Jon F Watchko

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (143)565.07 Total impact

  • Jon F. Watchko
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    ABSTRACT: "Common red blood cell disorders encountered in the normal newborn nursery include hemolytic disease of the newborn and resultant hyperbilirubinemia, anemia, and polycythemia. A less frequent clinically relevant hematologic issue in newborns to be covered herein is thrombocytopenia." Copyright © 2015 Elsevier Inc. All rights reserved.
    Pediatric Clinics of North America 01/2015; 62(2). DOI:10.1016/j.pcl.2014.11.011 · 2.12 Impact Factor
  • Jon F Watchko · Michael J Painter · Ashok Panigrahy
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    ABSTRACT: Investigators have hypothesized a range of subcortical neuropathology in the genesis of bilirubin-induced neurologic dysfunction (BIND). The current review builds on this speculation with a specific focus on the cerebellum and its connections in the development of the subtle neuromotor disabilities of BIND. The focus on the cerebellum derives from the following observations: (i) the cerebellum is vulnerable to bilirubin-induced injury; perhaps the most vulnerable region within the central nervous system; (ii) infants with cerebellar injury exhibit a neuromotor phenotype similar to BIND; and (iii) the cerebellum has extensive bidirectional circuitry projections to motor and non-motor regions of the brainstem and cerebral cortex that impact a variety of neurobehaviors. Future study using advanced magnetic resonance neuroimaging techniques have the potential to shed new insights into bilirubin's effect on neural network topology via both structural and functional brain connectivity measurements. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Seminars in Fetal and Neonatal Medicine 12/2014; 20(1). DOI:10.1016/j.siny.2014.12.004 · 3.03 Impact Factor
  • Jon F. Watchko · Darrell Triulzi
    Transfusion 11/2014; 54(11). DOI:10.1111/trf.12858 · 3.23 Impact Factor
  • Jon F. Watchko · M. Jeffrey Maisels
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    ABSTRACT: Low bilirubin kernicterus in preterm neonates, though rare, remains an unpredictable and refractory form of brain injury. Hypoalbuminemia, co-morbid CNS insult(s), infection, and inflammation are contributing causes that, in many cases, appear to interact in potentiating bilirubin neurotoxicity. Despite compulsive attention to serum bilirubin levels, and clinical and laboratory indices of neurotoxicity risk, low bilirubin kernicterus continues to be seen in contemporary NICUs. While efforts to refine and improve current treatment guidelines are certainly needed, such revision(s) will also have to take into account the risks and benefits of any intervention, including phototherapy.
    Seminars in Perinatology 09/2014; 38(7). DOI:10.1053/j.semperi.2014.08.002 · 2.68 Impact Factor
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    ABSTRACT: Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at-risk infants, while frequently showing increased T1-signal in these regions, may give false-positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy.
    Seminars in Perinatology 09/2014; 38(7). DOI:10.1053/j.semperi.2014.08.005 · 2.68 Impact Factor
  • M Jeffrey Maisels · Jon F Watchko
    Healthcare 09/2014; 3(1). DOI:10.1053/j.semperi.2014.08.001
  • Sanjiv B Amin · Vinod K Bhutani · Jon F Watchko
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    ABSTRACT: Central apnea, defined as cessation of breathing for ≥20s, is frequent in premature infants born at <34 weeks׳ gestation but uncommon among healthy late preterm (34(0/7)-36(6/7) weeks׳ gestation) and term (≥37 weeks׳ gestation) infants, where it is usually a clinical manifestation of a neurological or metabolic problem. There is growing evidence that marked unconjugated hyperbilirubinemia is associated with central apnea in neonates. This article explores the reported association between acute bilirubin encephalopathy and symptomatic apneic events in newborns and the possible mechanisms involved in the pathogenesis of this phenomenon. The prevalence of symptomatic apneic events in reports of acute bilirubin encephalopathy suggests this clinical finding should be considered a sign of bilirubin neurotoxicity.
    Seminars in Perinatology 09/2014; 38(7). DOI:10.1053/j.semperi.2014.08.003 · 2.68 Impact Factor
  • Jon F Watchko
    Journal of Pediatrics 07/2014; 165(1):64. DOI:10.1016/j.jpeds.2014.01.014 · 3.79 Impact Factor
  • Mamdouha Ahdab-Barmada · Jon F Watchko
    Pediatric Neurology 12/2013; 50(6). DOI:10.1016/j.pediatrneurol.2013.12.010 · 1.70 Impact Factor
  • Source
    Jon F Watchko · Claudio Tiribelli
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    ABSTRACT: The complex cascade of molecular and cellular events leading to bilirubin-induced neurotoxicity remains incompletely delineated. This review discusses bilirubin-induced brain damage and recent insights into its pathogenesis and prevention. Neonatal unconjugated hyperbilirubinemia and resultant clinical jaundice affect up to approximately 85% of newborns. Although this condition is generally a benign, transitional phenomenon, unconjugated bilirubin levels that can pose a direct threat of serious brain injury develop in a small proportion of neonates. Acute bilirubin encephalopathy may ensue and progress to kernicterus (chronic bilirubin encephalopathy), a permanent disabling neurologic condition that is classically characterized by the extrapyramidal movement disorders of dystonia, choreoathetosis, or both; hearing loss due to auditory neuropathy spectrum disorders; and oculomotor pareses.(1) These central nervous system (CNS) sequelae reflect the regional CNS topography of bilirubin-induced neuropathology, which ...
