Publications (16)64.76 Total impact
-
Article: Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury.
[show abstract] [hide abstract]
ABSTRACT: The brain contains a highly diversified complement of molecular species of a mitochondria-specific phospholipid, cardiolipin, which, because of its polyunsaturation, can readily undergo oxygenation. Using global lipidomics analysis in experimental traumatic brain injury (TBI), we found that TBI was accompanied by oxidative consumption of polyunsaturated cardiolipin and the accumulation of more than 150 new oxygenated molecular species of cardiolipin. RNAi-based manipulations of cardiolipin synthase and cardiolipin levels conferred resistance to mechanical stretch, an in vitro model of traumatic neuronal injury, in primary rat cortical neurons. By applying a brain-permeable mitochondria-targeted electron scavenger, we prevented cardiolipin oxidation in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, and markedly reduced behavioral deficits and cortical lesion volume. We conclude that cardiolipin oxygenation generates neuronal death signals and that prevention of it by mitochondria-targeted small molecule inhibitors represents a new target for neuro-drug discovery.Nature Neuroscience 08/2012; 15(10):1407-13. · 15.53 Impact Factor -
Article: Prevalence, Clinical Features and Management of Pediatric Magnetic Foreign Body Ingestions.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Foreign body (FB) ingestions are frequent in children. Whereas the majority of FBs pass spontaneously through the gastrointestinal tract, ingestion of magnetic FBs pose a particular risk for obstruction due to proximate attraction through the intestinal wall. STUDY OBJECTIVES: We aimed to identify the prevalence, clinical presentation, and management of magnetic FB ingestions at our tertiary care institution. METHODS: We performed a retrospective chart review of medical records of patients presenting to the pediatric Emergency Department (ED) or admitted to the hospital with FB ingestions from June 2003-July 2009. From those cases, patients with magnetic FB ingestions were identified. RESULTS: During the study period, 337,839 patients presented to the ED; 38 cases of magnetic FB ingestion were identified (prevalence 0.01%). Abdominal radiography was obtained in all cases. Ingestion of a single magnet occurred in 30 of 38 cases (79%). Of those, 4 patients underwent endoscopic removal due to signs of FB impaction in the esophagus or pylorus; no complications were noted. Ingestion of multiple magnets (range 2-6) occurred in 8 of 38 cases. Four of the 8 patients with multiple magnetic FBs (50%) presented with signs of peritonitis and required operative repair of multiple intestinal perforations. No deaths were identified. CONCLUSION: Although ingestion of a single magnetic FB may, in most cases, be managed as a simple FB ingestion, the ingestion of multiple magnetic FB is associated with a high risk of complication and requires aggressive management. We propose an algorithm for management of children with magnetic FB ingestions.Journal of Emergency Medicine 06/2012; · 1.31 Impact Factor -
Article: Increased cytochrome c in rat cerebrospinal fluid after cardiac arrest and its effects on hypoxic neuronal survival.
[show abstract] [hide abstract]
ABSTRACT: Cerebrospinal fluid (CSF) proteins may be useful biomarkers of neuronal death and ultimate prognosis after hypoxic-ischemic brain injury. Cytochrome c has been identified in the CSF of children following traumatic brain injury. Cytochrome c is required for cellular respiration but it is also a central component of the intrinsic pathway of apoptosis. Thus, in addition to serving as a biomarker, cytochrome c release into CSF may have an effect upon survival of adjacent neurons. In this study, we use Western blot and ELISA to show that cytochrome c is elevated in CSF obtained from pediatric rats following resuscitation from cardiac arrest. Using biotinylated human cytochrome c in culture media we show that cytochrome c crosses the cell membrane and is incorporated into mitochondria of neurons exposed to anoxia. Lastly, we show that addition of human cytochrome c to primary neuronal culture exposed to anoxia improves survival. To our knowledge, this is the first study to show cytochrome c is elevated in CSF following hypoxic ischemic brain injury. Results from primary neuronal culture suggest that extracellular cytochrome c is able to cross the cell membrane of injured neurons, incorporate into mitochondria, and promote survival following anoxia.Resuscitation 04/2012; · 3.60 Impact Factor -
Article: Polynitroxyl albumin and albumin therapy after pediatric asphyxial cardiac arrest: effects on cerebral blood flow and neurologic outcome.
[show abstract] [hide abstract]
ABSTRACT: Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 11/2011; 32(3):560-9. · 5.46 Impact Factor -
Article: "Lost in translation?" Noninvasive cerebral monitoring after cardiac arrest.
Critical care medicine 10/2011; 39(10):2379-80. · 6.37 Impact Factor -
Article: Unmasking sex-based disparity in neuronal metabolism.
