5 s) followed by a long-living light emission of +/- 80 s. Addition of the spin trap 4-POBN at different intervals, after the beginning of reaction revealed that a short-living free radical was produced in the case of serotonin and imidazole, but that with tryptophan, the initial radical rearranged into a relatively long-living radical, which was still formed when 4-POBN was added after 55 s (decreasing phase of uwCL).

Electron Spin Resonance Spectroscopy↗

Functional neuroanatomy of hypnotic state.

BACKGROUND: The aim of the present study was to describe the distribution of regional cerebral blood flow during the hypnotic state (HS) in humans, using positron-emission tomography (PET) and statistical parametric mapping. METHODS: The hypnotic state relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness." A group of 9 subjects under polygraphic monitoring received six H215O infusions and was scanned in the following order: alert-HS-HS-HS with color hallucination-HS with color hallucination-alert. PET data were analyzed using statistical parametric mapping (SPM95). RESULTS: The group analysis showed that hypnotic state is related to the activation of a widespread, mainly left-sided, set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal cortices and a few right-sided regions: occipital and anterior cingulate cortices. CONCLUSIONS: The pattern of activation during hypnotic state differs from those induced in normal subjects by the simple evocation of autobiographical memories. It shares many similarities with mental imagery, from which it differs by the relative deactivation of precuneus.

Adult↗

Effects of training on exercise-induced muscle damage and interleukin 6 production.

To address the question of whether the increased plasma concentration of interleukin 6 (IL-6) following strenuous muscular work could be related to exercise-induced muscle damage, 5 moderately active male volunteers underwent two isokinetic exercise sessions in the eccentric mode, separated by a period of 3 weeks during which the subjects underwent five training sessions. Before training, exercise was followed by severe muscle pain (delayed-onset muscle soreness; DOMS), and by significant increases in plasma IL-6 level and serum myoglobin concentration (SMb) (P < 0.001). After training, postexercise DOMS and SMb values were significantly lower than those measured before training. There was no significant difference between plasma IL-6 levels measured at the same time points before and after training. We conclude that the hypothetical relationship between exercise-induced muscle damage and increased postexercise levels of circulating IL-6 is not substantiated by the present results.

Adult↗

High concentrations of histamine stimulate equine polymorphonuclear neutrophils to produce reactive oxygen species.

OBJECTIVE AND DESIGN: Because high concentrations of histamine are locally released in inflammation, we investigated the effects of supraphysiological doses of histamine on the production of reactive oxygen species (ROS) by neutrophils. MATERIALS AND METHODS: Isolated equine neutrophils were activated by 10(-4) to 5 x 10(-3) M histamine. The production of ROS and free radicals was estimated by luminol-enhanced chemiluminescence (CL) and electron spin resonance (ESR) with spin trapping technique. In this model of histamine-stimulated neutrophils, we tested the antagonists of H1 and H2 histamine receptors, the role of Ca2+ and Mg2+, the role of staurosporine and pertussis toxin (inhibitors of protein kinase C and proteins G) and the effects of superoxide dismutase, catalase, hydroxyl radical scavengers (phenylalanine and mannitol) and N(G)-monomethyl-L-arginine (L-NMMA), inhibitor of NO-synthase. RESULTS: Histamine (from 10(-5) to 10(-3) M) stimulated neutrophils to produce CL and ESR signals characterized by spin adducts of superoxide anion and/or hydroxyl radicals. The CL response was inhibited by 10(-4) and 10(-3) M H1 receptor antagonists (promethazine, pyrilamine, and diphenhydramine), by Ca2+ and Mg2+ depletion and by 10 nmoles staurosporine. CL was partially inhibited by pertussis toxin (4 microg/ mL). The ESR signals were practically suppressed by pyrilamine (an H1 receptor antagonist) and superoxide dismutase, and partially inhibited by catalase, hydroxyl radical scavengers and L-NMMA (respectively 59, +/- 30% and 68% inhibition). CONCLUSIONS: High concentrations of histamine stimulated the neutrophils to product ROS and free radicals via H1 receptors and the NADPH-oxidase pathway.

