Cost minimisation of RSV prevention with palivizumab.
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Biomedical subjects
Publications and source records attributed to J H Simpson.
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BACKGROUND: Medication errors are common in the neonatal intensive care unit (NICU). Various strategies to reduce errors have been described in adult and paediatric patients but there are few published data on their effect in the NICU. AIM: To describe the medication errors occurring within an NICU, and assess the impact of a combined risk management/clinical pharmacist led education programme on these errors. METHODS: Medication errors were identified prospectively over one year by critical incident reporting. Four months into the study, a pharmacist led education programme was instituted. This involved a daily, cot side, pharmacist led review of medication orders. Each new member of pharmacy, nursing, or medical staff was also required to successfully complete a series of dose calculations. In addition, a risk management approach was used to make several changes in practice during the study period. RESULTS: A total of 105 errors were identified, four serious, 45 potentially serious, and 56 minor. The four serious errors included two tenfold dose miscalculations. Most (71%) of the errors were due to poor prescribing. After the introduction of our interventions, monthly medication errors fell from a mean (SD) of 24.1 (1.7) per 1000 neonatal activity days to 5.1 (3.6) per 1000 days (p < 0.001) in the following three months. The subsequent change over of junior medical staff was associated with a significant increase in medication errors to 12.2 (3.6) per 1000 neonatal activity days (p = 0.037). However, the number remained significantly less than before our interventions (p < 0.001). Three serious errors occurred in the first four months compared with one in the second eight month period, the latter corresponding to the six monthly change over of junior medical staff. CONCLUSIONS: Medication errors are common in NICUs. Fortunately, actual harm to an infant is rare. Interventions to reduce errors, particularly within the context of a risk management programme, are effective.
Slit is secreted by cells at the midline of the central nervous system, where it binds to Roundabout (Robo) receptors and functions as a potent repellent. We found that migrating mesodermal cells in vivo respond to Slit as both an attractant and a repellent and that Robo receptors are required for both functions. Mesoderm cells expressing Robo receptors initially migrate away from Slit at the midline. A few hours after migration, these same cells change their behavior and require Robo to extend toward Slit-expressing muscle attachment sites. Thus, Slit functions as a chemoattractant to provide specificity for muscle patterning.
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Slit is secreted by midline glia in Drosophila and functions as a short-range repellent to control midline crossing. Although most Slit stays near the midline, some diffuses laterally, functioning as a long-range chemorepellent. Here we show that a combinatorial code of Robo receptors controls lateral position in the CNS by responding to this presumptive Slit gradient. Medial axons express only Robo, intermediate axons express Robo3 and Robo, while lateral axons express Robo2, Robo3, and Robo. Removal of robo2 or robo3 causes lateral axons to extend medially; ectopic expression of Robo2 or Robo3 on medial axons drives them laterally. Precise topography of longitudinal pathways appears to be controlled by a combination of long-range guidance (the Robo code determining region) and short-range guidance (discrete local cues determining specific location within a region).
Previous studies showed that Roundabout (Robo) in Drosophila is a repulsive axon guidance receptor that binds to Slit, a repellent secreted by midline glia. In robo mutants, growth cones cross and recross the midline, while, in slit mutants, growth cones enter the midline but fail to leave it. This difference suggests that Slit must have more than one receptor controlling midline guidance. In the absence of Robo, some other Slit receptor ensures that growth cones do not stay at the midline, even though they cross and recross it. Here we show that the Drosophila genome encodes three Robo receptors and that Robo and Robo2 have distinct functions, which together control repulsive axon guidance at the midline. The robo,robo2 double mutant is largely identical to slit.
The aim of this study was to review retrospectively the safety and efficacy of a paediatric sedation protocol in a district general hospital radiology department. 256 children attended for CT scanning over a 40-month period. 40 children required sedation and were given quinalbarbitone. 34 (85%) of this group were adequately sedated. Of the children who received quinalbarbitone, 35 were under 5 years of age. 32 of this group (91.4%) were adequately sedated. Failures in children under 5 years were all caused by problems with administration whilst failures in the older children were due to paradoxical excitement. No problems with respiratory depression were encountered. Sedation can be safely performed in a district general hospital radiology department if a structured protocol is adhered to. Quinalbarbitone is a safe, effective oral agent in children under the age of 5 years.
