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During clinical trials of a human antihaemophilic globulin concentrate (HAHG) prepared from very fresh plasma by the method of Kekwick and Wolf (1957), it was observed (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) that the transfusion of this material into haemophiliacs was sometimes followed by reactions similar to those observed by Fox, Goldsmith, Kidd and Lewis (1961) after the intravenous injection of purified bradykinin. A chemically similar fraction (ETF), prepared from aged plasma, has been used for many years for the treatment of hypofibrino‐genaemia without any reported reactions. The reactions described by Maycock et al. (1963) were sufficiently frequent and severe to warrant an investigation of the kininogenic properties of HAHG and, for comparative purposes, of ETF. For reasons not understood, but clearly associated with the adoption of a modification of the original technique (Kekwick and Walton, 1965), reactions occurring during the transfusion of recently prepared batches of HAHG into haemophiliacs are now no greater in number and severity than those occurring during the transfusion of fresh plasma. Human plasma contains prokininogenases, the precursors of enzymes which hydrolyse protein substrates (kininogens, kallidinogens) to produce kinins, polypeptides which cause vasodilation and plain muscle constriction (Lewis, 1960). Activation of two of these proenzymes, kallikrein and plasminogen (profibrinolysin), could lead to the production of kinin in HAHG either during preparation, or during transfusion, and might cause the observed reactions.

MMCMJORk cholinesterase available. However, it should be possible to increase the pseudo-cholinesterase of the plasma in the dog and thus to lower the concentration of free succinylcholine or suxethonium so rapidly that even the low concentration of the drug required for inhibition of the true cholinesterase in that animal will be effectively attacked. We therefore injected a highly concentrated solution of pseudo-cholinesterase intravenously into four dogs in the course of operations for mastectomy or conditions requiring orthopaedic treatment, and compared the effect of equal amounts of suxethonium given before and after the pseudo-cholinesterase level of the plasma had been increased.As will be seen in Table III, after the pseudo-cholinesterase had been effectively raised succinylcholine was as short-acting in dog as it is known to be in man. To exclude the effects of premedication and the possibility that apnoea was due to artificial hyperventilation, one experiment was performed in which only thiopentone was used for induction and no artificial respiration was given during apnoea beyond one inflation per minute. Table IV shows that the raising of the pseudo-cholinesterase level was effective under these conditions. Blood-pressure readings were obtained throughout and allowed an exclusion of asphyxia. Both brevidil E and scoline were used and noted as such in terms of active cation. Discussion Our findings support the suggestion that the effect of succinylcholine and suxethonium is the outcome of an interplay between these compounds and the two cholinesterases. The fact that the dog is much more sensitive than man would then be explained by the finding of a six to eight times lower true cholinesterase concentration in the red cells. Similarly, the fact that the sensitivity of the dog can be lowered to levels seen in man by raising the pseudocholinesterase level of the plasma can be understood on the bases of these considerations. We have assumed that the two esterases in man and dog are the same enzymes, and that the differences in activity of blood and plasma are due to different enzyme concentrations. It is, of course, possible that there are species variations and that the affinities rather than the concentrations are different. However, the interplay between compounds and enzymes would have the same outcome whether the enzymes differ in concentration or in affinity. Apart from theories, our findings have two practical consequences: the absence of side-reactions in the dog when given human cholinesterase preparations justifies its trial in man in cases of succinylcholine sensitivity. The use of the enzyme will be of advantage in veterinary medicine, as it will convert succinylcholine and suxethonium from comparatively long-time relaxants into compounds acting for a few minutes only, thus bringing into the surgery of the dog the advantages found in the use of succinylcholine and suxethonium in man. Summary Dogs are more sensitive to suxethonium and succinylcholine than man. When injected with doses about o...

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CONGENITAL OBSTRUCTION OF INTESTINE hBnrr 767 MmWICAI Jouiu-x. strongly advocated (Rickham, 1952). Most paediatricians will agree that certain congenital abnormalities such as oesophageal atresias and genito-urinary malformations require the specialized surgical techniques available only at regional contres. Abdominal malformations of the alimentary tract, particularly obstructions of the small intestine, are probably the most urgent of the remedial congenital malformations. Early diagnosis and immediate pre-operative treatment are required. Available statistics suggest that after 96 hours the operative mortality even in the most capable hands is practically 100%. The delay and disturbance necessarily involved in transferring such cases from outlying hospitals to regional centres is unjustified. Rickham (1952) points out that a surgeon working in one hospital group is unlikely to see more than one or two such cases a year, and therefore unlikely to gather enough experience to deal correctly with the complicated surgical problems. On the other hand, the general surgeon, owing to the development of other surgical specialties, is a specialist in abdominal surgery, and neonata,l abdominal surgery should rightly remain within his province.