The Number of Endothelial Progenitor Cell Colonies in the Blood Is Increased in Patients With Angiographically Significant Coronary Artery Disease

ObjectivesThe objective of this study was to determine whether the number of endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) in peripheral blood was associated with the presence and severity of coronary artery disease (CAD) in patients undergoing coronary angiography.BackgroundPrevious studies have suggested an inverse relationship between levels of circulating EPCs/CACs and the presence of CAD or cardiovascular risk factors, whereas other studies have observed increased numbers of EPCs in the setting of acute ischemia. However, the criteria used to identify specific angiogenic cell subpopulations and methods of evaluating CAD varied in these studies. In the present study, we used rigorous criteria to identify EPCs and CACs in the blood of patients undergoing coronary angiography.MethodsThe number of EPCs and CACs were measured in the blood of 48 patients undergoing coronary angiography. Patients with acute coronary syndromes were excluded.ResultsCompared with patients without angiographically significant CAD, the number of EPCs was increased (1.11 ± 2.50 vs. 4.01 ± 3.70 colonies/well, p = 0.004) and the number of CACs trended higher (175 ± 137 vs. 250 ± 160 cells per mm2, p = 0.09) among patients with significant CAD. The highest levels of EPCs were isolated from patients subsequently selected for revascularization (5.03 ± 4.10 colonies/well).ConclusionsIn patients referred for coronary angiography, higher numbers of EPCs, and a trend toward higher numbers of CACs, were associated with the presence of significant CAD, and EPC number correlated with maximum angiographic stenosis severity. Endothelial progenitor cell levels were highest in patients with CAD selected for revascularization

Anatomical adjustments of the tree hydraulic pathway decrease canopy conductance under long-term elevated CO2_2

The cause of reduced leaf-level transpiration under elevated CO$_2$ remains largely elusive. Here, we assessed stomatal, hydraulic, and morphological adjustments in a long-term experiment on Aleppo pine (Pinus halepensis) seedlings germinated and grown for 22–40 months under elevated (eCO$_2$; c. 860 ppm) or ambient (aCO$_2$; c. 410 ppm) CO$_2$. We assessed if eCO$_2$-triggered reductions in canopy conductance (g$_c$) alter the response to soil or atmospheric drought and are reversible or lasting due to anatomical adjustments by exposing eCO$_2$ seedlings to decreasing [CO$_2$]. To quantify underlying mechanisms, we analyzed leaf abscisic acid (ABA) level, stomatal and leaf morphology, xylem structure, hydraulic efficiency, and hydraulic safety. Effects of eCO$_2$ manifested in a strong reduction in leaf-level g$_c$ (−55%) not caused by ABA and not reversible under low CO$_2$ (c. 200 ppm). Stomatal development and size were unchanged, while stomatal density increased (+18%). An increased vein-to-epidermis distance (+65%) suggested a larger leaf resistance to water flow. This was supported by anatomical adjustments of branch xylem having smaller conduits (−8%) and lower conduit lumen fraction (−11%), which resulted in a lower specific conductivity (−19%) and leaf-specific conductivity (−34%). These adaptations to CO$_2$ did not change stomatal sensitivity to soil or atmospheric drought, consistent with similar xylem safety thresholds. In summary, we found reductions of g$_c$ under elevated CO$_2$ to be reflected in anatomical adjustments and decreases in hydraulic conductivity. As these water savings were largely annulled by increases in leaf biomass, we do not expect alleviation of drought stress in a high CO$_2$ atmosphere

In vivo T1ρ and T2 mapping of articular cartilage in osteoarthritis of the knee using 3T MRI

SummaryObjectiveEvaluation and treatment of patients with early stages of osteoarthritis (OA) is dependent upon an accurate assessment of the cartilage lesions. However, standard cartilage dedicated magnetic resonance (MR) techniques are inconclusive in quantifying early degenerative changes. The objective of this study was to determine the ability of MR T1rho (T1ρ) and T2 mapping to detect cartilage matrix degeneration between normal and early OA patients.MethodSixteen healthy volunteers (mean age 41.3) without clinical or radiological evidence of OA and 10 patients (mean age 55.9) with OA were scanned using a 3Tesla (3T) MR scanner. Cartilage volume and thickness, and T1ρ and T2 values were compared between normal and OA patients. The relationship between T1ρ and T2 values, and Kellgren–Lawrence scores based on plain radiographs and the cartilage lesion grading based on MR images were studied.ResultsThe average T1ρ and T2 values were significantly increased in OA patients compared with controls (52.04±2.97ms vs 45.53±3.28ms with P=0.0002 for T1ρ, and 39.63±2.69ms vs 34.74±2.48ms with P=0.001 for T2). Increased T1ρ and T2 values were correlated with increased severity in radiographic and MR grading of OA. T1ρ has a larger range and higher effect size than T2, 3.7 vs 3.0.ConclusionOur results suggest that both in vivo T1ρ and T2 relaxation times increase with the degree of cartilage degeneration. T1ρ relaxation time may be a more sensitive indicator for early cartilage degeneration than T2. The ability to detect early cartilage degeneration prior to morphologic changes may allow us to critically monitor the course of OA and injury progression, and to evaluate the success of treatment to patients with early stages of OA

Ectopic ureter associated with uterine didelphys and obstructed hemivagina: preoperative diagnosis by MRI

