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Biomedical subjects

F Lefevre

Publications and source records attributed to F Lefevre.

At least 19 recordsLinked to original sources

[Evolution of the treatment of chronic post-traumatic aneurysms of the descending thoracic aorta: 30 years experience].

The authors present the early and late results of a series of 40 patients treated for chronic post-traumatic aneurysms of the descending thoracic aorta from 1975 to 2005. With the exception of a patient who died of an intra-pleural rupture before surgery, the patients were treated by aortotomy and prosthetic graft (N=17), aortotomy and direct suture (N=17) or endoprosthesis (N=5). The use of distal aortic perfusion in 22 patients enabled 17 direct sutures (77.3%) thanks to extensive mobilisation of the aortic arch. Endoprostheses have been used since 1997 in high surgical risk patients with severe comorbid conditions. There were no deaths, one transient paraparesia after simple aortic clamping, one reoperation for a haemothorax and four cases of dysphonia due to paralysis of the recurrent laryngeal nerve. Thirty-five patients (90%) were followed up for an average of 119.7 +/- 16.4 months. There were no clinical complications and the late morphological results were good in all cases with the exception of one type 1 endoprosthetic leak. The treatment of chronic post-traumatic aneurysms of the descending thoracic aorta gives excellent early and late results, justifying wide operative indications. The wish to avoid use of a prosthesis in young patients with a long life expectancy should give preference to conventional surgical techniques which, providing distal aortic perfusion is employed, allow direct suture of three quarters of cases. Endovascular treatment is reserved only for "poor surgical risks".

Accidents↗

Polarized porcine trophoblastic cell lines spontaneously secrete interferon-gamma.

Following the demonstration of high levels of interferon-gamma (IFN-gamma) synthesis by the pig trophectoderm around implantation, an adequate experimental system was established so as to study the regulation of endogenous IFN-gamma gene. Several stable cell lines have been isolated from Day 14 and 15 pig trophoblast, that could withstand indefinite growth when cultured on collagen-coated supports. Since no feeder cells were used for culture, and cell lines could be successfully cloned, these lines represent the first pure porcine trophoblastic (TB) cell lines isolated so far. These cells were shown to exhibit most differentiation markers of epithelial cells and in addition to express the porcine trophectoderm-specific antigen SN1-38. The TB cell line A (TBA) was characterized in more details upon culture on microporous filters, where a high apico-basal polarity could be obtained. In those conditions, a transient and acute interferon-gamma secretion was detected only in the apical medium. Moreover, the two trophoblast-specific mRNA of 1.3 and 1.4 kb that have been described in the blastocyst collected in vivo were shown to be synchronously transcribed. This polarized synthesis and secretion of IFN-gamma was correlated with the acquisition of maximal levels of electric resistance of TBA monolayers on filters, and was not observed on the same cells cultured on plastic. This differentiation was maintained over 30 passages, demonstrating that the induction of IFN-gamma secretion by pig conceptus is not maternally controlled. This cellular model will be of prime importance for studies on the developmental regulation of the IFN-gamma gene, and more generally for studies on relationship between secretion and polarity in transporting epithelia.

Animals↗

Directed evolution and Phenomics screening of new biocatalysts.

Biodiversity screening and directed evolution are two fruitful complementary approaches for the discovery and design of novel biocatalysts. A new technology for directed evolution, L-Shuffling, has been designed and patented by Proteus. L-Shuffling technology offers several competitive advantages over other technologies including (i) directed evolution of large genes: L-Shuffling" means "Large-Shuffling"; (ii) high fidelity recombination and (iii) Control over location and frequency of recombination. The thousands of new recombinants generated by L-Shuffling can be further screened for their biochemical characteristics using Phenomics. Phenomics is a proprietary functional HTS technology designed and patented by Proteus for the screening of natural biodiversity as well as biodiversity generated by combinatorial biology. Phenomics is a function to gene structure approach which provides an alternative to genomics and proteomics. The traditional limits of expression libraries are thereby circumvented especially those related to cytotoxic products in usual or specific surrogate hosts. The quality of the answer given by the screening is directed dependent on the quality of the question asked. Thanks to a new substrates synthesis technology named CLIPS-O, the company can design highly specific molecules simulating the chemical structure and energetic state of the industrial substrates. The whole process of novel biocatalysts discovery has been automated using commercially available high throughput robotics.

Bacteria↗

Induction of porcine cytokine mRNA expression after DNA immunization and pseudorabies virus infection.

