minerva

1
1186 being obtained in treating a case of infection with Dibothriocephalus latus, which is known to cause an anaemia of the primary type. In a third paper, by Cohn, Minot, Alles, and Salter appearing in the May number of the Journal of Biological Chemistry, an interesting account is given of the methods employed in making liver extracts. Further- purification of the extract referred to in the other two communications has been obtained by precipitation with phosphotungstic acid. A fraction of this precipitate is formed of phospho- tungstates of a substance which contains about 19 per cent. of nitrogen, and which is probably of the nature of a polypeptide or a nitrogenous base ; only 0-6 g. of this is necessary per day to produce a good reticulocyte response in a case of pernicious anaemia. Hitherto it has been necessary to test such extracts by observing their effect on patients, but it is mentioned that F. R. Sabin, of New York, -has recently found that abnormally rapid develop- - ment takes place in the megaloblasts of chick embryo preparations treated with potent liver extract. Also alterations in human reticulocytes in the presence of extract have been observed by Emerson. The advantage of this discovery to those engaged in the study of the specific substance contained in liver "will at once be obvious. EXCESS OF IRRADIATED ERGOSTEROL. IT has always seemed possible, though not very -probable, that injury might be caused by excessive doses of any vitamin. Several workers have attributed certain symptoms to administration of an excess of vitamin A or of vitamin B, but the specificity of the intoxications described has not been definitely estab- lished. A. Kreitmair and T. Moll (1928), however, give an account of a hypervitaminosis with vitamin D, - which sounds really alarming. Their attention was focused on the subject by an article in which W. Pfannenstiel 2 (1927) described the effect of feeding half-grown rabbits with various doses of a preparation of irradiated ergosterol. Small doses raised the bactericidal power of the blood, but large doses caused severe cachexia and death. This observation agreed with the experience of Kreitmair and Moll, who had noticed that a daily dose of 20 mg. of irradiated ergosterol brought about the death of white mice in about six days. They therefore decided to make a much more thorough examination, using a variety of animals and noting the symptoms carefully. For white mice they found that 1 mg. daily was a lethal dose, when continued for 20 days ; larger doses caused more rapid death, but a smaller one, 0’5 mg., only caused loss of weight. For rats a dose of 5 mg. daily was lethal, for guinea-pigs 40 mg., for cats 5 mg., and for dogs 5 mg. per kg. of body-weight, but for fowls 50 mg. had no ill-effect, and for axolotls a dose of 10 mg. was innocuous. At autopsy an enormously rich deposit of lime was found, particu- larly in the walls of the vessels, in the heart muscle, stomach wall, lungs, kidneys, and intercostal muscu- lature. The large vessels and often the small ones, too, were converted into rigid tubes. The spleen was often markedly atrophic and the small intestine showed haemorrhagic inflammation of the mucous membrane. The picture was thus one of severe vascular sclerosis, to which the other symptoms were regarded as secondary, and it varied in severity with the species of animal. In discussing their results, the writers recall the well-known cholesterol sclerosis which can be induced in rabbits, experimentally after five or six months’ feeding with a daily dose of at least 0.1 g. cholesterol daily. They state that a similar ergosterol sclerosis occurs after two to three months’ feeding with non- irradiated ergosterol, while the sclerosis just described, due to feeding with irradiated ergosterol, is acute in 1 A. Kreitmair and T. Moll : Münch. med. Woch., 1928, lxxv., 637. 2 W. Pfannenstiel : Klin. Woch., 1927, xlviii., 2310. eight to fourteen days. It is clear from their own experiments that the time which symptoms of sclerosis take to develop is inversely proportional to the dose. Unfortunately, the authors do not mention what was , the dose of non-irradiated ergosterol to which they refer. This is important, for it must be remembered that when ergosterol is irradiated, it is not all immediately converted into vitamin D ; a certain portion remains unchanged. In absence of further evidence, it is possible that the sclerosis which Kreitmair and Moll observed to develop in feeding large doses of irradiated ergosterol may be due to the unchanged ergosterol and not to the vitamin ; but to whichever element the effect may be due, the fact’remains that large doses of irradiated ergosterol are toxic. This need not, however, cause uneasiness. The authors point out how enormous is the toxic dose, relative to the known dose needed to cure rickets. For the rat, for instance, the toxic dose is greater than 1 mg., while the healing dose is 1/10,000 mg. If we calculate the toxic dose for a man on the basis of that for the cat, it is found that 100 mg. daily would be needed to produce ill-effects in man. According to A. Hottinger 3 (1927) only 5 mg. daily are needed to cure an adult human being suffering from late rickets, tetany, or osteo- malacia. The risk of overdosage in an adult thus seems to be very small. Dr. H. Mackay pointed out in THE LANCET of May 5th (p. 924) that nothing was known as to the possible effect of overdosage in an infant, and recommended discretion in the use of antirachitic preparations. It is reassuring to learn that in animals the margin between therapeutic and toxic doses of vitamin D is so great, but the fact that definite pathological changes have been recorded lends point to her warning. MINERVA. THE twenty-ninth issue" of this admirable year book of the learned world follows the twenty-eighth, after an interval of less than two vears. The time has been sufficient to expand the volumes, which are already rather stout to bear the name of the slim goddess of wisdom ; and, as Dr. Gerhard Ludtke expresses it, the abundance of material threatens to burst the bounds of a year book. In the last issue it was decided to print the names of the members of large scientific academies, and it is personal details of this kind which have increased the size of the volumes, to the great convenience of those who have to refer to them, as we are happy to testify. In the interval the publisher has issued a Minerva Index, containing all the scientific institutes mentioned in the year book arranged topographically, and this third volume will be issued later, bound up with the name-index of the two volumes now before us. The editor of the year book is following more and more the practice of making the entries in the language of the country con- cerned, so far as that language is of world-wide dis- tribution. He justifies against all gainsayers his custom of keeping close to the current postal addresses of names and institutions, although the usual (pre-war) alternative names are given in print of similar size. An asterisk calls attention to information which has not been revised for this issue, and may therefore be somewhat behind the date of revision which, for the rest of the book, is Nov. 1st, 1927. Information regarding medical and technical societies in North America has again been extended, and a welcome innovation is the standardisation of Slavonic names by Dr. Kuziela. Dr. Lüdtke again acknowledges the editorial help of Dr. Friedrich Richter, and especially that of Frl. Chr. Pilger ; their work must have been colossal. The first volume contains, as frontispiece, a portrait of the Spanish scientist, S. Ramon Cajal, and the second that of Dr. Kriisz, general director of the Prussian State Library. 3 A. Hottinger : Zeitsch. f. Kinderheilk., 1927, xliv., 3-4. 4 2 Vols., 1457 and 1306 pp. Vol. 3 will contain 960 pp. Subs. price for the 3 vols M. 80, increased to M. 90 after full publication. Berlin and Leipzig: Walter de Gruyter and Co.