Uterine didelphys with obstructed hemivagina and ipsilateral renal anomalies is a rare congenital malformation of the female urogenital tract. While the urinary anomalies almost always involve renal agenesis, we report a rare case of a 17-year-old girl with the malformation associated with ectopic ureteral insertion into the obstructed hemivagina, which was diagnosed preoperatively by MR imaging. To the best of our knowledge, preoperative MR imaging diagnosis of the ectopic ureter associated with this syndrome has not been previously reported. Accurate preoperative diagnosis of ectopic ureteral insertion associated with this syndrome is important for surgical planning

Comparative study of imaging at 3.0 T versus 1.5 T of the knee

The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student’s t tests with a significance threshold of p < 0.05. Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p < 0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p < 0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Assessment of cartilage-dedicated sequences at ultra-high-field MRI: comparison of imaging performance and diagnostic confidence between 3.0 and 7.0 T with respect to osteoarthritis-induced changes at the knee joint

The objectives of the study were to optimize three cartilage-dedicated sequences for in vivo knee imaging at 7.0 T ultra-high-field (UHF) magnetic resonance imaging (MRI) and to compare imaging performance and diagnostic confidence concerning osteoarthritis (OA)-induced changes at 7.0 and 3.0 T MRI. Optimized MRI sequences for cartilage imaging at 3.0 T were tailored for 7.0 T: an intermediate-weighted fast spin-echo (IM-w FSE), a fast imaging employing steady-state acquisition (FIESTA) and a T1-weighted 3D high-spatial-resolution volumetric fat-suppressed spoiled gradient-echo (SPGR) sequence. Three healthy subjects and seven patients with mild OA were examined. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diagnostic confidence in assessing cartilage abnormalities, and image quality were determined. Abnormalities were assessed with the whole organ magnetic resonance imaging score (WORMS). Focal cartilage lesions and bone marrow edema pattern (BMEP) were also quantified. At 7.0 T, SNR was increased (p < 0.05) for all sequences. For the IM-w FSE sequence, limitations with the specific absorption rate (SAR) required modifications of the scan parameters yielding an incomplete coverage of the knee joint, extensive artifacts, and a less effective fat saturation. CNR and image quality were increased (p < 0.05) for SPGR and FIESTA and decreased for IM-w FSE. Diagnostic confidence for cartilage lesions was highest (p < 0.05) for FIESTA at 7.0 T. Evaluation of BMEP was decreased (p < 0.05) at 7.0 T due to limited performance of IM-w FSE. Gradient echo-based pulse sequences like SPGR and FIESTA are well suited for imaging at UHF which may improve early detection of cartilage lesions. However, UHF IM-w FSE sequences are less feasible for clinical use

Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair

Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS

BackgroundUpon treatment with biopharmaceuticals, the immune system may produce anti-drug antibodies (ADA) that inhibit the therapy. Up to 40% of multiple sclerosis patients treated with interferon beta (IFN beta) develop ADA, for which a genetic predisposition exists. Here, we present a genome-wide association study on ADA and predict the occurrence of antibodies in multiple sclerosis patients treated with different interferon beta preparations.MethodsWe analyzed a large sample of 2757 genotyped and imputed patients from two cohorts (Sweden and Germany), split between a discovery and a replication dataset. Binding ADA (bADA) levels were measured by capture-ELISA, neutralizing ADA (nADA) titers using a bioassay. Genome-wide association analyses were conducted stratified by cohort and treatment preparation, followed by fixed-effects meta-analysis.ResultsBinding ADA levels and nADA titers were correlated and showed a significant heritability (47% and 50%, respectively). The risk factors differed strongly by treatment preparation: The top-associated and replicated variants for nADA presence were the HLA-associated variants rs77278603 in IFN beta -1a s.c.- (odds ratio (OR)=3.55 (95% confidence interval=2.81-4.48), p=2.1x10(-26)) and rs28366299 in IFN beta -1b s.c.-treated patients (OR=3.56 (2.69-4.72), p=6.6x10(-19)). The rs77278603-correlated HLA haplotype DR15-DQ6 conferred risk specifically for IFN beta -1a s.c. (OR=2.88 (2.29-3.61), p=7.4x10(-20)) while DR3-DQ2 was protective (OR=0.37 (0.27-0.52), p=3.7x10(-09)). The haplotype DR4-DQ3 was the major risk haplotype for IFN beta -1b s.c. (OR=7.35 (4.33-12.47), p=1.5x10(-13)). These haplotypes exhibit large population-specific frequency differences. The best prediction models were achieved for ADA in IFN beta -1a s.c.-treated patients. Here, the prediction in the Swedish cohort showed AUC=0.91 (0.85-0.95), sensitivity=0.78, and specificity=0.90;patients with the top 30% of genetic risk had, compared to patients in the bottom 30%, an OR =73.9 (11.8-463.6, p=4.4x10(-6)) of developing nADA. In the German cohort, the AUC of the same model was 0.83 (0.71-0.92), sensitivity=0.80, specificity=0.76, with an OR=13.8 (3.0-63.3, p=7.5x10(-4)).ConclusionsWe identified several HLA-associated genetic risk factors for ADA against interferon beta, which were specific for treatment preparations and population backgrounds. Genetic prediction models could robustly identify patients at risk for developing ADA and might be used for personalized therapy recommendations and stratified ADA screening in clinical practice. These analyses serve as a roadmap for genetic characterizations of ADA against other biopharmaceutical compounds