Brain death in children: a retrospective review of patients at a paediatric intensive care unit.

PURPOSE: Among patients in paediatric intensive care units (PICUs), death is sometimes inevitable despite advances in treatment. Some PICU patients may have irreversible cessation of all brain function, which is considered as brain death (BD). This study investigated demographic and clinical differences between PICU patients with BD and those with cardiopulmonary death. METHODS: All children who died in the PICU at a university-affiliated trauma centre between October 2002 and October 2018 were included in this retrospective study. Demographics and clinical characteristics were compared between patients with BD and patients with cardiopulmonary death. RESULTS: Of the 2784 patients admitted to the PICU during the study period, 127 died (4.6%). Of these 127 deaths, 22 (17.3%) were BD and 105 were cardiopulmonary death. Length of PICU stay was shorter for patients with cardiopulmonary death than for patients with BD (2 vs 8.5 days, P=0.0042). The most common mechanisms of injury in patients with BD were hypoxic-ischaemic injury (40.9%), central nervous system infection (18.2%), and traumatic brain injury (13.6%). The combined proportion of accident and trauma-related injury was greater in patients with BD than in patients with cardiopulmonary death (27.3% vs 3.8%, P<0.001). Organ donation was approved by the families of four of the 22 patients with BD (18.2%) and was performed successfully in three of these four patients. CONCLUSIONS: These findings emphasise the importance of injury prevention in childhood, as well as the need for education of the public regarding acceptance of BD and support for organ donation.

Nanocorrugation-Induced Forces between Electrically Neutral Metallic Objects.

Recent advances in nanotechnology have created tremendous excitement across different disciplines, but in order to fully control and manipulate nanoscale objects, we must understand the forces at work at the nanoscale, which can be very different from those that dominate the macroscale. We show that there is a kind of curvature-induced force that acts between nanocorrugated electrically neutral metallic surfaces. Absent in flat surfaces, such a force owes its existence entirely to geometric curvature and originates from the kinetic energy associated with the electron density, which tends to make the profile of the electron density smoother than that of the ionic background and hence induces curvature-induced local charges. Such a force cannot be found using standard classical electromagnetic approaches, and we use a self-consistent hydrodynamics model as well as first-principles density functional calculations to explore the character of such forces. These two methods give qualitatively similar results. We found that the force can be attractive or repulsive, depending on the details of the nanocorrugation, and its magnitude is comparable to light-induced forces acting on plasmonic nano-objects.

Ceftriaxone ameliorates motor deficits and protects dopaminergic neurons in 6-hydroxydopamine-lesioned rats.

Parkinson's disease is caused by the degeneration of dopaminergic neurons in substantia nigra. There is no current promising treatment for neuroprotection of dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.-R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky, S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher, P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature433, 73-77). In the present study, efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and amelioration of motor deficits in a rat model of Parkinson's disease were investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats. Using behavioral tests, grip strength and numbers of apomorphine-induced contralateral rotation were declined in the ceftriaxone-treated group. More importantly, cell death of dopaminergic neurons was found to decrease. In addition, both the protein expression and immunoreactivity for GLT-1 were up-regulated. The present results strongly indicate that ceftriaxone is a potential agent in the treatment of Parkinson's disease.

Nurse-administered propofol-alfentanil sedation using a patient-controlled analgesia pump compared with opioid-benzodiazepine sedation for outpatient colonoscopy.

BACKGROUND AND STUDY AIM: Nurse-administered propofol sedation (NAPS) and patient-controlled sedation using patient-controlled analgesia (PCA) pumps are gaining increasing popularity for gastrointestinal endoscopy. We compared the safety and efficacy of NAPS using PCA pumps with diazemuls-pethidine sedation (DPS) for outpatient colonoscopy. PATIENTS AND METHODS: In a prospective randomized controlled trial patients underwent outpatient colonoscopy with sedation by either NAPS or DPS. For NAPS, following intravenous loading of 0.8 mg/kg propofol, mixtures of 14.3 mg propofol and 35 microgram alfentanil were titrated by nurses using a PCA pump. For DPS, 0.1 mg/kg diazemuls and 0.5 mg/kg pethidine were given as intravenous bolus; further titration was administered as half doses at the endoscopist's discretion. Adequacy of sedation was measured by the Observer's Scale for Sedation and Alertness (OSSA) score (range 1-5). RESULTS: Between July 2005 and June 2006, 88 patients were randomly allocated to NAPS and 90 to DPS. The groups were comparable for baseline characteristics and procedure time. With NAPS, levels of sedation both during colonoscopic intubation and at reaching the cecum were significantly deeper than with DPS (OSSA 3 vs. 5, P < 0.0001). There were no significant differences in cardiopulmonary complication rates, pain scores, satisfaction scores, and patients' willingness to repeat colonoscopy with the same sedation. Drugs cost for NAPS was higher than for DPS (Hong Kong dollars [HKD] 98.34 vs. 5.01). CONCLUSION: Despite higher costs, nurse-administered propofol-alfentanil sedation using a PCA pump can provide deeper conscious sedation, comparable satisfaction, and similar complication risks compared with conventional opioid-benzodiazepine sedation.