[show abstract] [hide abstract]
ABSTRACT: Both classic and emerging literature point to sex-based disparity in neuronal metabolism. While detectable under baseline conditions, this phenomenon appears to be exaggerated or sometimes unmasked in neurons by cellular stress. A complex sex-dependent response to nutrient deprivation, excitotoxicity, oxidative/nitrositive stress, oxygen-glucose deprivation, and chemical toxicity has been observed in neurons in vitro, as well as after various insults including ischemic or traumatic brain injury in vivo. Importantly, sex-based disparity in response to diverse therapeutics has been seen in neurons in culture, contemporary animal models of brain injury, and in human disease. These have clear implications for pharmacological design of therapeutics targeting central nervous system diseases involving both males and females, and preclinical testing of promising agents.Current pharmaceutical design 09/2011; 17(35):3854-60. · 4.41 Impact Factor -
Article: Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: effects on oxidative stress.
[show abstract] [hide abstract]
ABSTRACT: To determine the effects of normoxic vs. hyperoxic resuscitation on oxidative stress in a model of pediatric asphyxial cardiac arrest. Prospective, interventional study. University research laboratory. Postnatal day 16-18 rats (n = 5 per group). Rats underwent asphyxial cardiac arrest for 9 min. Rats were randomized to receive 100% oxygen, room air, or 100% oxygen with polynitroxyl albumin (10 mL·kg⁻¹ intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation. Shams recovered in 100% oxygen or room air after surgery. Physiological variables were recorded at baseline to 1 hr after resuscitation. At 6 hrs after asphyxial cardiac arrest, levels of reduced glutathione and protein-thiols (fluorescent assay), activities of total superoxide dismutase and mitochondrial manganese superoxide dismutase (cytochrome c reduction method), manganese superoxide dismutase expression (Western blot), and lipid peroxidation (4-hydroxynonenal Michael adducts) were evaluated in brain tissue homogenates. Hippocampal 3-nitrotyrosine levels were determined by immunohistochemistry 72 hrs after asphyxial cardiac arrest. Survival did not differ among groups. At 1 hr after resuscitation, Pao2, pH, and mean arterial pressure were decreased in room air vs. 100% oxygen rats (59 ± 3 vs. 465 ± 46 mm Hg, 7.36 ± 0.05 vs. 7.42 ± 0.03, 35 ± 4 vs. 45 ± 5 mm Hg; p < .05). Rats resuscitated with 100% oxygen had decreased hippocampal reduced glutathione levels vs. sham (15.3 ± 0.4 vs. 20.9 ± 4.1 nmol·mg protein⁻¹; p < .01). Hippocampal manganese superoxide dismutase activity was significantly increased in 100% oxygen rats vs. sham (14 ± 2.4 vs. 9.5 ± 1.6 units·mg protein⁻¹, p < .01), with no difference in protein expression of manganese superoxide dismutase. Room air and 100% oxygen plus polynitroxyl albumin groups had hippocampal reduced glutathione and manganese superoxide dismutase activity levels comparable with sham. Protein thiol levels were unchanged across groups. Compared with all other groups, rats receiving 100% oxygen had increased immunopositivity for 3-nitrotyrosine in the hippocampus and increased lipid peroxidation in the cortex. Resuscitation with 100% oxygen leads to increased oxidative stress in a model that mimics pediatric cardiac arrest. This may be prevented by using room air or giving an antioxidant with 100% oxygen resuscitation.Critical care medicine 11/2010; 39(2):335-43. · 6.37 Impact Factor -
Article: Limping in toddlers: pelvic abscess presenting with transient synovitis picture.
[show abstract] [hide abstract]
ABSTRACT: Limping is a common presenting pediatric complaint, caused by conditions originating in the lower extremities as well as in anatomical areas surrounding the hip joint. Pathologic processes presenting with limping include trauma, inflammation, infection, and malignancy. In this report, we present a case of pelvic abscess presenting with limping in a toddler. We review common conditions presenting with limping in this age group, and discuss laboratory and radiographic evaluation of limping in toddlers. A 20-month-old previously healthy boy presented for evaluation of limping and history of fever. The physical examination was suggestive of transient synovitis. Radiological evaluation revealed normal hip X-ray study, a normal complete blood count, and a moderately increased erythrocyte sedimentation rate. Due to the persistence of limping, tenderness over the inguinal area and subsequent development of edema over the inguinal area, magnetic resonance images of the hip and pelvis were obtained, which revealed a pelvic abscess. The patient improved after ultrasound-guided drainage of the abscess and a course of intravenous antibiotics. Although transient synovitis is the most common pathology that causes limping in toddlers, limping can also be a presentation of pelvic pathology. Thus, in this age group, a detailed physical examination of the patient with special emphasis on structures adjacent to the hip joint is extremely important. Laboratory evaluation and additional imaging help confirm the suspected diagnosis.Journal of Emergency Medicine 10/2010; 41(6):623-6. · 1.31 Impact Factor -
Article: Cardiac arrest in children.
