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Biomedical subjects

F Fauvelle

Publications and source records attributed to F Fauvelle.

At least 19 recordsLinked to original sources
PubMed2003

[In vitro uranyle affinity of per (3,6-anhydro-2-O-carboxyméthyle)-alpha-cyclodextrin and conditions required for in vivo application].

Per (3.6-anhydro-2-O-carboxymethyle)- alpha-cyclodextrin ([1]) is a polydentate analog of EDTA, a well-known cation chelating reagent. [1] exhibits strong affinities in vitro for lanthanids, cobalt and also for uranyl cations. Hence, a 1:1 stoechiometry and a high affinity for uranyle (6<logK<7) is found in vitro. Moreover, [1] is not hemolytic and exhibits not lettral properties in mice (LD(50)=42mM). In vivo injection at supralethal amounts of uranyl complex of [1] prevents immediate death in mice while unable to protect against later death. Pharmacocinetic studies show that a dissociation of the complex occurs lead to the release of free uranyle. Other complexation assays using [1] grafted tissues show that chelating properties for lead and uranyle differ from thoses observed in vitro.

Animals↗
PubMed2003

Hydrolytic properties of per (3,6-anhydro, 2-O-carboxymethyl) alpha cyclodextrin complexes of Ce (III) and Eu (III): application to soman (GD) degradation.

Per (3,6-anhydro-2-O-carboxymethyle) alpha-cyclodextrin ([ACX]) is a polydentate analog of EDTA, a well-known cation chelating reagent. ACX exhibits strong affinities in vitro for uranyl, cobalt and also for lanthanids such as Europium and Cerium. The hydrolytic activities of ACX-Eu and ACX-Ce complex were directly tested on an organophosphorous compound: the neurotoxic Soman (GD), an inhibitor of acetylcholinesterase (ACHE from rat brain). It was found a three fold reduction of soman activity when measured in the presence of Ce-ACX complex. Conversely, Eu-ACX effect did not result in soman inhibition variation under physiological conditions. It is suggested that, considering usual organometallic complex of cyclodextrin, such direct complexes would be of interest in the design of pseudo-enzyme systems for phosphoester hydrolysis.

Animals↗
PubMed2003

[Impact of medical prescription computerisation on the incidence of adverse drug effects].

INTRODUCTION: Adverse drug effects are a significant public health problem. Prescription errors are responsible for a significant proportion of these adverse effects. METHODS: We have aimed to improve the link between generation of and interpretation of a prescription through computerisation. The prescription sheet, which is generated daily, was organised to allow care planning without the need to re-copy out treatments on the sheet. A prescription aid was available which was based on a core group of drugs commonly used in our respiratory service. The aim of the study was to compare the various types of errors observed during 6 weeks of computerized prescriptions (229 files) to a retrospective series of handwritten prescriptions of the service at an identical time (184 files) the previous year. The case-mix was identical for both analysed periods. RESULTS: The total number of technical prescribing errors in the 1,599 handwritten lines (49.27% error) was significantly higher (p<0.001) than the 1,805 computerized prescriptions lines (42.88% error). The errors of copying (p<0.001), eligibility (p<0.001) and incorrect spelling (p<0.05) were the main sources of error which were significantly reduced by computerisation. CONCLUSION: Computerised prescription is likely to reduce the incidence of prescribing errors and adverse drug effects.

Clinical Pharmacy Information Systems↗
PubMed2001

Comparison of two methods to obtain a desired first isepamicin peak in intensive care patients.

A randomized multicenter study in intensive care unit (ICU) patients, evaluated the capacity of a Bayesian method to obtain an optimal first isepamicin (ISP) peak of 80 mg/L in comparison to a fixed loading dose (LD). Patients (n=236) over 18 years of age were enrolled from 6 September 1997 to 17 July 1999 and randomly assigned to received ISP in a calculated dose (CD) or a loading dose (LD) of 25 mg/kg body weight. The CD was estimated using a specific population model with Bayesian methodology implemented in the PKS program (Abbott PKS, Abbott Diagnostics, Rungis, France). The data required included age, body weight, height, gender and serum creatinine. ISP disposition is described by a one-compartment model. Blood samples were drawn 1 and 24 h after the start of infusion for fluorescence polarization immunoassay measurement of serum ISP concentrations. The predictive performance was assessed by computing bias and precision. Peak concentrations were significantly higher in CD group than the LD group (84.2 +/- 28.6 vs. 74.7 +/- 24.1 mg/L, respectively; P=0.008), but trough levels were comparable. The optimal ISP peak was attained by a significantly higher percentage of CD patients (P=0.018), and by significantly more CD patients on mechanical ventilation (P=0.025), and with simplified acute physiological scores (SAPS) > 35 (P=0.002). Pharmacokinetic parameters were similar for the two groups with large interindividual variations. Mean (+/- SD) volume of distribution of ventilated patients (72%) was significantly higher than of nonventilated patients (23.31 +/- 7.35 vs. 20.60 +/- 6.30 L, respectively; P=0.001). No relationship was found between the volume of distribution and SAPS. Total clearance was significantly correlated with estimated CLCR (creatinine clearance) (P=0.0001). Precision (RMSE) is better for CD than for LD strategy, respectively 27.96 and 28.66 mg/L. The Bayesian method was significantly more accurate and performed particularly well in ventilated patients and patients with high SAPS, compare to an LD of 25 mg/kg to obtain a first ISP peak of 80 mg/L in ICU patients. Therefore, a fixed dose of 28.5 mg/kg would be also adequate to reach a peak of 80 mg/L.