Highly spin-polarized field emissions induced by quantum size effects in ultrathin films of Fe on W(001).

Spin-polarized field emissions from Fe pseudomorphic ultrathin films on W(001) surfaces are studied by density functional calculations. We found that nearly completely spin-polarized field emission currents can be realized in two and four Fe layers on W(001) and that these systems have the additional advantages of thermal stability and low work functions. The unusually high spin polarizations of the field emission current is traced to the Fe film's quantum size effects leading to spin-polarized quantum well states and surface resonance states.

Isolated ventricular non-compaction presenting with ventricular tachycardia.

Isolated ventricular non-compaction is a rare congenital cardiomyopathy, manifested morphologically as prominent myocardial trabeculations and deep inter-trabecular recesses that communicate with the ventricular cavity. Heart failure is the most common presenting condition. Other manifestations include arrhythmia and cardioembolic events. This report is illustrative of isolated ventricular non-compaction in a 78-year-old woman. The diagnosis was made when she presented with ventricular tachycardia many years after a stroke. She subsequently underwent implantation of a cardioverter-defibrillator. This report documents an uncommon presentation of this disease entity in the oldest patient at presentation as yet reported in the literature.

PTP1B regulates neurite extension mediated by cell-cell and cell-matrix adhesion molecules.

N-cadherin and beta1-integrin adhesion and signaling play important roles in growth cone adhesion and guidance. Each of these adhesion receptor systems is composed of multiprotein complexes, and both adhesion and downstream signaling events are regulated through the interaction of protein tyrosine kinases and phosphatases with many of the proteins that make up these complex systems. Work from our laboratory reported that the nonreceptor protein tyrosine phosphatase PTP1B is localized to adherens junctions and focal adhesion complexes and regulates both N-cadherin- and beta1-integrin-mediated adhesion. PTP1B appears to modulate integrin-mediated adhesion through regulation of src activation and cadherin-mediated adhesion through dephosphorylation of beta-catenin. We have continued these studies and report that PTP1B is localized to the tips of growing neurites and that introduction of a noncatalytic mutant of PTP1B into PC12 cells results in inhibition of N-cadherin- and beta1-integrin-mediated neurite outgrowth but is without effect on neurite outgrowth on poly-L-lysine. Moreover, suppressing the level of PTP1B in primary embryonic chick neural retina cells using antisense oligonucleotides also inhibits N-cadherin- and beta1-integrin-mediated neurite outgrowth. Neither of these techniques reduces the levels of expression of either adhesion receptor. We conclude that PTP1B is a regulatory component of the molecular complex required for both N-cadherin and beta1-integrin-mediated axon growth.

Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan.

N-cadherin and beta1-integrins play decisive roles in morphogenesis and neurite extension and are often present on the same cell. Therefore, the function of these two types of adhesion systems must be coordinated in time and space to achieve the appropriate cell and tissue organization. We now show that interaction of the chondroitin sulfate proteoglycan neurocan with its GalNAcPTase receptor coordinately inhibits both N-cadherin- and beta1-integrin-mediated adhesion and neurite outgrowth. Furthermore, the inhibitory activity is localized to an NH(2)-terminal fragment of neurocan containing an Ig loop and an HA-binding domain. The effect of neurocan on beta1-integrin function is dependent on a signal originating from the cadherin cytoplasmic domain, possibly mediated by the nonreceptor protein tyrosine kinase Fer, indicating that cadherin and integrin engage in direct cross-talk. In the developing chick, neural retina neurocan is present in the inner plexiform layer from day 7 on, and the GalNAcPTase receptor becomes restricted to the inner nuclear layer and the ganglion cell layer (as well as the fiber layer), the two forming a sandwich. These data suggest that the coordinate inhibition of cadherin and integrin function on interaction of neurocan with its receptor may prevent cell and neurite migration across boundaries.

Growth hormone binding sites in tilapia (Oreochromis mossambicus) liver.

