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Biomedical subjects

A Laurent

Publications and source records attributed to A Laurent.

At least 19 recordsLinked to original sources

Laparoscopy as a routine approach for left lateral sectionectomy.

BACKGROUND: Since 1997, the authors have performed laparoscopic left lateral sectionectomy of lesions of the liver in preference to open surgery. The aim of this study was to assess the outcome. METHODS: Between October 1997 and March 2005, 36 laparoscopic left lateral sectionectomies were performed using five trocars and a small incision for specimen retrieval. Liver resection was performed mainly using a harmonic scalpel and staplers. The Pringle manoeuvre was used in 24 patients. RESULTS: The mean patient age was 55.2 (range 31-80) years. Twelve patients had underlying cirrhosis. Surgery was performed for 20 malignant lesions and 16 benign lesions with a mean size of 42.7 (range 5-110) mm. Conversion to laparotomy occurred in one patient. The mean operating time was 171.5 (range 90-240) min. Operatiing time and use of the Pringle manoeuvre were significantly decreased in the second half of the series. Mean blood loss was 208 (range 50-600) ml. No transfusion was required. There were no deaths. Two patients had postoperative complications (one incisional hernia and one pneumonia). The median postoperative stay was 5.2 days. CONCLUSION: The laparoscopic approach to left lateral sectionectomy was safe and feasible in this series and could be considered as a routine approach in selected patients.

Adult↗

Release of ibuprofen from beads for embolization: in vitro and in vivo studies.

Ibuprofen (IBU) loaded polyvinyl alcohol-based hydrogel beads (IBU-BB) were designed to alleviate side effects such as inflammation and pain following uterine artery embolization for the treatment of leiomyomata. The present in vitro and in vivo study examines whether IBU-BB provide a sustained-release of the drug. In vitro release studies of IBU from IBU-BB (10, 50, 100 mg/mL), IBU solution (PEDEA) and IBU powder were compared using the T apparatus and the beaker method. The pharmacokinetic profile of IBU release was examined in vivo, following sheep uterine artery embolization with 100 mg/mL IBU-BB or after intra-arterial injection of IBU solution. IBU-BB can deliver high concentrations of the drug over time. The in vitro release from IBU-BB was markedly slower compared to IBU solution. Increasing the concentration of loaded IBU from 10 to 100 mg/mL decreased the rate of release. IBU release from the T apparatus was slower than the release in the beaker. In vivo, the release of the drug was progressive, without the early peak observed with IBU solution. A high level of correlation was obtained between in vivo and in vitro (T apparatus) results. Theoretically, IBU-BB could sustainably release high concentrations of IBU at the site of the uterine fibroids, which makes it a promising approach for the control of post-embolization pain.

Animals↗

[French adaptation of the Hopkins Verbal Learning Test].

INTRODUCTION: A number of tests are currently used in clinical and research settings for the assessment of patients with memory deficits. Among them, the Hopkins Verbal Learning Test (HVLT) is particularly appropriate for the longitudinal follow-up of patients with memory disorders because it exists in six parallel forms, and therefore avoids the risk of learning effect at retest. Since a test with these characteristics is not available in French, we decided to adapt a French version of the HVLT. METHODS: 180 normal subjects participated in the study. Their mean age was 41 years (SD=11), and they had had on average 12 years of schooling (SD=3). The subjects were randomly divided into 6 groups of 30 subjects. One of the six forms of the French version of the HVLT was administered orally to each group of subjects. Each form consisted of a list of 12 words belonging to 3 different semantic categories. For the construction of the French version of the HVLT, we adopted the same procedure as used in the original version of the test taking into account the French lexical and semantic characteristics of the items. In the first part of the test, the list was administered three times to the subjects. Following each administration, subjects were asked for an immediate free recall. Twenty minutes later, used for intercurrent tasks, subjects were asked for a delayed free recall, which was immediately followed by a recognition memory task. In this task, subjects listened to a list of 24 words, 12 belonging to the studied list and 12 were distractors; the subjects were asked to recognize the 12 studied words. RESULTS: The subjects' performance was equivalent in the six forms of the test, except for the immediate recall of Form 3 (which was excluded from the test). No significant difference emerged in free recall, delayed free recall, and recognition across the five remaining forms of the test. CONCLUSION: Our study provides a useful tool for the longitudinal evaluation of patients with memory impairment and may become the test of reference in European longitudinal clinical trials. The French adaptation of the HVLT represents only a first step, because it needs to be standardized, in order to provide norms, and validated, in order to provide values of sensitivity and specificity.

