Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI

Phonon attenuation in the GHz regime : Measurements and simulations with a visco-elastic material model

Aluminum and PMMA thin film samples are investigated regarding their mechanical properties like speed of sound and attenuation. Aluminum is often used as a transducer layer for pump probe laser measurements and different PMMA types have a large importance in the nanoimprinting technique. The measurements are performed on a short pulse laser pump probe setup, where bulk wave packets in the GHz regime are excited and detected using near infrared laser pulses of less than 100 fs duration. This contact-free and non-destructive measurement method is explained. In order to extract the attenuation precisely from the measurements, the entire experimental setup is simulated numerically: The heat distribution and the thermo-elastic wave excitation caused by the laser pulse, the mechanical wave propagation, and the photo-acoustic detection. By means of the visco-elastic modeling of the wave propagation, the simulations are fitted to the measurements by tuning the attenuation parameters in the numerical model. In this way it is possible to extract the attenuation from the measurements. First, two different types of Aluminum on a sapphire substrate are analyzed: Electron beam evaporated Aluminum and sputtered Aluminum, respectively. The thicknesses of the Aluminum films are in the range of 300 nm. It turns out that the attenuation is much higher in the sputtered Aluminum film. Afterwards, PMMA thin films used for nanoimprinting with thicknesses between 300 and 600 nm are analyzed. The PMMA thin films are spincoated onto a Silicon wafer and covered with an Aluminum transducer layer. The very good agreement between the measurements and simulations of the stacked samples allows a reliable determination of the attenuation in the PMMA films in the GHz regime

Co-infection of Influenza B and Streptococci causing severe pneumonia and septic shock in healthy women

<p>Abstract</p> <p>Background</p> <p>Since the Influenza A pandemic in 1819, the association between the influenza virus and <it>Streptococcus pneumoniae </it>has been well described in literature. While a leading role has been so far attributed solely to Influenza A as the primary infective pathogen, Influenza B is generally considered to be less pathogenic with little impact on morbidity and mortality of otherwise healthy adults. This report documents the severe synergistic pathogenesis of Influenza B infection and bacterial pneumonia in previously healthy persons not belonging to a special risk population and outlines therapeutic options in this clinical setting.</p> <p>Case Presentation</p> <p>During the seasonal influenza epidemic 2007/2008, three previously healthy women presented to our hospital with influenza-like symptoms and rapid clinical deterioration. Subsequent septic shock due to severe bilateral pneumonia necessitated intensive resuscitative measures including the use of an interventional lung assist device. Microbiological analysis identified severe dual infections of Influenza B with <it>Streptococcus pyogenes </it>in two cases and <it>Streptococcus pneumoniae </it>in one case. The patients presented with no evidence of underlying disease or other known risk factors for dual infection such as age (< one year, > 65 years), pregnancy or comorbidity.</p> <p>Conclusions</p> <p>Influenza B infection can pose a risk for severe secondary infection in previously healthy persons. As patients admitted to hospital due to severe pneumonia are rarely tested for Influenza B, the incidence of admission due to this virus might be greatly underestimated, therefore, a more aggressive search for influenza virus and empirical treatment might be warranted. While the use of an interventional lung assist device offers a potential treatment strategy for refractory respiratory acidosis in addition to protective lung ventilation, the combined empiric use of a neuraminidase-inhibitor and antibiotics in septic patients with pulmonary manifestations during an epidemic season should be considered.</p

Oligosaccharyltransferase Inhibition Induces Senescence in RTK-Driven Tumor Cells

Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high throughput screen and lead compound optimization campaign that delivered a cell permeable inhibitor (NGI-1). NGI-1 targets the oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. In non-small cell lung cancer cells NGI-1 blocks cell surface localization and signaling of the EGFR glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or FGFR) for survival. In these cell lines OST inhibition causes cell cycle arrest accompanied by induction of p21, autofluorescence, and changes in cell morphology; all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor tyrosine kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells

The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil

Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection

Survey of childhood empyema in Asia: Implications for detecting the unmeasured burden of culture-negative bacterial disease

<p>Abstract</p> <p>Background</p> <p>Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia.</p> <p>Methods</p> <p>We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using <it>ICD</it>-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema.</p> <p>Results</p> <p>During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. <it>Staphylococcus aureus </it>(n = 126) was the most common organism isolated, followed by <it>Streptococcus pneumoniae </it>(n = 83), <it>Pseudomonas aeruginosa </it>(n = 37) and <it>Klebsiella </it>(n = 35) and <it>Acinetobacter </it>species (n = 34).</p> <p>Conclusion</p> <p>The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. <it>S. pneumoniae </it>was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.</p

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well-characterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Most patients made new sputum IgA responses to the adhesins UspA1 and Hag, along with the surface protein UspA2. A smaller proportion of patients made new sputum IgA responses to the iron-regulated proteins TbpB and CopB and to lipooligosaccharide. These results have important implications in understanding the mucosal immune response to M. catarrhalis in the setting of COPD and in elucidating the elements of a protective immune response

Identification of Surface Antigens of Moraxella catarrhalis as Targets of Human Serum Antibody Responses in Chronic Obstructive Pulmonary Disease

Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response

Phonon attenuation in the GHz regime : Measurements and simulations with a visco-elastic material model

Aluminum and PMMA thin film samples are investigated regarding their mechanical properties like speed of sound and attenuation. Aluminum is often used as a transducer layer for pump probe laser measurements and different PMMA types have a large importance in the nanoimprinting technique. The measurements are performed on a short pulse laser pump probe setup, where bulk wave packets in the GHz regime are excited and detected using near infrared laser pulses of less than 100 fs duration. This contact-free and non-destructive measurement method is explained. In order to extract the attenuation precisely from the measurements, the entire experimental setup is simulated numerically: The heat distribution and the thermo-elastic wave excitation caused by the laser pulse, the mechanical wave propagation, and the photo-acoustic detection. By means of the visco-elastic modeling of the wave propagation, the simulations are fitted to the measurements by tuning the attenuation parameters in the numerical model. In this way it is possible to extract the attenuation from the measurements. First, two different types of Aluminum on a sapphire substrate are analyzed: Electron beam evaporated Aluminum and sputtered Aluminum, respectively. The thicknesses of the Aluminum films are in the range of 300 nm. It turns out that the attenuation is much higher in the sputtered Aluminum film. Afterwards, PMMA thin films used for nanoimprinting with thicknesses between 300 and 600 nm are analyzed. The PMMA thin films are spincoated onto a Silicon wafer and covered with an Aluminum transducer layer. The very good agreement between the measurements and simulations of the stacked samples allows a reliable determination of the attenuation in the PMMA films in the GHz regime