Acute Disease↗
PubMed2001

Association between hospital-acquired infections and patients' transfers.

OBJECTIVE: To assess the risk of nosocomial infection in transferred patients and to determine whether transfer is only a risk marker or is independently associated with nosocomial infection. DESIGN: Retrospective analysis. SETTING: A 400-bed general hospital in the Paris area. PATIENTS: All the patients hospitalized on the days of the surveys were included. METHODS: Epidemiological analysis of data collected in four annual nosocomial infection prevalence surveys conducted between 1993 and 1996. RESULTS: Of the 1,326 patients included in the four surveys, 70 (5.3%) had been transferred from another hospital and 199 (15.0%) from another ward of our hospital. Transferred patients more frequently had known risk factors of nosocomial infection: age >65 years (P<10(-5)), a length of hospital stay >7 days on the day of the survey (P<10(-6)), at least one invasive procedure (34.2% vs 27.2%; P<.05), a recent surgical intervention (P<.05), and an immunosuppression (P<.01). The prevalence rate of infected patients was 6.7% (95% confidence interval, 5.3-8.1). The risk of being infected on a given day was more than 4 times higher in transferred patients (P<10(-6)); however, the risk was similar between patients transferred from another hospital (20.0%) and patients transferred within the hospital (17.1%). The multivariate analysis performed by logistic regression showed that intrahospital transfer, a length of hospital stay >7 days, and having had at least one invasive procedure were independent risk factors of infection. CONCLUSION: According to this study, patient transfer is both a risk marker (associated with several known risk factors) and independently associated with nosocomial infection. The origin of a transferred patient is readily known at admission. It would be useful to adopt specific measures for such patients, particularly if they have other risk factors of nosocomial infection, both to protect them and to prevent transmission of the infection to other hospitalized patients.

Aged↗
PubMed2001

3-Benzamido, ureido and thioureidoimidazo[1,2-a]pyridine derivatives as potential antiviral agents.

This work reports the synthesis and the antiviral activities of 3-benzamido, 3-phenylureido and 3-phenylthioureido derivatives in the imidazo[1,2-a]pyridine series. The structure was proven by NMR spectroscopy. The synthesized compounds were evaluated against a large number of viruses. The 3-phenylthioureido derivative 7 showed moderate activity against human cytomegalovirus (HCMV) in vitro. The crystallographic data for 8 are also reported and explain the absence of activity against human immunodeficiency virus (HIV).

Anti-HIV Agents↗
PubMed2001

[Effect of cyclodextrins on fungal degradation of fluorene].

The purpose of this study was to improve the bioavailability of fluorene (PAH) by the use of complexing agents, cyclodextrins. The biodegradation tests were performed in liquid medium batches; fluorene was quantified by HPLC. Experimental results showed the enhancement of fluorene degradation by Penicillium italicum and Phanerochaete chrysosporium in the presence of branched cyclodextrins.

Biological Availability↗
PubMed2000

[Substituted cyclodextrins as chelating reagents for ethers, thioethers and yperite].

The complexation of mustard gas Cl(CH(2))(2)S(CH(2))(2) Cl, HD, yperite) and of ethers and thioethers derivatives by cyclodextrins: natural alpha-cyclodextrin (ACD) and substituted B-cyclodextrins was studied by NMR. A 1/1 stoechiometry was found in all cases, while affinity constants were found relatively weak (from 5 M(-1) to 100 M(-1)). However, these results show that chelation of HD by cyclodextrins can be reasonably expected, especially if chemical modifications provide stronger affinity constants.

Antidotes↗
PubMed2000

13C-NMR spectrum field and temperature dependence of 13CO bound to hemoglobin.

