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Summary The iirteruciion ojnitrous oxide and vitamin B, and its implications are not the exclusive terrilory Key words Annesthetic..\, gases; nitrous oxide.It is remarkable that B,, chemists, and particularly those who lirst discovered the interaction with nitrous oxide, have until now had only minimal contact with clinicians. The first publication of the discovery of the interaction' was followed by an interval of 10 years before clinicians became generally aware that a problem existed.As a first step towards establishing a dialogue between basic scientists and clinicians in the field, an interdisciplinary Bedford Square Seminar was held on 26 January 1988. Invited speakers and discussants included many of the lcading chemists, haematologists, neurologists and anaesthetists in this country who had worked in the field during the last 20 years.Thc seminar opened with a review by Professor B. Golding (Department of Organic Clzemistrjl, University oJ Newcastk.-zrpon-?we) of the basic biochemistry of B,, and its role 111 man as a cofactor for the enzymes, methionine synthase and inethylinalonyl CoA mutase. The reactivity of the cobalt atom at the centre of the corrinoid ring (which closely resembles the tetrapyrrole ring of haemoglobin) was considered in detail, with particular reference to the potential naturc of its reaction with nitrous oxide and subscqucnt change in valency. The possibility was also considcrcd of the formation of a cobalt-carbon bond with alkyl halide anaesthetics. Earlier ncgative studies with halothane did not exclude this possibility because of the lability (for example, photosensitivity) of the bond.Professor J.M. Pratt (Department of Chemistry. L'niniversitj o / ' Surrcy) provided the background of his discovery of the it/ vifro nonenzymic interaction of nitrous oxide and B,,. It started with expcriments of his own, undertaken 'out of sheer curiosity' in 1963, and completed by two project students; it was published under the authorship of Banks, Henderson and Pratt as a preliminary note in l967* and a full paper in 196S1. Both escaped the notice o f the medical profession for several years. However, a brief note of the interaction appcars in Professor Pratt's textbook of vitamin B, published in 1972.3 Professor Pratt concludcd with thc challenging hypothesis that B,, had an earlier role in evolution for thc mctabolism of methane before oxygen appeared in the earth's atmospherc, and was used for methyl transfer reactions which still occur in certain bacteria.In discussion, Dr J. Amess (Department of Haematology, St Bartholomeir. ' s Hospitao explained that during 1914-76 he observed intensive care unit paticnts who developed megaloblastic bone marrow change secondary to prolonged ventilation with nitrous oxide. This had been previously reported by Lassen4 during 1956 but its pathogenesis had remained unexplained. In association with t l r J. Burman, it was shown that the results of the deoxyuridine suppression tests. on the bone marrow from these patients, were idcntical to those found in vi...
Summary The iirteruciion ojnitrous oxide and vitamin B, and its implications are not the exclusive terrilory Key words Annesthetic..\, gases; nitrous oxide.It is remarkable that B,, chemists, and particularly those who lirst discovered the interaction with nitrous oxide, have until now had only minimal contact with clinicians. The first publication of the discovery of the interaction' was followed by an interval of 10 years before clinicians became generally aware that a problem existed.As a first step towards establishing a dialogue between basic scientists and clinicians in the field, an interdisciplinary Bedford Square Seminar was held on 26 January 1988. Invited speakers and discussants included many of the lcading chemists, haematologists, neurologists and anaesthetists in this country who had worked in the field during the last 20 years.Thc seminar opened with a review by Professor B. Golding (Department of Organic Clzemistrjl, University oJ Newcastk.-zrpon-?we) of the basic biochemistry of B,, and its role 111 man as a cofactor for the enzymes, methionine synthase and inethylinalonyl CoA mutase. The reactivity of the cobalt atom at the centre of the corrinoid ring (which closely resembles the tetrapyrrole ring of haemoglobin) was considered in detail, with particular reference to the potential naturc of its reaction with nitrous oxide and subscqucnt change in valency. The possibility was also considcrcd of the formation of a cobalt-carbon bond with alkyl halide anaesthetics. Earlier ncgative studies with halothane did not exclude this possibility because of the lability (for example, photosensitivity) of the bond.Professor J.M. Pratt (Department of Chemistry. L'niniversitj o / ' Surrcy) provided the background of his discovery of the it/ vifro nonenzymic interaction of nitrous oxide and B,,. It started with expcriments of his own, undertaken 'out of sheer curiosity' in 1963, and completed by two project students; it was published under the authorship of Banks, Henderson and Pratt as a preliminary note in l967* and a full paper in 196S1. Both escaped the notice o f the medical profession for several years. However, a brief note of the interaction appcars in Professor Pratt's textbook of vitamin B, published in 1972.3 Professor Pratt concludcd with thc challenging hypothesis that B,, had an earlier role in evolution for thc mctabolism of methane before oxygen appeared in the earth's atmospherc, and was used for methyl transfer reactions which still occur in certain bacteria.In discussion, Dr J. Amess (Department of Haematology, St Bartholomeir. ' s Hospitao explained that during 1914-76 he observed intensive care unit paticnts who developed megaloblastic bone marrow change secondary to prolonged ventilation with nitrous oxide. This had been previously reported by Lassen4 during 1956 but its pathogenesis had remained unexplained. In association with t l r J. Burman, it was shown that the results of the deoxyuridine suppression tests. on the bone marrow from these patients, were idcntical to those found in vi...
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