Σκοπός. Yπεργλυκαιμία του stress (ΥΣ) χαρακτηρίζεται η παρουσία υπεργλυκαιμίας σε μη διαβητικούς ασθενείς σε παρουσία διαφόρων παραγόντων στρες όπως τραύμα, έγκαυμα, χειρουργείο, έμφραγμα μυοκαρδίου και σήψη. Σκοπός της μελέτης είναι η διερεύνηση της υπεργλυκαιμίας του stress σε βαριά σηπτικούς ασθενείς και η επίδρασης της στην παραγωγή προ και αντι- φλεγμονωδών κυτταροκινών όπως IL-6, IL-10, TNF-alpha and TGF-beta 1 και στην τελική έκβαση ασθενών με βαριά σήψη. Μέθοδος. Μελετήσαμε 265 σηπτικούς ασθενείς που εισήχθηκαν σε 3 παθολογικές κλινικές της ΝΔ Ελλάδος στη διάρκεια ενός έτους. Οι ασθενείς χωρίστηκαν σε 3 ομάδες ανάλογα με το γλυκαιμικό τους προφίλ κατά το πρώτο 24ωρο της εισαγωγής τους: ασθενείς με στρες υπεργλυκαιμία (ομάδα ΥΣ,ν=45), με σακχαρώδη διαβήτη (ομάδα ΣΔ,ν=67),και με φυσιολογικές τιμές σακχάρου (ομάδα ΦΓ,ν=153). Ως ΥΣ ορίστηκε η παρουσία γλυκόζης νηστείας 126mg/dl ή τυχαίας τιμής 200 mg/dl σε ≥2 μετρήσεις. Η βαρύτητα της σήψης εκτιμήθηκε με SOFA score. Σε 62 από τους ασθενείς μετρήθηκαν επιπλέον οι κυτταροκίνες TNF-alpha , IL-6 , IL-10 and TGFb-1 μέσα στο πρώτο 24ωρο της εισαγωγής. Αποτελέσματα. Ποσοστό 39.4% των βαριά σηπτικών ασθενών είχαν υπεργλυκαιμία, ενώ 15.3% είχε υπεργλυκαιμία του στρες προκαλούμενη από σήψη. Δεν παρατηρήθηκε κληρονομικό ιστορικό σακχαρώδη διαβήτη στην ομάδα ΥΣ. Υψηλότερο ποσοστό ασθενών με υπεργλυκαιμία του στρες απεβίωσε συγκριτικά με αυτούς με φυσιολογικές τιμές γλυκόζης (42.5 % vs 13.6 %) και αυτούς με σακχαρώδη διαβήτη 42.5 % vs 24.6%). Η ομάδα ΣΔ είχε χειρότερη πρόγνωση από την ομάδα ΦΓ (24.6% vs 13.6 %). Θετική συσχέτιση παρατηρήθηκε μεταξύ των τιμών γλυκόζης αίματος νηστείας των ομάδων ΣΔ και ΥΣ και τη βαρύτητα της σήψης όπως εκφράζεται από το SOFA score. Η ομάδα ΥΣ είχε υψηλότερο SOFA score και επίπεδα IL-6 και IL-10 από τις ομάδες ΣΔ και ΦΓ. Είχε επίσης υψηλότερα επίπεδα TNF-alpha από την ομάδα ΣΔ αλλά όχι από την ομάδα ΦΓ. Δεν παρατηρήθηκε διαφορά στα επίπεδα TGFb-1μεταξύ των 3 ομάδων. Οι επιζώντες είχαν υψηλότερες τιμές IL-10 από αυτούς που απεβίωσαν, δεν παρατηρήθηκε διαφορά για IL-6, TNF-alpha, το λόγο IL-10/TNF-alpha και TGFb-1 μεταξύ των 3 ομάδων. Οι τιμές της IL-10, οι μέσες τιμές νηστείας γλυκόζης και η ηλικία ανευρέθηκαν ως προγνωστικοί παράγοντες σχετιζόμενοι με την πρόγνωση. Συμπεράσματα: Η υπεργλυκαιμία συμπεριλαμβανόμενης και της υπεργλυκαιμίας που παρουσιάζεται στα πλαίσια του στρες παρατηρείται συχνά σε ασθενείς με βαριά σήψη. Η υπεργλυκαιμία του στρες φαίνεται να μη σχετίζεται με ανθρωπομετρικά χαρακτηριστικά και να σχετίζεται με βαρύτερη νόσο. Η υπεργλυκαιμία του στρες συνοδεύεται με αυξημένη παραγωγή κυταροκινών και με κακή έκβαση σε ασθενείς με βαριά σήψη. / Aims /hypothesis. Stress hyperglycemia is a medical term referring to elevation of blood glucose levels in the absence of diabetes due to various kinds of stress, like trauma, burn injury, surgery, myocardial infraction and sepsis. The aim of our study was to investigate the clinical and laboratory characteristics of severe septic patients with baseline hyperglycemia and the impact of hyperglycemia on the final outcome. e also studied whether stress hyperglycemia affects the production of the main pro- and anti-inflammatory cytokines and the 28 days hospital mortality in patients with severe sepsis. Methods-Patients: A total of 265 patients admitted with severe sepsis in three major Hospitals in South-Western Greece, during a 1-year period, were included in the study. Patients were divided in three groups according to their glycemic profile at admission: patients with stress hyperglycemia (group SH, n=45), diabetes mellitus (group DM, n=67) and normal glucose level (group NG, n=153). Hyperglycemia was defined as an admission or in-hospital fasting glucose level of ≥126 mg/dl, or a random blood glucose level of ≥ 200mg/dl on ≥ 2 determinations. The serum levels of the cytokines TNF-alpha, IL-6, IL-10 and TGFb-1 were measured in 62 patients with severe sepsis within 24 hours after admission. Results: 39.4% of septic patients had baseline hyperglycemia with 15.3% having sepsis-induced stress hyperglycemia. No family history was noted in the SH group. A higher percentage of septic patients with stress hyperglycemia died compared to patients with normal glucose levels (42.5 % vs. 13.6 %) and diabetics (42.5 % vs. 24.6%). Group DM had also a poorer prognosis than group NG (24.6% vs. 13.6 %). A positive correlation was detected between the fasting blood glucose levels of groups DM and SH and the severity of sepsis indicated by SOFA score. Group SH had higher SOFA score and levels of IL-6 and IL-10 than group DM and group NG. It also had higher levels of TNF-alpha than group DM but not group NG. There was no difference in the levels of TGFb-1 among the 3 groups. Survivors had higher levels of IL-10 than no survivors, no difference was detected for IL-6, TNF-alpha, IL-10/TNF-alpha ratio and TGFb-1. Interleukin-10 values, mean fasting glucose values and age were found as prognostic factors associated with outcome. Conclusions: Baseline hyperglycemia, including stress induced hyperglycemia is common in patients with severe sepsis. Stress induced hyperglycemia seems not to be related with anthropometric characteristics and is related to a more severe disease. Stress hyperglycemia is associated with increased cytokine production and an adverse clinical outcome in patients with severe sepsis.

