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Pediatric neurotoxicity

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https://www.readbyqxmd.com/read/29773196/reconsideration-of-the-immunotherapeutic-pediatric-safe-dose-levels-of-aluminum
#1
James Lyons-Weiler, Robert Ricketson
FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29771861/vincristine-associated-neuropathy-with-antifungal-usage-a-kaiser-northern-california-experience
#2
Mina Nikanjam, Aida Sun, Mark Albers, Kristine Mangalindin, Eyun Song, Hyma Vempaty, Danny Sam, Edmund V Capparelli
The dose-limiting toxicity for vincristine is peripheral neuropathy which can be potentiated with concurrent usage of azole antifungals. The current retrospective study assessed the incidence of concurrent vincristine and azole antifungal usage to determine if it led to increased neurotoxicity for the Kaiser Northern California pediatric acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma patient population. Data were obtained from the electronic medical record (2007 to 2014). In total, 130 subjects received at least one dose of vincristine for ALL or Hodgkin lymphoma (median age 9, 88% ALL, 58% male, 47% Caucasian)...
May 16, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29694960/kynurenine-pathway-in-autism-spectrum-disorders-in-children
#3
Vesna Bryn, Robert Verkerk, Ola H Skjeldal, Ola Didrik Saugstad, Heidi Ormstad
BACKGROUND: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. METHODS: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46...
April 25, 2018: Neuropsychobiology
https://www.readbyqxmd.com/read/29685658/novel-founder-intronic-variant-in-slc39a14-in-two-families-causing-manganism-and-potential-treatment-strategies
#4
Lance H Rodan, Marissa Hauptman, Alissa M D'Gama, Anita E Qualls, Siqi Cao, Karin Tuschl, Fatma Al-Jasmi, Jozef Hertecant, Susan J Hayflick, Marianne Wessling-Resnick, Edward T Yang, Gerard T Berry, Andrea Gropman, Alan D Woolf, Pankaj B Agrawal
Congenital disorders of manganese metabolism are rare occurrences in children, and medical management of these disorders is complex and challenging. Homozygous exonic mutations in the manganese transporter SLC39A14 have recently been associated with a pediatric-onset neurodegenerative disorder characterized by brain manganese accumulation and clinical signs of manganese neurotoxicity, including parkinsonism-dystonia. We performed whole exome sequencing on DNA samples from two unrelated female children from the United Arab Emirates with progressive movement disorder and brain mineralization, identified a novel homozygous intronic mutation in SLC39A14 in both children, and demonstrated that the mutation leads to aberrant splicing...
April 6, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29664690/methadone-as-the-initial-long-acting-opioid-in-children-with-advanced-cancer
#5
Kevin Madden, Sarah Mills, Seyedeh Dibaj, Janet L Williams, Diane Liu, Eduardo Bruera
BACKGROUND: Methadone is an attractive medication for treating children with advanced cancer with pain as it is the only long-acting opioid available as a liquid. However, it is not frequently used due to concerns about potential toxicities and side effects. OBJECTIVE: Evaluate the efficacy and safety of methadone as the first long-acting opioid in children with advanced cancer. DESIGN: Retrospective chart review of 52 consecutive patients referred to Pediatric Supportive Care for pain management started on methadone as their first long-acting opioid...
April 17, 2018: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/29624028/uncommon-occurrence-of-high-piperacillin-tazobactam-and-meropenem-plasma-concentrations-and-concomitant-absence-of-neurotoxicity-in-pediatrics
#6
Alessio Mesini, Anna Loy, Giuseppe Losurdo, Cristina Moroni, Sebastiano Barco, Giuliana Cangemi, Andrea Moscatelli, Francesco Risso, Elio Castagnola
No abstract text is available yet for this article.
April 5, 2018: Minerva Anestesiologica
https://www.readbyqxmd.com/read/29579407/modulatory-effect-of-curcumin-on-ketamine-induced-toxicity-in-rat-thymocytes-involvement-of-reactive-oxygen-species-ros-and-the-phosphoinositide-3-kinase-pi3k-protein-kinase-b-akt-pathway
#7
Svetlana Pavlovic, Zorica Jovic, Radmila Karan, Dane Krtinic, Gorana Rankovic, Mladjan Golubovic, Jelena Lilic, Voja Pavlovic
Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 μM) for 24 hours...