Injection of plasmid DNA encoding pseudorabies virus (PRV) glycoprotein into pig muscle has been shown to result in protective immunity against lethal infection. Here, pigs were vaccinated by a single coinjection of three plasmids encoding PRV glycoproteins gB, gC, and gD, with plasmid expressing porcine granulocytemacrophage colony-stimulating factor (GM-CSF) or porcine interferon-alpha (IFN-alpha). DNA immunization induced a primary T cell-mediated response characterized by low rates of IFN-gamma, interleukin-2 (IL-2), and IL4 mRNA in peripheral blood mononuclear cells (PBMC). Very low rates of PRV-specific IgG1 and the absence of IgG2 were obtained. Codelivery of plasmid expressing GM-CSF or IFN-alpha had no effect on cytokine mRNA expression or on B cell response. After a high virulent challenge, high levels of cytokine mRNA, mainly IFN-gamma, and high secondary antibody (Ab) response were induced in all DNA-vaccinated pigs. Codelivery of GMCSF gene significantly increased both Th immune response (i.e., IFN-gamma and IL-4 mRNA expression) and clinical protection but had no effect on secondary B immune response. Codelivery of IFN-alpha gene had no beneficial effect on secondary T and B cell immune responses.

Animals↗

Ketogenic diet for the treatment of refractory epilepsy in children: A systematic review of efficacy.

OBJECTIVES: To systematically review and synthesize the available evidence on the efficacy of the ketogenic diet in reducing seizure frequency for children with refractory epilepsy. DATA SOURCES: Medline searches were performed using the keywords epilepsy/therapy, dietary therapy, and epilepsy, and the text word ketogenic diet. The Cochrane Library of clinical trials was searched using the term ketogenic diet. Bibliographies of recent review articles and relevant primary research reports, as well as Current Contents were reviewed for additional relevant citations. STUDY SELECTION: Studies were selected for inclusion in the review that reported the reduction of seizure frequency following treatment with the ketogenic diet in children with refractory epilepsy. The outcome measures used were the percentage of patients with: 1) complete elimination of seizures, 2) >90% reduction in seizures, and 3) >50% reduction in seizures. RESULTS: The evidence consists entirely of uncontrolled studies. Of 11 studies identified for this review, 9 are retrospective series of patients from a single institution. Two studies are prospective, 1 of which is a multicenter trial. The results of these studies are consistent in showing that some children benefit from the ketogenic diet, demonstrated by a significant reduction in seizure frequency. Estimates of the rates of improvement by combined analysis (confidence profile method) are complete cessation of all seizures in 16% of children (95% confidence interval [CI]: 11.0-21.7); a greater than 90% reduction in seizures in 32% (95% CI: 25.3-39.8); and a greater than 50% reduction in seizures in 56% (95% CI: 41.2-69.7). It is unlikely that this degree of benefit can result from a placebo response and/or spontaneous remission. CONCLUSIONS: Although controlled trials are lacking, the evidence is sufficient to determine that the ketogenic diet is efficacious in reducing seizure frequency in children with refractory epilepsy.

Child↗

Analytical and clinical performance of a detergent-based homogeneous LDL-cholesterol assay: a multicenter evaluation.

BACKGROUND: LDL-cholesterol (LDL-C) concentrations currently are determined in most clinical laboratories using the Friedewald calculation. This approach has several limitations and may not always meet the current total error recommendation in LDL-C measurement of </=12% established by the National Cholesterol Education Program. METHODS: In a multicenter study, we evaluated the analytical and clinical performance of a homogeneous LDL-C assay (LDL-C(Roche); Roche Diagnostics, Indianapolis, IN) in a comparison with a beta-quantification method. RESULTS: This direct assay correlated highly with a beta-quantification method (r = 0.968; y = 1.037x - 95.8 mg/L; n = 355; 95% confidence intervals, 1.011-1.063 for the slope and -129.5 to 62.0 mg/L for the y-intercept) and met the current total error requirement. The assay was not affected significantly by concentrations of hemoglobin up to 6000 mg/L or bilirubin up to 500 mg/L. However, a negative bias of 10% was seen when triglyceride concentrations exceeded 10 000 mg/L. At the medical decision cut-point range, the LDL-C(Roche) assay showed positive predictive values of 91-100% and negative predictive values of 80-99%. Furthermore, the clinical utility of the assay seemed unaffected in samples obtained postprandially. CONCLUSIONS: The homogeneous LDL-C(Roche) assay meets the currently established analytical performance goals and may be useful for the diagnosis and management of hyperlipidemic patients.

Bilirubin↗

[Evaluation of a new sequence of magnetic resonance cholangio-pancreatography in thick cut and one shot acquisition].

