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ACHYLIA GASTRICA AND PERNICIOUS ANÆMIA.
873
good for national character to have this oppor- point, therefore, Smith and Timmis’s paper presents tunity for doing charitable work, and this opportunity nothing new. At first sight it appea,rs incomprehensible that these would be lost in the creation of a State medical service I am. Sir. vours faithfullv. authors were unable to isolate ergotamine from official ergot, but reflection suggests the question GEOFFREY EVANS. London, N.W., Oct. 9th, 1930. whether this failure was not due, at least in part, to the method of isolation ; this, notwithstanding it is
the fact that Smith and Timmis do not attach any importance to Stoll’s "protective " methods of extraction. Since Smith and Timmis do not give any figures stating the yield of crystalline alkaloids, SIR,—Two cases, reports of which will appear in the it is impossible to form an opinion as to the efficiency October number of the Guy’s Hospital Reports, of their method of isolation from a quantitative indicate that free hydrochloric acid itself is of more point of view. Comparative chemical methods will be importance in preventing the development of Addison’s discussed in another and more appropriate place, anaemia and subacute combined degeneration of the and, at present, I would only mention that Smith and spinal cord than would appear from the important Timmis by their method obtain not only ergotamine, investigations of Castle and his colleagues referred but also its transformation product ergotaminine. A This proves that their method does not sufficiently to in your annotation of Oct. llth (p. 809). was on a a man with performed take care of the sensitivity of ergotamine. By the gastro-jejunostomy gastric ulcer and a normal curve of acidity. His " protection " method ergotamine only and no symptoms disappeared, but two years ergotaminine is obtained from fresh ergot. The later he developed typical Addison’s anaemia with transformation of the primary alkaloid ergotamine early subacute combined degeneration of the cord into ergotaminine, which latter substance is very and Hunterian glossitis, apparently as a result difficultly soluble, and, consequently, also very of the achlorhydria which was now present owing to difficult to isolate, may occasionally lead to the the complete neutralisation of the free acid in his mistaken conclusion that ergot contains no, or very ACHYLIA GASTRICA AND PERNICIOUS ANÆMIA. To the Editor of THE LANCET.
digestive
stomach by the alkaline duodenal juices entering through the stoma. In the second case (the third of the kind I have seen) treatment of the gastritis, which I thought was the cause of his achlorhydria, led to the reappearance of free acid in the gastric contents of a man with severe Addison’s anaemia. Here again the only gastric factor concerned in the development of the disease appears to have been the absence of free hydrochloric acid.-I
am.
Sir.
vours
faithfullv.
ARTHUR New
F. HURST.
Lodge Clinic, Oct. 13th, 1930. THE ALKALOIDS OF ERGOT
To the Editor
of
THE LANCET.
little, ergotamine. It has
been stated, to my knowledge, that the ergotamine, properties of which are now so well known, can be obtained by one method only. It is, however, an indisputable fact that its first isolation in a pure state was effected by Stoll’s " protective " method, and that that method still furnishes the best yield obtainable and the purest product. This conclusion represents the result of my ten years’ experience obtained in the manufacture of ergotamine on a technical commercial scale. It is, of course, quite possible that Smith and Timmis did not have any official ergot rich in ergotamine at their disposal. On the other hand, A. W. Forst3 has isolated ergotamine alongside ergotoxine from official ergot, while we ourselves have frequently succeeded in obtaining ergotamine in a considerable yield, and in some cases alongside ergotoxine from the varieties examined by Smith and Timmis-i.e., Portuguese, CzechoSlovakian, and Hungarian4 ergots. The most definite proof of the fact that ergotamine exists in official ergot is provided by practical experience on a very large scale. During the past ten years the Sandoz Chemical Works, Basle, have extracted ergotamine, by the pound, from many tons of official ergot of rye by the "protective" method, and the ergotamine tartrate thus obtained has been, and still is, used in the preparation of Femergin and Gynergen products. No variety of ergot other than ergot of rye has ever been dealt with in the Sandoz Chemical never
