- Email: [email protected]
CARCINOGENS IN HEATED ANIMAL FATS ?
1448 that it wears off being attributable to variations in the intensity of the disease. Whether this is true or not, many patients are today treated with iodine when operation is not contemplated; and many are given the drug for longer periods than 14 days before operation ; especially as there are frequent exceptions to the rule that an iodine-free patient can be made fit for operation in this time. As Lehman and Shearburnpoint out, the criteria of fitness for operation in cases of toxic goitre are not easily laid down. Having studied the postoperative course of their cases in relation to the preoperative condition and treatment they find on the whole no correlation between the length of preparation and the severity of the postoperative reaction ; and this also applies when only a group of cases having initial basal metabolic rates between +36 and +45 are considered. A classification according to severity (as measured by the initial B.M.R.) also shows no simple relation between the different groups and the postoperative reaction. This inconsistency may be explained by the fact that the B.M.R. does not indicate the true severity of the illness ; it takes no account of the extent of visceral damage. At the time just before operation moreover the disease may be in an upward phase in one person and a downward phase in another. Lehman and Shearburn’s observations suggest that there is no advantage in prolonging iodine treatment once the patient appears to be safe for operation. As to what constitutes a safe condition they conclude that no rigid rules are useful, each
patient being a separate problem. But evidently the experienced clinician can say with considerable accuracy when a patient is ready ; for in expert hands thyroidectomy has become one of the safest of major operations. FLYING AT MODERATE ALTITUDES
IT is widely supposed height of, say, 15,000
that repeated flights at a ft. help the airman to acclimatise himself to low atmospheric pressures. Monaco2 holds that, on the contrary, they are harmful. The aviator’s acclimatisation to high altitudes differs from that of a mountaineer; for the pilot stays only a very short time at the new level and quickly returns to the ground. Gradual adaptation to new conditions is thus rendered impossible, and according to Monaco the frequent alternation between extremes upsets the physiological mechanism. Whereas a stay on a high mountain induces an increase in the number of erythrocytes, repeated high flights cause, after a time, anaemia. True, an increase in red blood-cells has been observed in airmen, but Monaco says that it is merely temporary, is due to anoxoemia, and can only be demonstrated during and immediately after a single high flight. On the pilot’s return to earth it soon disappears and is succeeded by a progressive fall in the number of erythrocytes. Monaco claims that the results of his experiments are confirmed by the practical observations of Martin Flack and his collaborators that pilots after repeated high flights become less tolerant of them ; and of Armstrong3 that symptoms of intolerance are manifested by American commercial pilots flying not more than three hours a day at an average height of 750013,500 ft. He also reports that in Italy, during a period of ten years, sickness has been 56 per cent. Lehman, E. P., and Shearburn, E. W., Ann. Surg. May, 1939, p. 712. 2. Monaco, B., Ann. Igiene, Roma, April, 1939, p. 249. 3. Armstrong, H. G., J. Aviat. Med. 1938, 9, 84. 1.
among airmen than in the other services, a strict medical examination on entry. The trouble is ascribed to the deficiency of oxygen at high altitudes and the consequent lowering of the oxygen tension in the alveoli, producing anoxia of the tissues, shown chiefly by a diminution of reflexes. Monaco cites Strughold and Treutler as showing that even at a height of only 7500 ft. there is an obvious diminution of the patellar reflex if a respirator is not used, and he concludes that a respirator should always be worn after a height of 6000 ft. has been reached-preferably one containing a mixture of gases and with a pressure of oxygen gradually increasing pari passu with the alteration in barometric pressure.
