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1.
Paediatr Anaesth ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367703

RESUMO

BACKGROUND: Posterior spinal instrumentation and fusion is an established surgical procedure for the correction of adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring is standard practice for this procedure. Anesthetic agents can have different, but significant, effects on neurophysiological monitoring outcomes. AIM: To determine if intravenous lidocaine infusion therapy has an impact on the intraoperative neurophysiological monitoring during posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis. METHODS: Following ethical approval, we conducted a retrospective review of charts and the archived intraoperative neurophysiological data of adolescents undergoing posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring data included the amplitude of motor evoked potentials and the amplitude and latency of somatosensory evoked potentials. A cohort who received intraoperative lidocaine infusion were compared to those who did not. RESULTS: Eighty-one patients were included in this analysis, who had surgery between February 4, 2016 and April 22, 2021: 39 had intraoperative intravenous lidocaine infusion and 42 did not. Based on hourly snapshot data, there was no evidence that lidocaine infusion had a detrimental effect on the measured change from baseline for MEP amplitudes in either lower (mean difference 41.9; 95% confidence interval -304.5 to 388.3; p = .182) or upper limbs (MD -279.0; 95% CI -562.5 to 4.4; p = .054). There was also no evidence of any effect on the measured change from baseline for SSEP amplitudes in either lower (MD 16.4; 95% CI -17.7 to 50.5; p = .345) or upper limbs (MD -2.4; 95% CI -14.5 to 9.8; p = .701). Finally, there was no evidence of a difference in time to first reportable neurophysiological event (hazard ratio 1.13; 95% CI 0.61 to 2.09; p = .680). CONCLUSIONS: Data from these two cohorts provide preliminary evidence that intravenous lidocaine infusion has no negative impact on intraoperative neurophysiological monitoring during PSIF for adolescent idiopathic scoliosis.

2.
J Pediatr Hematol Oncol ; 41(6): e359-e370, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30702467

RESUMO

BACKGROUND: Recent studies have shown that cell cycle events are tightly controlled by complex and shared activities of a select group of kinases. Among these, polo-like kinases (Plks) are regulatory mitotic proteins that are overexpressed in several types of cancer and are associated with poor prognosis. MATERIALS AND METHODS: We have evaluated, in preclinical in vitro studies, the activity of a panel of Plk inhibitors against cell lines derived from refractory pediatric leukemia, as well as primary leukemia cells, in culture. Through in vitro growth inhibition studies, Western blot analysis for the expression and activation of key regulators of cell growth and survival and gene silencing studies, we specifically examined the ability of these agents to induce cytotoxicity through the activation of apoptosis and their capacity to interact and modulate the expression and phosphorylation of Aurora kinases. RESULTS: Our findings show that the various Plk-1 inhibitors in development show potential utility for the treatment of pediatric leukemia and exhibit a wide range of phosphorylation and target modulatory capabilities. Finally, we provide evidence for a complex interregulatory relationship between Plk-1 and Aurora kinases enabling the identification of synergy and biologic correlates of drug combinations targeting the 2 distinct enzyme systems. DISCUSSION: This information provide the rationale for the evaluation of Plk-1 as an effective target for therapeutics in refractory pediatric leukemia and indicate compensatory activities between Plk-1 and Aurora kinases, providing insight into some of the complex mechanisms involved in the process of cell division.


Assuntos
Apoptose , Aurora Quinases/antagonistas & inibidores , Azepinas/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Leucemia/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pteridinas/farmacologia , Pirimidinas/farmacologia , Proliferação de Células , Humanos , Leucemia/tratamento farmacológico , Leucemia/enzimologia , Células Tumorais Cultivadas , Quinase 1 Polo-Like
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