The New England journal of medicine
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The ATP-sensitive potassium (K(ATP)) channel, composed of the beta-cell proteins sulfonylurea receptor (SUR1) and inward-rectifying potassium channel subunit Kir6.2, is a key regulator of insulin release. It is inhibited by the binding of adenine nucleotides to subunit Kir6.2, which closes the channel, and activated by nucleotide binding or hydrolysis on SUR1, which opens the channel. The balance of these opposing actions determines the low open-channel probability, P(O), which controls the excitability of pancreatic beta cells. We hypothesized that activating mutations in ABCC8, which encodes SUR1, cause neonatal diabetes. ⋯ Dominant mutations in ABCC8 accounted for 12 percent of cases of neonatal diabetes in the study group. Diabetes results from a newly discovered mechanism whereby the basal magnesium-nucleotide-dependent stimulatory action of SUR1 on the Kir pore is elevated and blockade by sulfonylureas is preserved.
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We prospectively evaluated a clinical prediction rule to be used by emergency medical technicians (EMTs) trained in the use of an automated external defibrillator for the termination of basic life support resuscitative efforts during out-of-hospital cardiac arrest. The rule recommends termination when there is no return of spontaneous circulation, no shocks are administered, and the arrest is not witnessed by emergency medical-services personnel. Otherwise, the rule recommends transportation to the hospital, in accordance with routine practice. ⋯ The use of a clinical prediction rule for the termination of resuscitation may help clinicians decide whether to terminate basic life support resuscitative efforts in patients having an out-of-hospital cardiac arrest.
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Randomized Controlled Trial Multicenter Study
Early inhaled nitric oxide therapy in premature newborns with respiratory failure.
The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain. ⋯ Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov].).
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Editorial Comment
Paying for performance in the United States and abroad.
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Randomized Controlled Trial
Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence.
The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence. ⋯ Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283 [ClinicalTrials.gov].).