higher despite
CARCINOGENS IN HEATED ANIMAL FATS ? TEN years ago E. L. Kennaway found that substances carcinogenic for the skin were formed when living cells, such as yeast cells or human skin, were subjected in a hydrogen atmosphere to temperatures of 700°-900° C. in such a way that slow destruction with the formation of tarry material was brought about. The same thing happened when cholesterol, a constituent of all living tissues, was treated in this way. When tarry material thus obtained was applied to the skin of mice malignant tumours developed at the site of application. The carcinogenic effect produced was a local one. Taking these observations as his starting-point, Prof. E. M. P. Widmark of the University of Lund has treated the skin of mice with alcohol- or petroleum-extracts of roasted coffee, browned butter and horse muscle heated to 275° C. The results, which he summarises in a preliminary note in Nature of June 10, are very puzzling. When the skin was painted with the extracts no effects were observed in the skin, but of 23 female mice which survived a period of application, 9 developed carcinoma of the mamma ; no such tumours developed in the males. It will be noticed that in these experiments, unlike Kennaway’s, the carcinogenic effect was not a local one. Of 26 control animals (sex not treated with extracts of the same foodstuffs stated) not previously heated only 1 developed a tumour in the mamma. The incidence of spontaneous tumours in the untreated female mice is stated to be 10 per cent. and the appearance of such tumours in 9 of the 23 treated animals seems unlikely therefore to have been fortuitous. But to explain this result is not easy. It is now well known that mammary tumours can be produced in mice by painting the skin with solutions of cestrogenic substances, although the skin itself remains intact. But in such experiments the males develop mammary carcinoma almost as readily as the females, and even if prolonged treatment with oestrogens does not produce tumours of the breast it promotes development of mammary-gland tissue in the males, together with atrophy of the testis. In females, again, such treatment leads to changes in the uterus and vagina readily visible to the naked eye ; and Prof. Widmark makes no reference to the presence of such changes. One would therefore have to consider whether his tumours were due to a new group of substances which, though devoid of cestrogenic activity, are specifically carcinogenic for the mainma. Before inquiring into this possibility it will be advisable to await the publication of a detailed paper, which is promised, and the confirmation of the findings by other workers. Widmark does not mention the publications of Prof. A. H. Roffo of Buenos Aires, who for a number
1449 of years has been studying the effects produced in cholesterol by irradiation, by which this substance acquires carcinogenic properties when applied to the skin. Similar chemical changes can be brought about by heating cholesterol, and last year Roffopublished a detailed report in which he claimed to have produced cancer in the stomach of rats fed for about two years on a diet of bread and milk with the addition of equal parts of animal fats containing cholesterol, heated for thirty minutes to 350° C. A large number of animals were used and the paper is copiously illustrated with photomicrographs. These certainly show ulcerations and extensive hyperplasia of the gastric mucous membrane which Roffo describes as carcinomatous. But there were no metastases and the histological evidence for the malignancy of the lesions produced is, so far as one can judge from the photographs, not convincing. The lesions may have been due to the direct action on the gastric mucous membrane - of the cholesterol chemically altered by heating; but there is also the possibility that they resulted from interference with the usual gastric functions, caused by excess of fat in the diet. The verdict on the allegation that the processes used in preparing food-such as frying, roasting and grilling-may produce carcinogenic substances is therefore" not proven." But in view of its importance the subject should be fully investigated. There appear to be two distinct questions that require an The first is, Do these processes of cooking answer. substances which, when tested by the usual produce method of applying them to the skin, give rise to skin cancer, or, as Widmark claims, mammary cancer ? The second question is, Do these substances when ingested produce gastric cancer ? If the answer to the second question is " No " the answer to the first would be mainly of academic interest. In order to exclude from the feeding experiments the possible fallacy of producing digestive disturbances by an excess of fat in the diet, it would perhaps be well to give the experimental animals the heated fats in the form in which they are usually consumed in actual foodstuffs, such as meat or fish which has been
roasted, grilled
or
fried.
THE NATURE OF CREATIVE ACTIVITY
HITHERTO the study of creative activity has been the preserve of the philosopher and the art critic. The few psychologists, like Vernon Green and Bullough, who have experimented in psychological sesthetics, have not been in a position to use clinical material to substantiate their theories. In fact, it is doubtful whether they would have thought it possible that either psychological medicine or neurology could have helped very much. Psychiatrists have for a long time been interested in the paintings and modellings of psychotics, but the art critic has spurned their intrusions. Shaw rapped Max Nordau over the knuckles in his " Sanity of Art," and Roger Fry, more gently perhaps, replied to Freud in " What the Artist wants of Psycho-analysis." Nevertheless, psycho-analysis has illuminated the deeper issues involved in the artistic creative impulse, explaining the obscurities of artistic content, the choice of material, and the wish-fulfilments of the artist. Not enough, however, has been done to explain the processes in painting and sculpture which are so obviously associated with the conditions of visual experience, and other sensory components have not been adequately explored. 1. Bol. Inst. Med. exp.
Cáncer, 1938, no. 48, p. 407.
