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Biomedical subjects

D Chassard

Publications and source records attributed to D Chassard.

At least 91 records · Page 5Linked to original sources
PubMed1994

Metabolic effects of a D-beta-hydroxybutyrate infusion in septic patients: inhibition of lipolysis and glucose production but not leucine oxidation.

OBJECTIVE: To study the effect of a D-beta-hydroxybutyrate infusion on protein metabolism, lipolysis, and endogenous glucose production in septic patients. DESIGN: Prospective, randomized trial. SETTING: Intensive care unit (ICU) and metabolic unit at a university hospital. PATIENTS: Twelve ICU patients with sepsis and six healthy normal subjects. INTERVENTIONS: Septic patients were administered 4-hr infusions of either D-beta-hydroxybutyrate or a control solution, 12 hrs after parenteral nutrition was replaced with an isotonic saline infusion. MEASUREMENTS AND MAIN RESULTS: The appearance and oxidation rates of leucine (L[1-13C]leucine) and endogenous glucose production (D[6,6-2H2]glucose), plasma fatty acids, and glycerol values were measured before and at the end of infusion of D-beta-hydroxybutyrate or control solution. Unlike the control test, the D-beta-hydroxybutyrate infusion decreased glucose production, fatty acids, and glycerol concentrations, but failed to decrease the leucine oxidation rate. CONCLUSION: Exogenous ketone-bodies infusion decreased lipolysis and glucose production in septic patients but had no beneficial effect on protein metabolism, as evaluated with L[1-13C]leucine.

3-Hydroxybutyric Acid↗
PubMed1994

Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on didanosine therapy.

We report two cases of fulminant hepatic failure in HIV-1-infected patients treated with didanosine (ddI). Clinical manifestations including vomiting, diarrhoea and dyspnoea were identical in both cases. Biological data mainly revealed hepatic failure and lactic acidosis. Histological examination of liver biopsies showed diffuse microvesicular steatosis. The outcome was fatal in both patients. The only comparable case previously reported (Lai et al., 1991) showed close similarities in the clinical, biological and histological manifestations with microvesicular steatosis. This prompted us to suspect that ddI might be responsible for fulminant hepatitis in all three AIDS patients. This toxic effect may be added to the list of potential adverse events occurring during ddI therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Metabolic impact and complications of intra-uterine resection].

Hysteroscopic surgery with the use of a resectoscope are currently going through major developments. They are often aimed at healthy women who consider having relatively minor surgery. Many complications can affect endometrial resection. Some metabolic complications due to the irrigating liquid have been identified recently in gynaecological surgery, and can be defined as the whole group of clinical symptoms linked to the passage of the irrigation liquid into systemic circulation. Neurological and cardiovascular disorders are due to an acute dilutional hyponatremia and to the very toxicity of glycol and/or of its metabolites. The way the irrigating liquid is resorbed has an effect on the order in which these accidents happen. The duration of the resection, its depth, as well as the intrauterine pressure are the three factors which make it easier for a clinical syndrome to appear. Whatever the mechanism responsible, the clinical and biological consequences are the same and can be more or less serious, depending on how much liquid has been resorbed: they are non-existent up to one liter, and appear between 1.5 and 2 liters. Recent studies have shown that natremia and glycinemia are closely and inversely related. By taking a number of precautions, accidents--which are relatively rare but can be very serious--could be prevented.

Endometrium↗
PubMed1992

The pharmacokinetics of tiopronin and its principal metabolite (2-mercaptopropionic acid) after oral administration to healthy volunteers.

We have studied the pharmacokinetics of tiopronin and its principal metabolite, 2-mercaptopropionic acid (2-MPA) in healthy volunteers after the oral administration of 500 mg (2 Acadione tablets), followed by simultaneous assay of the two compounds in plasma over a period of 48 h using a new method (emission of fluorescence after HPLC and post-column derivatization by pyrene-maleimide). The absorption of tiopronin was slow (tmax between 4 and 6 h) and the plasma concentrations subsequently fell biexponentially. The principal metabolite 2-MPA appeared later in the plasma (tmax between 10 and 12 h after a lag-time of 3 h) then disappeared monoexponentially. About 15% of the tiopronin was metabolized to 2-MPA.

Administration, Oral↗
PubMed1992

Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans.

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.

3-Hydroxybutyric Acid↗
PubMed1992

Catheter fracture and embolisation in a totally implanted venous access catheter (TIVAC) following shoulder trauma.

A totally implanted intravenous catheter (TIVAC) was placed via the subclavian vein in a 32-year-old male patient with HIV infection for intermittent drug therapy. 8 months after insertion, a catheter fracture was noted with embolisation of the distal part into the heart. This accident was related to shoulder trauma with a downward movement of the clavicle. In active patients alternatives to the subclavian approach for TIVAC need to be considered.

Journal Article↗
PubMed1992

Pharmacokinetics of 2-(alpha-thenoylthio)-propionylglycine (TTPG) in healthy volunteers--an oral dose-proportionality investigation.

