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Biomedical subjects

L Bernard

Publications and source records attributed to L Bernard.

At least 19 recordsLinked to original sources
PubMed2006

[Outpatient parenteral antimicrobial therapy (OPAT) in bone and joint infections].

The medical treatment of many bone and joint infections (including chronic osteomyelitis, prosthetic joint infection, and septic arthritis) requires prolonged intravenous antimicrobial therapy. For some patients, this treatment could be administered outside the hospital in a program that offers outpatient parenteral antimicrobial therapy (OPAT). In France, we have no registry of patients receiving OPAT. Initiation of this program requires specific criteria based on a patient evaluation and selection, and an interdisciplinary team of professionals committed to high-quality patient care. Various vascular access devices and infusion pump therapy are used to administer OPAT. The most common parenteral agents for OPAT are beta-lactams and glycopeptids (specifically vancomycin). Antimicrobial courses are stopped prematurely in 3 to 10% of the cases because of an adverse reaction or vascular access complications. Several published studies demonstrate the effectiveness of OPAT and higher patient satisfaction than hospital care. In addition, OPAT is clearly more cost-effective than intravenous therapy provided in the hospital setting. Some diagnoses, such as cellulites, community-acquired pneumonia, and endocarditis may be managed with OPAT.

Anti-Bacterial Agents↗
PubMed2006

Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.

Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are characterized by aberrant cytoplasmic localization of NPM, due to mutations within its last coding exon (exon 12) that cause a frameshift and the formation of novel C-termini. We report here our investigations on the molecular basis for the aberrant localization of mutated NPM. Alignment of the C-terminus of the various NPM mutants revealed the obligatory presence of four amino-acid residues that match a CRM1-dependent nuclear export signal (NES). Single alanine-substitutions at these sites provoked nuclear re-localization, while fusion of the mutated C-terminus to a heterologous nuclear protein induced CRM1-dependent cytoplasmic localization. Molecular characterization of one exceptional AML carrying cytoplasmic NPM and germ line exon 12 revealed a somatic mutation in the splicing donor site of exon 9 that caused the formation of a functional NES. It appears, therefore, that AMLs are frequently characterized by gain-of-function mutations of NPM that create functional NES, suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention.

Acute Disease↗
PubMed2006

Tuberculosis treatment duration in France: From guidelines to daily practice.

BACKGROUND: Guidelines for tuberculosis (TB) recommend 6 months of treatment except for meningeal TB, where a 9- to 12-month course may be preferred. METHODS: In order to assess whether practices in France are in agreement with those guidelines, we performed an anonymous audit of the policy of French physicians, focusing on TB treatment duration and corticosteroid use according to the TB presentation. RESULTS: Sixty-six completed forms were analyzed. Reported treatment duration was usually 6 months for pulmonary TB (91% of physicians) and miliary TB (45%), 9 months for pulmonary TB in HIV-infected patients (42%) and for TB lymphadenitis (57%), and 12 months for TB meningitis (79%) and osteo-articular TB (65%). Corticosteroid use was systematic for meningitis (80%) and pericarditis (65%). CONCLUSION: This study reveals discrepancies between guidelines and daily practice for TB treatment duration in France: We observed a very high reported rate of unnecessary, prolonged treatment for most extrapulmonary TB.

Journal Article↗
PubMed2006

Aseptic meningitis after intrathecal baclofen injection.

STUDY DESIGN: Two case reports of aseptic meningitis after intrathecal baclofen injection. OBJECTIVES: To report an unusual complication of intrathecal baclofen injection during test injections. SETTING: Department of Neurological Rehabilitation, R Poincaré Hôpital (Paris-Ile de France-Ouest University). CASE REPORTS: We present two cases of chemical meningitis after intrathecal baclofen injections by lumbar puncture. These cases presented with febrile meningeal syndromes during the 24 h following intrathecal baclofen injection. Direct cerebrospinal fluid (CSF) examination and CSF cultures were negative. An intense cellular reaction was observed with a marked predominance of neutrophils. Meningitis resolved spontaneously over 3-4 days. CONCLUSIONS: Chemical meningitis is a rare complication of intrathecal baclofen injections that must be recognized. It is a diagnosis of exclusion and its pathophysiological mechanism remains unclear.