    New England Journal of Medicine 11/2013; 369(21):2021-2030. DOI:10.1056/NEJMra1308124 · 55.87 Impact Factor
  • M J Maisels · J F Watchko
    Journal of perinatology: official journal of the California Perinatal Association 07/2013; 33(7):579. DOI:10.1038/jp.2013.6 · 2.07 Impact Factor
  • Jon F Watchko
    The Journal of pediatrics 02/2013; 162(6). DOI:10.1016/j.jpeds.2013.01.044 · 3.79 Impact Factor
  • J F Watchko · M Kaplan · A R Stark · D K Stevenson · V K Bhutani
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    ABSTRACT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States. Neonatal testing for G6PD deficiency is not yet routine and the American Academy of Pediatrics recommends testing only in jaundiced newborns who are receiving phototherapy whose family history, ethnicity, or geographic origin suggest risk for the condition, or for infants whose response to phototherapy is poor. Screening tests for G6PD deficiency are available, are suitable for use in newborns and have been used in birth hospitals. However, US birth hospitals experience is limited and no national consensus has emerged regarding the need for newborn G6PD testing, its effectiveness or the best approach. Our review of current state of G6PD deficiency screening highlights research gaps and informs specific operational challenges to implement universal newborn G6PD testing concurrent to bilirubin screening in the United States.Journal of Perinatology advance online publication, 21 February 2013; doi:10.1038/jp.2013.14.
    Journal of perinatology: official journal of the California Perinatal Association 02/2013; 33(7). DOI:10.1038/jp.2013.14 · 2.07 Impact Factor
  • Jon F Watchko · Michael J Painter · Ashok Panigrahy
    Japanese journal of radiology 02/2013; 31(4). DOI:10.1007/s11604-013-0181-0 · 0.84 Impact Factor
  • Source
    Monica J Daood · Mitchell Hoyson · Jon F Watchko
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    ABSTRACT: Background: Hazardous levels of bilirubin produce oxidative stress in vitro and may play a role in the genesis of bilirubin-induced neurologic dysfunction (BIND). We hypothesized that the antioxidants taurourosdeoxycholic acid (TUDCA), 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), and minocycline (MNC) inhibit oxidative stress and block BIND in hyperbilirubinemic j/j Gunn rat pups that were given sulfadimethoxine to induce bilirubin encephalopathy. Methods: At peak postnatal hyperbilirubinemia, j/j Gunn rat pups were dosed with sulfadimethoxine to induce bilirubin encephalopathy. Pups were given TUDCA, PMIN, MNC, or vehicle pretreatment (15 min before sulfadimethoxine). After 24 h, BIND was scored by using a rating scale of neurobehavior and cerebellar tissue 4-hydroxynonenal and protein carbonyl dinitrophenyl content were determined. Nonjaundiced heterozygous N/j pups served as controls. Results: Administration of sulfadimethoxine induced BIND and lipid peroxidation but not protein oxidation in hyperbilirubinemic j/j pups. TUDCA, PMIN, and MNC each reduced lipid peroxidation to basal levels observed in nonjaundiced N/j controls, but only MNC prevented BIND. Conclusion: These findings show that lipid peroxidation inhibition alone is not sufficient to prevent BIND. We speculate that the neuroprotective efficacy of MNC against BIND involves action(s) independent of, or in addition to, its antioxidant effects.
    Pediatric Research 08/2012; 72(5). DOI:10.1038/pr.2012.111 · 2.31 Impact Factor
  • Source
    M J Maisels · J F Watchko · V K Bhutani · D K Stevenson
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    ABSTRACT: We provide an approach to the use of phototherapy and exchange transfusion in the management of hyperbilirubinemia in preterm infants of <35 weeks of gestation. Because there are limited data for evidence-based recommendations, these recommendations are, of necessity, consensus-based. The recommended treatment levels are based on operational thresholds for bilirubin levels and represent those levels beyond which it is assumed that treatment will likely do more good than harm. Long-term follow-up of a large population will be needed to evaluate whether or not these recommendations should be modified.
    Journal of perinatology: official journal of the California Perinatal Association 06/2012; 32(9):660-4. DOI:10.1038/jp.2012.71 · 2.07 Impact Factor
  • Jon F Watchko
    The Journal of pediatrics 05/2012; 161(2):179-80. DOI:10.1016/j.jpeds.2012.04.001 · 3.79 Impact Factor
  • Source
