ABSTRACT
Primary neurological injury in children can be induced by diverse intrinsic and extrinsic factors including brain trauma, tumors, and intracranial infections. Regardless of etiology, increased intracranial pressure (ICP) as a result of the primary injury or delays in treatment may lead to secondary (preventable) brain injury. Therefore, early diagnosis and aggressive treatment of increased ICP is vital in preventing or limiting secondary brain injury in children with a neurological insult. Present management strategies to improve survival and neurological outcome focus on reducing ICP while optimizing cerebral perfusion and meeting cerebral metabolic demands. Targeted therapies for increased ICP must be considered and implemented as early as possible during and after the initial stabilization of the child. Thus, the emergency physician has a critical role to play in early identification and treatment of increased ICP. This article intends to identify those patients at risk of intracranial hypertension and present a framework for the emergency department investigation and treatment, in keeping with contemporary guidelines. Intensive care management and the treatment of refractory increases in ICP are also outlined.
Subject(s)
Emergencies , Intracranial Hypertension/therapy , Analgesia/methods , Barbiturates/therapeutic use , Brain Damage, Chronic/etiology , Brain Damage, Chronic/prevention & control , Brain Ischemia/etiology , Brain Ischemia/prevention & control , Child , Combined Modality Therapy , Craniotomy , Critical Care/methods , Critical Care/standards , Diagnostic Imaging , Early Diagnosis , Emergency Medical Services/methods , Emergency Medical Services/standards , Encephalocele/etiology , Encephalocele/prevention & control , Humans , Hypertonic Solutions/therapeutic use , Hypoglycemia/etiology , Hypoglycemia/prevention & control , Hyponatremia/etiology , Hyponatremia/prevention & control , Intracranial Hypertension/diagnosis , Intracranial Hypertension/drug therapy , Intracranial Hypertension/etiology , Intracranial Hypertension/physiopathology , Practice Guidelines as Topic , Resuscitation/methods , Risk Factors , Seizures/etiology , Seizures/prevention & controlABSTRACT
Anaplastic thyroid carcinoma is an aggressive form of cancer with no treatment. Angiogenesis inhibitors, such as TNP-470, a synthetic derivative of fumagillin, have been shown to reduce tumor size and increase survival in heterotopic animal models of thyroid cancer. Our goals were to determine the effect of TNP-470 on anaplastic thyroid cancer using an orthotopic murine model, to identify the molecular pathways of TNP-470 actions on endothelial cells, and to determine the non-endothelial tumor effects of TNP-470. We injected human anaplastic thyroid carcinoma cells (DRO'90) into the thyroid glands of nude mice. Mice received TNP-470 (30 mg/kg) s.c. for 6 weeks. TNP-470 prolonged survival and reduced liver metastases. TNP-470 had direct cytotoxic effects on anaplastic thyroid carcinoma cells in vitro and in vivo. Paradoxically, TNP-470 increased vascular endothelial growth factor secretion from tumor cells in vitro and in vivo. However, there was no associated increase in tumor microvessel density. In endothelial cells, TNP-470 prevented vascular endothelial growth factor-induced endothelial permeability, intercellular gap formation, and ruffle formation by preventing Rac1 activation.