In studying the peculiarities of primitive art, children’s drawings and psychotic productions, Dr. Viktor L6wenfeld’1 of Vienna has appreciated the importance of direct visual experience in the normal artistic vision; he has also realised the importance of tactile and kinsesthetic sensibility, which art critics like Berenson have disclosed in the " tactile values " expressed by certain paintings, for example Massacio and the early Botticelli. Spanish critics have tried to correlate El Greco’s distortions with his alleged myopic astigmatism. Dr. Lowenfeld has confined his research primarily to the artistic productions of the blind and the partially blind. These people use non-visual imagery because they must, and consequently tactile and kinaesthetic values The haptic enter into their creative activities. type is above all concerned with projecting his inner experience into the picture. Such experience adds a new dimension to the work. In fact Dr. Lowenfeld’s researches go a long way to explain many characteristics of primitive art, modern expressionism and so-called distortions. His thesis is a solid contribution to psychology and is calculated to add much to artistic criticism and to a future science of esthetics.’ NITROUS FUMES
MEDICAL students will recall the acrid, not altogether unpleasant, fumes when they dissolved copper or silver in strong nitric acid. In lesser degree the same smell is sometimes apparent in the street on the leeward side of a brazier used by workmen. Nitrous fumes are in fact generated whenever air is heated strongly either by flame, glowing fuel, or hot surfaces of any kind. What is not very generally known is that nitric oxide may be poisonous in any concentration above 1 in 100,000; a dilution of 1 in 10,000, although it seems mildly irritant only to throat and chest, is dangerous to life if inhaled for a few minutes. In a case investigated by Dr. R. L. Guthrie at Poplar in 1934 death was shown to have been caused by nitrous fumes given off from an acetylene superwarmer used in the Dunbar Castle when lying in the West India Dock. An inspector of factories then stated in evidence that 102 parts per million of nitric oxide were given off when the appliance used by the dead man was tested in the ship. Medical evidence proved that death was due to asphyxia caused by the fumes. A. Holste records2 several cases of nitrous-fume poisoning of firemen, one of whom developed cedema of the lungs which proved fatal, while an increase in hemoglobin and red bloodcells was common to all. Recently R. J. Wright-
Smith described3 a
case
in which death from intense
pulmonary cedema and acute bronchiolitis followed a job of welding for eight hours in a closed tank which had contained sea water. In this case phosgene poisoning was not excluded ; they have in common an interval of well-being which may lead the victim to carry on long after he should have reported sick. The detection of nitrous fumes is important in view of the probability that they may be evolved in dangerous amounts during many industrial operations carried out with the aid of heat. Leaflet No. 5 of the valuable series issued by the Department of Scientific and Industrial Research (H.M. Stationery Office. 3d.) describes a trustworthy method of detection, based on the diazo-reaction of P. Griess which is 1. The Nature of Creative Activity. Trench, Trubner and Co. 1939. 2. Zbl. GewHyg. 1936, 23, 183. 3. J. industr. Hyg. 1939, 21, 24.
London : Kegan Paul,
Pp. 272.
21s.
patient being a separate problem. But evidently the experienced clinician can say with considerable accuracy when a patient is ready ; for in expert hands thyroidectomy has become one of the safest of major operations. FLYING AT MODERATE ALTITUDES
IT is widely supposed height of, say, 15,000
that repeated flights at a ft. help the airman to acclimatise himself to low atmospheric pressures. Monaco2 holds that, on the contrary, they are harmful. The aviator’s acclimatisation to high altitudes differs from that of a mountaineer; for the pilot stays only a very short time at the new level and quickly returns to the ground. Gradual adaptation to new conditions is thus rendered impossible, and according to Monaco the frequent alternation between extremes upsets the physiological mechanism. Whereas a stay on a high mountain induces an increase in the number of erythrocytes, repeated high flights cause, after a time, anaemia. True, an increase in red blood-cells has been observed in airmen, but Monaco says that it is merely temporary, is due to anoxoemia, and can only be demonstrated during and immediately after a single high flight. On the pilot’s return to earth it soon disappears and is succeeded by a progressive fall in the number of erythrocytes. Monaco claims that the results of his experiments are confirmed by the practical observations of Martin Flack and his collaborators that pilots after repeated high flights become less tolerant of them ; and of Armstrong3 that symptoms of intolerance are manifested by American commercial pilots flying not more than three hours a day at an average height of 750013,500 ft. He also reports that in Italy, during a period of ten years, sickness has been 56 per cent. Lehman, E. P., and Shearburn, E. W., Ann. Surg. May, 1939, p. 712. 2. Monaco, B., Ann. Igiene, Roma, April, 1939, p. 249. 3. Armstrong, H. G., J. Aviat. Med. 1938, 9, 84. 1.