Sepsis is a devastating, life-threatening disease and a major problem for many newborns; it develops rapidly and requires expertise to identify the early, subtle signs to prevent death or disability. Evidence from nursing practice and philosophic inquiry indicates that nurses use diverse ways of knowing in their assessments. The purpose of this research was to address research questions concerning two areas: 1) Neonatal Intensive Care Unit (NICU) nurses’ patterns of knowing in the assessment of infants with sepsis as related to dimensions of nursing practice; and 2) Test the psychometric properties of the Newborn Scale of Sepsis (SOS) as a diagnostic or assessment tool. The theoretical framework incorporated the epistemological theories of nurses Carper and Benner and philosopher of science Nagel. This study employed a prospective, correlational design with a convenience sample of 119 NICU nurses. Twenty-eight of these nurses also completed the Newborn SOS to document their assessments of 62 newborns for sepsis. Two instruments were used: 1) The 16-item norm-referenced Nursing Patterns of Knowing (POK) scale (ɑ = .82 and item-scale correlations ≥ 0.33), and 2) The 13-item Newborn Scale of Sepsis (SOS), developed to assist the novice nurse to assess for signs of sepsis (ɑ = .65 and interrater reliability of 96.3%). Descriptive, psychometric, and correlational analyses were applied to the research questions. Results indicated that the more clinically experienced NICU nurses used a more integrated pattern of knowing when assessing newborns for signs of sepsis. The more experienced and competent nurses incorporated empirical, aesthetic and personal knowing in their assessments. More experienced nurses also used less authority-based knowing. More diversity in work experiences was negatively correlated with the sociopolitical pattern of knowing. Psychometric properties of the Newborn SOS indicated that, while its sensitivity was very good, its low specificity limited its usefulness as a diagnostic tool. It was concluded that the Newborn SOS can be used to assist novice nurses in developing pattern recognition of newborn sepsis. The Nursing POK has strong potential for use in a wide variety of studies examining nursing patterns of knowing in assessment of critical health conditions.

