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Biomedical subjects

C Lefebvre

Publications and source records attributed to C Lefebvre.

At least 19 recordsLinked to original sources

Prior TIA, lipid-lowering drug use, and physical activity decrease ischemic stroke severity.

OBJECTIVE: To determine clinical and pharmacologic factors that could influence the initial severity and short-term outcome of cerebral ischemia. METHODS: In a cross-sectional hospital-based study of patients with acute supratentorial ischemic stroke, we systematically collected medical history, previous leisure-time physical activity, current and previous treatments, blood pressure, temperature, blood glucose, fibrinogen, NIH Stroke Scale (NIHSS) score at admission, and outcome at day 8. Factors potentially associated with initial stroke severity and outcome were selected by univariate analyses and then validated in logistic regression analyses with lower severity of stroke at admission (NIHSS 0 to 5) or good outcome at day 8 (modified Rankin Scale 0 to 1, Barthel Index 95 to 100) as dependent variables. RESULTS: In 362 consecutive patients (median age 70 years, range 16 to 97 years; 195 women), independent factors associated with a lower severity at admission were previous leisure-time physical activity (adjusted odds ratio [OR] 1.67, 95% CI 1.07 to 2.66), TIA (adjusted OR 2.28, 95% CI 1.06 to 4.87) and treatment with lipid-lowering drug (adjusted OR 1.76, 95% CI 1.02 to 3.03). Previous treatment with lipid-lowering drug and leisure-time physical activity were also independent factors associated with a good short-term outcome. CONCLUSION: Both regular physical activity and lipid-lowering drugs should be prospectively evaluated to determine whether they reduce the severity of ischemic stroke.

Adolescent↗

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

Adolescent↗

[Endometriosis and infertility].

Relationship between infertility and endometriosis is still controversial. Many mechanisms have been reported such as anatomical disorders, biologic and cytological modifications of peritoneal liquid, functional ovarian and endometrial disorders, reduced embryo quality. Management of infertility related to endometriosis is difficult and no consensus has been published yet. Following recent clinical data, therapeutic strategies are discussed.

Endometriosis↗

Prestroke dementia in patients with atrial fibrillation. Frequency and associated factors.

BACKGROUND AND PURPOSE: Prestroke dementia is frequent but usually not identified. Non-valvular atrial fibrillation (NVAF) is independently associated with an increased risk for dementia. However, the frequency and determinants of prestroke dementia in patients with NVAF have never been evaluated. OBJECTIVE: The aim of this study was to determine the frequency of prestroke dementia and associated factors in patients with a previously known NVAF. METHODS: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II (SAFE II), an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke in French and Italian centers. Prestroke dementia was evaluated by the IQCODE in patients with a reliable informant. Patients were considered as demented before stroke when their IQCODE score was > or = 104. RESULTS: of 204 patients, 39 (19.1%; 95% confidence interval [CI]: 13.7%-24.5%) patients met criteria for prestroke dementia. The only variable independently associated with prestroke dementia was increasing age (adjusted odds ratio for 1 year increase in age: 1.10; 95 % CI: 1.04-1.17), and there was a nonsignificant tendency for previous ischemic stroke or TIA and arterial hypertension. CONCLUSION: One fifth of stroke patients with a previously known NVAF were already demented before stroke. The main determinant of prestroke dementia is increasing age. A large cohort is necessary to identify other determinants.

Age Factors↗

Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP.

The inhibitor of apoptosis protein, XIAP, is frequently overexpressed in chemoresistant human tumours. An antisense oligonucleotide (AEG 35156/GEM 640) that targets XIAP has recently entered phase I trials in the UK. Method validation data are presented on three pharmacodynamic assays that will be utilised during this trial. Quantitative RT-PCR was based on a Taqman assay and was confirmed to be specific for XIAP. Assay linearity extended over four orders of magnitude. MDA-MB-231/U6-E1 cells and clone X-G4 stably expressing an RNAi vector against XIAP were chosen as high and low XIAP expression quality controls (QCs). Within-day and between-day coefficients of variation (CVs) in precision for cycle threshold (CT) and delta CT values (employing GAPDH and beta 2 microglobulin as housekeepers) were always less than 10%. A Western blotting technique was validated using a GST-XIAP fusion protein as a standard and HeLa cells and SF268 (human glioblastoma) cells as high and low XIAP expression QCs. Specificity of the final choice of antibody for XIAP was evaluated by analysing a panel of cell lines including clone X-G4. The assay was linear over a 29-fold range of protein concentration and between-day precision was 29% for the low QC and 23% for the high QC when normalised to GAPDH. XIAP protein was also shown to be stable at -80 degrees C for at least 60 days. M30-Apoptosense plasma Elisa detects a caspase-cleaved fragment of cytokeratin 18 (CK18), believed to be a surrogate marker for tumour cell apoptosis. Generation of an independent QC was achieved through the treatment of X-G4 cells with staurosporine and collection of media. Measurements on assay precision and kit-to-kit QC were always less than 10%. The M30 antigen (CK18-Asp396) was stable for 3 months at -80 degrees C, while at 37 degrees C it had a half-life of 80-100 h in healthy volunteer plasma. Results from the phase I trial are eagerly awaited.