SIR,-The annotation with this title which appeared in THE LANCET of Sept. 20th (p. 652) points to the conclusion that official ergot of rye contains no ergotamine whatever, and that, consequently, this substance cannot be regarded as the true active principle of official ergot of rye. I am under the necessity of correcting these erroneous conclusions, which are based on a paper by S. Smith and G. M. Timmis,l and, equally, I must refute any suggestion that ergotamine, which has been used for many years in the manufacture of Femergin (Gynergen) preparations, is not produced exclusively from ergot of rye. As far back as 1923, in a paper communicated to Die Naturwissenschaften,2 I emphasised the fact that Works. For nearly ten years ergotamine preparations ergotamine does not exist in all commercial specimens have been used in an ever-increasing measure, and of ergot, and, in addition, that the content of ergotoxine also varies enormously, depending on either hundreds of experimental and clinical research the age or source of the drug. In this paper I workers have shown that ergotamine possesses all especially pointed out that there are several specimens the specific properties of official ergot. As yet no of commercial ergot which contain no ergotamine such clinical literature exists on ergotoxine. While at all, and that ergot had been investigated " which, in 1923 the British Pharmaceutical Codex (p. 412) although it still contained traces of ergotoxine, still denied recognition to ergotoxine as a clinically yielded no ergotamine, whereas from other samples efficient active principle of ergot, ergotamine already of ergot practically the total amount of crude alka- possessed extensive clinical literature, providing loids, obtained in a good yield, could be transformed evidence to the fact that it was regarded as the active into the beautiful crystals of ergotamine." On this 3 Arch. Exp. Path. Pharm., 1926, cxiv., 132. 4 One kilo of ergot of rye collected by Prof. Issekutz in the 1 Jour. Chem. Soc., June, 1930, p. 1390. neighbourhood of Sceged (Hungary) in 1928 yielded in my 2 Berlin, 1923, p. 705. laboratory 0·5 g. pure crystals of the ergotamine (acetone water).
good for national character to have this oppor- point, therefore, Smith and Timmis’s paper presents tunity for doing charitable work, and this opportunity nothing new. At first sight it appea,rs incomprehensible that these would be lost in the creation of a State medical service I am. Sir. vours faithfullv. authors were unable to isolate ergotamine from official ergot, but reflection suggests the question GEOFFREY EVANS. London, N.W., Oct. 9th, 1930. whether this failure was not due, at least in part, to the method of isolation ; this, notwithstanding it is
the fact that Smith and Timmis do not attach any importance to Stoll’s "protective " methods of extraction. Since Smith and Timmis do not give any figures stating the yield of crystalline alkaloids, SIR,—Two cases, reports of which will appear in the it is impossible to form an opinion as to the efficiency October number of the Guy’s Hospital Reports, of their method of isolation from a quantitative indicate that free hydrochloric acid itself is of more point of view. Comparative chemical methods will be importance in preventing the development of Addison’s discussed in another and more appropriate place, anaemia and subacute combined degeneration of the and, at present, I would only mention that Smith and spinal cord than would appear from the important Timmis by their method obtain not only ergotamine, investigations of Castle and his colleagues referred but also its transformation product ergotaminine. A This proves that their method does not sufficiently to in your annotation of Oct. llth (p. 809). was on a a man with performed take care of the sensitivity of ergotamine. By the gastro-jejunostomy gastric ulcer and a normal curve of acidity. His " protection " method ergotamine only and no symptoms disappeared, but two years ergotaminine is obtained from fresh ergot. The later he developed typical Addison’s anaemia with transformation of the primary alkaloid ergotamine early subacute combined degeneration of the cord into ergotaminine, which latter substance is very and Hunterian glossitis, apparently as a result difficultly soluble, and, consequently, also very of the achlorhydria which was now present owing to difficult to isolate, may occasionally lead to the the complete neutralisation of the free acid in his mistaken conclusion that ergot contains no, or very ACHYLIA GASTRICA AND PERNICIOUS ANÆMIA. To the Editor of THE LANCET.
digestive
stomach by the alkaline duodenal juices entering through the stoma. In the second case (the third of the kind I have seen) treatment of the gastritis, which I thought was the cause of his achlorhydria, led to the reappearance of free acid in the gastric contents of a man with severe Addison’s anaemia. Here again the only gastric factor concerned in the development of the disease appears to have been the absence of free hydrochloric acid.-I
am.