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    ABSTRACT: Gene therapy studies for Duchenne muscular dystrophy (DMD) have focused on viral vector-mediated gene transfer to provide therapeutic protein expression or treatment with drugs to limit dystrophic changes in muscle. The pathological activation of the nuclear factor (NF)-κB signaling pathway has emerged as an important cause of dystrophic muscle changes in muscular dystrophy. Furthermore, activation of NF-κB may inhibit gene transfer by promoting inflammation in response to the transgene or vector. Therefore, we hypothesized that inhibition of pathological NF-κB activation in muscle would complement the therapeutic benefits of dystrophin gene transfer in the mdx mouse model of DMD. Systemic gene transfer using serotype 9 adeno-associated viral (AAV9) vectors is promising for treatment of preclinical models of DMD because of vector tropism to cardiac and skeletal muscle. In quadriceps of C57BL/10ScSn-Dmd(mdx)/J (mdx) mice, the addition of octalysine (8K)-NF-κB essential modulator (NEMO)-binding domain (8K-NBD) peptide treatment to AAV9 minidystrophin gene delivery resulted in increased levels of recombinant dystrophin expression suggesting that 8K-NBD treatment promoted an environment in muscle tissue conducive to higher levels of expression. Indices of necrosis and regeneration were diminished with AAV9 gene delivery alone and to a greater degree with the addition of 8K-NBD treatment. In diaphragm muscle, high-level transgene expression was achieved with AAV9 minidystoophin gene delivery alone; therefore, improvements in histological and physiological indices were comparable in the two treatment groups. The data support benefit from 8K-NBD treatment to complement gene transfer therapy for DMD in muscle tissue that receives incomplete levels of transduction by gene transfer, which may be highly significant for clinical applications of muscle gene delivery.
    Molecular Medicine 01/2012; 18(1):466-76. DOI:10.2119/molmed.2011.00404 · 4.51 Impact Factor
  • Chapter: Neonatology
    M. Jeffrey Maisels · Jon F. Watchko
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    ABSTRACT: The indications for the treatment of hyperbilirubinemia and the methods used for treatment vary according to the individual circumstances. Thus, treatment of hyperbilirubinemia can be prophylactic, when the purpose is to prevent further increase in the total serum bilirubin (TSB) level, or therapeutic, where the objective is to rapidly decrease a TSB level that is a threat to the infant. In some units, phototherapy is initiated soon after birth in all infants whose birth weight is <1000 g, irrespective of the TSB level. The TSB level can be lowered (or prevented from increasing further) in one of three ways: a) exchange transfusion, which removes bilirubin mechanically; b) phototherapy, which converts bilirubin to products that can bypass the liver’s conjugating system and be excreted in the bile or the urine without further metabolism and c) pharmacologic agents that interfere with heme degradation and bilirubin production, accelerate the normal metabolic pathways for bilirubin clearance, or inhibit the enterohepatic circulation of bilirubin.
    Neonatology, 01/2012: pages 629-640; , ISBN: 978-88-470-1404-6
  • Source
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    ABSTRACT: The activation of nuclear factor κB (NF-κB) contributes to muscle degeneration that results from dystrophin deficiency in human Duchenne muscular dystrophy (DMD) and in the mdx mouse. In dystrophic muscle, NF-κB participates in inflammation and failure of muscle regeneration. Peptides containing the NF-κB Essential Modulator (NEMO) binding domain (NBD) disrupt the IκB kinase complex, thus blocking NF-κB activation. The NBD peptide, which is linked to a protein transduction domain to achieve in vivo peptide delivery to muscle tissue, was systemically delivered to mdx mice for 4 or 7 weeks to study NF-κB activation, histological changes in hind limb and diaphragm muscle and ex vivo function of diaphragm muscle. Decreased NF-κB activation, decreased necrosis and increased regeneration were observed in hind limb and diaphragm muscle in mdx mice treated systemically with NBD peptide, as compared to control mdx mice. NBD peptide treatment resulted in improved generation of specific force and greater resistance to lengthening activations in diaphragm muscle ex vivo. Together these data support the potential of NBD peptides for the treatment of DMD by modulating dystrophic pathways in muscle that are downstream of dystrophin deficiency.
    Neurobiology of Disease 05/2011; 43(3):598-608. DOI:10.1016/j.nbd.2011.05.008 · 5.08 Impact Factor

Publication Stats

2k Citations
565.07 Total Impact Points


  • 1993–2014
    • University of Pittsburgh
      • • Department of Pediatrics
      • • Division of Newborn Medicine
      • • Department of Medicine
      • • Department of Orthopaedic Surgery
      • • Magee Womens Research Institute
      Pittsburgh, Pennsylvania, United States
  • 1988–2014
    • Magee-Womens Hospital
      • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Università degli Studi di Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 2003
    • University of California, Los Angeles
      • Department of Pediatrics
      Los Angeles, CA, United States
  • 1999–2003
    • University of Oslo
      • Department of Paediatrics
      Kristiania (historical), Oslo County, Norway
  • 1995–1998
    • Mayo Clinic - Rochester
      • Department of Anesthesiology
      Рочестер, Minnesota, United States
  • 1985–1991
    • University of Washington Seattle
      • Department of Pediatrics
      Seattle, Washington, United States