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Pediatric neurotoxicity

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https://www.readbyqxmd.com/read/28697165/association-of-cyp3a5-expression-and-vincristine-neurotoxicity-in-pediatric-malignancies-in-turkish-population
#1
Hülya Kayilioğlu, Ulker Kocak, Derya Kan Karaer, Emriye F Percin, Ertan Sal, Funda Tekkesin, Melek Isik, Nergiz Oner, Fatma B Belen, Ebru Yilmaz Keskin, Arzu Okur, Meryem Albayrak, Zuhre Kaya, Faruk G Pinarli, Idil Yenicesu, Ceyda Karadeniz, Aynur Oguz, Turkiz Gursel
Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated...
July 10, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28654034/use-of-a-piglet-model-for-the-study-of-anesthetic-induced-developmental-neurotoxicity-aidn-a-translational-neuroscience-approach
#2
Emmett E Whitaker, Christopher Z Zheng, Bruno Bissonnette, Andrew D Miller, Tanner L Koppert, Joseph D Tobias, Christopher R Pierson, Fedias L Christofi
Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans...
June 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28600697/neurotoxicity-of-cyclosporine%C3%A2-a-in-children-with-steroid-resistant-nephrotic-syndrome-is-cytotoxic-edema-really-an-unfavorable-predictor-of-permanent-neurological-damage
#3
Danica Batinić, Danko Milošević, Boris Filipović-Grčić, Marija Topalović-Grković, Nina Barišić, Daniel Turudić
BACKGROUND: Cyclosporine A-associated neurotoxicity has been reported mainly after organ transplantation. Only a small number of children with steroid-resistant nephrotic syndrome and cyclosporine A-associated neurotoxicity have been reported. PATIENTS: We report three children, aged 4, 11, and 15, with steroid-resistant nephrotic syndrome and cyclosporine A-associated neurotoxicity. In two of the patients, primary diagnosis was idiopathic nephrotic syndrome, and in one it was IgA nephropathy...
June 9, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28586779/effect-of-anesthesia-on-the-developing-brain-infant-and-fetus
#4
Dean B Andropoulos
The potential for commonly used anesthetics and sedatives to cause neuroapoptosis and other neurodegenerative changes in the developing mammalian brain has become evident in animal studies over the past 15 years. This concern has led to a number of retrospective studies in human infants and young children, and some of these studies observed an association between exposure to general anesthesia as an infant, and later neurobehavioral problems in childhood. This association is particularly evident for prolonged or repeated exposures...
June 7, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28580726/the-first-case-of-domino-split-liver-transplantation-in-maple-syrup-urine-disease
#5
Uta Herden, Jun Li, Lutz Fischer, Florian Brinkert, Martin Blohm, René Santer, Bjoern Nashan, Enke Grabhorn
The enzymatic defect in MSUD results in accumulation of neurotoxic metabolites of BCAAs. LTX has shown to be a feasible strategy in patients non-responsive to diet. Because of sufficient enzyme activity in extrahepatic tissues in healthy people, the MSUD liver graft is a suitable domino organ. We present the first case of a technical challenging ex situ split of a MSUD domino organ transplanted into two pediatric recipients. The domino graft donor was a 21-year-old female (58 kg) suffering from MSUD with recurrent metabolic decompensation despite strict diet...
June 5, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28555178/central-nervous-system-complications-in-children-receiving-chemotherapy-or-hematopoietic-stem-cell-transplantation
#6
REVIEW
Duccio Maria Cordelli, Riccardo Masetti, Daniele Zama, Francesco Toni, Ilaria Castelli, Emilia Ricci, Emilio Franzoni, Andrea Pession
Therapy-related neurotoxicity greatly affects possibility of survival and quality of life of pediatric patients treated for cancer. Central nervous system (CNS) involvement is heterogeneous, varying from very mild and transient symptoms to extremely severe and debilitating, or even lethal syndromes. In this review, we will discuss the broad scenario of CNS complications and toxicities occurring during the treatment of pediatric patients receiving both chemotherapies and hematopoietic stem cell transplantation...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28487636/elamipretide-ss-31-ameliorates-isoflurane-induced-long-term-impairments-of-mitochondrial-morphogenesis-and-cognition-in-developing-rats
#7
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/28470388/pediatric-anesthesia-and-neurotoxicity-what-the-radiologist-needs-to-know
#8
REVIEW
Katherine Barton, Joshua P Nickerson, Timothy Higgins, Robert K Williams
The use of cross-sectional imaging in the pediatric population continues to rise, particularly the use of MRI. Limiting motion artifact requires cooperative subjects who do not move during imaging, so there has been an increase in the need for pediatric sedation or anesthesia. Over the last decade, concern has increased that exposure to anesthesia might be associated with long-term cognitive deficits. In this review we report current understanding of the effects of anesthesia on the pediatric population, with special focus on long-term developmental and cognitive outcomes, and suggest how radiologists can use new technologies or imaging strategies to mitigate or minimize these potential risks...
