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ÆTIOLOGY OF PELLAGRA AND THE NUTRITIVE VALUE OF MAIZE
282
being administered, for medicine not
enthusiasm, despite
(oh,
such
I turn round and view the future with confidence but with conservatism within and credulity
only
credulity !)
without.
ÆTIOLOGY OF PELLAGRA AND THE NUTRITIVE VALUE
OF
MAIZE
A REVIEW
THE acceptance of pellagra as a nutritional disease is largely due to the labours of Joseph Goldberger and his colleagues of the United States public health service in the long series of clinical researches carried out from 1920 to 1930. These workers narrowed the problem of the aetiology when they "showed that a typical " diet could be rendered maize pellagra-producing wholesome by addition of dried yeast. Their investigations also included much important experimental work on " black tongue," the disease characterised by anaemia, stomatitis, and diarrhoea, which is produced in dogs when fed on diets consisting largely of maize, resembling those on which human pellagra develops in regions where the disease is endemic. This disorder is considered, with justification, to be the canine analogue of the human disease; the amounts of different foods (yeast, milk, meat, eggs, &c.) which when added to the " maize " diets were found to prevent and cure black-tongue formed a series exactly parallel with the series that prevented and cured human pellagra. The preventive dietary factor for black-tongue was found not only in dried yeast but also in a protein-free yeast extract ; it was resistant to autoclaving, and could be concentrated by adsorption on fuller’s earth, as in the " preparation of Goldberger’s P-P (pellagra-preventive) solid." More recent work has confirmed the above analogy ; pellagra has been cured with autoclaved yeast by Spies and other workers in U.S.A., and good results have lately been reported from Egypt by Ellinger, Hassan, and Taha (1937a) with an aqueous yeast extract which had been autoclaved at 120° for five hours. More recently, experiments at the Institute of Animal Pathology at Cambridge, carried out in collaboration with the division of nutrition of the Lister Institute, have shown that young pigs also fail to thrive on Goldberger’s black-tongue maize diets and suffer from dermatitis and diarrhoea (Birch, Chick, and Martin 1937). Later the diarrhoea increases in severity, and is accompanied by complete loss of appetite ; death ensues unless the diet is changed. Addition of autoclaved yeast extract renders the diets satisfactory and causes swift cures of gravely sick animals. Monkeys also sicken, develop diarrhoea, and die on Goldberger’s maize diets (Harris 1937a), but rats thrive on them (Birch, Chick, and Martin 1937). The fact that the material that renders such diets wholesome is present in an aqueous yeast extract suggested at once some connexion with the group of B vitamins, while its stability at high temperatures pointed to the portion of the B-vitamin complex which has been called vitamin B2 (vitamin G in America), itself now known to be complex in nature. One constituent, lactoflavin (or riboflavin), has been isolated in the pure state, and at least two additional substances of nutritional importance are known to be present in an autoclaved yeast extract (Edgar and Macrae 1937). One of these is adsorbed on fuller’s earth together with lactoflavin, but can be separated after elution ; the second is found in the filtrate from the fuller’s earth adsorption. Fractions with
similar chemical and nutritive properties have also been isolated from sources other than yeast, such as liver extract and rice-polishings. Not only yeast extract but also liver extract and preparations made from it have proved curative for pellagra and black-tongue (Voegtlin et al. 1920, Ruffin and Smith 1937, Fouts et al. 1936). Pure lactoflavin has no curative action for either disease (Dann 1936, Koehn and Elvejhem 1936,’Sebrell et al. 1937). This pigment is one constituent of the yellow oxidation enzyme, the ferment widely distributed in living animal tis’sues discovered by Warburg and Christian. This enzyme, which is concerned with important oxidation processes normally occurring in living animal tissues, needs for its action the presence of a co-enzyme named by Warburg co-dehydrase II, and shown to contain nicotinic acid amide (combined with adenine and carbohydrate and phosphoric acid groups). Cozymase, the co-enzyme which is specially concerned in the alcoholic fermentation of yeast, has a composition almost identical with that of co-dehydrase II, and both are contained in yeast extract. In the attempts to identify the nutritive essentials contained in yeast and liver extracts, attention was naturally turned to the co-enzymes and their constituents. A preparation of nicotinic acid amide, isolated from liver extract, was found a few months ago to cure black-tongue in dogs by Elvehjem and his colleagues (1937) at Madison ; pure nicotinic acid also proved active. The significance of this was and obvious discovery reports of the treatment of human pellagra soon appeared. Fouts, Helmer, Lepkovsky, and Jukes (1937) describe the cure of 4 cases in the Indianapolis Hospital, maintained upon a diet on which pellagrins do not improve, when 0-5 to 1’0 g. nicotinic acid was given daily by mouth. Smith, Ruffin, and Smith (1937), working at the Duke University School of Medicine, Durham, North Carolina, give the details of a particularly interesting case of a man, aged 42, who had suffered from recurrent pellagra for fifteen years, and showed all the typical symptoms, including mental aberration. The nicotinic acid was given intravenously or intramuscularly in daily doses of 60 mg., with dramatic results. There was improvement in the appetite within 24 hours, in