Biomedical subjects

G Durrieu

Publications and source records attributed to G Durrieu.

At least 19 recordsLinked to original sources

PubMed2006

A weighted bootstrap method for the determination of probability density functions of freshwater distribution coefficients (Kds) of Co, Cs, Sr and I radioisotopes.

The objective of the study was to provide global probability density functions (PDFs) representing the uncertainty of distribution coefficients (Kds) in freshwater for radioisotopes of Co, Cs, Sr and I. A comprehensive database containing Kd values referenced in 61 articles was first built and quality scores were affected to each data point according to various criteria (e.g. presentation of data, contact times, pH, solid-to-liquid ratio, expert judgement). A weighted bootstrapping procedure was then set up in order to build PDFs, in such a way that more importance is given to the most relevant data points (i.e. those corresponding to typical natural environments). However, it was also assessed that the relevance and the robustness of the PDFs determined by our procedure depended on the number of Kd values in the database. Owing to the large database, conditional PDFs were also proposed, for site studies where some parametric information is known (e.g. pH, contact time between radionuclides and particles, solid-to-liquid ratio). Such conditional PDFs reduce the uncertainty on the Kd values. These global and conditional PDFs are useful for end-users of dose models because the uncertainty and sensitivity of Kd values are taking into account.

Cesium↗

PubMed2005

COX-2 inhibitors and arterial hypertension: an analysis of spontaneous case reports in the Pharmacovigilance database.

OBJECTIVE: To evaluate the main characteristics of case reports of arterial hypertension (AH) related to COX-2 inhibitor (coxib) use in real-life practice. METHODS: This study was based on spontaneous reports of adverse drug reactions (ADRs) submitted to the French Pharmacovigilance system. Associations between AH and the different groups of those using non-steroidal anti-inflammatory drugs (NSAIDs: rofecoxib, celecoxib and non-selective NSAIDs) were compared using calculation of the odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: In France, between 1 April 2000 and 30 November 2003, 34 AH cases related to coxibs were reported. Case reports include predominantly patients older than 65 years, with a previous story of essential AH. Most AH (60%) occurred during the first 15 days of treatment. The AH was reported significantly more frequently for rofecoxib than celecoxib. The OR for development of AH with rofecoxib versus celecoxib was 3.3 (1.6-6.9). The AH was also reported more frequently with coxib (2.8%) than with non-selective NSAID (0.5%) use, OR = 5.9 (3.8-9.0). CONCLUSION: This study shows that coxibs are associated with a risk of AH in real-life practice. More spontaneous reports of AH to the French Pharmacovigilance system concern rofecoxib than celecoxib (and coxibs than non-selective NSAIDs). This ADR is of special epidemiological importance due to both the risks of AH and the large use of coxibs.

Adult↗

PubMed2004

Fertility and outcomes of pregnancy after chemotherapy in a sample of childbearing aged women.

The aim of the study was to review the characteristics and outcomes of pregnancies occurring in women of childbearing age after chemotherapy for malignant disease. Between November 1998 and October 1999, a total of 16 patients who were treated for ovary (three), mole (one), vaginal (one), breast (four), Hodgkin's disease (four), lung (one), melanoma (one) and osteosarcoma (one) carcinoma were identified and retrospectively questioned about their fertility status. All the 16 women included in this study received at least one alkylating agent. Five patients (31%) experienced anomalies of hormonal cycle during and after the treatment. All of them recovered normal cycle without consequence of fertility. Caesarean section was performed in seven of 20 (35%) pregnancies with known outcomes. No obstetrical events were reported. The 16 women had 21 pregnancies resulting in 18 normal infants, one newborn with a minor abnormality (tallus foot), one spontaneous abortion and one lost of follow-up to 6 months of pregnancy. The present survey suggests that cytotoxic drug exposure had no deleterious effects on subsequent pregnancies. A prospective and systemic survey would be the only means able to clarify the actual cancer therapy on reproductive outcome and to investigate the long-term effects in the progeny.