Antineoplastic Agents↗

Human albumin solution for resuscitation and volume expansion in critically ill patients.

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in August 2004. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 32 trials meeting the inclusion criteria and reporting death as an outcome. There were 1632 deaths among 8452 trial participants. For hypovolaemia, the relative risk of death following albumin administration was 1.01 (95% confidence interval 0.92, 1.10). This estimate was heavily influenced by the results of the SAFE trial which contributed 91% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.40 (1.11, 5.19) and for hypoalbuminaemia the relative risk was 1.38 (0.94, 2.03). There was no substantial heterogeneity between the trials in the various categories (chi-square = 21.86, df = 25, p =0.64). The pooled relative risk of death with albumin administration was 1.04 (0.95, 1.13). REVIEWERS' CONCLUSIONS: For patients with hypovolaemia there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trial.

Blood Proteins↗

[Amiodarone liver toxicity about two cases and review of literature].

INTRODUCTION: Amiodarone can induced hepatic dysfunction. OBSERVATIONS: We describe two patients who developed hepatotoxicity presenting suggestive histological features. The outcome was fatal in one case but lesions were reversible in the second case upon treatment interruption. CONCLUSION: These observations show the necessity of hepatic monitoring of patients treated with amiodarone in order to detect potentially severe hepatotoxicity.

Aged↗

Teledentistry in the United States: a new horizon of dental care.

Teledentistry has been developing since 1994 as a means to allow dental professionals to communicate with one another over long distances. It allows collaboration by multiple practitioners regarding a patient and the necessary treatment for this patient. Teledentistry can be greatly utilized with rural communities or those of underserved populations. It would increase the accessibility of specialists, besides decreasing time and cost associated with specialty consultations. Real-time videoconferencing and store and forward techniques are the mostly commonly used methodologies for teledentistry. Teledentistry will become more widely seen and utilized by the increase in digital media found in dental practices.

Dental Health Services↗

[Genetic changes in chronic lymphocytic leukemia].

Chronic B-cell leukemias (CLL) are characterised by a striking cytogenetic signature composed of multiple recurrent chromosomal imbalances involving specific chromosomal regions i.e. 13q, 11q, 12q, 17p et 6q (decreasing order of frequency). These chromosomal aberrations may be found in up to 80% of the cases either as isolated or associated anomalies. They can also appear during the course of the disease suggesting their secondary nature. Furthermore, and at variance with other B-cell proliferations like lymphomas or myelomas, balanced translocations involving immunoglobulin (Ig) gene locus are rare. In addition to their interest in patient diagnosis and follow-up, these tumour-specific genetic markers also harbor important prognostic significance : isolated 13q deletions correlate with prolonged survival whereas both 17p and 11q partial deletions are independent predictors of rapid disease progression and short survival times in multivariate analyses. Genetic analyses as well as the first transcriptome studies of CLL reveal 1) a common mechanism of transformation and/or cell of origin, 2) the existence of at least two prognostic subgroups based on Ig mutational status.

Chromosome Aberrations↗

A comparison of handsearching versus MEDLINE searching to identify reports of randomized controlled trials.

This study aims to compare handsearching to a basic MEDLINE search for the identification of reports of randomized trials in specialized health care journals. Twenty-two specialized health care journals, published in the U.K., were handsearched for all reports of controlled trials (as defined by the Cochrane Collaboration). The reports of trials, which were judged to be definitely randomized, were identified from a random sample of three years per journal and form one element of this study. A MEDLINE search using the publication type terms 'randomized controlled trial' and 'controlled clinical trial' was also performed for the same journal years. The reports of trials retrieved by handsearching were then compared against those retrieved from the MEDLINE search, to identify differences in retrieval between the two techniques. Reports of randomized trials identified by the MEDLINE search but not found by handsearching were individually assessed to see if they met the Cochrane eligibility criteria for a report of a randomized trial. A total of 714 reports of randomized trials were found by using a combination of both handsearching and MEDLINE searching. Of these, 369 (52 per cent) were identified only by handsearching and 32 (4 per cent) were identified only by MEDLINE searching. Of the reports identified only by handsearching, 252 had no MEDLINE record, of which 232 (92 per cent) were meeting abstracts or published in supplements; 117 (25 per cent) of the 462 reports of randomized trials which had a MEDLINE record were missed by the electronic search because they did not have either of the publication type terms 'randomized controlled trial' or 'controlled clinical trial'. This proportion varied depending on when the reports of randomized trials were published (that is, before or after the introduction of the MEDLINE publication type terms above). The highest additional yield from handsearching compared to MEDLINE searching was for reports of randomized trials published prior to 1991 and from handsearching the non-MEDLINE indexed parts of a journal. The results of this study suggest that a combination of MEDLINE and handsearching is required to identify adequately reports of randomized trials.

