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https://www.readbyqxmd.com/read/28540765/an-update-on-pediatric-bronchiectasis
#1
Danielle F Wurzel, Anne B Chang
The prevalence and awareness of bronchiectasis not related to cystic fibrosis (CF) is increasing and it is now recognized as a major cause of respiratory morbidity, mortality and healthcare utilization worldwide. The need to elucidate the early origins of bronchiectasis is increasingly appreciated and has been identified as an important research priority. Current treatments for pediatric bronchiectasis are limited to antimicrobials, airway clearance techniques and vaccination. Several new drugs targeting airway inflammation are currently in development...
May 25, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28533163/grin2b-gain-of-function-mutations-are-sensitive-to-radiprodil-a-negative-allosteric-modulator-of-glun2b-containing-nmda-receptors
#2
Brice Mullier, Christian Wolff, Zara Amanda Sands, Philippe Ghisdal, Pierandrea Muglia, Rafal Marian Kaminski, Véronique Marie André
De novo gain of function mutations in GRIN2B encoding the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor have been linked with epileptic encephalopathies, including infantile spasms. We investigated the effects of radiprodil, a selective GluN2B negative allosteric modulator and other non-selective NMDA receptor inhibitors on glutamate currents mediated by NMDA receptors containing mutated GluN2B subunits. The experiments were performed in Xenopus oocytes co-injected with the following human mRNAs: GRIN1/GRIN2B, GRIN1/GRIN2B-R540H, GRIN1/GRIN2B-N615I and GRIN1/GRIN2B-V618G...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28526162/pharmacologic-considerations-of-anesthetic-agents-in-pediatric-patients-a-comprehensive-review
#3
REVIEW
Alan D Kaye, Charles J Fox, Ira W Padnos, Ken P Ehrhardt, James H Diaz, Elyse M Cornett, Debbie Chandler, Sudipta Sen, Shilpadevi Patil
Acute pain in the pediatric population has important differences in terms of biology, intrapopulation variation, and epidemiology. Discussion as to the pharmacologic considerations of anesthetic agents, such as induction agents, neuromuscular blockers, opioids, local anesthetics, and adjuvant agents, is presented in this article. Special considerations and concerns, such as risk for propofol infusion syndrome and adverse potential side effects of anesthesia agents, are discussed. Anesthesiologists managing pediatric patients need to have a firm understanding of physiologic and pharmacologic differences compared with the adult population...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#4
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28520538/treatment-strategies-for-paradoxical-hypertension-following-surgical-correction-of-coarctation-of-the-aorta-in-children
#5
Peter P Roeleveld, Eline G Zwijsen
BACKGROUND: Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin-angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies. METHODS: Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children...
May 2017: World Journal for Pediatric & Congenital Heart Surgery
https://www.readbyqxmd.com/read/28516235/clinical-imaging-and-genotypical-features-of-three-deceased-and-five-surviving-cases-with-ada2-deficiency
#6
Sezgin Sahin, Amra Adrovic, Kenan Barut, Serdal Ugurlu, Eda Tahir Turanli, Huri Ozdogan, Ozgur Kasapcopur
Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases...
May 17, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28510298/drugs-for-children
#7
S Ito
The "Therapeutic Orphan" status of children is gradually improving, but our efforts to eliminate off-label/off-evidence use must be sustained for safer and more effective pediatric drug therapy. This is even more important in resource-scarce settings, because of the increasing child population in those regions. The juncture of pediatric pharmacology and global child health represents an emerging field of clinical pharmacology illuminating a crucial societal need on a global scale.
June 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28506869/model-based-clinical-dose-optimization-for-phenobarbital-in-neonates-an-illustration-of-the-importance-of-data-sharing-and-external-validation
#8
Swantje Völler, Robert B Flint, Leo M Stolk, Pieter L J Degraeuwe, Sinno H P Simons, Paula Pokorna, David M Burger, Ronald de Groot, Dick Tibboel, Catherijne A J Knibbe
BACKGROUND: Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. METHODS: TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2...