Adult↗

Bioequivalence of an ezetimibe/simvastatin combination tablet and coadministration of ezetimibe and simvastatin as separate tablets in healthy subjects.

OBJECTIVE: To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to the coadministration of ezetimibe and simvastatin as separate tablets (EZE + SIMVA). METHODS: In this open-label, randomized, 2-part, 2-period crossover study, 96 healthy subjects were randomly assigned to participate in each part of the study (Part I or II), with each part consisting of 2 single-dose treatment periods separated by a 14-day washout. Part I consisted of Treatments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treatments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood samples were collected up to 96 hours post-dose for determination of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuronide), simvastatin and simvastatin acid (the most prevalent active metabolite of simvastatin) concentrations. Ezetimibe and simvastatin acid AUC(0-last) were predefined as primary endpoints and ezetimibe and simvastatin acid Cmax were secondary endpoints. Bioequivalence was achieved if 90% confidence intervals (CI) for the geometric mean ratios (GMR) (single tablet/coadministration) of AUC(0-last) and Cmax fell within prespecified bounds of (0.80, 1.25). RESULTS: The GMRs of the AUC(0-last) and Cmax for ezetimibe and simvastatin acid fell within the bioequivalence limits (0.80, 1.25). EZE/ SIMVA and EZE + SIMVA were generally well tolerated. CONCLUSIONS: The lowest and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together. Given the exact weight multiples of the EZE/SIMVA tablet and linear pharmacokinetics of simvastatin across the marketed dose range, bioequivalence of the intermediate tablet strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) was inferred, although these dosages were not tested directly. These results indicate that the safety and efficacy profile of EZE + SIMVA coadministration therapy can be applied to treatment with the EZE/SIMVA tablet across the clinical dose range.

Adolescent↗

Pharmacokinetics of rabeprazole following single intravenous and oral administration to healthy subjects.

The study was designed to determine the absolute bioavailability of 20 mg rabeprazole tablets in normal, healthy subjects in comparison with intravenous administration of 20 mg rabeprazole. Twenty-eight healthy subjects were enrolled in this study. The study was a randomized, balanced, open-label, 2-period crossover study. Each subject was randomized at the beginning of the study to receive either a single 20 mg dose of rabeprazole intravenously or orally during Period 1. Following a 7-day washout period, all subjects received the alternate formulation during Period 2. Intravenous dose was given in constant infusion over five minutes. The absolute bioavailability of rabeprazole was 51.8%. The elimination half-life of rabeprazole sodium (1.47 +/- 0.82 h) after oral administration was significantly longer than the elimination half-life after intravenous administration (1.02 +/- 0.63 h), probably due to slower rate of absorption than that of elimination. The mean total body clearance was 283 +/- 98 ml/minutes following a 20 mg intravenous dose. The administration of rabeprazole sodium was safe as evidenced by the lack of serious adverse events and the rapid resolution of the mostly mild adverse events that occurred during the study. Both treatments were well-tolerated throughout the study. Rabeprazole was well-absorbed after oral administration.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Sonographic findings in Beckwith-Wiedemann syndrome related to H19 hypermethylation.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with congenital malformations and tumour predisposition. BWS results from variable mutations or epigenetic modifications of imprinted genes in the 11p15 chromosomal region. We present a fetus with mild general overgrowth and bilateral enlarged echogenic kidneys with loss of the corticomedullary differentiation in which prenatal diagnosis of BWS was suspected. The rest of the fetal anatomy and the amniotic fluid volume appeared normal. After termination of the pregnancy, molecular analysis confirmed the diagnosis of BWS by showing an isolated hypermethylation of the H19 gene.

