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E Legrand

Publications and source records attributed to E Legrand.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Mycobacterium avium-intracellulare complex: phenotypic and genotypic markers and the molecular basis for interspecies transmission].

The Mycobacterium avium complex (MAC) comprises a heterogeneous group of slowly-growing mycobacteria that are pathogenic for both humans and animals. Two genetically distinct species within MAC are M. avium, which tends to infect HIV-infected patients, and M. intracellulare more common among immunocompetent individuals. Contrary to M. intracellulare which relates to a single species, M. avium is separated into three subspecies; M. avium subsp. avium, a major opportunistic pathogen leading to a disseminated disease among terminal AIDS patients; M. avium subsp. paratuberculosis, causing Johne's disease among ruminants and implicated in Crohn's disease among humans; and M. avium subsp. silvaticum, a pathogen affecting birds that may cause chronic enteritis among calves but has not yet been associated with human disease. With the exception of mycobactin-dependent growth of M. paratuberculosis, most of the biochemical and cultural tests cannot discriminate among the three subspecies of M. avium. However, recently developed molecular methods and fingerprinting of strains using insertion sequences allows not only to distinguish among them but also further to explore the polymorphism of human and animal isolates. Numerous studies have underlined the probable role of various ecological niches (water, dust, soil, pigs, poultry and ruminants etc.) as a possible source of contamination for AIDS patients. This paper reviews the phenotypic and genotypic markers and epidemiology of M. avium complex organisms and current knowledge of the molecular basis of of inter-species transmission.

Animals↗
PubMed2000

[Osteoporosis in males].

A shorter life expectancy, a higher peak bone mass and the absence of distinct menopause equivalent explain the lower incidence of osteoporotic fractures in men. In contrast to women, osteoporosis in younger men is in most cases secondary. Causes such as prolonged glucocorticoid therapy, ethanol abuse, hypogonadism and gastrointestinal disorders are now well recognized. The impact of cigarette smoking, low calcium intake, vitamin D deficiency, hypercalciuria and thyrotoxicosis is more controversial but seems to constitute real risk factors for bone loss. Furthermore increased propensity to fall also plays a major role in fracture risk, particularly in alcoholic patients and in elderly men with neurologic disorders.

Age Distribution↗
PubMed2000

[Recent developments of spoligotyping as applied to the study of epidemiology, biodiversity and molecular phylogeny of the Mycobacterium tuberculosis complex].

Spoligotyping (for 'spacer-oligonucleotide-typing'), a rapid method for genotyping of Mycobacterium tuberculosis complex using the principle of reverse hybridization, is based on the structure of the direct repeat (DR) locus. The DR locus is made up of a variable number of 36 bp DR repeats that are separated by unique inter-DR sequences of 35 to 41 bp. Fast and highly discriminatory, spoligotyping is an useful alternative to the IS6110-RFLP reference method for molecular typing of M. tuberculosis, in particular for isolates possessing five or few copies of IS6110. In this paper, we review the state of the art of spoligotyping through its main current applications. After a brief introduction to the principle of the technique and its description, we successively review recently published results concerning the molecular epidemiology of tuberculosis in humans and cattle, and discuss the main genotyping strategies currently in use to fingerprint the M. tuberculosis complex organisms. We also describe the recent applications of spoligotyping to study ancient DNA and report on recent developments of this technique to study the biodiversity of the M. tuberculosis complex, its contribution towards improved taxonomy and phylogenetics of the M. tuberculosis complex. Last but not least, potential applications of spoligotyping to study DNA recombination mechanisms are also discussed.

Animals↗
PubMed1999

Bone mineral density and vertebral fractures in men.

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score < -1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward's triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3-2.8) for spine BMD to 2.3 (1.5-3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1-2.5) for spine BMD to 2.6 (1.7-4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score < -2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score < -2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia.

Absorptiometry, Photon↗
PubMed1999

Postantibiotic effects of rifampin, amikacin, clarithromycin and ethambutol used alone or in various two-, three- and four-drug combinations against Mycobacterium avium.