Adult↗
PubMed2006

Polymorphism of the cell wall-anchoring domain of the autolysin-adhesin AtlE and its relationship to sequence type, as revealed by multilocus sequence typing of invasive and commensal Staphylococcus epidermidis strains.

We sequenced the adhesin-cell wall-anchoring domain of the atlE gene of 49 invasive and commensal Staphylococcus epidermidis strains. We identified 22 alleles, which could be separated into two main groups: group 1 (alleles 1 and 6 to 16, 32/49 strains) and group 2 (alleles 2 to 5 and 17 to 22, 17/49 strains). Allele 1 (the type strain sequence) was by far the most prevalent (21 of 49 strains). Multilocus sequence typing showed a clear relationship between the atlE allele and the sequence type (ST), with the "nosocomial" ST27 clone and closely related STs expressing group 1 alleles.

Adhesins, Bacterial↗
PubMed2005

[Cervical spondylodiscitis: one pathogen may hide another].

A 54-year-old man presented with tuberculous spondylodiscitis associated to E. coli found in an intervertebral disc space needle biopsy. The enterobacteria came from a cholecystitis. The patient was cured by medical treatment, consisting in a non-surgical immobilization, antitubercular quadritherapy in association with a specific antibiotic treatment. No other case of spondylodiscitis caused by a mycobacterial coinfection pathogen has been reported so far.

Anti-Bacterial Agents↗
PubMed2005

[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy].

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.

Antiviral Agents↗
PubMed2005

Use of genotypic identification by sodA sequencing in a prospective study to examine the distribution of coagulase-negative Staphylococcus species among strains recovered during septic orthopedic surgery and evaluate their significance.

A total of 212 coagulase-negative Staphylococcus strains recovered prospectively during 119 surgeries for proven or suspected bone and joint infection (BJI) were identified by sodA sequencing. These strains were identified as 151 Staphylococcus epidermidis isolates, 15 S. warneri isolates, 14 S. capitis isolates, 9 S. hominis isolates, 6 S. lugdunensis isolates, 5 S. haemolyticus isolates, 4 S. caprae isolates, 4 S. pasteuri isolates, 3 S. simulans isolates, and 1 S. cohnii isolate. Only S. epidermidis, S. lugdunensis, S. capitis, and S. caprae were found to be infecting organisms and were involved, respectively, in 35 (81.4%), 3 (7.0%), 3 (7.0%), and 2 (4.6%) cases of BJI.

Adult↗
PubMed2005

Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids.

Fourteen Alpine goats at midlactation were fed a diet of hay and concentrate (55:45), without (control) or with formaldehyde-treated linseed (FLS) or oleic sunflower oil (OSO) at 11.2 or 3.5% of dry matter intake, respectively, in a 3 x 3 Latin Square design with three 3-wk periods. Milk yield was lower in goats fed FLS than control or OSO (2.13 vs. 2.32 kg/d). Milk fat content was higher with FLS or OSO than control (40.8 vs. 33.8 g/kg). Formaldehyde-treated linseed and OSO caused a significant decrease (23 and 18%, respectively) of C10 to C17 fatty acids secretion compared with control. The secretion of cis-9 C18:1 and cis-9, trans-11 C18:2 were increased 1.44- and 1.54-fold for FLS and 1.78- and 1.36-fold for OSO, compared with control. The C18:3 (n-3) secretion was increased 2.61-fold with FLS compared with control. Milk cis-9 C14:1/C14:0, cis-9 C16:1/C16:0, and cis-9 C18:1/C18:0 ratios decreased with the supplemented diets compared with control. Mammary stearoyl-CoA desaturase mRNA and activity were decreased by the lipid supplements, whereas no significant change was observed for acetyl-CoA carboxylase and fatty acid synthase. The activities of glucose-6-phosphate dehydrogenase, malic enzyme, and glycerol-3-phosphate dehydrogenase were not affected by the lipid supplements. Mammary lipoprotein lipase mRNA increased with OSO, whereas lipoprotein lipase activity tended to decrease with FLS compared with control. Milk lipoprotein lipase activity sharply decreased with lipid supplement (by 59 and 71%, for FLS and OSO, respectively). The changes in milk fatty acid profile due to FLS and OSO supplements were partly related to changes in the levels of mammary enzyme activities or mRNA.

