Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies.

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.

Project for Universal Management of Airways - part 1: concept and methods.

Multiple professional groups and societies worldwide have produced airway management guidelines. These are typically targeted at the process of tracheal intubation by a particular provider group in a restricted category of patients and reflect practice preferences in a particular geographical region. The existence of multiple distinct guidelines for some (but not other) closely related circumstances, increases complexity and may obscure the underlying principles that are common to all of them. This has the potential to increase cognitive load; promote the grouping of ideas in silos; impair teamwork; and ultimately compromise patient care. Development of a single set of airway management guidelines that can be applied across and beyond these domains may improve implementation; promote standardisation; and facilitate collaboration between airway practitioners from diverse backgrounds. A global multidisciplinary group of both airway operators and assistants was assembled. Over a 3-year period, a review of the existing airway guidelines and multiple reviews of the primary literature were combined with a structured process for determining expert consensus. Any discrepancies between these were analysed and reconciled. Where evidence in the literature was lacking, recommendations were made by expert consensus. Using the above process, a set of evidence-based airway management guidelines was developed in consultation with airway practitioners from a broad spectrum of disciplines and geographical locations. While consistent with the recommendations of the existing English language guidelines, these universal guidelines also incorporate the most recent concepts in airway management as well as statements on areas not widely addressed by the existing guidelines. The recommendations will be published in four parts that respectively address: airway evaluation; airway strategy; airway rescue and communication of airway outcomes. Together, these universal guidelines will provide a single, comprehensive approach to airway management that can be consistently applied by airway practitioners globally, independent of their clinical background or the circumstances in which airway management occurs.

Alkaliphilic Bacillus species show potential application in concrete crack repair by virtue of rapid spore production and germination then extracellular calcite formation.

AIMS: Characterization of alkaliphilic Bacillus species for spore production and germination and calcite formation as a prelude to investigate their potential in microcrack remediation in concrete. METHODS AND RESULTS: Conditions, extent and timing of endospore production was determined by dark-field light microscopy; germination induction and kinetics were assessed by combining reduction in optical density with formation of refractile bodies by phase-contrast microscopy. Bacillus pseudofirmus was selected from several species as the most suitable isolate. Levels and timing of calcium carbonate precipitated in vitro by B. pseudofirmus were evaluated by atomic absorption spectroscopy and structural identity confirmed as calcite and aragonite by Raman spectroscopy and FTIR. The isolate produced copious spores that germinated rapidly in the presence of germinants l-alanine, inosine and NaCl. Bacterial cells produced CaCO3 crystals in microcracks and the resulting occlusion markedly restricted water ingress. CONCLUSIONS: By virtue of rapid spore production and germination, calcium carbonate formation in vitro and in situ, leading to sealing of microcracks, B. pseudofirmus shows clear potential for remediation of concrete on a commercial scale. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial sealing of microcracks should become a practicable and sustainable means of increasing concrete durability.

Forces generated by Macintosh and GlideScope® laryngoscopes in four airway-training manikins.

We measured forces generated by Macintosh and GlideScope(®) laryngoscope blades during airway intubation by 16 participants in four manikins: Laerdal(®) SimMan; TruCorp AirSim™ Advance; Laerdal(®) Airway Management Trainer; and Ambu(®) Airway Man. Both laryngoscopes generated the least force in the Laerdal Airway Management Trainer and the most in the Ambu Airway Man. The respective median (IQR [range]) forces generated by the Macintosh blade were 2 (1-4 [1-7]) N vs 9 (7-13 [5-16]) N, p = 0.00004, with peak forces 9 (5-11 [3-16]) N vs 18 (12-22 [3-31]) N, p = 0.0004. The respective average and peak forces generated by the GlideScope blade were 1 (1-2 [0-3]) N vs 4 (3-5 [2-6]) N, p = 0.00001, and 4 (2-7 [0-12]) N vs 7 (4-9 [3-18]) N, p = 0.054.

