[The unexpectedly difficult airway -- a plea for the oxford-non-kinking-tube]. / Der unerwartet schwierige Atemweg -- Ein Plädoyer für den Oxford-Non-Kinking-Tubus.

The skill to safely manage the unexpectedly difficult airway is expected from every anaesthetist. The strategies to safely overcome this severe problem have to be adapted to the given equipment and the individual aptitude and skills of the respective colleague. The algorithms for management of the difficult airway should be as simple as possible, and one cannot assume that devices for fibre-optic intubation are available at every site. Indispensable, however, is the availability of face masks, naso- and oropharyngeal airways and laryngeal mask airways in different sizes at each induction site. This paper is especially devoted to recalling the Oxford non-kinking tube and its specific way of handling, as a lot of cases of unexpectedly difficult airway can be safely managed with this tool. Alternatives to safeguarding the difficult airway are the intubation laryngeal mask airway or the esophago-tracheal combitube. For managing the worst case, the "cannot ventilate - cannot intubate" disaster, instruments for percutaneous punction of the trachea and devices for oxygen insufflation must be readily available in every theatre.

Minimal-flow anaesthesia with controlled ventilation: comparison between laryngeal mask airway and endotracheal tube.

BACKGROUND AND OBJECTIVE: Minimal- and low-flow anaesthesia (fresh gas flow below 1 L min(-1)) provide many advantages, including reduced cost, conservation of body heat and airway humidity. An airtight seal is essential between the airway device and the airway of the patient. Therefore, we investigated whether the airtight seal created by a laryngeal mask airway allows controlled ventilation of the lungs when the fresh gas flow is reduced to 0.5 L min(-1) and compared this with an endotracheal tube. METHODS: In a prospective clinical study, 207 patients were managed using a laryngeal mask or an endotracheal tube. After intravenous induction of anaesthesia and 15 min of high fresh gas flow, the flow was reduced to 0.5 L min(-1). The breathing system was monitored for airway leaks, and the patients were assessed for complications after airway removal and postoperative discomfort. RESULTS: Both the laryngeal mask and endotracheal tube allowed fresh gas flow reduction to 0.5 L min(-1) in 84.7% and 98.3% of cases respectively (small leaks: 12% laryngeal mask, 1.7% endotracheal tube). Three patients with the laryngeal mask (3.3%) had airway leaks that were too large to permit any reduction in the fresh gas flow. CONCLUSIONS: The use of the laryngeal mask airway was more likely to be associated with a gas leak than use of an endotracheal tube; however, if modern anaesthesia machines and monitors are used, in 96.7% of the patients managed with a laryngeal mask a reduction in the fresh gas flow to 0.5 L min(-1) was possible. The incidence of coughing and postoperative complaints (sore throat, swallowing problems) was higher after use of an endotracheal tube.

¿Será el xenón el anestésico inhalatorio del futuro? / Will be xenon the inhalatory anesthesic of the future?

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Canadian biotechnology start-ups, 1991-1997: the role of incumbents' patents and strategic alliances in controlling competition.

Fligstein (1996) contends that organizations act to exploit the institutional context in which they are embedded so as to stabilize the competition they face. Drawing on Fligstein's theoretical analysis, we conceptualize incumbent biotechnology firms' patent-ing and alliance-building activities as attempts to stabilize and control potential competition and analyze how these activities shape rates of founding in the Canadian biotechnology industry. We find that increases in the level and concentration of incumbents' patenting discourage founding, particularly in human application sectors of the industry where development and approval processes are more costly and time consuming. Incumbents' horizontal alliances depress start-ups; vertical alliances stimulate start-ups. Our findings highlight how technology appropriation and strategic alliances structure the competitive dynamics and evolution of high-technology, knowledge-intensive industries.

Multiple roles for TnpI recombinase in regulation of Tn5401 transposition in Bacillus thuringiensis.

Tn5401 is a class II transposable element derived from the gram-positive bacterium Bacillus thuringiensis. The 4,837-bp transposon encodes a Tn3-like transposase (TnpA) and an integrase-like recombinase (TnpI) and is notable for its unusually long 53-bp terminal inverted repeats (TIRs). The tnpA and tnpI genes are transcribed from a common promoter, designated P(R), that is subject to negative regulation by TnpI. The TIRs of Tn5401 each contain a 38-bp sequence that can be aligned with the 38- to 40-bp TIR sequences of Tn3-like transposons and an adjacent 12-bp sequence that binds TnpI. This unique juxtaposition of TnpA and TnpI binding sites suggests that TnpI may regulate the binding or catalytic activity of TnpA. The results of the present study indicate that TnpI, in addition to functioning as a site-specific recombinase and as a transcriptional repressor, is required for TnpA binding to the TIRs of Tn5401.

Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.

The effects of soy protein (40 g/d) containing moderate and higher concentrations of isoflavones on blood lipid profiles, mononuclear cell LDL receptor messenger RNA, and bone mineral density and content were investigated in 66 free-living, hypercholesterolemic, postmenopausal women during a 6-mo, parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, during which subjects followed a National Cholesterol Education Program Step I low-fat, low-cholesterol diet, all subjects were randomly assigned to 1 of 3 dietary groups: Step I diet with 40 g protein/d obtained from casein and nonfat dry milk (CNFDM), Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56), or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein (ISP90). Total and regional bone mineral content and density were assessed. Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group (P < 0.05). HDL cholesterol increased in both ISP56 and ISP90 groups (P < 0.05). Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM (P < 0.05). Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group (P < 0.05). Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women. However, only the higher isoflavone-containing product protected against spinal bone loss.

Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women.

The long-term clinical effects of soy protein containing various amounts of isoflavones on lipoproteins, mononuclear cell LDL receptor messenger RNA concentrations, and other selected cardiovascular risk factors are not well known. Sixty-six hypercholesterolemic, free-living, postmenopausal women were investigated during a 6-mo parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, all subjects were randomly assigned to 1 of 3 dietary groups (all with 40 g protein): a National Cholesterol Education Program (NCEP) Step 1 diet with protein from casein and nonfat dry milk (control), an NCEP Step 1 diet with protein from isolated soy protein containing moderate amounts of isoflavones (ISP56), or an NCEP Step 1 diet with protein from isolated soy protein containing high amounts of isoflavones (ISP90). Non-HDL cholesterol in both the ISP56 and ISP90 groups was reduced compared with the control group (P < 0.05), whereas total cholesterol was not changed. HDL cholesterol increased in both the ISP56 and ISP90 groups (P < 0.05), whereas the ratio of total to HDL cholesterol decreased significantly in both groups compared with the control (P < 0.05). Mononuclear cell LDL receptor messenger RNA concentrations increased in subjects consuming ISP56 or ISP90 compared with the control (P < 0.05). These results indicate that soy protein, with different amounts of isoflavones, may decrease the risk of cardiovascular disease via improved blood lipid profiles, and that the mechanism by which apolipoprotein B-containing lipoproteins were depressed may be via alterations in LDL receptor quantity or activity.

Engineering Bacillus thuringiensis bioinsecticides with an indigenous site-specific recombination system.

The cry genes of Bacillus thuringiensis encode a diverse group of crystal-forming proteins that exhibit insecticidal activity, particularly against the larvae of lepidopteran, coleopteran, and dipteran insects. The efficacy of B. thuringiensis-based biopesticides may be improved through the genetic manipulation of these genes. A gene transfer system has been developed for the introduction and maintenance of cloned insecticidal cry genes on small plasmids in B. thuringiensis. This vector system combines a B. thuringiensis plasmid replicon and an indigenous site-specific recombination system that allows for the selective removal of ancillary or foreign DNA from the recombinant bacterium after introduction of the Cry-encoding plasmid. The site-specific recombination system is useful for engineering strains with unique combinations of cry genes, resulting in new active ingredients with improved insecticidal properties.

Regulation of insecticidal crystal protein production in Bacillus thuringiensis.

The production of insecticidal crystal proteins (ICPs) in Bacillus thuringiensis normally coincides with sporulation, resulting in the appearance of parasporal crystalline inclusions within the mother cell. In most instances, the temporal and spatial regulation of ICP gene expression is determined at the transcriptional level by mother-cell-specific sigma factors that share homology with sigma E and sigma K from Bacillus subtilis. The cryIII ICP genes are a notable exception; these genes are transcribed from sigma A-like promoters during vegetative growth, are induced or derepressed at the onset of stationary phase, and are overexpressed in sporulation mutants of B. thuringiensis blocked in the phosphorylation of Spo0A, a key regulator of sporulation initiation. Transcription alone, however, cannot account for the impressive ability of this bacterium to accumulate insecticidal proteins. A variety of post-transcriptional and post-translational mechanisms also contribute to the efficient production of ICPs in B. thuringiensis, thus making this bacterium a cost-effective biological control agent.