the mental condition after 48 hours, and in the skin and the face within 3 days, and the cure was complete in 12 days. Promising results have also been reported from Cairo with cases receiving 0,3g. nicotinic acid daily by mouth (Hassan, see Harris 1937b), and the successful treatment of 15 cases by Dr. T. B. Spies at Cincinnati is described on another page of this issue. Dramatic cures have been. obtained at Cambridge (Chick et al. 1938) when pigs which had become gravely ill after being fed for 3-4 months on a pellagrous diet were given 60 mg. nicotinic acid daily. The appetite returned in 24 hours, the diarrhoea abated in a few days, the dermatitis cleared up, and a new coat of hair was grown. The pigs soon began to grow and put on weight at an accelerated rate, so that in 3 months they weighed as much as their litter-mates which had been properly fed. NUTRITIVE VALUE OF MAIZE
What explanation
do the above researches afford pellagra among maize-eating populations7 Experimental researches on the nutritive value of maize, as compared with that of other cereals, have been actively and continuously carried on ever since the association of pellagra with maizeeating was recognised as a fact. Attention was naturally first turned to the nutritive value of the of the
occurrence
of
283 maize
proteins, seeing
that
a
large part
of these
consist of zein, a protein which is deficient in the essential amino-acids tryptophane and lysine. The results of experimental work on this subject have
indicated, however, that if enough is eaten the other proteins contained in the maize kernel, the glutenins
and globulins, will make good the deficiencies of the zein. Nor as regards the content of known vitamins does maize seem to be inferior to wheat, for example. Vitamin A, of which only traces are found in wheat, is relatively abundant in the yellow variety of maize. The unmilled grains of both cereals are well supplied with vitamin Bl and contain fair amounts of the vitamin-Bg complex, with the exception of lactoflavin in which both are poor and maize poorer than wheat (Copping 1936). Lactoflavin deficiency, however, does not appear to be connected with the cause of pellagra. Nicotinic acid, which may now be regarded as an hitherto unrecognised dietary essential, is a relatively simple compound, of composition CsHb02N (pyridene (3-monocarbogylic acid), and the work described above suggests that pellagra among maize-eaters may be due to a deficiency of nicotinic acid in maize, as compared with other cereals. No chemical methods are at present available for the estimation of small quantities of nicotinic acid in such substances, which would afford a direct answer to this question, and for the present the only evidence is that obtained from biological tests. In the experiments on young pigs at Cambridge, referred to above, the diet was found to be just adequate when the whole ground maize (83 per cent.) it contained was replaced by a mixture of whole wheat and barley, or when the pigs receiving a diet of maize and purified casein were bedded on wheaten straw of which they consumed considerable amounts. As already stated, young rats will thrive on diets composed almost exclusively of maize if the whole grain be given; when milled maize is substituted the defects can be corrected by yeast extract but not by nicotinic acid, nor can nicotinic acid or nicotinic acid amide replace any of the separate B2 vitamins required by the rat (Macrae and Edgar 1937, Cook, Clarke and Light 1937). Experiments on the rat, with which so much important nutritional research has been done in the past, have again afforded only misleading indications as to the aetiology of pellagra. The rat is evidently unsuitable for an investigation of the nutritive value of cereals for the human race, and the dog or pig seems to be a more suitable experimental animal for future work in this field. SECONDARY PELLAGRA
A note is perhaps needed upon the relation of the above argument to the aetiology of the sporadic cases of pellagra arising among populations which eat no maize. These cases, usually known as " secondary pellagra," display symptoms similar to those of the endemic disease, and in the later stages may also show some degree of mental disorder. Secondary pellagra develops after a long period of illness in which the absorptive capacity of the digestive tract has been severely disturbed-e.g., after dysentery or long-continued diarrhoea, in alcoholic addiction, or after operation or cancer involving the stomach or small intestine. Diarrhoea is also a common symptom of endemic pellagra and the infestation with internal parasites that is often present is held by some investigators to be an important contributory cause of the disease (Ellinger, Hassan, and Taha 1937b). Many cases of secondary pellagra have been treated with
and liver extract as successfully as those of endemic pellagra, and an interesting example is published in our present issue by Dr. Yudkin, Dr. Hawksley, and Prof. Drummond. The fruitful series of investigations by Spies and his co-workers at Lakeside Hospital, Cleveland, were carried out chiefly on cases of "alcoholic" pellagra. One may assume that in these cases the disease is caused by defective absorption of the essential dietary factor from diets in which it is not abundant, and medication with yeast or liver extract There is, seems to be a useful preventive measure. however, no satisfactory explanation of the fact that in the United States, where pellagra is endemic, addiction to alcohol should often be followed by this disease, whereas elsewhere polyneuritis, which may be curable by the antiberi-beri vitamin B,. (Joliffe and Colbert 1936), should be the more usual result. Possibly a careful scrutiny of the diets might reveal the reason.
