Microvascular retinal changes in patients presenting with acute coronary syndromes.

BACKGROUND: Retinal microvascular changes predict cardiovascular morbidity and mortality independent of classical risk factors. However, it is unclear which retinal changes characterize patients with established coronary artery disease (CAD), and in particular, with acute coronary syndromes (ACS). The aim of the present preliminary study was to assess retinopathy in these patients. METHODS: 43 consecutive patients with ACS and 19 consecutive patients with stable CAD were investigated. Among the patient group with ACS, 20 patients presented with ST-Elevation Myocardial Infarction (STEMI) and 23 patients presented with Non-STEMI (NSTEMI). Standardized protocols were used and retinal fundus photography was taken within 48 h post-coronary angiography to assess retinopathy and general arteriolar narrowing as arterio-venous ratio (AVR). Clinical and laboratory cardiovascular risk factors were recorded. RESULTS: Despite comparable age and comparable frequency of diabetes and hypertension, patients with ACS had a much higher likelihood for retinal microaneurysms and dot bleedings than patients with stable CAD (17 (40%) vs. 1 (5%) patients, OR 11.77; 95%CI 1.43-96.59; p=0.006). Performing multivariate analysis, this association remains significant (OR 20.5, 95%CI 1.6-255, p=0.019). CAD patients presented more often with focal signs of arteriovenous nicking / focal vasoconstriction (10 (53%) vs. 9 (21%) patients, OR 4.2; 95%CI 1.31-13.4; p=0.018), however after multivariate analysis this association lost significance. The AVR was comparably low in both groups. CONCLUSION: Patients with ACS present more often with dot bleedings and microaneurysms. These findings provide preliminary evidence that retinal fundus examination may be useful to contribute to the risk profile of patients, enabling a more intensive survey and care.

Differentiation of monocyte-derived dendritic cells under the influence of platelets.

BACKGROUND: Monocytapheresis has been established to collect a sufficient number of monocytes (MO) for differentiation to dendritic cells (DC) as a cancer vaccine. Platelets (Plt) are invariably found as a contaminant in the final monocytapheresis product. The aim of this study was to investigate DC differentiation under the influence of Plt with regard to their function and phenotype. METHODS: MO were isolated and co-cultured with autologous Plt at different MO:Plt ratios (1:1.7, 1:5, 1:15, 1:45 and 1:135) in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-12p70 release after ligation of CD40L was determined in the supernatant by enzyme-linked immunosorbent assay (ELISA). For T-cell stimulation, tetanus toxoid was added to immature DC and maturation was induced by adding cytokines (IL-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E(2)). Stimulated T cells were analyzed for activation and proliferation as well as for intracellular cytokines by flow cytometry. RESULTS: All DC cultures were strongly positive for CD83. At a contaminating concentration of 5 Plt/MO, matured DC showed the highest expression of HLA-DR, CD80 and CD86, inducing a strong T-cell proliferation with high production of IL-4 and interferon-gamma. The highest level of IL-12p70 production was observed by the same DC group. DISCUSSION: Plt did not negatively influence DC maturation but enhanced the expression of co-stimulatory molecules and the release of IL-12. Functionally this was reflected by a strong T-cell response that involved T-helper 1 (Th1)- as well as Th2-biased T cells. Our findings show that controlling the Plt concentration may provide important advantages for the generation of DC for use in immunotherapy.

Gadolinium-based coronary angiography in patients with contraindication for iodinated x-ray contrast medium: a word of caution.

BACKGROUND: In coronary angiography, the use of contrast agents containing iodine still defines the gold standard. In patients with contraindications for iodine exposition, gadolinium has been considered to be a safe alternative to standard iodinated contrast medium for coronary angiography. The aim of the present study was to assess the safety and technical quality of gadolinium-based coronary angiography. METHODS: Nineteen consecutive patients with contraindication to iodinated contrast medium underwent gadolinium-based coronary angiography. Contraindications included previous anaphylactic shock or severe allergic reaction to iodinated contrast medium (n = 13) or thyrotoxicosis (n = 6). Gadolinium was diluted 1:1 with sodium chloride before application. Patients were clinically observed for potential side effects, and renal function was assessed by determination of creatinine values and calculation of creatinine clearance in pre- and postprocedural blood samples. Image quality was evaluated by two independent observers, and classified into three different categories (grade 1, high diagnostic quality; grade 2, moderate diagnostic quality; and grade 3, poor quality). RESULTS: During angiography, a mean of 32.6 +/- 10.9 mL (range 10-45 mL) gadolinium was used. No patient developed a significant impairment of renal function within 24 hours after the examination (mean creatinine value preprocedural: 1.12 +/- 0.15 mg/dL, postprocedural: 6 hours 1.15 +/- 0.18 mg/dL, 24 hours 1.13 +/- 0.16 mg/dL) (baseline vs. 6 hours P = 0.23, baseline vs. 24 hours P = 0.66, 6 hours vs. 24 hours P = 0.12) (mean creatinine clearance preprocedural: 73.8 +/- 18 mg/dL, postprocedural: 6 hours 71.7 +/- 16.8 mg/dL, 24 hours 73.2 +/- 17.8 mg/dL) (baseline vs. 6 hours P = 0.2, baseline vs. 24 hours P = 0.71, 6 hours vs. 24 hours P = 0.21). Four patients (21%) suffered severe complications due to gadolinium application, such as malignant cardiac arrhythmias (n = 3) and hemodynamic decompensation (n = 1). Image quality was generally reduced in comparison to iodine contrast coronary angiography, but was adequate for diagnostic purposes (13 patients [68.4%] had reasonably good picture contrast [grade 2.1 +/- 0.3]; in 6 patients [31.6%], image quality was satisfactory [grade 2.6 +/- 0.13]). Opacification of distal vessels as compared to proximal segments was remarkably reduced. CONCLUSIONS: Gadolinium-based coronary angiography is a potential alternative technique in patients with allergy to iodinated contrast medium or thyrotoxicosis with reduced, but acceptable, image quality for diagnostic purposes. Nevertheless, possible life-threatening side effects and complications have to be considered.