Elizabeth Papathanassoglou

Leptin receptor expression and signaling in lymphocytes: Kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice

Leptin has direct effects not only on neuroendocrine function and metabolism, but also on T cell-mediated immunity. We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4+, CD8+, B cells, and monocyte/macrophages. ObR expression is up-regulated following cell activation, but with different kinetics, in different lymphocyte subsets. Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. Leptin also promotes lymphocyte survival in vitro by suppressing Fas-mediated apoptosis. B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. Moreover, CD4+ T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. Taken together, our data further support the notion that nutritional status acting via leptin-dependent mechanisms may alter the nature and vigor of the immune response.

Does programmed cell death (apoptosis) play a role in the development of multiple organ dysfunction in critically ill patients? a review and a theoretical framework.

Objectives: To critically review the current understanding of the pathophysiologic events leading to the development of secondary multiple organ dysfunction (MODS) in critical illness and to examine the role of apoptosis (programmed cell death) as a mechanism involved in the progression of MODS. Data Sources: Research and review articles published since 1982 on the pathophysiology of MODS, particularly the role of cytokines, reactive oxygen species, heat shock proteins, and apoptosis. Research and review articles on the physiology of apoptosis. Articles include human/animal and in vitro/in vivo studies. Data Extraction: The most prevalent mediating factors of MODS were examined for their potential to induce apoptosis, as reported in the literature. The combination of several of the above factors was also examined in terms of apoptosis‐triggering potential. Data Synthesis: Specific pathophysiologic conditions related to the onset of MODS have been shown to affect apoptotic rates in organ tissue cells and their respective endothelial cells in animal and in vitro models. These conditions include the following: a) increased release of inflammation‐related cytokines; b) increased production of oxygen free radicals associated with ischemia/reperfusion injury and states of low tissue perfusion; c) expression and release of heat shock proteins from tissue cells and the liver; d) elevated glucocorticoid concentrations after adrenal cortex activation; and e) release of bacterial products into the systemic circulation. Conclusion: The most important MODS‐related pathophysiologic conditions known to date have been shown to affect programmed cell death rates in almost all cell types. Organ‐specific cell death involving both parenchymal and microvasculature endothelial cells is conceivably underlying organ dysfunction. The hypothesis that increased apoptotic rates are involved in organ dysfunction may provide a unifying theory for the pathophysiology of MODS.

Determinants of Procedural Pain Intensity in the Intensive Care Unit. The Europain® Study

RATIONALE Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Expression of Fas (CD95) and Fas ligand on peripheral blood mononuclear cells in critical illness and association with multiorgan dysfunction severity and survival.

ObjectiveThis was an exploratory study with three goals: a) to quantify the expression of the apoptotic receptor Fas and its ligand (FasL) on peripheral blood mononuclear cells (PBMCs) in patients with, or at risk for, multiple organ dysfunction syndrome (MODS); b) to compare this expression with the respective expression in matched controls; and c) to explore the association with MODS severity and survival. DesignRepeated-measures correlational and cross-sectional design. SettingThe surgical, medical, and the trauma/burn intensive care unit of an academic institution. PatientsThirty-five adult, critically ill patients meeting the diagnostic criteria for systemic inflammatory response syndrome (SIRS) with MODS, or at risk for MODS, were followed for 14 days. Thirty-five non-SIRS controls matched with patients for age, gender, and race comprised the control group. InterventionsPeripheral blood sampling every 48 hrs. Measurements/Main Results T cells were considerably depleted in SIRS/MODS patients (p < .001), and Fas and FasL expression on PBMCs (flow cytometric analysis) was elevated significantly compared with controls (p < .001). In contrast to controls, non-T cells were the major sources of Fas and FasL in SIRS/MODS patients (p < .01). Expression of Fas and FasL exhibited a bimodal correlation with severity (p < .03). High severity patients demonstrated increasing Fas and FasL expression with increasing severity in contrast to declining expression in moderately severe patients. Fas and FasL measurements were significantly and positively associated with the likelihood of survival (p < .05). ConclusionsDysregulation in the expression of apoptotic receptors Fas and FasL, at least in PBMCs, may be involved in the pathophysiology of SIRS, the related lymphocytopenia, and the onset of MODS and the related morbidity and mortality rates.