13Carbon monoxide (CO), when bound to hemoglobin, yields (13)C NMR resonances (CO-Fe resonances). 100% CO liganded tetrameric hemoglobin ((13)C-labelled CO) was prepared for (13)C-NMR observation. The information about exchange kinetics between the four subunits (2alpha and 2B), were derived by changing the temperature (in the range 275-313K) and the observation frequency (4.7T, 9.4T and 18.8T). The first results confirmed previous observations of slow exchange between free and bound (2alpha and 2B together) CO. Besides, the exchange between alpha and B subunits were found slow at the NMR timescale, even under 313K and 4.7T conditions. Furthermore, intermediate temperatures (283-303K) allowed the observation of broad unresolved lines at 9.4T, corresponding both to CSA contribution and exchange linebroadening. Finally, low temperatures (less than 277K, at 9.4T) provided four relatively broad - but clearly distinguishable lines - indicating that a slow exchange rate was reached between four Fe-CO geometries on the subunits. This also indicated that two main Fe-CO orientations were different, even between similar chains (alpha1-alpha2 and B1-B2).

Carbon Isotopes↗
PubMed1999

Association between institutionalization and carriage of multiresistant bacteria in the elderly at the time of admission to a general hospital.

The impact of institutionalization on the carriage of multiresistant bacteria among the elderly was assessed prospectively by comparing the carriage rate in institutionalized patients over 70 years of age to the carriage rate in patients over 70 living at home (58 patients/group). Nares, skin, and rectal swabs were obtained within 24 h of admission to the hospital. Among the 20 carriers identified, 75% came from institutions. Significantly, institutionalized patients were incontinent (P < 0.001), less autonomous than those living at home (P < 10(-6)), and had taken antibiotics recently (P < 0.02). The primary characteristics associated with bacterial colonization were institutional living (P < 0.02), having at least one underlying disease (P < 0.001), dependence (Karnofsky index < or = 50; P < 0.02), recent treatment with antibiotics (P < 0.02), and the presence of skin lesions (P < 0.02). Among the risk factors identified, institutionalization can be readily determined upon admission; systematic communication of carrier status of transfer patients would improve overall patient care.

Aged↗
PubMed1999

[Surgical antibiotic prophylaxis: point evaluation of practices].

Compliance of prophylactic antimicrobial therapy (PAMT) in surgical patients with consensus-based recommendations was evaluated at the Montfermeil Hospital Center, France, in 1996, based on data for given days. All patients who had surgery on the study days were included. Data on the patient, surgery, and PAMT were collected. Practices were evaluated based on seven criteria: need for PAMT, type of drug used, dosage, time of first administration in relation to the time the incision was made, time of administration during surgery, administration time schedule, and total duration. Of the 93 patients who had surgery on one of the five study days, 59.1% received PAMT. All seven evaluation criteria were met in 68.2% of cases. Failure to adhere to the recommended time of first administration was the most common form of noncompliance.

Anti-Bacterial Agents↗
PubMed1998

Mechanism of alpha-cyclodextrin induced hemolysis. 2. A study of the factors controlling the association with serine-, ethanolamine-, and choline-phospholipids.

A nuclear magnetic resonance (NMR) spectroscopy and molecular modeling study of the interaction between alpha-cyclodextrin (alpha-CD) and phospholipids with serine, ethanolamine, or choline headgroups is presented. The experimental approach is based on 31P and 1H NMR measurements on small unilamellar vesicles (SUV), multilamellar systems (MLV), and aqueous suspensions of lipids using a direct complex preparation with alpha-CD. Molecular dynamics computer simulations are used to investigate the trajectory of alpha-CD in the vicinity of a membrane surface and the influence of the charge and dipole moment of the phospholipid headgroups. These factors of charge and orientation of dipole moment seem to play a key role in the interaction of phospholipids with alpha-CD and reflect very well the experimentally observed selectivity of the phospholipid -alpha-CD approach. However, with this approach, there is no evidence for the formation of a complex with the phospholipid headgroup (except for phosphatidylinositol) that results from electrostatic forces. Rather, after a possible extraction of the lipid from the membrane, a classical inclusion of the sn-2 chain in the cavity of alpha-CD occurs. This step depends on the alkyl chain length and saturation state of the lipids as well as on their organization (i.e., as vesicles or dispersions). Based on our results, chemical modifications of the alpha-CD molecule to control the hemolytic properties of alpha-CD are discussed.

Computer Simulation↗
PubMed1998

Interaction of per 3,6-anhydro-alpha cyclodextrins (alpha 36CD) and lead-alpha 36CD complex with biological systems.