yeast
REFERENCES
(1937) Biochem. J. 31, 2065. Chick, H., Macrae, T. F., Martin, A. J. P., and Martin, C. J. (1938) Ibid (in the press). (Reported at the meeting of the Biochemical Society on Jan. 14th.) Copping, A. M. (1936) Ibid, 30, 849. Dann, W. J. (1936) J. Nutrit. 11, 451. Edgar, C. E., and Macrae, T. F. (1937) Biochem. J. 31, 886. Ellinger, P., Hassan, A., and Taha, M. M. (1937a) Lancet, 2, 1188. (1937b) Ibid, p. 755. Elvehjem, C. A., Madden, R. J., Strong, F. M., and Woolley, D. W. (1937) J. Amer. chem. Soc. 59, 1767. Fouts, P. J., Lepkovsky, S., Helmer, O. M., and Jukes, T. H. (1936) Proc. Soc. exp. Biol., N.Y. 35, 245. Helmer, O. M., Lepkovsky, S., and Jukes, T. H. (1937) Ibid, 37, 405. Harris, L. J. (1937a) Biochem. J. 31, 1414. (1937b) Lancet, 2, 1467. Joliffe, N., and Colbert, C. N. (1936) J. Amer. med. Ass. 107, 642. Koehn, C. J., and Elvehjem, C. A. (1936) J. Nutrit. 11, 67. Macrae, T. F., and Edgar, C. E. (1937) Biochem. J. 31, 2225. Ruffin, J. M., and Smith, D. T. (1937) Sth. med. J., Nashville, 30, 4. Sebrell, W. H., Hunt, D. J., and Onstott, R. H. (1937) Publ. Hlth Rep., Wash. 52, 235. Smith, D. T., Ruffin, J. M., and Smith, S. G. (1937) J. Amer. med. Ass. 109, 2054. Voegtlin, C., Neill, M. H., and Hunter, A. (1920) U.S. Publ. Birch, T. W., Chick, H., and Martin, C. J.
—
—
—
-
-
Hlth Serv. Bull. No. 116.
PARIS
(FROM
OUR OWN
CORRESPONDENT)
MORE ABOUT THE 40-HOUR WEEK THE hospital world is divided into two camps over the effects of shorter hours on the morals of the hospital staffs. Monsieur Mourier, head of the public hospital services in Paris, is the leading figure in one camp, and in his address to the Academy of Medicine on Dec. 21st he showed that the Paris hospital mortality had fallen slightly since the introduction of the 40-hour week. In both camps there are now said to be bulky dossiers of evidence, and however tempting it may be to suspect that the Mourier dossier contains a soupcon of official whitewash, we also have the declaration of Prof. Sergent, who, speaking with the retrospective impartiality of a surgeon on the retired list, paid a glowing tribute before the Academy to the remarkable devotion with which the great majority, if not all, of the subordinate members of hospital staffs fulfil their duties. PROFESSIONAL SECRECY AND DEATH CERTIFICATES
The agenda of the annual meeting of the Confédération des Syndicats Médicaux Francais put in a nutshell the most pressing problems with which the French medical profession is confronted to-day. One of these is the vexed question of the wording of death certificates. Article 378 of the penal code
being administered, for medicine not
enthusiasm, despite
(oh,
such
I turn round and view the future with confidence but with conservatism within and credulity
only
credulity !)
without.
