BACKGROUND:Th ere are few data regarding mechanical ventilation and ARDS in the ED. Th is could be a vital arena for prevention and treatment.

Papillomaviruses contain small double-stranded DNA genomes that are maintained in persistently infected mammalian host epithelia as nuclear plasmids and rely upon the host replication machinery for replication. Papillomaviruses encode a DNA helicase, E1, which can specifically bind to the viral genome and support DNA synthesis. Under some conditions in mammalian cells, E1 is not required for viral DNA synthesis, leading to the hypothesis that papillomavirus DNA can be replicated solely by the host replication machinery. This machinery is highly conserved among eukaryotes. We and others found that papillomavirus DNA could replicate in a simple eukaryote, Saccharomyces cerevisiae. Specifically, papillomavirus DNA could substitute for the function of the autonomously replicating sequence (ARS) and centromere (CEN) elements that are normally both required for the stable replication of extrachromosomal DNAs in yeast. Furthermore, this form of replication in yeast was E1 independent. In this study, we map the elements in the human papillomavirus type 16 (HPV16) genome that can substitute for yeast ARS and CEN elements. A single element, termed rep, was identified that can substitute for ARS, and multiple elements, termed mtc, could substitute for CEN. The location of one of these mtc elements overlaps the location of rep, and this approximately 1,000-bp region of HPV16 was sufficient to support stable replication of a bacterial-yeast shuttle plasmid deleted of both ARS and CEN elements.Papillomaviruses contain small double-stranded circular DNA genomes that are replicated in the natural mammalian host epithelial cells as nuclear plasmids. Two viral gene products, E1 and E2, contribute to the replication of papillomaviral genomes via their recognition and function at the E1-dependent origin of replication, a cis-element that maps to the 3Ј end of the long control region (LCR) in the viral genome (30, 31). E1, a DNA helicase that assembles as a hexamer, recruits DNA polymerase ␣ and unwinds DNA at the E1-dependent origin of replication (E1 ori) (7,20,26,31,34). E1 has functional and structural homology to cellular DNA helicases, including Werner's and Bloom's syndrome gene products, and the minichromosome maintenance family of helicases (23). E2, a transcriptional transactivator, also contributes to viral DNA replication by interacting with E1 and increasing the efficiency of E1 binding to the E1 ori (33), a function that can be overcome at high levels of E1 protein (8,27). In addition, E2 can contribute to the stable inheritance of papillomavirus DNA to daughter cells during cell division (24), likely by tethering the viral genomes to host chromosomes during mitosis (3,16,29). The replication of the viral genome is tightly controlled during the viral life cycle, and this control is tied to the differentiation of the host epithelial tissue, and the regulation of expression and function of E1 and E2 likely contribute to the control of viral DNA replication during the viral life cycle (1,22,36).Prior studies of bovine pap...

BackgroundEndotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability.Methods/designA randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients.DiscussionThe overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population.Trial registrationClinicaltrials.gov: NCT02105415. 31 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0687-0) contains supplementary material, which is available to authorized users.

Case seriesPatient: Male, 77 • Male, 25 • Male, 63 • Male, 70 • Male, 70 • Female, 61Final Diagnosis: —Symptoms: Hypotension • respiratory failureMedication: Ketamine • Propofol • EtomidateClinical Procedure: Endotracheal intubationSpecialty: Critical Care MedicineObjective:Educational Purpose (only if useful for a systematic review or synthesis)Background:Endotracheal intubation is a common procedure performed for critically ill patients that can have immediate life-threatening complications. Induction medications are routinely given to facilitate the procedure, but most of these medications are associated with hypotension. While etomidate is known for its neutral hemodynamic profile, it has been linked with increased mortality in septic patients and increased morbidity in trauma patients. Ketamine and propofol are effective anesthetics with counteracting cardiovascular profiles. No data are available about the use of this combination in critically ill patients undergoing endotracheal intubation.Case Series:We describe 6 cases in which the combination of ketamine and propofol (“ketofol”) was used as an induction agent for endotracheal intubation in critically ill patients with a focus on hemodynamic outcomes. All patients received a neuromuscular blocker and fentanyl, while 5 patients received midazolam. We recorded mean arterial pressure (MAP) 1 minute before induction and 15 minutes after intubation with the combination. Of the 6 patients, 5 maintained a MAP ≥65 mmHg 15 minutes after intubation. One patient was on norepinephrine infusion with a MAP of 64 mmHg, and did not require an increase in the dose of the vasopressor 15 minutes after intubation. No hemodynamic complications were reported after any of the intubations.Conclusions:This case series describes the use of the “ketofol” combination as an induction agent for intubation in critically ill patients when hemodynamic stability is desired. Further research is needed to establish the safety of this combination and how it compares to other induction medications.

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