In Vitro Inhibition of Coagulase-Negative Staphylococci by Vancomycin/Aminoglycoside-Loaded Cement Spacers

Background:: Successful treatment of allograft infections by the temporary implantation of an antibiotic-loaded polymethylmethacrylate cement spacer depends on the diffusion of antibiotics out of the cement and inhibition of bacterial growth in the surrounding tissue. We investigated with an in vitro model how long antibiotics are released by the cement and if gentamicin-resistant coagulase-negative staphylococci (CNS) are inhibited by vancomycin mixed with the gentamicin-loaded cement. Materials and Methods:: Four formulations of antibiotic-loaded cement disks, i.e. gentamicin, tobramycin, vancomycin and tobramycin combined with vancomycin, respectively, were used to test the inhibition of eight isolates of Staphylococcus epidermidis and two reference strains of Staphylococcus aureus by an agar diffusion test on Mueller-Hinton (MH) agar similar to the routine laboratory disk diffusion method. Moreover, cement spacer cylinders loaded with gentamicin alone or combined with vancomycin were submerged in MH agar for weeks and the capacity to inhibit five different isolates of S. epidermidis was measured. Results:: The size of the inhibition zones around the antibiotic-loaded cement disks correlated with the minimal inhibitory concentration (MIC) of the antibiotics against the tested strains. All five strains of S. epidermidis were inhibited by vancomycin-loaded cement spacers for at least 30 days. However, two gentamicin-resistant S. epidermidis strains with MICs of 4 mg/l and 16 mg/l could not be inhibited longer than 3 days by the gentamicin-loaded cement spacer. Conclusion:: The in vitro data suggest that antibiotic-loaded cement spacers inhibit susceptible bacteria for 4-6 weeks. The addition of vancomycin to commercial aminoglycoside-loaded cements might be helpful in allograft infections in tumor patients to inhibit a broad range of bacteria including gentamicin-resistant CNS very commonly found in such infection

CMS Barrel Pixel Detector Overview

The pixel detector is the innermost tracking device of the CMS experiment at the LHC. It is built from two independent sub devices, the pixel barrel and the end disks. The barrel consists of three concentric layers around the beam pipe with mean radii of 4.4, 7.3 and 10.2 cm. There are two end disks on each side of the interaction point at 34.5 cm and 46.5 cm. This article gives an overview of the pixel barrel detector, its mechanical support structure, electronics components, services and its expected performance.Comment: Proceedings of Vertex06, 15th International Workshop on Vertex Detector

Compact Frontend-Electronics and Bidirectional 3.3 Gbps Optical Datalink for Fast Proportional Chamber Readout

The 9600 channels of the multi-wire proportional chamber of the H1 experiment at HERA have to be read out within 96 ns and made available to the trigger system. The tight spatial conditions at the rear end flange require a compact bidirectional readout electronics with minimal power consumption and dead material. A solution using 40 identical optical link modules, each transferring the trigger information with a physical rate of 4 x 832 Mbps via optical fibers, has been developed and commisioned. The analog pulses from the chamber can be monitored and the synchronization to the global HERA clock signal is ensured.Comment: 13 pages, 10 figure

Familial Transmission of a Serious Disease—Producing Group A Streptococcus Clone: Case Reports and Review

Invasive group A streptococcus (GAS) infections are emerging diseases; however, person-to-person transmission of invasive GAS producing life-threatening infection has been observed rarely. We report a small intrafamilial cluster of life-threatening GAS infections. A previously healthy 47-year-old father developed necrotizing fasciitis of the neck. Two days later, his 16-year-old daughter developed streptococcal angina, pneumonia, and pleural empyema. Both patients had signs of streptococcal toxic shock syndrome. Pulsed field gel electrophoresis revealed that the M6 strains of GAS isolated from the father and daughter had identical patterns. Cases of person-to-person transmission of invasive GAS infection reported in the literature are also reviewe

Ablation of β1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation

Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of β1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of β1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured β1 integrin–null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. β1 integrin–null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where β1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for β1 integrins in prolactin signaling. This study demonstrates that β1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Mechanical Design and Material Budget of the CMS Barrel Pixel Detector

The Compact Muon Solenoid experiment at the Large Hadron Collider at CERN includes a silicon pixel detector as its innermost component. Its main task is the precise reconstruction of charged particles close to the primary interaction vertex. This paper gives an overview of the mechanical requirements and design choices for the barrel pixel detector. The distribution of material in the detector as well as its description in the Monte Carlo simulation are discussed in detail