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121.
AMJ van Wegberg RAF Evers JGM Burgerhof E van Dam M.R. Heiner-Fokkema MCH Janssen MC de Vries FJ van Spronsen 《Molecular genetics and metabolism》2021,132(1):49-55
BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis. 相似文献
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Jesse D. Sutton Ryan P. Mynatt Keith S. Kaye Kyle P. Murray Michael J. Rybak Jason M. Pogue 《Antimicrobial agents and chemotherapy》2015,59(9):5470-5474
To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n = 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P = 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P = 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P = 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted. 相似文献
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Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: Possible role of nucleoside kinase(s) 总被引:33,自引:20,他引:33
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Dennis A. Carson Jonathan Kaye J. E. Seegmiller 《Proceedings of the National Academy of Sciences of the United States of America》1977,74(12):5677-5681
Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have shown that through the action of specific kinases, nucleosides can be "trapped" intracellularly in the form of 5'-phosphates. We therefore measured the ability of newborn human tissues to phosphorylate adenosine and deoxyadenosine, the substrate of adenosine deaminase, and also inosine, deoxyinosine, guanosine, and deoxyguanosine, the substrates of purine nucleoside phosphorylase. Substantial activities of adenosine kinase were found in all tissues studied, while guanosine and inosine kinases were detected in none. However, the ability to phosphorylate deoxyadenosine, deoxyinosine, and deoxyguanosine was largely confined to lymphocytes. Adenosine deaminase, but not purine nucleoside phosphorylase, showed a similar lymphoid predominance. Other experiments showed that deoxyadenosine, deoxyinosine, and deoxyguanosine were toxic to human lymphoid cells. The toxicity of deoxyadenosine was reversed by the addition of deoxycytidine, but not uridine, to the culture medium. Based upon these and other experiments, we propose that in adenosine deaminase and purine nucleoside phosphorylase deficiency, toxic deoxyribonucleosides produced by many tissues are selectively trapped in lymphocytes by phosphorylating enzyme(s). 相似文献
126.
David M Kaye Arthur Preovolos Tanneale Marshall Melissa Byrne Masahiko Hoshijima Roger Hajjar Justin A Mariani Salvatore Pepe Kenneth R Chien John M Power 《Journal of the American College of Cardiology》2007,50(3):253-260
OBJECTIVES: The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart. BACKGROUND: Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems. METHODS: We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad-beta-galactosidase (AdLacZ). RESULTS: Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 +/- 3% to 50 +/- 4%; p < 0.001), whereas a further decline occurred in the AdLacZ group (34 +/- 4% to 27 +/- 3%; p < 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p < 0.05). In conjunction, AdS16E-treated animals showed significant improvement in the expression of PLN and Ca2+-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression. CONCLUSIONS: We report the development of a novel closed-loop system for cardiac gene therapy. Using this approach delivery of AdS16E reversed HF progression in a large animal HF model. 相似文献
127.
Benjamin Poh Paul Cashin Kaye Bowers Travis Ackermann Yeng Kwang Tay Arun Dhir Daniel Croagh 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(7):629-634
Introduction
Minimally-invasive options for the management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy include laparoscopic and endoscopic approaches. This study reviews the effectiveness of both approaches in an emergency setting.Methods
A retrospective chart review was performed for a cohort of patients who underwent laparoscopic cholecystectomy. Outcomes assessed were duct clearance, the number of procedures performed (NPP), length of stay (LOS) and complication rate.Results
A total of 182 patients who underwent emergency laparoscopic cholecystectomies received intervention for choledocholithiasis. The duct clearance rate was lower in the laparoscopic group, 63% versus 86% (P = 0.001). However, the median NPP was also lesser in the laparoscopic group, 1 (interquartile range (IQR) 1–2) versus 2 (IQR 2–2) (P < 0.001), as was the median LOS, 5 days (IQR 3–8) versus 7 days (IQR 6–10) (P = 0.009). Forty-eight laparoscopic endobiliary stents were attempted; stent deployment was successful in 37 patients. A larger proportion of patients with laparoscopic endobiliary stents had duct clearance by endoscopic retrograde cholangiopancreatography (ERCP) compared with those without, although this was not statistically significant (P = 0.208).Conclusion
Laparoscopic clearance is not as effective as post-operative ERCP in an emergency cohort, but is associated with fewer procedures required and a shorter inpatient stay. Thus, laparoscopic clearance may still be an attractive option for surgeons especially where conditions are favourable during an emergency laparoscopic cholecystectomy. 相似文献128.
Erin E. Reilly Roxanne E. Rockwell Ana L. Ramirez Leslie K. Anderson Tiffany A. Brown Christina E. Wierenga Walter H. Kaye 《European eating disorders review》2020,28(2):199-210
Despite initial data suggesting positive treatment outcomes for adolescent eating disorder day‐hospital programmes (DHPs), existing studies have included limited follow‐up, small samples, and a focus on restricting‐type eating disorders. To address these gaps, we explored naturalistic outcomes for an adolescent eating disorders DHP. Adolescent participants (N = 265) completed measurements at treatment admission, discharge (n = 170), and various lengths of follow‐up (n = 126; Mfollow up = 278.87 days). Results from multilevel models indicated significant increases in body weight for the anorexia nervosa group throughout treatment and maintenance of increased body weight from discharge to follow‐up. In bulimic spectrum disorders, binge eating and purging significantly decreased from intake to discharge and did not change from discharge to follow‐up. Across the entire sample, eating disorder symptoms decreased from intake to discharge and did not change from discharge to follow‐up. Further, anxiety and depression decreased over the course of treatment and continued to decrease over the follow‐up period. The current investigation represents the first study to explore longitudinal DHP outcomes within adolescent bulimic spectrum eating disorders. Our findings also highlight many challenges inherent in conducting naturalistic research; it is critical that the field continue to develop solutions to the barriers inherent in conducting longitudinal research on eating disorder treatment. 相似文献
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