At the outset it may be stated that there is no longer any reason to doubt that adult scurvy and infantile scurvy are one and the same disease, having an identical pathogenesis. For many years, far longer than the facts warranted, there was discussion whether Barlow’s disease was true scurvy or merely a form or a complication of rickets, or perhaps a distinct hemorrhagic disease. This question may be relegated to the past, so that we may proceed to consider the pathogenesis of scurvy in the infant and in the adult under a common heading.
There is no need of studying all the theories which have been advanced to account for scurvy. They have been manifold and most of them have died a natural death. For many years the potassium deficiency theory, suggested by Garrod, gained wide acceptance. That scurvy should be attributed to a lack of this salt is readily comprehensible in view of the abundance of potassium in the antiscorbutic foodstuffs, the fruits and the vegetables. It was not long before it was evident that this was not the correct solution, as the salts of potassium served neither to prevent nor to cure scurvy. This theory was accordingly modified to include only organic potassium. Experiment, however, failed to support the validity of this hypothesis, and it was gradually abandoned.
Another theory which had a short but popular career was the citric acid theory, which was maintained vigorously by Netter. This explanation seemed logical in view of the marked potency of the citrous fruits, and particularly when it was shown that human milk contains a greater percentage of the salts of citric acid than cow’s milk, and that some of these salts are lost in the course of heating. This hypothesis withstood neither the practical test nor chemical investigation. It was found that the various salts of citric acid, either singly or in combination, are unable to cure scurvy. This treatment has been employed repeatedly on man and on animals with little or no success; we also have resorted to it in vain. It was shown, furthermore, that it rested on an insecure chemical basis, as boiled milk contains but 0.1 g. per litre less citric acid than raw milk—an amount which is negligible from a therapeutic point of view.
Before considering what may be termed the prevailing theories, a few lines must be devoted to the acidosis theory championed by Sir Almroth Wright. According to this writer scurvy is due primarily to an excess of acid compared with alkaline food.5 A theory of this nature was open to verification, and soon collapsed when put to the test. It was found, in the first place, that an addition of alkali was unable to cure experimental scurvy. It may be added that we have found it of no value in infantile scurvy. Holst and Froelich pointed out that potatoes and peas, two excellent antiscorbutic vegetables, have an alkaline and not an acid ash; that adding hydrochloric acid to dandelion juice improves rather than diminishes its potency; that 1 g. of cabbage, which suffices to protect a guinea-pig from scurvy, does not contain sufficient alkali to neutralize an acid state; and, finally, that scurvy is not encountered in the well-established acidosis of diabetes.
Let us turn to some of the current theories of the etiology of scurvy. For years many have held to the toxic theory, believing that poisons either were consumed in the food or formed in the intestine by means of bacterial action. At present this view is held by the minority. The situation in this respect may be compared to that of beriberi, about which there is also no consensus of opinion, a minority attributing it to the action of an unknown toxin.
A consideration of the clinical course of scurvy sheds but little light on this aspect, and can be interpreted as well for as against the action of a toxin. The nervous system, which is well known to be particularly vulnerable to toxins, is but slightly affected—the cardiorespiratory phenomena (indicating an involvement of the pneumogastric nerves), the occasional changes in the optic disks, and the abnormality of the tendon reflexes constitute the aggregate. In a general way it may be stated that the symptoms resemble those brought about by poisons of various kinds—the cottonseed poisoning in swine, the toxic products of the wheat embryo, or even mercurial poisoning in man.6 The nervous symptoms, especially the irritability of the heart, remind one of the enterogenous intoxication or enterotoxic polyneuritis described by Von Noorden. Such analogies are interesting and suggestive, but can be accorded little weight in deciding the question at issue.
