The use of high-flow nasal oxygen during airway management in a child with epidermolysis bullosa dystrophica and a difficult airway.

The role of high-flow nasal oxygen in paediatric anaesthesia has been emerging in recent years. However, literature regarding its benefits in paediatric difficult airway management is limited. In this case report, we describe the use of high-flow nasal oxygen during airway management of a child with a difficult airway due to epidermolysis bullosa dystrophica in whom the use of a facemask would have been potentially harmful. Deep sedation was achieved with propofol and remifentanil while maintaining spontaneous breathing before flexible bronchoscopic tracheal intubation was attempted. However, on attempted tracheal intubation difficulty was encountered due to poor visualisation and contact bleeding. Tracheal intubation was eventually successful after converting to videolaryngoscopy. Oxygenation was maintained throughout the process despite deep sedation and a long procedure time. Moreover, no skin abrasions or mucosal injury resulted from the use of high-flow nasal oxygen. We conclude that high-flow nasal oxygen has a valuable role during airway management for a child with a predicted difficult airway when the use of a facemask would have been potentially harmful.

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures.

In view of the possible crosstalks between hematopoiesis and neuropoiesis, we evaluated two microenvironments, murine neonatal neural cell line C17.2 and primary embryonic aorta-gonad-mesonephros (AGM) stromal cells, on the ex vivo expansion of CD34+ cells from human cord blood. In a contact culture system, C17.2 or AGM cells significantly enhanced the expansion of CD34+ cells to a panel of early and committed hematopoietic progenitor cells. In a noncontact transwell system, pre-established C17.2 cells significantly increased the expansion of total nucleated cells, CD34+ cells and multilineage colony forming cells (P<0.01). Expanded cells were infused into nonobese diabetic/severe-combined immunodeficient mice. The engraftment of human (hu)CD45+ cells in the bone marrow of these mice was consistently higher in all the 10 experiments conducted with the support of C17.2 cells when compared with those in respective control groups (11.9 vs 2.43%, P=0.03). Using RT-PCR and Southern blot analysis, we showed that AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and neurotrophic factors. Our data provided the first evidence on the promoting effects of a neural progenitor cell line on hematopoiesis at a noncontact condition. The mechanism could be mediated by the expression of multilineage regulatory factors.

Calcium regulation of calcineurin phosphatase activity by its B subunit and calmodulin. Role of the autoinhibitory domain.

Calcineurin (CaN) contains an autoinhibitory element (residues 457-482) 43 residues COOH-terminal of the calmodulin-binding domain (Hashimoto, Y., Perrino, B. A., and Soderling, T. R. (1990) J. Biol. Chem. 265, 1924-1927) that regulates the Ca(2+)-dependent activation of its phosphatase activity. Substitution of Arg476 and Arg477 or Asp467 to Ala in the autoinhibitory peptide 457-482 significantly decreased its inhibitory potency. CaN A subunits with these residues mutated to Ala were coexpressed with the Ca(2+)-binding B subunit using the baculovirus/Sf9 cell system. Kinetic analysis showed that although the purified mutants had no activity in the absence of calcium, they were less dependent than the wild-type enzyme on calcium and calmodulin for activity. To determine if additional autoinhibitory motifs were present in the COOH terminus of calcineurin, the A subunit was truncated at residues 457 or 420 and co-expressed with B subunit. The Vmax values of both truncation mutants with or without Ca2+ were increased relative to wild-type calcineurin. The increased Ca(2+)-independent activity of CaN420 relative to CaN457 indicates the presence of additional autoinhibitory element(s) within residues 420-457. CaN420 had similar high Vmax values with or without Ca2+, but the Km value for peptide substrate was increased 5-fold to 125 microM in the absence of Ca2+. The Km values of all the expressed calcineurin species were increased in the absence of Ca2+. The CaN A or CaN A420 subunits alone have low Vmax and high Km (115 microM) values even in the presence of Ca2+. These results indicate that 1) there are several autoinhibitory motifs between the CaM-binding domain and the COOH terminus that are relieved by Ca2+ binding to CaM and the B subunit, 2) Ca2+ binding to the B subunit also regulates enzyme activity by lowering the Km of the catalytic subunit for substrate, 3) binding of the B subunit is required for high Vmax values even after removal of the autoinhibitory domain. These results are consistent with synergistic activation of calcineurin by Ca2+ acting through both CaM and the B subunit.

Severe bronchospasm in an asthmatic patient following alcuronium and D-tubocurarine.

An asthmatic patient developed intense bronchospasm immediately following the administration of alcuronium and d-tubocurarine in the same anaesthetic. Intradermal test was positive for both of these drugs but negative for thiopentone and suxamethonium, both of which were given prior to alcuronium. The differential diagnosis and the possible mechanism of the reaction are discussed.

Potentiation of the estrogenic activity of stilbestrol by spiro (cyclohexane-1,2'-indan)-1',4-dione.

During the investigation of a series of spiro compounds having approximately similar molecular dimensions to naturally occurring estrogens, the novel compound spiro(cyclohexane-1,2'-indan)-1',4-dione was prepared. The pretreatment of mice with this estrogenically inactive compound was found to potentiate the estrogenic activity of stilbestrol.