Information Storage and Retrieval↗

[Contribution of ovarian and uterine color Doppler in medically assisted reproduction techniques (ART)].

Along the menstrual cycle and during pregnancy, small blood vessels proliferate within the uterus and the ovulating ovary. Angiogenic factors such as VEGF are involved in this phenomenon. In the ovulating ovary, neo-angiogenesis spreads progressively inside the dominant follicle wall and plays a role in the maintenance of the corpus luteum, under the influence of LH (or HCG during pregnancy). In ART, the measure of the blood flow is interesting since it correlates to the number and quality of harvested oocytes. Follicle hypoxia may impair chromosomal organization and separation within the oocyte. This neo-angiogenesis is also important in endometrium, in particular for embryo implantation. Ultrasounds with Doppler allow to estimate the endometrial receptivity, especially in IVF cycles. It is assumed that chance for ongoing pregnancy is almost zero if: endometrial thickness is < 8 mm; uterine pulsatility index (PI) is > 3. Doppler ultrasounds are a useful and even mandatory complement to standard vaginal ultrasonoghraphy in ART. It can be viewed as an indicator of the endometrial and follicular "well-being".

Endometrium↗

Early transvaginal ultrasonography versus early cerclage in women with an unclear history of incompetent cervix.

OBJECTIVE: Our aim was to compare outcomes in women with a questionable history of incompetent cervix, followed up with early transvaginal ultrasonography, with outcomes in women who had early cerclage. STUDY DESIGN: Charts were reviewed and patients identified for incompetent cervix from our obstetric database from 1995 through 1997. We included women who had an unclear history of incompetent cervix as follows: second-trimester loss or termination, > or =3 first-trimester terminations, cone biopsy or loop electrosurgical excision, or exposure to diethylstilbestrol. The primary outcome variable was gestational age at delivery. RESULTS: A total of 106 women were included, 45 in the early cerclage group and 61 in the early transvaginal ultrasonography group. The mean gestational age at delivery was 35.1 weeks for the early cerclage group versus 36.1 weeks for the early transvaginal ultrasonography group. CONCLUSION: In women with an unclear history of incompetent cervix, early cerclage does not appear to offer significant benefit over early transvaginal ultrasonography.

Adult↗

Mos activates MAP kinase in mouse oocytes through two opposite pathways.

Activation of mitogen-activated protein kinase (MAPK) in maturing mouse oocytes occurs after synthesis of Mos, a MAPKKK. To investigate whether Mos acts only through MEK1, we microinjected constitutively active forms of MEK1 (MEK1S218D/S222D referred herein as MEK*) and Raf (DeltaRaf) into mouse oocytes. In mos(-/-) oocytes, which do not activate MAPK during meiosis and do not arrest in metaphase II, MEK* and DeltaRaf did not rescue MAPK activation and metaphase II arrest, whereas Mos induced a complete rescue. MEK* and DeltaRaf induced cleavage arrest of two-cell blastomeres. They induced MAPK activation when protein phosphatases were inhibited by okadaic acid, suggesting that Mos may inhibit protein phosphatases. Finally, in mos(-/-) oocytes, MEK* induced the phosphorylation of Xp42(mapk)D324N, a mutant less sensitive to dephosphorylation, showing that a MAPK phosphatase activity is present in mouse oocytes. We demonstrate that active MAPKK or MAPKKK cannot substitute for Mos to activate MAPK in mouse oocytes. We also show that a phosphatase activity inactivates MAPK, and that Mos can overcome this inhibitory activity. Thus Mos activates MAPK through two opposite pathways: activation of MEK1 and inhibition of a phosphatase.

Animals↗

Asymmetric division in mouse oocytes: with or without Mos.

