Search PubMed⌕ Search

Biomedical subjects

A Durand

Publications and source records attributed to A Durand.

At least 109 records · Page 6Linked to original sources

Intertrial reliability of work measurements recorded during concentric isokinetic knee extension and flexion in subjects with and without meniscal tears.

Intertrial reliability of work measurements was studied in 19 men with a partial medial meniscal tear (ME group) and in 10 men with no history of knee injury (control group). Three maximal voluntary concentric contractions of the muscles involved in knee extension (KE) and knee flexion (KF) were performed on a dynamometer at 30 degrees and 180 degrees/s using a preloading protocol. The subjects moved their legs through an arc of 90 degrees, and the work produced in the constant-velocity phase between 70 and 20 degrees of KE was computed for each trial. In ME group subjects able to perform three consecutive contractions (n = 12-14), high intertrial intraclass correlation coefficients (ICCs) were found (ICCs = .86-.92), except for KE work measurements at 180 degrees/s (ICC = .67). In the control group subjects, high ICCs were obtained for KE work measurements (ICCs = .87 and .95), whereas the low ICCs obtained for KF work measurements (ICCs = .64 and .79) increased to .86 and .93 when the first trial was removed. In both groups, a significant increase was found over the trials for KF measurements at 180 degrees/s and KE measurements at 30 degrees/s, but work measurements were shown to peak at the second trial. The results of this study suggest that the work produced on the second trial reflects a subject's maximal capacity. [Durand A, Malouin F, Richards CL, Bravo G. Intertrial reliability of work measurements recorded during concentric isokinetic knee extension and flexion in subjects with and without meniscal tears.

Adult↗

Effects of nicardipine on pulmonary and systemic vascular reactivity to oxygen in patients with pulmonary hypertension secondary to chronic obstructive lung disease.

We compared the acute effects of nicardipine and a placebo on the response of pulmonary and systemic circulation to different inspiratory fractional concentrations of O2 (FiO2) in 10 patients with pulmonary hypertension secondary to chronic obstructive lung disease. After catheterization of the pulmonary and femoral arteries, gas mixtures containing 15, 21, and 30% O2 were randomly administered for 20 min each during infusion of saline and then nicardipine (0.06 mg/kg/min). Plasma nicardipine level was maintained at 30 ng/ml. During nicardipine infusion, cardiac index (CI) was significantly higher (+20%, p less than 0.05) than during placebo infusion, with no change in mean pulmonary artery pressure (MPAP). Pulmonary resistances also decreased significantly (-20%) during nicardipine. No change in arterial or mixed venous O2 contents was noted. Mean arterial pressure (MAP) and systemic resistances decreased significantly with nicardipine. Inhaling a hyperoxic mixture was followed by a significant decrease in arterial pressure during placebo infusion; this was not observed during nicardipine. In contrast with systemic circulation, the response of the pulmonary circulation to different FiO2 levels was unaffected by nicardipine.

Blood Gas Analysis↗

1H nuclear magnetic resonance and clinical studies of interaction of calcium antagonists and hypoglycemic sulfonylureas.

The hypoglycemic effect of gliclazide is mainly due to its action on ATP stimulated K+ channels, but the calcium ionophoretic effect of this drug may also be involved in its physiological properties. Using 1H NMR we demonstrated the antiionophoretic effect of nifedipine and diltiazem. We attempted to verify whether this in vitro interaction also occurs in vivo. A clinical trial, was performed on patients treated concomitantly with gliclazide and nifedipine or diltiazem. Results showed that no in vivo interaction occurred. The discrepancy between in vivo and in vitro results may be explained by a too weak plasma concentration in the case of nifedipine and by a large plasma protein binding in the case of diltiazem.

Adenosine Triphosphate↗

Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes.

