Ease and comfort of pre-oxygenation with high-flow nasal oxygen cannulae vs. facemask: a randomised controlled trial.

The Difficult Airway Society recommends that all patients should be pre-oxygenated before the induction of general anaesthesia, but this may not always be easy or comfortable and anaesthesia may often be induced without full pre-oxygenation. We tested the hypothesis that high-flow nasal oxygen cannulae would be easier and more comfortable than facemasks for pre-oxygenation. We randomly allocated 199 patients undergoing elective surgery aged ≥ 10 years to pre-oxygenation using either high-flow nasal oxygen or facemask. Ease and comfort were assessed by anaesthetists and patients on 10-cm visual analogue scale and six-point smiley face scale, respectively. Secondary endpoints included end-tidal oxygen fraction after securing a definitive airway and time to secure an airway. A mean difference (95%CI) between groups in ratings of -0.76 (-1.25 to -0.27) cm for ease of use (p = 0.003) and -0.45 (-0.75 to -0.13) points for comfort (p = 0.006), both favoured high-flow nasal oxygen. A mean difference (95%CI) between groups in end-tidal oxygen fraction of 3.89% (2.41-5.37%) after securing a definitive airway also favoured high-flow nasal oxygen (p < 0.001). There was no significant difference between groups in the number of patients with hypoxaemia (Sp O2 < 90%) or severe hypoxaemia (Sp O2 < 85%) lasting ≥ 1 min or ≥ 2 min; in the proportion of patients with an end-tidal oxygen fraction < 87% in the first 5 min after tracheal intubation (52.2% vs. 58.9% in facemask and high-flow nasal oxygen groups, respectively; p = 0.31); or in time taken to secure an airway (11.6 vs. 12.2 min in facemask and high-flow nasal oxygen groups, respectively; p = 0.65). In conclusion, we found pre-oxygenation with high-flow nasal oxygen to be easier for anaesthetists and more comfortable for patients than pre-oxygenation with a facemask, with no clinically relevant differences in end-tidal oxygen fraction after securing a definitive airway or time to secure an airway. The differences in ease and comfort were modest.

Chronic antigen ingestion protects ovalbumin sensitized mice from severe manifestation of Leishmania major infection.

In the present work, the development of experimental leishmaniasis was examined in sensitized BALB/c mice that were chronically fed with antigen. After an oral challenge with egg white solution, the ovalbumin (Ova)-sensitized mice showed an increase in serum anti-Ova IgE and IgG1 antibodies. Lesions induced by Leishmania major infection were reduced by the ingestion of Ova in sensitized mice, as assessed by reduced footpad growth, lower parasite loads and improved pathological outcome compared to sham sensitized mice. Moreover, such findings were connected to a shift to a Th1 response involving higher IFN-gamma production and serum levels of IgG2a anti-Leishmania antigens. The data appear to corroborate the suggestion that chronic ingestion of an antigen by sensitized mice modulates the immunological system through a shift in cytokine release, exhibiting a healing response and resistance to L. major infection.

What are we injecting with our drugs?

In preparation for a case, an anaesthetist opened a 20 ml glass vial of propofol and aspirated the propofol into a syringe via a blunt drawing-up needle. Increased resistance was felt with aspiration. On inspection, a shard of glass was found at the tip of the drawing-up needle. The shard was presumed to be from the propofol ampoule, and to have fallen into the solution upon snapping open its glass tip. This illustrative case raises the issue of contamination of drugs by particles introduced during the drawing-up process. It also highlights the possibility that during the drawing-up process, intravenous drugs may become contaminated not just with particles, but with microorganisms on the surface of the particles. In this article, we discuss relevant recent research of the implications of this type of drug contamination. We draw attention to the need for meticulous care in drawing up and administering intravenous drugs during anaesthesia, particularly propofol.

Reliability of patellar height indices in children with cerebral palsy and spina bifida.

BACKGROUND: The Koshino (KI) and Caton-Deschamps (CDI) indices are used to measure patellar height in children, with the CDI showing excellent reliability in typically developing (TD) children. Reliability of such measures in children with cerebral palsy (CP) and spina bifida (SB) is unknown. METHODS: Lateral knee radiographs were reviewed retrospectively for children with TD (n = 49), CP (n = 48) and SB (n = 42). Five raters took measurements from radiographs twice, at least two weeks apart. Measurements included the CDI, Insall-Salvati Index (ISI) and KI. Systematic variability (bias) and random variability were examined using repeated measures ANOVA, 95% limits of agreement (LOA) and coefficients of variation (CV). RESULTS: Mean values of all three indices differed among raters (p < 0.0001). A significant difference was seen between the first and second measurements for CDI and KI indicating a learning effect. LOA ranges were large for the CDI (intra-rater: 0.37-0.95, inter-rater: 0.60-1.04) and ISI (intra-rater: 0.25-0.49, inter-rater: 0.51-0.57) for all patient groups. The KI showed a clinically acceptable range for TD participants (intra-rater: 0.14-0.16, inter-rater: 0.11-0.14) with larger ranges for CP (intra-rater: 0.26-0.33, inter-rater 0.0.2-0.35) and SB patients (intra-rater: 0.23-0.27, inter-rater: 0.19-0.25). CVs were lowest (best) for KI (3.8% to 7.4%) and highest (worst) for CDI (14.7% to 23.1%) for all three groups. Results were similar for patients with both open and closed physes. CONCLUSIONS: The KI is the most reliable patellar height measure for paediatric patients with TD, CP and SB, with either open or closed physes. The KI is more complex and experience may be important for valid, reliable measurement.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice.

