Repeated attempts improve tracheal tube insertion time using the intubating laryngeal airway in a mannequin

Study ObjectiveTo determine if repeated performance of endotracheal tube insertion via the intubating laryngeal airway (ILA) would shorten insertion time in mannequins.DesignProspective study.SettingClinical Skills Laboratory, Department of Anesthesia, Toronto Western Hospital.Participants65 department anesthesiologists.MeasurementsAfter a video training session, anesthesiologists with no previous experience with the ILA performed 5 consecutive ILA-guided tracheal tube intubations on a mannequin. Each participant completed Task 1: insertion of an ILA; Task 2: blind insertion of a tracheal tube through the ILA, and Task 3: removal of the ILA. The time required for each task and the total intubation time for the three tasks over the 5 attempts were recorded. These times were compared using repeated-measures analysis of variance. The success rate among the 5 attempts was compared using Chi-Square analyses.Main ResultsA total of 65 anesthesiologists performed 5 ILA-guided tracheal intubations each. Total intubation time decreased from the first to the fifth attempt (92.6 ± 22.7 sec, 74.5 ± 19.2 sec, 66.5 ± 16.5 sec, 65.9 ± 19.9 sec, and 60.8 ± 16.3 sec; P < 0.001). Significant differences in intubation times were noted between the first and second, and the second and third attempts (P < 0.001 and P = 0.02, respectively). The success rate did not change over the 5 attempts (84.6%, 89.2%, 84.6%, 89.2%, and 90.8%; P = 0.737).ConclusionsTotal intubation time decreased by 34% (92.6 to 60.8 sec) over the 5 attempts in mannequins. The success rate ranged from 84.6% to 90.8% and did not differ significantly over the 5 attempts.     

Maternal germline-specific effect of DNA ligase I on CTG/CAG instability

The instability of (CTG)?(CAG) repeats can cause >15 diseases including myotonic dystrophy, DM1. Instability can arise during DNA replication, repair or recombination, where sealing of nicks by DNA ligase I (LIGI) is a final step. The role of LIGI in CTG/CAG instability was determined using in vitro and in vivo approaches. Cell extracts from a human (46BR) harbouring a deficient LIGI (～3% normal activity) were used to replicate CTG/CAG repeats; and DM1 mice with >300 CTG repeats were crossed with mice harbouring the 46BR LigI. In mice, the defective LigI reduced the frequency of CTG expansions and increased CTG contraction frequencies on female transmissions. Neither male transmissions nor somatic CTG instability was affected by the 46BR LigI - indicating a post-female germline segregation event. Replication-mediated instability was affected by the 46BR LIGI in a manner that depended upon the location of Okazaki fragment initiation relative to the repeat tract; on certain templates, the expansion bias was unaltered by the mutant LIGI, similar to paternal transmissions and somatic tissues; however, a replication fork-shift reduced expansions and increased contractions, similar to maternal transmissions. The presence of contractions in oocytes suggests that the DM1 replication profile specific to pre-meiotic oogenesis replication of maternal alleles is distinct from that occurring in other tissues and, when mediated by the mutant LigI, is predisposed to CTG contractions. Thus, unlike other DNA metabolizing enzymes studied to date, LigI has a highly specific role in CTG repeat maintenance in the maternal germline, involved in mediating CTG expansions and in the avoidance of maternal CTG contractions.     

Lighted stylet-guided intubation via the intubating laryngeal airway in a patient with Hallermann-Streiff syndrome

Purpose

Hallermann-Streiff syndrome is a congenital syndrome associated with oculomandibulofacial abnormalities and potentially difficult airways. This case report describes the novel use of a lighted stylet-guided tracheal tube insertion through a new supraglottic airway, the intubating laryngeal airway (ILA?), in a patient with Hallermann-Streiff syndrome who had anticipated difficult airway.

