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Kerlin B.A.,Nationwide Childrens Hospital | Kerlin B.A.,Ohio State University | Kerlin B.A.,Nationwide Childrens Hospital Research Institute
American Journal of Hematology | Year: 2012

Venous thromboembolism (VTE) is an increasingly common complication encountered in tertiary care pediatric settings. The purpose of this review is to summarize the epidemiology, current and emerging pharmacotherapeutic options, and management of this disease. Over 70% of VTE occur in children with chronic diseases. Although they are seen in children of all ages, adolescents are at greatest risk. Pediatric VTE is associated with an increased risk of in-hospital mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in survivors. In recent years, anticoagulation with low molecular weight heparin has emerged as the mainstay of therapy, but compliance is limited by its onerous subcutaneous administration route. New anticoagulants either already approved for use in adults or in the pipeline offer the possibility of improved dose stability and oral routes of administration. Current recommended anticoagulation course durations are derived from very limited case series and cohort data, or extrapolations from adult literature. However, the pathophysiologic underpinnings of pediatric VTE are dissimilar from those seen in adults and are often variable within groups of pediatric patients. Clinical studies and trials in pediatric VTE are underway which will hopefully improve the quality of evidence from which therapeutic guidelines are derived. © 2012 Wiley Periodicals, Inc. Source

Armstrong K.R.,Ohio State University | Armstrong K.R.,Nationwide Childrens Hospital Research Institute | Chamberlin H.M.,Ohio State University
Molecular Genetics and Genomics | Year: 2010

Excretory renal organs are critical in animals for osmoregulation and the elimination of waste. Renal organs across a range of species exhibit cellular and molecular similarities. For example, class III POU-homeodomain transcription factors are expressed in the renal organs of many invertebrates and vertebrates. However, the functional role for these factors is not well characterized. To better understand the role of class III POU-homeodomain proteins in animal excretory systems, we have characterized a set of genes expressed in the Caenorhabditis elegans excretory cell, and determined their regulation by the POU-III transcription factor CEH-6. Our molecular and biochemical studies show that CEH-6 regulates a subset of genes expressed in the excretory cell. Additionally, we find that the CEH-6-dependent genes share two molecular features: They contain at least one octamer regulatory element and they encode for transport and channel proteins. This work suggests that a role for POU-III factors in renal organs is to coordinate the expression of a set of functionally related genes. © 2009 Springer-Verlag. Source

Jadcherla S.R.,Ohio State University | Jadcherla S.R.,Nationwide Childrens Hospital Research Institute | Wang M.,Nationwide Childrens Hospital Research Institute | Vijayapal A.S.,Medical College of Wisconsin | Leuthner S.R.,Medical College of Wisconsin
Journal of Perinatology | Year: 2010

