Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease.

BACKGROUND: Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. METHODS: We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. RESULTS: In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). CONCLUSION: PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.

The intestinal tissue homeostasis - the role of extracellular matrix remodeling in inflammatory bowel disease.

Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the intestinal mucosa.Areas covered: The aim of this review is to highlight the importance of the ECM in relation to the pathogenesis of IBD, while addressing basement membrane and interstitial matrix remodeling, and the processes of wound healing of the intestinal tissue in IBD.Expert opinion: In IBD, basement membrane remodeling may reflect the integrity of the intestinal epithelial-cell homeostasis. The interstitial matrix remodeling is associated with deep inflammation such as the transmural inflammation as seen in fistulas and intestinal fibrosis leading to fibrostenotic strictures, in patients with CD. The interplay between wound healing processes and ECM remodeling also affects the tissue homeostasis in IBD. The interstitial matrix, produced by fibroblasts, holds a very different biology as compared to the epithelial basement membrane in IBD. In combination with integration of wound healing, quantifying the interplay between damage and repair to these sub compartments may provide essential information in IBD patient profiling, mucosal healing and disease management.

High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Is distribution of cold stenotherms constrained by temperature? The case of the Arctic fairy shrimp (Branchinecta paludosa O.F. Müller 1788).

Small water bodies in cold climate respond fast to global warming, and species adapted to such habitats may be valuable indicators for climate change. We investigated the geographical and physiological temperature limits of the Arctic fairy shrimp (Branchinecta paludosa), which is common in cold water arctic ponds, but at present retracts its range in alpine areas along its southern outreach of Norway. Seasonal logging of water temperatures along an altitudinal transect revealed an upper temperature limit of 12.7°C for its presence, which closely matched a calculated upper temperature limit of 12.9°C throughout its entire Norwegian range. Field data hence point to cold stenotherm features, which would be consistent with its Arctic, circumpolar distribution. Lab experiments, on the other hand, revealed a linear increase in respiration over 10-20°C. When fed ad libitum somatic growth increased with temperature, as well, without negative physiological impacts of higher temperatures. The absence of Branchinecta paludosa in ponds warmer than 13°C could still be due to a mismatch between temperature dependent metabolism and limited energy supply in these ultraoligotrophic water bodies. We discuss the concept of cold stenothermy in this context, and the impacts of regional warming on the future distribution of the Arctic fairy shrimp.

Negative regulation of HIF in skeletal muscle of elite endurance athletes: a tentative mechanism promoting oxidative metabolism.

The transcription factor hypoxia-inducible factor (HIF) has been suggested as a candidate for mediating training adaptation in skeletal muscle. However, recent evidence rather associates HIF attenuation with a trained phenotype. For example, a muscle-specific HIF deletion increases endurance performance, partly through decreased levels of pyruvate dehydrogenase kinase 1 (PDK-1). HIF activity is regulated on multiple levels: modulation of protein stability, transactivation capacity, and target gene availability. Prolyl hydroxylases (PHD1-3) induces HIF degradation, whereas factor-inhibiting HIF (FIH) and the histone deacetylase sirtuin-6 (SIRT6) repress its transcriptional activity. Together, these negative regulators introduce a mechanism for moderating HIF activity in vivo. We hypothesized that long-term training induces their expression. Negative regulators of HIF were explored by comparing skeletal muscle tissue from moderately active individuals (MA) with elite athletes (EA). In elite athletes, expression of the negative regulators PHD2 (MA 73.54 ± 9.54, EA 98.03 ± 6.58), FIH (MA 4.31 ± 0.25, EA 30.96 ± 7.99) and SIRT6 (MA 0.24 ± 0.07, EA 11.42 ± 2.22) were all significantly higher, whereas the response gene, PDK-1 was lower (MA 0.12 ± 0.03, EA 0.04 ± 0.01). Similar results were observed in a separate 6-wk training study. In vitro, activation of HIF in human primary muscle cell culture by PHD inactivation strongly induced PDK-1 (0.84 ± 0.12 vs 4.70 ± 0.63), providing evidence of a regulatory link between PHD activity and PDK-1 levels in a relevant model system. Citrate synthase activity, closely associated with aerobic exercise adaptation, increased upon PDK-1 silencing. We suggest that training-induced negative regulation of HIF mediates the attenuation of PDK-1 and contributes to skeletal muscle adaptation to exercise.