If a toxin is to be regarded as the proximate cause of infantile scurvy, the question naturally arises as to the nature of the toxin. Is it exogenous or endogenous? There is sound basis for believing that the hypothetical poison is not introduced preformed in the food. In the first place, infantile scurvy frequently develops in babies who receive milk of the very best grade indeed, in contradistinction to rickets, this is not preËminently a disease of the poor. Furthermore, there is no relation between the concentration of the food mixture and its liability to induce scurvy. For example, if among a large number of infants receiving pasteurized milk from a common source, some are given the milk diluted by one-half, others given it diluted by one-third, and still others whole milk, the last group will show the least tendency to scurvy, which we should not expect were the poison contained in the food. Nor is it at all uncommon to encounter scurvy in an infant which has been fed with a very dilute milk mixture. Another side of this question should, however, be mentioned—stale pasteurized milk is more apt to produce scurvy than the freshly pasteurized, but here again the injury is in inverse ratio rather than in direct ratio to the amount consumed. There are reports of adult scurvy having been occasioned by decomposed food, such as Torup’s investigation of Nansen’s polar expedition, but the diet had not been faultless in other respects. The experiments of Jackson and Harley, who produced scurvy in monkeys by feeding tainted tinned meat, cannot be unreservedly accepted, as they are substantiated by no pathological examination of the bones, and the diarrhoea and the blood and mucus in the stools do not suggest simple scurvy.
Of those who held to the toxic origin of scurvy the majority had in mind an endogenous toxin, although the conception of the nature of this poison varied greatly. The minority report of the American Pediatric Society states that “scurvy appears to be a chronic ptomaine poisoning due to the absorption of toxins.” Neumann considered scurvy a chronic poisoning, formed probably from the albumin of the milk, and considered the fact that the infant refused to take the harmful food as weighty evidence of its toxic nature. Kohlbrugge included scurvy in his group of “fermentive diseases,” due to the overgrowth of harmful bacteria in the intestine, which are normally restrained by the acid reaction of the chyme. McCollum and Pitz, on the basis of a study of experimental scurvy, suggested that as the result of a break in the metabolism it might be due to the retention of fÆces and consequent absorption of toxins. Still more recently Gerstenberger suggested that as the result of the break in the metabolism of carbohydrates, a defunctioning substance, possibly oxalic acid, is produced, which has a strong affinity for calcium.
It is of no avail to discuss these various hypotheses—the formation of intestinal toxins—except where they are based on observations which can be tested and controlled. This is true solely of the relation of constipation to scurvy, and we shall confine ourselves therefore to a consideration of this aspect of the question.
There can be no question whether retention of fÆces of itself can bring about scurvy; this is excluded by the marked instances of constipation frequently encountered among thriving babies. The majority of bottle-fed babies and a large number of the breast-fed suffer from a greater or less degree of constipation. On looking over our records of infantile scurvy from this point of view, and comparing them with non-scorbutic infants, we have not been able to note a characteristic distinction. Some of the infants had normal stools, others suffered from constipation, while the records of a great number showed occasional loose stools. Furthermore, in cases of latent or subacute infantile scurvy, it was of no moment whether a laxative was given or whether constipation was induced by means of opium. The report of the American Pediatric Society shows that the majority have had a similar experience; the bowels were regular in seventy-four instances, irregular in fifteen, constipated in one hundred and twenty-six, and diarrhoeal in seventy-seven. In this connection, it may be pointed out that the preparation termed “malt soup,” the diet which in our experience has been most frequently associated with scurvy, is essentially laxative, and, on the other hand, that one of the most potent antiscorbutics is potato, which has no definite laxative property. It may be added, as noted elsewhere, that scurvy developed in infants in spite of their receiving cod liver oil or olive oil for long periods. It is evident, therefore, that the retention of fÆces is not the essential factor in the etiology of scurvy. Its secondary rÔle, especially after scurvy has developed, will be considered later in this chapter.