Abnormalities, Drug-Induced↗

PubMed2000

Statistical analysis of mitochondrial pathologies in childhood: identification of deficiencies using principal component analysis.

Mitochondrial pathologies are a heterogeneous group of metabolic disorders that are frequently characterized by anomalies of oxidative phosphorylation, especially in the respiratory chain. The identification of these anomalies may involve many investigations, and biochemistry is a main tool. However, considering the whole set of biochemical data, the interpretation of the results by the traditionally used statistical methods remains complex and does not always lead to an unequivocal conclusion about the presence or absence of a respiratory chain defect. This arises from three main problems: (a) the absence of an a priori-defined control population, because the determination of the control values are derived from the whole set of investigated patients, (b) the small size of the population studied, (c) the large number of variables collected, each of which creates a wide variability. To cope with these problems, the principal component analysis (PCA) has been applied to the biochemical data obtained from 35 muscle biopsies of children suspected of having a mitochondrial disease. This analysis makes it possible for each respiratory chain complex to distinguish between different subsets within the whole population (normal, deficient, and, in between, borderline subgroups of patients) and to detect the most discriminating variables. PCA of the data of all complexes together showed that mitochondrial diseases in this population were mainly caused by multiple deficits in respiratory chain complexes. This analysis allows the definition of a new subgroup of newborns, which have high respiratory chain complex activity values. Our results show that the PCA method, which simultaneously takes into account all of the concerned variables, allows the separation of patients into subgroups, which may help clinicians make their diagnoses.

Adolescent↗

PubMed1999

Detection of quantitative trait loci associated with alcohol-dependence: use of model-free sib-pair method and combined segregation-linkage analysis based on regressive models.

Two linkage methods were used to detect loci underlying neurophysiological measures associated with alcohol dependence 1) the Haseman-Elston (H-E) sib pair method for genome-wide search, and 2) the combined segregation-linkage (CSL), based on regressive models, to confirm positive linkages found by the genome screening. Among 14 linkage results that were significant at the 0.5% level using H-E, the CSL method leads to similar p-values in only three cases but to higher p-values in all others. Investigation of these discrepancies shows that assumptions (normality and homoscedasticity of the error term) of H-E least-squares regression method are not verified. A robust estimator of slope parameters without assuming any distribution function for the linear model error terms increases the p-values and reduces the difference between H-E and CSL results. Alternatively, the CSL approach may lack power when multiple genes with small effects are involved.

Alcoholism↗

PubMed1998

Clinical pharmacology of befloxatone: a brief review.

Clinical pharmacology studies of befloxatone, a new selective reversible inhibitor of monoamine oxidase-A (MAO-A), have addressed safety, with special emphasis on tyramine interactions, and have also investigated pharmacokinetics (PK) and pharmacodynamics in terms of both MAO-A inhibition (using 3,4-dihydroxyphenylglycol, DHPG, as a pharmacological activity marker) and effects on psychomotor and cognitive function, in young and elderly healthy volunteers. Clinical and laboratory safety data were satisfactory in healthy volunteers given single doses of up to 160 mg or repeated doses of up to 80 mg/day for 7 days. Tyramine interaction studies showed that the expected potentiation of the tyramine pressor effect occurred with a safety margin that was so wide as to make dietary restrictions unnecessary with dosages of up to 20 mg once daily in clinical settings. Absorption was rapid (tmax = 2 h), terminal halflife was about 11 h, and PK parameters increased linearly with the dose. Befloxatone induced a dose-dependent decrease in plasma DHPG levels from 2.5 mg upwards, and a 10-mg dose provided sub-maximal activity (80% DHPG decrease) of 24 h duration. No sedative or stimulant effects were detected using several batteries of psychometric tests. Befloxatone was devoid of deleterious effects on memory in young volunteers, and exhibited the EEG profile of a non-sedative antidepressant. In summary, available clinical pharmacology studies confirm that befloxatone is a safe and potent RIMA with no potential for inducing deleterious CNS effects.