ÆTIOLOGY OF PELLAGRA AND THE NUTRITIVE VALUE
OF
MAIZE
A REVIEW
THE acceptance of pellagra as a nutritional disease is largely due to the labours of Joseph Goldberger and his colleagues of the United States public health service in the long series of clinical researches carried out from 1920 to 1930. These workers narrowed the problem of the aetiology when they "showed that a typical " diet could be rendered maize pellagra-producing wholesome by addition of dried yeast. Their investigations also included much important experimental work on " black tongue," the disease characterised by anaemia, stomatitis, and diarrhoea, which is produced in dogs when fed on diets consisting largely of maize, resembling those on which human pellagra develops in regions where the disease is endemic. This disorder is considered, with justification, to be the canine analogue of the human disease; the amounts of different foods (yeast, milk, meat, eggs, &c.) which when added to the " maize " diets were found to prevent and cure black-tongue formed a series exactly parallel with the series that prevented and cured human pellagra. The preventive dietary factor for black-tongue was found not only in dried yeast but also in a protein-free yeast extract ; it was resistant to autoclaving, and could be concentrated by adsorption on fuller’s earth, as in the " preparation of Goldberger’s P-P (pellagra-preventive) solid." More recent work has confirmed the above analogy ; pellagra has been cured with autoclaved yeast by Spies and other workers in U.S.A., and good results have lately been reported from Egypt by Ellinger, Hassan, and Taha (1937a) with an aqueous yeast extract which had been autoclaved at 120° for five hours. More recently, experiments at the Institute of Animal Pathology at Cambridge, carried out in collaboration with the division of nutrition of the Lister Institute, have shown that young pigs also fail to thrive on Goldberger’s black-tongue maize diets and suffer from dermatitis and diarrhoea (Birch, Chick, and Martin 1937). Later the diarrhoea increases in severity, and is accompanied by complete loss of appetite ; death ensues unless the diet is changed. Addition of autoclaved yeast extract renders the diets satisfactory and causes swift cures of gravely sick animals. Monkeys also sicken, develop diarrhoea, and die on Goldberger’s maize diets (Harris 1937a), but rats thrive on them (Birch, Chick, and Martin 1937). The fact that the material that renders such diets wholesome is present in an aqueous yeast extract suggested at once some connexion with the group of B vitamins, while its stability at high temperatures pointed to the portion of the B-vitamin complex which has been called vitamin B2 (vitamin G in America), itself now known to be complex in nature. One constituent, lactoflavin (or riboflavin), has been isolated in the pure state, and at least two additional substances of nutritional importance are known to be present in an autoclaved yeast extract (Edgar and Macrae 1937). One of these is adsorbed on fuller’s earth together with lactoflavin, but can be separated after elution ; the second is found in the filtrate from the fuller’s earth adsorption. Fractions with
similar chemical and nutritive properties have also been isolated from sources other than yeast, such as liver extract and rice-polishings. Not only yeast extract but also liver extract and preparations made from it have proved curative for pellagra and black-tongue (Voegtlin et al. 1920, Ruffin and Smith 1937, Fouts et al. 1936). Pure lactoflavin has no curative action for either disease (Dann 1936, Koehn and Elvejhem 1936,’Sebrell et al. 1937). This pigment is one constituent of the yellow oxidation enzyme, the ferment widely distributed in living animal tis’sues discovered by Warburg and Christian. This enzyme, which is concerned with important oxidation processes normally occurring in living animal tissues, needs for its action the presence of a co-enzyme named by Warburg co-dehydrase II, and shown to contain nicotinic acid amide (combined with adenine and carbohydrate and phosphoric acid groups). Cozymase, the co-enzyme which is specially concerned in the alcoholic fermentation of yeast, has a composition almost identical with that of co-dehydrase II, and both are contained in yeast extract. In the attempts to identify the nutritive essentials contained in yeast and liver extracts, attention was naturally turned to the co-enzymes and their constituents. A preparation of nicotinic acid amide, isolated from liver extract, was found a few months ago to cure black-tongue in dogs by Elvehjem and his colleagues (1937) at Madison ; pure nicotinic acid also proved active. The significance of this was and obvious discovery reports of the treatment of human pellagra soon appeared. Fouts, Helmer, Lepkovsky, and Jukes (1937) describe the cure of 4 cases in the Indianapolis Hospital, maintained upon a diet on which pellagrins do not improve, when 0-5 to 1’0 g. nicotinic acid was given daily by mouth. Smith, Ruffin, and Smith (1937), working at the Duke University School of Medicine, Durham, North Carolina, give the details of a particularly interesting case of a man, aged 42, who had suffered from recurrent pellagra for fifteen years, and showed all the typical symptoms, including mental aberration. The nicotinic acid was given intravenously or intramuscularly in daily doses of 60 mg., with dramatic results. There was improvement in the appetite within 24 hours, in the mental condition after 48 hours, and in the skin and the face within 3 days, and the cure was complete in 12 days. Promising results have also been reported from Cairo with cases receiving 0,3g. nicotinic acid daily by mouth (Hassan, see Harris 1937b), and the successful treatment of 15 cases by Dr. T. B. Spies at Cincinnati is described on another page of this issue. Dramatic cures have been. obtained at Cambridge (Chick et al. 1938) when pigs which had become gravely ill after being fed for 3-4 months on a pellagrous diet were given 60 mg. nicotinic acid daily. The appetite returned in 24 hours, the diarrhoea abated in a few days, the dermatitis cleared up, and a new coat of hair was grown. The pigs soon began to grow and put on weight at an accelerated rate, so that in 3 months they weighed as much as their litter-mates which had been properly fed. NUTRITIVE VALUE OF MAIZE
