PubMed Health⌕ Search

Biomedical subjects

N Richard

Publications and source records attributed to N Richard.

At least 19 recordsLinked to original sources
PubMed2005

Identifying primary stressors impacting macroinvertebrates in the Salinas River (California, USA): relative effects of pesticides and suspended particles.

Laboratory dose-response experiments with organophosphate and pyrethroid pesticides, and dose-response experiments with increasing particle loads were used to determine which of these stressors were likely responsible for the toxicity and macroinvertebrate impacts previously observed in the Salinas River. Experiments were conducted with the amphipod Hyalella azteca, the baetid mayfly Procloeon sp., and the midge Chironomus dilutus (Shobanov, formerly Chironomus tentans). The results indicate the primary stressor impacting H. azteca was pesticides, including chlorpyrifos and permethrin. The mayfly Procloeon sp. was sensitive to chlorpyrifos and permethrin within the range of concentrations of these pesticides measured in the river. Chironomus dilutus were sensitive to chlorpyrifos within the ranges of concentrations measured in the river. None of the species tested were affected by turbidity as high as 1000 NTUs. The current study shows that pesticides are more important acute stressors of macroinvertebrates than suspended sediments in the Salinas River.

Amphipoda↗
PubMed2004

[Influenza in pediatric intensive cure unit].

OBJECTIVES: The purpose was to identify clinical presentation leading to admission to PICU of children affected by influenza, to describe predisposing factors and outcome and to propose preventive measures. METHODS: Ten years (1989-1999) retrospective study carried out in the ten beds PICU. Every child in PICU with an influenza positive culture was enrolled. RESULTS: Twenty four cases collected, aged two weeks-15 years (m =43 months), 19 males. Acute respiratory failure (16/24 =67%) was the first manifestation: pneumonia (13), bronchiolitis (2), status asthmaticus (1). Eleven children had underlying diseases including five immunocompromized. Thirteen patients required mechanical ventilation (mean duration: 22 days), seven developed ARDS (4 immunocompromized) and three died. Central nervous system was the second system affected (8 cases). Four exhibited a chronical cerebral disease and five presented afebrile status epilepticus which required i.v. barbiturates and mechanical ventilation (mean duration: 22 hours). One presented encephalitis, one an apparent life-threatening event, both had a favorable outcome. One child exhibited severe hyperpyrexia and died from multiorgan failure. CONCLUSION: Severe forms of influenza are rare in children but may lead to life-threatening conditions and death(16.5%). Most occur in children with underlying disease, particularly immunocompromized who may exhibit ARDS.

Adolescent↗
PubMed2003

Integrated assessment of the impacts of agricultural drainwater in the Salinas River (California, USA).

The Salinas River is the largest of the three rivers that drain into the Monterey Bay National Marine Sanctuary in central California. Large areas of this watershed are cultivated year-round in row crops and previous laboratory studies have demonstrated that acute toxicity of agricultural drainwater to Ceriodaphnia dubia is caused by the organophosphate (OP) pesticides chlorpyrifos and diazinon. In the current study, we used a combination of ecotoxicologic tools to investigate incidence of chemical contamination and toxicity in waters and sediments in the river downstream of a previously uncharacterized agricultural drainage creek system. Water column toxicity was investigated using a cladoceran C. dubia while sediment toxicity was investigated using an amphipod Hyalella azteca. Ecological impacts of drainwater were investigated using bioassessments of macroinvertebrate community structure. The results indicated that Salinas River water downstream of the agricultural drain is acutely toxic to Ceriodaphnia, and toxicity to this species was highly correlated with combined toxic units (TUs) of chlorpyrifos and diazinon. Laboratory tests were used to demonstrate that sediments in this system were acutely toxic to H. azteca, which is a resident genus. Macroinvertebrate community structure was moderately impacted downstream of the agricultural drain input. While the lowest macroinvertebrate abundances were measured at the station demonstrating the greatest water column and sediment toxicity and the highest concentrations of pesticides, macroinvertebrate metrics were more significantly correlated with bank vegetation cover than any other variable. Results of this study suggest that pesticide pollution is the likely cause of laboratory-measured toxicity in the Salinas River samples and that this factor may interact with other factors to impact the macroinvertebrate community in the system.

