Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.     

Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing’s sarcoma A673-xenograft growth and normalize tumor vascular architecture

Increasing experimental evidence suggests that IGF-1 may modulate tumor angiogenesis via activation of the expression of VEGF in Ewing sarcomas and rhabdomyosarcomas. This study investigates the effects of the PEGylated Adnectins? CT-322, a VEGFR2-inhibitor and AT580Peg40, an IGF-1R inhibitor, as monotherapy and in combination in a murine A673 xenograft tumor model. The combination of Adnectins CT-322 and AT580Peg40 revealed a 83?% reduction in tumor growth, a nearly 5 times lower vessel density, less necrotic areas and less appearance of intussusceptive angiogenesis. Monotherapy with IGF-1R or CT-322 revealed equally a significant inhibition of tumor and vessel growth. Combinatory inhibition of IGF-1R and VEGFR2 shows a downregulation of IGF-binding protein 2 and a compensatory upregulation of VEGF levels. Immunohistological analysis showed remodeling vascular effects of CT-322-treatment or combination therapy. The vascular architecture in Adnectin-treated tumors was characterized by a strong normalization of vasculature. 3D-evaluation in microvascular corrosion casts showed significantly higher intervascular and interbranching distances in Adnectin-treated tumors. CT-322-treatment and combinatory inhibition reveal a significant reduction of intussusceptive angiogenesis. These pronounced effects on tumor vasculature suggest potential therapeutic benefit of combinatorial IGF1- and VEGF- pathways inhibition in Ewing’s sarcoma.     

Verletzungen und Überlastungsschäden im Motorrad-Enduro-Sport

According to public opinion, enduro- motorcycling is a dangerous sports. Little is known of accident mechanism during a competition and overuse injuries in enduro- motorcycling. Aim of this study is to evaluate accident and injury patterns as well as overuse syndromes.To detect overuse injuries volunteering athletes were examined immediately before and after each run. Six percent of all started riders sustained an accident. Two percent got injured of which 80% were of superficial kind. More then 50% of all examined riders presented overuse injuries with predominance at the forearm, the wrist and the hand. The transient carpal tunnel syndrome and the beginning compartment syndrome of the forearm flexors were established as diagnosis. Coolpacks and simple vibration blockers led to subjective improvement. Competitive enduro- motorcycling is an average risky sports. The incidence of overuse reactions is evident in more of 50% of all riders and is hence a relevant issue in sports medicine.     

From the Cover: Rice yields in tropical/subtropical Asia exhibit large but opposing sensitivities to minimum and maximum temperatures

Data from farmer-managed fields have not been used previously to disentangle the impacts of daily minimum and maximum temperatures and solar radiation on rice yields in tropical/subtropical Asia. We used a multiple regression model to analyze data from 227 intensively managed irrigated rice farms in six important rice-producing countries. The farm-level detail, observed over multiple growing seasons, enabled us to construct farm-specific weather variables, control for unobserved factors that either were unique to each farm but did not vary over time or were common to all farms at a given site but varied by season and year, and obtain more precise estimates by including farm- and site-specific economic variables. Temperature and radiation had statistically significant impacts during both the vegetative and ripening phases of the rice plant. Higher minimum temperature reduced yield, whereas higher maximum temperature raised it; radiation impact varied by growth phase. Combined, these effects imply that yield at most sites would have grown more rapidly during the high-yielding season but less rapidly during the low-yielding season if observed temperature and radiation trends at the end of the 20th century had not occurred, with temperature trends being more influential. Looking ahead, they imply a net negative impact on yield from moderate warming in coming decades. Beyond that, the impact would likely become more negative, because prior research indicates that the impact of maximum temperature becomes negative at higher levels. Diurnal temperature variation must be considered when investigating the impacts of climate change on irrigated rice in Asia.     

Multidetector-row computed tomography and magnetic resonance imaging of atherosclerotic lesions in human ex vivo coronary arteries

In the present study, we tested the ability of multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) to identify and retrospectively characterize atherosclerotic lesions in human ex vivo coronary arteries. Thirteen ex vivo hearts were studied with MDCT and MRI. MDCT-images were obtained with an isotropic voxel size of 0.6mm(3). MR images were obtained with an in-plane resolution of 195 microm and 3mm slice thickness. All images were matched with histopathology sections. For both modalities, the sensitivity for the detection of any atherosclerotic lesion was evaluated, and a retrospective analysis of plaque morphology according to criteria defined by the American Heart Association (AHA) was performed. At histopathology, 28 atherosclerotic lesions were found. 21 and 23 of these lesions were identified by MDCT and MRI, respectively. Both modalities detected a small number of false-positive lesions. After retrospective matching with histopathology, MDCT as well as MRI were able to differentiate typical morpholocigal features for fatty, fibrous or calcified plaque components. Using the information presented in this study, in vivo coronary artery wall imaging using MDCT as well as MRI could be facilitated and supported for future investigations on this subject.