What explanation
do the above researches afford pellagra among maize-eating populations7 Experimental researches on the nutritive value of maize, as compared with that of other cereals, have been actively and continuously carried on ever since the association of pellagra with maizeeating was recognised as a fact. Attention was naturally first turned to the nutritive value of the of the
occurrence
of
283 maize
proteins, seeing
that
a
large part
of these
consist of zein, a protein which is deficient in the essential amino-acids tryptophane and lysine. The results of experimental work on this subject have
indicated, however, that if enough is eaten the other proteins contained in the maize kernel, the glutenins
and globulins, will make good the deficiencies of the zein. Nor as regards the content of known vitamins does maize seem to be inferior to wheat, for example. Vitamin A, of which only traces are found in wheat, is relatively abundant in the yellow variety of maize. The unmilled grains of both cereals are well supplied with vitamin Bl and contain fair amounts of the vitamin-Bg complex, with the exception of lactoflavin in which both are poor and maize poorer than wheat (Copping 1936). Lactoflavin deficiency, however, does not appear to be connected with the cause of pellagra. Nicotinic acid, which may now be regarded as an hitherto unrecognised dietary essential, is a relatively simple compound, of composition CsHb02N (pyridene (3-monocarbogylic acid), and the work described above suggests that pellagra among maize-eaters may be due to a deficiency of nicotinic acid in maize, as compared with other cereals. No chemical methods are at present available for the estimation of small quantities of nicotinic acid in such substances, which would afford a direct answer to this question, and for the present the only evidence is that obtained from biological tests. In the experiments on young pigs at Cambridge, referred to above, the diet was found to be just adequate when the whole ground maize (83 per cent.) it contained was replaced by a mixture of whole wheat and barley, or when the pigs receiving a diet of maize and purified casein were bedded on wheaten straw of which they consumed considerable amounts. As already stated, young rats will thrive on diets composed almost exclusively of maize if the whole grain be given; when milled maize is substituted the defects can be corrected by yeast extract but not by nicotinic acid, nor can nicotinic acid or nicotinic acid amide replace any of the separate B2 vitamins required by the rat (Macrae and Edgar 1937, Cook, Clarke and Light 1937). Experiments on the rat, with which so much important nutritional research has been done in the past, have again afforded only misleading indications as to the aetiology of pellagra. The rat is evidently unsuitable for an investigation of the nutritive value of cereals for the human race, and the dog or pig seems to be a more suitable experimental animal for future work in this field. SECONDARY PELLAGRA
A note is perhaps needed upon the relation of the above argument to the aetiology of the sporadic cases of pellagra arising among populations which eat no maize. These cases, usually known as " secondary pellagra," display symptoms similar to those of the endemic disease, and in the later stages may also show some degree of mental disorder. Secondary pellagra develops after a long period of illness in which the absorptive capacity of the digestive tract has been severely disturbed-e.g., after dysentery or long-continued diarrhoea, in alcoholic addiction, or after operation or cancer involving the stomach or small intestine. Diarrhoea is also a common symptom of endemic pellagra and the infestation with internal parasites that is often present is held by some investigators to be an important contributory cause of the disease (Ellinger, Hassan, and Taha 1937b). Many cases of secondary pellagra have been treated with
and liver extract as successfully as those of endemic pellagra, and an interesting example is published in our present issue by Dr. Yudkin, Dr. Hawksley, and Prof. Drummond. The fruitful series of investigations by Spies and his co-workers at Lakeside Hospital, Cleveland, were carried out chiefly on cases of "alcoholic" pellagra. One may assume that in these cases the disease is caused by defective absorption of the essential dietary factor from diets in which it is not abundant, and medication with yeast or liver extract There is, seems to be a useful preventive measure. however, no satisfactory explanation of the fact that in the United States, where pellagra is endemic, addiction to alcohol should often be followed by this disease, whereas elsewhere polyneuritis, which may be curable by the antiberi-beri vitamin B,. (Joliffe and Colbert 1936), should be the more usual result. Possibly a careful scrutiny of the diets might reveal the reason.
