Beyond Negligence Administrative Compensation for Adverse Medical Outcomes
American College of Obstetricians and Gynecologists, 409 12th Street, SW, Washington, DC 20024, USA.Obstetrics and Gynecology (Impact Factor: 4.37). 05/2010; 115(5):896-903. DOI: 10.1097/AOG.0b013e3181da8612
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ABSTRACT: Nitric oxide synthases (NOSs) share two invariant tryptophan residues within a conserved helical lariat that is part of the pterin-binding site and dimer interface. We mutated Staphylococcus aureus NOS Trp-314 (to alanine, phenylalanine, tyrosine and histidine) and Trp-316 (to alanine, phenylalanine and tyrosine) and characterized the effects of mutation on heme environment, quaternary structure, enzymatic activity, and substrate affinity. With arginine present, all saNOS variants bound heme with native thiolate ligation, formed high spin ferric complexes and were dimeric. All variants catalyze the peroxide-dependent oxidation of N-hydroxy-l-arginine, at rates from 10% to 55% of wild type activity. Arginine-free proteins are dimeric with the exception of W314A. Arginine affinity for all variants decreases with increasing temperature between 15 and 42 °C but is precipitous for position-314 variants. Previous structural and biophysical characterization of NOS oxygenase domains demonstrated that the protein can exist in either a tight or loose conformation, with the former corresponding to the active state of the protein. In the position-314 variants it is likely that the loose conformation is favoured, owing to the loss of a hydrogen bond between the indole side chain and the polypeptide backbone of the helical lariat.Archives of Biochemistry and Biophysics 02/2011; 506(2):165-72. DOI:10.1016/j.abb.2010.11.024 · 3.04 Impact Factor
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ABSTRACT: Obstetric caregivers are plagued with lawsuits alleging negligence for suboptimal outcomes. Some of those claims are unjustified, but many have merit. We are obligated to create systems designed to minimize the potential for errors that harm our patients. A variety of safety initiatives have been shown to improve patient outcomes in several centers in the United States, but it has been difficult to document the expected association between those results and reduced liability premiums. Furthermore, some individuals and institutions have been reluctant to adopt safety tools such as electronic fetal monitoring certification for all staff working on their Labor and Delivery floor, protocols for managing common clinical scenarios, simulation drills for dealing with uncommon dangerous events, and pre-procedure checklists because of the paucity of evidence based data documenting the effectiveness of those approaches. It is time to move forward with these and other safety initiatives in a serious national attempt to eliminate all preventable adverse patient outcomes in our specialty.American journal of obstetrics and gynecology 02/2011; 205(1):7-9. DOI:10.1016/j.ajog.2010.12.020 · 3.97 Impact Factor
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