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20% loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100%) and increased mucus production (483%). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

Extemporaneous compounding in veterinary practice: a New Zealand perspective.

AIMS: The aims of this study were to explore the extent of extemporaneous compounding in veterinary centres throughout New Zealand and to determine whether pharmacists could collaborate with veterinarians to improve this service in New Zealand. METHODS: Questionnaires were sent to 200 randomly selected veterinarians in New Zealand. Semi-structured interviews were also conducted with selected participants from four animal facilities (zoos, research facilities and animal shelters) and two compounding pharmacies. RESULTS: Of the 200 veterinarian questionnaire recipients, 99 responded. Ten replies were withdrawn from the study giving a response rate of 44.5%. Of these 89, 33 (37%) compounded in their practice. Of the 33 compounding professionals, 3 (9%) compounded daily for animals under their care; 11 (34%) weekly, 18 (54%) monthly and 1 (3%) compounded yearly. Compounding was done by 29/33 (88%) veterinarians, 16/33 (48%) veterinary nurses or 6/33 (18%) others. It was carried out due to the unavailability of commercial products, or the need for dose adjustment to ease administration or improve compliance. The animals most commonly requiring veterinary compounding were dogs (21/33; 64%), cats (19/33; 58%) or cattle (15/33; 46%). Products which were commonly compounded included cyclosporin eye drops, methimazole gels and potassium bromide solutions. Issues commonly faced when compounding included unavailability of dosage forms (18/33; 55%) or appropriate ingredients (14/33; 42%), stability (12/33; 36%), time constraints (10/33; 30%) or unavailability of equipment (9/33; 27%). Reasons given for not compounding included medicines being commercially available (38/56; 68%), pharmacy compounding for those particular practices (24/56; 43%), lack of training (21/56; 38%), ingredients (16/56; 29%) or equipment (15/56; 11%). All participants who worked with a pharmacist (11/33; 33%) described this relationship as beneficial and indicated they would continue to do so in the future. CONCLUSIONS: Veterinary extemporaneous compounding exists in New Zealand. As pharmacists have extensive knowledge in formulating medications and compounding they could be of greater value to veterinarians and their patients. Educating both professions on the opportunities available to them from this collaboration could be an important step forward. CLINICAL RELEVANCE: This study provides new information regarding extemporaneous compounding for veterinary patients in New Zealand.

Structural and function modification of DNA by mitomycin C. Mechanism of the DNA sequence specificity of mitomycins.

Mitomycin C (MC) is a clinically used antitumor agent, which upon reductive activation activates and cross-links DNA. The covalent products of alkylation and cross-linking by the unnatural synthetic enantiomer of MC (ent-MC) were isolated as drug-deoxyguanosine monoadducts and drug-deoxyguanosine bisadducts and were fully characterized structurally. Specificity of alkylation and cross-linking of guanines in the CpG.CpG sequence was observed by ent-MC, similarly to that observed previously by MC. These findings define the mechanism of recognition of the CpG.CpG sequence of DNA by the mitomycins in the minor groove. In contrast, the natural MC metabolite, 2,7-diaminomitosene (2,7-DAM) which lacks the aziridine alkylator function is shown to recognize and alkylate guanines only the GpG.CpC sequence in the major groove, by a different mechanism. Thoughts on the molecular evolution of the basic mitomycin structure as a very efficient lethal DNA cross-linker are discussed.

Mitosene-DNA adducts. Characterization of two major DNA monoadducts formed by 1,10-bis(acetoxy)-7-methoxymitosene upon reductive activation.

Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the formation of various DNA adducts. Reduction is a necessary event for adduct formation to occur. This reductive activation was performed under hypoxic conditions in various ways: (1) chemically, using a 2-fold excess of sodium dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3) electrochemically on a mercury pool working electrode, and (4) catalytically, using a H2/PtO2 system. Five different mitosene-DNA adducts were detected. These adducts were also present when poly(dG-dC) was used instead of DNA, but were absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1, 10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable adduct formation, demonstrating the importance of good leaving groups for efficient adduct formation by these mitosenes. Finally, two of the adducts were isolated and their structures elucidated, using mass spectrometry, 1H NMR and circular dichroism (CD). The structures were assigned as the diastereoisomers N2-(1"-n-hydroxymitosen-10"-yl), 2'-deoxyguanosine (n = alpha or beta). These type of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a guanosylic group, are different from the well-known mitomycin C 2'-deoxyguanosine monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor causing this switch. Evidence is presented that the 7-substituent of mitosenes also influences their DNA alkylation site. Adducts 4 and 5 represent the first isolated and structurally characterized covalent adducts of DNA and a synthetic mitosene.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20 percent loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129 percent for IgG1 and 164 percent for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45 percent Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100 percent) and increased mucus production (483 percent). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.