May 3, 2017: Pediatric Radiology
https://www.readbyqxmd.com/read/28468529/pharmacogenomics-in-pediatric-acute-lymphoblastic-leukemia-promises-and-limitations
#9
Zeina N Al-Mahayri, George P Patrinos, Bassam R Ali
Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28463790/dexmedetomidine-inhibits-activation-of-the-mapk-pathway-and-protects-pc12-and-ng108-15-cells-from-lidocaine-induced-cytotoxicity-at-its-maximum-safe-dose
#10
Qiong Wang, Yonghong Tan, Na Zhang, Yingyi Xu, Wei Wei, Yingjun She, Xiaobao Bi, Baisong Zhao, Xiangcai Ruan
The developing brains of pediatric patients are highly vulnerable to anesthetic regimen (e.g., lidocaine), potentially causing neurological impairment. Recently, dexmedetomidine (DEX) has been used as an adjunct for sedation, and was shown to exert dose-dependent neuroprotective effects during brain injury. However, the maximum safe dose of DEX is unclear, and its protective effects against lidocaine-related neurotoxicity need to be confirmed. In this study, PC12 and NG108-15 cells were used to estimate safe, non-cytotoxic doses of DEX...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28439753/abating-mercury-exposure-in-young-children-should-include-thimerosal-free-vaccines
#11
REVIEW
José G Dórea
Pediatric immunization is essential to prevent, control and eradicate children`s infectious diseases. Newborns and infants in less developed countries have a concentrated schedule of Thimerosal-containing vaccines (TCVs); pregnant mothers are also immunized with TCVs. Metabolic changes during early development are demonstrably an important risk factor for ethylmercury (EtHg) effects on neurodevelopment, while exposure to Thimerosal sensitizes susceptible individuals to life-long contact dermatitis. Concerns regarding toxicity of Hg have moved rich nations to withdraw it from medicines and, in particular, Thimerosal from pediatric vaccines; it has been more than 20 years since rich countries started using Thimerosal-free vaccines...
April 24, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28435999/neonatal-propofol-anesthesia-changes-expression-of-synaptic-plasticity-proteins-and-increases-stereotypic-and-anxyolitic-behavior-in-adult-rats
#12
Desanka Milanovic, Vesna Pesic, Natasa Loncarevic-Vasiljkovic, Vladimir Avramovic, Vesna Tesic, Vesna Jevtovic-Todorovic, Selma Kanazir, Sabera Ruzdijic
Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain...
April 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28424016/acute-brain-injury-following-illicit-drug-abuse-in-adolescent-and-young-adult-patients-spectrum-of-neuroimaging-findings
#13
Shai Shrot, Andrea Poretti, Elizabeth W Tucker, Bruno P Soares, Thierry Agm Huisman
The use of illicit drugs is currently a major medical problem among adolescents. Several illicit drugs have a high abuse potential and can be neurotoxic causing high morbidity and mortality. The clinical manifestation of adolescents with acute drug-induced neurotoxicity is often characterized by non-specific symptoms and findings. Early diagnosis is important to prevent death and permanent long-term neurological impairments. We report on clinical and neuroimaging findings in five adolescents with acute brain imaging following illicit drug intoxication to highlight the role of neuroimaging findings in the diagnostic work-up of pediatric acute drug-induced neurotoxicity...
April 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28424007/anesthetic-related-neurotoxicity-and-neuroimaging-in-children-a-call-for-conversation
#14
Kara A Bjur, Eric T Payne, Michael E Nemergut, Danqing Hu, Randall P Flick
Each year millions of young children undergo procedures requiring sedation or general anesthesia. An increasing proportion of the anesthetics used are provided to optimize diagnostic imaging studies such as magnetic resonance imaging. Concern regarding the neurotoxicity of sedatives and anesthetics has prompted the US Food and Drug Administration to change labeling of anesthetics and sedative agents warning against repeated or prolonged exposure in young children. This review aims to summarize the risk of anesthesia in children with an emphasis on anesthetic-related neurotoxicity, acknowledge the value of pediatric neuroimaging, and address this call for conversation...
