Jensen A.R.,Indiana University |
Doster D.L.,Indiana University |
Hunsberger E.B.,Indiana University |
Manning M.M.,Indiana University |
And 8 more authors.
Shock | Year: 2016
Objective: Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: human adipose-derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared with differentiated cellular controls following ischemic intestinal injury, and improved outcomes with hASC therapy would be associated with preservation of intestinal histological and tight junction architecture, and lower levels of systemic inflammation following intestinal injury. Methods: hASCs and keratinocytes (differentiated cellular control) were cultured on polystyrene flasks at 37°C in 5% CO 2 in air. Adult male C57Bl6J mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 min with a noncrushing vascular clamp. Following ischemia, the clamp was removed, and the intestines were returned to the abdominal cavity. Before abdominal closure, 2 million hASCs or keratinocytes in 250 μL of phosphate-buffered saline (carrier for cells and control solution) were infused into the peritoneum. Animals were allowed to recover for 12 or 24 h (perfusion, histology, cytokine, and immunofluoresence studies), or 7 days (survival studies). Intestinal perfusion was assessed by laser Doppler imaging. Intestinal tissue segments were stained with hematoxylin and eosin, as well as antibodies for the tight junction protein claudin-1. Separate aliquots of intestine, liver, and lung tissue were homogenized and assessed for inflammatory cytokines via multiplex beaded assay. Results: Animals administered hASCs following intestinal ischemia and reperfusion (I/R) injury had significantly greater 7-day survival and better postischemic recovery of mesenteric perfusion compared with vehicle or keratinocyte therapy. hASCs also abated intestinal mucosal destruction, facilitated preservation of intestinal tight junctions, and decreased the systemic inflammatory response to injury. Conclusions: Human adipose-derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal I/R injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia. © 2016 by the Shock Society.
Rhee C.J.,Section of Neonatology |
Rhee C.J.,Baylor College of Medicine |
Kibler K.K.,Baylor College of Medicine |
Brady K.M.,Baylor College of Medicine |
And 3 more authors.
Pediatrics | Year: 2013
New noninvasive methods for monitoring cerebrovascular pressure reactivity coupled with a blood-based assay for brain-specific injury in preterm infants could allow early diagnosis of brain injury and set the stage for improved timing and effectiveness of interventions. Using an adaptation of near-infrared spectroscopy, we report a case of a very low birth weight infant undergoing hemoglobin volume index monitoring as a measure of cerebrovascular pressure reactivity. During the monitoring period, this infant demonstrated significant disturbances in cerebrovascular pressure reactivity that coincided with elevation of serum glial fibrillary acidic protein and new findings of brain injury on head ultrasound. This case report demonstrates the potential of emerging noninvasive monitoring methods to assist in both detection and therapeutic management to improve neurologic outcomes of the very low birth weight neonate. Copyright © 2013 by the American Academy of Pediatrics.
Khajeh L.,Rotterdam University |
Cherian P.J.,Rotterdam University |
Swarte R.M.,Section of Neonatology |
Smit L.S.,Section of Pediatric Neurology |
Lequin M.H.,Erasmus MC Sophia
Journal of Child Neurology | Year: 2014
Apneic neonatal seizures can present as apparent life-threatening events. We report a newborn with unexplained episodes of apnea associated with cyanosis and desaturation, starting on the first day postpartum. Biochemical tests were normal. Central nervous system infections as well as abnormalities of upper airways and cardiovascular system were excluded. Brain monitoring using amplitude-integrated electroencephalography (aEEG) was inconclusive. Continuous monitoring using video EEG revealed epileptic seizures originating from the left temporal region as the cause of the apneas. Magnetic resonance imaging (MRI) of the brain showed a developmental malformation of the left frontal and temporal lobes. The patient became seizure free after treatment with antiepileptic medication. This report illustrates that brain monitoring using amplitude-integrated EEG alone could miss focal neonatal seizures. When clinical suspicion of apneic seizures is high in infants with apparent life threatening events, multichannel polygraphic video-EEG monitoring is indicated. Prompt diagnosis and treatment can be life saving. © The Author(s) 2013.
Kramer E.L.,Section of Neonatology |
Hardie W.D.,Cincinnati |
Mushaben E.M.,Section of Neonatology |
Acciani T.H.,Section of Neonatology |
And 5 more authors.