[show abstract] [hide abstract]
ABSTRACT: Major advances in the field of pediatric cardiac arrest (CA) were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners.Journal of Emergencies Trauma and Shock 07/2010; 3(3):267-72. -
Chapter: Rodent Model of Pediatric Asphyxial Cardiac Arrest
[show abstract] [hide abstract]
ABSTRACT: A model of asphyxial cardiac arrest in 17-day old rats is described. This clinically relevant model includes a period of hypoxemia followed by ischemia and resuscitation. Continuous physiologic monitoring is performed before, during, and after the insult. Graded insults produce consistent and dose-dependent brain injury with histological damage and behavioral impairment. The details of the procedures, along with outcome assessments and applications, are discussed.12/2008: pages 103-113; -
Article: Magnetic resonance imaging assessment of regional cerebral blood flow after asphyxial cardiac arrest in immature rats.
[show abstract] [hide abstract]
ABSTRACT: Cerebral blood flow (CBF) alterations after asphyxial cardiac arrest (CA) are not defined in developmental animal models or humans. We characterized regional and temporal changes in CBF from 5 to 150 mins after asphyxial CA of increasing duration (8.5, 9, 12 min) in postnatal day (PND) 17 rats using the noninvasive method of arterial spin-labeled magnetic resonance imaging (ASL-MRI). We also assessed blood-brain barrier (BBB) permeability, and evaluated the relationship between CBF and mean arterial pressure after resuscitation. After all durations of asphyxia CBF alterations were region dependent. After 8.5- and 9-min asphyxia, intense subcortical hyperemia at 5 min was followed by return of CBF to baseline values by 10 mins. After 12-min asphyxia, hyperemia was absent and hypoperfusion reached a nadir of 38% to 65% of baselines with the lowest values in the cortex. BBB was impermeable to gadoteridol 150 mins after CA. CBF in the 12-min CA group was blood pressure passive at 60 min assessed via infusion of epinephrine. ASL-MRI assessment of CBF after asphyxial CA in PND 17 rats reveals marked duration and region-specific reperfusion patterns and identifies possible new therapeutic targets.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 11/2008; 29(1):197-205. · 5.46 Impact Factor -
Article: Current and future therapies of pediatric cardiopulmonary arrest.
[show abstract] [hide abstract]
ABSTRACT: To review contemporary guidelines and therapies for pediatric cardiac arrest and discuss potential novel therapies. Key articles and guidelines in the field were reviewed along with recent publications in the fields of neurointensive care and neuroscience germane to cerebral resuscitation. A total of 45 articles were reviewed. The majority of arrests in the pediatric population are asphyxial in origin--which differs importantly from the adult population. The International Consensus on CPR guidelines are discussed, including good quality CPR, chest compressions without interruptions, resuscitation with 100% oxygen and subsequent titration of oxygen to normal oxygen saturations, correct dose of epinephrine, and use of hypothermia in the first 12-24 hours. Novel therapies that showed success in animal studies, such as hypertensive reperfusion, thrombolytics, hemodilution and extracorporeal CPR are also discussed. With only 30% return of spontaneous circulation, 12% survival to hospital discharge and 4% intact neurologic survival, pediatric cardiac arrest remains an area of intense research for therapies to improve its outcomes. In addition to the rapid implementation of basic and advanced life support interventions, new therapies that may have value include mild hypothermia, extracorporeal support, promotion of cerebral blood flow and other more novel therapies targeting oxidative stress, excitotoxicity, neuronal death, and rehabilitation.The Indian Journal of Pediatrics 07/2008; 75(6):609-14. · 0.52 Impact Factor -
Article: Emergency department management of the pediatric patient with supraventricular tachycardia.
[show abstract] [hide abstract]
ABSTRACT: Supraventricular tachycardia (SVT) is the most common tachyarrhythmia that necessitates treatment in children. It is characterized by a rapid and regular heart rate, which generally exceeds 180 beats per minute in children and 220 beats per minute in adolescents. Supraventricular tachycardia results from conduction of electrical impulses along an accessory connection from the atrium to the ventricle (atrioventricular reentry tachycardias: orthodromic or antidromic) or conduction within the atrioventricular node (atrioventricular node reentry tachycardia). Emergency department management of SVT depends on the patient's clinical status. Treatment of a stable patient with SVT includes vagal maneuvers and adenosine, whereas treatment of an unstable patient requires synchronized cardioversion. This article presents an overview of the etiology, pathophysiology, and clinical presentation of SVT and discusses the emergency department management of an infant or child with SVT.Pediatric emergency care 04/2007; 23(3):176-85; quiz 186-9. · 0.92 Impact Factor -
Article: Preterminal gasping and effects on the cardiac function.
