Rebecca Darrah
Case Western Reserve University
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Featured researches published by Rebecca Darrah.
Journal of Genetic Counseling | 2014
Elinor Langfelder-Schwind; Barbara Karczeski; Michelle N. Strecker; Joy B Redman; Elaine A Sugarman; Christina Zaleski; Trisha Brown; Steven Keiles; Amy Powers; Sumheda Ghate; Rebecca Darrah
PurposeTo provide practice recommendations for genetic counselors whose clients are considering cystic fibrosis (CF) carrier testing or seeking information regarding CF molecular test results. The goals of these recommendations are to: 1) Provide updated information about the natural history, diagnosis, and treatment of CF and related conditions. 2) Supplement genetic counselors’ knowledge and understanding of the available carrier screening and diagnostic testing options. 3) Describe the current state of genotype/phenotype correlations for CFTR mutations and an approach to interpreting both novel and previously described variants. 4) Provide a framework for genetic counselors to assist clients’ decision-making regarding CF carrier testing, prenatal diagnosis, and pregnancy management. Disclaimer The practice guidelines of the National Society of Genetic Counselors (NSGC) are developed by members of the NSGC to assist genetic counselors and other health care providers in making decisions about appropriate management of genetic concerns; including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue, and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the NSGC practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are only current as of their publication date, and are subject to change without notice as advances emerge.In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health care provider’s best medical judgment based on the clinical circumstances of a particular patient or patient population.Practice guidelines are published by NSGC for educational and informational purposes only, and NSGC does not “approve” or “endorse” any specific methods, practices, or sources of information.
NMR in Biomedicine | 2014
Ying Gao; Candida L. Goodnough; Bernadette O. Erokwu; George W. Farr; Rebecca Darrah; Lan Lu; Katherine M. Dell; Xin Yu; Chris A. Flask
Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright
Journal of Cystic Fibrosis | 2013
Rebecca Darrah; Ilya R. Bederman; Anna L. Mitchell; Craig A. Hodges; Cara K. Campanaro; Mitchell L. Drumm; Frank J. Jacono
BACKGROUND Altered ventilatory pattern and increased energy expenditure are facets of the complex cystic fibrosis (CF) phenotype. It is not known whether these are inherent attributes of CF, secondary consequences of lung infection or other disease complications. METHODS Studies were performed in congenic C57BL/6J, F508del (Cftr((tm1kth))) and CF gut-corrected (F508del) mice. Ventilatory patterns were measured using whole-body plethysmography. Indirect calorimetry was used to determine oxygen consumption, carbon dioxide production and resting energy expenditure. RESULTS CF mice (F508del and F508del gut-corrected) have a significantly faster respiratory rate and increased ventilatory pattern variability as compared to non-CF mice. F508del but not CF gut-corrected mice had significantly increased energy expenditure per gram body weight. CONCLUSIONS CF mice exhibit a faster, more variable ventilatory pattern. These changes were present in the absence of detectable infection or illness due to gastrointestinal obstruction. Increased resting energy expenditure does not completely account for these differences.
Journal of Cystic Fibrosis | 2016
Rebecca Darrah; Anna L. Mitchell; Cara K. Campanaro; Eric S. Barbato; Paul Litman; Abdus Sattar; Craig A. Hodges; Mitchell L. Drumm; Frank J. Jacono
BACKGROUND Altered pulmonary function is present early in the course of cystic fibrosis (CF), independent of documented infections or onset of pulmonary symptoms. New initiatives in clinical care are focusing on detection and characterization of preclinical disease. Thus, animal models are needed which recapitulate the pulmonary phenotype characteristic of early stage CF. METHODS We investigated young CF mice to determine if they exhibit pulmonary pathophysiology consistent with the early CF lung phenotype. Lung histology and pulmonary mechanics were examined in 12- to 16-week-old congenic C57bl/6 F508del and R117H CF mice using a forced oscillation technique (flexiVent). RESULTS There were no significant differences in the resistance of the large airways. However, in both CF mouse models, prominent differences in the mechanical properties of the peripheral lung compartment were identified including decreased static lung compliance, increased elastance and increased tissue damping. CF mice also had distal airspace enlargement with significantly increased mean linear intercept distances. CONCLUSIONS An impaired ability to stretch and expand the peripheral lung compartment, as well as increased distances between gas exchange surfaces, were present in young CF mice carrying two independent Cftr mutations. This altered pulmonary histopathophysiology in the peripheral lung compartment, which develops in the absence of infection, is similar to the early lung phenotype of CF patients.
