Presenilin proteins play critical roles in the proteolytic processing of both Notch and amyloid precursor protein (APP). Presenilin itself undergoes endoproteolytic processing to generate an N-terminal and C-terminal fragment. As demonstrated previously, overexpression of presenilin 1 (PS1) holoprotein does not change the levels of the N-terminal and C-terminal fragments (NTF and CTF). When we coexpress the PS1 NTF and CTF, marked increases in the cellular levels of these fragments are seen. By coexpressing the PS1 NTF and CTF, we demonstrate conclusively that a noncovalent complex of the NTF and CTF is the active species of presenilin. However, although the PS1 NTF͞CTF complex is necessary for ␥-secretase activity, it is not sufficient. Independent overexpression of the PS1 NTF and CTF was also used to show that the Asp-257 and Asp-385 mutations in PS1 decrease A production by a direct effect on ␥-secretase activity and not by the inhibition of PS1 endoproteolysis.
Oxandrolone has been shown to improve lean muscle mass in patients with burns. Hepatic dysfunction is a known side effect of treatment with oxandrolone. The purpose of this study was to examine the incidence of hepatic dysfunction in our series of burn patients receiving oxandrolone. Fourteen patients who received oxandrolone (5 mg, n = 8; 10 mg, n = 6) were identified from our prospectively collected burn database. The records of 61 control patients also were reviewed. Demographics such as age, comorbidities, and burn size were recorded. The incidence of hepatic dysfunction was determined by the presence of abnormal liver function tests. The study and control groups were similar in age and burn size. Two of the eight (25%) oxandrolone patients receiving 5 mg and four of the six (67%) oxandrolone patients receiving 10 mg had evidence of hepatic dysfunction. Twenty six of the 61 (43%) control patients had evidence of hepatic dysfunction (P = NS). There appears no significant increased incidence of hepatic dysfunction in burn patients who received oxandrolone compared to those who did not.
The process of development of ECMO retrieval was enabled by the preexistence of a high-volume experienced medical retrieval service. Although ECMO retrieval is not a new concept, we describe an entire process for ECMO retrieval that we believe will benefit other retrieval service providers. The increased workload of ECMO retrieval during the swine flu pandemic has led to refinement in the system and process for the future.
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