Continuous, on-line, real-time measurement of cardiac output and derived cardiorespiratory variables in the critically ill

A previously reported monitoring system provided continuous direct measurements of oxygen consumption and intravascular pressures. These data were combined with interval measurements of cardiac output and blood oxygen saturations to derive various hemodynamic and oxygen transport variables. This system has now been modified so that cardiac output is measured continuously in real-time.     

Elevated levels of platelet microparticles in carotid atherosclerosis and during the postprandial state

Background

Platelet microparticles (PMPs) possess proatherogenic and procoagulant properties which may play a role in atherogenesis and subsequent thromboembolic complications. The present study was conducted to investigate the possible relationship between carotid atherosclerosis and plasma concentrations of PMPs, and elucidate if plasma levels of PMPs were affected by postprandial hypertriglyceridemia.

Methods and results

Subjects with ultrasound-assessed carotid atherosclerotic plaques (echogenic; n = 20 and echolucent; n = 20), assessed by ultrasonography, and subjects without carotid plaques (n = 20) were recruited from a population-based study and underwent a standard fat tolerance test. Subjects with carotid plaques had significantly higher levels of large PMPs than subjects without carotid atherosclerotic plaques (96.7 ± 50.4 µg/l versus 56.1 ± 34.9 µg/l), after adjustments for traditional cardiovascular risk factors and use cardiovascular drugs (p = 0.021). Plasma PMPs were not associated with plaque echogenicity. Postprandial hypertriglyceridemia induced a similar increase in plasma PMPs within all groups. Significant correlations were found between an increase in plasma triglycerides and percent elevation in total PMPs (r = 0.29, p < 0.05) and large PMPs (r = 0.34, p < 0.01) in the postprandial phase.

Conclusions

Individuals with echogenic and echolucent carotid atherosclerotic plaques have statistically significant elevation of large plasma PMPs compared to age/sex-matched normal controls. Postprandial hypertriglyceridemia induces a significant, similar increase in plasma PMPs in individuals with and without carotid atherosclerotic plaques which could be of pathophysiological importance in atherogenesis.     

The dorsal raphe nucleus--from silver stainings to a role in depression

Over a hundred years ago, Santiago Ramón y Cajal used a new staining method developed by Camillo Golgi to visualize, among many other structures, what we today call the dorsal raphe nucleus (DRN) of the midbrain. Over the years, the DRN has emerged as a multifunctional and multitransmitter nucleus, which modulates or influences many CNS processes. It is a phylogenetically old brain area, whose projections reach out to a large number of regions and nuclei of the CNS, particularly in the forebrain. Several DRN-related discoveries are tightly connected with important events in the history of neuroscience, for example the invention of new histological methods, the discovery of new neurotransmitter systems and the link between neurotransmitter function and mood disorders. One of the main reasons for the wide current interest in the DRN is the nucleus' involvement in depression. This involvement is particularly attributable to the main transmitter of the DRN, serotonin. Starting with a historical perspective, this essay describes the morphology, ascending projections and multitransmitter nature of the DRN, and stresses its role as a key target for depression research.     

TLR8‐mediated activation of human monocytes inhibits TL1A expression

TLR play important roles in inflammation and innate immune response to pathogens. TLR8 recognizes ssRNA and induces NF‐κB via MyD88 signaling. TL1A is a member of the TNF superfamily that markedly enhances IFN‐γ production by IL‐12/IL‐18‐stimulated peripheral and mucosal CD4⁺ T cells. TL1A expression is increased in the mucosa of patients with inflammatory bowel disease and is considered a key mediator of Crohn's disease (CD). We have previously shown that TL1A is strongly induced by immune complexes (IC) but not TLR ligands in antigen‐presenting cells. However, a potential interaction between these pro‐inflammatory signaling pathways has not been investigated. IC‐induced TL1A expression of monocytes was potently inhibited by a TLR8 or TLR7/8 ligand (R848) in a dose‐dependent manner. Furthermore, when co‐cultured with CD4⁺ T cells, TLR8 ligands inhibited TL1A production, resulting in almost complete inhibition of IFN‐γ production by the CD4⁺ T cells. Furthermore, we demonstrate that IFN‐α is not required for this suppressive effect by TLR8 signaling. Our data demonstrate for the first time a direct interaction between TLR and TL1A signaling pathways. TLR8 activation may be an important, novel pathway for targeted treatment of Th1‐mediated diseases, such as CD.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons

Background  

The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health.     

Der Dissens in der Public-Health-Ethik

Public health covers public activities linked with cure, prevention and health promotion directed to positively influence the health of populations. As far as these criteria are met, health policies are public health. Public health holds many ethical implications. Resources and health opportunities are redistributed, ends and means of public health as well as rights and duties have to be discussed, and conflicts exist between targets. Ethical policy counselling is an important complement to natural and social scientific policy counselling. However, ethical counselling cannot solve conflicts about values and norms nor does it claim to do so. There are different theories and approaches, recommended principles differ and are in conflict with each other. It must not be expected that a generally accepted frame for public health ethical policy counselling will be developed. Public health ethics can develop an ordering effect and enforce more clarity for actors about their values and norms, but in case of unresolvable dissent between experts it can also be misused to give support to the legitimation of political decisions. Orientation of consulting activities towards the “pragmatistic model” (Habermas) and a counselling of the civil society is promising to prevent such exploitation.