Moral Professional Personhood: ethical reflections during initial clinical encounters in nursing education

Moral agency is an important constituent of the nursing role. We explored issues of ethical development in Greek nursing students during clinical practice at the beginning of their studies. Specifically, we aimed to explore students’ lived experience of ethics, and their perceptions and understanding of encountered ethical conflicts through phenomenological analysis of written narratives. The process of developing an awareness of personal values through empathizing with patients was identified as the core theme of the students’ experience. Six more common themes were identified. Development of the students’ moral awareness was conceptualized as a set of stages, commencing with empathizing with patients and nurses, moving on to taking a moral stand and, finally, concluding by becoming aware of their personal values and showing evidence of an emerging professional moral personhood. The notions of empathy, caring and emotion were in evidence throughout the students’ experience. Implications for practice and nurse education are discussed.

Serum leptin levels are higher but are not independently associated with severity or mortality in the multiple organ dysfunction/systemic inflammatory response syndrome: a matched case control and a longitudinal study

Hypercatabolism and immune dysfunction are closely associated with the development of systemic inflammatory response–multiple organ dysfunction (SIRS/MODS) in critical illness. It remains unclear however, whether leptin, an adipocyte‐derived hormone whose levels are influenced by several cytokines and which regulates immune function, food‐intake and energy expenditure is independently related to the development of and/or severity and mortality from SIRS/MODS.

Anxiety Levels and Related Symptoms in Emergency Nursing Personnel in Greece

INTRODUCTION Several studies provide evidence for the association between work stress and mild psychiatric morbidity among emergency nurses. These symptoms have not been explored in Greek nursing personnel employed in emergency departments. The aim of this descriptive correlational study was to investigate the presence of anxiety and stress symptoms among emergency nursing personnel in Greece. METHODS The sample was composed of nursing personnel employed in emergency departments of 8 adult General hospitals in Greece (N = 213). The Hamilton Anxiety Scale was applied for the quantitative assessment of anxiety symptoms, along with demographic, vocational, and educational data. Descriptive statistics were explored, and nonparametric comparisons, as well as correlational tests, were performed. RESULTS Anxiety levels were found to be mild (1.102 ± 0.53), with women (P = .021, Mann-Whitney U test) and nursing personnel employed in public sector hospitals (P = .029, Mann-Whitney U test) having higher anxiety level scores. In addition, a statistically significant mild correlation was observed between work experience in the emergency department and anxiety states (τ = 0.178, P = .011). The most commonly reported manifestations of mild psychiatric symptomatology were sleep disturbances (2.32 ± 1.2), anxious mood (1.57 ± 1.1), and depressed mood (2.38 ± 1.2), with 24.8% of the participants reporting very severe sleep disturbance, 23.9% reporting very severe depressive mood, and 10.7% reporting very severe anxious mood. DISCUSSION Hospital administrators need to be aware of the extent of workplace stress and subsequent anxiety symptoms that exist in emergency nurses. Staff counseling, continuing professional education, and empowerment strategies may need to be implemented to prevent psychiatric morbidity, as well as job dissatisfaction and resignations.

Soluble fas levels correlate with multiple organ dysfunction severity, survival and nitrate levels, but not with cellular apoptotic markers in critically ill patients

Apoptosis is a mode of programmed cell death (PCD). Transduction of apoptotic signals results in cellular suicide. Organ specific apoptosis has been proposed as a factor in multiple organ dysfunction syndrome (MODS). Fas is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form (circulating fas, sfas). In this exploratory study, we investigated the association of sfas with severity, survival, known mediators of multiple organ dysfunction, and cellular apoptotic markers on peripheral blood mononuclear cells (PBMC) in a group of 35 patients with MODS and in 35 matched controls. Critically ill patients with MODS had significantly elevated sfas levels compared to controls over time (P < .001). Increased serum concentration of circulating fas was associated with increased severity of multiple organ dysfunction. Non-survivors exhibited significantly higher sfas levels compared to survivors (P < .01) and increasing sfas was inversely associated with the likelihood of survival (P < .05). Circulating fas levels correlated highly with serum nitrate concentration, but not with fas and fasL expression on PBMC of critically ill patients. TNF-alpha and IL-6, although they appear to be mediators of both apoptosis and MODS, had no association with sfas. These results are suggestive of the need for further investigation on the role of apoptotic signaling in the development of MODS. They also suggest a potential prognostic value of sfas for SIRS/MODS clinical outcomes.