March 21, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29550867/non-sedation-of-the-neonate-for-radiologic-procedures
#8
REVIEW
Richard B Parad
On Dec. 16, 2016, the U.S. Food and Drug Administration (FDA) released a warning regarding the potential neurotoxicity of anesthesia and sedation agents on the developing brain in children younger than 3 years and in women during their 3rd trimester of pregnancy. These concerns have relevance to the pediatric radiologist who must take into consideration how the child's state might impact image quality. In this review the author provides background on the special concerns in the potentially highest-risk group, pre-term and term neonates, and provides guidance and rationale for the avoidance of sedation in procedural imaging of the newborn...
April 2018: Pediatric Radiology
https://www.readbyqxmd.com/read/29550513/lipid-profiling-as-an-effective-approach-for-identifying-biomarkers-adverse-events-associated-with-pediatric-anesthesia
#9
Cheng Wang, Xianlin Han, Fang Liu, Tucker A Patterson, Joseph P Hanig, Merle G Paule, William Slikker
Adverse effects related to central nervous system (CNS) function in pediatric populations may, at times, be difficult, if not impossible to evaluate. Prolonged anesthetic exposure affects brain excitability and anesthesia during the most sensitive developmental stages and has been associated with mitochondrial dysfunction, aberrant lipid metabolism and synaptogenesis, subsequent neuronal damage, as well as long-term behavioral deficits. There has been limited research evaluating whether and how anesthetic agents affect cellular lipids, the most abundant components of the brain other than water...
March 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29502215/identification-of-a-less-toxic-vinca-alkaloid-derivative-for-use-as-a-chemotherapeutic-agent-based-on-in-silico-structural-insights-and-metabolic-interactions-with-cyp3a4-and-cyp3a5
#10
Nikhat Saba, Alpana Seal
Vinca alkaloids are chemotherapeutic agents used in the treatment of both pediatric and adult cancer patients. Cytochrome P450 3A5 (CYP3A5) is 9- to 14-fold more efficient at clearing vincristine than cytochrome P450 3A4 (CYP3A4) is. However, patients who express an inactive form of the polymorphic CYP3A5 enzyme suffer from severe neurotoxicity during vincristine treatment, resulting in chemotherapy failure. Previous studies have found that the addition of new features to the parent drug can enhance its binding affinity to tubulin manyfold and could therefore yield novel anticancer drugs...
March 4, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29501685/ketamine-induced-neurotoxicity-blocked-by-n-methyl-d-aspartate-is-mediated-through-activation-of-pkc-erk-pathway-in-developing-hippocampal-neurons
#11
Sufang Jiang, Xuze Li, Wei Jin, Xiaofeng Duan, Lijun Bo, Jiangli Wu, Rui Zhang, Ying Wang, Rongtian Kang, Lining Huang
Ketamine, a non-competitive N-methyl d-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis...
April 23, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29498961/short-term-recovery-of-balance-control-association-with-chemotherapy-induced-peripheral-neuropathy-in-pediatric-oncology
#12
Laura S Gilchrist, Lynn R Tanner
PURPOSE: To describe the incidence and short-term recovery of balance control in children and adolescents receiving neurotoxic treatment for noncentral nervous system cancers and to investigate the association of chemotherapy-induced peripheral neuropathy and balance control. METHODS: Sixty-five children and adolescents diagnosed with leukemia, lymphoma, or other solid tumors were tested 3 to 6 months into treatment and 3 and 6 months following treatment using the Bruininks-Oseretsky Balance Subscale and Pediatric Modified Total Neuropathy Scale scores of chemotherapy-induced peripheral neuropathy (CIPN)...
April 2018: Pediatric Physical Therapy
https://www.readbyqxmd.com/read/29490377/lithium-treatment-in-children-and-adolescents
#13
Anne Duffy, Paul Grof
INTRODUCTION: There is a resurgence of interest in lithium treatment of bipolar disorders in part related to its unique anti-suicidal and neuroprotective effects. METHODS: This is a narrative review of key studies pertaining to the effectiveness and tolerability of lithium treatment in pediatric populations. RESULTS: Evidence supports that lithium is an effective and generally well-tolerated acute treatment for pediatric mania compared to placebo...
