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Ravindra Arya, Katrina Peariso, Marina Gaínza-Lein, Jessica Harvey, Ann Bergin, J Nicholas Brenton, Brian T Burrows, Tracy Glauser, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Iván Sánchez Fernández, Dmitry Tchapyjnikov, Angus A Wilfong, Korwyn Williams, Tobias Loddenkemper
PURPOSE: To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). METHODS: RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug...
April 27, 2018: Epilepsy Research
I Sánchez Fernández, M Gaínza-Lein, N S Abend, A E Anderson, R Arya, J N Brenton, J L Carpenter, K E Chapman, J Clark, W D Gaillard, T A Glauser, J L Goldstein, H P Goodkin, A R Helseth, M C Jackson, K Kapur, Y-C Lai, T L McDonough, M A Mikati, A Nayak, K Peariso, J J Riviello, R C Tasker, D Tchapyjnikov, A A Topjian, M S Wainwright, A Wilfong, K Williams, T Loddenkemper
OBJECTIVE: To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). METHODS: This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th percentiles [p25 -p75 ]) age of 3...
May 8, 2018: Neurology
Alexandra J Borst, Dmitry Tchapyjnikov
Pyridox(am)ine-5-phosphate oxidase deficiency is an inborn error of vitamin B6 metabolism that is characterized by neonatal seizures, requiring lifelong therapy with pyridoxal-5-phosphate. We present the first case of a patient with pyridox(am)ine-5-phosphate oxidase deficiency and mild hemophilia A, whose bleeding symptoms were exacerbated by the vitamin B6 therapy essential for his epileptic disorder. This report expands the spectrum of known vitamin B6 toxicity and demonstrates a need for vigilance in monitoring for bleeding symptoms in patients requiring pyridoxine or pyridoxal-5-phosphate supplementation...
April 2018: Pediatrics
Marina Gaínza-Lein, Iván Sánchez Fernández, Michele Jackson, Nicholas S Abend, Ravindra Arya, J Nicholas Brenton, Jessica L Carpenter, Kevin E Chapman, William D Gaillard, Tracy A Glauser, Joshua L Goldstein, Howard P Goodkin, Kush Kapur, Mohamad A Mikati, Katrina Peariso, Robert C Tasker, Dmitry Tchapyjnikov, Alexis A Topjian, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper
Importance: Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. Objective: To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. Design, Setting, and Participants: This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group...
April 1, 2018: JAMA Neurology
Monisha Sachdev, Marina Gaínza-Lein, Dmitry Tchapyjnikov, Yong-Hui Jiang, Tobias Loddenkemper, Mohamad A Mikati
PURPOSE: To report novel clinical manifestations of KCNA2 mutation related epileptic encephalopathy. METHODS: Blood samples were sent for whole exome and Sanger sequencing. Seizure types were characterized by clinical criteria and EEG recording. RESULTS: KCNA2 mutations have been reported in 10 cases who presented with focal, absence, generalized tonic-clonic or myoclonic astatic seizures. Here we describe 3 patients with previously unreported, more severe manifestations...
October 2017: Seizure: the Journal of the British Epilepsy Association
Dmitry Tchapyjnikov, Alexandra J Borst
Immune checkpoint inhibitors are a novel group of immunotherapeutic agents for the treatment of cancer. Immune-related adverse events, including neurological symptoms, have been associated with these agents. We present the case of an adolescent with refractory Hodgkin lymphoma treated with nivolumab, a PD1 inhibitor, who developed Hashimoto thyroiditis, posterior reversible encephalopathy syndrome causing seizures, as well as urinary retention, truncal/appendicular spasticity, dysphagia, and a progressive encephalopathy that was clinically consistent with a diagnosis of progressive encephalopathy with rigidity and myoclonus, a stiff-person-syndrome spectrum disorder...
September 2017: Journal of Immunotherapy
Nina Fainberg, Amy Harper, Dmitry Tchapyjnikov, Mohamad A Mikati
Landau-Kleffner syndrome (LKS) has been demonstrated in the past to respond to immunotherapy. Recently, some cases of LKS have been shown to be secondary to glutamate receptor (GRIN2A) mutations. Whether such cases respond to immunotherapy is not known. Here, we present the case of a 3-year-old boy with LKS found to have a GRIN2A heterozygous missense mutation, whose clinical symptoms and EEG responded to a course of combination oral steroids and monthly infusions of intravenous immunoglobulin. He then relapsed after discontinuation of this therapy, and responded again after a second course of intravenous immunoglobulin...