Agriculture↗
PubMed2003

[Pneumocystis carinii infections in a pediatric intensive care unit: a retrospective study 1980-2002].

OBJECTIVE: The objective of this study was to ascertain the clinical and epidemiological characteristics of Pneumocystis carinii pneumonia (PCP) cases admitted to the Pediatric Intensive Care Unit (PICU). PATIENTS AND METHODS: A retrospective study was carried out for the 10 PCP cases admitted to the PICU from 1980 to 2002. The variables studied were: age, sex, PRISM, underlying diseases, immunological status, clinical manifestations, radiology, response to therapy and clinical follow up. RESULTS: Age of the patients varied between 5 months and 15 years and 4 months and there were 7 females and 3 males. Underlying diseases included: AIDS (3 cases), renal transplant (2 cases), West syndrome (1 case), cancer (4 cases). All presented an acute respiratory failure and 8/10 needed mechanical ventilation (mean duration: 14 days). All were treated by trimethoprim-sulfamethoxazole and 6/10 received steroids. Only one child died. CONCLUSION: PCP is rare and affects mainly immunocompromised children who exhibit ARDS. Steroids treatment is now considered as an useful therapeutic adjuvant. A preventive treatment should be administered to children at risk.

Adolescent↗
PubMed2002

fMRI retinotopic mapping--step by step.

fMRI retinotopic mapping provides detailed information about the correspondence between the visual field and its cortical representation in the individual subject. Besides providing for the possibility of unambiguously localizing functional imaging data with respect to the functional architecture of the visual system, it is a powerful tool for the investigation of retinotopic properties of visual areas in the healthy and impaired brain. fMRI retinotopic mapping differs conceptually from a more traditional volume-based, block-type, or event-related analysis, in terms of both the surface-based analysis of the data and the phase-encoded paradigm. Several methodological works related to fMRI retinotopic mapping have been published. However, a detailed description of all the methods involved, discussing the steps from stimulus design to the processing of phase data on the surface, is still missing. We describe here step by step our methodology for the complete processing chain. Besides reusing methods proposed by other researchers in the field, we introduce original ones: improved stimuli for the mapping of polar angle retinotopy, a method of assigning volume-based functional data to the surface, and a way of weighting phase information optimally to account for the SNR obtained locally. To assess the robustness of these methods we present a study performed on three subjects, demonstrating the reproducibility of the delineation of low order visual areas.

Algorithms↗
PubMed2002

[Ma Huang, from dietary supplement to abuse].

Dietary supplements containing Ma Huang (chinease ephedra) are available on the web sites and dietary shops in USA. They are widely promoted and used as a mean of weight reduction and energy enhancement. They contain Ma Huang alone or combined with Guarana (caffeine), creatine, St John's wort, carnitine and are proposed with different labels. Numerous reports of adverse reactions and acute intoxication related to these products use were described in the medical literature. In the light of the severity of these cases, some of which resulted in permanent injury and death, the Food and Drug Administration has proposed limits on the dose and duration of use of such supplements. A review of 140 reports submitted to the FDA between June 1997 and March 1999, 47% involved cardiovascular symptoms, 18% neurological symptoms. Severe hypertension was the single most frequent adverse effect followed by tachycardia, myocardial infarction, stroke, seizure. Ten events resulted in death and 13 produced permanent impairment. In France, ampleness of the use of dietary supplements containing ephedra alkaloids is unknown. Two French recent severe poisonings (one with "ripped Fuel" for losing weight and the other with "Energy pills" in a body builder) show that there is serious health risks for the chronic users. Dietary supplements are not subject to control under "la Direction Générale de la Santé". Informations for general public, medical community and health-care authorities are necessary to be aware of potential health hazards of these products use.

Cardiovascular Diseases↗
PubMed2001

Analysis of polarization effects on nanoscopic objects in the near-field optics.

This paper deals with the analysis of polarization around nanoscopic objects in near-field optics. The objects are illuminated through a transparent glass substrate under the condition of total internal reflection. The use of dielectric and metallic materials in the optical images is discussed. Using numerical simulations based on the Green's dyadic technique, we compute the total transmitted intensity of the scattered light and the different Cartesian components associated with the electric field in the attenuated total reflection configuration at constant height. The role of localized plasmon resonance is brought to the fore in the optical images of nanoscopic metallic objects. This paper shows that it is possible to reduce the interferences due to backward scattering from nanoscopic objects thanks to this polarimetry analysis.