Oats (Avena sativa) reduce atherogenesis in LDL-receptor-deficient mice.

AIM: The cholesterol-lowering properties of oats, largely ascribed to its contents of soluble fibers, beta-glucans, are well established, whereas effects on atherogenesis are less well elucidated. Oats also contains components with reported antioxidant and anti-inflammatory effects that may affect atherogenesis. In this work we examined effects of oat bran on plasma cholesterol, markers of inflammation, eNOS expression and development of atherosclerosis in LDL-receptor-deficient (LDLr(-/-)) mice. METHODS AND RESULTS: Female LDLr(-/-) mice were fed Western diet+/-oat bran. Two concentrations of oat bran (40 and 27%) were compared regarding effects on plasma lipids. There was a dose-dependent reduction of plasma cholesterol by 42 and 20% with 40 and 27% oat bran, respectively. Both concentrations also lowered plasma triglycerides (by 45 and 33%) and relative levels of plasma LDL+VLDL. The reduction of plasma lipids was accompanied by increased faecal excretion of cholesterol and bile acids. Oat bran (40%) efficiently reduced atherosclerotic lesion area in the descending aorta (-77%) and aortic root (-33%). Plasma levels of fibrinogen and soluble vascular cell adhesion molecule-1 (VCAM-1) were significantly lower, and immunofluorescence of aortic sections revealed a 75% lower expression of VCAM-1 in oat-fed mice. The expression of eNOS protein in the aortic wall was increased in mice fed oat bran. CONCLUSIONS: Oat bran supplemented to a Western diet lowers plasma cholesterol, reduces levels of some inflammatory markers, increases eNOS expression and inhibits atherosclerotic lesion development in LDLr(-/-) mice. It remains to be investigated which components in oats contribute to these effects.

Volume overload in patients treated with continuous ambulatory peritoneal dialysis associated with reduced circadian blood pressure variation.

BACKGROUND: While a high blood pressure (BP) in patients receiving maintenance ambulatory peritoneal dialysis (CAPD) is associated with congestive heart failure and an increased mortality, the relevance of diurnal variations in BP is unknown. METHODS: In a prospective study, we enrolled 76 prevalent patients receiving stable CAPD (age 60.4 +/- 13.8 years; 37 males). BP was measured over 24 h using an automated device. We also performed routine clinical and biochemical measurements, as well as the Karnofsky index to evaluate physical activity. Volume status was assessed using bioimpedance analysis. RESULTS: 69 patients (with an average time on dialysis of 24.4 +/- 22.5 months) completed the study. Of these, 16 patients experienced a drop in BP >10% at night (dippers), while 53 patients did not (non-dippers). Comparing these two groups, dippers had significantly lower extracellular water (ECW) (13.8 +/- 2.1 vs. 15.9 +/- 3.3 l; p < 0.05), normalized extracellular water (nECW) (0.22 +/- 0.05 vs. 0.26 +/- 0.04 l/m; p < 0.05), and serum albumin (38.2 +/- 2.9 vs. 35.9 +/- 3.7 g/l; p < 0.05). Age, Karnofsky index, vintage, residual renal Kt/V and peritoneal Kt/V, total Kt/V, dose of antihypertensive drugs, mean systolic and diastolic BP did not significantly differ between these groups. Correlation analysis showed the coefficient of variation (CV) of BP positively correlated with E/T (r(2) = 0.292; p < 0.05), diabetic (r(2) = 0.267; p < 0.05), male (r(2) = 0.257; p < 0.05), nECW (r(2) = 0.278; p < 0.05) and ECW (r(2) = 0.249; p < 0.05) negatively correlated with albumin (r(2) = -0.280; p < 0.05). Furthermore, in a multivariate linear regression model, E/T, albumin and sex were independently associated with CV for BP. CONCLUSIONS: We show that reduced BP variation is common in CAPD patients and associated with volume overload and hypoalbuminemia. Furthermore, the relationship between nutritional, inflammatory status and dipping needs further studies.

Bispectral index monitoring: appreciated but does not affect drug dosing and hypnotic levels.