The postantibiotic effects (PAEs) of rifampin, amikacin, clarithromycin, and ethambutol were determined radiometrically against five AIDS-associated isolates of Mycobacterium avium. and were found to be 20.8+/-3.4. 18.4+/-2.5, 11.8+/-1.7. and 2.4+/-0.9 h, respectively. Various two-, three- or four-drug combinations were also screened: the PAEs for a two-drug combination were generally longer than individual drugs (mean PAE of 13.8+/-1.5 to 29.2+/-7.4 h instead of 2.4+/-0.9 to 18.4+/-2.5 h for single drugs). The addition of a third drug further increased the mean PAE to a range of 21.0+/-2.6 to 32.4+/-6.1 h. Both rifampin+clarithromycin and rifampin+amikacin were the most potent two-drug combinations resulting in longer PAEs than individual drugs, whereas rifampin+amikacin+clarithromycin was the most potent three-drug combination. Parallel viable count determinations showed a good correlation between the PAE results obtained by the radiometric method or by bacterial viability assessment. These results are useful in planning future clinical investigations to clarify the possible implication of PAE in drug schedule and dosage, a line of information that is urgently needed to guide the drug administration in M. avium-infected AIDS patients, who are presently over-burdened with the administration of too many drugs for HIV-treatment and opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1999

[Histomorphometric measurement of the architecture of the trabecular bone in osteoporosis: comparative study of several methods].

Osteoporosis is now defined as a disease characterized by a decreased bone mass associated with micro-architectural modification of trabecular bone leading to an increased fragility and to bone fractures. Various histomorphometric methods have been described to measure bone architecture on histological sections. However, not all of methods are strictly equivalent and some of them appear able to detect differences earlier in the course of the disease. We have compared 8 histomorphometric methods known to characterize the architecture of trabecular bone in 55 male osteoporotic patients. Measurements were done on transiliac bone biopsies: Trabecular number, thickness and separation (Tb.N, Tb.Th, Tb.Sp); Trabecular Bone Pattern Factor (TBPf); Euler-Poincaré's number (E); Interconnectivity Index (ICI); strut analysis of the trabecular network with the ratio of nodes/free-end (N/F); star volume of the bone marrow (Vm) and trabeculae (Vtrab) and the Kolmogorov fractal dimension of the trabecular boundaries (D). Relationships between the various architectural parameters were studied by hierarchical cluster analysis. Linear, hyperbolic and exponential correlations were found between trabecular bone volume (BV/TV) and architectural parameters. Cluster analysis demonstrates the link between these architectural parameters. ICI, E and TBPf which reflect the amount of open/closed marrow cavities clustered together and appeared related to Tb.Sp, which are indicators of the mean size of marrow cavities. Tb.Th, Vm and N/F flocked together as they reflect the trabecular size. Tb.N and D segregated together and seemed to best describe the trabecular network complexity. These histomorphometric techniques are correlated but correlations may be linear or non linear. Several histomorphometric techniques need to be used in parallel to appreciate the pathophysiological mechanisms of osteoporotic states.

Bone and Bones↗
PubMed1999

[Trabecular bone microarchitecture and male osteoporosis].