Adult↗

MR temperature measurement in liver tissue at 0.23 T with a steady-state free precession sequence.

MRI can be used for monitoring temperature during a thermocoagulation treatment of tumors. The aim of this study was to demonstrate the suitability of a 3D steady-state free precession sequence (3D Fast Imaging with Steady-State Precession, 3D TrueFISP) for MR temperature measurement at 0.23 T, and to compare it to the spin-echo (SE) and spoiled 3D gradient-echo (3D GRE) sequences. The optimal flip angle for the TrueFISP sequence was calculated for the best temperature sensitivity in the image signal from liver tissue, and verified from the images acquired during the thermocoagulation of excised pig liver. Factors influencing the accuracy of the measured temperatures are discussed. The TrueFISP results are compared to the calculated values of optimized SE and 3D GRE sequences. The accuracy of TrueFISP in the liver at 0.23 T, in imaging conditions used during thermocoagulation procedures, is estimated to be +/-3.3 degrees C for a voxel of 2.5 x 2.5 x 6 mm(3) and acquisition time of 18 s. For the SE and GRE sequences, with similar resolution and somewhat longer imaging time, the uncertainty in the temperature is estimated to be larger by a factor of 2 and 1.2, respectively.

Animals↗

Iodine-containing cellulose mixed esters as radiopaque polymers for direct embolization of cerebral aneurysms and arteriovenous malformations.

The present study deals with the synthesis and characterization of radiopaque polymers which could, when solubilized in an appropriate water-miscible solvent, be useful embolic materials for the treatment of cerebral aneurysms and arteriovenous malformations. For this purpose cellulose (both microcrystalline and powdered) and partially substituted cellulose acetate (two different viscosity grades) were selected as starting materials to prepare iodine-containing polymers through various synthetic routes. The materials obtained were characterized by IR and NMR spectroscopy, molecular weight, iodine content, radiopacity and solubility in selected injectable organic solvents. The embolic liquids were evaluated for their precipitation behavior in a phosphate buffer solution (pH 7.4) mimicking physiological conditions using an in vitro aneurysm model. A sheep model was also used to assess in vivo the radiopacity and precipitation properties of a highly concentrated solution of a cellulose acetate 2,3,4-triiodobenzoate mixed ester. All materials with 4-iodo- and 2,3,5-triiodobenzoyl groups gave sufficient radiopacity to be regarded as possible embolization materials, whereas iododeoxycellulose and iododeoxycellulose acetate were not radiopaque because of their low iodine content. Esters synthesized using cellulose as starting material were not soluble in the selected organic solvents due to the presence of many residual hydroxyl groups, but could be used for other biomedical applications where insoluble radiopaque materials are used. In contrast, solubility of the materials as well as satisfactory precipitation properties were ensured using cellulose acetate as the starting material. In conclusion, cellulose acetate iodobenzoate mixed esters dissolved in diglyme or dimethyl isosorbide (dimethyl sulfoxide is probably less appropriate because of its toxicity and hemolytic properties) could be useful embolic liquids for the treatment of cerebral aneurysms or arteriovenous malformations.

Angiography, Digital Subtraction↗

WCST performance and schizotypal features in the first-degree relatives of patients with schizophrenia.

