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Columbus, OH, United States

Ohkuni K.,Nationwide Childrens Hospital
Transcription | Year: 2012

Centromeres are specialized chromosomal loci that are essential for proper chromosome segregation. Recent data show that a certain level of active transcription, regulated by transcription factors Cbf1 and Ste12, makes a direct contribution to centromere function in Saccharomyces cerevisiae. Here, we discuss the requirement and function of transcription at centromeres. Source

Tobias J.D.,Nationwide Childrens Hospital
Pediatric Emergency Care | Year: 2013

Objective: The objective of this review was to provide a general descriptive account of the physical properties, end-organ effects, therapeutic applications, and delivery techniques of nitrous oxide (N2O) as used in the arena of procedural sedation. Data Source: A computerized bibliographic search regarding the applications of nitrous for provision of sedation and analgesia during procedures with an emphasis on the pediatric population was performed. Results: The end-organ effects of N2O have been well described in the operating room setting. Aside from its effects on the central nervous system of sedation and analgesia, N2O may alter intracerebral dynamics and alter cerebral blood flow and intracranial pressure especially in patients with altered intracranial compliance. Effects on ventilation include a dose-related depression of ventilatory function and control of upper airway patency. These effects are generally limited in the absence of comorbid diseases and potentiated by other sedative and analgesic agents. The more clinically significant respiratory effect of N2O on ventilatory function is a dose-dependent depression of the ventilatory response to hypoxemia. Hemodynamic effects include a mild direct depressant effect on myocardial function, which in the absence of comorbid cardiac disease is generally compensated by stimulation of the sympathetic nervous system. Nitrous oxide may potentially aggravate pulmonary hypertension. Additional physiologic effects on neurologic and hematologic function may result in inactivation of the enzyme, methionine synthetase. Recent concern has also been raised regarding the potential effects of N2O on immune function and its relationship to perioperative surgical site infections. Given differences in the solubility, N2O will diffuse into and significantly expand gas-filled cavities. Chronic exposure of health care works to N2O is also a concern. Although there are limited data in the literature to clearly substantiate concerns regarding the reproductive toxicity of occupational exposure to N2O, appropriate scavenging and use of other techniques are mandatory. Nitrous oxide has been shown to be effective for a variety of minor surgical procedures such as venipuncture, intravenous cannula placement, lumbar puncture, bone marrow aspiration, laceration repair, dental care, and minor dermatologic procedures. It is generally as effective as midazolam, with several studies demonstrating it to be more effective. However, its utility is not as great in severely painful procedures such as fracture reduction. Demonstrated advantages to parenteral sedation include a more rapid onset and a shorter recovery time with the majority of patients preferring it to over other agents or agreeing to its use for subsequent procedures. The literature also suggests increased success rates with simple procedures such as intravenous cannula placement when compared with placebo. In general, life-threatening adverse events have not been reported. Most common adverse effects include dysphoria and vomiting. For more painful procedures, combination with another agent may be used, and in all cases, topical or infiltrative local anesthesia is recommended. Conclusions: In general, N2O is a useful adjunct for procedural sedation. Given the variety of procedures performed in the pediatric patient, ongoing research is required to identify the most appropriate and effective use of this agent. This may be particularly relevant when evaluating its use for procedures associated with significant pain. In these scenarios, the combination of N2O with other agents needs to be evaluated. Given the potential for adverse effects, strict adherence to published guidelines regarding procedural sedation and monitoring is suggested. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Klebanoff M.A.,Nationwide Childrens Hospital
Obstetrics and Gynecology | Year: 2011

Objective: To estimate the association between fish consumption and erythrocyte omega-3 long-chain polyunsaturated fatty acids and preterm birth in a high-risk cohort. Methods:This was an ancillary study to a randomized trial of omega-3 supplementation to prevent preterm birth in women with at least one previous spontaneous preterm delivery. Dietary fish intake was assessed by questionnaire and erythrocyte fatty acids were measured at enrollment (16-21 completed weeks of gestation). The association between fish consumption and preterm delivery was modeled with linear and quadratic terms. Rssults: The probability of preterm birth was 48.6% among women eating fish less than once a month and 35.9% among women eating fish more often (P<.001). The adjusted odds ratio for preterm birth among women reporting moderately frequent fish consumption (three servings per week) was 0.60 (95% confidence interval 0.38-0.95), with no further reduction in preterm birth among women who consumed more than three servings of fish per week. Erythrocyte omega-3 levels correlated weakly but significantly with frequency of fish intake (Spearman r=0.22, P<.001); women in the lowest quartile of erythrocyte omega-3 levels were more likely to report consuming less than one fish meal per month (40.3%) than were women in the highest three quartiles (26.3%, P<.001). CONCLUSION:: Moderate fish intake (up to three meals per week) before 22 weeks of gestation was associated with a reduction in repeat preterm birth. More than moderate consumption did not confer additional benefit. These results support the recommendations of the U.S. Food and Drug Administration and the American Congress of Obstetricians and Gynecologists for fish consumption during pregnancy. © 2011 The American College of Obstetricians and Gynecologists. Source

Each year, 1 million people are seen in an emergency department for seizures or epilepsy. We implemented a care management checklist for patients with frequent visits. A database was searched for patients with the highest number of emergency department visits and/or unplanned hospitalizations in 2011. Four patients were selected. A care management checklist was implemented in 2012. Compliance with the office visits, number of emergency department visits and/or hospitalizations, and the associated costs were tracked following implementation of the checklist for 2011 and 2012. These 4 epilepsy patients accounted for 46 visits in the year 2011 with associated health care costs of $380,209. Following a year using a care management checklist, the same patients accounted for 11 visits with a cost reduction of $188,130. Using a care management checklist was useful in these 4 epilepsy patients to decrease emergency department visits and/or unplanned hospitalizations. A limitation of this study is its small numbers. © The Author(s) 2013. Source

Smith M.A.,U.S. National Cancer Institute | Houghton P.,Nationwide Childrens Hospital
Clinical Cancer Research | Year: 2013

The high rate of negative clinical trials and failed drug development programs calls into question the use of preclinical testing as currently practiced. An important issue for the in vitro testing of agents that have advanced into the clinic is the use of clinically irrelevant concentrations in reports making claims for anticancer activity, as illustrated by publications for sorafenib, vorinostat, and metformin. For sorafenib, high protein binding leads to a dichotomy between concentrations active in the 10% serum conditions commonly used for in vitro testing and concentrations active in plasma. Failure to recognize this distinction leads to inappropriate claims of activity for sorafenib based on the micromolar concentrations commonly used for in vitro testing in low serum conditions. For vorinostat and metformin, results using in vitro concentrations higher than those achievable in patients are reported despite the availability of publications describing human pharmacokinetic data for each agent. We encourage journal editors and reviewers to pay greater attention to clinically relevant concentrations when considering reports that include in vitro testing of agents for which human pharmacokinetic data are available. Steps taken to more carefully scrutinize activity claims based on in vitro results can help direct researchers away from clinically irrelevant lines of research and toward lines of research that are more likely to lead to positive clinical trials and to improved treatments for patients with cancer. ©2013 AACR. Source

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