In vitro metabolism of digoxin and its cleavage-related compounds was investigated using hepatocytes in primary culture and microsomal fractions both isolated from human livers. On these models, digoxin (DG3) and digoxigenin bisdigitoxoside (DG2) were not shown to be significantly metabolized in vitro in man. Therefore, it appeared that the stepwise cleavage of DG3 and DG2 sugars was not cytochrome P450 dependent. This enzymatic system probably plays a minor role in humans for this particular reaction. However, digoxigenin monodigitoxoside (DG1) and digoxigenin (DG0) which are known to be formed after intra-gastric hydrolysis of DG3, were extensively converted to polar compounds (mainly glucuronides). In addition, using human liver microsomes, a wide variability in UDP-glucuronyl transferase (UDPGT) activities responsible for DG1 glucuronidation was demonstrated. These results suggest that two main factors may contribute to the overall interindividual variability of digoxin biotransformation: 1), the individual intra-gastric pH which influences the sugar cleavage leading to DG1 and DG0; ii), a variability in the level of the hepatic UDPGT specific for digitalis compounds conjugation.

Biotransformation↗

Metabolism of minaprine in human and animal hepatocytes and liver microsomes--prediction of metabolism in vivo.

1. The metabolism of minaprine and its major metabolite p-hydroxyminaprine were studied using hepatocytes and liver microsomes from different species. Metabolism of this drug in vitro was then compared with in vivo data already published. 2. Our results showed that the major metabolic route (4-hydroxylation of the aromatic ring) is the same in the two experimental systems. Other in vivo biotransformation pathways (i.e. N-oxidation, reductive ring cleavage, N-dealkylation, oxidation) were also confirmed in hepatocytes. 3. Similar inter-species variability was observed both in vitro and in vivo. The present study has led to the same conclusion as previous in vivo metabolic investigations, namely, that metabolism in the dog quantitatively differs from that observed in other animal species. 4. These results clearly demonstrate that in vitro models (i.e. isolated hepatocytes and liver microsomes) are powerful tools in predicting the metabolic pathways of a drug in man and animal species.

Adsorption↗

Influence of the measurement location on the resistance index in the umbilical arteries: a hemodynamic approach.

A computer model was used to study the primary factors generating the reduction in resistance index, (S-D)/S, values observed by ultrasonic Doppler measurements in the umbilical artery, from the fetal insertion to the placental insertion (S represents the amplitude of the systolic peak and D the amplitude of the diastolic peak). This hemodynamic approach shows that the placental resistance is the primary factor, the viscosity and the cord length playing secondary roles. Clinically, the position of the measurement along the cord is an important factor. To increase the sensitivity of the index, the Doppler measurement must be performed near the fetal insertion, whereas a measurement near the placental insertion will make the Doppler examination more specific.

Blood Flow Velocity↗

Intestinal absorption of drugs: digitalis binding and transport by brush-border membrane vesicles from human duodenum.

The intestinal epithelial cell layer is the first major barrier to absorption encountered by xenobiotics. An understanding of the mechanism and sites of drug absorption and metabolism is thus a critical first step in developing orally active compounds. In this context human brush-border membrane vesicles obtained from multi-organ donor intestines have been purified. This model has been validated and used to investigate the duodenal absorption of drugs "in vitro", namely digitalis. It is well established that digitalis compounds present great variability in their respective "in vivo" bioavailability in human (60-90% for digoxin, 0% for ouabain). These particular characteristics prompted us to determine whether this membrane model constitutes a suitable tool in predicting the bioavailability or intestinal transport processes of these molecules. The uptake of [3H] digoxin and [3H] ouabain by membrane vesicles incubated in media of increasing osmolarities demonstrated that: i/two factors are involved in the uptake processes of digoxin: membrane binding and intravesicular transport (osmotic sensitive), ii/ for ouabain, no osmotic sensitivity was observed, indicating that no transport process occurred, but only membrane binding processes. These results are in complete agreement with the absolute bioavailability data reported for man "in vivo". This human brush-border model constitutes an interesting approach to the intestinal absorption phenomena which are known to be among the factors influencing the bioavailability of orally administered drugs.