Measurement of forces applied during Macintosh direct laryngoscopy compared with GlideScope® videolaryngoscopy.

Laryngoscopy can induce stress responses that may be harmful in susceptible patients. We directly measured the force applied to the base of the tongue as a surrogate for the stress response. Force measurements were obtained using three FlexiForce Sensors(®) (Tekscan Inc, Boston, MA, USA) attached along the concave surface of each laryngoscope blade. Twenty-four 24 adult patients of ASA physical status 1-2 were studied. After induction of anaesthesia and neuromuscular blockade, laryngoscopy and tracheal intubation was performed using either a Macintosh or a GlideScope(®) (Verathon, Bothell, WA, USA) laryngoscope. Complete data were available for 23 patients. Compared with the Macintosh, we observed lower median (IQR [range]) peak force (9 (5-13 [3-25]) N vs 20 (14-28 [4-41]) N; p = 0.0001), average force (5 (3-7 [2-19]) N vs 11 (6-16 [1-24]) N; p = 0.0003) and impulse force (98 (42-151 [26-444]) Ns vs 150 (93-207 [17-509]) Ns; p = 0.017) with the GlideScope. Our study shows that the peak lifting force on the base of the tongue during laryngoscopy is less with the GlideScope videolaryngoscope compared with the Macintosh laryngoscope.

Depressive symptoms in early pregnancy disrupt attentional processing of infant emotion.

BACKGROUND: Growing evidence suggests that perinatal depression is associated with disrupted mother-infant interactions and poor infant outcomes. Antenatal depression may play a key role in this cycle by disrupting the development of a maternal response to infant stimuli. The current study therefore investigated the impact of depressive symptoms on the basic cognitive processing of infant stimuli at the beginning of pregnancy. METHOD: A total of 101 women were recruited by community midwives and tested at an average gestation of 11 weeks. An established computerized paradigm measured women's ability to disengage attention from infant and adult faces displaying negative positive and neutral emotions. Depressive symptoms were measured using a computerized interview (the Clinical Interview Schedule). RESULTS: The effect of infant emotion on women's ability to disengage from infant faces was found to be influenced by depressive symptoms. Non-depressed pregnant women took longer to disengage attention from distressed compared with non-distressed infant faces. This bias was not, however, seen in women experiencing depressive symptoms. There was a difference of -53 (s.d.=0.7) ms (95% confidence interval -90 to -14, p=0.007) between those with and without depressive symptoms in this measure of attentional bias towards distressed infant faces. CONCLUSIONS: Our results suggest that depressive symptoms are already associated with differential attentional processing of infant emotion at the very beginning of childbearing. The findings have potential implications for our understanding of the impact of depressive symptoms during pregnancy on the developing mother-infant relationship.

Thalamic reticular system and central grey: self-stimulation.

Rats will press a bar that brings about stimulation of midline thalamic reticular, periventricular, and central grey brain regions. In the latter two regions stimulation can also cause pain or fear.

Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump.

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.

An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas.

PURPOSE AND METHODS: Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin. RESULTS: Between 1987 and 1989, 340 eligible patients were randomized. Significantly more myelosuppression, a higher response rate (17% v 32%; P < .002) and longer time to progression (4 v 6 months; P < .02) were observed for patients who received ifosfamide. An overall survival advantage for the two-drug regimen (12 v 13 months; P = .04) was not significant by multivariate analysis. CONCLUSION: In all three randomized trials of doxorubicin with and without ifosfamide (Eastern Cooperative Oncology Group [ECOG], European Organization for Research and Treatment of Cancer [EORTC], and this study), the response rate was higher for the ifosfamide-containing arm, significantly so in this and the ECOG studies. An improved response rate may be particularly important for the preoperative management of high-grade, borderline resectable lesions or pulmonary metastases, particularly in younger patients. In older patients, or for low-to intermediate-grade lesions, doxorubicin and DTIC followed by ifosfamide on progression is preferred.