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome. Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death. Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

The sympathetic nervous system (SNS) is part of an integrative network that functions to restore homeostasis following injury and infection. The SNS provides negative feedback control over inflammation through the secretion of catecholamines from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Central autonomic structures receive information regarding the inflammatory status of the body and reflexively modulate SNS activity. Evidence suggests that inflammation and infection can also directly regulate ACC function. However, the precise alterations in ACC function that occur in response to regional inflammation, systemic inflammation and exposure to bacterial products have yet to be fully characterized. The present thesis was therefore performed to test the hypothesis that gastrointestinal (GI) and systemic inflammation modulate ACC Ca2+ signaling, and that ACCs possess the ability to directly detect microbe-associated molecular patterns (MAMPs). Ca2+ signaling was assessed in single ACCs isolated from control mice and mice with GI or systemic inflammation using Ca2+ imaging and perforated patch clamp electrophysiology. Acute and chronic GI inflammation consistently reduced high-K+-stimulated Ca2+ transients in ACCs through an inhibition of voltage-gated Ca2+ current. In contrast, systemic inflammation significantly enhanced high-K+-stimulated Ca2+ transients and catecholamine secretion through an increase in Ca2+ release from the endoplasmic reticulum. Incubation of control ACCs in serum obtained from mice with systemic inflammation produced a similar increase in Ca2+ signaling, suggesting that circulating mediators play an important role in this response. To determine whether ACCs can directly detect MAMPs, Ca2+ signaling, excitability and neurotransmitter release were assessed in control ACCs and ACCs incubated in media containing lipopolysaccharide (LPS). Unlike GI and systemic inflammation, LPS did not affect ACC Ca2+ signaling. However, LPS dose- and time-dependently hyperpolarized ACC resting membrane potential and enhanced large conductance Ca2+-activated K+ currents. Consistent with membrane hyperpolarization, LPS reduced ACC excitability and inhibited neuropeptide Y release. These effects were mediated by Toll-like receptor 4 and nuclear factor-κB. In summary, GI and systemic inflammation produce opposite effects on ACC Ca2+ signaling through distinct mechanisms, and ACCs can directly detect MAMPs. These findings extend our knowledge of the complex integration performed by the immune system-nervous system network during health and disease. / Thesis (Ph.D, Physiology) -- Queen's University, 2013-08-20 17:15:23.945

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Ulm, Univ., Diss., 2009.

Thesis (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2003.

Zugl.: Giessen, University, Diss., 2007.