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Mesenchymal stem cells (MSCs) are a source of adult multipotent cells important in tissue regeneration. Murine MSCs are known to proliferate poorly in vitro under normoxia. The aim of this study is to analyze the interaction of nonphysiological high oxygen and low-dose γ-irradiation onto growth, senescence, and DNA damage. Tri-potent bone marrow-derived MSCs from p53 wildtype and p53-/- mice were cultured under either 21% or 2% O2. Long-term observations revealed a decreasing ability of wildtype mMSCs to proliferate and form colonies under extended culture in normoxia. This was accompanied by increased senescence under normoxia but not associated with telomere shortening. After low-dose γ-irradiation, the normoxic wildtype cells further increased the level of senescence. The number of radiation-induced γH2AX DNA repair foci was higher in mMSCs kept under normoxia but not in p53-/- cells. P53-deficient MSCs additionally showed higher clonogeneity, lower senescence levels, and fewer γH2AX repair foci per cell as compared to their p53 wildtype counterparts irrespective of oxygen levels. These results reveal that oxygen levels together with γ-irradiation and p53 status are interconnected factors modulating growth capacity of BM MSCs in long-term culture. These efforts help to better understand and optimize handling of MSCs prior to their therapeutic use.

Background/aim: The use of cardenolides in the treatment of cardiac insufficiency is well-established. However, the potential of cardenolides in tumor therapy has not been comprehensively studied. The aim of the present study was to characterize the cytotoxic effects of the new semisynthetic cardenolide analog AMANTADIG (3β-[2-(1-amantadine)-1-on-ethylamine]-digitoxigenin), and the cardenolide digitoxin on leukemia and urological tumor cell lines., Materials and Methods: The anti-proliferative effects of AMANTADIG and digitoxin on leukemia and urological cancer cell lines were analyzed using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction viability assay., Results: AMANTADIG and digitoxin exhibited anti-proliferative activities against the leukemia cell lines in the low nanomolar range. The prostate cancer and renal cell carcinoma cell lines were equally sensitive to AMANTADIG and digitoxin, however, the leukemia cell lines were more sensitive to both cardenolides., Conclusion: The new cardenolide analog AMANTADIG appears effective in cell growth inhibition of leukemia and urological tumor cell lines., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Since September 2005 our patients with acute endoprosthetic infection are treated, next to the normal wound debridement, with a full automatic vacuum drain system (V.A.C. instill system). This therapy unit entail a three step program. Based on the well known vacuum therapy, the new system contains an additional fluid drain and affecting period with an antibiotic or antiseptic instillation therapy. In the last half year we were able to treat five patients with endoprosthetic infection by using this therapy unit. In our opinion, we have a successfull method of treating patients with acute, infected big joints after endoprosthetic implantation. The therapy unit of V.A.C. instill is quickly available and easy to learn. Next to much better comfort for the patients the most advantage is to leave the prosthetic inside during the infection management with the new therapy unit. Further results in treating acute joint infections after endoprosthetic implantation must been shown, if this new method is to be the new standard in daily clinical routine.

Between January 1, 1987, and December 31, 1997, an isoelastic polyacetal resin prosthesis was used in 50 patients with metastatic bone disease to reconstruct pathologic or impending fractures of the humeral diaphysis. Fifty-seven operations were performed, including seven revision surgeries. The patients were assessed before and after surgery for limb function and quality of life using a modified Karnofsky scale. The mean survival time was 440 days. Ninety-one percent of the operations resulted in restoration or improvement of quality of life. Limb function was good or excellent in more than 80% of the patients after surgery. Breaking of the implant (n = 3), loosening of the implant (n = 2), periprosthetic fracture (n = 1), hematoma (n = 2), infection (n = 1), and one radial nerve paralysis were the main complications. In the cases of implant failure, the prosthesis broke at the site of a locking screw that was inserted across the prosthetic shaft in the cementless implantation technique. This kind of complication could be avoided by using bone cement for implantation or additional plate osteosynthesis between the prosthesis and humeral shaft. The isoelastic diaphyseal prosthesis offers a promising method of treating patients with metastatic lesions of the humeral shaft.