yeast
REFERENCES
(1937) Biochem. J. 31, 2065. Chick, H., Macrae, T. F., Martin, A. J. P., and Martin, C. J. (1938) Ibid (in the press). (Reported at the meeting of the Biochemical Society on Jan. 14th.) Copping, A. M. (1936) Ibid, 30, 849. Dann, W. J. (1936) J. Nutrit. 11, 451. Edgar, C. E., and Macrae, T. F. (1937) Biochem. J. 31, 886. Ellinger, P., Hassan, A., and Taha, M. M. (1937a) Lancet, 2, 1188. (1937b) Ibid, p. 755. Elvehjem, C. A., Madden, R. J., Strong, F. M., and Woolley, D. W. (1937) J. Amer. chem. Soc. 59, 1767. Fouts, P. J., Lepkovsky, S., Helmer, O. M., and Jukes, T. H. (1936) Proc. Soc. exp. Biol., N.Y. 35, 245. Helmer, O. M., Lepkovsky, S., and Jukes, T. H. (1937) Ibid, 37, 405. Harris, L. J. (1937a) Biochem. J. 31, 1414. (1937b) Lancet, 2, 1467. Joliffe, N., and Colbert, C. N. (1936) J. Amer. med. Ass. 107, 642. Koehn, C. J., and Elvehjem, C. A. (1936) J. Nutrit. 11, 67. Macrae, T. F., and Edgar, C. E. (1937) Biochem. J. 31, 2225. Ruffin, J. M., and Smith, D. T. (1937) Sth. med. J., Nashville, 30, 4. Sebrell, W. H., Hunt, D. J., and Onstott, R. H. (1937) Publ. Hlth Rep., Wash. 52, 235. Smith, D. T., Ruffin, J. M., and Smith, S. G. (1937) J. Amer. med. Ass. 109, 2054. Voegtlin, C., Neill, M. H., and Hunter, A. (1920) U.S. Publ. Birch, T. W., Chick, H., and Martin, C. J.
—
—
—
-
-
Hlth Serv. Bull. No. 116.
PARIS
(FROM
OUR OWN
CORRESPONDENT)
MORE ABOUT THE 40-HOUR WEEK THE hospital world is divided into two camps over the effects of shorter hours on the morals of the hospital staffs. Monsieur Mourier, head of the public hospital services in Paris, is the leading figure in one camp, and in his address to the Academy of Medicine on Dec. 21st he showed that the Paris hospital mortality had fallen slightly since the introduction of the 40-hour week. In both camps there are now said to be bulky dossiers of evidence, and however tempting it may be to suspect that the Mourier dossier contains a soupcon of official whitewash, we also have the declaration of Prof. Sergent, who, speaking with the retrospective impartiality of a surgeon on the retired list, paid a glowing tribute before the Academy to the remarkable devotion with which the great majority, if not all, of the subordinate members of hospital staffs fulfil their duties. PROFESSIONAL SECRECY AND DEATH CERTIFICATES
The agenda of the annual meeting of the Confédération des Syndicats Médicaux Francais put in a nutshell the most pressing problems with which the French medical profession is confronted to-day. One of these is the vexed question of the wording of death certificates. Article 378 of the penal code