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Biomedical subjects

D Chassard

Publications and source records attributed to D Chassard.

At least 37 records · Page 2Linked to original sources

Diffusion of isepamicin into cancellous and cortical bone tissue.

The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of isepamicin at a dose of 15 mg/Kg, and the results were correlated to microbiologic data to estimate the clinical efficacy of isepamicin in bone infections. In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 15 mg/Kg dose of isepamicin. Plasma and bone tissue samples were collected a mean 1.3 hours later and analyzed by a high-pressure liquid chromatography method. Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 53.5 Kg, mean creatinine clearance, 58.5 mL/min) were enrolled. The mean +/- SD plasma concentration of isepamicin at the time of bone removal was 43.0 +/- 10.4 microg/mL. The mean +/- SD isepamicin concentrations were 11.6 +/- 7.1 microg/mL in cancellous bone tissue and 12.0 +/- 7.3 microg/mL in cortical bone tissue. The mean +/- SD ratios of isepamicin concentration in bone and plasma (bone/plasma) were 0.28 +/- 0.14 for cancellous bone tissue and 0.31 +/- 0.20 for cortical bone tissue. The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.

Adult↗

Slow release caffeine and prolonged (64-h) continuous wakefulness: effects on vigilance and cognitive performance.

Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow-release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double-blind, randomised, placebo controlled, two-way crossover study. A total of 300-mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD-NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop's test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00-04:00 h, 14:00-16:00 h) and hypervigilance (10:00-12:00 h, 22:00-00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop's test (P=0.048). We showed that 300-mg SRC given twice daily during a 64-h SD is able to antagonize the impairment produced on vigilance and cognitive functions.

Adult↗

Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine model.

Sevoflurane is widely used in anaesthetic protocols for patients undergoing surgical procedures. However, there are no reports on the influence of sepsis on minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans. The aim of this study was to test the hypothesis that sepsis could alter the MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication, anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline haemodynamic recording included electrocardiography, carotid artery blood pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(SEV) was determined using incremental changes in sevoflurane concentration until purposeful movement appeared. Pigs were assigned randomly to two groups: the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h after infusion. Significant increases in mean artery pulmonary pressure, filling, epinephrine and vascular pulmonary resistances occurred in the sepsis group. MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%] and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These data indicate that MAC(SEV) is significantly decreased in this normotensive septic pig model.

Analgesics↗

Influence of sepsis on minimum alveolar concentration of desflurane in a porcine model.

The effect of sepsis on the minimum alveolar concentration of desflurane (MAC(DES)) in humans and other animals has not been reported previously. The aim of this study was to test the hypothesis that sepsis might alter MAC(DES) in a normotensive septic porcine model. Twenty-four young healthy pigs were premedicated with ketamine 10 mg kg(-1 )i.m and then anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Baseline MAC(DES) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(DES) was determined by changing desflurane concentrations stepwise until purposeful movement appeared. Pigs were randomly assigned to two groups of 12 animals: the saline group received a 1 h i.v. infusion of saline solution while the sepsis group received a 1 h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolaemic haemodynamic status. In both groups, MAC(DES) was evaluated 5 h after infusion. Significant increases in heart rate, cardiac output, mean pulmonary artery pressure and pulmonary vascular resistance occurred in the sepsis group. MAC(DES) was 9.2% (95% confidence interval (CI) 6.8-10.6%) for the saline group and 6.7% (95% CI: 4.7-10.4) for the sepsis group (P<0.05). These data indicate that MAC(DES) is significantly decreased in this normotensive hyperkinetic septic porcine model.

Anesthetics, Inhalation↗

The analgesic effect of sufentanil combined with ropivacaine 0.2% for labor analgesia: a comparison of three sufentanil doses.

UNLABELLED: The combination of opioids with local anesthetics is commonly used for epidural labor analgesia. We examined whether increasing sufentanil in doses of 5, 10, and 15 microg prolonged the duration of labor analgesia produced by ropivacaine. One hundred healthy parturients in the first stage of labor who requested epidural analgesia were enrolled. Parturients were randomized to receive 12 mL ropivacaine 0.2% alone or with sufentanil 5 microg, sufentanil 10 microg, or sufentanil 15 microg. The duration of analgesia, pain score, degree of motor blockade (using a four-point Bromage scale), heart rate, blood pressure, respiratory rate, oxygen saturation, and incidence of nausea and pruritus were recorded. The mean duration of epidural analgesia was 96 +/- 32 min for patients without sufentanil, 134 +/- 27 min for Group 5 (p < 0.01 versus control), 135 +/- 33 min for Group 10 (p < 0.01 versus control), 130 +/- 33 min for Group 15 (p < 0.01 versus control) without differences among sufentanil groups. Between 30 and 90 min, the sufentanil groups (5 microg, 10 microg, and 15 microg) had lower pain scores than the control group (p < 0.01 versus control) but there were no differences among the sufentanil groups. No patient in any group had a Bromage score more than 1. No significant difference was found for opioid-related side effects. We conclude that 5-10 or 15 microg sufentanil induced a similar prolongation of analgesia when combined with ropivacaine 0.2% for initiation of labor analgesia. IMPLICATIONS: We studied the effect of adding one of three possible sufentanil doses to epidural ropivacaine 0.2% for labor analgesia. Adding sufentanil increased the duration of analgesia but there was no advantage in adding more than 5 microg of sufentanil.

