The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be eliminated by pressures of approximately 100 atm (refs 3, 4). However, the effects of anaesthetics are not always reversed in model systems, where there is evidence that the pattern of pressure reversal varies significantly. We now find that pressure fails to reverse the effects of anaesthetics on the freshwater shrimp (Gammarus pulex), although the sensitivity of these crustaceans to anaesthetics is comparable with that of higher animals. This is hard to reconcile with traditional bio-physical mechanisms and indicates that anaesthetics may act at a specific protein site rather than having a general effect on cell membranes. The pharmacology of pressure in mammals seems to be more similar to that of strychnine than of any other central stimulant. As glycine, whose action is blocked by strychnine, is absent as a neurotransmitter in the arthropod central nervous system, we believe that this substance may be involved in determining pressure-anaesthetic interactions in vertebrates.

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The anaesthetic potencies of binary mixtures of the gases argon (Ar), nitrous oxide (N2O) and sulphur hexafluoride (SF6) have been measured using mice. The mixtures SF6-N2O and N2O-Ar showed additive behaviour, whereas the constituents of the mixture SF6-Ar were non-additive, having a smaller total potency than expected. Further experiments on this mixture with Italian Great Newts and on the carbon tetrafluoride mixtures CF4-Ar and CF4-SF6 with mice suggested that the anomalous potencies may arise from specific pulmonary effects associated with the breathing of SF6 accompanied by a high pressure of some other gas.

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Background The evidence base behind new melanoma treatments is rapidly accumulating. This is not necessarily reflected in current guidance. A recent UK-based expert consensus statement, published in JPRAS, has called for updates to the widely accepted 2015 National Institute for Health and Care Excellence (NICE) guideline for melanoma (NG14). We aimed to compare the quality of NG14 to all other melanoma guidelines published since. Methods We conducted a systematic search of PubMed, Medline, and online clinical practice guideline databases to identify melanoma guidelines published between 29th July 2015 and 23rd August 2021 providing recommendations for adjuvant treatment, radiotherapy, surgical management, or follow-up care. Three authors independently assessed the quality of identified guidelines using the Appraisal of Guidelines for Research & Evaluation Instrument II (AGREE II) assessment tool, which measures six domains of guideline development. Inter-rater reliability was assessed by Kendall's coefficient of concordance (W). Results Twenty-nine guidelines were included and appraised with excellent concordance (Kendall's W for overall guideline score 0.88, p<0.001). Overall, melanoma guidelines scored highly in the domains of ‘Scope and purpose’ and ‘Clarity of presentation’, but poorly in the ‘Applicability’ domain. The NICE guideline on melanoma (NG14) achieved the best overall scores. Conclusion Melanoma treatment has advanced since NG14 was published, however, the NICE melanoma guideline is of higher quality than more recent alternatives. The planned update of NG14 in 2022 is in demand.