OBJECTIVES: The effectiveness of a second protease inhibitor in patients who failed an initial protease inhibitor is unclear but believed to be low. It has been postulated, however, that patients who fail nelfinavir may respond differently. We therefore assessed the virologic response to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir. METHODS: A total of 26 patients enrolled in the nelfinavir clinical trials AG506 and AG511 at our two sites who failed (two consecutive HIV viral loads > 5000 copies/ml; branched DNA assay) were switched to a combination of stavudine 40 mg twice daily, lamivudine 150 mg twice daily, ritonavir 400 mg twice daily and saquinavir 400 mg twice daily. RESULTS: The mean viral load at enrollment in this study was 46 674 copies/ml (range, 1075-146400 copies/ml). The median CD4 cell count was 222 x 10(6)/l (range, 82-448 x 10(6)/l). The median duration of nelfinavir use with a detectable viral load before the switch occurred was 48 weeks. Two patients discontinued the study at 3 weeks. All of the remaining patients (n = 24) reached undetectable viral loads (< 500 copies/ml) that were sustained at week 24 in 17 (71%) out of 24 subjects. The most frequent baseline mutations in the protease gene prior to switching were D30N (13 out of 18), N88D (eight out of 18) and M36I (eight out of 18). The presence or absence of these mutations was not predictive of a short-term virologic response. CONCLUSIONS: Most patients who failed a nelfinavir-containing regimen responded to a switch to a combination regimen with saquinavir-ritonavir.
It has been proposed that AlF4- can serve as a tetrahedral pseudophosphate bound to guanosine diphosphate (GDP) [or other nucleoside diphosphates (NDP)] in G-protein systems. In a previous paper [D. J. Nelson and R. B. Martin, J. Inorg. Biochem. 43, 37 (1991)], 19F and 1H NMR were used to analyze the ternary system Al(3+)-NDP-F- in aqueous solutions. Ternary complexes (NDP)AlFx (with x = 1-3) were identified, but no (NDP)AlF4 was found. In this paper, the equilibrium constants for ternary complex formation that were obtained in the previous paper were further tested in a more extensive 1H and 31P NMR study of speciation in systems that contained Al3+, F-, and adenosine 5'-diphosphate (ADP). The results of the study are in general support of previously derived constants for ternary complexes and also provide support for the existence at relatively high ADP concentration (approximately 10 mM) of a base-stacked intermolecular dihydroxy-di-Al3+ bridged ADP dimeric structure at an ADP to Al3+ molar ratio of 1:1. 31P NMR of the dimer reveals that each of the two Al3+ ions is bidentately coordinated to the alpha and beta phosphates of a single (but different) ADP molecule. Evidence is also presented for the existence at relatively low ADP concentration (approximately 0.5 mM) of a monomeric species in which a single Al3+ ion is coordinated to alpha and beta phosphates of a single ADP molecule. 1H NMR of the monomeric species reveals the expected "wrong-way chemical shift" of the adenine C8 proton upon Al3+ ion complexation to the phosphate chain.
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This study examines the effects of morphine (10 mg/70 kg body weight) versus placebo (isotonic saline) on experimentally induced cold pressor pain threshold and tolerance, on self-reports of psychological states and drug effects, observer ratings of psychological states, and performance on timed cognitive-motor tasks in 20 non-drug using, normal male volunteers (21-28 years of age). Morphine increased both threshold and tolerance for cold pressor pain, and also increased "euphoric" and decreased "clear thinking" responses on the respective scales. Morphine, in contrast to placebo, increased scores on depression, fatigue, and cognitive loss-dysfunction scales and decreased scores on carefree and "friendliness" scales. Three sets of psychological variables were observed to covary significantly: Measures of anxiety and hostility; reports of fatigue and cognitive dysfunction; and reports of carefree feelings and perceptions of clear thinking. While measures of hostility, fatigue, and cognitive dysfunction covaried positively, reports of carefree feelings and perception of clear thinking covaried negatively with increased pain threshold and tolerance. Anxiety, contrary to reports in the literature, also covaried positively with the pain measures. The results were interpreted as supporting a relationship between increased arousal of the nervous system and decreased pain sensitivity in conjunction with the known analgesic effects of morphine.
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