Exploration of the association between professional interactions and emotional distress of intensive care unit nursing personnel

&NA;Several studies provide evidence for the association between the quality of collaboration among intensive care unit (ICU) professionals and patients’ outcomes, as well as nurses’ moral distress and professional satisfaction. However, potential associations between collaboration and nurses’ mental health indices have not been explored. The aim of this descriptive correlational study was to investigate the degree of satisfaction from interaction among ICU nursing personnel, as well as between ICU nursing personnel and physicians, and potential associations with ICU nursing personnel’s anxiety symptoms. The sample consisted of ICU nursing personnel from 11 adult general hospitals in Greece (n = 229). Hamilton’s Anxiety scale was applied for the quantitative assessment of anxiety symptoms and Stamps’ Index of Work Satisfaction for the appraisal of nursing personnel’s satisfaction from professional interactions. Demographic, vocational, and educational data were also recorded. Descriptive statistics were explored, and group comparisons, correlation, and regression analysis were used. The average satisfaction score from interaction among nursing personnel was moderate to high (5.3 [SD, 1.0]) and from nurse-to-physician interaction was moderate (4.0 [SD, 1.4]) (scale range, 1-7). The score of satisfaction from nurse-to-physician interaction was negatively mildly correlated with participants’ (a) total anxiety score (&tgr; = −0.160, P = .001), (b) tension (&tgr; = −0.125, P = .015), and (c) depressive symptoms (&tgr; = −0.148, P = .005). Weak negative correlations were detected between satisfaction from interaction among nursing personnel and participants’ (a) total anxiety state (&tgr; = −0.139, P = .003), (b) tension (&tgr; = −0.137, P = .008), and (c) sleep disturbances (&tgr; = −0.150, P = .003). Overall, female respondents had higher levels of anxiety symptoms than male respondents (Mann-Whitney U, P = .007). Satisfaction from professional interaction was not a strong predictor of anxiety symptoms among ICU nursing personnel (R2 = 0.046, &bgr; < −0.15). Nursing personnel in Greek ICUs seem to be satisfied with the quality of relationships among them, as well as with physicians. Despite that anxiety symptoms associate with the degree of satisfaction from professional interaction, the latter may not be a significant indicator of ICU nurses’ well-being. Further qualitative research is needed to identify mediating factors.

Staffing and organisation of nursing care in cardiac intensive care units in Greece.

Purpose: To explore staffing and organisational characteristics of nursing care in cardiac intensive care units (CICUs) in Greece. Methodology: An exploratory descriptive survey design with additional cross-sectional comparisons was employed. A specifically developed survey-type questionnaire, addressed to nurse managers, was distributed to all CICUs in Greece. Results: The response rate was 76.2% (N=32 units). Nursing staff per bed ratios over 24 h (whole-time equivalent) were very low and exhibited a mean of 1.25 (±0.53). The total registered nurse to assistance nurse (RN/AN) ratio was 2.74, but a lot of variability was observed and in many units ANs operated in RNs positions. Only 42% of the nurses had participated at in-service continuing education programs and a systematic training program in cardio pulmonary resuscitation (CPR) was provided in only 12 (37.5%) units. The reported frequencies at which specific technical tasks were performed autonomously by nurses varied substantially and reflected a medium to low level of practice autonomy; the most frequently reported tasks were: peripheral IV line insertion, CPR chest compression, titration of vasoactive drugs and administration of analgesics. Higher percentages of nurses had received in-service training associated with the likelihood of performance of several technical tasks (P<0.03). Conclusions: Future studies need to explore the effect of these organisational characteristics on patient outcomes. The endorsement of nation-wide standards for nursing staffing and training in CICUs is imperative.