OBJECTIVES: To assess the accuracy and reproducibility of a new magnetic resonance cholangiopancreatography sequence (MRCP), using long echo time and "single shot" acquisition (providing high-contrast thick slices: 20 mm or more), in the morphological analysis of the biliary tree and pancreatic ducts. METHODS: Fifty four patients with biliary and/or pancreatic disease were investigated with MRCP "single shot" thick slices. Biliary ducts were explored with MRCP "single shot", coronal and oblique coronal 20 mm thick slices on a 256 x 256 matrix. Natives pictures were reviewed by three independent radiologists, from three different institutions. MRCP results were compared with reference examinations in 54 cases (direct biligraphy methods: 54, CT scan: 11, endoscopic ultrasonography: 6, surgery: 6). RESULTS: For detection of bile duct dilatation, the agreement of MRCP "single shot" thick slices was more than 96% (Kappa > 0.92) and the inter-observer agreement was excellent (Kappa=0.92). For detection of biliary tree and/or pancreatic duct obstruction, MRCP "single shot" thick slice sensitivity was above 89% and specificity was 75%. The malignant nature of the lesions was determined with a sensitivity of 100% and a specificity of 92%. MRCP "single shot" thick slices could not differentiate pancreatic carcinomas from distal main bile duct cholangiocarcinomas. MRCP "single shot" thick slices did not detect small stones ( 3 mm) of the common bile duct. CONCLUSION: The excellent sensitivity, specificity and inter-observer agreement of MRCP "single shot" thick slices can be used to limit invasive imaging methods in the diagnosis of extrahepatic cholestasis.

Adult↗

Genetic variation of the riparian pioneer tree species populus nigra. II. Variation In susceptibility to the foliar rust melampsora larici-populina

Partial resistance of Populus nigra L. to three races of the foliar rust Melampsora larici-populina Kleb. was studied in a field trial and in laboratory tests, using a collection of P. nigra originating from different places throughout France. No total resistance was found. The partial resistance was split into epidemiological components, which proved to be under genetic control. Various patterns of association of epidemiological components values were found. Principal components analysis revealed their relationships. Only 24% of the variance of the field susceptibility could be explained by the variation of the epidemiological components of susceptibility. This variable was significantly correlated with susceptibility to the most ancient and widespread race of the pathogen, and with the variables related to the size of the lesions of the different races. Analysis of variance showed significant differences in susceptibility between regions and between stands within one region. Up to 20% of variation was between regions, and up to 22% between stands, so that these genetic factors appeared to be more differentiated than the neutral diversity (up to 3.5% Legionnet & Lefevre, 1996). However, no clear pattern of geographical distribution of diversity was detected.

Journal Article↗

Screening for undetected mental disorders in high utilizers of primary care services.

OBJECTIVE: To define the prevalence and detection rates of mental disorders among high utilizers as compared with typical utilizers, and to examine the effect of case-mix adjustment on these parameters. DESIGN: Cross-sectional study. SETTING: General internal medicine outpatient clinic associated with an urban, academic medical center. PATIENTS: From patients attending a general medicine clinic, 304 were selected randomly in three utilization groups, defined by number of clinic visits: (1) high utilizers; (2) case-mix adjusted high utilizers; and (3) typical utilizers (control patients). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of any mental disorder was ascertained by the PRIME-MD screening instrument. Chart review on all patients was performed to ascertain mental disorders detected by primary care physicians. The prevalence of mood disorders was markedly higher in high utilizers (29%) than in adjusted high utilizers (15%) or controls (10%) (p <.001). Anxiety disorders were slightly, but not statistically, more prevalent in the group adjusted for case mix (16%) than in other high utilizers (12%) or controls (9%). Alcoholism was significantly more prevalent in controls (12%) than in adjusted (6%) or other high utilizers (3%) (p <.03). The discrepancy in detection rates between PRIME-MD and chart review for any mental disorder was less for high utilizers (37% vs 31%) as compared with adjusted high utilizers (31% vs 11%) or controls (24% vs 8%). CONCLUSIONS: Mood disorders are associated with a high overall burden of illness, while anxiety disorders are more predominant among outliers after case-mix adjustment. Detection rates differ substantially by utilization pattern. Screening efforts can be more appropriately targeted with knowledge of these patterns.

Adult↗

Predicting in-hospital mortality of patients receiving cardiopulmonary resuscitation: unit-weighted MultiODA for binary data.

Widely used, linear classification functions may be derived on the basis of several different statistical paradigms. Since, regardless of choice, analysis generally yields an equation with unwieldy intercept and attribute coefficients, researchers often construct simpler scoring schemes based on unit weights. Accordingly, for applications involving entirely binary data, we discuss a simple procedure for obtaining unit-weighted (that is, we restrict attribute coefficients to the values of 0, 1 or -1) MultiODA functions that explicitly maximize classification accuracy in the training sample. We illustrate this with an application involving prediction of in-hospital mortality of patients receiving cardiopulmonary resuscitation. In training analysis of 88 patients, unit-weighted MultiODA outperformed prior scoring schemes and logistic regression analysis. Unit-weighted MultiODA also yielded superior hold-out (cross-generalizability) validity for an independent sample of 26 patients.

Cardiopulmonary Resuscitation↗