Animals↗

Study of the protective effects of hyperimmune immunoglobulins G and M against endotoxin in mice and rats.

We prepared solutions of human IgM and IgG to various lipopolysaccharide (LPS) species. These were then tested, along with solutions of non-LPS specific human IgG or IgM, for their ability to confer passive immunity against experimental endotoxemia in two animal models. The immunoglobulins were first tested for an effect on the lethality induced by seven different LPSs in actinomycin-D sensitized mice, or by three different bacteria in normal mice. When the immunoglobulins were administered 1 h before challenge, a small protective effect was observed. This protection was dependent upon both the anti-LPS agent, the chemical composition of the LPS, or the strain of gram-negative bacteria used for injection. The anti-LPS IgM and IgG preparations reduced the mortality induced by Escherichia coli but not by Serratia marcescens or Klebsiella pneumoniae, indicating protection by strain-specific antibodies. When the antibodies were preincubated with LPS or bacteria for 30 min before administration, almost complete protection was seen. The influence of these immunoglobulin preparations or of human albumin (as a control) on the hypotensive and vascular-permeabilizing effects of LPS in rats was then studied. A dose-dependent inhibitory effect was observed with IgG preparations and albumin. At 200 mg/kg, anti-LPS IgG reduced the effects of LPS, while at 400 mg/kg, both anti-LPS and normal IgG preparations showed protection, as did human albumin used at the same dose. The IgM-enriched preparation worsened the initial hypotensive phase after LPS, whereas the anti-LPS IgM significantly reduced the second phase of the hypotension, but only at the largest dose of 400 mg/kg. In this second model using the rat, a clear difference between the activity of IgG and IgM was thus observed. We conclude that pretreatment with human immunoglobulins from large plasma pools modestly, but significantly, attenuated the effects of murine and rat Gram-negative sepsis, but that protection was incomplete. Our results suggest that single regimen intervention strategies may not be sufficient to influence the course of the disease.

Animals↗

Influence of human anti-lipopolysaccharide immunoglobulins on tissue distribution and clearance of lipopolysaccharide in rats.

To examine the influence of passive immunization on the biological fate of injected lipopolysaccharide (LPS), we used a human IgG preparation (anti-LPS IgG) rich in antibodies to a large panel of smooth and rough purified LPS extracts as well as a normal IgG preparation (standard IgG). Our approach was to compare the uptake of 125I-labeled LPS by the tissues of saline or IgG-treated rats. After intravenous injection, one fraction of 125I-labeled Escherichia coli O55:B5 LPS is rapidly taken up by tissues, while another fraction remained in the blood. Uptake of 125I-labeled LPS was principally observed into the liver and spleen. In rats treated prophylactically with standard IgG, these tissues accumulated significantly larger amount of LPS than the tissues of rats treated with anti-LPS IgG. Nevertheless, both IgG preparations increased the specific binding of LPS by the liver and spleen. High levels of homologous unlabeled LPS decreased the uptake of LPS by the liver, presumably by occupying tissue receptors, whereas in the presence of E. coli O127:B8 LPS, an increase of the uptake of 125I-labeled LPS by the liver and lungs was observed. The pharmacokinetics and tissue distribution of LPS-IgG complexes pre-formed in vitro were compared. In the presence of standard IgG, a unexpected increase of the uptake of LPS by the tissues was recorded, whereas LPS-anti-LPS IgG complexes decreased the binding of 125I-labeled LPS to the tissues. On the other hand, the vascular effects induced by LPS did not appear to be modified in rats pretreated with either IgG preparation. In conclusion, although passive immunization against LPS slightly modified the uptake and clearance of LPS, neither in vitro nor in vivo formation of LPS-anti-LPS IgG complexes afforded a very significant protection against the toxic effects of LPS.

