Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing. Whether prospective use of a retrospectively developed algorithm that incorporates CYP2C9 genotype and nongenetic factors can ameliorate the propensity to bleeding and delay in achieving a stable warfarin dose is unknown. We initiated warfarin therapy in 48 orthopedic patients tailored to the following variables: CYP2C9 genotype, age, weight, height, gender, race, and use of simvastatin or amiodarone. By using pharmacogenetics-based dosing, patients with a CYP2C9 variant achieved a stable, therapeutic warfarin dose without excessive delay. However compared to those without a CYP2C9 variant, patients with a variant continued to be at increased risk (hazard ratio 3.6, 95% confidence interval 1.4-9.5, p = 0.01) for an adverse outcome (principally INR > 4), despite pharmacogenetics-based dosing. There was a linear relationship (R(2) = 0.42, p < 0.001) between the pharmacogenetics-predicted warfarin doses and the warfarin maintenance doses, prospectively validating the dosing algorithm. Prospective, perioperative pharmacogenetics-based dosing of warfarin is feasible; however, further evaluation in a randomized, controlled study is recommended.

The SFD provides a very feasible, efficient, relatively safe, and cost effective method to treat complex intracranial aneurysms without the use of adjunct coiling.

No abstract

Acute multiple sclerosis (MS) lesions have the characteristic magnetic resonance imaging (MRI) features of increased diffusion weighted imaging (DWI) and increased apparent diffusion coefficient (ADC). This well recognized imaging pattern is felt to represent increased free water content due to vasogenic edema and demyelination. 1 Rarely, MS lesions have increased DWI and decreased ADC signal in the acute phase, a pattern that mimics the radiographic features of acute stroke. 2-4 Such diverse disorders as primary central nervous system lymphoma, abscess, hemorrhage, and post-stroke Wallerian-like degeneration can also have true restricted diffusion. 5-7 Restricted diffusion in selected acute MS lesions likely represents early cytotoxic edema. However, the reduced ADC signal usually converts to normal or increased signal over the