Current drug targets
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Current drug targets · Nov 2012
ReviewMaking the most of pathological specimens: molecular diagnosis in formalin-fixed, paraffin embedded tissue.
The development of commercial reagents designed specifically for use with formalin-fixed paraffin-embedded (FFPE) tissue has unlocked the diagnostic potential of this prolific resource. The availability of archival FFPE tissue and tissue from current patients make it an ideal resource for molecular testing. ⋯ In particular, the cross-linking and processing present problems in the extraction and isolation of DNA, RNA and protein and affect their use in downstream analysis. Here we will discuss some of the problems of FFPE tissue, how they can be overcome and how FFPE material can be used within clinical molecular diagnostics.
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Current drug targets · Jun 2012
ReviewGeneral anesthetics in pediatric anesthesia: influences on the developing brain.
Millions of newborn and infants receive anesthetic, sedative and analgesic drugs for surgery and painful procedures on a daily basis. However, recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models. This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia. ⋯ Conversely, painful stimuli without analgesia and anesthesia have been implicated in triggering neuro-apoptosis in juvenile mammalian models. Published retrospective reviews demonstrate temporary neurological sequelae after prolonged anesthetic exposure in young children and larger studies identify long-term neurodevelopmental impairment after neonatal surgery and anesthesia. This paper examines the evidence for the effects of commonly used anesthetics on neuronal structure and neurocognitive function in laboratory models and reviews the relevant clinical human epidemiologic data.
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Hypovolemia is the most common cause of circulatory failure in children and may lead to critical tissue perfusion and eventually multiple-organ failure. Administration of fluids to maintain or restore intravascular volume represents a common intervention after hemorrhagic shock occurring during surgical procedures or in patients with trauma. Notwithstanding, there is uncertainty whether the type of fluid may significantly influence the outcome, especially in pediatrics. ⋯ Hydroxyethylstarch (HES) preparations have been introduced recently, becoming very popular for vascular loading both in adults and children. However, the number of pediatric studies aimed at evaluating HES efficacy and tolerance is limited. Given the ongoing controversies on the use of colloids in childhood, this review will focus on the pharmacodynamics of synthetic and non synthetic colloids for the treatment of critical blood loss in pediatrics.
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Almost all children in the pediatric intensive care (PICU) need analgesia and/or sedation. Analgesics drugs are used to control pain from surgical incisions, drainages, vascular access or endotracheal suctioning. Sedatives are used to facilitate the delivery of nursing care, to facilitate mechanical ventilation, prevent self-extubation and to minimize patient discomfort. ⋯ However, behavioral evaluation tools based on patient responsiveness, cannot be used during the administration of neuromuscular blocking agents. Under this conditions it could be difficult to interpret the degree of sedation. EEG derived Monitoring devices may represents an useful tools of assessing the level of sedation, but there is insufficient evidence to support the routine use of the BIS monitor in PICU.
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Circulatory failure recognition and treatment represents an important issue in critically ill infants and children. Early diagnosis and prompt institution of adequate treatment may be life-saving for pediatric patients with cardiocirculatory instability in the setting of intensive care. However, the hemodynamic status of the critically ill child is poorly reflected by baseline vital parameters or laboratory blood tests. ⋯ Advanced hemodynamic monitoring consists - among others - of measuring cardiac output, predicting fluid responsiveness and calculating systemic oxygen delivery. Identification and quantifying of pulmonary edema has also been recently appreciated in pediatric critical care. In the last decade, the number of vasoactive drugs has increased, together with a better understanding of clinical application of both different monitoring devices and treatment strategies.