Since the findings concerning the Wisconsin Card Sorting Test (WCST) performance of healthy first-degree relatives of patients with schizophrenia are equivocal, it still remains unclear whether the WCST may serve as a neuropsychological indicator of vulnerability to schizophrenia. The aim of this study was to evaluate whether the first-degree relatives' schizotypal features could account for these discrepancies. The subjects were 24 schizophrenic probands, 49 of their first-degree relatives and 41 normal controls. The computerized version of the WCST was used and schizotypy features were assessed using four of Chapman's scales. The patient group performed worse on the WCST and had higher scores of schizotypy than the control group. The relatives group did not significantly differ from the control, neither on the WCST performance nor on the scores of schizotypy. However, the subgroup of relatives and the subgroup of patients with high scores on the negative dimension of schizotypy showed a worse performance on the WCST than the subgroups with low scores. There were no differences on the WCST performance between the subgroups with high vs. low scores on the positive dimension of schizotypy. Thus, discrepancies across studies could be explained by a confounding factor represented by the negative dimension of schizotypy.

Adult↗

MR monitoring of laser-induced lesions of the liver in vivo in a low-field open magnet: temperature mapping and lesion size prediction.

The aims of this study were, firstly, to monitor temperature with magnetic resonance (MR) during laser ablations performed in pig livers in vivo in a low-field open scanner (0.23T) and, secondly, to study the feasibility of lesion size prediction. Spin-echo (SE) images of 29 sec acquired during laser applications allowed calculation of temperature maps using T1 and M(0) temperature sensitivity. Temperature was also measured with thermocouples. Images of prediction of tissue damage were calculated using temperature maps and Arrhenius model. T2W sequences were acquired after the ablations. Animals were sacrificed immediately. Lesions were photographed macroscopically. Lesion surfaces were measured and compared in T2W images, temperature images, damage prediction images, and macroscopic pictures. A correlation exists between temperature measured with MR and with thermocouples (rho = 0.878; P < 0.001, Spearman test). Mean surface of predicted damaged tissue is consistent with mean early necrosis measured in macroscopic pictures. Early T2W images underestimate mean necrosis size. J. Magn. Reson. Imaging 2001;13:42-49.

Animals↗

MR monitoring of tumour thermal therapy.

Thermal therapy of tumour including hyperthermia and thermal ablation by heat or cold delivery requires on line monitoring. Due to its temperature sensitivity, Magnetic Resonance Imaging (MRI) allows thermal mapping at the time of the treatment. The different techniques of MR temperature monitoring based on water proton resonance frequency (PRF), longitudinal relaxation time T1, diffusion coefficient and MR Spectroscopic Imaging (MRSI) are reviewed and debated. The PRF method appears the most widely used and the most efficient at high magnetic field in spite of important drawbacks. The T1 method is the easiest method of visualisation of qualitative temperature distribution and quantitative measurement seems possible in the tissue surrounding the tumour up to a temperature of 45-65 degrees C. Despite its high temperature sensitivity, application of the diffusion method in vivo is restricted due to its high motion sensitivity. The recent MRSI technique seems very promising provided acquisition times can be reduced. Results from the literature indicate that MR temperature monitoring in vivo can be achieved in vivo with a precision of about 3 degrees C in 13 s for a voxel of 16 mm3 (1.5 x 1.5 x 7 mm) in 1.5 T scanners.

Animals↗

Bone reactions to nacre injected percutaneously into the vertebrae of sheep.

We have studied the osteogenic effects of nacre (mother of pearl) placed in experimental cavities prepared in the lumbar vertebrae of sheep. Some of cavities were filled with nacre, some with PMMA, and some were left empty. The vertebrae were removed 1, 8, 12 weeks after surgery, and assessed histologically and morphometrically. The nacre particles in the bone cavity and the surrounding intertrabecular spaces gradually dissolved beginning at 8 weeks after surgery. There were layers of newly formed bone, both woven and lamellar, in various stages of maturation in contact with or adjacent to the dissolving nacre. Quantitative assessment of the activation of bone formation adjacent to the cavities filled with nacre indicated significant activation of bone formation, which continued until week 12. There was also increased mineralization of the host bone at this time. There was no new bone formation in the empty cavities, or in those filled with PMMA. PMMA also caused necrosis of surrounding bone cells with a change in bone architecture and significant reductions in bone formation and mineralization. This study demonstrates that nacre stimulates bone-forming cells in vertebrae and appears to result in new bone formation.