Characterization of SNP1, a cell wall-degrading trypsin, produced during infection by Stagonospora nodorum.

Stagonospora (= Septoria) nodorum when grown in liquid culture with wheat cell walls as the sole carbon and nitrogen source secretes numerous extracellular depolymerases, including a rapidly produced, alkaline, trypsin-like protease (SNP1). The enzyme was purified 417-fold by cation exchange chromatography and has a molecular mass of 25 kDa on sodium dodecyl sulfate gels, pI 8.7, and pH optimum of 8.5. It cleaved peptide bonds on the carboxyl side of lysine or arginine, was strongly inhibited by the trypsin inhibitors aprotinin and leupeptin and weakly by phenylmethylsulfonyl fluoride, and its activity was stimulated by calcium. SNP1 has the characteristic, conserved, fungal, trypsin N terminus. Polymerase chain reaction (PCR) primers based on this sequence and the conserved trypsin active site were used to amplify a DNA fragment that facilitated isolation of the corresponding genomic clone from a lambda library of S. nodorum. The full-length sequence confirmed its identity as a trypsin-like protease containing the N-terminal sequence of the previously purified enzyme. Infected leaf tissue contained a protease, not present in controls, that coeluted with the fungal trypsin from cation exchange, and had properties (pI and inhibitor characteristics) similar to those of the fungal trypsin. SNP1 expression in planta was detected by Northern (RNA) blotting, reverse transcription PCR, and green fluorescent protein confocal microscopy. SNP1 released hydroxyproline from wheat cell walls. The release of hydroxyproline, together with its early expression in planta, suggests that SNP1 participates in the degradation of host cell walls during infection.

Cloning and characterisation of a gene encoding a cuticle-degrading protease from the insect pathogenic fungus Metarhizium anisopliae.

Metarhizium anisophilae (Ma) secretes a range of proteases when grown in vitro on insect cuticle. A trypsin-like serine protease, PR2, was purified from culture filtrates by anion exchange chromatography and the N-terminal sequence determined. Using oligodeoxyribonucleotide probes based on this sequence and that of the highly conserved trypsin active site, a gene was isolated from a lambda EMBL3 genomic library of Ma isolate ME1. Sequencing of the gene and RT-PCR revealed that the gene contains two introns which are 94 and 40 bp long. The deduced protein consists of 254 amino acids, has a putative signal sequence to allow transport into the endoplasmic reticulum and probably undergoes a second proteolytic processing step at its N terminus to yield the mature enzyme. The putative mature enzyme has extensive homology with other serine proteases of the trypsin subclass and, in particular, with the trypsin characterised from Fusarium oxysporum.

Activity-dependent changes in eye influence during monocular blockade: increases in the effects of visual stimulation on 2-DG uptake in the adult rat geniculostriate system.

We examined the effects of loss of monocular retinal activity on 2-deoxyglucose (2-DG) uptake in the adult rat geniculostriate system. Of particular interest was whether the influence of the normally functioning eye changed during long-term contralateral retinal silence. Group 1 rats were subjected to short-term (24 hours) and group 2 rats to long-term (21-90 days) monocular tetrodotoxin (TTX) blockade, and metabolic activity was assessed during exposure to square-wave gratings. Group 1 rats exhibited patterns of cortical glucose utilization commensurate with complete monocular loss of retinal activity: minimal 2-DG uptake in contralateral monocular area 17 and dorsal lateral geniculate nucleus (LGN), and a bilateral depression in the binocular regions; 2-DG uptake was highest in the monocular regions fed by the stimulated normal eye (in both area 17 and the LGN) and these regions appeared unaffected by the monocular blockade. After repeated injections of TTX (group 2), metabolic activity in binocular area 17 and binocular LGN increased bilaterally relative to the metabolically active monocular regions contralateral to the normal eye. Group 3 rats were monocularly TTX-injected for 30 or 60 days, and, 24 hours before 2-DG, all retinal activity was eliminated by means of binocular TTX injections or binocular enucleation. Glucose utilization in the binocular regions of both area 17 and the LGN in these rats was depressed to levels seen in monocular area 17 after complete and recent loss of activity from the contralateral eye, indicating that the metabolic increase which occurred in the binocular regions during long-term monocular retinal blockade was dependent upon the neuronal processing of retinal information from the non-TTX eye. We conclude that, in the adult rat, an activity-dependent, physiologically based shift in ocular influence occurred in the binocular geniculostriate system during long-term monocular retinal inactivation.