Elastic intramedullary nailing represents a new surgical concept in the treatment of unstable shaft fractures in children. The present case control study wanted to examine the superiority of intramedullary nailing in comparison to conservative therapeutic concepts which had been applied so far. 13 children with forearm fractures who were treated initially by conservative measures were compared to 13 other children who received a primary intramedullary nailing. With femoral fractures, 12 children were included in each group. In each patient pair age, type and localisation of the fracture were comparable. During the observation period (until the termination of final therapeutic measures or until the third year after injury) we examined clinical variables and subjective findings. Both therapeutic concepts led to comparably good functional results. Also subjective judgement of the therapeutic success did not differ between groups. However, with intramedullary nailing of shaft fractures of the femur the mean hospital length of stay (7.0 +/- 3.5 days) was significantly shorter than with initial conservative treatment (36.5 +/- 2.2 days, P < 0.05). Irrespective of the localisation of the fracture intramedullary nailing required significantly less x-ray examinations during the observation period. These results suggest intramedullary nailing to be the procedure of choice to treat unstable forearm and femoral fractures in children.

A 65-year-old woman with dermatomyositis for which she had been treated for ten years with prednisone (latterly 15 mg daily) suddenly experienced severe pain in the left thoracolumbar region. Cardiovascular, pulmonary and vertebral causes of the pain were excluded. But serological tests indicated inflammatory disease and the haemoglobin concentration was low (10.4 g/dl). Left pleural effusions were repeatedly aspirated and some haemorrhagic fluid obtained (haematocrit 0.31 in blood, 0.28 in the pleural effusion). Five days after admission her cardiovascular status became unstable and she developed respiratory failure (haemoglobin 7.6 g/dl). Chest radiograph showed increased pleural effusion. Subsequent thoracotomy revealed a left coagulothorax which was removed and flushed. During this procedure severe bleeding occurred from a covered perforation of the descending aorta, 1.5 x 1.5 cm in size. Although the aortic wall was thin, there was no aneurysm but arteriosclerotic changes and an external erosion near an abscessing mediastinitis, originating from a chronic purulent pleuritis and bronchopneumonia. The severe blood loss caused circulatory failure from which the patient could not be resuscitated.

Because of the increasing survival-time of tumor-patients bone metastasis is becoming an important subject in surgery. In the case of osteolysis of the femur a concept of treatment in consideration of various localisations is presented. In 81 patients with pathological fractures of the femur or osteolysis in this region from January 1987 to June 1992 96 stabilizing operations were performed. Almost one half of the patients suffered from breast carcinoma followed by hypernephroma, Plasmocytoma, bronchial-carcinoma and prostate-carcinoma. The average survival time after stabilization of the femur was 8.3 months. After the operation the condition of the patients improved on an average by 0.64 units of the modificated Karnowsky-Index. Surgical treatment of osteolysis in the femur is indicated either in pathological fractures or if instability is imminent. Moreover patients who suffer from severe pain should also receive palliative surgery. With regard to the site of the lesion various types of endoprostheses and osteosynthesic devices can be used. If the femoral neck or the intertrochanteric region is affected arthroplasty with cemented endoprosthesis may be performed. In subtrochanteric osteolysis long and thin endoprosthesis can be used as well as Gamma-nails. Pathological fractures in the shaft of the femur should be treated with intramedullary static locked nails, which can be strengthened by supplementary lateral plates. If the distal metaphysis of the femur is involved compound osteosynthesis with methylmethacrylate and dynamic condylar screws or angle plates can be used.

Resection of metastases gains more and more importance in day to day surgical work task. Mainly only liver- and pulmonary metastases can be resected with a curative aim, depending on the primary tumor and the metastasing cascade. According to tumor surgery a R0-resection is warranted. Whether a multimodal approach may improve long-term results by eliminating occult micrometastases should be answered by ongoing studies. Even in palliative situations complete resections of metastasis are preferred and in selected situations a multimodal approach may be chosen.

Lumbar burst fractures or massive tumorous destruction of the lumbar spine generally require a combined anterior-posterior surgical approach for adequate decompression and stabilization. Anatomical studies in 10 adult cadavers with 100 pedicle screw placements from a single strictly anterior approach showed that this new method represents a safe and promising way for stable lumbar spine instrumentation, avoiding the risks of a bilateral approach. The technique provides a stability comparable with bilateral instrumentation. Exact knowledge of the geometry of the corresponding vertebral bodies and the spinal canal by computed tomography scanning is a prerequisite for this surgical technique. First clinical applications using this technique reconfirm the experiences of the anatomical study.