Dual inhibition of cathepsin G and chymase reduces myocyte death and improves cardiac remodeling after myocardial ischemia reperfusion injury.

Early reperfusion of ischemic cardiac tissue increases inflammatory cell infiltration which contributes to cardiomyocyte death and loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Neutrophil- and mast cell-derived proteases, cathepsin G (Cat.G) and chymase, are released early after IR, but their function is complicated by potentially redundant actions and targets. This study investigated whether a dual inhibition of Cat.G and chymase influences cardiomyocyte injury and wound healing after experimental IR in mice. Treatment with a dual Cat.G and chymase inhibitor (DCCI) immediately after reperfusion blocked cardiac Cat.G and chymase activity induced after IR, which resulted in decreased immune response in the infarcted heart. Mice treated with DCCI had less myocardial collagen deposition and showed preserved ventricular function at 1 and 7 days post-IR compared with vehicle-treated mice. DCCI treatment also significantly attenuated focal adhesion (FA) complex disruption and myocyte degeneration after IR. Treatment of isolated cardiomyocytes with Cat.G or chymase significantly promoted FA signaling downregulation, myofibril degeneration and myocyte apoptosis. Conversely, treatment of cardiac fibroblasts with Cat.G or chymase induced FA signaling activation and increased their migration and differentiation to myofibroblasts. These opposite responses in cardiomyocytes and fibroblasts were blocked by treatment with DCCI. These findings show that Cat.G and chymase are key mediators of myocyte apoptosis and fibroblast migration and differentiation that play a role in adverse cardiac remodeling and function post-IR. Thus, dual targeting of neutrophil- and mast cell-derived proteases could be used as a novel therapeutic strategy to reduce post-IR inflammation and improve cardiac remodeling.

Treatment of intertrochanteric and subtrochanteric fractures with Ender's intramedullary rods.

A series of 100 patients was treated with Ender's rods for intertrochanteric fractures, subtrochanteric fractures and intertrochanteric pathologic lesions. Healing occurred within 4 months in all 85 of the patients who could be followed, and fractures were prevented in all 4 of the patients with pathologic lesions. Every patient who was ambulatory preoperatively regained ambulation within 3 months after surgery. Inhospital mortality for the series was 3%, compared to 8.4% for a 20-year series of 1,204 hip fractures treated by conventional means. Other advantages of the Ender's rod method are simplicity of the insertion procedure, minimal trauma and blood loss, uniform distribution of stress, early ambulation and weight bearing, and lower morbidity.

Distribution of small bowel tumors.

We have studied the anatomic distribution of 784 small bowel carcinomas and have analyzed available epidemiologic data to determine the relation of these rare cancers to other gastrointestinal tumors and to diet. The anatomic distribution of small bowel cancer in unusual: most tumors occur in the duodenum or proximal jejunum, relatively few tumors occur in the central bowel, and only in the lower ileum do the expected number of tumors appear. Review of available epidemiologic data shows a correlation between small bowel cancer and lower, but not upper gastrointestinal cancer. The incidence of small bowel cancer is positively correlated with protein and fat consumption.