Closed reduction and percutaneus Kirschner wire fixation for the treatment of dislocated calcaneal fractures: surgical technique, complications, clinical and radiological results after 2–10 years

Introduction To reduce complications, a minimally invasive technique for the treatment of dislocated intraarticular fractures of the calcaneus was used. Therefore previously described closed reduction and internal fixation techniques were combined and modified. Materials and methods Sixty-seven out of 92 calcaneal fractures could be retrospectively evaluated with an average follow-up time of 5.7 years (minimum 2-10 years follow-up). For radiographic evaluation, plain radiographs and CT scans were obtained. The Zwipp score was used for clinical evaluation. Sanders type II, III and IV fractures were diagnosed. Results Length of surgery averaged 61 min (range 20-175 min). The incidence of subtalar arthritis was correlated to the severity of fracture. Bohler's angle was restored in 70.1% (47 of 67) of the cases. On the last follow-up evaluation the average Zwipp score was 130 points (range 48-186 points). The majority (77.7%) of patients were content with their treatment result. The rate of significant complications was 6.5%. Discussion Compared to open techniques the presented minimally invasive technique showed comparable results with a low rate of serious complications and is a viable alternative for the treatment of intraarticular, dislocated calcaneal fractures

Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis.

Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1) in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE(-/-) mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1) to analyze which cells express GPx-1 within atherosclerotic lesions and (2) to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of lesions of the aortic sinus of ApoE(-/-) mice after 12 weeks on a Western type diet revealed that both macrophages and - even though to a less extent - smooth muscle cells contribute to GPx-1 expression within atherosclerotic lesions. In isolated mouse peritoneal macrophages differentiated for 3 days with macrophage-colony-stimulating factor (MCSF), GPx-1 deficiency increased oxidized low density-lipoprotein (oxLDL) induced foam cell formation and led to increased proliferative activity of peritoneal macrophages. The MCSF- and oxLDL-induced proliferation of peritoneal macrophages from GPx-1(-/-)ApoE(-/-) mice was mediated by the p44/42 MAPK (p44/42 mitogen-activated protein kinase), namely ERK1/2 (extracellular-signal regulated kinase 1/2), signaling pathway as demonstrated by ERK1/2 signaling pathways inhibitors, Western blots on cell lysates with primary antibodies against total and phosphorylated ERK1/2, MEK1/2 (mitogen-activated protein kinase kinase 1/2), p90RSK (p90 ribosomal s6 kinase), p38 MAPK and SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase), and immunohistochemistry of mice atherosclerotic lesions with antibodies against phosphorylated ERK1/2, MEK1/2 and p90RSK. Representative effects of GPx-1 deficiency on both macrophage proliferation and MAPK phosphorylation could be abolished by the GPx mimic ebselen. The present study demonstrates that GPx-1 deficiency has a significant impact on macrophage foam cell formation and proliferation via the p44/42 MAPK (ERK1/2) pathway encouraging further studies on new therapeutic strategies against atherosclerosis

Effects of MCSF on the phosphorylation of MAPKs.

<p>After pre-incubation for 3 days with 10 ng/ml MCSF, peritoneal macrophages were incubated for 5 and 15 min with 10 ng/ml MCSF. Cellular protein was extracted and protein samples (0.4 mg/ml) were analyzed by Western blot with specific antibodies: anti-phosphorylated MEK1/2 or anti-MEK1/2 (<b>A,</b> right), anti-phosphorylated ERK1/2 or anti-ERK1/2 (<b>B,</b> right), anti-phosphorylated p90RSK or anti-RSK1/2/3 (<b>C</b>, right), anti-phosphorylated p38 MAPK or anti-p38 MAPK (<b>D,</b> right) and anti-phosphorylated SAPK/JNK or anti-SAPK/JNK (<b>E</b>, right) antibodies (representative experiments). ß-Actin or Actin were used as control. Quantitative results were calculated by band densitometry with the intensity of phosphorylated MEK1/2, ERK1/2, p90RSK, p38 MAPK and SAPK/JNK normalized to the total MEK1/2, ERK1/2, RSK1/2/3, p38 MAPK and SAPK/JNK (<b>A–E</b>, left panels). Data represent mean ± SD of 3 separate experiments. *, **indicate statistically significant differences (*p<0.05, **p<0.01) compared with cells without MCSF treatment.</p

Localization of GPx-1 in mice atherosclerotic lesions.

<p>GPx-1 mRNA and protein expression, macrophages and SMCs in sequential sections of the aortic sinus of ApoE^−/− (<b>A, C</b>) and GPx-1^−/−ApoE^−/− (<b>B</b>) mice. <b>A,</b> GPx-1 mRNA expression was detected by <i>in situ</i>-hybridization (upper panels) and both macrophages and SMCs were detected by immunohistochemistry (middle panels, see Methods). Upper left panel: anti-sense probe; upper right panel: corresponding section hybridized with the sense probe for GPx-1 (no signal). <b>B,</b> Control sections of GPx-1^−/−ApoE^−/− mice showed no expression of GPx-1 mRNA, neither with the anti-sense nor with the sense probe (upper panels). The representative atherosclerotic lesion containes both macrophages (lower left panel) and SMCs (lower right panel). <b>C,</b> Representative double immunohistochemical staining for GPx-1 (brown) and macrophages (red; left panel) and GPx-1 (brown) and SMCs (red; right panel) in ApoE^−/− mice. Note the close intermingling and overlapping of the different antigens predominantly within the inner parts of the intima. In <b>A</b> to <b>C</b>, the vessel lumen is to the upper left-hand corner. The demarcation between intima and media is indicated by arrowheads.</p