Determining the Safety and Tolerability of Rapid Administration of Undiluted Intravenous Levetiracetam in Pediatrics.

Objective: Levetiracetam is widely used in the emergency setting. Safety and tolerability of undiluted levetiracetam is prevalent in adults but is limited in pediatrics. The purpose is to determine the safety and tolerability of rapid administration of undiluted levetiracetam in pediatric patients. Methods: A retrospective, single-center, observational study was conducted in pediatric patients who received undiluted levetiracetam intravenous push. The primary outcome was adverse reactions, extravasation, need for intravenous line replacement, and discontinuation due to adverse reactions. The secondary outcome was turnaround time between ordering and administering first doses. Results: One hundred fourteen patients were included. Injection site reactions occurred in 7 patients. Extravasation occurred in 4 patients. Two patients required intravenous line replacement. There were no adverse events leading to discontinuation of levetiracetam. No difference was seen in the time from order to administration. Conclusion: Rapid administration of undiluted levetiracetam in pediatric patients was safe and well tolerated.

Detecting early recovery of consciousness: a comparison of methods.

Early detection of the return of consciousness has important implications for prognosis and rehabilitation access. The aim of this study was to compare the Coma Recovery Scale-Revised (CRS-R) with individualised quantitative behavioural assessments (IQBA) to determine which method is capable of detecting command-following earlier and more consistently in persons with disorders of consciousness (DoC). Data from 27 patients with DoC, who underwent both assessments concurrently during inpatient rehabilitation, were retrospectively analysed. For each person, performance trajectories on the CRS-R auditory subscale item and IQBA dual command protocols were graphed together to identify earlier and more consistent evidence of consciousness; grouped data were analysed statistically. For 22 patients, IQBA more consistently documented consciousness than the CRS-R, whereas no patients showed the reverse pattern. For 14 of 20 analysable patients, IQBA provided earlier evidence of consciousness, for two patients CRS-R provided earlier evidence, and for four patients both methods provided initial evidence on the same day. These findings suggest that IQBA approaches can provide more consistent and earlier evidence of command-following than the comparable item on the CRS-R. Whether this advantage is due to the individualisation of IQBA or the greater volume of data gathered requires further research.

Nutrition as medical therapy.

Recent data support the use of nutritional agents for use as targeted medical therapy. This article reviews some of the pharmacologic roles that parenteral nutritional ingredients (selenium, lipid emulsion, insulin, and levocarnitine) can play in the setting of critical illness.

Involvement of protein kinase C and not of NF kappa B in the modulation of macrophage nitric oxide synthase by tumor-derived phosphatidyl serine.

Nitric oxide (NO) is one of the main cytotoxic effector molecules involved in the killing of tumor cells by macrophages. In macrophages, lipopolysaccharide (LPS) alone or in combination with IFN-gamma causes the generation of NO by an inducible form of NO synthase (iNOS). We have previously reported that macrophages from mammary tumor bearers have a downregulation of their NO production leading to a diminished cytotoxic activity. Further studies lead to the isolation and characterization of phosphatidyl serine (PS) as a NO inhibitory factor produced by mammary tumor cells. Pretreatment of macrophages with PS was shown to downregulate their cytotoxic potential and NO production upon stimulation with LPS. Activation of PS-pretreated macrophages with LPS and IFN-gamma resulted in higher levels of NO than those observed with LPS alone, but lower than those of untreated macrophages activated with LPS and IFN-gamma. These results correlated with the levels of iNOS RNA as detected by Northern blot analyses. A study of the expression and binding activity of the transcription factor NF kappa B in macrophages pretreated with PS revealed no differences with untreated macrophages. Investigation of the possible signaling pathways leading to the induction of iNOS revealed that in LPS-stimulated macrophages, increases in internal calcium concentration [Ca2+]i were not observed, while NO was normally produced even under calcium-deprived conditions. In contrast, an effective synergism of IFN-gamma with LPS in the production of NO by macrophages required an optimal increase in [Ca2+]i stimulated by IFN-gamma. This increment in [Ca2+]i was significantly reduced in PS-pretreated macrophages. Further experiments demonstrated that pretreatment of macrophages with PS did not change the normal pattern of tyrosine phosphorylation stimulated by LPS but strikingly inhibited PKC activity. Combinations of LPS and IFN-gamma did not alter the latter result, suggesting that IFN-gamma enhances LPS-induction of iNOS through a pathway other than activation of PKC. Importantly, expression of PKC isozymes in both untreated and PS-pretreated macrophages stimulated with LPS remained constant. Out data suggest that, in tumor bearers, PKC and not NF kappa B is the main target for PS to exert its NO inhibitory action on LPS-activated macrophages. An excess of PS in PS-PKC interaction may be responsible, at least in part, for this type of PKC inhibition. Furthermore, PS also appears to downregulate the rise in [Ca2+]i promoted by IFN-gamma in macrophages, reducing the synergism of this cytokine with LPS and leading to a less effective production of NO.