Adult↗

An evaluation of the Gram stain in protected bronchoalveolar lavage fluid for the early diagnosis of ventilator-associated pneumonia.

We investigated the usefulness and reliability of the Gram stain value versus quantitative cultures in the early diagnosis of ventilator-associated pneumonia (VAP) using the protected bronchoalveolar lavage (PBAL). One hundred four mechanically ventilated patients (age = 52 +/- 19; SAPS II = 38 +/- 15) with a strong suspicion of VAP were consecutively included. One hundred sixteen PBAL were performed and mini-bronchoalveolar lavage were analyzed using the Gram stain standard method and the conventional quantitative culture technique. VAP diagnosis was based on a positive quantitative culture of mini-bronchoalveolar lavage fluid (cutoff > or = 10(3) CFU/mL). A final diagnosis of VAP was established in 67 patients and there was no infection in 49 cases. Regarding detection of bacteria using the Gram stain, we found a sensitivity of 76.2%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 75.4%. There was a good agreement with the final diagnosis (kappa statistic 0.73; concordance 86.2%). The degree of qualitative agreement between Gram stain and quantitative cultures was analyzed in the VAP group: the correlation was complete in 39% (26 of 67 VAP), partial in 28% (19 of 67 VAP) and there was no correlation in 33% (22 of 67 VAP). We conclude that despite its overall "good agreement," the Gram stain is of limited use for the rapid diagnosis of VAP and unreliable for the early adaptation of empirical antimicrobial therapy when using the noninvasive PBAL procedure.

Adult↗

Oxidative stress status during exposure to propofol, sevoflurane and desflurane.

UNLABELLED: We evaluated the circulating and lung oxidative status during general anesthesia established with propofol, sevoflurane, or desflurane in mechanically ventilated swine. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were respectively performed via an internal jugular vein catheter and a nonbronchoscopic BAL for baseline oxidative activity measurements: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). A 4-h general anesthesia was then performed in the three groups of 10 swine: the Propofol group received 8 mg x kg(-1) x h(-1) of IV propofol as the sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration of desflurane; and the Sevoflurane group received 1.0 minimum alveolar concentration of sevoflurane. We observed significantly larger levels of MDA in plasma and BAL during desflurane exposure than with the other anesthetics. We also observed smaller concentrations of circulating GPX and alveolar GPX. We found a significant decrease for MDA measurements in the plasma and the pulmonary lavage during propofol anesthesia. We also found larger values of GPX measurements in the serum and the pulmonary lavage. No significant changes were observed when animals were exposed to sevoflurane. No significant changes were found for circulating concentrations of SOD during exposure to all anesthetics. In this mechanically ventilated swine model, desflurane seemed to induce a local and systemic oxidative stress, whereas propofol and sevoflurane were more likely to have antioxidant properties. IMPLICATIONS: Superoxide is an unavoidable byproduct of oxygen metabolism that occurs in various inflammatory reactions. Inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response. We evaluated the bronchoalveolar and systemic oxidative stress in swine during exposure to propofol and newer volatile anesthetics. Desflurane induces more lipid peroxidation than do the other anesthetics.

Anesthetics, Inhalation↗

Slow-release caffeine: a new response to the effects of a limited sleep deprivation.

STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine 300 and 600 mg are efficacious doses but the optimal dose (maximum effect without any side effects) for both men and women is after all 300 mg. Globally, there is no difference between placebo and caffeine during the recovery night period. CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance to maintain a good level of vigilance and performance during limited sleep deprivation.

Adolescent↗

Estimation of cardiac preload changes by systolic pressure variation in pigs undergoing pneumoperitoneum.