The dose linearity of 2-(alpha-thenoylthio)-propionylglycine (TTPG) pharmacokinetics after a single oral administration at three different TTPG doses (180, 540 and 1080 mg) was evaluated in 12 healthy volunteers according to an open, randomized, cross-over study with a 1-week wash-out period between each administration. The duration of the study, for each subject, was 4 weeks. Plasma concentration and urinary excretion of TTPG and its two systemic metabolites, namely propionylglycine (tiopronin) and thiophenecarboxylic acid (TCA) were assayed by a previously well validated HPLC method. Due to differences in the physical and chemical properties of these compounds, two assays were needed, one to measure TTPG and TCA as such, and one to measure derivatized tiopronin. Both used UV detection. TTPG, tiopronin and TCA were quickly detected in plasma, suggesting that the drug administered is rapidly absorbed and biotransformed, in part, in the systemic circulation into the two metabolites noted above. Time-to-peak for all three analytes showed a trend to increase with increasing doses of TTPG, being: 0.42, 0.40 and 0.67 h (P < 0.01) with TTPG; 0.53, 0.47 and 0.73 h (P < 0.05) with TCA; and 1.33, 2.13 and 2.58 h (P < 0.01) with tiopronin. Cmax showed the opposite behaviour with values (ng ml-1) normalized to the dose of 540 mg: 1235, 905 and 513 (P < 0.001) with TTPG; 888, 547 and 383 (P < 0.001) with TCA; and 7290, 6950 and 5170 (P < 0.01) with tiopronin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Acute respiratory insufficiency caused by diffuse pulmonary hemorrhage].

Two cases of adult respiratory distress syndrome due to diffuse pulmonary haemorrhage are reported. The first patient was treated with azathioprine, prednisolone, cyclosporine and ranitidine for haemorrhagic rectocolitis; the second has untreated primary biliary cirrhosis. Haemoptysis only occurred in the latter. Both had severe isolated hypoxaemia. Chest X-rays revealed bilateral alveolar infiltrates. Bronchoscopies showed a diffusely bleeding bronchial tree. Both patients recovered after having been mechanically ventilated with positive end-expiratory pressure for six and eight days respectively. The cause of the diffuse pulmonary haemorrhage was, in the first case, severe thrombocytopaenia (17,000 G.1-1) of central origin, and, in the other patient, an unspecified vasculitis. Diffuse pulmonary haemorrhage should be added to the list of possible causes of the adult respiratory distress syndrome.

Adult↗
PubMed1992

Effects of D-beta-hydroxybutyrate and long- and medium-chain triglycerides on leucine metabolism in humans.

Ketone bodies and/or fatty acids might play a protein-sparing role during prolonged fasting or parenteral nutrition. To assess this problem, we studied whole body leucine metabolism, using L-[1-13C]leucine in normal postabsorptive volunteers who received either long-chain triglycerides (LCT, 0.15 g.kg-1.h-1, 6 subjects), a 50-50 mixture of medium-chain triglycerides (MCT) and LCT (0.15 g.kg-1.h-1, 6 subjects), D-beta-hydroxybutyrate (540 mumol.kg-1.h-1, 6 subjects), or saline (4 subjects). Leucine concentration decreased only with MCT-LCT. Leucine flux decreased by 10-20% from basal in all groups. Leucine oxidation, which was corrected for the contribution to 13CO2 of the 13C natural abundance of the infused substrates, decreased during LCT infusion (0.31 +/- 0.02 to 0.24 +/- 0.01 mumol.kg-1.min-1, P less than 0.01), but was unaffected by MCT-LCT (despite plasma free fatty acid levels similar to those obtained with LCT), D-beta-hydroxybutyrate, or saline infusion. Therefore, 1) the effect of fatty acids on amino acid oxidation is not mediated by ketone bodies, 2) it depends on the fatty acid chain length, 3) long-chain fatty acids but not medium-chain fatty acids could play a protein-sparing role during parenteral nutrition.

3-Hydroxybutyric Acid↗
PubMed1991

Comparative bioavailability study of cefixime administered as tablets or aqueous solution.

The relative bioavailability of cefixime was studied in 24 healthy male volunteers, with each subject receiving a single 400mg dose of cefixime administered as an aqueous solution, a 400mg tablet and two 200mg tablets, in a randomised crossover sequence. Serum and urine samples were analysed using high-performance liquid chromatography. Peak cefixime levels were achieved 3 hours after administration of the solution vs 4 hours for the 2 tablet formulations; however, the extent of absorption was only slightly improved with the solution (by 14 and 7% compared with the 1 x 400 and 2 x 200mg tablets, respectively). The 400mg and 2 x 200mg tablets were found to be bioequivalent. The pharmacokinetic profile of the 400mg cefixime tablet (mean maximum plasma concentrations of 4.4 mg/L at 4 hours, area under the concentration-time curve of 34.4 mg/L.h, and apparent terminal elimination half-life of 3.7 hours) supports the clinical evaluation of a 400mg once-daily dosage regimen for cefixime.

Adult↗
PubMed1991

Pharmacokinetics of pyrimethamine in healthy young volunteers using a new solid phase extraction/HPLC method.