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Page 1: MINERVA

1186

being obtained in treating a case of infection withDibothriocephalus latus, which is known to cause ananaemia of the primary type.

In a third paper, by Cohn, Minot, Alles, and Salterappearing in the May number of the Journal ofBiological Chemistry, an interesting account is givenof the methods employed in making liver extracts.Further- purification of the extract referred to inthe other two communications has been obtainedby precipitation with phosphotungstic acid. Afraction of this precipitate is formed of phospho-tungstates of a substance which contains about19 per cent. of nitrogen, and which is probably of thenature of a polypeptide or a nitrogenous base ;only 0-6 g. of this is necessary per day to producea good reticulocyte response in a case of perniciousanaemia. Hitherto it has been necessary to testsuch extracts by observing their effect on patients,but it is mentioned that F. R. Sabin, of New York,-has recently found that abnormally rapid develop-- ment takes place in the megaloblasts of chick embryopreparations treated with potent liver extract. Alsoalterations in human reticulocytes in the presence ofextract have been observed by Emerson. Theadvantage of this discovery to those engaged in thestudy of the specific substance contained in liver"will at once be obvious.

EXCESS OF IRRADIATED ERGOSTEROL.

IT has always seemed possible, though not very-probable, that injury might be caused by excessivedoses of any vitamin. Several workers have attributedcertain symptoms to administration of an excess ofvitamin A or of vitamin B, but the specificity of theintoxications described has not been definitely estab-lished. A. Kreitmair and T. Moll (1928), however,give an account of a hypervitaminosis with vitamin D,- which sounds really alarming. Their attention wasfocused on the subject by an article in whichW. Pfannenstiel 2 (1927) described the effect offeeding half-grown rabbits with various doses of apreparation of irradiated ergosterol. Small dosesraised the bactericidal power of the blood, but largedoses caused severe cachexia and death. Thisobservation agreed with the experience of Kreitmairand Moll, who had noticed that a daily dose of 20 mg.of irradiated ergosterol brought about the death ofwhite mice in about six days. They therefore decidedto make a much more thorough examination, using avariety of animals and noting the symptoms carefully.For white mice they found that 1 mg. daily was alethal dose, when continued for 20 days ; larger dosescaused more rapid death, but a smaller one, 0’5 mg.,only caused loss of weight. For rats a dose of 5 mg.daily was lethal, for guinea-pigs 40 mg., for cats5 mg., and for dogs 5 mg. per kg. of body-weight, butfor fowls 50 mg. had no ill-effect, and for axolotls adose of 10 mg. was innocuous. At autopsy an

enormously rich deposit of lime was found, particu-larly in the walls of the vessels, in the heart muscle,stomach wall, lungs, kidneys, and intercostal muscu-

lature. The large vessels and often the small ones, too,were converted into rigid tubes. The spleen wasoften markedly atrophic and the small intestineshowed haemorrhagic inflammation of the mucousmembrane. The picture was thus one of severe

vascular sclerosis, to which the other symptoms wereregarded as secondary, and it varied in severity withthe species of animal.