BACKGROUND: Bispectral index (BIS) has been associated with benefits from less-deep anesthesia as well as preventing awareness, albeit not at the same time. We investigated how increasing experience from BIS in clinical practice affect the hypnotic level, drug consumption, as well as subjective opinions on this monitoring. METHODS: Eight certified registered nurse anesthetists (CRNAs) with previous experience from 88 (46-121) BIS monitored cases anesthetized 80 cases with concealed BIS, followed by 80 cases with available BIS. Additional education and training was followed by yet another 160 patients randomized to open or blindly recorded BIS. BIS levels, anesthetic gas consumption, fentanyl use, and subjective opinions on utility and reliability were investigated. RESULTS: After gaining initial experience from BIS monitoring, the fraction of time with BIS levels of 40-60 did not deteriorate in cases with concealed monitoring and no further improvement was found in subsequent cases with available data from the BIS monitoring, not even after additional training and encouragement to adhere to the 40-60 interval. Compared with the first experience from BIS monitoring the subjective opinions on utility had increased from 33 to 78 mm (100 mm visual analog scales) (P<0.0001). CONCLUSION: Although BIS became considerably appreciated, growing experience and repeated education had no impact on drug dosing and BIS levels.

Estrogen attenuates vascular expression of inflammation associated genes and adhesion of monocytes to endothelial cells.

OBJECTIVE: Investigate effects of estrogen at gene expression and functional levels in vascular wall cells treated with bacterial lipopolysaccharide (LPS). MATERIALS AND METHODS: Aortic segments from ovariectomized mice were treated with LPS for 24 h in the absence or presence of 17beta-estradiol (E2). Gene activity was determined by Affymetrix microarray analysis and real-time RT-PCR. Adhesion of [3H]-thymidine labelled human THP-1 monocytes to mouse bEnd.3 endothelial cells was determined by measuring radioactivity of DNA from co-culture homogenates. RESULTS: Analysis of global gene expression profiles revealed that 10 nM E2 attenuates LPS-induced (10 ng/ml) expression of genes coding for well-known acute-phase proteins, such as alpha-trypsin inhibitor heavy chain 4, serum amyloid A3 and lipocalin 2. The E2-induced down-regulation of these three genes observed by microarray was confirmed by realtime RT-PCR. Treatment with 500 ng/ml LPS increased adhesion of monocytes to endothelial cells more than two fold. Importantly, LPS-induced monocyte adhesion was fully prevented by 50 nM E2. CONCLUSION: Estrogen reduces expression of acute-phase protein genes and inhibits LPS-induced moncocyte adhesion to endothelial cells, suggesting that estrogen might have a vasculoprotective effect via this mechanism.

Working conditions, psychosocial resources and work stress in nurses and physicians in chief managers' positions.

The study investigated whether psychosocial work conditions, professional network, job support, social network and support, sick leave and salary were associated with work stress in nurses in chief manager' positions above ward level and physicians in clinical director positions. A sample consisting of 205 nurses and 274 physicians in chief managers' positions at higher structural level answered a questionnaire. Odds ratios were used for estimating the bivariate association between work stress and psychosocial resources. The result showed that both nurse managers (OR 6.8; 95% CI: 3.5-13.5) and clinical directors (OR 6.7; 95% CI: 3.6-12.5) exposed to high job demands had a significantly higher probability of high level of work stress. The results also indicated that the available psychosocial resources taken together inside and outside work did not balance the experienced work stress in nurse managers and the clinical directors who were exposed to high work demands. No relation was found between work stress and sick leave and salary.

Diabetes mellitus and cardiogenic shock in acute myocardial infarction.

AIMS: Cardiogenic shock is the leading cause of in-hospital mortality after acute myocardial infarction (MI). This study investigates the importance of age and preexisting diabetes mellitus on the incidence and prognosis of cardiogenic shock in a large group of consecutive patients with MI. METHODS AND RESULTS: Baseline characteristics and in-hospital complications to the infarction were prospectively recorded in 6676 patients with MI. Ten-year mortality was collected. Diabetes was present in 10.8% of the total population. A total of 443 developed cardiogenic shock with an incidence of 6.2% among nondiabetics and 10.6% among diabetics. Age, wall motion index, reinfarction, and the absence of thrombolytic treatment were significant independent predictors of mortality in patients with cardiogenic shock. Intriguingly, diabetes was not a significant predictor for short- and long-term mortality in this population. The 30-day and 5-year mortality rate was equally poor in both diabetic and nondiabetic patients with cardiogenic shock (diabetics: 30-day 63%, 5-year 91%; nondiabetics: 30-day 62%, 5-year 86%; p>0.05). CONCLUSIONS: Cardiogenic shock develops approximately twice as often among diabetics as among nondiabetic patients with acute MI. The prognosis of diabetics with cardiogenic shock is similar to the prognosis of nondiabetic patients with cardiogenic shock.

