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

Heterogeneity of accessory cells.

The results presented and discussed here not only confirm the existence of AC heterogeneity but also demonstrate that in vitro the function of many AC is restricted to the activation of some but not all T cell functions. It is of interest that the tumor cell lines tested independent of whether they were of B cell or macrophage origin, and the DC were unable to induce Thc, although they were full active in the stimulation of other T cell functions. Despite this marked difference in AC activity these results at this stage do not imply that only normal macrophages or macrophage-like cells are able to activate Thc. As the number of tumor cell lines so far tested is small, it is possible that in regard to Thc activation the wrong lines were used in our experiments. Only the testing of many more different tumor cell lines will provide the answer. The existence of a Thc inducing permanent AC line would greatly ease the difficult task to study the mechanisms of antigen-processing and presentation by AC as well as the mechanisms of T cell activation

Dichter en zijn droombeeld. Flemish & French Vocal score.

Reissued from Schott Frères plates. --- Imprint covered by label: Milano, A. Pigna. --- Cover title

Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros

The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34+ cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34+ cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34+ hematopoietic cells with HOXA expression that more closely resembles that of cord blood. The cultures generate a network of aorta-like SOX17+ vessels from which RUNX1C+ blood cells emerge, similar to hematopoiesis in the aorta-gonad-mesonephros (AGM). Nascent CD34+ hematopoietic cells and corresponding cells sorted from human AGM show similar expression of cell surface receptors, signaling molecules and transcription factors. Our findings provide an approach to mimic in vitro a key early stage in human hematopoiesis for the generation of AGM-derived hematopoietic lineages from hESCs