Sir.
vours
faithfullv.
ARTHUR New
F. HURST.
Lodge Clinic, Oct. 13th, 1930. THE ALKALOIDS OF ERGOT
To the Editor
of
THE LANCET.
little, ergotamine. It has
been stated, to my knowledge, that the ergotamine, properties of which are now so well known, can be obtained by one method only. It is, however, an indisputable fact that its first isolation in a pure state was effected by Stoll’s " protective " method, and that that method still furnishes the best yield obtainable and the purest product. This conclusion represents the result of my ten years’ experience obtained in the manufacture of ergotamine on a technical commercial scale. It is, of course, quite possible that Smith and Timmis did not have any official ergot rich in ergotamine at their disposal. On the other hand, A. W. Forst3 has isolated ergotamine alongside ergotoxine from official ergot, while we ourselves have frequently succeeded in obtaining ergotamine in a considerable yield, and in some cases alongside ergotoxine from the varieties examined by Smith and Timmis-i.e., Portuguese, CzechoSlovakian, and Hungarian4 ergots. The most definite proof of the fact that ergotamine exists in official ergot is provided by practical experience on a very large scale. During the past ten years the Sandoz Chemical Works, Basle, have extracted ergotamine, by the pound, from many tons of official ergot of rye by the "protective" method, and the ergotamine tartrate thus obtained has been, and still is, used in the preparation of Femergin and Gynergen products. No variety of ergot other than ergot of rye has ever been dealt with in the Sandoz Chemical never
SIR,-The annotation with this title which appeared in THE LANCET of Sept. 20th (p. 652) points to the conclusion that official ergot of rye contains no ergotamine whatever, and that, consequently, this substance cannot be regarded as the true active principle of official ergot of rye. I am under the necessity of correcting these erroneous conclusions, which are based on a paper by S. Smith and G. M. Timmis,l and, equally, I must refute any suggestion that ergotamine, which has been used for many years in the manufacture of Femergin (Gynergen) preparations, is not produced exclusively from ergot of rye. As far back as 1923, in a paper communicated to Die Naturwissenschaften,2 I emphasised the fact that Works. For nearly ten years ergotamine preparations ergotamine does not exist in all commercial specimens have been used in an ever-increasing measure, and of ergot, and, in addition, that the content of ergotoxine also varies enormously, depending on either hundreds of experimental and clinical research the age or source of the drug. In this paper I workers have shown that ergotamine possesses all especially pointed out that there are several specimens the specific properties of official ergot. As yet no of commercial ergot which contain no ergotamine such clinical literature exists on ergotoxine. While at all, and that ergot had been investigated " which, in 1923 the British Pharmaceutical Codex (p. 412) although it still contained traces of ergotoxine, still denied recognition to ergotoxine as a clinically yielded no ergotamine, whereas from other samples efficient active principle of ergot, ergotamine already of ergot practically the total amount of crude alka- possessed extensive clinical literature, providing loids, obtained in a good yield, could be transformed evidence to the fact that it was regarded as the active into the beautiful crystals of ergotamine." On this 3 Arch. Exp. Path. Pharm., 1926, cxiv., 132. 4 One kilo of ergot of rye collected by Prof. Issekutz in the 1 Jour. Chem. Soc., June, 1930, p. 1390. neighbourhood of Sceged (Hungary) in 1928 yielded in my 2 Berlin, 1923, p. 705. laboratory 0·5 g. pure crystals of the ergotamine (acetone water).