Current pharmaceutical design
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This paper will summarize the clinical features of transfusion-related acute lung injury (TRALI) before the experimental and clinical literature on the pathogenesis of TRALI is reviewed. Several mechanisms by which leukocyte antibodies induce TRALI have been unraveled. ⋯ In contrast, the pathomechanism behind non-immune TRALI (associated with the transfusion of blood components which do not contain antibodies) is less well understood, especially since the relevance of mechanisms proposed earlier is questioned by recent findings. The diversity of newly described factors contributing to TRALI supports the previously proposed threshold model of TRALI, and an extension of that model including newly defined multipliers and attenuators of TRALI is emerging.
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Normal cognitive development depends on the timely formation of meaningful neuronal circuitries. These, in turn, depend on the proper formation and functioning of neuronal synapses, which control the flow of information between neurons. The time period when synapse formation is most intense is referred to as synaptogenesis, coinciding with the peak of brain development. ⋯ Although a direct causal link between disturbed synaptogenesis and behavioral development is not yet established, several animal studies have confirmed that cognitive development of rodents and non-human primates could be permanently impaired after a single exposure to clinically-relevant general anesthetics. Clinical evidence is now beginning to emerge suggesting that very young children may be susceptible to anesthesia-induced impairment of behavioral development, cognitive in particular. This review will summarize some of the presently available evidence regarding anesthesia-induced effects on developmental synaptogenesis and intellectual functioning.
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Review
Pharmacokinetics of drugs in neonates: pattern recognition beyond compound specific observations.
Although the principles of drug disposition also apply in neonates, their specific characteristics warrant focussed assessment. Children display maturation in drug disposition, but this is most prominent in the first year of life. Besides maturational aspects of drug absorption and distribution, maturation mainly relates to (renal) elimination and (hepatic) metabolic clearance. ⋯ The description of a compound specific pattern is beyond compound specific relevance. The maturational patterns described and the extent of the impact of covariates can subsequently be applied to predict in vivo time-concentration profiles for compounds that undergo similar routes of elimination. Through improved predictability, such maturational models can serve to improve both the clinical care and feasibility and safety of clinical studies in neonates.
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Stress plays a role in most conceptualizations of the etiology of psychotic disorders. This is based on extensive research showing an association between the incidence of psychosis and psychosocial stress exposure (e.g., stressful life events and trauma) both in childhood and the weeks preceding a psychotic episode. There is also evidence of increased sensitivity to stressful events and dysregulation of biological stress systems. ⋯ The current paper reviews this research and discusses the possible mechanisms responsible for these associations. This discussion includes the possible effect of stress on the hypothalamic-pituitary-adrenal [HPA] axis and hippocampus, and the role adolescent developmental changes may play in mediating this effect. Further longitudinal research combining clinical and biological measures of stress with techniques designed to assess developmental change in neural structure and function, cellular mechanisms, and genetic and epigenetic factors are critical for elucidating the role stress plays in the pathophysiology of psychotic illness.
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Bronchoscopic procedures are at times intricate and the patients often very ill. These factors and an airway shared with the pulmonologist present a clear challenge to anesthesiologists. The key to success lies in the understanding of both the underlying pathology and procedure being performed combined with frequent two-way communication between the anesthesiologist and the pulmonologist. ⋯ Topics discussed in this review include anesthesia for advanced diagnostic procedures as well as for interventional/ therapeutic procedures. The latter includes bronchoscopic tracheal balloon dilation, tracheobronchial stenting, endobronchial electrocautery, bronchoscopic cryotherapy and other techniques. Special situations, such as tracheoesophageal fistula and mediastinal masses, are also considered.