Expression of anaphylatoxin receptors on platelets in patients with coronary heart disease.

OBJECTIVE: Inhibition of components of the complement system or of its receptors has been postulated as a concept for primary and secondary prevention in atherosclerosis and was applied in clinical trials. Although the anaphylatoxin-receptors C3aR and C5aR are commonly associated with inflammatory cells, in vitro studies suggested their expression also on platelets. METHODS AND RESULTS: Expression levels of C3aR and C5aR were measured by flow cytometry in a collective of 302 patients with documented coronary artery disease (CAD) including patients with stable CAD (n = 152), unstable angina (n = 54), acute myocardial infarction (AMI; Non-ST elevation myocardial infarction, n = 70, ST elevation MI, n = 26) or healthy controls (n = 21). Patients with stable CAD, unstable angina or AMI had significantly higher expression of C5aR on platelets in comparison to healthy controls (MFI 14.68 (5.2), 14.56 (5.18) and 13.34 (4.52) versus 10.68 (3.1)); p < 0.001). In contrast, the expression of C3aR on platelets was significantly enhanced in patients with stable and unstable CAD but not in patients with AMI compared to controls. While there was a strong correlation between the soluble ligands of these receptors C3a and C5a, we observed only a weak correlation with their receptors on platelets. Similarly, agonist induced aggregation (MEA, ADP, and TRAP) showed only a weak correlation with the expression level of anaphylatoxin - receptors on platelets. Of note, the expression of both anaphylatoxin-receptors on platelets strongly correlated with platelet activation as assessed with the surface activation marker P-selectin (r = 0.47, p > 0.001 for C3aR, r = 0.76 for C5aR, p < 0.001). Likewise, we observed a positive correlation of C3aR with other molecules associated with platelet activation such as SDF-1. CONCLUSION: In summary, we observed a positive correlation between the expression of anaphylatoxin-receptors C3aR and C5aR with platelet activation in patients with CAD. Further investigations are needed to study the clinical and mechanistic relevance of these findings.

Combination of high on-treatment platelet aggregation and low deaggregation better predicts long-term cardiovascular events in PCI patients under dual antiplatelet therapy.

High on-treatment platelet reactivity is associated with short-term major cardiovascular (CV) events in patients undergoing percutaneous coronary intervention (PCI). Maximum and final aggregation assessed by light transmission aggregometry (LTA) have both been used to predict short-term outcome after PCI, however their long-term prognostic impact remains controversial. There is currently no information regarding the prognostic role of deaggregation and its added value in combination with established aggregation parameters. About 1279 patients with symptomatic coronary artery disease (CAD) undergoing PCI were enrolled in this monocentric study. On-treatment platelet aggregation under clopidogrel maintenance therapy, as well as deaggregation was determined by maximum and final aggregation (5 min after adding of the agonist). Deaggregation was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints were the composite of myocardial infarction, stroke, and CV death or stent thrombosis according to the ARC criteria. Low deaggregation, defined as values in the lowest tertile (<1.5), was more frequent in patients with acute coronary syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS: 29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet reactivity, defined by the upper tertile of Aggmax and low deaggregation, was associated with significantly increased risk for combined long-term CV events. The combination of low deaggregation and high on-treatment platelet reactivity is associated with higher risk for recurrent events in patients with CAD undergoing PCI. Thus, deaggregation might be a more sensitive parameter providing added value in terms of risk prediction for long-term recurrent CV events in relation with established aggregation parameters.

The distance from the skin to the epidural and subarachnoid spaces in parturients scheduled for caesarean section.

BACKGROUND: The purpose of this study was to measure the skin to epidural space distance (SED), the skin to subarachnoid space distance (SSD) and the epidural to subarachnoid space distance (ESD) at the L3-4 interspace in parturients scheduled for caesarean section (CS) and to investigate whether any correlations exist between these distances and various physical and anthropometric parameters. METHODS: This study consisted of 332 parturients scheduled for CS. The epidural space was identified by noting the loss of resistance to air at the L3-4 intervertebral space with a Tuohy needle, thus permitting measurement of the SED. The spinal needle was introduced through the Tuohy needle and, after identification of the subarachnoid space, was locked in the epidural needle. The distance between the tip of the Tuohy needle and tip of spinal needle (ESD) was recorded. This number was added to the SED to obtain the SSD value. RESULTS: Mean values ± standard deviations for SED, SSD and ESD were 5.6 ± 1.6 cm, 6.5 ± 1.2 cm and 0.9 ± 0.5 cm, respectively. Statistically significant correlations were observed between SED, SSD and ESD with body mass index and body weight of the parturients, as well as between the SED and the parturient's height. Furthermore, a significant negative correlation was observed between the ESD and gestational age. Finally, a significant correlation existed between the SSD and ESD. CONCLUSION: Measurements of SED, SSD and ESD in parturients and the correlations between these distances to various physical and anthropometric parameters may be of potential value for combined spinal-epidural anesthesia (CSEA) in parturients scheduled for CS.

Treatment of neonatal diabetes insipidus with desmopressin.

We report a case of neurogenic diabetes insipidus in a premature infant. It was treated with desmopressin, which appears to be the drug of choice for the treatment of this disease in early infancy.