Reduction in the incidence of awareness using BIS monitoring.

BACKGROUND: Explicit recall (ER) is evident in approximately 0.2% of patients given general anaesthesia including muscle relaxants. This prospective study was performed to evaluate if cerebral monitoring using BIS to guide the conduction of anaesthesia could reduce this incidence significantly. PATIENTS AND METHODS: A prospective cohort of 4945 consecutive surgical patients requiring muscle relaxants and/or intubation were monitored with BIS and subsequently interviewed for ER on three occasions. BIS values between 40 and 60 were recommended. The results from the BIS-monitored group of patients was compared with a historical group of 7826 similar cases in a previous study when no cerebral monitoring was used. RESULTS: Two patients in the BIS-monitored group, 0.04%, had ER as compared with 0.18% in the control group (P < 0.038). Both BIS-monitored patients with ER were aware during intubation when they had high BIS values (> 60) for 4 min and more than 10 min, respectively. However, periods with high BIS = 4 min were also evident in other patients with no ER. Episodes with high BIS, 4 min or more, were found in 19% of the monitored patients during induction, and in 8% of cases during maintenance. CONCLUSIONS: The use of BIS monitoring during general anaesthesia requiring endotracheal intubation and/or muscle relaxants was associated with a significantly reduced incidence of awareness as compared with a historical control population.

Nurse managers' professional networks, psychosocial resources and self-rated health.

BACKGROUND: Nurse managers act under constant pressure to develop strategies in response to professional challenges within a changing and restructured health care system. When such environmental stress is present, they need access to sufficient psychosocial recourse. AIM: The study aimed to investigate whether nurse managers' professional networks, psychosocial work conditions, job support, social network and support were associated with self-rated health, sick-leave and salary. METHODS: From a total of 268 Swedish nurse managers, active in management positions, 205 (77%) agreed to participate in the study by answering a self-report questionnaire. Cronbach's alpha was used to calculate internal consistency. Odds ratios were used to estimate the bivariate association between self-rated health and psychosocial resources. RESULTS: Nurse managers exposed to high job demands had significantly increased odds for low self-rated health. It was also found that low level of support from professional network, job support, social network and social support outside work displayed increased odds for low self-rated health, independently of age, gender and education. There were additive (but no synergistic) effects found for job demand in combination with professional networks, job support and emotional support and in relation to self-rated health. CONCLUSION: The study showed that nurse managers exposed to high job demands had elevated odds for low self-rated health, regardless of level of psychosocial resources within or outside work. Two-thirds of the nurse managers who were affiliated to professional networks did not consider this a supporting factor in their management work. Those with low job support had increased odds for sick-leave compared with those with high support. No significant associations were found between psychosocial characteristics and salary.

Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development.

AIMS: Cardiogenic shock accounts for the majority of deaths following acute myocardial infarction. The majority of outcome data on this issue are, however, derived from single hospitals, referral centers or selected patients in randomized studies. The purpose of this study was to investigate incidence, outcome and prognostic significance of cardiogenic shock in 6676 consecutive patients with acute myocardial infarction. METHODS AND RESULTS: Demographic and clinical data including the presence of cardiogenic shock were prospectively collected in 6676 non-invasively managed patients with myocardial infarction consecutively admitted to 27 different hospitals during a 2-year period. Six-year mortality data were collected in 99.9% of the population. Cardiogenic shock developed in 444 patients (6.7%). In 59% of these patients cardiogenic shock developed within 48 h, 11% developed shock during days 3 and 4 and 30% later than 4 days after the infarction. Thirty-day and 6-year mortality was 62 and 88% among shock patients compared to 9 and 45% in non-shock patients. Patients with early shock development (days 1-2) had a significantly lower 30-day mortality (45%) than those with intermediate or late shock development (>80%) (P<0.05). In 30-day survivors, survival the following years was lower than in patients without cardiogenic shock but with post-infarction heart failure. CONCLUSIONS: In this nationwide prospectively collected registry, non-invasively managed consecutive myocardial infarct patients with cardiogenic shock had an extremely reduced life expectancy. Every attempt to improve treatment, prevention and identification of patients at risk of shock development should be strongly encouraged.

