[An evaluation of fatigue in patients with glioblastoma relapse treated with the combination of irinotecan-bevacizumab]. / Évaluation de la fatigue dans les glioblastomes en récidive traités par l'association irinotécan-bévacizumab.

OBJECTIVE: The combination of irinotecan-bevacizumab is effective in patients with glioblastoma relapse but fatigue is a commonly reported side effect. The objective of this study was to evaluate the level and evolution of fatigue in a series of patients treated with therapeutic combination. PATIENTS AND METHODS: We used two self-evaluation tools to quantify the physical and emotional aspects of this fatigue. The Norris Visual Analog Scale (VAS Norris) and the Multidimensional Fatigue Inventory-20 (MFI) tools were undertaken by 39 patients with glioblastoma relapse treated with irinotecan-bevacizumab, initially before the first cycle and thereafter with each cycle up until tumor progression. RESULTS: Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices. CONCLUSION: This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. We suspect that this is as a direct consequence of the treatment. There are however other confounding factors: insidious tumour progression not detected on follow-up imaging or delayed side effects of the initial radiotherapy-chemotherapy.

RhoA function in lamellae formation and migration is regulated by the alpha6beta4 integrin and cAMP metabolism.

Clone A colon carcinoma cells develop fan-shaped lamellae and exhibit random migration when plated on laminin, processes that depend on the ligation of the alpha6beta4 integrin. Here, we report that expression of a dominant negative RhoA (N19RhoA) in clone A cells inhibited alpha6beta4-dependent membrane ruffling, lamellae formation, and migration. In contrast, expression of a dominant negative Rac (N17Rac1) had no effect on these processes. Using the Rhotekin binding assay to assess RhoA activation, we observed that engagement of alpha6beta4 by either antibody-mediated clustering or laminin attachment resulted in a two- to threefold increase in RhoA activation, compared with cells maintained in suspension or plated on collagen. Antibody-mediated clustering of beta1 integrins, however, actually suppressed Rho A activation. The alpha6beta4-mediated interaction of clone A cells with laminin promoted the translocation of RhoA from the cytosol to membrane ruffles at the edges of lamellae and promoted its colocalization with beta1 integrins, as assessed by immunofluorescence microscopy. In addition, RhoA translocation was blocked by inhibiting phosphodiesterase activity and enhanced by inhibiting the activity of cAMP-dependent protein kinase. Together, these results establish a specific integrin-mediated pathway of RhoA activation that is regulated by cAMP and that functions in lamellae formation and migration.

Does imidacloprid seed-treated maize have an impact on honey bee mortality?

Beekeepers suspected maize, Zea mays L., treated with imidacloprid to result in substantial loss of honey bee (Hymenoptera: Apidae) colonies in Belgium. The objective of this study was to investigate the potential impact of maize grown from imidacloprid-treated seeds on honey bee mortality. A survey of 16 apiaries was carried out, and all maize fields treated or not with imidacloprid were located within a radius of 3,000 m around the observed apiaries. Samples of honey, beeswax, and bees were collected in three colonies per apiary and analyzed for pesticide contain by liquid chromatography-tandem mass spectrometry and gas chromatography-tandem mass spectrometry. We first found a significant correlation between the number of colonies per apiary and the mortality rates in an apiary. In addition, this mortality rate was inversely correlated with the surface of maize fields treated and not with imidacloprid, suggesting that this pesticide do not interact with bees' fitness. Moreover, a very large number of our samples contained acaricides either prohibited or ineffective against Varroa destructor (Anderson & Trueman) (Acari: Varroidae), suggesting that the treatment methods used by the beekeepers to be inadequate for mite control. Our results support the hypothesis that imidacloprid seed-treated maize has no negative impact on honey bees.

Development and validation of a multi-residue method for pesticide determination in honey using on-column liquid-liquid extraction and liquid chromatography-tandem mass spectrometry.

We report on the development and validation under ISO 17025 criteria of a multi-residue confirmatory method to identify and quantify 17 widely chemically different pesticides (insecticides: Carbofuran, Methiocarb, Pirimicarb, Dimethoate, Fipronil, Imidacloprid; herbicides: Amidosulfuron, Rimsulfuron, Atrazine, Simazine, Chloroturon, Linuron, Isoxaflutole, Metosulam; fungicides: Diethofencarb) and 2 metabolites (Methiocarb sulfoxide and 2-Hydroxytertbutylazine) in honey. This method is based on an on-column liquid-liquid extraction (OCLLE) using diatomaceous earth as inert solid support and liquid chromatography (LC) coupled to mass spectrometry (MS) operating in tandem mode (MS/MS). Method specificity is ensured by checking retention time and theoretical ratio between two transitions from a single precursor ion. Linearity is demonstrated all along the range of concentration that was investigated, from 0.1 to 20 ng g(-1) raw honey, with correlation coefficients ranging from 0.921 to 0.999, depending on chemicals. Recovery rates obtained on home-made quality control samples are between 71 and 90%, well above the range defined by the EC/657/2002 document, but in the range we had fixed to ensure proper quantification, as levels found in real samples could not be corrected for recovery rates. Reproducibility is found to be between 8 and 27%. Calculated CCalpha and CCbeta (0.0002-0.943 ng g(-1) for CCalpha, and 0.0002-1.232 ng g(-1) for CCbeta) show the good sensitivity attained by this multi-residue analytical method. The robustness of the method has been tested in analyzing more than 100 raw honey samples collected from different areas in Belgium, as well as some wax and bee samples, with a slightly adapted procedure.

Dynamic cervical plates: biomechanical evaluation of load sharing and stiffness.