[show abstract] [hide abstract]
ABSTRACT: Gasping, also known as agonal respirations, is the terminal pattern that occurs after anoxia or ischemia and is a universal phenomenon in mammals. In this article we review the physiology of gasping, the prevalence and significance of gasping in cardiac arrest, and the effects of gasping on cardiac function. Review relevant human and animal literature on gasping and cardiac function during gasping. Gasping originates in the medullary area of the central nervous system. Gasping is prevalent during cardiac arrest: it occurs in all animals during ventricular fibrillation, in a majority of infants (31 of 32) with sudden infant death syndrome, and in 30-40% of witnessed episodes of cardiac arrest in adults. Animal studies demonstrated that gasping is associated with a decrease in intrathoracic pressure during the inspiratory phase, which promotes venous return and an increase in intrathoracic pressure during the expiratory phase, which favors coronary perfusion. Gasping increases cardiac output and cardiac contractility in immature animals exposed to anoxia. Gasping is auto-resuscitative in immature mammals and improves the outcome of cardiopulmonary resuscitation in mature mammals. Gasping is associated with important cardiorespiratory changes: improved pulmonary gas exchange, increased venous return to the heart, increased cardiac output, cardiac contractility, aortic pressure, and coronary perfusion pressure.Critical Care Medicine 01/2007; 34(12 Suppl):S438-41. · 6.33 Impact Factor -
Article: Preterminal gasping during hypoxic cardiac arrest increases cardiac function in immature rats.
[show abstract] [hide abstract]
ABSTRACT: Newborn animals are more resistant to anoxia than older animals, partly due to an increased tolerance of the immature heart to anoxia. Newborn animals also have a more robust preterminal gasp. We investigated the relationship between gasping and cardiac function in immature and maturing rats exposed to anoxia. Immature postnatal day 7 (PND7) rats (n = 13) and maturing PND17 rats (n = 13) were exposed to 100% nitrogen (anoxia) for 10 min. Echocardiography was used to calculate cardiac contractility (CC) by left ventricular shortening fraction and cardiac output (CO) from Doppler velocity recordings of pulmonary artery blood flow. In a separate group of PND7 rats, CC and CO were recorded after the paralytic agent pancuronium was used to prevent gasping. Anoxia decreased CC and CO in PND7 and PND17 rats, followed by a partial and transient recovery. Gasping preceded recovery of CO and was required to sustain CO. Gasping in PND7 rats lasted longer (541 s versus 351 s, p < 0.01) and resulted in a greater recovery of CC and CO. Anoxia-induced gasping and the associated recovery of cardiac function were abolished by paralysis. Thus, anoxia-induced gasping transiently improves cardiac function, and more robust gasping in immature rats is associated with increased cardiac anoxic tolerance.Pediatric Research 09/2006; 60(2):174-9. · 2.70 Impact Factor -
Article: Breastfeeding-associated hypernatremia: are we missing the diagnosis?
[show abstract] [hide abstract]
ABSTRACT: To assess the incidence and complications of breastfeeding-associated hypernatremic dehydration among hospitalized neonates. Study A retrospective study was conducted at Children's Hospital of Pittsburgh over a 5-year period, to identify otherwise healthy term and near-term (> or =35 weeks of gestation) breastfed neonates (<29 days of age) who were admitted with serum sodium concentrations of > or =150 mEq/L and no explanation for hypernatremia other than inadequate milk intake. The incidence of breastfeeding-associated hypernatremic dehydration among 3718 consecutive term and near-term hospitalized neonates was 1.9%, occurring for 70 infants. These infants were born primarily to primiparous women (87%) who were discharged within 48 hours after birth (90%). The most common presenting symptom was jaundice (81%). Sixty-three percent of infants underwent sepsis evaluations with lumbar puncture. No infants had bacteremia or meningitis. Infants had hypernatremia of moderate severity (median: 153 mEq/L; range: 150-177 mEq/L), with a mean weight loss of 13.7%. Nonmetabolic complications occurred for 17% of infants, with the most common being apnea and/or bradycardia. There were no deaths. Hypernatremic dehydration requiring hospitalization is common among breastfed neonates. Increased efforts are required to establish successful breastfeeding.PEDIATRICS 10/2005; 116(3):e343-7. · 4.47 Impact Factor
Top co-authors
Top Journals
Institutions
-
2008–2011
-
University of Pittsburgh
- • Department of Pediatrics
- • Division of Pediatric Emergency Medicine
Pittsburgh, PA, USA
-
-
2006–2008
-
Childrens Hospital of Pittsburgh
- • Division of Pediatric Emergency Medicine
- • Department of Pediatrics
Pittsburgh, PA, USA
-