among airmen than in the other services, a strict medical examination on entry. The trouble is ascribed to the deficiency of oxygen at high altitudes and the consequent lowering of the oxygen tension in the alveoli, producing anoxia of the tissues, shown chiefly by a diminution of reflexes. Monaco cites Strughold and Treutler as showing that even at a height of only 7500 ft. there is an obvious diminution of the patellar reflex if a respirator is not used, and he concludes that a respirator should always be worn after a height of 6000 ft. has been reached-preferably one containing a mixture of gases and with a pressure of oxygen gradually increasing pari passu with the alteration in barometric pressure.
higher despite
CARCINOGENS IN HEATED ANIMAL FATS ? TEN years ago E. L. Kennaway found that substances carcinogenic for the skin were formed when living cells, such as yeast cells or human skin, were subjected in a hydrogen atmosphere to temperatures of 700°-900° C. in such a way that slow destruction with the formation of tarry material was brought about. The same thing happened when cholesterol, a constituent of all living tissues, was treated in this way. When tarry material thus obtained was applied to the skin of mice malignant tumours developed at the site of application. The carcinogenic effect produced was a local one. Taking these observations as his starting-point, Prof. E. M. P. Widmark of the University of Lund has treated the skin of mice with alcohol- or petroleum-extracts of roasted coffee, browned butter and horse muscle heated to 275° C. The results, which he summarises in a preliminary note in Nature of June 10, are very puzzling. When the skin was painted with the extracts no effects were observed in the skin, but of 23 female mice which survived a period of application, 9 developed carcinoma of the mamma ; no such tumours developed in the males. It will be noticed that in these experiments, unlike Kennaway’s, the carcinogenic effect was not a local one. Of 26 control animals (sex not treated with extracts of the same foodstuffs stated) not previously heated only 1 developed a tumour in the mamma. The incidence of spontaneous tumours in the untreated female mice is stated to be 10 per cent. and the appearance of such tumours in 9 of the 23 treated animals seems unlikely therefore to have been fortuitous. But to explain this result is not easy. It is now well known that mammary tumours can be produced in mice by painting the skin with solutions of cestrogenic substances, although the skin itself remains intact. But in such experiments the males develop mammary carcinoma almost as readily as the females, and even if prolonged treatment with oestrogens does not produce tumours of the breast it promotes development of mammary-gland tissue in the males, together with atrophy of the testis. In females, again, such treatment leads to changes in the uterus and vagina readily visible to the naked eye ; and Prof. Widmark makes no reference to the presence of such changes. One would therefore have to consider whether his tumours were due to a new group of substances which, though devoid of cestrogenic activity, are specifically carcinogenic for the mainma. Before inquiring into this possibility it will be advisable to await the publication of a detailed paper, which is promised, and the confirmation of the findings by other workers. Widmark does not mention the publications of Prof. A. H. Roffo of Buenos Aires, who for a number
1449 of years has been studying the effects produced in cholesterol by irradiation, by which this substance acquires carcinogenic properties when applied to the skin. Similar chemical changes can be brought about by heating cholesterol, and last year Roffopublished a detailed report in which he claimed to have produced cancer in the stomach of rats fed for about two years on a diet of bread and milk with the addition of equal parts of animal fats containing cholesterol, heated for thirty minutes to 350° C. A large number of animals were used and the paper is copiously illustrated with photomicrographs. These certainly show ulcerations and extensive hyperplasia of the gastric mucous membrane which Roffo describes as carcinomatous. But there were no metastases and the histological evidence for the malignancy of the lesions produced is, so far as one can judge from the photographs, not convincing. The lesions may have been due to the direct action on the gastric mucous membrane - of the cholesterol chemically altered by heating; but there is also the possibility that they resulted from interference with the usual gastric functions, caused by excess of fat in the diet. The verdict on the allegation that the processes used in preparing food-such as frying, roasting and grilling-may produce carcinogenic substances is therefore" not proven." But in view of its importance the subject should be fully investigated. There appear to be two distinct questions that require an The first is, Do these processes of cooking answer. substances which, when tested by the usual produce method of applying them to the skin, give rise to skin cancer, or, as Widmark claims, mammary cancer ? The second question is, Do these substances when ingested produce gastric cancer ? If the answer to the second question is " No " the answer to the first would be mainly of academic interest. In order to exclude from the feeding experiments the possible fallacy of producing digestive disturbances by an excess of fat in the diet, it would perhaps be well to give the experimental animals the heated fats in the form in which they are usually consumed in actual foodstuffs, such as meat or fish which has been
roasted, grilled
or
fried.
