Double-lumen tube tracheal intubation using a rigid video-stylet: a randomized controlled comparison with the Macintosh laryngoscope.

BACKGROUND: Despite an increasing need, there is limited experience of double-lumen endobronchial tube (DLT) placement using video laryngoscope. We evaluated DLT intubation using an OptiScope, a rigid video-stylet with a malleable tip derived from the Clarus Video System, in comparison with a Macintosh laryngoscope. METHODS: After airway evaluation and anaesthetic induction, Cormack and Lehane (C and L) grade was initially assessed in all patients using a Macintosh laryngoscope before tracheal intubation. The trachea was then intubated using either a Macintosh laryngoscope (n=200) or an OptiScope® (n=200). Success rate, intubation time, number of attempts at intubation, vocal cord view during intubation, need for external manipulation, and the incidences of oral mucosal or dental injury were compared between the two devices. RESULTS: Data were analysed for 397 patients. Intubation time with the OptiScope® was faster [median (inter-quartile range): 15 (12-19) s] than with the Macintosh [18(12-28) s] {mean difference [95% confidence interval (CI)}: 5.5 (3.8-13.2) s, P=0.010]. The success rate of the first intubation was higher with the OptiScope® than with the Macintosh [80.4% vs 89.9%, odds ratio (95% CI): 2.2 (1.22-3.87), P=0.036]. Initial view of the vocal cords was also better, although the final success rate was not different between devices. The need for external laryngeal manipulation, oral mucosal, or dental injury was lower with the OptiScope® compared with the Macintosh laryngoscope (all P<0.01). CONCLUSIONS: The OptiScope® provides faster tracheal intubation and a higher success rate for the first intubation with less trauma and a better vocal cord view than the Macintosh laryngoscope.

Comparison of desflurane and sevoflurane anaesthesia in relation to the risk of vagally mediated reflex bradycardia during gastrectomy.

OBJECTIVE: This study compared the risk of clinically significant reflex bradycardia during anaesthesia with sevoflurane or desflurane in patients undergoing gastrectomy. METHODS: In this randomized prospective study, 100 patients undergoing gastrectomy were assigned to receive sevoflurane (n=50) or desflurane (n=50) anaesthesia. No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to <50 beats/min, or a decrease to 50-59 beats/min if associated with a systolic arterial pressure of 70 mmHg in response to surgical manoeuvres. If reflex bradycardia developed, atropine or ephedrine were administered according to a predefined treatment protocol. RESULTS: Data from 85 patients were available for analysis. The proportion of patients with symptomatic reflex bradycardia in the sevoflurane and desflurane groups was similar (69.0% versus 55.8%, respectively) and both groups required a similar amount of atropine and/or ephedrine. CONCLUSIONS: Clinically significant reflex bradycardia occurred with a relatively high frequency during gastrectomy. Although desflurane is associated with sympathetic activation, it did not provide a protective effect against vagally mediated reflex bradycardia during gastrectomy compared with sevoflurane.

TCF-4 binds beta-catenin and is expressed in distinct regions of the embryonic brain and limbs.

The Tcf family of transcription factors, in association with beta-catenin, mediate Wnt signaling by transactivating downstream target genes. Given the function of wnt genes in neural development and organogenesis, Tcf transcription factors must be integral to the development of many embryonic tissues. In fact, the role of Tcf genes in axis formation in Xenopus and in segment polarity in Drosophila is well established. In this report, we have identified two isoforms of the mouse Tcf-4 gene. Tcf-4 expressing cells showed nuclear localization of beta-catenin. Although Tcf-4 RNA was widely distributed throughout embryogenesis, high levels of Tcf-4 expression were particularly evident in the developing CNS and limb buds. In extended streak stage embryos (E7.5), Tcf4 expression was detected in anterior endoderm. E8.5 embryos had Tcf-4 expression in rostral neural plate and in alternating rhombomeres of the hindbrain. By E9.5 and thereafter, expression in the hindbrain disappeared and strong expression was detected in the diencephalon. Strikingly Tcf-4 expression in the forebrain was undetected in Small eye mutant embryos indicating that Pax-6 is required for Tcf-4 expression in the forebrain. In developing limbs, Tcf-4 is readily detected starting at E10.5 and is limited to mesenchymal cells surrounding the areas of chondrification. These data indicate a function for Tcf-4 in neural and limb development, two tissues where Wnt signaling plays an essential role.

Differential expression and function of cadherin-6 during renal epithelium development.

The cadherin gene family encodes calcium-dependent adhesion molecules that promote homophilic interactions among cells. During embryogenesis, differential expression of cadherins can drive morphogenesis by stimulating cell aggregation, defining boundaries between groups of cells and promoting cell migration. In this report, the expression patterns of cadherins were examined by immunocytochemistry and in situ hybridization in the embryonic kidney, during the time when mesenchymal cells are phenotypically converted to epithelium and the pattern of the developing nephrons is established. At the time of mesenchymal induction, cadherin-11 is expressed in the mesenchyme but not in the ureteric bud epithelium, which expresses E-cadherin. The newly formed epithelium of the renal vesicle expresses E-cadherin near the ureteric bud tips and cadherin-6 more distally, suggesting that this primitive epithelium is already patterned with respect to progenitor cell types. In the s-shaped body, the cadherin expression patterns reflect the developmental fate of each region. The proximal tubule progenitors express cadherin-6, the distal tubule cells express E-cadherin, whereas the glomeruli express P-cadherin. Ultimately, cadherin-6 is down-regulated whereas E-cadherin expression remains in most, if not all, of the tubular epithelium. Antibodies generated against the extracellular domain of cadherin-6 inhibit aggregation of induced mesenchyme and the formation of mesenchyme-derived epithelium but do not disrupt ureteric bud branching in vitro. These data suggest that cadherin-6 function is required for the early aggregation of induced mesenchymal cells and their subsequent conversion to epithelium.

