Browsing by Author "Nguyen, Phuong D."

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    Stereoselective pharmacokinetics of stable isotope (+/-)-[13C]-pantoprazole: Implications for a rapid screening phenotype test of CYP2C19 activity
    (Wiley, 2011-11) Thacker, David L.; Modak, Anil; Nguyen, Phuong D.; Flockhart, David A.; Desta, Zeruesenay; Department of Medicine, IU School of Medicine
    AIMS: We have previously shown that the (±)-[(13) C]-pantoprazole breath test is a promising noninvasive probe of CYP2C19 activity. As part of that trial, plasma, breath test indices and CYP2C19 (*2, *3, and *17) genotype were collected. Here, we examined whether [(13) C]-pantoprazole exhibits enantioselective pharmacokinetics and whether this enantioselectivity is correlated with indices of breath test. METHODS: Plasma (-)- and (+)-[(13) C]-pantoprazole that were measured using a chiral HPLC were compared between CYP2C19 genotypes and correlated with breath test indices. RESULTS: The AUC( 0-∞) of (+)-[(13) C]-pantoprazole in PM (*2/*2, n = 4) was 10.1- and 5.6-fold higher that EM (*1/*1or *17, n = 10) and IM (*1/*2or *3, n = 10) of CYP2C19, respectively (P < 0.001). The AUC( 0-∞) of (-)-[(13) C]-pantoprazole only significantly differed between PMs and EMs (1.98-fold; P = 0.05). The AUC( 0-∞) ratio of (+)-/(-)-[(13) C]-pantoprazole was 3.45, 0.77, and 0.67 in PM, IM, and EM genotypes, respectively. Breath test index, delta over baseline show significant correlation with AUC( 0-∞) of (+)-[(13) C]-pantoprazole (Pearson's r = 0.62; P < 0.001). CONCLUSIONS: [(13) C]-pantoprazole exhibits enantioselective elimination. (+)-[(13) C]-pantoprazole is more dependent on CYP2C19 metabolic status and may serve as a more attractive probe of CYP2C19 activity than (-)-[(13) C]-pantoprazole or the racemic mixture.
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    The Lawnmower and the Pediatric Lower Extremity: A Catastrophic Combination
    (Open Science, 2024-02-26) Sathyanarayanan, Sairandri; Obinero, Chioma G.; Green, Jackson C.; Fallah, Kasra N.; Greives, Matthew R.; Chen, Wendy; Nguyen, Phuong D.; Surgery, School of Medicine
    Background: Lower extremity (LE) trauma within the pediatric population may be debilitating and have different implications and etiologies than in adults. Specifically, lawnmower injuries can cause catastrophic sequelae to the lower extremities, often requiring complex reconstruction or resulting in amputation. This study aims to present our experience with pediatric LE lawnmower injuries at one of the busiest level 1 trauma centers in the United States. Methods: An IRB-approved retrospective analysis was performed studying pediatric patients (age <18 years) who experienced LE trauma due to a lawnmower injury over a 5-year period (2012-2017). Patient demographics, perioperative data, and types of reconstruction were reviewed. Univariate analysis of the data was performed to examine trends in exposure and management of pediatric LE lawnmower injuries. Results: Twenty-three patients were identified with pediatric LE lawnmower injuries, of whom 82.6% were male. The patients had a median age of 6 years and a median Injury Severity Score (ISS) of 4. Over one-third (34.8%) of this cohort required immediate amputation. Additionally, 26.1% and 8.7% required local and free flap reconstruction, respectively. In comparison, only 3.6% and 2.3% of all traumatic pediatric LE injuries from the same time frame required local and free flaps, respectively. Conclusions: Lawnmower injuries to the LE can be devastating, causing long-term physical, emotional, and psychosocial consequences for pediatric patients and their families. The data in this study suggest that pediatric LE injuries from lawnmowers more often require complex reconstruction than other traumatic LE injuries. Rapid and effective decision-making by experienced surgeons is necessary to optimize the potential for limb salvage in pediatric LE lawnmower injuries. An algorithm of recommendations on when to transfer these types of injuries to more experienced tertiary centers is provided. Additional resources should be dedicated toward improving public awareness and industrial safety features to help prevent lawnmower injuries in pediatric patients.