TABLE 1
Fecal Flora of Scorbutic Infants Infant. | Diet. | Date. | Scorbutic condition. | Sourceof material. | Types of bacteria. | Remarks. |
M. | Malt soup and cereal | Dec.1 | Subacute | Rectum | B. acidoph. B. bifidus M. ovalis B. coli | {Normal infant’s flora. {Gram + bac. predominant. {No spore-bearing or putrefactive types. {B. acidoph. about 40% viable bact. |
| Do. | Dec.4 | Do. | Do. | Do. | Do. |
| Same, also 20c.c. liquid petrolatum, one week | Dec.11 | Subperiosteal hemorrhage | Do. | Do. | {Relatively more B. coli. {Many B. bifidus {No putrefactive bact. |
| Same diet, oil stopped, orange juice 10 days | Dec.21 | Markedly improved | Do. | Do. | Normal infants’ flora. Bacteria as above. |
| | | | | | |
K. | Malt soup and cereal | Dec. 11 | Subperiosteal hemorrhage | Rectum | Streptococci B. coli M. ovalis | {Gram - bacteria predominant. {B. coli gram + diploc. numerous. {B. acidoph. few. |
| Do. + orange juice (60c.c.), 8 days | Dec.21 | Markedly improved | Do. | B. bifidus B. coli Streptococci | {Gram + bac. predominant. {Many B. bifidus {Streptoc. unchanged. |
| | | | | | |
S. | Formula: Cream, water, flour, sugar, also cereal | Dec.21 | Mild scurvy | Rectum | B.lact.aerog. B. coli M. ovalis B. bifidus B. welchii | {Gram + and - bact. about equal. {Many lact. aerog. {Putrefactive bact. in minority. |
| Malt soup and cereal | Feb.11 | More marked | Do. | B.lact.aerog. M. ovalis B. bifidus Dipheroids | {Gram + bact. in great majority (B. bifidus). {Spore bearers very few. {Flora not at all putrefactive. |
In order to elucidate this question Torrey and Hess made a study of the relation of the intestinal flora to the scurvy of guinea-pigs and of infants. In guinea-pigs they found in the intestinal tract merely such bacteria as are encountered on the oats and hay fed these animals. The bacteria were few in number and hardly any were actively proteolytic. Furthermore, there was no change in the flora on adding antiscorbutic food, although the scorbutic symptoms disappeared. Recently Givens and Hoffman, as the result of a similar study, have come to the same conclusion. The investigation of infants led to similar results, and is illustrated in Table 1. It will be seen that the infants were all on a high carbohydrate diet, and that in two instances the flora was compared, not only during the active scorbutic process, but after orange juice had been given for a week or more. The bacteria were such as one should expect on a diet rich in carbohydrates; putrefactive organisms were present only in small numbers; and in the case in which they were most numerous (S), they had disappeared upon the subsequent examination, although the scurvy had become more marked. It is evident, therefore, that in the scurvy of infants as well as of guinea-pigs there is no overgrowth of putrefactive bacteria in the intestinal tract, and therefore no basis for the hypothesis of ptomaine or similar intoxication. Other poisons may, however, be absorbed from the intestine as the result of a prolonged deprivation of an essential vitamine.
There are those who believe that scurvy is of bacterial origin, some going so far as to regard it as a communicable disease. This viewpoint was maintained by the famous Boerhaave and supported with all the weight of his authority by Villemin in the seventeenth century. It is a view held by many, if not by the majority, of physicians in Russia to-day, and recently has been advanced by European army surgeons. This question illustrates in an interesting manner how the trend of the day influences medical thought—it has been suggested lately by Much and Baumbach that the scurvy microÖrganism may be carried by means of lice. But clinical experience points absolutely against the infectious nature of scurvy. Indeed, the only episode which lends any support to this opinion is its widespread and seemingly epidemic character; the fallacy of such deductions has been well illustrated in regard to beriberi, which for many years was regarded as an infectious and communicable disease. The fact that whenever scurvy occurs among a body of troops the officers are spared, constitutes convincing evidence against its communicability. This peculiarity of incidence was noted by Hoerschelman and others in the recent World War, and is referred to in the Report of the War of the Rebellion. Many of the earlier writers, in discussing the occurrence of ship scurvy, drew attention to the paucity of cases among the officers.
