Fc-gamma receptors are not involved in cartilage damage during experimental osteoarthritis.

OBJECTIVE: Fc-gamma receptors (FcγRs) have been shown to play a crucial role in cartilage degradation during experimental arthritis. Although most of their effect on cartilage degradation has been attributed to their potential to promote inflammation in the presence of immunoglobulins, activating FcγRs promote cartilage degeneration in antigen-induced arthritis (AIA) independently of the level of inflammation. This prompted us to investigate, whether FcγRs may also play a role in osteoarthritis (OA)-related cartilage degradation. METHODS: FcγR expression was measured by RT-PCR and FACS in murine cartilage tissue and chondrocytes. Experimental OA was induced by destabilisation of the medial meniscus (DMM) in WT mice and animals lacking either activating (Fc receptor γ-chain-deficient) or inhibitory (FcγRIIB-deficient) FcγRs. Cartilage damage was investigated histologically 8 weeks post-surgery by assessing proteoglycan loss and structural damage according to OARSI recommendations. Osteophyte size was measured to investigate alterations in bone turnover. RESULTS: Expression analyses revealed significant levels for all four types of murine FcγRs in mouse chondrocytes and cartilage tissue from newborn and 8-week-old mice. Surprisingly, yet, ablation of either activating or inhibitory FcγRs did not affect cartilage damage or bone turnover during DMM-induced OA in mice. CONCLUSION: While FcγRs appear to have a crucial role in cartilage degradation during inflammatory arthritis our data indicate that FcγRs do not influence cartilage destruction in experimental OA. This indicates that a certain threshold of inflammation is a prerequisite for FcγR-induced cartilage destruction in arthritis.

Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.

This observational study investigated which of the three most common definitions of intraoperative hypotension (IOH), reported in a published systematic literature review, were associated best with anaesthetists' administration of antihypo tensive medication (AHM). IOH and AHM use in anaesthetic procedures in a mixed surgical population (n = 2350) were also reviewed. The definitions were: arterial systolic blood pressure (SBP) < 100 mmHg or a fall in SBP of > 30% of the preoperative SBP baseline; arterial SBP < 80 mmHg; a fall in SBP of > 20% of the preoperative SBP. Accuracy of predicting AHM using these three definitions was 67%, 54% and 65%, respectively. Prediction by a new fourth definition, using an optimal threshold of minimal SBP falling to < 92 mmHg or by > 24% of preoperative baseline, was 68% accurate. In multivariate logistic analysis, age, volatile versus intravenous anaesthetics, medical history of arterial hypertension and all four definitions of IOH were associated with intraoperative AHM, however IOH was not associated with postoperative in-patient stay. The three original definitions correlated poorly with the anaesthetist's judgement about applying AHM. Anaesthetists make complex decisions regarding the relevance of IOH, considering various perioperative factors in addition to SBP. Age, physical status and duration and type of surgery showed better correlations with postoperative in-patient stay than IOH.

Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence.

AIM: Inadequate emergence after anesthesia in the adult patient may be distinguished by the patients' activity level into two subtypes: emergence delirium and hypoactive emergence. The aim of this study was to determine the incidence of inadequate emergence in its different forms, to identify causative factors and to examine the possible influence on postoperative length of stay in the recovery room and in the hospital. METHODS: In this prospective observational study, 1868 non-intubated adult patients who had been admitted to the recovery room were analyzed. Inadequate emergence was classified in its different forms according to the Richmond agitation and sedation scale (RASS) 10 minutes after admission to the recovery room. Emergence delirium was defined as a RASS score >or=+1, and hypoactive emergence was defined as a RASS score

Key performance indicators in intensive care medicine. A retrospective matched cohort study.

Expert panel consensus was used to develop evidence-based process indicators that were independent risk factors for the main clinical outcome parameters of length of stay in the intensive care unit (ICU) and mortality. In a retrospective, matched data analysis of patients from five ICUs at a tertiary university hospital, agreed process indicators (sedation monitoring, pain monitoring, mean arterial pressure [MAP] >or= 60 mmHg, tidal volume [TV] or= 80 and or= 60 mmHg and BG >or= 80 mg/dl were relevant for survival. Linear regression of the 634 patients showed that analgesia monitoring, PIP or= 60 mmHg, BG >or= 80 mg/dl and

Comparison of three scores to screen for delirium in the recovery room.

BACKGROUND: Delirium is often seen in the recovery room and is a predictor for postoperative delirium on the ward. However, monitoring to detect delirium in the recovery room as a basic prerequisite for early intervention is rarely used. The aim of this study was to identify a valid and easy-to-use test for early screening of delirium in the recovery room. METHODS: One hundred and fifty-four adult patients admitted to the recovery room during regular working hours were included. A screening assessment for delirium was performed in the recovery room by a trained research team at the time when the patient was judged to be 'ready for discharge'. Delirium monitoring was performed with the Confusion Assessment Method (CAM), the Delirium Detection Score (DDS), and the Nursing Delirium Screening Scale (Nu-DESC). The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria were used as the gold standard. RESULTS: Delirium in the recovery room was seen in 21 patients (14%) with the DSM-IV criteria, in 11 patients (7%) with the CAM, in four patients (3%) with the DDS, and in 37 patients (24%) with the Nu-DESC. Sensitivity and specificity were 0.43 and 0.98 for the CAM, 0.14 and 0.99 for the DDS, and 0.95 and 0.87 for the Nu-DESC, respectively. CONCLUSIONS: All scores used were very specific, but the CAM and the DDS were less sensitive compared with the gold standard. Overall, the Nu-DESC was the most sensitive test in the recovery room to detect delirium.

c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells.

Separate mechanisms for oncogenesis and metastasis have been postulated. We show here that prolonged and invasive cell migration, a key mechanism in cancer metastasis, is linked to c-erbB-2 signaling. Cell lines with c-erbB-2 and EGFR expression and transphosphorylation activity display a high transendothelial invasiveness in an endothelial-extracellular matrix model mimicking a capillary vessel wall in vitro. Tyrosine-phosphorylated c-erbB-2 receptors and EGFR are localized predominantly in areas of the cell with high membrane extension activity. On the molecular level, there is a subtle cross talk between the transmembrane signaling molecule c-erbB-2 and the actin cytoskeleton at multiple levels, including the generation of the second messenger PIP2 and the mobilization of the actin-regulatory protein gelsolin. Our data strongly suggest that c-erbB-2, especially in a heterodimer with EGFR, is closely involved in signaling pathways, inducing alterations in cell morphology that are required for a human breast cancer cell to become motile and conceivably metastatic.