125I-labeled bovine and tilapia growth hormones were used to assess the presence of growth hormone receptors in membranes prepared from tissues of the tilapia Oreochromis mossambicus. The highest level of specific binding was detected in liver membranes from animals of both sexes and the binding was protein-dependent. Tilapia growth hormone, bovine growth hormone, and ovine prolactin, but not tilapia prolactin, potently inhibited the hepatic binding of 125I-labeled bovine growth hormone. Scatchard analysis of the 125I-labeled bovine growth hormone binding data revealed a Bmax (maximum binding) value of 180 fmol/mg protein and a Kd (dissociation constant) value of 13 nM. Tilapia growth hormone potently inhibited hepatic binding of 125I-labeled tilapia growth hormone. Scatchard analysis revealed a single class of binding sites with Bmax and Kd values of 390 fmol/mg protein and 2.5 nM, respectively. Bovine growth hormone and ovine prolactin were less potent while tilapia prolactin was inactive in inhibiting hepatic 125I-labeled tilapia growth hormone binding.

Study of treatment variation in the radiotherapy of head and neck tumors using a fiber-optic on-line radiotherapy imaging system.

On-line radiotherapy imaging systems allow convenient daily acquisition of portal images for treatment verification. The information can also be used to study treatment variability. Using a prototype fiber-optic imaging system, we have measured the treatment variation of 17 head and neck patients. Daily digital portal images were acquired for the on-cord left and right lateral fields. Treatment variations were quantified using the Cumulative Verification Image Analysis (CVIA) method developed at our institute. In the CVIA method, daily portal images were aligned according to three anatomical points predefined on a digitized simulation, or prescription, image. After each image alignment, the block position was cumulated in a bit-map and superimposed on the prescription image to give a cumulative verification summary image. Iso-frequency distributions, or contours, of the block overlap were calculated and examined with respect to the prescription treatment area. The range of the treatment variation was large for the 17 patients. On average, separation of the 0% to 100% block overlap contours was about 10 mm, and the 20% to 80%, 5 mm. The block overlap contours were also used to calculate the frequency with which the prescription area as defined on the simulation film had been treated. The fraction of the prescription area treated depended on the accuracy of the treatment setup and patient repositioning, as expected. At best, approximately 95% of the prescribed area was irradiated 100% of the time during the entire course of radiotherapy. At worst, approximately 70% of the prescribed area was irradiated 100% of the time. These results demonstrate that despite immobilization, large setup variation can still occur. Presenting treatment variation data as population averages does not reflect on the large variation that may be observed in the individual patient.

Studies on tilapia hepatic growth hormone receptor.

Tilapia liver membranes were solubilized with 1% Triton X-100. The presence of growth hormone (GH) receptors was demonstrated by specific binding of radioiodinated tilapia GH (125I-tGH). The solubilized receptor possessed a molecular weight of around 400,000. It was adsorbed on Con A-Sepharose and DEAE BioGel A indicating that it contains carbohydrates and is acidic in character. Its protein nature was revealed by destruction of GH-binding activity by proteases. The involvement of essential sulfhydryl group was suggested by inhibition of 125I-tGH binding to the solubilized receptor by p-chloromercuribenzene sulfonate which could be reversed by dithioerythritol treatment.

Insulin-like growth factor I-like immunoreactivity in serum and tissues of the tilapia, Oreochromis mossambicus.

Tilapia serum was acidified with 0.5 M HCl and then chromatographed on an octadecasily-silica column. After washing with 4% acetic acid, the column was eluted with methanol. The eluate was evaporated to dryness. The sample cross-reacted in a human insulin-like growth factor I (IGF-I) radioimmunoassay, suggesting immunochemical similarity to human IGF-I. IGF-I-like immunoreactivity was present at high levels in tilapia liver. Other tissues containing IGF-I-like immunoreactivity included the gonad, kidney, heart, spleen, brain and muscle. The serum IGF-I-like immunoreactivity was attributed to substances with a molecular weight of 9,000 and 45,000 respectively, and it was elevated after treatment with bovine growth hormone and carp pituitary extract.

Metabolic effects of bovine growth hormone in the tilapia Oreochromis mossambicus.

1. Bovine growth hormone (bGH) was injected into tilapia intramuscularly at a dose of 50 micrograms/100 g/day for a total of five injections. Control fish received saline instead. 2. The serum concentrations of amino acid and glucose were significantly higher and hepatic glycogen concentration and glycogen synthetase activity significantly lower in the bGH-treated fish than those in the control fish. 3. The serum concentrations of protein, lipid and cholesterol, and the hepatic concentrations of protein and lipid, remained unaltered after bGH treatment. 4. The results suggest that bGH exerts anti-insulin effects in tilapia.