Animal Feed↗
PubMed2004

High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion.

OBJECTIVES: To compare the efficacy, ease of use and safety of intermittent vancomycin infusion (IVI) and continuous vancomycin infusion (CVI) in high-dose therapy of osteomyelitis. METHODS: Forty-four patients with an osteomyelitis requiring vancomycin for more than 4 weeks were prospectively included, 21 receiving IVI and 23, CVI. The target serum concentration of vancomycin was 20-25 mg/L. Pharmacokinetics, adverse effects, and clinical efficacy were recorded. RESULTS: The mean daily vancomycin dosing was the same in the two groups, but the serum vancomycin concentrations (trough or plateau) were lower in the IVI group than the CVI group (21.7 +/- 9.3 and 26.0 +/- 6.1 mg/L, respectively; P < 0.0001). The target concentrations were achieved quicker with CVI, and daily dosing was changed more frequently in the IVI group. After reaching the target, variability of vancomycin serum concentration (trough or plateau concentrations) was higher in the IVI group than in CVI group (standard deviation 7.9 mg/L vs. 5.6 mg/L, respectively; P = 0.001). CVI did not show clinical superiority, but adverse drug effects were more frequent in the IVI group as compared with the CVI group, 9 (42.9%) and 2 (8.7%), respectively (P = 0.03). Survival multiple regression using Cox's proportional hazard model showed that IVI (RR = 5.9, P = 0.03) and osteomyelitis of the foot (RR = 5.2, P = 0.01) were the only factors associated with adverse drug reactions leading to treatment termination. CONCLUSIONS: CVI is practical and effective, and may be a good alternative for patients requiring prolonged treatment with high vancomycin serum levels.

Anti-Bacterial Agents↗
PubMed2004

[Is bone infection of endogenous or exogenous origin? A pathophysiological approach].

Osteomyelitis is a bacterial implant in bone matrix. Infection occurs as a result of a bacteremia, an inoculation during aseptic or orthopedic surgery, or a contiguous infectious focus. Persistent and relapsing infection may be due to three situations: underlying conditions such as diabetes mellitus or rheumatoid arthritis, presence of foreign surgical implant, and a causative bacterial strain. The pathogenesis of osteomyelitis has been explored through various experimental models, involving mostly Staphylococcus (S. aureus, S. epidermidis) and has given new insights. Bacterial adherence to implanted devices or bone matrix via surface proteins is critical for bacterial survival. Further bacterial growth depends on various mechanisms: the capacity to exhibit matrix-embedded lifestyle known as biofilm and the ability for bacterial subpopulations to switch to a dormant metabolic state known as small colony variants. In addition to bacterial factors, the presence of foreign material induces a defect in local inflammatory response partly responsible for the high susceptibility to infection.

Bacteremia↗
PubMed2003

Serotonin syndrome after concomitant treatment with linezolid and citalopram.

Linezolid, a new synthetic antimicrobial, is an important weapon against methicillin-resistant Staphylococcus aureus (MRSA). Although there are reports of serotonin syndrome developing after concomitant use of linezolid and the selective serotonin reuptake inhibitor paroxitene, this report concerns a patient receiving citalopram who developed thrombocytopenia, serotonin syndrome, and lactic acidosis and died following long-term linezolid therapy.

Acetamides↗
PubMed2003

[Insulin resistance and polycystic ovary syndrome].

