Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2-K^b promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.     

The Exeter bipolar prosthesis in the active elderly patient: the results at 7 years

Summary Seventy one Exeter bipolar hemiarthroplasties were reviewed after a mean follow up of 3.2 years (range 1–7 years). Patients with displaced subcapital fractures were selected for operation on the basis of good mobility before the fracture. The operation was well tolerated and the mortality at 1 month and 6 months was 3.7% and 6.5% respectively. Using a newly devised hip scoring system 89% had a good or excellent result and 94% had no or only occasional pain. There was no radiological evidence of acetabular erosion.

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Résumé On a revu 71 hémi-arthroplasties bipolaires type Exeter. 3.2 ans en moyenne (de 1 à 7 ans) après l'opération. Celle-ci a été pratiquée chez les patients présentant une fracture sous-capitale avec déplacement, et qui avaient avant l'accident une bonne mobilité. Dans l'ensemble l'intervention a été bien supportée et la mortalité à un mois et à six mois était respectivement de 3.7% et de 6.5%. D'après un nouveau système de cotation de la hanche, 89% des résultats sont bons ou excellents et 94% des patients ne souffrent pas ou n'ont que des douleurs occasionnelles. Il n'y a pas de signes radiologiques d'usure du cotyle.

     

Emigration of selected subsets of {gamma}{delta}+ T cells from the adult murine thymus

Cells bearing the form of the TCR make up only 1–3% ofT cells in the adult murine thymus and peripheral lymphold organs.Evidence from studies of nude mice suggests that the developmentof at least some T cells is thymus dependent; however, untilnow it has not been directly demonstrated that cells are exportedfrom the thymus. In this paper we have used the technique oflabelling thymocytes in vivo with FITC, followed by flow cytometrlcanalysis to trace cells emigrating from the thymus to the spleen.Using this approach we have been able to demonstrate for thefirst time that T cells are exported from the adult murinethymus to the spleen. We also demonstrate that the cells emigratingto the spleen are a selected subset of thymocytes being heatstable antigen positive, Thy-1⁺, and expressing low levels ofCD44 (Pgp-1). In addition, investigation of TCR V; gene usageamong adult ⁺ thymocytes, recent emigrants, and spleen cells,indicated a selective emigration of cells expressing certainVgenes.     

The impact of multifocused interventions on sharps injury rates at an acute-care hospital.

OBJECTIVE: To determine the impact of a multifocused interventional program on sharps injury rates. DESIGN: Sharps injury data were collected prospectively over a 9-year period (1990-1998). Pre- and postinterventional rates were compared after the implementation of sharps injury prevention interventions, which consisted of administrative, work-practice, and engineering controls (ie, the introduction of an anti-needlestick intravenous catheter and a new sharps disposal system). SETTING: Sharps injury data were collected from healthcare workers employed by a mid-sized, acute-care community hospital. RESULTS: Preinterventional annual sharps injury incidence rates decreased significantly from 82 sharps injuries/1,000 worked full-time-equivalent employees (WFTE) to 24 sharps injuries/1,000 WFTE employees postintervention (P<.0001), representing a 70% decline in incidence rate overall. Over the course of the study, the incidence rate for sharps injuries related to intravenous lines declined by 93%, hollow-bore needlesticks decreased by 75%, and non-hollow-bore injuries decreased by 25%. CONCLUSION: The implementation of a multifocused interventional program led to a significant and sustained decrease in the overall rate of sharps injuries in hospital-based healthcare workers.     

Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.