Journal of Applied Physiology | Year: 2011
Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and chronic obstructive pulmonary disease. New therapeutic targets are needed as some patients are refractory to current therapies and develop progressive airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key regulator of cellular proliferation and survival. Treatment with the mTOR inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or whether its therapeutic effects are entirely mediated through immunosuppression. To address this question, we utilized transforming growth factor-α (TGF-α) transgenic mice null for the transcription factor early growth response-1 (Egr-1) (TGF-α Tg/Egr-1 ko/ko mice). These mice develop airway smooth muscle thickening and AHR in the absence of altered lung inflammation, as previously reported. In this study, TGF-α Tg/Egr-1 ko/ko mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-α induction. Rapamycin treatment prevented body weight loss, airway wall thickening, abnormal lung mechanics, and increases in airway resistance to methacholine after 3 wk of TGF-α induction. Increases in tissue damping and airway elastance were also attenuated in transgenic mice treated with rapamycin. TGF-α/Egr-1 ko/ko mice on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for α-smooth muscle actin and morphometric analysis showed that rapamycin treatment prevented airway smooth muscle thickening around small airways. Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels, indicated that rapamycin also attenuated fibrotic pathways induced by TGF-α expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-α-induced/EGF receptor-mediated reactive airway disease. Copyright © 2011 the American Physiological Society.
Love D.,SUNY at Stony Brook |
Li F.-Q.,SUNY at Stony Brook |
Burke M.C.,Medical Scientist Program MSTP |
Cyge B.,SUNY at Stony Brook |
And 6 more authors.
PLoS ONE | Year: 2010
The canonical Wnt/β-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/β-catenin antagonist Chibby (Cby). In support of its inhibitory role in canonical Wnt signaling, expression of b-catenin target genes is elevated in the Cby-/- lung. Notably, Cby protein is prominently associated with the centrosome/basal body microtubule structures in embryonic lung epithelial progenitor cells, and later enriches as discrete foci at the base of motile cilia in airway ciliated cells. At birth, Cby-/-lungs are grossly normal but spontaneously develop alveolar airspace enlargement with reduced proliferation and abnormal differentiation of lung epithelial cells, resulting in altered pulmonary function. Consistent with the Cby expression pattern, airway ciliated cells exhibit a marked paucity of motile cilia with apparent failure of basal body docking. Moreover, we demonstrate that Cby is a direct downstream target for the master ciliogenesis transcription factor Foxj1. Collectively, our results demonstrate that Cby facilitates proper postnatal lung development and function. © 2010 Love et al.
PubMed | McMaster University and Section of Neonatology
Type: Journal Article | Journal: Journal of perinatology : official journal of the California Perinatal Association | Year: 2016
Our objective was to evaluate the impact of a dedicated resuscitation and stabilization (RAS) room and process changes on infant stabilization time.A prospective quality improvement study was conducted on preterm infants in a tertiary care center. A dedicated RAS room, preresuscitation huddle, infant-isolette-ventilator pairing and improved documentation were implemented. The primary outcome was median time to stabilization and secondary outcomes were illness severity on day 1 and morbidity at discharge.A sustained reduction in median time to stabilization from 90min in the preimplementation phase to 72min in the sustainability phase was observed. All planned and iterative process changes were integrated into the RAS teams daily routine. Time to completion of procedures decreased, illness severity and morbidity remained unchanged.A dedicated RAS room adjacent to the delivery suite in conjunction with process changes improves efficiency of care.
Bashir R.A.,Section of Neonatology |
Swarnam K.,Section of Neonatology |
Vayalthrikkovil S.,Section of Neonatology |
Yee W.,Section of Neonatology |
And 2 more authors.
American Journal of Perinatology | Year: 2016
Objective To examine whether there is an association between peripherally inserted central venous catheter (PICC) insertion site and complication rates among preterm infants. Design We performed a retrospective analysis of the first PICCs placed in preterm infants in a tertiary neonatal intensive care unit between January 2006 and December 2010. The PICC-related complications resulting in catheter removal were compared based on site of insertion. Results Of the 827 PICCs, 593 (72%) were inserted in upper extremity. Lower extremity PICC group infants had higher illness severity (SNAP-II) score and more likely to be inserted later as compared with the upper extremity group. There was no significant difference in the total PICC-related complications between upper and lower extremity PICCs (31.3 vs. 26%; p > 0.05). Logistic regression analysis after adjusting for gestational age, day of line insertion, and SNAP-II score revealed that upper extremity PICCs were associated with increased risk of line infiltration (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 1.36–4.29) but not the total PICC complication (aOR, 1.29; 95% CI, 0.91–1.83). Conclusion There is no difference in total PICC-related complication between upper and lower extremity PICCs; however, the PICC-related mechanical complications vary depending on the site of insertion in preterm infants. Copyright © 2016, Thieme Medical Publishers. All rights reserved.