Polycystic ovary syndrome (PCOS) is a frequent disease, characterized by disturbed ovarian function with hyperandrogenism. Anovulation is secondary to an absence of follicular dominance. Apart from a primary ovarian defect, insulin resistance is observed in PCOS women, even in the absence of overweight. This insulin resistance could be secondary to a defect in the insulin transduction pathway, mainly by a defect in receptor phosphorylation. It enhances hyperandrogenism as it increases ovarian androgen production. Therefore treating insulin resistance by weight loss or drugs reducing insulin resistance might improve fertility of PCOS women. Metformin has been shown to reduce ovarian production, enhance ovulatory cycles and in some cases increase fertility. However, there are few randomized studies on large numbers of patients to prove an effect on pregnancies as well as on the occurrence of early pregnancy loss. There are currently no recommendation on dose and duration of metformin treatment. It is noteworthy that metformin has no authorization in France to be prescribed apart from diabetic patients' care. Considering the medical care of PCOS women, the cardiovascular risk needs to be taken into account. Therefore hypertension, dyslipidemia and diabetes must be treated in those women who need to be followed carefully all over their life.

Female↗
PubMed2003

The DNA sequence quality machine at IFOM: a simple Web-based tool for quantitative assessment of sequencing reactions.

DNA sequence quality is a factor of paramount importance in the world of modern genetic and genomics. Both the sequencing of Human Genome in the "post-draft" era [NHGRI Standard for quality of Human Genomic Sequences, Rev. 7 July (2002) where http://www.nhgri.nih.gov/Grant_info/Funding/ Statements/RFA/quality_standard.html is the HTTP address] and recent "high-throughput" approaches to genetic investigation such as SAGE [Velculescu, V.E., Zhang, L., Vogelstein, B. et al. (1995) "Serial analysis of gene expression", Science 270, 484-487] need a reliable, standardized measure of the quality of a sequencing reaction. The increasing importance of SNP studies also requires a stronger quality control on sequencing reactions by the final user. We propose here a simple, web-based tool for integrated sequence quality evaluation, high quality region quantitative value calculation and chromatogram display. This software is aimed at the small to medium DNA sequence laboratory or to the single researcher, interested in getting a quantitative measure of the sequence quality, browsing the chromatogram and checking the quality values base by base. The program is freely available from the IFOM bioinformatics web Server at http://bio.ifom-firc.it/Phred20/index.html.

Algorithms↗
PubMed2002

Effect of the methodology on circulating peptides determination and consequences on net flux measurements across the gastrointestinal tract of sheep.

Two methodologies for the measurement of peptide amino acids (PAA) in blood were compared to evaluate their effects on the measurement of the net flux of peptides across the gastrointestinal tract of sheep. These methods consisted of a chemical deproteinization of blood samples with sulfosalicylic acid (1.6 M, 0.1 ml for 1 ml of sample) or perchloric acid (1 M, 1 ml for 1 ml of sample) followed by ultrafiltration through a 3,000-Da cut-off filter (SSA + UF3 kD) or gel filtration through a Sephadex G-15 column (1,500-Da cut-off filter; PCA + G-15), respectively, prior to PAA analysis. Peptide concentrations as determined by amino acid concentrations before and after hydrolysis of samples were slightly greater with the SSA + UF3 kD (991 microM) than with the PCA + G-15 (605 microM) methodology. However, both methodologies gave similar net portal-drained viscera flux data in sheep fed on alfalfa pellets with histidine as the only significant uptake of peptide amino acid.

Amino Acids↗
PubMed2001

Characterization of the caprine stearoyl-CoA desaturase gene and its mRNA showing an unusually long 3'-UTR sequence arising from a single exon.

A 5-kb long transcript encoding the stearoyl-CoA desaturase (SCD) was identified by Northern-blot analysis of poly(A)+ mRNA from caprine lactating mammary gland. Complete sequencing of the SCD cDNA (5123 bp) revealed that the coding region (1080 nt) is followed by an unusually long (3.8 kb) 3'-UTR sequence, deriving from a single exon, in which a polymorphism, due to the deletion of a nucleotide triplet, was detected. The complete structural organization of the relevant gene has been determined. The transcription unit was shown to span a 15-kb region and to consist in six exons varying in size from 131 (3rd exon) to 4047 bp (6th exon), and five introns varying in size from 600 to 3700 bp. Using the fluorescence in situ hybridization technique, the SCD gene was localized to bovine and caprine chromosomes 26q21, and ovine chromosome 22q21.

3' Untranslated Regions↗