Journal Article↗
PubMed2001

A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine.

BACKGROUND: Many antidepressants are associated with sexual dysfunction, a side effect that may lead to patients' dissatisfaction and noncompliance with treatment. OBJECTIVE: This study compared the efficacy, tolerability, and effects on sexual functioning of bupropion sustained release (bupropion SR) and the selective serotonin reuptake inhibitor fluoxetine. METHODS: In this multicenter, randomized, double-blind, double-dummy, parallel-group study, patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d, fluoxetine 20 to 60 mg/d, or placebo for up to 8 weeks. Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits; tolerability was assessed primarily by monitoring adverse events. RESULTS: Four hundred fifty-six patients participated in the study, 150 receiving bupropion SR, 154 fluoxetine, and 152 placebo. The majority of patients in each group completed the study (63% each, bupropion SR [n = 94] and fluoxetine [n = 97]; 67%, placebo [n = 102]). Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms. Beginning at week 2 and continuing throughout the study, significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo (P < 0.001); similar results were seen in patients defined as clinical responders (> or =50% decrease from baseline in 21-item Hamilton Rating Scale for Depression [HAM-D] total score) (P < 0.001) and in those experiencing remission of depression (HAM-D total score <8) (P < 0.05). At various time points, worsened sexual functioning, sexual desire disorder, sexual arousal disorder, and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo. Both active treatments were well tolerated. CONCLUSIONS: Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression. Fluoxetine, however, was more frequently associated with sexual dysfunction compared with bupropion SR. Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning.

Adult↗
PubMed2001

Longitudinal changes in bone lead concentration: implications for modelling of human bone lead metabolism.

In this study, 539 occupationally exposed subjects received in vivo bone lead measurements using 109Cd excited K X-ray fluorescence (109Cd K XRF). Of these subjects, 327 had previously been measured five years earlier. Measurements were made from both tibia and calcaneus samples, taken to reflect cortical and trabecular bone, respectively. Changes in tibia lead concentration related negatively to initial tibia lead concentration and positively to both lead exposure between the measurement dates and initial calcaneus lead concentration. This finding confirmed and strengthened the interpretation of an earlier study involving fewer subjects. With the larger data set it was possible to examine subgroups of subjects. This showed that people aged less than 40 years had a shorter half-life for the release of lead from the tibia (4.9, 95% CI 3.6-7.8 years) than did those older than 40 (13.8, 95% CI 9.7-23.8 years). Similarly, less intensely exposed subjects (lifetime average blood lead < or = 25 micrograms dL-1) had a shorter tibia lead half-life (6.2, 95% CI 4.7-9.0 years) than those with a lifetime average blood lead > 25 micrograms dL-1 (14.7, 95% CI 9.7-29.9 years). Age and measures of lead exposure were strongly correlated; nevertheless, age matched subgroups with high and low intensity exposures showed clearance rates that were significantly different at the 10% level, with the lower exposure intensity again being associated with the faster clearance. These findings imply that current models of human lead metabolism should be examined with a view to adjusting them to account for kinetic rates varying with age and probably also with exposure level.

Adult↗
PubMed2000

Motoneuron differentiation of immortalized human spinal cord cell lines.

Human motoneuron cell lines will be valuable tools for spinal cord research and drug discovery. To create such cell lines, we immortalized NCAM(+)/neurofilament(+) precursors from human embryonic spinal cord with a tetracycline repressible v-myc oncogene. Clonal NCAM(+)/neurofilament(+) cell lines differentiated exclusively into neurons within 1 week. These neurons displayed extensive processes, exhibited immunoreactivity for mature neuron-specific markers such as tau and synaptophysin, and fired action potentials upon current injection. Moreover, a clonal precursor cell line gave rise to multiple types of spinal cord neurons, including ChAT(+)/Lhx3(+)/Lhx4(+) motoneurons and GABA(+) interneurons. These neuronal restricted precursor cell lines will expedite the elucidation of molecular mechanisms that regulate the differentiation, maturation and survival of specific subsets of spinal cord neurons, and the identification and validation of novel drug targets for motoneuron diseases and spinal cord injury.

Cell Differentiation↗
PubMed2000

Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.