In men the risk of fragility fractures increases as bone mineral density (BMD) declines but the mechanical strength of vertebrae is also dependent on the trabecular architecture. We have examined the relationships between architectural changes of trabecular bone and vertebral crush fractures in 44 male patients with osteoporosis (bone mineral density more than 2.5 SD below the young adult value). Spine radiographs, hip and lumbar spine BMD and transiliac bone biopsies were obtained for all subjects. Histomorphometric study was done on an image analyzer and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th) and number (Tb.N), Trabecular Bone Pattern factor (TBPf), Inter Connectivity Index (ICI), characterization of the trabecular network (Node count and Strut analysis) and Star volume of the marrow space. Eleven male patients, who were referred to our unit for the diagnosis a monoclonal gammopathy of undetermined significance, were selected as controls. The mean values of Tb.Th, Tb.N and Node count were found lower while TBPf, ICI and Star Volume were significantly higher in men with osteoporosis. Exponential regressions were found to best describe the relationships between BV/TV and the architectural parameters: TBPf (r = 0.94 p = 0.01), ICI (r = 0.63 p = 0.001), Star volume (r = 0.79 p = 0.001). There were no significant differences in age, vertebral and hip BMD, BV/TV and Tb.Th between patients with or without fracture. In contrast, in patients with at least one vertebral fracture, ICI and TBPf were significantly higher while Nodecount was lower. Our data suggest that an altered trabecular bone architecture is a major determinant of osteoporotic fractures in men.

Adult↗
PubMed1999

[Genotypic diversity of Mycobacterium tuberculosis in the Guiana-Antilles region].

This investigation dealt with 226 strains (1 isolate/patient) of Mycobacterium tuberculosis isolated in the French West Indies and French Guiana over a three-year period (1994-1996). The genotypic diversity of the isolates was investigated using various molecular markers; essentially two PCR-based rapid methods, namely spoligotyping and double-repetitive-element (DRE)-PCR, as well as three restriction fragment length polymorphism (RFLP)-based methods, namely IS6110-RFLP, DR-RFLP and PGRS-RFLP. Out of 226 isolates investigated, a total of 166 isolates were distributed in 31 spoligotype-defined clusters containing 2-31 strains, which corresponded to a rate of 73% of primary clustering. After secondary typing with DRE-PCR, IS6110-RFLP, DR-RFLP and/or PGRS-RFLP, molecular clonality was established for 73 isolates organised in 25 clusters (32% of clustered isolates). Considering one reactivation case per cluster, the rate of recent transmission was estimated to a minimal rate of 21%, however the available epidemiologic information led to the positive conclusion for only 14% of cases. The data obtained demonstrated the presence of common genotypes of M. tuberculosis among the three overseas French territories, i.e. Guadeloupe, Martinique and French Guiana. The results obtained during this retrospective study clearly indicate the importance of future prospective epidemiological investigations around the clustered cases of tuberculosis, so as to detect the persisting foci of endemic disease and characterize the chain of transmission as well as the subpopulations which are at an increased risk of contracting and/or propagating the disease. Last but not least, the present study also deals with a first phylogenetic approach of M. tuberculosis based on a comparison of the spoligotyping results obtained locally with those reported elsewhere in the world.

French Guiana↗
PubMed1998

Cyamemazine decreases ethanol intake in rats and convulsions during ethanol withdrawal syndrome in mice.

The effect of cyamemazine a dopamine D2 receptor antagonist on voluntary ethanol consumption in rats and on ethanol withdrawal in mice was examined. Male Sprague-Dawley rats were tested in a free choice (water and 10% ethanol) experiment and consumed 5 g/kg ethanol daily. Rats were treated daily IP with cyamemazine (0.5, 1, or 2 mg/kg) or acamprosate (100 mg/kg) during 2 weeks. Both acamprosate and 1 mg/kg cyamemazine significantly decreased ethanol intake by 45% without affecting either fluid or food intake. The lowest dose of cyamemazine had no effect on alcohol intake but increased food intake. The highest dose had no effect on any variables. During the post-treatment period, only 1 mg/kg cyamemazine decreased both ethanol and fluid intakes. Mice were made dependent on alcohol using a chocolate fluid diet containing increasing concentrations of alcohol and withdrawn after 9 days. Mice were treated with cyamemazine (1 or 0.5 mg/kg, respectively) or with the same doses of lorazepam acutely on the day of withdrawal or chronically (during alcohol treatment). Both chronic and acute cyamemazine and lorazepam treatments decreased convulsions during ethanol withdrawal. Both acute treatments decreased locomotor activity in control and alcohol dependent mice. Chronic treatment had no effect on locomotor activity. We suggest that cyamemazine could reduce alcohol consumption by antagonizing the activation of the dopaminergic pathways during the induction of alcohol dependence. The action of cyamemazine on 5-HT3 receptors could also explain its effect on alcohol convulsions during withdrawal convulsions.

