Cell adhesion molecules are critically involved in the multistep process of leukocyte recruitment in inflammation. The specific receptors used by polymorphonuclear leukocytes (PMN) for locomotion in extravascular tissue have as yet not been identified. By means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the 2β1 (VLA-2) integrin, though absent on blood PMN, is induced in extravasated PMN collected from human skin blister chambers, and rat PMN accumulated in the peritoneal cavity after chemotactic stimulation. Intravital time-lapse videomicroscopy was used to investigate chemoattractant-induced PMN locomotion in the rat mesentery in vivo. Local administration of function-blocking monoclonal antibody or peptide recognizing the 2β1 integrin reduced PMN migration velocity in the extravascular tissue by 73% ± 3% and 70% ± 10%, respectively ( means ± SD). The distance f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a collagen gel in vitro was markedly reduced by treatment with anti-2 mAbs or peptide, whereas no effect was observed with antibodies or peptides recognizing the 4β1 or 5β1integrins. Further evidence for a critical role of expression of 2β1 integrin in PMN locomotion in extravascular tissue was obtained in the mouse air pouch model of acute inflammation where chemoattractant-induced PMN recruitment was substantially inhibited by local anti-2 mAb treatment. Thus, expression of 2β1 integrin on extravasated PMN has been identified and a novel role of this receptor in regulating the extravascular phase of leukocyte trafficking in inflammation has been formulated.
Sepsis is the most frequent cause of death in the intensive care unit (ICU). A rapid and correct diagnosis and initiation of therapy is crucial for improving patient outcomes. The aim of this study was to compare the performance of calprotectin with the more widely used sepsis biomarker procalcitonin (PCT) in ICU patients. The performance of calprotectin and PCT as sepsis and prognostic markers for 30-d mortality was compared in a prospective, observational study in an eight-bed ICU. We investigated concentrations of the biomarkers in plasma collected at admission from all ICU patients admitted during a year (2012-2013, n ¼ 271) together with simplified acute physiology 3 scores (SAPS3) and sequential organ failure assessment (SOFA) scores. The receiver operating characteristic (ROC) analysis showed a higher area under the curve (AUC) value for calprotectin (0.79) than for PCT (0.49) when used as a sepsis marker. The calprotectin concentrations at admission were higher in non-survivors than in survivors at day 30. In our study, calprotectin was superior to PCT for distinguishing between ICU patients with sepsis and non-sepsis patients. Calprotectin also had higher predictive ability regarding 30-d mortality.
Pain is a problem that often has to be addressed in the prehospital setting. The delivery of analgesia may sometimes prove challenging due to problems establishing intravenous access or a harsh winter environment. To solve the problem of intravenous access, intranasal administration of drugs is used in some settings. In cases where vascular access was foreseen or proved hard to establish (one or two missed attempts) on the scene of the accident we use nasally administered S-Ketamine for prehospital analgesia. Here we describe the use of nasally administered S-Ketamine in 9 cases. The doses used were in the range of 0,45-1,25 mg/kg. 8 patients were treated in outdoor winter-conditions in Sweden. 1 patient was treated indoor. VAS-score decreased from a median of 10 (interquartile range 8-10) to 3 (interquartile range 2-4). Nasally administered S-Ketamine offers a possible last resource to be used in cases where establishing vascular access is difficult or impossible. Side-effects in these 9 cases were few and non serious. Nasally administered drugs offer a needleless approach that is advantageous for the patient as well as for health personnel in especially challenging selected cases. Nasal as opposed to intravenous analgesia may reduce the time spent on the scene of the accident and most likely reduces the need to expose the patient to the environment in especially challenging cases of prehospital analgesia. Nasal administration of S-ketamine is off label and as such we only use it as a last resource and propose that the effect and safety of the treatment should be further studied.
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