Human immunodeficiency virus (HIV) type 1 (HIV-1) variants were selected for resistance to the (+) and (-) enantiomers of a novel nucleoside analogue, 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine (dOTFC), by use of the infectious molecular clone HIV HXB2D and the human T-cell line MT-4. The dOTFC-resistant variants that were selected were 10-fold less sensitive than wild-type virus, and cloning and sequencing of the complete reverse transcriptase (RT)-coding region identified the mutation M184V. Studies with mutated recombinant HXB2D virus confirmed the importance of the M184V mutation in conferring resistance to (-)dOTFC in MT-4 cells, although no difference in sensitivity was observed in primary cells. The M184V substitution also displayed decreased susceptibility to (+)dOTFC. Selection with (+)dOTFC also produced variants which were 10-fold more resistant than the wild type, and a novel mutation, D67G, was identified following cloning and sequencing of the RT genes. The D67G mutation was introduced into HXB2D by site-directed mutagenesis, and the data obtained confirmed the importance of this mutation in conferring resistance to both (+)dOTFC and (-)dOTFC. Mutated recombinant molecular clone HXB2D-D67G was further selected with (+)dOTFC, and three of six clones sequenced contained both the D67G and M184V mutations, while the other three of the six clones contained only the D67G mutation. Clinical isolates of HIV-1 which are (-) 2'-deoxy-3'-thiacytidine-resistant also displayed resistance to both (+)dOTFC and (-)dOTFC.

Anti-HIV Agents↗
PubMed2000

Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC.

The patterns of resistance-conferring mutations that are selected in HIV-1 reverse transcriptase (RT) by the racemates of 2'-dideoxy-3'-oxa-4'-thiocytidine (+/-)dOTC and its fluorinated derivative (+/-)dOTFC were characterized. Genotypic and phenotypic analyses of HIV-1 clinical isolates and HXB2D variants selected with (+/-)dOTC and (+/-)dOTFC were performed in primary cells and in the MT-2 T cell line. HIV-1 variants selected with (+/-)dOTC or (+/-)dOTFC displayed fivefold decreased susceptibility to the respective compounds. A substitution of methionine to valine was identified at position 184 (M184V) in variants selected with (+/-)dOTC. In contrast, a mutation of lysine to arginine at position 65 (K65R) was found in variants selected with (+/-)dOTFC. These patterns of selected mutations differ from those seen with the individual enantiomers. Studies with mutated recombinant HXB2D-M184V and -K65R confirmed that these mutations are important for phenotypic resistance in MT-2 cells. Clinical isolates that display resistance to (-)2'-deoxy-3'-thiacytidine (3TC) also showed cross-resistance to (+/-)dOTC and (+/-)dOTFC. These studies demonstrate that similar genotypes may be selected by the dOTC and dOTFC compounds to those with the structurally related drug 3TC.

Deoxycytidine↗
PubMed1999

Anti-human immunodeficiency virus type 1 activity, intracellular metabolism, and pharmacokinetic evaluation of 2'-deoxy-3'-oxa-4'-thiocytidine.

The racemic nucleoside analogue 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism studies showed that dOTC is phosphorylated within cells via the deoxycytidine kinase pathway and that approximately 2 to 5% of dOTC is converted into the racemic triphosphate derivatives, which had measurable half-lives (2 to 3 hours) within cells. Both 5'-triphosphate (TP) derivatives of dOTC were more potent than 3TC-TP at inhibiting HIV-1 reverse transcriptase (RT) in vitro. The K(i) values for dOTC-TP obtained against human DNA polymerases alpha, beta, and gamma were 5,000-, 78-, and 571-fold greater, respectively, than those for HIV RT (28 nM), indicating a good selectivity for the viral enzyme. In culture experiments, dOTC is a potent inhibitor of primary isolates of HIV-1, which were obtained from antiretroviral drug-naive patients as well as from nucleoside therapy-experienced (3TC- and/or zidovudine [AZT]-treated) patients. The mean 50% inhibitory concentration of dOTC for drug-naive isolates was 1.76 microM, rising to only 2.53 and 2.5 microM for viruses resistant to 3TC and viruses resistant to 3TC and AZT, respectively. This minimal change in activity is in contrast to the more dramatic changes observed when 3TC or AZT was evaluated against these same viral isolates. In tissue culture studies, the 50% toxicity levels for dOTC, which were determined by using [(3)H]thymidine uptake as a measure of logarithmic-phase cell proliferation, was greater than 100 microM for all cell lines tested. In addition, after 14 days of continuous culture, at concentrations up to 10 microM, no measurable toxic effect on HepG2 cells or mitochondrial DNA replication within these cells was observed. When administered orally to rats, dOTC was well absorbed, with a bioavailability of approximately 77%, with a high proportion (approximately 16.5% of the levels in serum) found in the cerebrospinal fluid.

