Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and experimental human endotoxemia

Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF and cytokines in vivo in patients with meningococcal disease, in human experimental endotoxemia, and in whole blood cultures using a newly developed sensitive and specific enzyme-linked immunosorbent assay. Twenty patients with meningococcal disease were investigated. For the human endotoxemia model, 8 healthy volunteers were intravenously injected with 2 ng/kg Escherichia coli LPS. Whole blood from healthy volunteers was incubated with LPS or heat-killed meningococci. Macrophage migration inhibitory factor concentration in blood was increased during meningococcal disease and highest in the patients presenting with shock compared with patients without shock. Plasma concentration of MIF correlated with disease severity, the presence of shock and with the cytokines interleukin (IL) 1beta, IL-10, IL-12, and vascular endothelial growth factor, but not with TNF-alpha. MIF was not detected in blood in experimental endotoxemia, nor after stimulation of whole blood with LPS or meningococci, although high levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in patients with meningococcal disease and highest in the presence of shock. Macrophage migration inhibitory factor cannot be detected in a human endotoxemia model and is not produced by whole blood cells incubated with LPS or meningococci.     

Psychometric properties of the Confidence and Trust in Delivery Questionnaire (CTDQ): a pilot study

ABSTRACT: BACKGROUND: Assessing expecting mother's opinions prior to birth draws a comprehensive picture for the caregivers about their emotional state and their expectations. Some questionnaires to cover these aspects do exist. This study aims to present the psychometric properties of a new instrument, the Confidence and Trust in Delivery Questionnaire (CDTQ) a short but reliable a self-report instrument that focuses on confidence and trust as meaningful dimensions for expectant mothers. METHODS: A pilot validation study of 221 women 6 weeks before childbirth was conducted in Germany between October 2007 and June 2008. To detect structural relations between the items, factor and reliability analyses were applied to the CTDQ items. Factor analysis was performed by means of principal components analysis and varimax rotation. Internal reliability was assessed by Cronbach's alpha. External validation was performed using the sense of coherence (SOC) scale. RESULTS: The CTDQ comprises of 11 items. We found a 4-factor structure. The internal consistency of the whole item pool (Cronbach's alpha = 0.79) and the 4 subscales [confidence in labor (alpha = 0.82); partner's support (alpha = 0.62); trust in medical competency (alpha = 0.68); being informed (alpha = 0.60)] can be regarded as sufficient or even excellent. The 4 factors explained 69.6% of total variance. Except for a high intercorrelation (0.70) between "partner's support" and "trust in medical competence", the subscales show low intercorrelations, indicating an adequate independence of the respective subscales. Regarding the external validity we found minor respective moderate correlations with the SOC scale. CONCLUSIONS: Our data suggest that the CTDQ is a useful instrument to assess confidence and trust in delivery. With 4 clinically relevant dimensions, the CTDQ is now open for further studies in the field of labor.     

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses

Introduction

Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.

Methods

cTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event.

Results

Data from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI.Only 20% of definite MIs were recognised by the clinical team. There was no significant difference in mortality between recognised and non-recognised events.At the time of cTNT rise, 100 patients (70%) were septic and 58% were on vasopressors. Patients who were septic when cTNT was elevated had an ICU mortality of 28% compared to 9% in patients without sepsis. ICU mortality of patients who were on vasopressors at the time of cTnT elevation was 37% compared to 1.7% in patients not on vasopressors.

Conclusions

The majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.     

High impact of depression in heart failure: early diagnosis and treatment options

Depressive syndromes in chronic heart failure (CHF) are common and are associated with a poorer prognosis, particularly with increased morbidity and mortality. CHF as a severe physical disorder may increase the risk of developing depressive syndromes or vice-versa as an interaction of possible common psycho-organic etiological aspects. Depression in CHF is associated with impaired NYHA status and daily activities, resulting in enhanced hospitalisation rates and medical costs with a great impact on long-term health. Only a fraction of comorbid patients receives antidepressants. Therefore, identification of risk factors and prevention by optimizing cardiological and psychiatric therapeutic strategies appear essential for these patients. Early diagnosis and treatment of both CHF and depression may prevent further pathophysiological effects on the heart and brain. This review gives a comprehensive overview of the occurrence, risk factors and shared pathophysiology of depression in CHF, and focuses on improving insufficient diagnosis and therapy of depression. Special attention is given on the cardiac effects of psychopharmacological and alternate non-pharmacological antidepressant therapy in CHF. Recommendations are made for treating depression in CHF patients for a better prevention of this disabling physical and psychosocial condition.     

The effect of diamide (azodicarboxylic acid-bis-dimethylamide) on sulfhydryl group content, proteins, and the location of phosphatidylethanolamine in human blood platelets

Treatment of human blood platelets with the thiol-oxidizing agent, diamide, causes rapid oxidation of glutathione and alterations in aggregation and release reaction. Moreover, cross-linking of proteins was observed. Three high molecular weight bands of 200 - 240 X 10(3) daltons and a band of 66 X 10(3) daltons were involved in this process. After reduction with dithiotreitol the normal pattern was received. In contrast to the erythrocyte, the cross-linking of platelet proteins was not accompanied by a reorientation of phosphatidylethanolamine in the membrane. Also a considerably smaller effect of diamide on platelet protein sulfhydryl group content was measured.