Administration, Cutaneous↗

Arterial blood supply to the uterus in nonpregnant sheep: a pertinent model for clinical practice?

RATIONALE AND OBJECTIVES: Our goal was to study the arterial supply to the sheep uterus to compare its similarity with that of women and to evaluate the interest of this animal model for training in uterine artery embolization. METHODS: Ten nonpregnant sheep underwent aortography and selective study of the ovarian, internal iliac, uterine, and vaginal arteries. RESULTS: The uterus was supplied mainly by the uterine arteries in all sheep. The ovarian artery, which was identified in five sheep, had a thin anastomosis with the ipsilateral uterine artery at the tubal junction. The vaginal artery provided blood flow to the inferior part of the cervix and anastomosed with the ipsilateral uterine artery. CONCLUSIONS: Because uterine vascularization of nonpregnant sheep is similar to that of women, the sheep represents an appropriate model for experimental uterine artery embolization. This model should be used for interventional radiologists in training not familiar with endovascular navigation inside pelvic arteries.

Angiography↗

A pharmacokinetic study of intramuscular (i.m.) parecoxib sodium in normal subjects.

A single-center, double-blind, placebo-controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (i.m.) doses and the single maximum tolerated dose of parecoxib sodium, a prodrug of the novel COX-2 selective anti-inflammatory analgesic drug valdecoxib, in 56 healthy male volunteers, ages 18 to 45 years inclusive. Cohorts of up to 6 subjects in each dose schedule were administered either parecoxib sodium (1 mg, 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg) or matching placebo. Following i.m. administration, serial blood samples for measurement of plasma concentrations of parecoxib, valdecoxib, and valdecoxib metabolite (M1) were collected at predetermined intervals (from 15 minutes prior to dose and through 96 hours postdose). Urine collections were obtained for drug assay (from -12 to 0 hours, 0 to 12 hours, and 12 to 24 hours postdose). After i.m. administration, peak plasma concentrations of parecoxib were reached within 15 minutes and then declined rapidly as prodrug was converted to the active moiety, valdecoxib. Change in plasma concentrations of valdecoxib, which declined more slowly (t(1/2) = 5.4-9.9 hours), reflected transformation to several metabolites, one of which was the minor active metabolite M1. As measured by the AUC(0-infinity), Cmax, and XU(0-24) of valdecoxib, parecoxib sodium demonstrated dose proportionality when administered in the range of 1 mg to 40 mg of parecoxib. All single i.m. doses up to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20 mg/ml, were well tolerated.

Adolescent↗

Arthrodesis of lumbar spine transverse processes using nacre in rabbit.

This study compares the osteogenic effects of nacre and autogenous bone grafts in a rabbit model of lumbar spine transverse process arthrodesis. A total of 15 rabbits were processed for arthrodesis between the fifth and sixth lumbar vertebrae using nacre powder mixed with autologous blood or autogenous iliac crest bone. Control rabbits were sham operated. Sample vertebrae were removed from the nacre-implanted rabbits at 2, 5, and 11 weeks postsurgery. The autogenous bone graft and sham-operated groups were processed for histological study 11 weeks postsurgery. The results for the three groups were compared at 11 weeks. The nacre-implanted samples taken at 2 weeks showed that the nacre was well tolerated by the host tissue. Endochondral bone formation was seen in the region of the dissolving nacre particles by 5 weeks. The newly formed bone formed a solid fusion between the transverse processes in one-third of the rabbits. There was still new bone formation at 11 weeks at the nacre implant site. Two-thirds of the rabbits had formed a solid fusion. Light microscopy also showed new bone formation 11 weeks after the autologous bone graft. All rabbits had a solid fusion. This initial study indicates that nacre can induce spinal fusion in an acceptable percentage of cases.

Animals↗