Faculty Bibliography

Cold exposure injuries comprise nonfreezing injuries that include chilblain (aka pernio) and trench, or immersion, foot, as well as freezing injuries that affect core body tissues resulting in hypothermia of peripheral tissues, causing frostnip or frostbite. Frostbite, the most serious peripheral injury, results in tissue necrosis from direct cellular damage and indirect damage secondary to vasospasm and arterial thromboses. The risk of frostbite is influenced by host factors, particularly alcohol use and smoking, and environmental factors, including ambient temperature, duration of exposure, altitude, and wind speed. Rewarming for frostbite should not begin until definitive medical care can be provided to avoid repeated freeze-thaw cycles, as these cause additional tissue necrosis. Rewarming should be rapid and for an affected limb should be performed by submersion in warm water at 104 degrees to 107.6 degrees F (40 degrees to 42 degrees C) for 15 to 30 minutes. Debridement of necrotic tissues is generally delayed until there is a clear demarcation from viable tissues, a process that usually takes from 1 to 3 months from the time of initial exposure. Immediate escharotomy and/or fasciotomy is necessary when circulation is compromised. In addition to the acute injury, frostbite is associated with late sequelae that include altered vasomotor function, neuropathies, joint articular cartilage changes, and, in children, growth defects caused by epiphyseal plate damage

Benign osteoblastoma is a rare tumor of bone that has been reported in a variety of skeletal locations. A case of an isolated benign osteoblastoma in the sternum of an 11-year-old boy is described. In the chest wall, osteoblastoma has been reported in the ribs, and rarely in the sternum. To the authors' knowledge, this is the first report of an isolated sternal osteoblastoma in a child presented in the literature. The clinical and radiologic presentation of osteoblastoma is discussed, as well as an approach for reconstruction of the sternal defect following removal of the tumor. Experience with sternal reconstruction in the pediatric population is limited. This case demonstrates that osteoblastoma of the sternum can be successfully treated with wide resection and that sternal defect reconstruction can be accomplished successfully in a child.

Although the process of mammary tumorigenesis requires multiple genetic events, it is unclear to what extent carcinogenesis proceeds through preferred secondary pathways following a specific initiating oncogenic event. Similarly, the extent to which established mammary tumors remain dependent on individual mutations for maintenance of the transformed state is unknown. Here we use the tetracycline regulatory system to conditionally express the human c-MYC oncogene in the mammary epithelium of transgenic mice. MYC encodes a transcription factor implicated in multiple human cancers. In particular, amplification and overexpression of c-MYC in human breast cancers is associated with poor prognosis, although the genetic mechanisms by which c-MYC promotes tumor progression are poorly understood. We show that deregulated c-MYC expression in this inducible system results in the formation of invasive mammary adenocarcinomas, many of which fully regress following c-MYC deinduction. Approximately half of these tumors harbor spontaneous activating point mutations in the ras family of proto-oncogenes with a strong preference for Kras2 compared with Hras1. Nearly all tumors lacking activating ras mutations fully regressed following c-MYC deinduction, whereas tumors bearing ras mutations did not, suggesting that secondary mutations in ras contribute to tumor progression. These findings demonstrate that c-MYC-induced mammary tumorigenesis proceeds through a preferred secondary oncogenic pathway involving Kras2.