May 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28506866/non-maturational-covariates-for-dynamic-systems-pharmacology-models-in-neonates-infants-and-children-filling-the-gaps-beyond-developmental-pharmacology
#9
Karel Allegaert, Sinno H P Simons, Dick Tibboel, Elke Krekels, Catherijne Knibbe, John van den Anker
Pharmacokinetics and -dynamics show important changes throughout childhood. Studies on the different maturational processes that influence developmental pharmacology have been used to create population PK/PD models that can yield individualized pediatric drug dosages. These models were subsequently translated to semi-physiologically or physiology-based PK (PBPK) models that support predictions in pediatric patient cohorts and other special populations. Although these translational efforts are crucial, these models should be further improved towards individual patient predictions by including knowledge on non-maturational covariates...
May 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28490206/pharmacokinetics-pharmacodynamics-and-pharmacogenetics-associated-with-nonsteroidal-anti-inflammatory-drugs-and-opioids-in-pediatric-cancer-patients
#10
Jonathan Constance, Sarah Campbell, Amit A Somani, Venkata Yellepeddi, Katie Owens, Catherine Sherwin
Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer...
May 11, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28488805/breastfeeding-considerations-for-mothers-of-infants-with-neonatal-abstinence-syndrome
#11
Amy P Holmes, Holly N Schmidlin, Eliana N Kurzum
Breastfeeding offers many benefits to both mother and baby. Breastfeeding is generally recommended for mothers of infants with neonatal abstinence syndrome (NAS) unless some associated risk outweighs the benefits. Evidence indicates that infants with NAS who receive human milk require less pharmacologic treatment and have shorter hospital lengths of stay. Perhaps the greatest barrier to breastfeeding for women with opioid dependence is the inaccurate and inconsistent information they receive from different sources, including health care professionals...
May 10, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28487636/elamipretide-ss-31-ameliorates-isoflurane-induced-long-term-impairments-of-mitochondrial-morphogenesis-and-cognition-in-developing-rats
#12
Jing Wu, Shuangying Hao, Xiao-Ru Sun, Hui Zhang, Huihui Li, Hongting Zhao, Mu-Huo Ji, Jian-Jun Yang, Kuanyu Li
Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA)-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31) on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND) 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28481700/pediatric-status-epilepticus-improved-management-with-new-drug-therapies
#13
Alberto Verrotti, Michela Ambrosi, Piero Pavone, Pasquale Striano
Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28461862/effectiveness-of-coenzyme-q10-on-echocardiographic-parameters-of-patients-with-duchenne-muscular-dystrophy
#14
Forod Salehi, Aliakbar Zeinaloo, Hamid Reza Riasi, Alireza Sepehri Shamloo
BACKGROUND: Myocardial damage is a common complication in patients with Duchenne muscular dystrophy (DMD) that occurs due to myocardial replacement by fat and fibrosis. In recent years, efforts have been made toward finding new pharmacological agents with fewer complications which can be used as prophylactic before the symptoms. Coenzyme Q10 plays a central role in production of bioenergy in heart muscle and antioxidant in reperfusion condition of myocardial damaged muscle and leads to membrane stability and prevents cell death...
March 2017: Electronic Physician
https://www.readbyqxmd.com/read/28461505/suppressors-and-activators-of-jak-stat-signaling-at-diagnosis-and-relapse-of-acute-lymphoblastic-leukemia-in-down-syndrome
#15
Omer Schwartzman, Angela Maria Savino, Michael Gombert, Chiara Palmi, Gunnar Cario, Martin Schrappe, Cornelia Eckert, Arend von Stackelberg, Jin-Yan Huang, Michal Hameiri-Grossman, Smadar Avigad, Geertruy Te Kronnie, Ifat Geron, Yehudit Birger, Avigail Rein, Giulia Zarfati, Ute Fischer, Zohar Mukamel, Martin Stanulla, Andrea Biondi, Giovanni Cazzaniga, Amedeo Vetere, Bridget K Wagner, Zhu Chen, Sai-Juan Chen, Amos Tanay, Arndt Borkhardt, Shai Izraeli
Children with Down syndrome (DS) are prone to development of high-risk B-cell precursor ALL (DS-ALL), which differs genetically from most sporadic pediatric ALLs. Increased expression of cytokine receptor-like factor 2 (CRLF2), the receptor to thymic stromal lymphopoietin (TSLP), characterizes about half of DS-ALLs and also a subgroup of sporadic "Philadelphia-like" ALLs. To understand the pathogenesis of relapsed DS-ALL, we performed integrative genomic analysis of 25 matched diagnosis-remission and -relapse DS-ALLs...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28460701/effective-management-of-pain-and-anxiety-for-the-pediatric-patient-in-the-emergency-department
#16
REVIEW
Virginia B Young
Inadequate treatment of pain for children in the emergency department is a persistent problem. Health care professionals are bound by ethical principles to provide adequate pain management; in children, this may be challenging owing to cognitive and developmental differences, lack of knowledge regarding best practices, and other barriers. Studies have concluded that immediate assessment, treatment, and reassessment of pain after an intervention are essential. Self-report and behavioral scales are available...