Effect of early revascularisation in cardiogenic shock complicating acute myocardial infarction. A single center experience.

BACKGROUND: Five to 10% of patients with acute myocardial infarction develop cardiogenic shock and the majority of these patients are expected to die within the first few weeks. In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect of early invasive revascularisation on mortality. METHODS: Thirty-six consecutive patients who developed cardiogenic shock less than 48 h after MI were retrospectively evaluated and divided into two treatment groups. One group received early invasive revascularisation (n=24) and the other group had no early invasive revascularisation, but received similar conventional intensive care medical treatment (n=12). RESULTS: Baseline characteristics and hemodynamic variables were similar in both groups. Apart from invasive revascularisation and the use of intra aortic balloon counterpulsation (IABP), treatment strategies did not differ between the two groups. Thirty-day mortality was 21% in the revascularised group of patients and 58% in the non-revascularised group (P<0.05). CONCLUSIONS: Our data support previous observations suggesting that an aggressive treatment strategy including early invasive revascularisation and IABP is associated with improved short and long-term survival in patients with cardiogenic shock. Since early revascularisation appears safe with a considerable treatment benefit, this approach must be considered in patients with short shock duration early after MI.

Nurse managers' management direction and role over time.

This study illuminates how 27 nurse managers experienced management direction and roles over a time period of three years. Fourteen of the nurse managers worked full-time in management positions during the time, while 13 during the same time completed a professional development course in advanced nursing at master-degree level. Two main directions were identified. One focused on management from the perspective of power and power transference, and the other focused on management from the perspective of theoretical knowledge related to nursing development.

Influence of nursing management education on management direction and role.

The authors discuss how 13 nurse managers in Sweden experienced management direction and the management role before and 1 year after a professional development course in advanced nursing at the masters-degree level. The nurse managers related theoretical knowledge to an increased awareness of further possibilities inherent in managerial positions. They stressed the importance of networking for future support and growth.

Management from four different perspectives.

AIM: This study intended to illuminate nursing management in a developing organization from the perspectives of nurse managers, chief physicians, hospital directors and politicians. BACKGROUND: Increased responsibility in a changing health care system makes it important that nurses occupy advantageous positions so that they may safeguard and facilitate the development of their core area. METHODS: Open-ended taped interviews were conducted with 15 nurse managers, 11 chief physicians, three hospital directors and three politicians from three Swedish cities. FINDINGS: The main theme found was power and three dependent themes were identified as; power within activities, being in power and freedom to act. CONCLUSION: The four professional groups related their opinion of nursing management to the needs and interests of their own group. Acceptance or nonacceptance between the groups was discussed in terms of the concept of knowledge, which was interpreted as being a more acceptable topic for discussion than the phenomenon of power.

Inhibitory effect of gastrin peptides on triacylglycerol secretion in Hep G2 cells.

OBJECTIVES: To determine whether human liver cells respond to gastrin peptides by reducing their secretion of triacylglycerols, as recently observed in rat hepatocytes. DESIGN: Cells of the human hepatoblastoma cell line Hep G2 were incubated with pentagastrin and heptadeca gastrin, followed by lipid analysis of media and cells. METHODS: Cultivation of cells; analyses of triacylglycerols, cholesterol and protein; statistical analysis. RESULTS: As the secretion of triacylglycerols in Hep G2 cells incubated with basal medium (Eagle's minimum essential medium with non-essential amino acids, penicillin, streptomycin and glutamine) is only about 20% of the triacylglycerol secretion reported for human liver cells, the possibility of detecting statistically significant effects of gastrin peptides on lipid secretion is reduced compared to the situation in normal hepatocytes. However, by a combined addition of 0.1 mmol/l albumin-bound oleate, 10 mmol/l sodium butyrate and 0.1 mg/ml dextran sulphate to the basal medium, the triacylglycerol secretion in Hep G2 cells was found to be more than twice as high as in cells incubated with basal medium alone. With this supplemented medium a biphasic concentration-dependent statistically significant inhibitory effect of both pentagastrin and heptadeca gastrin on triacylglycerol secretion in Hep G2 cells was demonstrated. CONCLUSION: These results indicate that gastrin peptides may play a role in the regulation of lipoprotein secretion in human liver cells.