BACKGROUND: Variations in systolic pressure arterial waveform (SPV) and its component have been shown to be a reasonable indicator of left ventricular preload. Creation of a pneumoperitoneum (PMOP) by insufflation of CO2 increases intrathoracic pressure, leading to overestimation of preload as assessed by pressure methods. The purpose of this study was to compare SPV with other standard methods in anaesthetized pigs. METHODS: We measured SPV and its DeltaDown component (deltaDown), pulmonary artery occlusion pressure (PAOP) and left ventricular short-axis cross-sectional area using transthoracic echocardiography (TTE) in 7 pigs, at baseline, after 12 mmHg PMOP and after an intravascular load with 10 ml/kg hydroxylethylstarch (HES). RESULTS: PMOP increased SPV from 12.9+/-4.9 to 16.9+/-5.5 mmHg (P<0.05) and decreased pulmonary compliance, with no change in PAOP or end-diastolic area assesssed by TTE. Intravascular volume loading significantly decreased SPV from 16.9+/-5.5 to 11.2+/-4.9 mmHg and deltaDown from 9.9+/-7.1 to 5.2+/-4.5 (P<0.05), and increased PAOP and end-diastolic area. Significant correlation between changes in deltaDown and EDA was noted following HES (r=0.78, P<0.05). CONCLUSION: In anaesthetized pigs, the creation of a PMOP alters SPV, likely by decreasing lung compliance. Once PMOP is established, changes in cardiac preload could be estimated by SPV analysis.

Animals↗

Metabolic acidosis and respiratory acidosis impair gastro-pyloric motility in anesthetized pigs.

UNLABELLED: Acidosis impairs smooth muscle function in various organs. However, the effects of acidosis on the gastroduodenal tract are unknown while its dysfunction has potential perioperative harmful consequences. We investigated the effects of metabolic (MA) and respiratory acidosis (RA) on upper gut motility in tracheally ventilated pigs whose anesthesia was induced with halothane and maintained with alpha-chloralose-urethane administration (IV). Increased dead space and perfusion of hydrochloric acid 1 N (150 mL over 30 min) were used to induce RA and MA, respectively. Measurements of fundic tone using an electronic barostat, antro-pyloroduodenal phasic motility with perfused manometry and antro-duodenal electric control activity by electromyography were used to evaluate gastroduodenal function. Acidosis increased the fundic tone as reflected by a decrease in barostat volumes from 275+/-83 to 194+/-88 mL for MA and from 278+/-93 to 236+/-106 mL for RA. Pyloric and duodenal basal tones were not affected by either acidosis. A decrease in pyloric contraction amplitude from 95+/-24 to 62+/-26 mm Hg during MA and from 94+/-26 to 64+/-20 mm Hg during RA was observed. Both acidosis altered antral control activity that became dysrhythmic. Acidosis could be implicated in perioperative complications, such as gastroparesis, emesis, and regurgitation of gastric contents. IMPLICATIONS: Metabolic and respiratory acidosis mainly affects gastric antral rhythms and has a major effect on fundic tone. Acidosis could be implicated in perioperative complications, such as gastroparesis, emesis, and regurgitation of gastric contents.

Acidosis↗

Effect of SR49059, an orally active V1a vasopressin receptor antagonist, in the prevention of dysmenorrhoea.

OBJECTIVE: To investigate the clinical effect of SR49059 when given shortly before the onset of menstruation as a preventative treatment of dysmenorrhoea. DESIGN: A double-blind, randomised, placebo-controlled, cross-over trial in complete block design (three periods, three treatments). SETTING: A clinical research organisation in Paris, France. PARTICIPANTS: Women aged 18-35 years suffering from primary dysmenorrhoea. INTERVENTIONS: In each of three menstrual cycles, women reported to the study centre and were given a daily dose of either placebo, 100 mg or 300 mg SR49059 from a minimum of 4 hours up to a maximum of three days before the onset of bleeding and/or menstrual pain. If this did not control the pain, women were allowed once a day to take a second dose of study treatment providing that at least 4 hours had passed since the first drug intake. MAIN OUTCOME MEASURES: Intensity of menstrual pain recorded by means of a visual analogue scale. Rating of symptoms of dysmenorrhoea (mainly back and pelvic pain) in relation to functional capacity (Sultan score). Self-assessment of menstrual blood loss in a menstrual diary record. RESULTS: Analysis of intensity of menstrual pain, as recorded by visual analogue scale and Sultan pain score (back and pelvic pain) during the first 24 hours of dysmenorrhoea, showed a dose-related effect of SR49059. The 300 mg dose of SR49059 was significantly more effective than placebo. Similarly, a dose-related effect of SR49059 was shown on total Sultan score. SR49059 was well tolerated and no significant effect on the bleeding pattern was noted. CONCLUSIONS: This study showed for the first time a therapeutic effect of an orally active vasopressin V1a receptor antagonist in the prevention of dysmenorrhoea. Further studies are required to examine effect mechanisms and determine effective doses.

Administration, Oral↗