Clinical, genetic, and cardiac magnetic resonance imaging findings in primary desminopathies

We report the clinical, genetic and cardiac magnetic resonance imaging (MRI) findings in 11 German patients with heterozygous E245D, D339Y, R350P and L377P desmin mutations and without cardiac symptoms. Clinical evaluation revealed a marked variability of skeletal muscle, respiratory and cardiac involvement even between patients with identical mutations, ranging from asymptomatic to severely affected. While echocardiography did not show any pathological findings in all 11 patients, cine MRI revealed focal left ventricular hypertrophy in 2 patients and MR delayed enhancement imaging displayed intramyocardial fibrosis in the left ventricle in 4 patients indicating early myocardial involvement. Our data argue against distinct genotype-phenotype correlations and suggest that comprehensive cardiac MRI is superior to conventional echocardiography for the detection of early and clinically asymptomatic stages of cardiomyopathy in desminopathy patients. Therefore, cardiac MRI may serve as a screening tool to identify patients at risk, which might benefit from early pharmacological and/or interventional (e.g. implantable cardioverter-defibrillator devices) therapy.     

Filters in autologous blood retransfusion systems affect the amount of blood cells retransfused in total knee arthroplasty: a pilot study

A pilot study was undertaken to evaluate whether filters integrated in postoperative retransfusion systems affect the amount of blood cells retransfused after total knee arthroplasty. Twenty-two consecutive patients received either the Donor retransfusion system (n=12 patients) or the Bellovac ABT retransfusion system (n=10). Both systems differ with respect to the type of filter, a Pall Lipiguard filter and a Sangopur filter, respectively. At the beginning of the retransfusion, blood samples were taken before and after the filter. The filter of the Donor system significantly decreased the amount of leukocytes and erythrocytes, whereas the filter of the Bellovac system did not. As a result the haemoglobin level of retransfused blood with the Donor system was significantly lower than with the Bellovac system. It can be concluded that the type of filter integrated in two postoperative autologous blood retransfusion systems significantly affected the amount of blood cells retransfused in patients undergoing total knee arthroplasty.     

Morphologic changes in the vastus medialis muscle in patients with osteoarthritis of the knee

OBJECTIVE: To investigate the frequency of structural changes in the vastus medialis muscle in patients with osteoarthritis (OA) of the knee. METHODS: Specimens of vastus medialis muscle from 78 patients with end-stage OA of the knee undergoing total joint arthroplasty were examined histopathologically. Morphologic changes were assessed in relation to clinical features that might have contributed to muscle injury. RESULTS: All muscle specimens exhibited atrophy of type 2 fibers. In 32% of the patients, atrophy of type 1 fibers was also noted. Fiber type grouping of type 1 fiber in 15% of the patients and type 2 fiber in 37%, indicating reinnervation, led to the diagnosis of neurogenic muscular atrophy in 32% of the patients; selective atrophy of type 2 fiber in 68% of the specimens was interpreted as possibly resulting from pain-associated disuse. Signs of muscle degeneration and regeneration were found in 65% and 96% of the samples, respectively. Soft tissue changes indicating long-term disease, such as calcification, fibrosis, and lipomatosis, were frequently observed (in 69%, 71%, and 94% of the patients, respectively). Statistical analysis of clinical and morphologic parameters revealed a significant association between degenerative muscle changes and the presence of a varus deviation of the leg axis. CONCLUSION: Patients with OA of the knee frequently exhibit muscle changes, with probable multifactorial etiology. Selective atrophy of type 2 fibers might reflect pain-related immobilization of a limb. Changes such as neurogenic muscular atrophy, muscle fiber degeneration, and regeneration might contribute as cofactors in the development or progression of OA.     

The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo

In addition to the ARF/p53 pathway, the DNA damage response (DDR) has been recognized as another oncogene-provoked anticancer barrier in early human tumorigenesis leading to apoptosis or cellular senescence. DDR mutations may promote tumor formation, but their impact on treatment outcome remains unclear. In this study, we generated ataxia telangiectasia mutated (Atm)-proficient and -deficient B-cell lymphomas in Emu-myc transgenic mice to examine the role of DDR defects in lymphomagenesis and treatment sensitivity. Atm inactivation accelerated development of lymphomas, and their DNA damage checkpoint defects were virtually indistinguishable from those observed in Atm+/+-derived lymphomas that spontaneously inactivated the proapoptotic Atm/p53 cascade in response to Myc-evoked reactive oxygen species (ROS). Importantly, acquisition of DDR defects, but not selection against the ARF pathway, could be prevented by lifelong exposure to the ROS scavenger N-acetylcysteine (NAC) in vivo. Following anticancer therapy, DDR-compromised lymphomas displayed apoptotic but, surprisingly, no senescence defects and achieved a much poorer long-term outcome when compared with DDR-competent lymphomas treated in vivo. Hence, Atm eliminates preneoplastic lesions by converting oncogenic signaling into apoptosis, and selection against an Atm-dependent response promotes formation of lymphomas with predetermined treatment insensitivity.