Alcohol Deterrents↗
PubMed1998

Different patterns of extension and recurrence in algodystrophy.

A true recurrence at exactly the same site is quite unusual in algodystrophy. Local or regional extension is possible. The bone scan is an easy way to demonstrate that the areas successively affected are not the same. An apparent local recurrence could in fact be a microscopic compression fracture of trabecular bone or cortical fractures or part of a factitious disorder.

Adult↗
PubMed1998

Further vascular, bone and autonomic investigations in algodystrophy.

Direct clinical observation is the most common means of diagnosing algodystrophy. Further investigations may be helpful to rule out other pathological conditions, such as occult or stress fractures or avascular osteonecrosis and to obtain a better understanding of algodystrophy. Transient vascular hyperpermeability in the affected part is well demonstrated by the clinical findings, the MRI signs, and the three-bone scan features. 99m Technectium EHDP bone scan provides an evaluation of the vascular abnormalities and of the osteoblastic activity. Dermal microcirculation and its reactions to sympathetic stimuli are investigated by laser doppler fluximetry and videophotometric capillaroscopy. Perhaps the sweat test does unveil what might be specific about algodystrophy. The amount of bone loss in algodystrophy in a few weeks or months is what might be expected over 10 years during the natural history of uncomplicated osteoporosis. An initial fracture is undoubtedly an initiating event in the appearance of algodystrophy, but patients suffering from algodystrophy may still have significant osteoporosis for a long period and hence be at risk for fracture. Densitometry could be an aid to the diagnosis and probably to monitoring treatment as well. The local colonization of fibroblasts following the transient stage of hyperpermeability must be kept in mind to explain the results of joint, bone, muscles or neurological investigations in late algodystrophy.

Absorptiometry, Photon↗
PubMed1998

Mechanism of action of acamprosate. Part I. Characterization of spermidine-sensitive acamprosate binding site in rat brain.

It has been suggested that the anticraving drug, acamprosate, acts via the glutamatergic system, but the exact mechanism of action is still unknown. The aim of this study was to characterize [3H]acamprosate binding and establish whether this showed any relation to sites on the NMDA receptor complex. We found saturable specific binding of [3H]acamprosate to rat brain membranes with a KD of 120 microM and a Bmax of 450 pmol/mg of protein. This acamprosate binding site was sensitive to inhibition by spermidine (IC50: 13.32 +/- 1.1 microM; Hill coefficient = 1.04), and arcaine and glutamate both potentiated the inhibitory effect of spermidine. Acamprosate binding to the acamprosate binding site was also sensitive to inhibition by divalent cations (Ca2+, Mg2+, and Sr2+). Conversely, acamprosate displaced [14C]spermidine binding from rat brain membranes with an IC50 of 645 microM and a Hill coefficient = 1.74. This inhibitory effect of acamprosate was not affected by arcaine, and was associated with a significant reduction in Bmax and binding affinity for spermidine, suggesting an allosteric interaction between acamprosate and a spermidine binding site. These data are consistent with an effect of acamprosate on the NMDA receptor protein complex, and acamprosate was also found to alter binding of [3H]dizocilpine to rat brain membranes. When no agonists were present in vitro (minimal NMDA receptor activation), acamprosate markedly potentiated [3H]dizocilpine binding at concentrations in the 5 to 200 microM range. However, under conditions of maximal receptor activation (100 microM glutamate, 30 microM glycine), acamprosate only inhibited [3H]dizocilpine binding (at concentrations concentrations >100 microM). When these binding studies were performed in the presence of 1 microM spermidine, the enhancing effects of acamprosate on [3H]dizocilpine binding were inhibited. The results show that acamprosate binds to a specific spermidine-sensitive site that modulates the NMDA receptor in a complex way. Together, with data from al Quatari et al. (see next paper), this work suggests that acamprosate acts as "partial co-agonist" at the NMDA receptor, so that low concentrations enhance activation when receptor activity is low, whereas higher concentrations are inhibitory to high levels of receptor activation. This may be relevant to the clinical effects of acamprosate in alcohol-dependent patients during abstinence.