Adult↗

PubMed1998

[Phylogeny of fungi responsible for smut of plants based on ITS sequence analysis].

Phylogenetic relationships among fungi belonging to the family of Ustilaginaceae (genera Microbotryum, Spacelotheca, Ustilago, Sporisorium) are inferred from a parsimony analysis using the ITS sequences of nuclear ribosomal genes. The introduction in the phylogeny of sequences from species of Suillus, Puccinia and Taphrina as outgroup shows the polyphyletism of this family. These results support the division of this taxon into two groups: Ustilaginaceae s. str. formed only by the pathogens of Poaceae, and Microbotryaceae constituted by the pathogens of Dicotyledons. Furthermore, we proposed to extend the host plant spectrum of Ustilaginaceae s. str. to all the Monocotyledons. Several discriminating characteristics are listed to support this distinction.

DNA, Plant↗

PubMed1997

Identification of mitochondrial deficiency using principal component analysis.

The mitochondrial pathologies are a heterogeneous group of metabolic disorders that are characterized by anomalies of oxidative phosphorylation, especially in the respiratory chain. The diagnosis of these pathologies involves many investigations among which biochemical study is at present the main tool. However, the analysis of the results obtained during such study remains complex and often does not make it possible to conclude clearly if a patient is affected or not by a biochemical and/or bioenergetic deficiency. This arises from two main problems: 1. The determination of control values from the whole set of variable values (affected and unaffected people). 2. The small size of the population studied and the large number of variables collected which present a rather large variability. To cope with these problems, the principal component analysis method is applied to the results obtained during our biochemical studies. This analysis makes it possible for each respiratory chain complex, to distinguish clearly two subsets of the whole population (affected and unaffected people) as well as to detect the variables which are the most discriminative.

Adolescent↗

PubMed1996

Pharmacodynamics and pharmacokinetics of two dose regimens of befloxatone, a new reversible and selective monoamine oxidase inhibitor, at steady state in healthy volunteers.

The pharmacodynamic equipotency of 2 dose regimens (5 mg twice daily versus 10 mg once daily) of befloxatone, a new reversible and selective monoamine oxidase A (MAO-A) inhibitor, after single and multiple doses for 6 days was examined in a randomized, double-blind, three-way crossover, placebo-controlled trial of 12 healthy volunteers. Plasma levels of the deaminated metabolite 3-4 dihydroxyphenylglycol (DHPG), as measured by high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, were used as an index of MAO inhibition. A single dose of befloxatone produced a significant dose-related reduction in plasma DHPG levels, as shown by the decrease in the 24-hour area under the concentration-time curve (AUC0-24) of DHPG, which peaked 2 hours after administration and persisted over 24 hours. Both dose regimens provided equipotent extent and duration of MAO-A inhibition at steady state, suggesting a once daily dosage should be sufficient for most patients. The pharmacokinetic bioavailability at steady state of both dose regimens was also similar. The concentration-time effect curve after a single dose revealed a hysteresis corresponding to the delay necessary to elicit MAO inhibition and/or elimination of DHPG. The relationship between plasma levels of DHPG and/or elimination of plasma concentrations of DHPG and befloxatone after a single dose can be modeled using the Emax model with a mean EC50 of 4.75 ng/mL, and suggests the presence of a maximal response from the single dose. This model permits prediction of steady-state levels of DHPG.

Adult↗

PubMed1996

Effects of befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects.

Befloxatone is a new reversible and selective monoamine oxidase (MAO-A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double-blind, five-way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long-term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.

Adult↗

PubMed1996

A study of dopaminergic sensitivity in Parkinson's disease: comparison in "de novo" and levodopa-treated patients.

