The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease

The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.

Bovine pericardium based non-cross linked collagen matrix for successful root coverage, a clinical study in human

Introduction The aim of this study was to clinically assess the capacity of a novel bovine pericardium based, non-cross linked collagen matrix in root coverage. Methods 62 gingival recessions of Miller class I or II were treated. The matrix was adapted underneath a coronal repositioned split thickness flap. Clinical values were assessed at baseline and after six months. Results The mean recession in each patient was 2.2 mm at baseline. 6 Months after surgery 86.7% of the exposed root surfaces were covered. On average 0,3 mm of recession remained. The clinical attachment level changed from 3.5 ± 1.3 mm to 1,8 ( ± 0,7) mm during the observational time period. No statistically significant difference was found in the difference of probing depth. An increase in the width of gingiva was significant. With a baseline value of 1.5 ± 0.9 mm an improvement of 2.4 ± 0.8 mm after six month could be observed. 40 out of 62 recessions were considered a thin biotype at baseline. After 6 months all 62 sites were assessed thick. Conclusions The results demonstrate the capacity of the bovine pericardium based non-cross linked collagen matrix for successful root coverage. This material was able to enhance gingival thickness and the width of keratinized gingiva. The percentage of root coverage achieved thereby is comparable to existing techniques. This method might contribute to an increase of patient's comfort and an enhanced aesthetical outcome.

Age, sex, and performance influence the visuospatial working memory network in childhood

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.

Added value of coronary artery calcium score as an adjunct to gated SPECT for the evaluation of coronary artery disease in an intermediate-risk population

The coronary artery calcium (CAC) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease (CAD). The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population. METHODS: Seventy-seven prospectively recruited patients with intermediate risk (as determined by the Framingham Heart Study 10-y CAD risk score) and referred for coronary angiography because of suspected CAD underwent stress (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging (MPI) and CT CAC scoring within 2 wk before coronary angiography. The sensitivity and specificity of SPECT alone and of the combination of the 2 methods (SPECT plus CAC score) in demonstrating significant CAD (>/=50% stenosis on coronary angiography) were compared. RESULTS: Forty-two (55%) of the 77 patients had CAD on coronary angiography, and 35 (45%) had abnormal SPECT results. The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results (889 +/- 836 [mean +/- SD] vs. 286 +/- 335; P < 0.0001). Similarly, with rising CAC scores, a larger percentage of patients had CAD. Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT. SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76% and 91%, respectively. Combining SPECT with the CAC score (at a cutoff of 709) improved the sensitivity of SPECT (from 76% to 86%) for the detection of CAD, in association with a nonsignificant decrease in specificity (from 91% to 86%). CONCLUSION: The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results.

Cardiac image fusion from stand-alone SPECT and CT: clinical experience

Myocardial perfusion imaging with SPECT (SPECT-MPI) and 64-slice CT angiography (CTA) are both established techniques for the noninvasive evaluation of coronary artery disease (CAD). Three-dimensional (3D) SPECT/CT image fusion may offer an incremental diagnostic value by integrating both sets of information. We report our first clinical experiences with fused 3D SPECT/CT in CAD patients. METHODS: Thirty-eight consecutive patients with at least 1 perfusion defect on SPECT-MPI (1-d adenosine stress/rest SPECT with (99m)Tc-tetrofosmin) and 64-slice CTA were included. 3D volume-rendered fused SPECT/CT images were generated and compared with the findings from the side-by-side analysis with regard to coronary lesion interpretation by assigning the perfusion defects to their corresponding coronary lesion. RESULTS: The fused SPECT/CT images added information on pathophysiologic lesion severity in 27 coronary stenoses (22%) of 12 patients (29%) (P<0.001). Among 40 equivocal lesions on side-by-side analysis, the fused interpretation confirmed hemodynamic significance in 14 lesions and excluded functional relevance in 10 lesions. In 3 lesions, assignment of perfusion defect and coronary lesion appeared to be reliable on side-by-side analysis but proved to be inaccurate on fused interpretation. Added diagnostic information by SPECT/CT was more commonly found in patients with stenoses of small vessels (P=0.004) and involvement of diagonal branches (P=0.01). CONCLUSION: In addition to being intuitively convincing, 3D SPECT/CT fusion images in CAD may provide added diagnostic information on the functional relevance of coronary artery lesions.

Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT

PURPOSE: To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS: All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS: A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION: Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Experience and attitudes towards CAM--a survey of internal and psychosomatic patients in a German university hospital

Complementary and alternative medicine (CAM) is popular in Germany. In a consecutive survey the experiences with CAM and the need for a CAM consultation among inpatients of the departments of cardiology (CL), gastroenterology (GE), oncology (OL) and psychosomatics (PS) of the University Hospital Freiburg (FUH) were questionned. Exclusion criteria were inability to understand the questions or a Karnofsky Index < 30%. Four hundred thirty-five patients were included. Three hundred and fifty patients, 100 each in the departments of CL, GE and OL, and 50 in PS answered the questionnaires. Eighty-five patients (20%) refused. Among the 350 patients 26% had previously visited a CAM physician and 19% had visited a CAM therapist (Heilpraktiker). Information about CAM was obtained mainly by television, radio and family members. Frequently used therapies for the current disease were physical training (21%), diet (19%), massage (19%), vitamins/trace elements (19%), herbs (13%), acupuncture (10%) and homeopathy (7%). The highest frequency of CAM use had PS patients, followed by GE, OL and CL patients. High effectivity (> or = 70%) for the current disease, rated on a scale of 4 degrees, had for CL patients physical exercise and massage, for GE patients herbal treatment and for OL patients diet. Physical exercise, diet, massage and herbal treatment generally had better ratings than homeopathy, acupuncture and vitamins. 65% would welcome a CAM center and 53% asked for a consultation about CAM at FUH. OL and GE patients had the strongest (58%), PS patients a lower (52%) and patients with cardiovascular diseases the lowest (43%) interest in a CAM consultation. Twenty-five percent believed, that CAM can help to cope better with their disease. Predictors for a positive attitude towards CAM were young age, aversion to chemical medications (Spearman correlation r = 0.22), desire to participate in therapeutic decisions (r = 0.29), motivation to change, if recommended, the life style (r = 0.31) and desire for a holistic treatment (r = 0.37).

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function

BACKGROUND Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (i.e., 5 to 7 days) or late (i.e., 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up.

ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy

Anticancer drug therapy activates both molecular cell death and autophagy pathways. Here we show that even sublethal concentrations of DNA-damaging drugs, such as etoposide and cisplatin, induce the expression of autophagy-related protein 5 (ATG5), which is both necessary and sufficient for the subsequent induction of mitotic catastrophe. We demonstrate that ATG5 translocates to the nucleus, where it physically interacts with survivin in response to DNA-damaging agents both in vitro and in carcinoma tissues obtained from patients who had undergone radiotherapy and/or chemotherapy. As a consequence, elements of the chromosomal passenger complex are displaced during mitosis, resulting in chromosome misalignment and segregation defects. Pharmacological inhibition of autophagy does not prevent ATG5-dependent mitotic catastrophe, but shifts the balance to an early caspase-dependent cell death. Our data suggest a dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus.