Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Molecular genetic studies on vascular tumors are rare. Recently, possible involvement of MYC and KDR has been documented in a subset of angiosarcomas of soft tissue. We performed a cytogenetic analysis of primary angiosarcomas of bone (n = 13) and soft tissue (n = 5) using high density array‐comparative genomic hybridization (array‐CGH). Regions of interest were validated by fluorescence in situ hybridization (FISH). Antibodies for candidate genes (SKI, MYC, KDR, and MAPK9) were selected and immunohistochemistry was performed. Six angiosarcomas of bone and four angiosarcomas of soft tissue showed chromosomal losses, gains, and high level amplifications. Cluster analysis identified two groups: a group with a complex genetic profile and a group with only few genetic aberrations. Five regions of interest were selected, which were located at chromosome bands 1p36.23, 2q32‐34, 5q35, 8q24, and 17q21.32‐24.2. Interphase FISH confirmed the high‐level amplifications. Immunohistochemical analysis showed high expression of MYC (16/60), MAPK9 (63/69), and SKI (52/62). There were no differences between the two groups with regards to location, immunohistochemical expression nor survival. In summary, we identified two subgroups of angiosarcoma: those with few or no gross aberrations and those which show numerous genetic aberrations consisting of chromosomal losses, gains and high level amplifications or complex aberrations. The most common finding was amplification of 2q and 17q in both angiosarcoma of bone and soft tissue, suggesting overlap in tumorigenesis irrespective of their location. We show MYC amplification in primary angiosarcoma indicating this is not entirely specific for radiation‐induced angiosarcoma. © 2014 Wiley Periodicals, Inc.     

Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure

To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound‐induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent–toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short‐ (1 day) and long‐term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l^?1) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long‐term exposure set‐up, a concentration of 500 µl l^?1 DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l^?1 DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l^?1 DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l^?1 in this organism. In the second part of our study, we propose a statistical approach to account for solvent–toxicant interactions and discuss full‐scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea. Copyright © 2014 John Wiley & Sons, Ltd.     

The effects of a hearing education program on recreational noise exposure,attitudes and beliefs toward noise,hearing loss,and hearing protector devices in young adults

Excessive recreational noise exposure in young adults might result in noise-induced hearing loss (NIHL) and tinnitus. Inducing behavioral change in young adults is one of the aims of a hearing conservation program (HCP). The goal of the current study was to evaluate the effect of a hearing education program after 6 months in young adults in relation to knowledge regarding their individual hearing status. The results of a questionnaire regarding the weekly equivalent recreational noise exposure, attitudes and beliefs toward noise, and hearing loss and hearing protector devices (HPDs) were compared between both sessions. Seventy-eight young adults completed the questionnaire concerning recreational noise exposure, youth attitude to noise scale (YANS), and beliefs about hearing protection and hearing loss (BAHPHL). Their hearing status was evaluated based on admittance measures, audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion-product otoacoustic emissions (DPOAEs). The main analysis consisted of a mixed model analysis of variance with dependent variables of either the noise exposure or the scores on (subscales of) YANS and BAHPHL. The independent variables were hearing status and session one versus session two. There was a significant decrease in recreational noise exposure and several (sub) scales of YANS and BAHPHL between both the sessions. This behavioral change resulted in a more frequent use of HPDs in 12% of the participants. However, the behavioral change was not completely related to the knowledge of young adults’ individual hearing status. To prevent hearing damage in young people, investing in HCPs is necessary, apart from regulating sound levels and its compliance at various leisure-time activities. Also, the long-term effect of HCPs and their most cost-efficient repetition rates should be further investigated.     

Medical Treatment in Coronary Patients: Is there Still a Gender Gap? Results from European Society of Cardiology EUROASPIRE V Registry

Cardiovascular Drugs and Therapy - This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). Analyses were based on the ESC...     

State-of-the art review: Noncompaction cardiomyopathy in pediatric patients

Heart Failure Reviews - Noncompaction cardiomyopathy (NCCM) is a disease characterized by hypertrabeculation, commonly hypothesized due to an arrest in compaction during fetal development. In 2006,...     

The value of serologic markers in indeterminate colitis: a prospective follow-up study

BACKGROUND & AIMS: In the absence of pathognomonic markers for Crohn's disease (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease depends on a compendium of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity to the individual disorders. In 10% of cases of colitis, no differentiation can be made between CD and UC; these patients are diagnosed with indeterminate colitis (IC). We evaluated the value of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing IC. METHODS: Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up prospectively. RESULTS: A definitive diagnosis has been reached for 31 of 97 patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10 patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS: Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity.     

Diagnostic characteristics of a gelatin based Waaler-Rose assay (Serodia-RA) for the detection of rheumatoid factor

OBJECTIVE: To evaluate the diagnostic usefulness of a gelatin based Waaler Rose assay (Serodia-RA) for the detection of rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: RF was measured by Serodia-RA and rate nephelometry in 90 patients with RA according to the revised ACR criteria and 102 patients with rheumatological diseases other than RA. Sensitivity, specificity, accuracy, likelihood ratios, and area under the curve using receiver operating characteristics (ROC) analysis were determined for both tests. Agreement between assays was assessed on 1657 consecutive samples. RESULTS: At equal specificity, Serodia-RA tended to be more sensitive than rate nephelometry (0.66 v 0.58; p = 0.04). ROC plots showed an area under the curve of 0.843 for Serodia-RA and 0.784 for nephelometry, providing further evidence that Serodia-RA was slightly better at differentiating between RA and non-RA arthropathy. Good agreement was found between both assays. CONCLUSION: Serodia-RA is slightly more accurate than rate nephelometry for the detection of RF in RA, and a combination of both assays only marginally improves the diagnostic usefulness of RF detection. Use of two tests for detection of RF is not recommended. One test for detection of RF together with a more specific test, such as antibodies to cyclic citrullinated peptide, is suggested.     

Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis

OBJECTIVE: To study prospectively the daily practice effectiveness of a step-down early rheumatoid arthritis (RA) treatment strategy. METHODS: Patients with severe RA and no contra-indications were proposed step-down therapy, the others step-up. Step-down patients received a modified combination therapy in early RA (COBRA) regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly, combined with step-down oral prednisolone (start 60 mg daily, fast tapering to 7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were randomized to maintenance therapy with either SPS or MTX if disease activity score-28 (DAS28) was acceptably low. The step-up group started disease-modifying anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted at follow-up, based on DAS28. DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use were registered 4-monthly for 2 yrs. RESULTS: Nineteen patients received step-down and 52 step-up treatment. More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up, whereas the number of adverse events was comparable. MTX proved to be the most effective maintenance therapy after step-down. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group. CONCLUSIONS: In daily practice, a step-down treatment strategy for early RA is more effective than a step-up approach.     

Changes in mortality of acute myocardial infarction as a function of a changing treatment during the last two decades

Forty years ago, after the establishment of coronary care units, a significant decrease in mortality of acute myocardial infarction was noted. Twenty years ago, the break-through of thrombolysis realized once again a significant decrease in mortality. In this study we compare, in a rather small community hospital, the mortality and safety of thrombolytic therapy in acute myocardial infarction with a more conventional, conservative medical therapy. We examined all cases of acute myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and mortality rate after a six month period. To be included in the study, acute myocardial infarction had to fulfill particular inclusion criteria. A total of 1863 cases of acute myocardial infarction were included. The mortality rate of patients with acute myocardial infarction treated with thrombolytic agents was strikingly lower and statistically very significantly different (p < 0.001) in comparison with the mortality rate of patients treated with heparin or coumarine derivatives. The mortality rate dropped from 10.57% in the coumarine group and from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the anistreplase group and 4.00% in the streptokinase subgroup. The complications directly connected to the treatment did not seem to be different between the five groups, and they were also not more frequent by using thrombolytic agents. In the last 20 years, better preventive measures (life habits, diet, medication) and trials to better control the risk factors have not influenced greatly the average amount of cholesterol in patients with an acute myocardial infarction. Also the percentage of patients with high blood pressure has hardly decreased over the last 20 years. The mortality associated with acute myocardial infarction has decreased significantly with the use of thrombolytics. In most cases, thrombolytics are administered routinely and safely. In this way, they are the first choice therapy for myocardial infarction in smaller hospitals. To obtain excellent coronary patency, thrombolytic agents with a long half-life and with PAI-1 resistance are required in the future. The current measures and medical therapies seem to be insufficient to control the risk factors for coronary atherosclerosis.