Animals↗

Oral status and nutrition in the institutionalized elderly.

OBJECTIVES: To evaluate, in an elderly population, whether poor oral status might be a contributing factor to the development of undernutrition and might be associated with less eating pleasure, more subjective eating difficulty and increased mashed food consumption. METHODS: An oral examination and an evaluation of masticatory capacity were performed on 120 institutionalized elderly subjects. The nutritional assessment included serum albumin concentration, the Mini Nutritional Assessment and a questionnaire on eating habits. RESULTS: Edentulous subjects without dentures or with only one complete denture had significantly lower MNA scores than edentulous subjects with two complete dentures (p < 0.05). Edentulous subjects with two complete dentures more frequently reported taking pleasure from eating (p = 0.05), and had less frequent difficulties with hard foods (p = 0.01) than edentulous subjects without dentures or with only one complete denture. Mashed food consumption (p < 0.01) was also reported more frequently in edentulous subjects without dentures or with only one complete denture. Subjects with two complete dentures had similar or better MNA scores as dentate subjects with relatively few remaining teeth (10.4 +/- 7.8 teeth). About half of the subjects (53%) could not perform the masticatory test. These subjects had lower MNA scores (p = 0.001) and a larger proportion ate mashed food (p < 0.001) compared to those who were able to perform the test. CONCLUSIONS: Poor oral status (edentulous without dentures or with only one complete denture) increased difficulty in eating hard foods, increased mashed food consumption and decreased eating pleasure. It seemed also to put institutionalized subjects at higher risk of undernutrition.

Aged↗

[Red cell substitutes: perfluorocarbon emulsions and hemoglobin solutions].

OBJECTIVE: To review the current data on perfluorocarbon (PFC) emulsions and haemoglobin (Hb) solutions. DATA SOURCES: For this paper we analysed the literature using Medline search along with major review articles. DATA SELECTION AND EXTRACTION: The collected articles were reviewed and selected according to their quality and originality. DATA SYNTHESIS: PFCs are synthetic fluorinated hydrocarbons capable of dissolving, at increased FIO2, large amounts of oxygen. They deliver oxygen at tissular level, and are administered as emulsions containing particles of around 0.1 micron, reaching the smallest vessels. They are exhaled unchanged by the lungs within 7 days. The first clinically used PFC was Fluosol-DA 20%. Currently, Oxyfluor 40% and Oxygent 60% are under evaluation. PFCs are not true blood substitutes, but rather a means to support tissue oxygenation during extreme haemodilution. Solutions of free Hb do not require compatibility testing and are fully saturated with oxygen at ambient FIO2. Hb is either human, bovine or recombinant Hb. In order to maintain adequate intravascular half-life and affinity for oxygen, the Hb molecules are modified by internal cross-linking, polymerisation and encapsulation. After promising results using animal models, some of these modified Hb solutions are now undergoing phase III clinical trials. Among these, diaspirin cross-linked haemoglobin (DCLHb) has been tested in cardiac and orthopaedic surgery, as well as in trauma patients. The initial results of these multicentre trials are currently being analysed.

Animals↗

Influence of induction of anaesthesia on intubating conditions one minute after rocuronium administration: comparison of ketamine and thiopentone.