June 2017: Critical Care Nursing Clinics of North America
https://www.readbyqxmd.com/read/28460699/case-study-of-high-dose-ketamine-for-treatment-of-complex-regional-pain-syndrome-in-the-pediatric-intensive-care-unit
#17
REVIEW
Tracy Ann Pasek, Kelli Crowley, Catherine Campese, Rachel Lauer, Charles Yang
Complex regional pain syndrome (CRPS) is a life-altering and debilitating chronic pain condition. The authors are presenting a case study of a female who received high-dose ketamine for the management of her CRPS. The innovative treatment lies not only within the pharmacologic management of her pain, but also in the fact that she was the first patient to be admitted to our pediatric intensive care unit solely for pain control. The primary component of the pharmacotherapy treatment strategy plan was escalating-dose ketamine infusion via patient-controlled-analgesia approved by the pharmacy and therapeutics committee guided therapy for this patient...
June 2017: Critical Care Nursing Clinics of North America
https://www.readbyqxmd.com/read/28457820/differential-roles-for-akt-and-mtorc1-in-the-hypertrophy-of-pten-mutant-neurons-a-cellular-model-of-brain-overgrowth-disorders
#18
Ina Nikolaeva, Tatiana M Kazdoba, Beth Crowell, Gabriella D'Arcangelo
Mutations in the PI3K/Akt/mTOR signaling pathway or in the upstream negative regulator Pten cause human brain overgrowth disorders, such as focal cortical dysplasia and megalencephaly, and are characterized by the presence of hypertrophic neurons. These disorders often have a pediatric onset and a high comorbidity with drug-resistant epilepsy; however, effective pharmacological treatments are lacking. We established forebrain excitatory neuron-specific Pten-deficient cultures as an in vitro model of brain overgrowth disorders, and investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and neuronal growth...
April 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28451624/tics-in-the-pediatric-population-pragmatic-management
#19
REVIEW
Christos Ganos, Davide Martino, Tamara Pringsheim
BACKGROUND: Primary tic disorders, notably Tourette syndrome, are very common movement disorders in childhood. However, the management of such patients still poses great therapeutic challenges to medical professionals. METHODS: Based on a synthesis of the available guidelines published in Europe, Canada, and the United States, coupled with more recent therapeutic developments, the authors provide a pragmatic guide to aid clinicians in deciding when and how to treat patients who have primary tic disorders...
March 2017: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/28450157/the-dual-mtor-kinase-inhibitor-tak228-inhibits-tumorigenicity-and-enhances-radiosensitization-in-diffuse-intrinsic-pontine-glioma
#20
Hiroaki Miyahara, Sridevi Yadavilli, Manabu Natsumeda, Jeffrey A Rubens, Louis Rodgers, Madhuri Kambhampati, Isabella C Taylor, Harpreet Kaur, Laura Asnaghi, Charles G Eberhart, Katherine E Warren, Javad Nazarian, Eric H Raabe
Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory pediatric brain tumor. Primary DIPG tumors harbor a number of mutations including alterations in PTEN, AKT, and PI3K and exhibit activation of mammalian Target of Rapamycin Complex 1 and 2 (mTORC1/2). mTORC1/2 regulate protein translation, cell growth, survival, invasion, and metabolism. Pharmacological inhibition of mTORC1 is minimally effective in DIPG. However, the activity of dual TORC kinase inhibitors has not been examined in this tumor type...
April 25, 2017: Cancer Letters
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