Prehospital use in emergency patients of a laryngeal mask airway by ambulance paramedics is a safe and effective alternative for endotracheal intubation.

BACKGROUND: In Dutch ambulance practice, failure or inability to intubate patients with altered oxygenation and/or ventilation leaves bag-valve mask ventilation as the only alternative, which is undesirable for patient outcome. A novel Laryngeal Mask Airway Supreme (LMA-S) device may be a suitable alternative. AIM: To evaluate the effectiveness and suitability of the LMA-S for emergency medical services in daily out-of-hospital emergency practice. METHODS: After a period of theoretical and practical training of ambulance paramedics in the use of the LMA-S, prospective data were collected on the utilisation of LMA-S in an observational study. Procedures for use were standardised and the evaluation included the number of direct intubation attempts before using LMA-S, attempts required, failure rate and the adequacy of ventilation. Data were analysed taking patient characteristics such as age and indication for ventilatory support into account. RESULTS: The LMA-S was used 50 times over a period of 9 months (33 involving cardiorespiratory arrest, 14 primary and three rescue). The LMA-S could be applied successfully in all 50 cases (100%) and was successful in the first attempt in 49 patients (98%). Respiratory parameters showed adequate oxygenation. All paramedics were unanimously positive about the utilisation of LMA-S because of the easiness of the effort of insertion and general use, and emphasised its value as a useful resource for patients in need. CONCLUSIONS: Ensuring ventilation support by using LMA-S by paramedics in prehospital emergency practice is safe and effective.

Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E.

The Cip/Kip family of cyclin-dependent kinase inhibitors (CKIs) has been implicated in mediating cell cycle arrest prior to terminal differentiation. In many instances, increased expression of CKIs immediately precedes mitotic arrest. However, the mechanism that activates CKI expression in cells that are about to stop dividing has remained elusive. Here we have addressed this issue by investigating the expression pattern of dacapo, a Cip/Kip CKI in Drosophila. We show that the accumulation of dacapo RNA and protein requires Cyclin E and that increased expression of Cyclin E can induce dacapo expression. We also show that the oscillation of the Cyclin E and Dacapo proteins are tightly coupled during ovarian endocycles. Our results argue for a mechanism where Cyclin E/Cdk activity induces Dacapo expression but only within certain windows that are permissive for dacapo expression.

A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis.

In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap expression in embryos parallels the exit of cells from the cell cycle. dap mutant embryos delay the normal cell cycle exit during development; many cells complete an additional cycle and subsequently become quiescent. Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle.

Uncoupling cell fate determination from patterned cell division in the Drosophila eye.

Cell proliferation and cell fate specification are under strict spatiotemporal control in the developing Drosophila eye. Cells excluded from five-cell preclusters synchronously enter a single additional cell cycle, the second mitotic wave, after which the remaining cells are sequentially recruited. When the second mitotic wave was blocked with the human cyclin-dependent kinase inhibitor p21CIP1/WAF1, each cell type was still specified. Hence, cell fate determination is regulated independently of the division pattern of precursor cells. However, the second mitotic wave is needed to generate appropriate numbers of each cell type. Moreover, p21 can arrest precursor cell proliferation and allow appropriate fate choice in vivo.

Reduced topoisomerase II activity in multidrug-resistant human non-small cell lung cancer cell lines.

Multidrug-resistant (MDR) cell lines often have a compound phenotype, combining reduced drug accumulation with a decrease in topoisomerase II. We have analysed alterations in topoisomerase II in MDR derivatives of the human lung cancer cell line SW-1573. Selection with doxorubicin frequently resulted in reduced topo II alpha mRNA and protein levels, whereas clones selected with vincristine showed normal levels of topo II alpha. No alterations of topo II beta levels were detected. To determine the contribution of topo II alterations to drug resistance, topo II activity was analysed by the determination of DNA breaks induced by the topo II-inhibiting drug 4'-(9-acridinylamino)methane-sulphon-m-anisidide (m-AMSA) in living cells, as m-AMSA is not affected by the drug efflux mechanism in the SW-1573 cells. The number of m-AMSA-induced DNA breaks correlated well (r = 0.96) with in vitro m-AMSA sensitivity. Drug sensitivity, however, did not always correlate with reduced topo II mRNA or protein levels. In one of the five doxorubicin-selected clones m-AMSA resistance and a reduction in m-AMSA-induced DNA breaks were found in the absence of reduced topo II protein levels. Therefore, we assume that post-translational modifications of topo II also contribute to drug resistance in SW-1573 cells. These results suggest that methods that detect quantitative as well as qualitative alterations of topo II should be used to predict the responsiveness of tumours to cytotoxic agents. The assay we used, which measures DNA breaks as an end point of topo II activity, could be a good candidate.