The single dose pharmacokinetics of pyrimethamine were determined in 12 healthy young volunteers using a newly developed fully automated analytical system which combines liquid solid extraction on disposable extraction columns and high performance liquid chromatography. This technique is highly sensitive (detection 1 ng/ml) and reproducible. Following a 50mg dose of the drug, the plasma concentration peaked at 0.48 0.13 g/ml (msd) and was attained 2.5 hours (median value) post dosing. Thereafter, the plasma level of pyrimethamine decreased slowly, the level at 336 hours after administration being still about 40 ng/ml. The area under the plasma concentration-time curve (AUC0-inf) was 56.8 18.4 h.mg/ml. The volume of distribution Vd was: 2.42 1.25 l/kg and the total clearance: 15.55 4.48 ml/h/kg. Urinary excretion represented about 20% to 40% of the dose after seven days of the administered dose.

Adult↗
PubMed1991

Comparative bioequivalence study of a new levothyroxine solution versus a reference L-thyroxine solution in normal healthy volunteers.

A bioequivalence study between a new Levothyroxine solution and a reference solution was performed in 12 healthy volunteers after one single 3000 g oral administration. Administrations were done according to a cross-over schedule with a three week wash-out period. Plasma profile of Levothyroxine was determined for 72 hours, clinical tolerance being appreciated for 10 days after each administration. No statistical difference was reported for pharmacokinetic parameters and clinical tolerance was good.

Adult↗
PubMed1990

Relationship between preoperative amiodarone treatment and complications observed during anaesthesia for valvular cardiac surgery.

Two groups of ASA physical status class III and IV patients undergoing cardiac surgery were reviewed in an attempt to obtain more conclusive data concerning dangerous interactions between amiodarone and anaesthesia. The amiodarone group (Group 1, ten patients, cumulative dose 10 g) was compared with a control group (nine patients, Group 2). Amiodarone (A) and desethylamiodarone (NA) concentrations in plasma and myocardium were measured and haemodynamic and antiarrhythmic effects were analysed. Throughout anaesthesia haemodynamic status was similar in both groups. No correlation was found between A/NA and cardiac index changes. No patients needed intraaortic blood pressure augmentation or developed low systemic vascular resistances. Pacemaker dependency was similar in both groups and there was no evidence of increased anaesthetic risk. An excellent antiarrhythmic effect was obtained during the postoperative period. We conclude that preoperative treatment with amiodarone is effective against postoperative arrhythmias.

Adult↗
PubMed1989

Auditory evoked potentials during propofol anaesthesia in man.

The effects of propofol on auditory evoked potentials were studied in nine patients undergoing otorhinolaryngology surgery. After recording of basal evoked potentials patients received propofol 2 mg kg-1 over 2-3 min for induction of anaesthesia. Potentials were recorded every 10 min (T1, T2, T3). During T1, T2, T3, the infusion rates of propofol for maintenance of anaesthesia were respectively 7, 5 and 3 mg kg-1 h-1 consecutively. Middle latency component was affected markedly. Brainstem waves latencies I, III, V were increased significantly, while amplitude waves I, III, V remained constant.

Adult↗
PubMed1989

Open-heart surgery in a patient with a high oxygen affinity haemoglobin variant.

A man in heart failure with a high oxygen affinity haemoglobin variant (Hb Rainier) underwent a mitral commissurotomy with the aid of cardiopulmonary bypass. Pre-operatively, a total blood exchange transfusion was carried out to prevent potential hypoxic and thrombo-embolic complications. No complications occurred in the postoperative period.

Adult↗
PubMedDate not supplied

Which bioequivalence study for a racemic drug? Application to milnacipran.

Milnacipran, a new non tricyclic antidepressant drug, is a racemic mixture (F2207) composed of two enantiomers: F2695 and F2696, both demonstrated to be active. A randomized open label, single-dose latin square study was undertaken in 24 healthy volunteers to compare, based on racemate data, the relative bioavailability of two new formulations to that of a reference formulation. Later on, as suggested by actual regulatory trend, analysis was carried out on enantiomer data, although in a supportive way. Bioequivalence was assessed on calculation of 90% confidence intervals for log-transformed Cmax and AUC(0-infinity) and on Wilcoxon test for Tmax with a 5% level of significance. Based on racemate data, both test formulations were demonstrated to be equivalent to the reference capsule in terms of Cmax and AUC-(0-infinity). Differences in Tmax reached statistical significance, although their mean magnitude was small, and probably not relevant when related to antidepressant long-term therapy. When considering the test capsule - reference capsule comparison, the equivalence demonstrated for the racemate reflect that of each enantiomer. On the contrary, equivalence between the test tablet and the reference capsule demonstrated for the racemate, is not supported by both enantiomers as Cmax of F2696 fails to reach bioequivalence criteria, making more uncertain the conclusion of bioequivalence. From this experience, it seems than when equivalence is demonstrated close to the limits for the racemate, it is difficult, especially for a low variability drug such as milnacipran, to comply with equivalence criteria for both enantiomers.

Adult↗