When we turn to bacteriological studies we find that some years ago Ausset claimed to have isolated “a pasteurella type of organism” from a case of infantile scurvy, and suggested it as the causative agent of this disorder. On the other hand, Hart, Rehn, Hirschsprung, von Starck, Schmorl, and recently Boerich, have failed to find bacteria in the blood, although the total number of cultures must be admitted to have been small. Czerny and Keller report negative bacterial growth from fluid aspirated from affected joints.
The only articles considering this important question from the experimental side are those of Jackson and Moody, and of Moore, who conclude tentatively that scurvy may be a bacterial infection. Jackson and Moody cultivated a diplococcus from the tissues of scorbutic animals after death, reproduced hemorrhages by inoculating cultures of these microÖrganisms into the circulation, and recovered the bacteria from the tissues some weeks later. Their results are open to the criticism that bacteria were found only after death, and that all blood cultures during life proved negative. An article by Moore, however, which has just appeared from this same laboratory, states that “an organism of the streptococcus viridans type was isolated from the blood” in a case of adult scurvy. In one instance we recovered an organism of this type from the blood of an infant suffering from scurvy. It is highly important that more blood cultures should be carried out in the course of human or animal scurvy, and that particular note should be made of the stage of the disorder when they are taken.
There is no doubt that invasion of the blood-stream does occur readily in the course of scurvy, but this takes place generally after the disease has developed and must be regarded as a secondary phenomenon and therefore unessential from an etiologic standpoint. Indeed one of the striking and important symptoms of scurvy is the marked susceptibility to infection (furunculosis, nasal diphtheria, “grippe,” etc.), which comes about as the result of the nutritional disturbance. An excellent example of this interrelationship is the “epidemic” of hemorrhagic scurvy described in the chapter on symptomatology. Hemorrhages coming about in this way should be regarded as focal complications rather than as truly scorbutic. It should be realized that, at the present time, it is not possible to distinguish between local symptoms which are truly nutritional or scorbutic in nature, and those which are bacterial and of secondary origin.
The newest theory, and the one at present most widely accepted, is the vitamine (accessory factor) theory. It was evident to Lind in the seventeenth century that scurvy could be prevented and cured by means of fruits or vegetables, a fact which became increasingly clear to succeeding generations. Until the latter part of the nineteenth century, however, this miraculous virtue of plants stimulated little inquiry and no research. As far back as 1841 Budd realized that “the explanation depended on the study of organic chemistry, and the experiments of physiologists,” but until recently it was not perceived that the solution of the problem involved the introduction of a new chemical factor. This view suddenly took shape after Eijkman in 1897 showed the nature of polyneuritis in fowl, and Hopkins in 1906, going a step farther, demonstrated the necessity of one or more unidentified food factors for the normal nutrition of the rat. The work which established this novel theory on a scientific basis in relation to scurvy was the classic investigation of Holst and Froelich, referred to so frequently in connection with experimental scurvy. These investigators showed that the mere drying of vegetables was sufficient to deprive them of their antiscorbutic power, although from a chemical standpoint they seemed unaltered; that high degrees of heat had generally the same effect; that under certain conditions these foods withstood prolonged heating, demonstrating that the antiscorbutic factor was not a ferment; that acids and alkalies played no essential rÔle in the etiology; that fats, proteins and carbohydrates were not significant factors; that as little as 1.0 g. of cabbage suffices to afford protection to a guinea-pig. In other words, by a process of exclusion they showed that it is a disorder due to the lack of an unidentified food factor.
