Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system

Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production and that this explains the cardiovascular toxicity associated with COX-2 inhibition, yet the evidence for this relies on indirect evidence from urinary metabolites. Here we have used a range of experimental approaches to explore which isoform drives the production of prostacyclin in vitro and in vivo. Our data show unequivocally that under physiological conditions it is COX-1 and not COX-2 that drives prostacyclin production in the cardiovascular system, and that urinary metabolites do not reflect prostacyclin production in the systemic circulation. With the idea that COX-2 in endothelium drives prostacyclin production in healthy individuals removed, we must seek new answers to why COX-2 inhibitors increase the risk of cardiovascular events to move forward with drug discovery and to enable more informed prescribing advice.     

The virtual dental home: implications for policy and strategy

Widely recognized problems with the U.S. health care system, including rapidly increasing costs and disparities in access and outcomes also exist in oral health. If oral health systems are to meet the "Triple Aim" of improving the experience of care, improving the health of populations, and reducing per capita costs of health care, new and innovative strategies will be needed including new regulatory, delivery, and financing systems. The virtual dental home is one such system.     

Common blood laboratory values are associated with cognition among older inpatients referred for neuropsychological testing

The purpose of this study was to examine the relationship between common laboratory values and cognitive functioning among 129 inpatients referred for neuropsychological evaluation. Laboratory values were recorded at admission, at the time point closest to neuropsychological evaluation, and at the time of peak metabolic derangement. Cognitive status was evaluated with the modified Mini-Mental State Exam. Patients with hyperglycemia, hypochloremia, and/or elevated creatinine at admission exhibited cognitive deficits. Patients with hyperglycemia, hyperchloremia, hypernatremia, hyperkalemia, leukocytosis, low hemoglobin, elevated blood urea nitrogen, and/or elevated creatinine at the time of peak metabolic derangement exhibited cognitive deficits. Different lab abnormalities at the time of peak metabolic derangement accounted for unique patterns of neuropsychological impairment. Lab values drawn at the time point closest to neuropsychological evaluation were not significantly associated with cognitive functioning. Results support and quantify common clinical beliefs that metabolic abnormalities are associated with global cognitive changes among elderly inpatients.     

Primary percutaneous coronary intervention in acute myocardial infarction

Primary percutaneous coronary intervention (PCI) has emerged as the preferred therapy for acute ST-segment elevation myocardial infarction (STEMI), as multiple randomized clinical trials and pooled analyses have shown improved clinical outcomes compared with medical reperfusion. Unfortunately, medical centers with 24-hour PCI capability are concentrated in urban areas, relegating many patients in the United States to inferior medical reperfusion. Ongoing substantial research efforts are directed at optimizing mechanical reperfusion, including refinements in adjuvant medical therapy and the use of drug-eluting stents in the catheterization laboratory. Research efforts are also focusing on the implementation of streamlined transfer systems from community centers to tertiary care centers, akin to systems used in the trauma model. Furthermore, experience with the performance of primary PCI at community centers without onsite surgical backup is growing. This article summarizes data regarding the current state, challenges, and future directions of primary PCI for STEMI, emphasizing adherence to current American College of Cardiology/American Heart Association guidelines.