The present study investigates dopaminergic sensitivity in Parkinson's disease (PD) through the measurement of neuroendocrine (growth hormone: GH, prolactin: PRL) and cardiovascular (blood pressure: BP, heart rate: HR) responses to low doses of apomorphine (5 micrograms/kg s.c.) in three groups of subjects: 13 normal volunteers (controls), 19 "de novo" never-treated PD patients, and 14 levodopa-treated PD patients. Apomorphine did not change BP and HR but significantly decreased PRL plasma levels in controls as well as in the two groups of PD patients. GH plasma levels significantly increased after apomorphine. There was no significant difference in the changes in neuroendocrine (GH, PRL) parameters in the two groups of PD patients in comparison with controls. However, "de novo" patients exhibited a significantly higher number of apomorphine-induced orthostatic symptoms (7 of 19) than did controls (0 of 13) or treated PD patients (2 of 14). These results show that hypothalamic dopaminergic sensitivity (studied through GH and PRL responses to apomorphine) is normal in PD. In contrast, because apomorphine-induced orthostatic hypotension is mainly due to the stimulation of peripheral dopaminergic receptors, our study suggests a peripheral dopaminergic hypersensitivity in some "de novo" never treated (but not in treated) PD patients.

Adult↗

PubMed1995

Pressor effect of oral tyramine during treatment with befloxatone, a new reversible monoamine oxidase-A inhibitor, in healthy subjects.

The interaction between tyramine and befloxatone, a new selective, reversible monoamine oxidase-A (MAO-A) inhibitor, was studied in a single-blind, parallel-group study in 30 healthy male volunteers whose fasting tyramine 30 dose (Tyr30) was 400 or 600 mg. Each subject completed a placebo run-in period followed by a befloxatone period. Befloxatone was given in repeated doses according to one of three regimens: befloxatone 20 mg once daily at the end of a meal rich in tyramine or befloxatone 10 or 20 mg twice daily 2 hours before a meal rich in tyramine. Subjects were given increasing daily doses of tyramine mixed with the meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (Tyr30). The mean Tyr30 decreased from 1220 mg (range, 600-1800 mg) during placebo to 290 mg (range, 150-500 mg) during befloxatone 20 mg once daily, 250 mg (range, 100-300) during befloxatone 10 mg twice daily, and 155 mg (range, 100-250 mg) during befloxatone 20 mg twice daily; corresponding to a potentiation factor of 5.2-, 6.5-, and 7.9-fold, respectively. The extent and the duration of the systolic blood pressure increase did not significantly differ between the placebo and the befloxatone regimens, except for a longer duration with the 20-mg twice daily regimen. These results are similar to those reported with the therapeutic dosage of other selective MAO-A inhibitors. They suggest that there would be little risk of hypertensive crisis in patients treated in clinical studies with befloxatone, and thus dietary restrictions appear to be unnecessary when the drug is given in a regimen of up to 20-mg once daily after meals.

Adult↗

PubMed1995

Relationships between kallikrein secretion, kallikrein excretion and beta-adrenoceptors in kidney cortical slices from neurogenic hypertensive dogs.

1. Sinoaortic denervation (SAD) in dogs is characterized by an increase in blood pressure and heart rate as well as the development of renal morphological lesions similar to those observed in essential hypertension in human subjects. To assess the effect of SAD on the secretion of kallikrein kinin systems (KKS), we studied the in vitro secretion of kallikrein by renal cortical slices of normal and neurogenic hypertensive dogs (1 and 18 months after SAD). The method using renal cortical slices allowed the study of secretion of kallikrein independently of renal perfusion pressure. The number of renal beta-adrenoceptors was measured by [125I]-cyanopindolol binding. 2. SAD was associated with a marked increase in urinary kallikrein excretion at one month and a significant decrease at 18 months when compared with controls. Both changes were statistically significant (P < 0.05). Concurrently, a progressive increase in in vitro kallikrein secretion was observed (+80 +/- 10% and +179 +/- 48%, 1 and 18 months after SAD, respectively). Moreover, the cortical slices obtained from sinoaortic denervated dogs contained more kallikrein than the control cortical slices (+32 +/- 16% and +55 +/- 7%, 1 and 18 months after SAD, respectively). 3. Renal beta-adrenoceptor number significantly (P < 0.05) decreased 18 months after SAD from 18 +/- 2 to 8 +/- 3 fmol mg-1 protein without any change in affinity constant. 4. Although there was no test of association, because the number of renal beta-adrenoceptors decreased whereas kallikrein secretion increased, the present data could suggest a beta-adrenoceptor-mediated inhibition of kallikrein secretion. These results show that although the urinary kallikrein is decreased, the tissue secretory capacities are enhanced. This could suggest a renal compensatory mechanism possibly involved in tissue protection in dogs after SAD, although such a mechanism is not sufficient to reverse hypertension.