Clinical features

A 26-year-old male with Hallermann-Streiff syndrome was scheduled for a vitrectomy. The patient had mandibulofacial dystocia with a bird-like appearance, a mouth opening of 4 cm, a receding chin, and a Mallampati class 3 examination. The surgeon requested muscle paralysis and no movement during surgery. After receiving midazolam, fentanyl and propofol, a size 3.5 ILA? was inserted and lung ventilation was easy to perform. A 7.5-mm internal diameter tracheal tube was mounted on a lighted stylet with its inner rigid stylet removed. After succinylcholine administration, the lighted stylet-tracheal tube assembly was inserted via the ILA? until the transillumination just vanished below the sternal notch. The lighted stylet was removed, the circuit was connected, and capnography confirmed tracheal placement of tube. The ILA? was deflated and left in situ. Upon emergence from anesthesia, the tracheal tube, and subsequently the ILA?, were removed without complications.

Conclusions

This case presents a novel use of a lighted stylet-guided tracheal tube insertion through the ILA? in a patient with Hallermann-Streiff syndrome. This intubation technique can be considered in patients with difficult airways as a primary route of intubation, or as a secondary rescue strategy.     

A conserved role for Hox paralog group 4 in regulation of hematopoietic progenitors

Regulatory circuits that control stem cell fate decisions can be identified and understood by manipulating individual regulatory elements genetically. While impractical in the rare somatic stem cells of primary tissue, this approach is feasible in embryonic stem cells differentiated in vitro into the somatic stem cell type of interest. We present an improved highly efficient targeting system allowing genes to be integrated into a predetermined, doxycycline-inducible locus, and corresponding inducible embryonic stem cell lines to be generated rapidly. We apply this system to evaluate a key hematopoietic progenitor cell regulatory element, HoxB4, and its mammalian paralogs, whose effects have not yet been tested in this context. We show that all Hox paralog group 4 members, A4, B4, C4, and D4, have similar effects on hematopoietic stem and progenitor self-renewal in vitro, and thus classify Hox paralog group 4 as promoting self-renewal. Each paralog group 4 member both promotes proliferation and inhibits differentiation, enabling the exponential expansion of hematopoietic progenitors from the c-kit(+)/CD41(+) cell fraction of day 6 murine embryoid bodies. By evaluating a set of deletion mutants we show that sequences in addition to the homeodomain and hexapeptide motif are required for this activity. These results highlight the utility of this expression system to perform functional and structural analyses of genetic regulators of cell fate decisions.     

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease

Aims/hypothesis  

A high prevalence of diabetes contributes to excess CHD in Indian Asians, but the underlying mechanisms are unclear. Heart rate, heart rate variability (HRV) and baroreflex sensitivity (BRS) are measures of cardiac autonomic function that are disturbed by hyperglycaemia and predict CHD. We compared these measures in Indian Asians and Europeans, and sought explanations for the observed differences.     

Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells

Silymarin and, one of its constituents, silibinin exert strong efficacy against prostate cancer (PCA); however, anticancer efficacy and associated mechanisms of other components of silymarin, which is a mixture of flavonolignans, are largely unknown. Here we have assessed the anticancer efficacy of two pure compounds isosilybin B and isosilybin A, isolated from silymarin, in human prostate carcinoma LNCaP and 22Rv1 cells. Isosilybin B and isosilybin A treatment resulted in growth inhibition and cell death together with a strong G(1) arrest and apoptosis in both the cell lines. In the studies examining changes in cell cycle and apoptosis regulators, isosilybin B and isosilybin A resulted in a decrease in the levels of both cyclins (D1, D3, E and A) and cyclin-dependent kinases (Cdk2, Cdk4 and cell division cycle 25A), but caused an increase in p21, p27 and p53 levels, except in 22Rv1 cells where isosilybin B caused a decrease in p21 protein level. Isosilybin B- and isosilybin A-induced apoptosis was accompanied with an increase in the cleavage of poly (ADP-ribose) polymerase, caspase-9 and caspase-3 and a decrease in survivin levels. Compared with LNCaP and 22Rv1 cells, the antiproliferative and cytotoxic potentials of isosilybin B and isosilybin A were of much lesser magnitude in non-neoplastic human prostate epithelial PWR-1E cells suggesting the transformation-selective effect of these compounds. Together, this study for the first time identified that isosilybin B and isosilybin A, two diastereoisomers isolated from silymarin, have anti-PCA activity that is mediated via cell cycle arrest and apoptosis induction.