Subsequent studies, carried out within the past few years, have served only to strengthen this viewpoint. For example, an “artificial orange juice” composed of the various salts, citric acid, and sucrose in the proportions in which they are found in the natural juice, failed, in the experience of Hess and Unger, to protect or to cure guinea-pigs—demonstrating that this preparation did not contain the essential factor. In the same way, Harden and Zilva were able to protect animals from scurvy with a preparation of lemon juice which had been almost entirely deprived of its salts. It is needless to multiply these examples. It is sufficient to state that there has been no investigation during the last years of intensive study of scurvy, which has tended to weaken the vitamine hypothesis. It may be stated, therefore, that experiments have demonstrated that scurvy is due essentially to the lack of a specific vitamine. It is unwise to proceed farther and place it in the group of so-called “deficiency diseases,” including beriberi, pellagra, etc., unless the reservation is made that these several diseases may present marked differences. It is quite possible that one may be what might be termed a simple deficiency disease, whereas another may have important additional etiologic factors. At any rate, unless it is realized that there has been no proof that all are due to similar deficiencies, we may, by stamping them all alike and by grouping them together, be misled into taking their close relationship for granted. In regard to scurvy, there may well be other etiologic factors, but they are of a secondary character. Bacterial invasion has been referred to in this connection, and it is possible that toxins are absorbed from the intestine after nutrition has been disturbed. Diarrhoea and digestive disturbances may play a rÔle. Whether the total intake of food or the correlation of its constituents—protein, carbohydrate, fat and salts—affects the action of the vitamine, is one which has not been well studied clinically or experimentally. In regard to beriberi, it is claimed that there is a direct ratio between the quantity of carbohydrate ingested and the amount of vitamine required. No such interrelationship exists in regard to scurvy. This was evident a few years ago (1917) when some infants receiving pasteurized milk, prepared with the addition of 3 per cent. flour, did not tend to develop scurvy more readily than others receiving simple pasteurized milk. A consideration of the antiscorbutic vitamine will be postponed for a subsequent chapter.
Etiology.—In considering infantile scurvy we are concerned almost entirely with the artificially-fed baby. It is true that in the literature we meet with scattered reports of scurvy in breast-fed babies and that these cases seem to constitute a noteworthy group; in point of fact, they are comparatively few. The collective investigation of the American Pediatric Society includes ten infants who had been given breast milk exclusively, and Concetti adds another ten in his compilation of 682 cases.7 In spite of their paucity these cases require separate consideration because they represent an important aspect from an etiologic standpoint. How are we to explain the fact that human milk may lead to rather than protect against this disorder? On investigating more closely it is found that these cases differ in several important respects from the group which has been artificially fed. They are of a different age; instead of being in the second half year of life they are generally but a few months old. Furthermore, the signs are not the same. The hemorrhages involve the upper extremities fully as frequently as the lower extremities, and often appear at unusual sites—for example, on the scalp or as large subcutaneous effusions at various parts of the body. In many instances it has been noted that the nursing mothers were suffering from some debilitating disease such as tuberculosis or syphilis, or had an insufficient supply of milk, or that there had been some other unusual factor, as Freund has shown in an article devoted to this particular aspect. It is not necessary, however, to fall back on these attendant circumstances to exclude from consideration many of the cases. For example, Crandall’s case of “scurvy in an infant of six weeks” should be invalidated, not because, as Freund suggests, the mother had rheumatism and insufficient milk, but because of the age of the infant, and the course of the disease; first one arm was involved, then the other, then hemorrhages appeared on the skin, and finally it was cured by giving a teaspoonful of fresh cream before each nursing. Had the baby really suffered from scurvy it could not have been cured by this means. Southgate’s case must also be rejected, not because the mother was tuberculous but in view of the symptoms—the arms and legs were pseudoparetic, “the legs, feet and hands were double their normal size,” and moderately large hemorrhages were present on the back and chest. It seems hardly necessary to discuss in detail the score of cases which comprise this group, as, in general, the same criticism applies to all. Some evidently were congenital syphilis, still more must be regarded as sepsis, and others as unknown toxic conditions. Apart from these cases the question must be considered whether scurvy can occur in a breast-fed infant. Personally, we have never met with a case of this kind, and, as Finkelstein aptly remarks, there has been “no necropsy of a breast-fed case or conclusive X-ray picture.” It seems possible only if an infant, for a period of months, has obtained a scanty supply of milk, or when the milk has been exceedingly deficient in the antiscorbutic vitamine. Even under such conditions it does not seem possible for scurvy to become manifest in six weeks (Crandall’s case), or in four weeks, as in a case reported by the American Pediatric Society, unless we believe that the infant suffered also from a certain degree of intrapartum or congenital scurvy. In view of the fact that an infant requires about one pint of milk to furnish it with an adequate daily quota of the antiscorbutic factor, it is theoretically possible, under extreme conditions, for it to become scorbutic, in spite of being nursed at the breast. Such an occurrence must be regarded as exceedingly rare, far more so than the current statistics illustrate, for considerably less than a pint of milk a day will prevent the appearance of manifest scurvy for a period of several months. Some of the reported cases may have been latent scurvy, rendered acute by a complicating bacterial infection.