Low-flow anaesthesia.

Although many anaesthesia machines are equipped with circle rebreathing systems, inhalational anaesthesia remains frequently performed using relatively high fresh-gas flows. The major advantages of rebreathing techniques can be achieved only if the fresh-gas flow is reduced to 1 l.min-1 or less. Although there are potential risks associated with low-flow anaesthesia, modern anaesthesia machines meet all the technical requirements for the safe use of low-flow techniques if they are used in conjunction with equipment for monitoring inhaled and exhaled gas concentrations; these monitors are already increasingly available and, in the near future, are likely to become an obligatory safety standard in many countries. For both economic and ecological reasons, the use of new inhalational anaesthetics, with low tissue solubility and low anaesthetic potency, can be justified only if the efficiency of administration is optimised by using low-flow anaesthetic techniques.

TnpI recombinase: identification of sites within Tn5401 required for TnpI binding and site-specific recombination.

The Bacillus thuringiensis class II transposon Tn5401 encodes a recombinase protein, TnpI, that mediates the resolution of cointegrate molecules generated as intermediates during Tn5401 transposition by the TnpA transposase. This recombination event requires a specific target site, or internal resolution site, at which TnpI binds and catalyzes the exchange of DNA strands. Gel mobility shift assays and DNase I footprinting analyses were used to localize the TnpI binding region to the sequence extending from nucleotides 637 to 747 of Tn5401. Deletions within this region blocked TnpI-mediated recombination in vivo. The 12-bp sequence ATGTCC RCTAAY, present in four copies within the TnpI binding region, is proposed to be the recognition sequence for TnpI binding. TnpI also binds to a single copy of this sequence located within the 53-bp terminal inverted repeats of Tn5401. The unique juxtaposition of recombinase and transposase binding sites at the terminal inverted repeats of Tn5401 suggests that TnpI regulates the binding and/or catalytic activity of TnpA transposase.

The genetic basis of the aggregation system in Bacillus thuringiensis subsp. israelensis is located on the large conjugative plasmid pXO16.

The aggregation phenotypes Agr+ and Agr- of Bacillus thuringiensis subsp. israelensis are correlated with a conjugation-like plasmid transfer and characterized by the formation of aggregates when the bacteria are socialized during exponential growth. We present evidence for the association of the Agr+ phenotype with the presence of the large (135-MDa) self-transmissible plasmid pXO16.

Overexpression of Bacillus thuringiensis HknA, a histidine protein kinase homology, bypasses early Spo mutations that result in CryIIIA overproduction.

The Bacillus thuringiensis CryIIIA insecticidal crystal protein (ICP) is a vegetatively expressed protein that is toxic to coleopteran insect larvae. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the asporogenous B. thuringiensis subsp. morrisoni strain EG1351, which harbors the native cryIIIA-encoding 88-MDa plasmid, showed a 2.5-fold overproduction of the CryIIIA protein compared with that of an isogenic wild-type strain. Further studies showed that neither CryIIIA protein synthesis nor CryIIIA protein processing was affected in strain EG1351 during vegetative growth. In an attempt to characterize the EG1351 mutation by complementation of function, the hknA gene was identified and cloned from a B. thuringiensis cosmid library. Primer extension analysis of hknA mRNA in wild-type B. thuringiensis demonstrated that the hknA gene is transcribed during vegetative growth from a sigma A-like promoter. Multiple copies of either the hknA gene or the Bacillus subtilis kinA (spoIIJ) gene were shown to bypass the sporulation defect in strain EG1351 as well as a spo0F mutation in B. thuringiensis EG1634. Additional studies showed that the hknA gene was not defective in strain EG1351. The results of this study suggest that hknA encodes a novel histidine protein kinase involved in B. thuringiensis sporulation. We also propose that the CryIIIA-overproducing phenotype of strain EG1351 is most likely due to a defect in the phosphorylation of Spo0A and confirm that CryIIIA production is not dependent on sporulation.

Tn5401 disruption of the spo0F gene, identified by direct chromosomal sequencing, results in CryIIIA overproduction in Bacillus thuringiensis.

The Bacillus thuringiensis spo0F gene was identified by chromosomal DNA sequencing of sporulation mutants derived from a B. thuringiensis transposon insertion library. A spo0F defect in B. thuringiensis, which was suppressed by multicopy hknA or kinA, resulted in the overproduction of the CryIIIA insecticidal crystal protein.