Animals↗

PubMed1994

Relationship between arterial blood pressure disturbances and alpha adrenoceptor density.

To investigate the influence of blood pressure disturbances on human platelet alpha 2-adrenoceptor density, we studied 7 normotensive Parkinsonians with orthostatic hypotension and 23 mild essential hypertensive patients. Plasma catecholamine levels were measured by HPLC and alpha 2-adrenoceptor number and affinity determined by [3H]-yohimbine binding. Alpha-adrenergic reactivity was investigated by blood pressure response to noradrenaline infusion in Parkinsonians and by adrenaline-induced platelet aggregation in hypertensive patients. In Parkinsonians with orthostatic hypotension, in comparison with Parkinsonians without orthostatic hypotension and normotensive control subjects age and sex matched, noradrenaline plasma levels were significantly lower (62 +/- 11, 195 +/- 14 and 219 +/- 13 pg. ml-1 respectively, p < 0.05), platelet alpha 2-adrenoceptor number was significantly higher (313 +/- 52, 168 +/- 9 and 174 +/- 4 fmol.mg-1 protein respectively, p < 0.05) and the noradrenaline dose required for a 25 mm Hg increase of systolic blood pressure significantly lower (0.19 +/- 0.03, 0.86 +/- 0.11 and 0.68 +/- 0.10 microgram.Kg-1 respectively, p < 0.05). In hypertensive patients, in comparison with normotensive control subjects age and sex matched, plasma noradrenaline levels remained unchanged (306 +/- 68 vs 246 +/- 28 pg.ml-1) whereas both platelet alpha 2-adrenoceptor number (137 +/- 15 vs 177 +/- 15 fmol.mg-1 protein, p < 0.05) and velocity of adrenaline-induced platelet aggregation were significantly decreased. These results indicate that platelet alpha 2-adrenoceptor density is related to blood pressure values. In Parkinsonians with orthostatic hypotension, the up-regulation of alpha 2-adrenoceptors was induced by the decrease of endogenous catecholamines. In contrast, in essential hypertension a down-regulation of alpha 2-adrenoceptors was observed in spite of no significant increase of catecholamine levels. These results suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptor regulatory mechanisms.

Aged↗

PubMed1993

Effects of yohimbine on plasma catecholamine levels in orthostatic hypotension related to Parkinson disease or multiple system atrophy.

Different pathophysiological mechanisms may underly orthostatic hypotension (OH) observed in neurological degenerative disorders. The present study investigates the responses to the pharmacological activation of sympathetic pathways induced by yohimbine (0.2 mg/kg orally) through measurements of plasma catecholamine levels in parkinsonian patients with (n = 9) or without OH (n = 11), in patients with multiple system atrophy (MSA) plus OH (n = 9), and in controls (n = 6). Basal norepinephrine plasma levels in parkinsonian patients with OH (71 +/- 11 pg/ml) were significantly lower (p < 0.05) than in parkinsonian patients without OH (280 +/- 25 pg/ml) or in controls (259 +/- 48 pg/ml). In patients with MSA plus OH, basal catecholamine plasma levels were in the normal range (344 +/- 54 pg/ml). Yohimbine significantly increased norepinephrine (p < 0.05) but not epinephrine plasma levels in all groups. However, the increment obtained in parkinsonian patients with OH (+53 +/- 18 pg/ml) remained significantly lower (p < 0.05) than in parkinsonian patients without OH or in controls (+638 +/- 140 and +457 +/- 103 pg/ml, respectively) as well as in MSA plus OH (+633 +/- 142 pg/ml). Yohimbine failed to modify the blood pressure and heart rate at the dose used. The results suggest that the yohimbine test is useful to elucidate the site of the dysfunction of the efferent sympathetic pathways in these two conditions. In Parkinson disease with OH, the lesion is both central and postganglionnic, whereas in MSA it is only centrally located.

