Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls.

BACKGROUND: Endothelial progenitor cells (EPC) are of major importance in vascular repair under healthy circumstances. Vascular injury in need of repair occurs frequently in ANCA-associated vasculitis (AAV). A specialized T cell subset enhancing EPC function and differentiation has recently been described. These angiogenic T cells (Tang) may have an important impact on the vascular repair process. Therefore, the aim of our study was to investigate EPC and Tang in AAV. METHODS: Fifty-three patients suffering from AAV and 29 healthy controls (HC) were enrolled in our study. Forty-four patients were in remission, nine patients were in active state of disease. Patients were either untreated or were under monotherapy with low-dose steroids (max. 5 mg/day) at the time of sampling. Circulating EPC and Tang were determined by flow cytometry (FACS). The functional capacity of EPC was assessed by established cell culture methods. RESULTS: Circulating EPC were significantly decreased in AAV as compared to HC. The capacity of EPC to differentiate and proliferate was differentially impaired in patients as compared to HC. The outgrowth of endothelial colony-forming cells (ECFC) was severely decreased in patients whereas colony-forming units-endothelial cell (CFU-EC) outgrowth was unaffected. ECFC and CFU-EC differentiation was strictly T cell-dependent. Patients with a relapsing disease course had an impaired ECFC outgrowth and expansion of Tang as compared to patients with a stable, nonrelapsing disease. CONCLUSIONS: The differentiation process of EPC is impaired in AAV. This may favor insufficient vascular repair promoting a relapsing disease course. Finally, these factors may explain a higher cardiovascular morbidity as has been previously documented in AAV.

Solving a cold case of haemolysis: back to the basics.

Membrane disorders comprise an important group of inherited haemolytic anaemias. Diagnostic work-up starts with examination of the blood smear, followed by osmotic gradient ektacytometry. In special cases DNA analysis is performed to confirm the diagnosis. For this purpose a next-generation sequencing-based method has been developed. The combination of these techniques established the correct diagnosis in a case of haemolytic anaemia of unknown cause.

Significance of haemodynamic variables in coronary care unit for prediction of survival after acute myocardial infarction.

In order to assess the value of haemodynamic monitoring in the coronary care unit for long term prognosis after recovery of an acute myocardial infarction, the records of two groups of consecutive patients were reviewed retrospectively. From 254 patients, 32 (13%) died in the hospital and nine patients had to be excluded from subsequent follow-up for various reasons. Four year mortality among the 213 patients who were discharged from the hospital and could be followed up was 26%. Of the haemodynamic variables measured on admission a high pulmonary capillary wedge pressure, exceeding 18 mmHg, and a low mixed venous oxygen saturation, less than 60%, were not only associated with a high hospital but also with a high four year mortality, whereas a low systolic blood pressure (less than 100 mmHg), an important prognosticator during admission to hospital, was only of minor significance thereafter. A negative value on admission of a specific index 0.24 X systolic blood pressure (mmHg) -0.217 X pulmonary capillary wedge pressure (mmHg)+0.234 X mixed venous oxygen saturation (%)-13.1 developed for the prediction of short term survival was also associated with a much higher four year mortality than a positive value. Low cardiac index on admission could be correlated with high mortality during the first two years after discharge, whereas only 9% of patients with a higher cardiac index died. Haemodynamic monitoring in the coronary care unit is thus not only relevant for the immediate prognosis, but a high mortality risk during hospital stay persists for several years after discharge.

Cardiovascular responses to increasing plasma concentrations of AQ-A 39 Cl, a new compound with negative chronotropic effects.

5,6-Dimethoxy-2-((3[(alpha-(3,4-dimethoxy) phenylethyl)-methylamino]propyl))-phthalimidine hydrochloride (AQ-A 39 Cl, in the following briefly called AQ-A 39) is a new compound with a structure similar to that of verapamil and which exhibits a specific bradycardic effect by a direct action on the sinus node. In nine anesthetized pigs the compound produced a dose-dependent decrease in heart rate up to 35%. For concentrations less than 1500 ng . ml-1, the drug exerted only minor effects on myocardial contractility (less than 5%), but for concentrations greater than 2000 ng . ml-1 negative inotropic properties became apparent and cardiac output decreased up to 25%, in spite of an increase in stroke volume. Left ventricular filling pressure and systemic vascular resistance were not affected. Myocardial O2-consumption also decreased dose-dependently up to 35%. The reduction in heart rate was not the only factor in determining the magnitude of this decrease as substantial decreases (25-30%) were also observed when, during drug administration, the heart rates were raised to 120 and 150 beats . min-1, respectively by means of coronary sinus pacing. The decrease in myocardial O2-consumption was reflected by decreases in both coronary blood flow and myocardial O2-extraction, while coronary vascular resistance did not change. The cardiovascular profile of AQ-A 39 indicated that, especially for arterial plasma concentrations lower than 1500 ng . ml-1, the drug may be useful in the treatment of tachycardias and in lowering myocardial O2-demand, without adverse effects on cardiovascular performance.

Stomal dysfunction following partial gastrectomy.

The case is reported of a man aged 57 years in whom after partial gastrectomy, gastric emptying remained impaired for a long period of time. The disorder was caused by stomal dyfunction. After 74 days' conservative therapy, mostly on an outpatient basis, passage through the stomach recurred spontaneously. Successful conservative therapy of such a long duration has not previously been reported in the literature. Protracted obstruction of the stoma after partial gastrectomy is rare. On the basis of data in the literature and of personal experience the author advocates prolonged conservation therapy, unless there exists definite proof of a mechanical obstruction.