Objective: Feeding problems are an important area of neonatal morbidity that requires attention. We defined the feeding milestones related to transition to per oral feeding among premature infants based on gestational (GA) and postmenstrual ages (PMA), and elucidated the co-morbidity variables affecting with these skills. Study Design: Feeding progress was tracked during the first hospitalization in a retrospective study involving 186 infants. We measured the age at acquisition of first feedings, maximum gavage feedings and maximum oral feedings. Resource usage measures included the total length of hospital stay (LOS), duration of gavage tube and duration of respiratory support. Effects of perinatal and co-morbidity factors on the acquisition of feeding milestones were evaluated. ANOVA, t-test, Wilcoxon rank sum test, χ2 test, univariate and multivariate analysis, stepwise linear regression analysis and logistic regression analysis were applied as appropriate. Data were presented as mean±s.d., or as stated. P<0.05 was considered significant. Result: We stratified the data into three groups based on GA at birth: <28.0 weeks (group-1), 28.0 to 32.0 weeks (group-2) and 32.0 to 35.0 weeks (group-3). Compared with group-3, group-1 needed four-fold more ventilation and five-fold more continuous positive airway pressure (CPAP) duration (all P<0.001); whereas group-2 needed two-fold more CPAP duration. Age at first feed correlated with age at full gavage feedings and age at full oral feedings (r=0.53 and r=0.71, both P<0.0001). Age at full gavage feedings correlated with age at full oral feedings (r=0.81, P<0.0001). Univariate analysis was significant for GA age, hypotension, the effects of gastroesophageal reflux, and duration of ventilation and CPAP on the PMA at maximal oral feedings (all P<0.05); multivariate analysis for these variables was also significant (R 2=0.58, P<0.0001). The success rate for oral feedings at discharge accelerated with GA maturation and caffeine use; on the other hand, the need for respiratory support and management of positive blood culture were associated with failure rates (P<0.05). Conclusion: Infants < 28 weeks GA have significant feeding delays with respect to initiation and progression to maximal gavage and oral feedings, as well as prolonged LOS. Infants >28 weeks GA attained successful feeding milestones by similar PMA. Specific aero-digestive co-morbidities significantly affected maximal oral feeding milestone. Delays in achieving maximum gavage and maximum oral feeding milestones suggest delays with the development of control and regulation of foregut motility. © 2010 Nature Publishing Group All rights reserved. Source

Hasenstab K.A.,Nationwide Childrens Hospital Research Institute | Jadcherla S.R.,Nationwide Childrens Hospital Research Institute | Jadcherla S.R.,Ohio State University
Journal of Pediatrics | Year: 2014

Objective To test the hypothesis that proximal aerodigestive clearance mechanisms mediated by pharyngoesophageal motility during spontaneous respiratory events (SREs) are distinct in infants with apparent life threatening events (ALTEs). Study design Twenty infants (10 with proven ALTE, 10 healthy controls) had pharyngoesophageal manometry to investigate motility changes concurrent with respiratory events detected by respiratory inductance plethysmography and nasal thermistor methods. We measured changes in resting upper esophageal and lower esophageal sphincter pressures, esophageal peristalsis characteristics, and gastroesophageal reflux. Statistical analysis included mixed models; data presented as mean ± SD, median (range), or percentage. Results Infants with ALTE (vs controls) had: (1) delays in restoring aerodigestive normalcy as indicated by more frequent (P =.03) and prolonged SREs (P <.01); (2) a lower magnitude of protective upper esophageal sphincter contractile reflexes (P =.01); (3) swallowing as the most frequent esophageal event associated with SREs (84%), with primary peristalsis as the most prominent aerodigestive clearance mechanism (64% vs 38%, P <.01); (4) a higher proportion of failed esophageal propagation (10% vs 0%, P =.02); and (5) more frequent mixed apneic mechanisms (P <.01) and more gasping breaths (P =.04). Conclusions In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility characterized by frequent primary peristalsis and significant propagation failure, thus suggestive of dysfunctional regulation of swallow-respiratory junction interactions. Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract. Copyright © 2014 Elsevier Inc. All rights reserved. Source

Kelly L.E.,Nationwide Childrens Hospital Research Institute | El-Hodiri H.M.,Nationwide Childrens Hospital Research Institute | El-Hodiri H.M.,Ohio State University
Development Genes and Evolution | Year: 2016

Nkx5 family members are homeobox transcription factors important for sensory organ development. Several members of the Nkx5 family are expressed in the eye, brain, developing ear, and lateral line. Members of this family have been previously identified in medaka, chick, and mouse. Here, we characterize two members of the Nkx5 family, Nkx5.3 and SOHo, in Xenopus laevis. We verify the identity of X. laevis Nkx5.3 and SOHo by phylogenetic comparison to chicken, medaka, and zebrafish orthologs. Both Nkx5.3 and SOHo are expressed in the developing eye, ear, lateral line system, and cranial neurons as determined by in situ hybridization. © 2016 Springer-Verlag Berlin Heidelberg Source

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