Aged↗

PubMed1992

Parkinson's disease and weight loss: a study with anthropometric and nutritional assessment.

In order to investigate a putative weight loss in patients with Parkinson's disease, an anthropometric and biochemical study was undertaken. We compared body weight and indexes of fat [body mass index (BMI), tricipital skinfold] and lean [midarm muscle area (MMA), calf circumference] mass in men and women suffering from idiopathic Parkinson's disease with normal controls. We found that women suffering from Parkinson's disease exhibited a significant weight loss (-8.5%) and decreased calf circumference when compared with controls. A decrease (-4.3%) in total body weight was also found in men with Parkinson's disease but the difference did not reach the level of significance. Protein biochemical markers of nutritional status (albumin, prealbumin, retinol binding protein, transferrin) were normal in Parkinson's disease patients. The present study demonstrates the occurrence of weight loss in a large population of patients with Parkinson's disease. The putative mechanisms involved in the weight loss are discussed.

Aged↗

PubMed1991

Effects of levodopa and bromocriptine on blood pressure and plasma catecholamines in parkinsonians.

Blood pressure (BP), heart rate (HR), plasma noradrenaline (NA), and adrenaline (A) levels in the lying and standing position were compared in patients with Parkinson's disease (PD) and control subjects. Three groups of PD patients (stage 2 and 3) were investigated: six patients deprived of antiparkinsonian drugs from 48 h, seven levodopa + benserazide-treated patients, and seven bromocriptine-treated patients. BP, HR, NA, and A were similar at rest and in the standing position in controls and in PD patients deprived of antiparkinsonian drugs from 48 h. Chronic treatment with levodopa (+ benserazide) failed to modify BP, HR, NA, and A. Bromocriptine decreased BP, HR, and NA (but not A) at rest. In PD patients treated with levodopa (+ benserazide) or bromocriptine alone, the rise in NA (but not A) elicited by standing up was reduced. These results indicate that (a) stages 2 to 3 of Parkinson's disease are not accompanied by major changes in autonomic cardiovascular function and (b) dopaminergic drugs blunted the sympathetic response to standing up.

Aged↗

PubMed1991

Absence of arterial hypertension despite chronic plasma noradrenaline elevation: evidence for down-regulation of alpha-adrenoceptors. A case report.

A 44 year old-healthy female presented chronic and stable high levels of plasma noradrenaline (NA) without any major change in adrenaline. The diagnosis of phaeochromocytoma was discarded. These increased levels of NA offered an unique opportunity to investigate under in vivo conditions a putative regulation of alpha-adrenoceptors by this endogenous catecholamine. Infusion rates of exogenous NA up to 0.74 micrograms/kg per min were unable to induce any change in blood pressure (or heart rate) in the subject, In contrast, in normotensive controls, an increase in blood pressure (+ 15 mm Hg) was observed with 0.39 micrograms/kg per min. The magnitude of yohimbine-induced increase in plasma NA was similar in the subject and in the controls. Platelet alpha 2-adrenoceptors evaluated by specific [3H]-yohimbine binding showed a significantly lower level in the subject when compared to controls. The results show that a sustained increase in plasma NA is able to induce down-regulation of alpha-adrenoceptors. This down-regulation can explain the lack of arterial hypertension despite the increased sympathetic tone.

Adult↗