STUDY DESIGN: An in vitro biomechanical study using a simulated cervical corpectomy model to compare the load-sharing properties and stiffnesses of two static and two dynamic cervical plates. OBJECTIVES: To evaluate the load-sharing properties of the instrumentation with a full-length graft and with 10% graft subsidence and to measure the stiffness of the instrumentation systems about the axes of flexion-extension, lateral bending, and axial torsion under these same conditions. SUMMARY OF BACKGROUND DATA: No published reports comparing conventional and dynamic cervical plates exist. METHODS: Six specimens of each of the four plate types were mounted on ultra-high molecular weight polyethylene-simulated vertebral bodies. A custom four-axis spine simulator applied pure flexion-extension, lateral bending, and axial torsion moments under a constant 50 N axial compressive load. Load sharing was calculated through a range of applied axial loads up to 120 N. The stiffness of each construct was calculated in response to +/-2.5 Nm moments about each axis of rotation with a full-length graft, a 10% shortened graft, and no graft. ANOVA and Fisher's post hoc test were used to determine statistical significance (alpha < or = 0.05). RESULTS: The two locked cervical plates (CSLP and Orion) and the ABC dynamic plate were similar in flexion-extension, lateral bending, and torsional stiffness. The DOC dynamic plate was consistently less stiff. The Orion plate load shared significantly less than the other three plates with a full graft. Both the ABC and the DOC plates were able to load share with a shortened graft, whereas the conventional plates were not. CONCLUSIONS: All plates tested effectively load share with a full-length graft, whereas the two dynamic cervical plates tested load share more effectively than the locked plates with simulated graft subsidence. The effect of dynamization on stiffness is dependent on plate design.

Segmental pedicle screw fixation or cross-links in multilevel lumbar constructs. a biomechanical analysis.

BACKGROUND CONTEXT: The placement of segmental pedicle screws and cross-links in short segment posterior pedicle screw constructs has been shown to increase the construct stiffness in some planes. To date, no studies have looked at the contributions of segmental pedicle screw and cross-link placement in longer constructs. PURPOSE: To evaluate the influence of segmental pedicle screw and/or cross-link placement on flexion/extension, lateral bending and axial torsion stiffness in two- and three-level posterior pedicle screw fixation constructs. STUDY DESIGN/SETTING: An in vitro biomechanical analysis of two- and three-level posterior pedicle screw constructs with and without segmental fixation and/or cross-links was performed using calf lumbar spines. Stiffness of the constructs was compared. METHODS: Six calf lumbar specimens were used to test stiffness in one-, two- and three-level posterior pedicle screw fixation constructs in 12 configurations. A custom-made, four-axis spine simulator applied pure cyclical (+/-5 Nm) flexion/extension, lateral bending and axial torsion moments at 0.1 Hz under a constant 50-N axial compressive load. The stiffness of each construct was calculated about each axis of rotation. Data were analyzed using nonparametric techniques with statistical significance determined at alpha less than .05. RESULTS: The stiffness of the instrumented spines were significantly greater than the noninstrumented intact spines in all loading conditions for one-, two- and three-level constructs. There were no significant changes in flexion/extension stiffness with the addition of either the cross-links or the segmental pedicle screws. In lateral bending, the addition of segmental pedicle screws significantly increased the stiffness in the two- and three-level constructs. The addition of two cross-links increased lateral bending stiffness in the longer three-level constructs, with little change in the two-level constructs. In axial torsion, the progressive addition of cross-links showed a tendency toward increased stiffness in both the two- and three-level constructs. Segmental pedicle screws further increased torsional stiffness of the longer, three-level constructs. CONCLUSIONS: As the use of segmental spinal instrumentation progresses from one to two and three levels, the contribution of cross-links and segmental pedicle screws to the overall construct stiffness increases.

[Epidemiology of Brucellosis. Trial evaluation of the incidence of clinical and infraclinical forms (author's transl)]. / Epidémiologie des brucelloses. Essai d'évaluation de l'incidence des formes cliniques et infracliniques.

The incidence of clinical and infraclinical human brucellosis was estimated by survey undertaken in 1976 on a representative sample of the population of the Vaucluse (France) district. It is shown that, by combining research of late hypersensitivity and serologic tracking in 2084 individuals, the incidence of diagnosed clinical brucellosis, in the Vaucluse district is at least 3 to 5 times more important than the incidence evaluated by the official notifications, and that there are 10 times more infraclinical or non diagnosed brucellosis than diagnosed brucellosis. The results show the need of triple investigation by interview, serology and hypersensitivity test (complementarity of the three technics) so as to evaluate the true morbidity of this anthropozoonosis.

Pulmonary recruitment protocol for organ donors: a new strategy to improve the rate of lung utilization.

Because lung transplantation is the only effective therapy for terminal respiratory failure, the demand for donor lungs has increased steadily. However, the number of donors has remained fairly constant over the years, which results in an increasing duration of waiting for lung transplantation. To overcome the lack of organs, various strategies have been developed by transplant centers including use of marginal donors. To increase the lung utilization rate in multiorgan donors, we implemented a simple lung recruitment protocol involving a brief period of controlled sustained inflation. In 2005, the lung utilization rate in the transplant program at our institution was only 20% in multiorgan donors. With the lung recruitment protocol, the rate of lung utilization for transplantation increased to 33%, in 2006, 24% in 2007, and 24% in 2008. Following the lung recruitment protocol, the arterial oxygen tension/fraction of inspired oxygen ratio increased to greater than 15% in more than 40% of donors. We were able to improve gas exchange sufficiently that as many as two-thirds of the lungs were suitable for transplantation. During the protocol, no complications were reported, and no patient became hemodynamically unstable, precluding organ procurement. We believe that optimization of multiorgan donor management with simple interventions may improve oxygenation, reducing the number of inadequate donor lungs and increasing the overall donor pool and organ availability.