We compared the effect of thiopentone and ketamine on intubating conditions after rocuronium 0.6 mg.kg-1 in two groups of patients (n = 16 each), aged 21-44 years, undergoing elective surgery. Premedication consisted of alprazolam 1 mg by mouth 1 h before surgery. All patients received midazolam 2 mg intravenously 2 min before intravenous administration of thiopentone 5 mg.kg-1 or ketamine 2.5 mg.kg-1. Muscle relaxation was provided by rocuronium 0.6 mg.kg-1. One minute after rocuronium administration, tracheal intubation was performed within 15 s by a skilled anaesthetist blinded to the treatment group assignment. Intubating conditions were graded as excellent, good, fair or poor on the basis of jaw relaxation, position of vocal cords and diaphragmatic response. Neuromuscular transmission was assessed at the adductor pollicis muscle using a TOF-GUARD monitor. Excellent and good intubating conditions were obtained in 100% of patients in the ketamine group and in 50% of patients in the thiopentone group (p = 0.002). Jaw relaxation was similar in both groups but vocal cord conditions were better and the diaphragmatic response less marked in the ketamine group compared with the thiopentone group (p = 0.002). The degree of neuromuscular block [% decrease of T1, mean (SD)] at the time of intubation was similar: 51.8 (25)% (ketamine group) and 54.3 (23.1)% (thiopentone group). We conclude that ketamine 2.5 mg.kg-1 provides better intubating conditions than thiopentone 5 mg.kg-1 1 min after administration of rocuronium 0.6 mg.kg-1.

Adult↗

Effect of epidural bupivacaine on the relationship between the bispectral index and end-expiratory concentrations of desflurane.

We compared the relationship between the bispectral index and end-tidal desflurane concentrations in 20 patients undergoing elective surgery. Patients received epidurally either 10 ml saline (group S) or 10 ml bupivacaine 0.125% with epinephrine 1/800 000 (group B) before induction of anaesthesia with sufentanil (0.15 microgram.kg(-1)) and propofol (2 mg.kg(-1)); muscle relaxation was obtained with cisatracurium (0.2 mg.kg(-1)). Patients lungs were ventilated to maintain end-tidal desflurane at 3% in O2/N2O (50/50) until 5 min after skin incision, followed by two consecutive 10 min periods at end-tidal desflurane 6% and 9%. bispectral index values were recorded before induction, at 3% desflurane before and 5 min after skin incision, and at 6% and 9% end-tidal desflurane. Bispectral index decreased with increasing end-tidal desflurane concentration (ANOVA: p < 0.05). The decrease in bispectral index was significant between pre-induction, 3% and 6% desflurane. No significant difference was observed at 3% desflurane before and after skin incision, or between 6 and 9% desflurane. The relationship between bispectral index and end-tidal desflurane concentration was fitted by a linear regression in each group. No significant difference in bispectral index was observed between the groups at any time. We conclude that bispectral index decreases with increasing desflurane concentration and that this relationship is not affected by epidural 0.125% bupivacaine.

Adolescent↗

New evaluation therapies for sepsis.

This article presents an analysis of the literature of the last 2 years on the treatment of sepsis and septic shock. It appears that most of the antimediator therapies applied in phase II or III clinical trials yielded disappointing results. But, many other therapeutic approaches are proposed or are ongoing, and many papers report critical analysis of the reasons for the lack of success of past clinical trials.

Journal Article↗

Effects of two calculated plasma sufentanil concentrations on the hemodynamic and bispectral index responses to Mayfield head holder application.

The effects of two calculated plasma sufentanil (SUF) concentrations on the hemodynamic and bispectral index (BIS) responses to Mayfield head holder (MH) application were studied in 20 patients scheduled for intracranial surgery. Premedication consisted of hydroxyzine, alprazolam, and atropine given orally 1 hour before surgery. Anesthesia was provided with propofol (PPF) and SUF using a target-controlled infusion device. Patients were randomly assigned to one of two groups according to calculated plasma concentrations: 3 microg/mL(-1) of PPF and 0.5 ng/mL(-1) of SUF in group I (GI) and 3 microg/mL(-1) of PPF and 1 ng/mL(-1) of SUF in group II (GII). The MH was fixed 33.0+/-6.6 minutes (mean +/- SD) after induction. Systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as well as heart rate (HR) and BIS were recorded 1 minute before pinning (baseline) as well as 1 minute (P1), 2 minutes (P2), and 3 minutes (P3) after pinning. Multivariate repeat-measured analyses of variance were applied to the baseline-subtracted measurements of hemodynamic and BIS values. Groups were compared using the Student's t test, and P < .05 was considered to be statistically significant. Patients' characteristics, baseline hemodynamic values, and BIS values were similar in both groups. A significant overall time effect was observed for all variables, but no significant overall SUF effect was detected. Increases in SAP, MAP, DAP, and HR did not differ significantly between groups. The increase in hemodynamic variables did not exceed 20% of baseline value in either group. In contrast, at P1, the increase in BIS over the baseline value was significantly higher in GI (15.0+/-7.9) than in GII (6.7+/-6.5). In conclusion, MH application was associated with a significant, although not clinically relevant, increase in hemodynamic variables whatever the calculated plasma SUF concentration (0.5 or 1.0 ng/mL(-1)). In contrast, the increase in BIS observed at pinning was significantly higher in patients with the lowest calculated plasma SUF concentrations. This suggests that the BIS response to noxious stimulation is modulated by the analgesic regimen.