March 2016: Epileptic Disorders: International Epilepsy Journal with Videotape
Dmitry Tchapyjnikov, Yuedan Li, Trairak Pisitkun, Jason D Hoffert, Ming-Jiun Yu, Mark A Knepper
Vasopressin is a peptide hormone that regulates renal water excretion in part through its actions on the collecting duct. The regulation occurs in part via control of transcription of genes coding for the water channels aquaporin-2 (Aqp2) and aquaporin-3 (Aqp3). To identify transcription factors expressed in collecting duct cells, we have carried out LC-MS/MS-based proteomic profiling of nuclei isolated from native rat inner medullary collecting ducts (IMCDs). To maximize the number of proteins identified, we matched spectra to rat amino acid sequences using three different search algorithms (SEQUEST, InsPecT, and OMSSA)...
February 4, 2010: Physiological Genomics
Patricia A Gonzales, Trairak Pisitkun, Jason D Hoffert, Dmitry Tchapyjnikov, Robert A Star, Robert Kleta, Nam Sun Wang, Mark A Knepper
Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space. Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers...
February 2009: Journal of the American Society of Nephrology: JASN
Jason D Hoffert, Robert A Fenton, Hanne B Moeller, Brigitte Simons, Dmitry Tchapyjnikov, Bradley W McDill, Ming-Jiun Yu, Trairak Pisitkun, Feng Chen, Mark A Knepper
Vasopressin controls water excretion through regulation of aquaporin-2 (AQP2) trafficking in renal collecting duct cells. Using mass spectrometry, we previously demonstrated four phosphorylated serines (Ser256, Ser261, Ser264, and Ser269) in the carboxyl-terminal tail of rat AQP2. Here, we used phospho-specific antibodies and protein mass spectrometry to investigate the roles of vasopressin and cyclic AMP in the regulation of phosphorylation at Ser269 and addressed the role of this site in AQP2 trafficking...
September 5, 2008: Journal of Biological Chemistry
Ming-Jiun Yu, Trairak Pisitkun, Guanghui Wang, Juan F Aranda, Patricia A Gonzales, Dmitry Tchapyjnikov, Rong-Fong Shen, Miguel A Alonso, Mark A Knepper
In the renal collecting duct, vasopressin controls transport of water and solutes via regulation of membrane transporters such as aquaporin-2 (AQP2) and the epithelial urea transporter UT-A. To discover proteins potentially involved in vasopressin action in rat kidney collecting ducts, we enriched membrane "raft" proteins by harvesting detergent-resistant membranes (DRMs) of the inner medullary collecting duct (IMCD) cells. Proteins were identified and quantified with LC-MS/MS. A total of 814 proteins were identified in the DRM fractions...
September 2008: American Journal of Physiology. Cell Physiology
Mitsi A Blount, Janet D Klein, Christopher F Martin, Dmitry Tchapyjnikov, Jeff M Sands
UT-A1 is regulated by vasopressin and is localized to the apical membrane and intracellular compartment of inner medullary collecting duct (IMCD) cells. UT-A3 is also expressed in the IMCD and is regulated by forskolin in heterologous systems. The goal of the present study is to investigate mechanisms by which vasopressin regulates UT-A3 in rat IMCD. In fresh suspensions of rat IMCD, forskolin increases the phosphorylation of UT-A3, similar to UT-A1. Biotinylation studies indicate that UT-A3 is located in the plasma membrane...
October 2007: American Journal of Physiology. Renal Physiology
Travis J Polletto, Anthony K Ngo, Alexei Tchapyjnikov, Ken Levin, Danh Tran, Nathaniel M Fried
BACKGROUND AND OBJECTIVES: Endoscopic applications of the Erbium:YAG laser have been limited due to the lack of a suitable optical fiber delivery system. The purpose of this study was to compare the transmission of Er:YAG laser radiation through germanium oxide trunk fibers with silica and sapphire fiber tips for potential use in contact tissue ablation during endoscopy. STUDY DESIGN/MATERIALS AND METHODS: Er:YAG laser radiation with a wavelength of 2.94 microm, pulse length of 300 microseconds, pulse energies from 5 to 1,360 mJ, coupled into pulse repetition rates of 3-10 Hz, was through 1-m-long germanium oxide fibers with either 1-cm-long, 550-microm-diameter silica or sapphire tips...
September 2006: Lasers in Surgery and Medicine
Trairak Pisitkun, Jared Bieniek, Dmitry Tchapyjnikov, Guanghui Wang, Wells W Wu, Rong-Fong Shen, Mark A Knepper
The inner medullary collecting duct (IMCD) is an important site of vasopressin-regulated water and urea transport. Here we have used protein mass spectrometry to investigate the proteome of the IMCD cell and how it is altered in response to long-term vasopressin administration in rats. IMCDs were isolated from inner medullas of rats, and IMCD proteins were identified by liquid chromatography/tandem mass spectrometry (LC-MS/MS). We present a WWW-based "IMCD Proteome Database" containing all IMCD proteins identified in this study (n = 704) and prior MS-based identification studies (n = 301)...
April 13, 2006: Physiological Genomics
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