Metabolic activity in striate and extrastriate cortex in the hooded rat: contralateral and ipsilateral eye input.

The extent of changes in glucose metabolism resulting from ipsilateral and contralateral eye activity in the posterior cortex of the hooded rat was demonstrated by means of the C-14 2-deoxyglucose autoradiographic technique. By stimulating one eye with square wave gratings and eliminating efferent activation from the other by means of enucleation or intraocular TTX injection, differences between ipsilaterally and contralaterally based visual activity in the two hemispheres were maximized. Carbon-14 levels in layer IV of autoradiographs of coronal sections were measured and combined across sections to form right and left matrices of posterior cortex metabolic activity. A difference matrix, formed by subtracting the metabolic activity matrix of cortex contralateral to the stimulated eye from the ipsilateral "depressed" matrix, emphasized those parts of the visual cortex that received monocular visual input. The demarcation of striate cortex by means of cholinesterase stain and the examination of autoradiographs from sections cut tangential to the cortical surface aided in the interpretation of the difference matrices. In striate cortex, differences were maximal in the medial monocular portion, and the lateral or binocular portion was shown to be divided metabolically into a far lateral contralaterally dominant strip along the cortical representation of the vertical meridian, and a more medial region of patches of more or less contralaterally dominant binocular input. Lateral peristriate differences were less than those of striate cortex, and regions of greater and lesser monocular input could be distinguished. We did not detect differences between the two hemispheres in either anterior or medial peristriate areas, thus indicating either completely binocular input (which seems unlikely given the retinotopic organization of these regions), or a greater dependence than in the lateral peristriate on inputs that were not affected by the visual manipulations.

Superiority of conventional culture technique over rapid detection of group A Streptococcus by optical immunoassay.

An optical immunoassay (OIA) has been reported to be more sensitive than conventional culture for the detection of Group A Streptococcus, eliminating the need for culture. We attempted to confirm the sensitivity and specificity through a laboratory quantitation study and a clinical trial. OIA did not detect Group A Streptococcus below 10(5) colony forming units (CFU). Culture detected Streptococcus to 10(2) CFU from the inoculated swab. In the clinical study, throat swabs were obtained from 77 patients in an outpatient clinic. Compared with culture, the sensitivity of OIA was 78% and the specificity was 90%. These results demonstrate that OIA was less sensitive than culture in seeded experiments and missed 22% of positives in clinical practice. Our study, contrary to previous reports, suggests that OIA is not sensitive enough to be used as the sole assay for Group A Streptococcus pharyngitis.

Movement and novelty of a square wave display affect 2-deoxyglucose uptake in the rat visual system.

The [14C]2-deoxy-glucose (2-DG) autoradiographic technique revealed that movement and novelty of a visual display affected rat visual system metabolic activity. Hooded rats were monocularly tested in a surround consisting of patterns of black and white, horizontal and vertical, square wave gratings of different spatial frequencies. For one group this display remained immobile ('stationary' group), and for the other group the display intermittently rotated at 1.5 rpm ('moving' group). Each of these main groups was subdivided such that half had six sessions of prior exposure to the test display ('experienced' group) and half had no prior exposure ('novel' group). The movement groups showed relatively greater 2-DG uptake than the stationary groups in the superior colliculus and in the caudal lateral posterior nucleus, while the novel groups showed greater uptake than the experienced groups in visual cortex.