This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goals of this study are to: (1) compare in a randomized, blinded, prospective fashion the metabolic and clinical impact of routine intraoperative N2O exposure (vs. an anesthetic regimen identical except that N2O is omitted) on elderly patients; (2) examine clinical, demographic, biochemical and genetic features that may distinguish such postoperative changes from those patients without pre-existing cobalamin deficiency and in patients receiving anesthesia without N2O, or that may influence or predict the risk or expression in individual patients; (3) characterize the details of homocysteine and methionine metabolism in early cobalamin deficiency by measuring plasma levels of a broad range of metabolites, study the changes after exposure to N2O and after recovery compared with control subjects, and correlate the metabolic patterns with clinical outcomes as well as with relevant genetic polymorphisms affecting 3 relevant enzymes; and (4) examine the genetic polymorphisms for association with subclinical cobalamin deficiency and with increased (or decreased) susceptability to the metabolic and clinical effects of N2O exposure, in addition to the above mentioned comparison with metabolite levels.
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