It might be expected that by ascertaining the occurrence of infantile scurvy in countries where it is endemic, we could learn under what conditions and how frequently breast-fed babies develop this disorder. Approaching the question from this angle, it is found that the available data is meagre and not entirely convincing. Peculiarly enough infantile scurvy has rarely been reported from Russia, where scurvy is, in many sections, endemic. For example, although Tschudakoff, who personally examined over 10,000 persons, in connection with the great scurvy epidemic in Russia (1898–99) found 11.11 per cent. of the people suffering from this disease, he did not meet with a single case under the age of five years. Fuerst writes that Filatow, the celebrated Russian children’s specialist, declared that he knew of no instance of Barlow’s disease described in the Russian literature.8 Shortly after the recent war scurvy broke out among the wet-nurses in an infant asylum in Vienna. A very few of the infants nursed by these women developed the disorder, far fewer than might have been expected (personal communication). Hopkins recently wrote a communication to the effect that in the island of Aruba, in the Dutch West Indies, they had been unable to grow any crops in 1912, 1913, 1914, that 3000 cases of scurvy had developed there during the year 1915, and that in 1917 it was again being noted. In answer to a personal inquiry regarding the occurrence of scurvy among the infants of Aruba, he wrote that “infantile scurvy is very rare,” although “most all of the babies are breast-fed for about a year.”9
On the other hand, descriptions of the coincidence of scurvy in mother and nursling are even more fragmentary; in fact, we have been able to find but two reports of this kind. The one most frequently cited is that of Cheadle, which consists merely of the following bald statement: “With the exception of one or two doubtful cases, of which the details of breast-feeding and diet are imperfectly given, the only instances of scurvy arising in sucklings are those when the nursing mother has been suffering from scurvy at the time.” The other report has been gleaned from a recent editorial in the British Medical Journal, which refers to the above mentioned outbreak of scurvy in Vienna, affecting in some cases both mothers and breast-fed infants.
It is difficult to pass judgment on this question in view of the paucity of data. In the near future, probably, when we learn in detail about the epidemics of scurvy which occurred during and immediately following the war, we shall be in a better position to weigh its pros and cons. In view of the above data it does not seem that nursing infants readily develop scurvy, even though their mothers do not obtain a full quota of antiscorbutic vitamine in their food. This appears to be the clinical result, whatever its interpretation may be. It cannot be explained on the assumption that human milk contains a particularly large quota of this factor. In a test carried out to elucidate this question it was found that eight ounces a day of breast milk was insufficient to alleviate the symptoms in a case of scurvy, and that twelve ounces barely sufficed. This milk was from a woman who was on a liberal diet containing an adequate supply of vegetables. It had been previously demonstrated that sixteen ounces of cow’s milk is sufficient to cure infantile scurvy, so that it is evident that human and cow’s milk do not differ essentially in this respect. There are, however, other factors to be considered—for example, the incomparable freshness of the milk suckled from the breast, which may endow it with additional potency, or the possibility that the lack of vitamine may be compensated for by the large quantity of milk consumed. It also may not be entirely immaterial whether the vitamine is supplied in one dose, as, for example a daily feeding of orange or tomato juice, or whether this factor is furnished to the infant in frequent small quantities in the mother’s milk throughout the day. In this connection we cannot help contrasting the relation of beriberi to breast feeding. As is well known, infants which develop beriberi are almost always nursed and not bottle-fed, and show signs of this disorder, although the mothers are in apparent health, and give no clinical evidence of disease.