Biological Availability↗

Strength recovery and muscle activation of the knee extensor and flexor muscles after arthroscopic meniscectomy. A pilot study.

Maximal isokinetic strength and electromyographic activity of the operated leg were measured preoperatively and one, two, three, and eight weeks postoperatively after a partial medial meniscectomy by arthroscopy in a group of ten patients. Strength deficits, measured with a Kin-Com dynamometer using a static preloading protocol, were found in comparison with a group of matched healthy subjects preoperatively and three and eight weeks postoperatively in the knee extensors. These deficits were related to previously unreported modifications in the shape of the moment-angle curves and a tendency to lower activation levels of the vastus medialis (VM) but not the vastus lateralis or rectus femoris muscles. No deficits were found in the knee flexors preoperatively or three and eight weeks postoperatively, but the medial hamstrings activation level was lower for movements at 30 degrees per second. During flexion movements, the percentage of coactivation of the antagonist VM was significantly greater than healthy values at 30 degrees and 180 degrees per second. These results clearly indicate that neuromuscular recovery is not complete when return to work is advocated three to four weeks postoperatively. Such findings suggest the need for a rehabilitation program to promote recovery of the knee muscles in workers with a physically demanding occupation.

Adult↗

Direct high-performance liquid chromatographic determination of the enantiomers of alfuzosin in plasma on a second-generation alpha 1-acid glycoprotein chiral stationary phase.

A direct liquid chromatographic method was developed for the determination of the enantiomers of alfuzosin in human plasma, without derivatization, on a chiral alpha 1-acid glycoprotein column. The influence of pH, of uncharged organic solvents and of a cationic modifier (tetrabutylammonium) of the mobile phase on retention and enantioselectivity was evaluated. The enantiomers and an internal standard, structurally related to alfuzosin, were extracted from plasma with dichloromethane-diethyl ether from alkaline solution, then separated with a mobile phase of 0.025 M phosphate buffer (pH 7.4) containing 0.025 M tetrabutylammonium bromide-acetonitrile (94:6, v/v). The limit of quantification for each isomer was 1 ng/ml. The method has been applied to the determination of the pharmacokinetic profile of alfuzosin enantiomers in healthy volunteers after intravenous administration of the racemate.

Chromatography, High Pressure Liquid↗

Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients.

The pharmacokinetics of propofol were determined in nine patients (seven men, two women, (mean +/- SD) 55.8 +/- 21.2 yr, 65.2 +/- 8 kg) requiring prolonged mechanical ventilation of their lungs. After an initial dose of 1-3 mg/kg, propofol was administered iv at 3 mg/kg/h for 72 h. Arterial blood samples were collected at selected times during and up to 72 h after infusion. Propofol whole blood concentrations were determined by high-performance liquid chromatography with fluorescence detection. Individual pharmacokinetic parameters were estimated by noncompartmental analysis. Derived pharmacokinetic parameters showed a long terminal phase (T1/2 = 1878 +/- 672 min), a large volume of distribution at steady state (Vdss = 1666 +/- 756 l), and a high total body clearance (Cl = 1.57 +/- 0.56 l/min). While the propofol terminal elimination half-life is longer than that previously reported, emergence from sedation after prolonged administration will be governed by both redistribution mechanisms arising from the large distribution volumes and elimination from the body.

Adult↗

Effects of age and antiepileptic drugs on plasma levels and kinetics of clobazam and N-desmethylclobazam.