Journal of Clinical Microbiology | 2014
Theodore Spilker; Amy Leber; Mario J. Marcon; Duane W. Newton; Rebecca Darrah; Peter Vandamme; John J. LiPuma
ABSTRACT The differentiation of Bordetella species, particularly those causing human infection, is problematic. We found that sequence analysis of an internal fragment of nrdA allowed differentiation of the currently named Bordetella species. Analysis of 107 “Bordetella” isolates recovered almost exclusively from human respiratory tract specimens identified several putative novel species.
Journal of Cystic Fibrosis | 2016
Kai Jiang; Sen Jiao; Megan Vitko; Rebecca Darrah; Chris A. Flask; Craig A. Hodges; Xin Yu
BACKGROUND Altered cardiac function has been observed in cystic fibrosis transmembrane regulator (CFTR) knockout mice. However, whether this alteration is a direct effect of CFTR disruption in the heart, or is secondary due to systemic loss of CFTR, remains to be elucidated. METHODS Cardiac function of mice with muscle-specific or global knockout of CFTR was evaluated at baseline and under β-stimulation by MRI in vivo. Myocyte contractility and Ca2+ transients were measured in vitro. RESULTS Both CFTR knockout models showed increased twist and torsion at baseline. Response to β-stimulation was unaltered in muscle-specific CFTR knockout mice and was slightly decreased in global CFTR knockout mice. Aortic diameter was also decreased in both mouse models. No difference was observed in myocyte contractility and Ca2+ transients. CONCLUSIONS CFTR disruption leads to increased myocardial contractility at baseline, which may trigger untoward myocardial remodeling in CF patients that is independent of lung diseases.
Scientific Reports | 2017
Christian E. Anderson; Shannon B. Donnola; Yun Jiang; Joshua Batesole; Rebecca Darrah; Mitchell L. Drumm; Susann M. Brady-Kalnay; Nicole F. Steinmetz; Xin Yu; Mark A. Griswold; Chris A. Flask
Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI’s ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC – MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This “multi-color” MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.
Magnetic Resonance in Medicine | 2018
Christian E. Anderson; Charlie Y. Wang; Yuning Gu; Rebecca Darrah; Mark A. Griswold; Xin Yu; Chris A. Flask
The regularly incremented phase encoding–magnetic resonance fingerprinting (RIPE‐MRF) method is introduced to limit the sensitivity of preclinical MRF assessments to pulsatile and respiratory motion artifacts.
Respiratory Physiology & Neurobiology | 2017
Carl B. Gillombardo; Rebecca Darrah; Thomas E. Dick; Michael W. Moore; Nathan Kong; Michael J. Decker; Fang Han; Motoo Yamauchi; Mathias Dutschmann; Sausan Azzam; Kingman P. Strohl
RATIONALE Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. CONCLUSIONS The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea.
Biological Research For Nursing | 2016
Rebecca Darrah; Rebecca Nelson; Elizabeth G. Damato; Michael J. Decker; Anne L. Matthews; Craig A. Hodges
Introduction: Cystic fibrosis (CF) is a complex disease that includes both pulmonary and gastrointestinal challenges, resulting in decreased weight. Pulmonary symptoms of CF are extremely variable. Greater body mass at an early age is associated with improved pulmonary function, but it is unknown at what age weight becomes predictive of pulmonary disease severity. The purpose of this study was to investigate the relationship between birth weight and pulmonary function in CF. Methods: Birth weight and pulmonary data were obtained. Linear regressions were used to examine the relationship between these two variables. A one-tailed t-test was used to compare birth weights between CF patients and the national average. Results: Birth weight was significantly lower in babies with CF and correlated with pulmonary disease at ages 6 and 10 years but not with age at which Pseudomonas aeruginosa colonization was observed. Discussion: These data suggest that CF growth deficiency has prenatal origins. Early nutritional intervention for babies with CF and a low birth weight is warranted to maximize pulmonary potential.