Animals↗
PubMed1998

Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT1A receptors. This affected markedly the affinity ratios of certain compounds. For example, (+/-)-idazoxan was only 3.6-fold selective for h alpha2A versus h5-HT1A but 51-fold selective for r alpha2A versus r5-HT1A receptors. Conversely, yohimbine was tenfold selective for h alpha2A versus h5-HT1A adrenoceptors but 4.2-fold selective for r alpha2A versus r5-HT1A receptors. Nevertheless, both atipamezole and DMT were highly selective for both rat and human alpha2A versus rat or human 5-HT1A receptors. In conclusion, these data indicate that: (1) the agonist DMT and the antagonist atipamezole are the ligands of choice to distinguish alpha2-mediated from 5-HT1A-mediated actions, whilst several of the other compounds show only low or modest selectivity for alpha2A over 5-HT1A receptors; (2) caution should be exercised in experimental and clinical interpretation of the actions of traditionally employed alpha2 ligands, such as clonidine, yohimbine and (+/-)-idazoxan, which exhibit marked agonist activity at 5-HT1A receptors.

Adrenergic alpha-Agonists↗
PubMed1997

Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1.

Reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) has low fidelity compared with RTs of other retroviruses and cellular DNA polymerases. We and others have previously found that the fidelity of DNA-dependent DNA polymerization (DDDP) of M184V-mutated HIV-1 RT is significantly higher than that of wild-type RT. Viruses containing the M184V substitution are highly resistant to (-)-2'-dideoxy-3'-thiacytidine (3TC) in vitro and in patients treated with 3TC monotherapy. It was of interest to determine the fidelity of RNA-dependent DNA polymerization (RDDP) of M184V RT compared with wild-type because this step occurs first in reverse transcription; errors made during this step may be copied in subsequent polymerization steps. Using an in vitro mispaired primer extension assay, M184V-mutated RT exhibited 3-49-fold decreased frequency of mispair extension compared with wild-type RT. Fidelity differences between M184V and wild-type RT were most marked in extension of A:G (49-fold) and A:C (16-fold) mispairs, with only a marginal (3-fold) decrease in the extension of A:A mispairs. RT containing a methionine to isoleucine (M184I) mutation showed only slight increases in RDDP fidelity compared with wild-type, ranging from 1.5- to 6-fold increases. Of the three RTs tested, wild-type RT was the most error-prone, with mispair extension frequencies ranging from 6.674 x 10(-1) to 7.454 x10(-2).

DNA↗
PubMed1997

Enterotoxin production by staphylococci isolated from foods in France.

Two hundred and thirteen Staphylococcus aureus and 51 other staphylococcal strains were isolated from 121 foodstuffs of current consumption and two cutaneous samples. Their ability to produce staphylococcal enterotoxins was tested and S. aureus strains were biotyped. The S. aureus strains (30.5%) produced at least one of the five known staphylococcal enterotoxins whereas coagulase negative staphylococci did not produce any of them. The raw milk cheeses analysed were primarily contaminated by strains belonging to animal or unspecified biovars. Only 15.9% of the S. aureus strains isolated from these products produced enterotoxins whereas 43% were found to be enterotoxigenic amongst the S. aureus strains isolated from the other foodstuffs. The scheme of biotyping used seems to be reliable, allowing the classification of 73.7% of the strains. S. aureus strains of human biovar origin were most often enterotoxigenic and enterotoxin C was the predominant type identified. It was produced by 66% of the enterotoxigenic strains, singly or in combination with other enterotoxins. Approximately 77% of the human strains also produced enterotoxin C, which is an amazing epidemiological distinctive feature of the strains studied. Moreover ELISA tests used in this work exhibit problems of specificity.

Animals↗