The authors monitored the plasma levels of clobazam (CLO) and its principal metabolite, N-desmethylclobazam (NCLO) during chronic treatment of more than 400 epileptic patients receiving different co-medications, such as phenytoin (PH), carbamazepine (CBZ), sodium valproate (VPA) and phenobarbital (PB). This study investigated the influence of age and antiepileptic drugs on plasma levels of CLO and NCLO. Plasma concentrations measured 3 hr after morning administration of CLO varied from 30 to 700 [formula; see text] for CLO, and from 160 to 7000 [formula; see text] for NCLO. Plasma levels of CLO were higher in patients aged 20-30 years. NCLO concentrations increased with age up to 20 years. Coadministered antiepileptic compounds significantly decreased maximal plasma levels of CLO. Moreover, PH and CBZ a significantly increased the plasma levels of NCLO. Results on the influence of CBZ on CLO kinetics were confirmed in a group of ten patients receiving PB and VPA and later PB, VPA and CBZ as CLO associated drugs. The influence of VPA on the pharmacokinetics parameters of CLO was also evaluated in a patient in the latter group.

Adolescent↗

[Clinical pharmacokinetics of navelbine after oral administration, in vitro metabolism and interindividual variability].

Navelbine (NVB) (5'-noranhydrovinblastine) is a new semi-synthetic vincaalkaloid (VA) exhibiting a high affinity for tubulin and considerable anticancer activity in patients. A better hematologic tolerance and a weak neurotoxicity have been reported for this drug as compared to other VA. Moreover, NVB presents a relatively high bioavailability and a good digestive tolerance, thus offering original perspectives for the treatment of ambulatory cancer patients. A clinical pharmacokinetic study of NVB was carried out on 12 patients after oral administration of the drug. The pharmacokinetic parameters were similar to those of intravenous administration and also showed a high interindividual variability. Studies on the in vitro metabolism of NVB using hepatic microsomal fractions from 22 different donors demonstrated the formation of 3 metabolites. The biotransformation rate quantitatively varies from one human liver specimen to another, a fact which could be, in part, at the origin of the interindividual variability of the therapeutic response.

Administration, Oral↗

[Synovial cyst of the hip with venous compression. Diagnosis using x-ray computed tomography. A case report].

The authors report a case of synovial cyst developed about the serous bursae of the psoas iliaca muscle. It occurred in a 82 years old woman with a severe degenerative arthritis after hip dysplasia. The cyst has been revealed by a compression syndrome of the iliaca vein. Diagnosis has been made by CT. Physiopathology, clinics, diagnosis and treatment of this rare affection complete this case.

Aged↗

Rapid determination of the benzodiazepine antagonist flumazenil, Ro 15-1788, by high performance liquid chromatography.

A sensitive (2 ng/mL) and specific method for the determination of the benzodiazepine antagonist Ro 15-1788 or flumazenil is described. Following a simple extraction, the compound is analyzed by reversed phase high performance liquid chromatography (HPLC) and detection at 245 nm. The method was applied to plasma specimens collected from patients receiving a single dose of this drug.

Benzodiazepines↗

Ion exchange paper adsorption and thin-layer chromatography for detection of chloroquine in urine for the study of chemosensitivity of Plasmodium falciparum.

With a view to determining the chemosensitivity of Plasmodium falciparum to chloroquine, two qualitative tests for the detection of this antimalarial agent in urine were compared in Central African schoolchildren: the test of Dill and Glazko and a thin-layer chromatography technique involving ion exchange and extraction. Results obtained with 149 subjects showed the marked superiority in specificity and sensitivity of the chromatography test. This is of particular interest when selecting subjects before a therapeutic trial is undertaken. After administration of a single dose of chloroquine (10 mg kg-1) to 14 schoolchildren, both urinary detection tests gave positive results at 24 and 48 hours. However, on day 7 all results with the chromatography test were positive, while 57% of false negatives were recorded by the Dill and Glazko test.

Animals↗

Reversal of acute renal failure following percutaneous transluminal recanalization of an atherosclerotic renal artery occlusion.

Thrombosis of the renal artery to a single functioning kidney is a known cause of anuric acute renal failure in atherosclerotic hypertensive patients. In the present report, recovery of renal function rapidly occurred following transluminal recanalization of the occluded artery with a 7F catheter after a 5-week period of anuria. The most interesting feature was that improvement of renal artery permeability was observed following a minimal interventional procedure.

Acute Kidney Injury↗