May 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28417855/optimization-of-pediatric-pet-ct
#15
REVIEW
Marguerite T Parisi, Mohammed S Bermo, Adam M Alessio, Susan E Sharp, Michael J Gelfand, Barry L Shulkin
PET/CT, the most common form of hybrid imaging, has transformed oncologic imaging and is increasingly being used for nononcologic applications as well. Performing PET/CT in children poses unique challenges. Not only are children more sensitive to the effects of radiation than adults but, following radiation exposure, children have a longer postexposure life expectancy in which to exhibit adverse radiation effects. Both the PET and CT components of the study contribute to the total patient radiation dose, which is one of the most important risks of the study in this population...
May 2017: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/28346057/the-role-of-germline-variants-in-chemotherapy-outcome-in-brain-tumors-a-systematic-review-of-pharmacogenetic-studies
#16
REVIEW
Marije J Klumpers, Marieke Jh Coenen, Corrie Em Gidding, D Maroeska Wm Te Loo
AIM: This systematic review provides an overview of publications concerning pharmacogenetic research in pediatric patients with medulloblastoma and low-grade glioma. MATERIALS & METHODS: Three electronic databases searches including a manual search were performed to identify studies investigating potential interactions between germline variants and chemotherapy efficacy and toxicity. RESULTS: Out of 3570 citations, 21 studies were included...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28320216/a-neurologic-dysfunction-scoring-protocol-for-jaundiced-neonates-requiring-exchange-transfusion
#17
Bolajoko O Olusanya, Folashade B Osibanjo, Adeniyi A Ajiboye, Oluwafemi E Ayodele, Adebanke A Odunsi, Serah M Olaifa, Abieyuwa A Emokpae
AIM: To evaluate the performance of a neurologic assessment protocol among jaundiced infants requiring exchange transfusion (ET). METHODS: We identified infants in a referral children's hospital who received ET and those who met the American Academy of Pediatrics (AAP) criteria for ET based on total serum bilirubin (TSB) levels. The performance of a bilirubin-induced neurologic dysfunction (BIND-M) scoring protocol for acute bilirubin encephalopathy (ABE) in detecting infants treated with ET in both groups was investigated by logistic regression analysis and c-statistic...
March 20, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28319548/tanshinone-iia-attenuates-sevoflurane-neurotoxicity-in-neonatal-mice
#18
Yimeng Xia, Heng Xu, Chenfei Jia, Xiaodong Hu, Yu Kang, Xiaoxuan Yang, Qingsheng Xue, Guorong Tao, Buwei Yu
BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics...
April 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28299754/optimizing-the-benefit-of-cns-radiation-therapy-in-the-pediatric-population-part-1-understanding-and-managing-acute-and-late-toxicities
#19
REVIEW
Lindsay S Rowe, Andra V Krauze, Holly Ning, Kevin A Camphausen, Aradhana Kaushal
Radiation therapy continues to be a key component in the management of pediatric malignancies. Increasing the likelihood of cure while minimizing late treatment toxicity in these young patients remains the primary goal. Within the realm of central nervous system neoplasms, efforts to further improve the efficacy of radiation therapy continue, while balancing risks of damage to uninvolved tissue. Radiation therapy can result in second malignancies, as well as cerebrovascular, neurotoxic, neurocognitive, endocrine, psychosocial, and quality-of-life effects...
March 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28283552/anaesthetic-considerations-for-surgery-in-newborns
#20
Constance S Houck, Amy E Vinson
Almost 30 years ago, the American Academy of Pediatrics Committee on Fetus and Newborn coauthored a policy statement strongly advocating for the use of anaesthesia in all neonates stating 'local or systemic pharmacologic agents now available permit relatively safe administration of anesthesia or analgesia to neonates undergoing surgical procedures and that such administration is indicated according to the usual guidelines for the administration of anesthesia to high-risk, potentially unstable patients'. With current techniques and advanced monitoring, preterm and full-term infants routinely undergo surgical procedures under general anaesthesia to repair congenital defects that were lethal in years past...
July 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
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