In both vertebrates and invertebrates, meiotic divisions in oocytes are typically asymmetric, resulting in the formation of a large oocyte and small polar bodies. The size difference between the daughter cells is usually a consequence of asymmetric positioning of the spindle before cytokinesis. Spindle movements are often related to interactions between the cell cortex and the spindle asters [1,2]. The spindles of mammalian oocytes are, however, typically devoid of astral microtubules, which normally connect the spindle to the cortex, suggesting that another mechanism is responsible for the unequal divisions in these oocytes. We observed the formation of the first polar body in wild-type oocytes and oocytes derived from c-Mos knockout mice [3]. In wild-type oocytes, the meiotic spindle formed in the centre of the cell and migrated to the cortex just before polar-body extrusion. The spindle did not elongate during anaphase. In mos-/- oocytes, the spindle formed centrally but did not migrate, although an asymmetric division still took place. In these oocytes, the spindle elongated during anaphase and the pole closest to the cortex moved while the other remained in place. Thus, a compensation mechanism exists in mouse oocytes and formation of the first polar body can be achieved in two ways: either after migration of the spindle to the cortex in wild-type oocytes, or after elongation, without migration, of the first meiotic spindle in mos-/- oocytes.

Animals↗

Evidence that DHPG-induced nociception depends on glutamate release from primary afferent C-fibres.

We examined whether enhanced glutamate release contributes to the expression of persistent spontaneous nociceptive behaviours (SNBs) in rats induced by intrathecal (i.t.) administration of the selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG). Pretreatment with drugs that have been shown to inhibit glutamate release, including a group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group III mGluR agonist L-2-amino-4-phosphonobutyrate (L-AP4), or the use-dependent sodium channel blockers 3,5-diamino-6-(2,3-diclorophenyl)-1,2,4-triazine (lamotrigine) and 2-amino-6-trifluoromethoxybenzothiazole (riluzole), produced dose-dependent reductions in (RS)-DHPG-induced SNBs. We have also shown that incubation of rat lumbar spinal cord slices with (RS)-DHPG potentiates 4-aminopyridine-evoked (4-AP) release of glutamate. Furthermore, we found that destruction of unmyelinated primary afferent C-fibres by neonatal capsaicin treatment significantly reduced (RS)-DHPG-induced SNBs in adult rats. Together, these results suggest that (RS)-DHPG-induced nociception is dependent on spinal glutamate release, probably from primary afferent C-fibres.

4-Aminopyridine↗

Allergic contact dermatitis caused by skin painting (pseudotattooing) with black henna, a mixture of henna and p-phenylenediamine and its derivatives.

BACKGROUND: Skin painting (pseudotattooing) with henna is traditionally performed mainly in Muslim or Hindu persons. Recently, transient artists have begun using black henna mixtures to temporarily paint the skin. Emergence of allergic contact dermatitis after application indicates the presence of a skin sensitizer in such preparations and poses future risks. OBSERVATIONS: Four patients developed allergic contact dermatitis after skin painting with black henna performed in France, Egypt, and the United States. The delay of symptoms suggested previous sensitization in 1 patient and active sensitization in 3 patients. Of 3 patients who underwent patch testing, the results were positive for p-phenylenediamine in 3 patients and for p-toluylenediamine in 1 patient. These sensitizers are found in hair dye preparations. CONCLUSIONS: The mixtures used by the artists possibly contained natural henna, a rare and weak skin sensitizer, and likely contained chemical coloring agents, diaminobenzenes, such as p-phenylenediamine and/or diaminotoluenes. The long duration of skin contact, the high concentrations of sensitizing materials, and the lack of a neutralizing agent dramatically increase the risk of skin sensitization, which is why such substances are prohibited for direct skin application. Because of the worldwide vogue of skin painting, future cases of sensitization to p-phenylenediamine and diaminobenzenes or diaminotoluenes are expected.

Adult↗

Human albumin solution for resuscitation and volume expansion in critically ill patients. The Albumin Reviewers.

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Controlled Trials Register, Medline, Embase and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in November 1999. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. We assessed publication bias using the regression test for funnel plot asymmetry. MAIN RESULTS: We found 30 trials meeting the inclusion criteria and reporting death as an outcome. There were 156 deaths among 1419 trial participants. For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death following albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia the relative risk was 1.69 (1.07 to 2.67). The pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Overall, the risk of death in patients receiving albumin was 14% compared to 8% in the control groups, an increase in the risk of death of 6% (3% to 9%). These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. REVIEWER'S CONCLUSIONS: There is no evidence that albumin administration reduces the risk of death in critically ill patients with hypovolaemia, burns or hypoalbuminaemia, and a strong suggestion that it may increase the risk of death. These data suggest that the use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of a rigorously conducted randomised controlled trial.

Blood Proteins↗