The interactions of per (3,6 anhydro) alpha cyclodextrin (alpha 36CD) and of lead-alpha 36CD complex with biological systems were tested by NMR, ESR and electronic microscopy using erythrocytes and model membranes. It was found that the haemolytic activity of alpha 36CD alone was seven fold lower than that of natural alpha cyclodextrin (evaluated by the concentration inducing 50% haemolysis, DH50 = 35 mM). Conversely, the formation of the complex resulted in an increase of haemolytic properties, with DH50 of 1 mM. The mechanism proposed was an increased membrane diffusion by endocytosis of the complex, leading to higher amounts of intracellular lead.

Chelating Agents↗
PubMed1998

[Specific features of nosocomial infections in the elderly at a general hospital center. 5 surveys of annual prevalence].

Specific features of nosocomial infections in patients aged 70 years or older admitted to a short-term care medical department in a 400-bed general hospital were studied to assist in designing nosocomial infection control programs for this population. Data from five annual prevalence surveys were evaluated retrospectively. The 517 patients aged 70 years or older were compared to the 1093 patients younger than 70 years. The older patients were more likely to have risk factors for nosocomial infections including severe disease (36.2% vs 19.1%; P < 10(-6)), referral from another department (24.6% vs 17.5%; P < 0.01), a long hospital stay duration (8.5 days vs 3.5 days), mechanical ventilation (4.3% vs 1.6%; P < 0.01), an indwelling urinary catheter (12.0% vs 4.0%; P < 10(-7)), and a long median duration of urinary catheterization (6 days vs 2 days). The prevalence of nosocomial infections was increased nearly two-fold in the older patients (10.3% vs 5.6%; P < 0.01), although the difference was statistically significant only for urinary tract infections (5.4% vs 1.4%; P < 10(-5)), particularly in patients without urinary catheters. After exclusion of all patients with urinary tract infections, the prevalence of nosocomial infections was similar in the older and younger patients (4.3% vs 3.7%) despite a persistently higher frequency of risk factors for nosocomial infection in the older group. These results indicate that urinary tract infection should be the main target of programs aimed at minimizing nosocomial infection in elderly patients admitted to short-term care facilities. Faultless technique is essential during urinary catheter insertion. High-quality nursing care contributes substantially to the prevention of urinary tract infection in noncatheterized patients with urinary incontinence or neurologic disorders.

Aged↗
PubMed1997

Mechanism of alpha-cyclodextrin-induced hemolysis. 1. The two-step extraction of phosphatidylinositol from the membrane.

It has been suggested that the interaction of cyclodextrins with the lipid components of the erythrocyte membranes is the determining factor in the hemolysis induced by these cyclic oligosaccharides. In the case of alpha-cyclodextrin (cyclomaltohexose), phospholipids have been identified as the cell target. In our study, evidence for the interaction between alpha-cyclodextrin and different phospholipids has been obtained using synthetic membranes. Since phosphatidylinositol (PI) showed the strongest affinity for alpha-cyclodextrin, it has been selected to investigate the respective contributions of the polar head group and the aliphatic chains to the association process using 31P, 2H, and 1H NMR spectroscopy. In this work, we describe the two-step extraction of PI from the membrane following its association with alphaCD: a cyclodextrin molecule is first attracted to the membrane surface by electrostatic remote interactions and associates with the lipid head group. Then the whole PI molecule is extracted, and inclusion of its unsaturated sn-2 acyl chain into another alphaCD molecule occurs in the bulk.

Cyclodextrins↗
PubMed1997

[Study by NMR of the modifications of brain lipid composition related to the tumor processes].

1H, 13C, 31P and 14N NMR spectroscopies were used to investigate the lipid composition of brain tumors (GL6 glioma) in rats, by comparison with controlateral hemispheres. Comparative indexes derived from NMR signal intensities were used to establish the statistical analysis. It was found that sterol metabolism and sphingolipid/glycerolipids ratio are significantly modified when a tumor is present.

Animals↗
PubMed1997

NMR study of per(3,6-anhydro) alpha cyclodextrin as a potential agent for the biological decontamination of lead.

The ability of per(3,6-anhydro) alpha cyclodextrin(3,6CD) to capture lead from a preformed glutathion (GSH)-lead complex was investigated by NMR spectroscopy. Such a removal strongly depends on the nature and pH of the buffer used in the competition experiments. It was found that an almost complete removal of lead can be achieved at pH 5.5, especially when lead nitrate is used. The capture also strongly depends on the nature of the lead species as well as of the counter ion present in the medium. These observations imply that decontamination of lead by this process should be optimal under acidic conditions, i.e. in the acidic tractus (stomach). Conversely, lead decontamination at neutral pH was of poor efficiency or required a large excess of (3,6CD). This was particularly the case when human plasma was used as solvent.

Chelating Agents↗