Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation.

AIMS: We aimed to clarify whether determination of levels of soluble CD40 ligand (sCD40L) could predict subsequent thrombo-embolic events in patients with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Forty-four consecutive outpatients (mean age: 58 +/- 6 years, 20 male) with chronic NVAF who were not receiving aspirin and had no thrombus or spontaneous echo contrast (SEC) on left atrium (LA) or left atrial appendage (LAA) were included in the study. The patients had no history of an embolic event and were followed up 24 +/- 2 months for thrombo-embolic events. sCD40L was determined at the enrollment. All patients were evaluated by means of SEC and thrombus formation by transoesophageal echocardiography at the end of follow-up period. Twelve (27%) patients had SEC and 2 (5%) patients had thrombus on LAA. Ischaemic stroke occurred in 2 (4.5%) patients and transient ischaemic attack developed in 4 (9%) patients during follow-up. sCD40L was significantly higher in patients with LASEC (0.41 +/- 0.05 vs. 0.16 +/- 0.04 ng/mL, P = 0.02) and embolic events (0.74 +/- 0.05 vs. 0.19 +/- 0.03 ng/mL, P = 0.001) than in those without. sCD40L levels were significantly related to the LASEC grade (R = 0.377, P = 0.02). In multivariable analysis, while independent variables for SEC or thrombus formation were LA diameter, sCD40L levels, and the duration of AF, independent variables for cerebrovascular events were the existence of SEC or thrombus formation on LAA, and sCD40L level. CONCLUSION: Plasma sCD40L may prospectively predict stroke in AF. sCD40L may provide useful marker to identify patients at high thrombo-embolic risk with NVAF.     

Unilateral diaphragmatic paralysis and segmental motor paresis following herpes zoster

We report the case of a 73-year-old woman who complained of acute onset of pain and weakness of her left shoulder and proximal arm muscles 3 weeks after a diagnosis of herpes zoster. Electromyography revealed involvement of the C5-6 myotomes and the upper trunk of the brachial plexus. Chest X-ray and electromyographic studies documented paralysis of the left diaphragm. One year after onset, muscle strength returned to normal, but radiographic and electrophysiologic findings of diaphragm paralysis were unchanged.     

Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. alpha-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.     

Antistaphylococcal activity of DX-619, a new des-F(6)-quinolone, compared to those of other agents

The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC(50)s/MIC(90)s (microg/ml) against 131 Staphylococcus aureus strains (32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 microg/ml and sitafloxacin at 1.0 microg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 microg/ml after <50 days of selection compared to 16 to >32 microg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains.     

ST-segment elevation in lead augmented vector right may also be caused by diffuse left main coronary artery vasospasm without fixed stenosis

ST-segment deviation in lead augmented vector right (aVR) is useful for evaluating patients with acute coronary syndrome (ACS). The ST-segment elevation in this aVR in the patient with clinically suspected acute coronary syndrome suggests a strong possibility of left main coronary artery (LMCA) obstruction due to fixed stenosis. In this article, we report the first case, to our knowledge, of ST-segment elevation in lead aVR due to diffuse LMCA spasm.     

Levosimendan versus dobutamine in heart failure patients treated chronically with carvedilol

Introduction : Although beta‐blockers are highly effective in the treatment of heart failure (HF), many patients with HF receiving a beta‐blocker continue to become decompensated and require hospitalization for worsening HF. Levosimendan and dobutamine are used to manage decompensated HF, but their comparative effects on left ventricular (LV) function in patients prescribed beta‐blockers are unknown. Aims : The aim of this study was to compare the effects of dobutamine and levosimendan on LV systolic and diastolic functions in chronic HF patients treated chronically with carvedilol. Forty patients with chronic HF who had NYHA class III to IV symptoms, a LV ejection fraction (LVEF) <40%, and ongoing treatment with carvedilol were enrolled in this randomized (1:1), dobutamine controlled, open‐label study. Before and 24 h after treatment, LVEF, mitral inflow peak E and A wave velocity, E/A ratio, the deceleration time of the E wave (DT), isovolumic relaxation time (IVRT), peak systolic (Sm) and early diastolic (Em) mitral annular velocity, and systolic pulmonary artery pressure (SPAP) were measured by echocardiography. Results : Levosimendan produced a statistically significant increase in LVEF (28 ± 5% vs. 33 ± 3%), Sm (6.5 ± 1.2 cm/s vs. 7.4 ± 0.9 cm/s), DT (120 ± 10 ms vs. 140 ± 15 ms), and Em (7.5 ± 0.4 cm/s vs. 8.1 ± 0.5 cm/s) and significant decrease in E/A ratio (2.1 ± 0.3 vs. 1.7 ± 0.4) and SPAP (55 ± 5 mmHg vs. 40 ± 7 mmHg). No significant change occurred in LV systolic and diastolic function parameters, or SPAP with dobutamine treatment. Levosimendan did not significantly alter the heart rate (72 ± 4 bpm vs. 70 ± 3 bpm), systolic (105 ± 5 mmHg vs. 102 ± 4 mmHg), or diastolic blood pressure (85 ± 5 mmHg vs. 83 ± 5 mmHg) whereas with dobutamine treatment, all these parameters significantly increased. Conclusions : Dobutamine and levosimendan have different effects on LV functions in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated HF receiving long‐term carvedilol.     

Effect of Non‐Surgical Periodontal Treatment on Gingival Crevicular Fluid and Serum Endocan,Vascular Endothelial Growth Factor‐A,and Tumor Necrosis Factor‐Alpha Levels

Background: Periodontitis is a chronic inflammatory disease that occurs due to the interaction between pathogenic microorganisms and host defenses. Endocan is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Aims of the study are to determine serum and gingival crevicular fluid (GCF) endocan levels in the pathogenesis of periodontal diseases, supported with vascular endothelial growth factor (VEGF‐A) and tumor necrosis factor (TNF)‐alpha levels. This study additionally aims to evaluate correlation between GCF endocan levels, VEGF‐A, and TNF‐α levels with periodontal probing depth (PD). Methods: The study consists of two groups: group 1 (n = 20), healthy individuals; group 2 (n = 20), individuals with generalized chronic periodontitis (CP). Clinical measurements were recorded; GCF and serum samples were obtained from each participant before and 6 weeks after therapy. Levels of biomarkers were measured by enzyme‐linked immunosorbent assay. Intergroup comparisons of biochemical and clinical parameters were analyzed by Kruskal–Wallis/Bonferroni‐adjusted Mann–Whitney U test using statistical software. Results: Serum and GCF endocan, VEGF‐A, and TNF‐α levels were significantly higher in patients with CP than in healthy individuals (P <0.001) and decreased after treatment (P <0.03). A significant correlation was observed between GCF TNF‐α and PD (4 mm ≤ PD ≤5 mm and PD ≥6 mm). A significant relationship was found among GCF endocan and TNF‐α, VEGF‐A, CAL, and GI for all groups (P <0.05). Conclusions: Endocan and TNF‐α levels, both in GCF and serum, increased from health to periodontitis and decreased with non‐surgical periodontal treatment. Within the limits of the study, endocan may be considered as a potential inflammatory marker for periodontal disease.