Acamprosate↗
PubMed1997

Course of specific T lymphocyte cytotoxicity, plasma and cellular viral loads, and neutralizing antibody titers in 17 recently seroconverted HIV type 1-infected patients.

Relationships were sought between specific anti-HIV cytotoxic T lymphocyte (CTL) responses (against structural and regulatory proteins of the HIV-1 LAI isolate) and plasma and cellular viral loads (VLs) in 17 recently HIV-1-infected patients including 3 displaying asymptomatic primary infection (PI) followed up for 12 months. Plasma VL was correlated directly with CD8 counts and inversely with CD4 counts. Cytotoxic reactions were observed in all patients and directed mainly against structural proteins. The earliest CTL responses were against Gag and Env proteins detected in 87 and 75% of the subjects, respectively, within the first month following PI. Anti-Env and Gag cytotoxic responses were inversely correlated with the plasma VL. Reactions against the pol gene products were thought to be either less involved in or less efficient for the initial decrease of viremia. Responses against regulatory gene products were weak and variable, apart from Nef, which was recognized by half of the subjects. Neutralizing antibodies were not detected before month 3, and were found only in six patients at subsequent times. Two of three patients with asymptomatic PI had a low viral burden and either a delayed response or one limited to a few protein CTL responses, suggesting that the magnitude of the CTL response depends on the initial plasma VL. The third patient displayed viral and CTL parameters identical to those of the patients with symptomatic PI. However, two subjects with symptomatic PI exhibited similarly low plasma VL and moderate CTL responses. Overall, the results suggest that the CTL response may not be the sole factor controlling viremia.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Postantibiotic effect of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin against Mycobacterium avium.

Antimycobacterial drugs acting efficiently against Mycobacterium avium complex have in common low MICs and MBC/MIC ratios. The recently reported clinical efficacy of some of the newer drugs is also clearly linked to their pharmacokinetic properties such as higher serum level and/or intracellular concentrations and half-life. In the present investigation, comparative postantibiotic effects (PAEs) of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin were investigated. Bacteria were exposed to MIC, MIC x 4 and MIC x 8 concentrations of each drug for 2 h, the drug was removed by centrifugation and cells were thoroughly washed and resuspended in drug-free medium. Growth was compared to control organisms which underwent a similar treatment (but without drugs) and PAEs were assessed using the equation "T-C", where T equals the time required for colony counts to increase by 1 log10 in test samples after antibiotic exposure and C equals the time for 1 log10 growth in control. Our results underlined two distinct patterns concerning PAE: pattern I included drugs for which PAE (in hours) was dose-dependent and varied (for MIC, MIC x 4 and MIC x 8 concentrations) for amikacin (10.3 +/- 1.7, 14.7 +/- 1.9 and 17.7 +/- 4.1), rifampin (28.0 +/- 7.6, 62.0 +/- 18.5 and 71.0 +/- 3.2) and clarithromycin (2.6 +/- 1.0, 15.0 +/- 4.0 and 22.0 +/- 4.0), whereas pattern II included drugs with a stable PAE, relatively independent of the drug concentrations: sparfloxacin (11.0 +/- 2.5, 12.3 +/- 6.4 and 13.0 +/- 2.1) and clofazimine (26.0 +/- 2.8, 28.8 +/- 2.5 and 27.3 +/- 1.3). These results may be useful for guidance in scheduling of drug administration in M. avium-infected AIDS patients overburdened with too many drugs given for various opportunistic infections.

Amikacin↗