Alprazolam↗

Red blood cell substitutes: fluorocarbon emulsions and haemoglobin solutions.

The problems posed by transfusion of homologous blood have led to the development of substances able to replace the gas transporting properties of blood. Perfluorocarbons (PFCs) emulsions and modified haemoglobin (Hb) solutions have been developed for this goal and are now tested in clinical assays. PFCs are synthetic fluorinated hydrocarbons, capable of dissolving large quantities of oxygen (O2; without binding) at high inspired concentrations of O2, and of delivering this O2 to the tissues. They are administered as emulsions containing particles with a diameter of approximately 0.2 micron, capable of entering the microcirculation. They are eliminated unchanged by the lungs within several days. Fluosol-DA 20% was the first PFC emulsion used in clinical practice. Currently, Oxygent, a second generation PFC emulsion, is being evaluated in clinical studies. The PFCs are not blood substitutes, but rather a means to ensure tissue oxygenation during extreme haemodilution. Solutions of free Hb do not have the antigenic characteristics of the blood groups, and do not require compatibility testing. They are fully saturated with O2 at ambient FiO2. The Hbs used are derived from either human or bovine sources, or via recombinant DNA technology. In order to maintain satisfactory intravascular half-life and O2 affinity, the Hb molecules are modified by adding internal crosslinks, by polymerization, and/or by encapsulation. After promising animal studies, several of these modified Hb solutions are now being studied in Phase III clinical trials. Among them, diaspirin cross-linked haemoglobin (DCLHb) has been used in cardiac and orthopaedic surgery, and for resuscitation of traffic accident victims. The initial results of multicentre trials are now being analysed.

Aspirin↗

Plasma myeloperoxidase level and polymorphonuclear leukocyte activation in horses suffering from large intestinal obstruction requiring surgery: preliminary results.

Myeloperoxidase (MPO) is a specific enzyme of neutrophil azurophilic granules with a strong oxidative activity. Thanks to a radioimmunoassay of equine myeloperoxidase, the authors have observed a significantly higher plasma level of MPO in horses operated for strangulation obstruction of the large intestine (n = 6) than in horses suffering from a non-strangulating displacement of the large intestine (n = 9). For the 2 groups, 3 phases were distinguished: reception (P1), intensive care (P2) and terminal phase (P3). The mean peak values of MPO for these phases were 121.6 ng/mL (P1), 168.6 ng/mL (P2), and 107.0 ng/mL (P3) for the non-strangulating group, and 242.6 ng/mL (P1); 426.0 ng/mL (P2), and 379.5 ng/mL (P3) for the strangulation group. The variations of the mean peak values of plasma MPO were significantly different between the 2 groups and between the different phases. A significant increase of the least square means of MPO was observed between P1 and P2. A significant decrease of the least square means of the number of circulating leukocytes was observed between P1 and P3. Polymorphonuclear neutrophil activation could play a major role in the pathogenesis of acute abdominal disease and endotoxic shock.

Acute Disease↗