Reduced CD3-mediated protein tyrosine phosphorylation in anergic CD4+ and CD8+ T cells.

Mice inoculated i.v. with superantigens exhibit long lived Ag-specific T cell tolerance. An in vitro model for this phenomenon is the ensuing unresponsiveness of Th1 T cell clones activated via the TCR/CD3 complex in the absence of co-stimulation. We have previously demonstrated alterations in TCR-mediated early protein tyrosine phosphorylation events in Th1 clones anergic for IL-2 production. In this study, we demonstrate unresponsiveness in CD4+ and CD8+ T cells from V beta 8.1 transgenic mice inoculated i.v. with the superantigen Mls-1a. The unresponsiveness of both CD4+ and CD8+ T cells involves defective IL-2 production upon restimulation, with CD4+ T cells exhibiting an additional defect in IL-2 utilization. The transgenic model allowed study of T cell signaling in a relatively homogeneous population of unresponsive cells without elaborate purification of Ag-reactive populations. Both CD4+ and CD8+ T cells exhibit altered tyrosine phosphorylation of two protein substrates upon CD3-mediated restimulation. The substrates involved, p38 and p75, are of identical size to substrates similarly affected in anergic Th1 clones. Altered tyrosine phosphorylation is therefore closely associated with defective IL-2 production in these three anergic T cell types, and may play a role in the maintenance of anergy.

Altered protein tyrosine phosphorylation in anergic Th1 cells.

Clonal anergy as a mechanism for tolerance in T lymphocytes can be studied using an in vitro culture system, in which cloned CD4+ Th1-type murine T cells are rendered anergic for IL-2 transcription. The long-lasting molecular changes in anergic cells that prevent the response to Ag restimulation are not yet known. To determine whether the TCR might be uncoupled from normal intracellular signaling pathways, we investigated the response of anergic T cells to Ag, to anti-CD3 antibodies, or to anti-CD4 antibody restimulation in terms of early protein tyrosine phosphorylation events. Tyrosine phosphorylation of the CD3 zeta chain was apparently normal. In contrast, defects in the induction of tyrosine phosphorylation of three major T cell protein substrates were demonstrated. Altered phosphorylation correlated with functional nonresponsiveness for proliferation and reversal of anergy by growth in exogenous IL-2 resulted in reversal of the phosphorylation defects as well as in recovery of Ag responsiveness. These results suggest that specific defects in tyrosine phosphorylation pathways required for the induction of IL-2 synthesis may help to explain nonresponsiveness to Ag in tolerant T cells.

Anergic Th1 cells express altered levels of the protein tyrosine kinases p56lck and p59fyn.

Tolerance in T lymphocytes can result from clonal anergy, or paralysis, of Ag-specific T cells. To investigate the molecular mechanisms responsible for anergy, a system in which tolerance can be induced in vitro was employed. Anergy, as defined by long-lived nonresponsiveness to normal antigenic stimulation for IL-2 production, was produced in cloned murine CD4+ Th1 cells. Here we report that such anergic Th1 cells express constitutively reduced amounts of the protein tyrosine kinase p56lck and constitutively elevated levels of the protein tyrosine kinase p59fyn. Because protein tyrosine phosphorylation is known to be important for the normal induction of IL-2 synthesis, these results suggest that T cell anergy may be maintained, at least in part, by alterations in tyrosine phosphorylation signaling events.

The role of clonal selection in the pathogenesis of an autoreactive human B cell lymphoma.

To study the association of autoimmunity and human B cell neoplasia, we have established a model of a B cell lymphoma which expresses a pathogenic autoantibody of defined specificity. The Ig VH gene expressed in this neoplasm was analyzed longitudinally using clinical specimens taken from the splenic lymphoma (S) at diagnosis and from lymph node relapses 3 and 4 yr later (N3 and N4). Southern analysis and oligonucleotide hybridization experiments demonstrated that clonally related predominant and minor tumor cell populations were present in S at diagnosis, and that the minor population became the predominant population in the relapse specimens, N3 and N4. Although the Ig specificity and idiotype were the same at diagnosis and at both relapses, analysis of the expressed VH gene sequences showed 14 base changes between S and N3, and 2 further changes at N4. Little sequence heterogeneity was observed at each sampling time, indicating that the ongoing mutation frequency was low. The relevant germline precursor VH gene was determined from autologous germline DNA and compared to the expressed genes. Based on the pattern of shared and unshared mutations, we were able to establish the genealogic relationship of the germline VH gene and the expressed clonotypes of S, N3 and N4. Taken together, the findings from Southern blotting, oligonucleotide hybridization, and sequence analysis permit us to describe a molecular aspect of tumor progression, "clonotypic shift", wherein subpopulations of the malignant clone, marked by different V gene clonotypes, emerge and predominate at different time points in the evolution of the lymphoma. Furthermore, the sequential and nonrandom pattern of the VH mutations, correlated with the observed conservation of autospecificity and idiotype, implies that clonal selection may have influenced the pathogenesis of the lymphoma.