Mechanisms of failure to decontaminate the gut with polymixin E, gentamicin and amphotericin B in patients in intensive care.

The objective of the present work was to assess the possible mechanisms of the poor efficiency of selective decontamination of the digestive tract (SDD) in medical and surgical intensive care unit (ICU) patients. Sixty-four consecutive mechanically ventilated patients received gut decontamination with polymixin E, gentamicin and amphotericin B via a nasogastric tube and were assessed for oropharyngeal, gastric and fecal colonization and for the presence of each antibiotic in the stomach and feces. A decrease in fecal colonization with Escherichia coli was observed over 20 days but not with other gram-negative bacteria or gram-positive cocci. Fifteen and 26% of the fecal colonizing gram-negative bacteria were resistant to polymixin E and gentamicin, respectively, at admission. These proportions increased to up to 50% after 16 days of treatment. Although 50% of staphylococci were initially sensitive to gentamicin, all strains were resistant to this drug after four days of SDD. Both antibiotics were found in concentrations of less than 20 micrograms/g in 11 of 38 stools. Of these 38 stools, nine were not contaminated, 20 were colonized with resistant bacteria and 16 with strains sensitive to one antibiotic present in the stool. Therefore, the poor efficiency of gut decontamination observed was probably due to the great proportion of resistant strains on admission of the patients, to the selection of such resistant strains with SDD, to poor intestinal transit of the antibiotics, and to inactivation of the drugs by the feces. These results support stringent monitoring of fecal colonization in patients undergoing SDD in order to detect the fecal carriage of gram-positive and multiresistant gram-negative bacteria

Mode of onset of torsade de pointes in congenital long QT syndrome

Objectives.We sought to describe the mode of onset of spontaneous torsade de pointes in the congenital long QT syndrome.Background.Contemporary classifications of the long QT syndrome (LQTS) refer to the congenital LQTS as “adrenergic dependent” and to the acquired LQTS as “pause dependent.” Overlap between these two categories has been recognized, and a subgroup of patients with “idiopathic pause-dependent torsade” has been described. However, it is not known how commonly torsade is preceded by pauses in the congenital LQTS.Methods.We reviewed the electrocardiograms (ECGs) of all our patients with congenital LQTS evaluated for syncope or sudden death (30 patients). Documentation of the onset of torsade de pointes was available for 15 patients. All these patients had “definitive LQTS” by accepted clinical and ECG criteria.Results.Pause-dependent torsade de pointes was clearly documented in 14 of the 15 patients (95% confidence interval 68% to 100%). The cycle length of the pause leading to torsade was 1.3 ± 0.2 times longer than the basic cycle length, and most pauses leading to torsade were unequivocally longer than the preceding basic cycle length (80% of pauses were >80 ms longer than the preceding cycle length).Conclusions.The “long-short” sequence, which has been recognized as a hallmark of torsade de pointes in the acquired LQTS, plays a major role in the genesis of torsade in the congenital LQTS as well. Our findings have important therapeutic implications regarding the use of pacemakers for prevention of torsade in the congenital LQTS

Revision of the World Meteorological Organization Global Atmosphere Watch (WMO/GAW) CO2 calibration scale

The NOAA Global Monitoring Laboratory serves as the World Meteorological Organization Global Atmosphere Watch (WMO/GAW) Central Calibration Laboratory (CCL) for CO2 and is responsible for maintaining the WMO/GAW mole fraction scale used as a reference within the WMO/GAW program. The current WMO-CO2-X2007 scale is embodied by 15 aluminum cylinders containing modified natural air, with CO2 mole fractions determined using the NOAA manometer from 1995 to 2006. We have made two minor corrections to historical manometric records: fixing an error in the applied second virial coefficient of CO2 and accounting for loss of a small amount of CO2 to materials in the manometer during the measurement process. By incorporating these corrections, extending the measurement records of the original 15 primary standards through 2015, and adding four new primary standards to the suite, we define a new scale, identified as WMO-CO2-X2019. The new scale is 0.18&thinsp;&micro;mol&thinsp;mol&minus;1 (ppm) greater than the previous scale at 400&thinsp;ppm CO2. While this difference is small in relative terms (0.045&thinsp;%), it is significant in terms of atmospheric monitoring. All measurements of tertiary-level standards will be reprocessed to WMO-CO2-X2019. The new scale is more internally consistent than WMO-CO2-X2007 owing to revisions in propagation and should result in an overall improvement in atmospheric data records traceable to the CCL. &nbsp;</p

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Experiments with CO₂-in-air reference gases in high-pressure aluminum cylinders

Long-term monitoring of carbon dioxide (CO2) in the atmosphere is key for a better understanding of the processes involved in the carbon cycle that have a major impact on further climate change. Keeping track of large-scale emissions and removals (sources and sinks) of CO2 requires very accurate measurements. They all have to be calibrated very carefully and have to be traceable to a common scale, the World Meteorological Organization (WMO) CO2 X2007 scale, which is maintained by the National Oceanic and Atmospheric Administration (NOAA) Earth System Research Laboratory (ESRL) in Boulder, CO, USA. The international WMO GAW (Global Atmosphere Watch) program sets as compatibility goals for the required agreement between different methods and laboratories ±0.1&thinsp;µmol&thinsp;mol−1 for the Northern Hemisphere and ±0.05&thinsp;µmol&thinsp;mol−1 for the Southern Hemisphere. The reference gas mixtures used to pass down and distribute the scale are stored in high-pressure aluminum cylinders. It is crucial that the standards remain stable during their entire time of use. In this study the tested vertically positioned aluminum cylinders showed similar CO2 enrichment during low-flow conditions (0.3&thinsp;L&thinsp;min−1), which are similar to flows often used for calibration gases in practical applications. The average CO2 enrichment was 0.090±0.009&thinsp;µmol&thinsp;mol−1 as the cylinder was emptied from about 150 to 1&thinsp;bar above atmosphere. However, it is important to note that the enrichment is not linear but follows Langmuir's adsorption–desorption model, where the CO2 enrichment is almost negligible at high pressures but much more pronounced at low pressures. When decanted at a higher rate of 5.0&thinsp;L&thinsp;min−1 the enrichment becomes 0.22±0.05&thinsp;µmol&thinsp;mol−1 for the same pressure drop. The higher enrichment is related to thermal diffusion and fractionation effects in the cylinder, which were also dependent on the cylinder's orientation and could even turn negative. However, the low amount of CO2 adsorbed on the cylinder wall and the fact that the main increase happens at low pressure lead to the conclusion that aluminum cylinders are suitable to store ambient CO2-in-dry-air mixtures provided they are not used below 20&thinsp;bar. In cases where they are used in high-flow experiments that involve significant cylinder temperature changes, special attention has to be paid to possible fractionation effects.</p