High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

Ramipril increases the protein level of skeletal muscle IRS-1 and alters protein tyrosine phosphatase activity in spontaneously hypertensive rats

To investigate mechanisms by which angiotensin converting enzyme (ACE)-inhibition increases insulin sensitivity, spontaneously hypertensive (SH) rats were treated with or without ramipril (1 mg/kg per day) for 12 weeks. Insulin binding and protein levels of insulin receptor substrate-1 (IRS-1), p85-subunit of phosphatidylinositol 3'-kinase (p85) and Src homology 2 domain-containing phosphatase-2 (SHP2) were then determined in hindlimb muscle and liver. Additionally, protein tyrosine phosphatase (PTPase) activities towards immobilized phosphorylated insulin receptor or phosphorylated IRS-1 of membrane (MF) and cytosolic fractions (CF) of these tissues were measured. Ramipril treatment increased IRS-1-protein content in muscle by 31+/-9% (P<0.05). No effects were observed on IRS-1 content in liver or on insulin binding or protein expression of p85 or SHP2 in both tissues. Ramipril treatment also increased dephosphorylation of insulin receptor by muscle CF (22.0+/-1.0%/60 min compared to 16.8+/-1.5%/60 min; P<0.05), and of IRS-1 by liver MF (37.2+/-1.7%/7.5 min compared to 33.8+/-1.7%/7.5 min; P<0.05) and CF (36.8+/-1.0%/7.5 min compared to 33.2+/-1.0%/7.5 min; P<0.05). We conclude that the observed effects of ACE-inhibition by ramipril on the protein expression of IRS-1 and on PTPase activity might contribute to its effect on insulin sensitivity.

Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits

BACKGROUND: The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH. METHODS: CVS was induced using the one-haemorrhage rabbit model and confirmed by digital subtraction angiography of the rabbits' basilar artery on day 5. Prior to sacrifice, local CSF and basilar arterial plasma samples were obtained by a transclival approach to the basilar artery. Systemic arterial plasma samples were obtained. ET-1 levels were determined by immunometric technique (pg/ml +/- SEM) and total nitrate/nitrite level spectrophotometrically (micromol/l +/- SEM). FINDINGS: Angiographic CVS was documented after SAH induction (n = 12, P < 0.05). The ET-1 level in CSF was significantly elevated by 27.3% to 0.84 +/- 0.08 pg/ml in SAH animals (n = 7) in comparison to controls (0.66 +/- 0.04 pg/ml, n = 7, P < 0.05). There was no significant difference in ET-1 levels in systemic and basilar arterial plasma samples of SAH animals compared to controls. A significant lack of local NO metabolites was documented in basilar arterial plasma after SAH (36.8 +/- 3.1 micromol/l, n = 6) compared to controls (61.8 +/- 6.2 micromol/l, n = 6, P < 0.01). CONCLUSION: This study demonstrates that an elevated ET-1 level in CSF and local lack of NO in the basilar arterial plasma samples are associated with CVS after experimental SAH.

Independent association between lower level of social support and higher coagulation activity before and after acute psychosocial stress

OBJECTIVE: To investigate the relationship between social support and coagulation parameter reactivity to mental stress in men and to determine if norepinephrine is involved. Lower social support is associated with higher basal coagulation activity and greater norepinephrine stress reactivity, which in turn, is linked with hypercoagulability. However, it is not known if low social support interacts with stress to further increase coagulation reactivity or if norepinephrine affects this association. These findings may be important for determining if low social support influences thrombosis and possible acute coronary events in response to acute stress. We investigated the relationship between social support and coagulation parameter reactivity to mental stress in men and determined if norepinephrine is involved. METHODS: We measured perceived social support in 63 medication-free nonsmoking men (age (mean +/- standard error of the mean) = 36.7 +/- 1.7 years) who underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma D-dimer, fibrinogen, clotting Factor VII activity (FVII:C), and plasma norepinephrine at rest as well as immediately after stress and 20 minutes after stress. RESULTS: Independent of body mass index, mean arterial pressure, and age, lower social support was associated with higher D-dimer and fibrinogen levels at baseline (p < .012) and with greater increases in fibrinogen (beta = -0.36, p = .001; DeltaR(2) = .12), and D-dimer (beta = -0.21, p = .017; DeltaR(2) = .04), but not in FVII:C (p = .83) from baseline to 20 minutes after stress. General linear models revealed significant main effects of social support and stress on fibrinogen, D-dimer, and norepinephrine (p < .035). Controlling for norepinephrine did not change the significance of the reported associations between social support and the coagulation measures D-dimer and fibrinogen. CONCLUSIONS: Our results suggest that lower social support is associated with greater coagulation activity before and after acute stress, which was unrelated to norepinephrine reactivity.