THE NATURE OF CREATIVE ACTIVITY
HITHERTO the study of creative activity has been the preserve of the philosopher and the art critic. The few psychologists, like Vernon Green and Bullough, who have experimented in psychological sesthetics, have not been in a position to use clinical material to substantiate their theories. In fact, it is doubtful whether they would have thought it possible that either psychological medicine or neurology could have helped very much. Psychiatrists have for a long time been interested in the paintings and modellings of psychotics, but the art critic has spurned their intrusions. Shaw rapped Max Nordau over the knuckles in his " Sanity of Art," and Roger Fry, more gently perhaps, replied to Freud in " What the Artist wants of Psycho-analysis." Nevertheless, psycho-analysis has illuminated the deeper issues involved in the artistic creative impulse, explaining the obscurities of artistic content, the choice of material, and the wish-fulfilments of the artist. Not enough, however, has been done to explain the processes in painting and sculpture which are so obviously associated with the conditions of visual experience, and other sensory components have not been adequately explored. 1. Bol. Inst. Med. exp.
Cáncer, 1938, no. 48, p. 407.
In studying the peculiarities of primitive art, children’s drawings and psychotic productions, Dr. Viktor L6wenfeld’1 of Vienna has appreciated the importance of direct visual experience in the normal artistic vision; he has also realised the importance of tactile and kinsesthetic sensibility, which art critics like Berenson have disclosed in the " tactile values " expressed by certain paintings, for example Massacio and the early Botticelli. Spanish critics have tried to correlate El Greco’s distortions with his alleged myopic astigmatism. Dr. Lowenfeld has confined his research primarily to the artistic productions of the blind and the partially blind. These people use non-visual imagery because they must, and consequently tactile and kinaesthetic values The haptic enter into their creative activities. type is above all concerned with projecting his inner experience into the picture. Such experience adds a new dimension to the work. In fact Dr. Lowenfeld’s researches go a long way to explain many characteristics of primitive art, modern expressionism and so-called distortions. His thesis is a solid contribution to psychology and is calculated to add much to artistic criticism and to a future science of esthetics.’ NITROUS FUMES
MEDICAL students will recall the acrid, not altogether unpleasant, fumes when they dissolved copper or silver in strong nitric acid. In lesser degree the same smell is sometimes apparent in the street on the leeward side of a brazier used by workmen. Nitrous fumes are in fact generated whenever air is heated strongly either by flame, glowing fuel, or hot surfaces of any kind. What is not very generally known is that nitric oxide may be poisonous in any concentration above 1 in 100,000; a dilution of 1 in 10,000, although it seems mildly irritant only to throat and chest, is dangerous to life if inhaled for a few minutes. In a case investigated by Dr. R. L. Guthrie at Poplar in 1934 death was shown to have been caused by nitrous fumes given off from an acetylene superwarmer used in the Dunbar Castle when lying in the West India Dock. An inspector of factories then stated in evidence that 102 parts per million of nitric oxide were given off when the appliance used by the dead man was tested in the ship. Medical evidence proved that death was due to asphyxia caused by the fumes. A. Holste records2 several cases of nitrous-fume poisoning of firemen, one of whom developed cedema of the lungs which proved fatal, while an increase in hemoglobin and red bloodcells was common to all. Recently R. J. Wright-
Smith described3 a
case
in which death from intense
pulmonary cedema and acute bronchiolitis followed a job of welding for eight hours in a closed tank which had contained sea water. In this case phosgene poisoning was not excluded ; they have in common an interval of well-being which may lead the victim to carry on long after he should have reported sick. The detection of nitrous fumes is important in view of the probability that they may be evolved in dangerous amounts during many industrial operations carried out with the aid of heat. Leaflet No. 5 of the valuable series issued by the Department of Scientific and Industrial Research (H.M. Stationery Office. 3d.) describes a trustworthy method of detection, based on the diazo-reaction of P. Griess which is 1. The Nature of Creative Activity. Trench, Trubner and Co. 1939. 2. Zbl. GewHyg. 1936, 23, 183. 3. J. industr. Hyg. 1939, 21, 24.
London : Kegan Paul,
Pp. 272.
21s.