February 28, 2018: Pharmacopsychiatry
https://www.readbyqxmd.com/read/29483806/evaluation-of-two-non-myasthenic-patients-with-ptosis
#14
Serkan Kırık, Olcay Güngör, Sedat Işıkay, Can Acıpayam, Yasemin Çoban, Emre Çelik
Decreased height of the eyelid or the narrowing of the lid is called ptosis. Ptosis has several causes. Malignancy-related conditions such as Horner's syndrome, which causes unilateral ptosis in the pediatric age group, and patients with malignancy receiving chemotherapeutic treatment, are often secondary to these drugs and ptosis is a clue of underlying diseases. Underlying pathologies can lead to different clinical conditions such as cognitive impairment from coma, the presence of ptosis should be cautionary...
December 2017: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/29460824/comparison-of-cisplatin-with-lipoplatin-in-terms-of-ototoxicity
#15
Efe Serinan, Zekiye Altun, Safiye Aktaş, Emre Çeçen, Nur Olgun
OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS AND METHODS: House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study...
February 20, 2018: Journal of International Advanced Otology
https://www.readbyqxmd.com/read/29436137/caudal-and-intravenous-dexamethasone-as-an-adjuvant-to-pediatric-caudal-block-a-systematic-review-and-meta-analysis
#16
REVIEW
Change Zhu, Saiji Zhang, Zhiqing Gu, Yiru Tong, Rong Wei
BACKGROUND: Dexamethasone has become a popular additive for regional anesthesia. The aim of this meta-analysis was to assess the effectiveness of this additive on the duration of postoperative analgesia, postoperative vomiting, and possible adverse events in pediatrics. METHODS: We searched databases, conference records, and registered trials for randomized controlled trials. The databases included the Cochrane Library, JBI Database of Systematic Reviews, PubMed, ISI Web of Knowledge, Science-Direct, and Embase...
March 2018: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/29401076/smarttots-update-regarding-anesthetic-neurotoxicity-in-the-developing-brain
#17
Beverley A Orser, Santhanam Suresh, Alex S Evers
SmartTots (http://smarttots.org/) represents a public-private partnership between the International Anesthesia Research Society and the US Food and Drug Administration. Over the past 7 years, SmartTots has worked in collaboration with various stakeholders to determine whether anesthetic drugs have detrimental effects on the developing brain. SmartTots has funded clinical and preclinical studies, organized meetings, served as a repository of peer-reviewed information, and facilitated the development of consensus-based statements...
April 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29390337/linezolid-associated-optic-neuropathy-in-a-pediatric-patient-with-mycobacterium-nonchromogenicum-a-case-report
#18
Napoleón González Saldaña, Diego Mauricio Galvis Trujillo, Ana Maria Borbolla Pertierra, Ana Ivette Mondragón Pineda, Hugo Juárez Olguín
BACKGROUND: Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents. CASE: It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid. OBSERVATIONS: After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29319893/possible-role-of-cyp2b6-genetic-polymorphisms-in-ifosfamide-induced-encephalopathy-report-of-three-cases
#19
Thomas Duflot, Aude Marie-Cardine, Céline Verstuyft, Bruno Filhon, Tony Pereira, Nathalie Massy-Guillemant, Robinson Joannidès, Jérémy Bellien, Fabien Lamoureux
Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed...
January 10, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29319659/residual-neurological-symptoms-after-peripheral-nerve-blocks-for-pediatric-knee-surgery
#20
Robert J Tamai, Brian T Sullivan, Rushyuan J Lee
BACKGROUND: Peripheral nerve blocks (PNBs) provide excellent pain control and reduce the need for systemic analgesics in orthopaedic surgery. PNBs rarely cause complications; however, a few studies of adults have reported neurological complications during the early postoperative period. We investigated complications associated with the use of PNBs during pediatric knee surgery. METHODS: We reviewed the medical records of all 121 children (aged ≤18 y) who underwent knee surgery by 1 orthopaedic surgeon between October 2014 and September 2016...
March 2018: Journal of Pediatric Orthopedics
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