"Of course I will...": The combined effect of certainty and level of expectancies on persistence and performance

The importance of performance expectancies for the prediction of regulation of behavior and actual performance has long been established. Building on theories from the field of social cognition, we suggest that the level of performance expectancies, as well as the certainty of the expectancy, have a joint influence on an individual’s beliefs and behavior. In two studies (one cross sectional using a sample of secondary school students and one longitudinal using a sample of university students) we found that expectancies more strongly predicted persistence, and subsequent performance, the more certain the expectancy was. This pattern was found even if prior performance was controlled, as in Study 2. The data give an indication that it may be useful to include certainty as an additional variable in expectancy models.

Age differences in instability, contingency, and level of self-esteem across the life span

We investigated age differences in instability, contingency, and level of self-esteem from age 13 to 72 years, using data from 1386 individuals who participated in a diary study over 25 days. Instability and contingency of self-esteem decreased from adolescence to old age, whereas level of self-esteem increased. Big Five personality traits predicted the level, but not the slope, of the trajectories of self-esteem characteristics. Age differences in self-esteem characteristics did not merely reflect age differences in instability and level of positive and negative affect. Finally, self-esteem characteristics showed a stable pattern of interrelations across the life span. Overall, the findings suggest that people’s self-esteem tends to become better adjusted—i.e., more stable, less contingent, and higher—across the life course.

Bridging Research and Development : Partnership Actions for Mitigating Syndromes (PAMS) in the Swiss National Centre of Competence (NCCR) North-South - Capitalising on Experience

Within the framework of Switzerland’s international NCCR North-South research programme, Partnership Actions for Mitigating Syndromes (PAMS) are a practice-oriented component with a transdisciplinary approach. By linking research and development practice, they bring together researchers, practitioners and local communities in a common effort to test and evaluate research findings in concrete development contexts. They provide unique insights into innovative approaches and opportunities for promoting sustainable development in countries of the South and East. After an initial four-year phase, the PAMS projects implemented to date were evaluated in order to learn about their potentials and limits, as well as to decide on the direction of the component for the next phase of the programme. The present publication presents the results of this evaluation.

Level of incongruence during cardiac rehabilitation and prediction of future CVD-related hospitalizations plus all-cause mortality

Independent of traditional risk factors, psychosocial risk factors increase the risk of cardiovascular disease (CVD). Studies in the field of psychotherapy have shown that the construct of incongruence (meaning a discrepancy between desired and achieved goals) affects the outcome of therapy. We prospectively measured the impact of incongruence in patients after undergoing a cardiac rehabilitation program. We examined 198 CVD patients enrolled in a 8–12 week comprehensive cardiac rehabilitation program. Patients completed the German short version of the Incongruence Questionnaire and the SF-36 Health Questionnaire to measure quality of life (QoL) at discharge of rehabilitation. Endpoints at follow-up were CVD-related hospitalizations plus all-cause mortality. During a mean follow-up period of 54.3 months, 29 patients experienced a CVD-related hospitalization and 3 patients died. Incongruence at discharge of rehabilitation was independent of traditional risk factors a significant predictor for CVD-related hospitalizations plus all-cause mortality (HR 2.03, 95% CI 1.29–3.20, p = .002). We also found a significant interaction of incongruence with mental QoL (HR .96, 95% CI .92–.99, p = .027), i.e. incongruence predicted poor prognosis if QoL was low (p = .017), but not if QoL was high (p = .74). Incongruence at discharge predicted future CVD-related hospitalizations plus all-cause mortality and mental QoL moderated this relationship. Therefore, incongruence should be considered for effective treatment planning and outcome measurement.

The Level of Development and the Determinants of Productivity Growth

We examine the effects of technology on productivity growth by disaggregating total output into sectoral components, exploring the roles of investment and technology on productivity growth for countries in different income groups. We find that for low-income countries, investment is the most important determinant of productivity growth. While investment plays an important role in determining productivity growth in middle-income countries, additional effects resulting from technological change also emerge. Investment ceases to have a significant effect on productivity growth in high-income countries.