In discussing their results, the writers recall thewell-known cholesterol sclerosis which can be inducedin rabbits, experimentally after five or six months’feeding with a daily dose of at least 0.1 g. cholesteroldaily. They state that a similar ergosterol sclerosisoccurs after two to three months’ feeding with non-irradiated ergosterol, while the sclerosis just described,due to feeding with irradiated ergosterol, is acute in

1 A. Kreitmair and T. Moll : Münch. med. Woch., 1928, lxxv., 637.2 W. Pfannenstiel : Klin. Woch., 1927, xlviii., 2310.

eight to fourteen days. It is clear from their ownexperiments that the time which symptoms of sclerosistake to develop is inversely proportional to the dose.Unfortunately, the authors do not mention what was ,

the dose of non-irradiated ergosterol to which theyrefer. This is important, for it must be remembered thatwhen ergosterol is irradiated, it is not all immediatelyconverted into vitamin D ; a certain portion remainsunchanged. In absence of further evidence, it is

possible that the sclerosis which Kreitmair and Mollobserved to develop in feeding large doses of irradiatedergosterol may be due to the unchanged ergosteroland not to the vitamin ; but to whichever elementthe effect may be due, the fact’remains that large dosesof irradiated ergosterol are toxic. This need not,however, cause uneasiness. The authors point outhow enormous is the toxic dose, relative to the knowndose needed to cure rickets. For the rat, for instance,the toxic dose is greater than 1 mg., while the healingdose is 1/10,000 mg. If we calculate the toxicdose for a man on the basis of that for the cat, it isfound that 100 mg. daily would be needed to produceill-effects in man. According to A. Hottinger 3 (1927)only 5 mg. daily are needed to cure an adult humanbeing suffering from late rickets, tetany, or osteo-malacia. The risk of overdosage in an adult thusseems to be very small. Dr. H. Mackay pointed outin THE LANCET of May 5th (p. 924) that nothing wasknown as to the possible effect of overdosage in aninfant, and recommended discretion in the use ofantirachitic preparations. It is reassuring to learnthat in animals the margin between therapeutic andtoxic doses of vitamin D is so great, but the factthat definite pathological changes have been recordedlends point to her warning.

MINERVA.

THE twenty-ninth issue" of this admirable year bookof the learned world follows the twenty-eighth, afteran interval of less than two vears. The time has beensufficient to expand the volumes, which are alreadyrather stout to bear the name of the slim goddess ofwisdom ; and, as Dr. Gerhard Ludtke expresses it,the abundance of material threatens to burst thebounds of a year book. In the last issue it was decidedto print the names of the members of large scientificacademies, and it is personal details of this kindwhich have increased the size of the volumes, to thegreat convenience of those who have to refer tothem, as we are happy to testify. In the intervalthe publisher has issued a Minerva Index, containingall the scientific institutes mentioned in the year bookarranged topographically, and this third volume willbe issued later, bound up with the name-index of thetwo volumes now before us. The editor of the yearbook is following more and more the practice ofmaking the entries in the language of the country con-cerned, so far as that language is of world-wide dis-tribution. He justifies against all gainsayers his customof keeping close to the current postal addresses ofnames and institutions, although the usual (pre-war)alternative names are given in print of similar size.An asterisk calls attention to information which hasnot been revised for this issue, and may thereforebe somewhat behind the date of revision which, forthe rest of the book, is Nov. 1st, 1927. Informationregarding medical and technical societies in NorthAmerica has again been extended, and a welcomeinnovation is the standardisation of Slavonic namesby Dr. Kuziela. Dr. Lüdtke again acknowledgesthe editorial help of Dr. Friedrich Richter, andespecially that of Frl. Chr. Pilger ; their work musthave been colossal. The first volume contains, asfrontispiece, a portrait of the Spanish scientist,S. Ramon Cajal, and the second that of Dr. Kriisz,general director of the Prussian State Library.

3 A. Hottinger : Zeitsch. f. Kinderheilk., 1927, xliv., 3-4.4 2 Vols., 1457 and 1306 pp. Vol. 3 will contain 960 pp.

Subs. price for the 3 vols M. 80, increased to M. 90 after fullpublication. Berlin and Leipzig: Walter de Gruyter and Co.