Turning to a consideration of the artificially-fed infant, there exists a somewhat similar situation in regard to the occurrence of scurvy on a diet of raw cow’s milk. In almost all reports of this kind the quantitative viewpoint is entirely disregarded, and little or nothing is stated to indicate how much milk the infant consumed. And yet this factor is of essential importance in interpreting the cause of the nutritional failure. It is clear, for example, that if a baby receives but eight ounces daily of raw milk—one-half the requisite amount—it may well develop scurvy, notwithstanding the fact that the milk has not been heated. In addition to the quantity, there are other factors which play a greater or less rÔle in the relation of raw milk to the etiology of scurvy. It is no doubt of consequence whether the fodder of the cows was rich or very poor in the antiscorbutic factor, and, accordingly, whether the baby received what may be termed an “antiscorbutic-rich” or an “antiscorbutic-poor” milk. Furthermore, the age of the milk must be borne in mind, for we have found that even raw milk loses some of its potency on becoming stale.10
One of the mooted questions relative to the etiology of scurvy is the rÔle of heated milk, and more particularly of pasteurized milk. In view of the vogue which pasteurization has acquired in the large municipalities, especially in the United States, this aspect has assumed increasing importance, and deserves detailed investigation. Pasteurization has achieved so much in limiting the infectious diseases, especially the diarrhoeal disorders of infancy, that it has come to be looked upon as heresy to deprecate its virtues in any regard.
It has become increasingly evident that in the course of pasteurization milk loses an important measure of antiscorbutic vitamine. The term pasteurization, when employed in this connection, is not meant to be synonymous merely with the heating of milk to 140° to 165° F., but embraces the entire commercial process—the heating, handling, subsequent cooling, aging and all other factors involved. There can be no doubt that milk which has undergone this elaborate treatment has suffered in its antiscorbutic property. In 1914 Hess and Fish reported mild cases of scurvy occurring among infants who had received milk heated to a temperature of 165° F. for thirty minutes. This degree of heat is claimed by many physicians and hygienists, including the National Commission on Milk Standards, not to destroy its chemical constituents. Nevertheless typical cases of scurvy supervened after this diet had been followed for a period of six to nine months. Subsequent experience, published by Hess in 1917, with milk heated to only 145° F., served to confirm the previous observations. That these cases were true scurvy was proved by the fact that a cure resulted when raw milk was substituted. A similar experience in Berlin reported by Neumann and others was convincing, but was not heeded in this country. In 1901 one of the largest dairies in that city established a pasteurizing plant where all milk was raised to a temperature of about 60° C. After an interval of some months infantile scurvy began to be reported from various sources throughout the city. Neumann depicts the situation as follows: “Whereas, Heubner, Cassel and myself had seen only thirty-two cases of scurvy from 1896 to 1900, the number of cases suddenly rose from the year 1901, so that the same observers—not to mention a great many others—treated eighty-three cases in 1901 and 1902.” At a spirited meeting held by the Berlin Medical Society in 1903 to discuss this subject, Heubner was able to report 65 cases. An investigation was made, and the pasteurization discontinued. The result was almost immediate, the cases decreasing just as suddenly as they had increased. These reports and others demonstrate that unless additional antiscorbutic food is given, a diet of pasteurized milk will lead to the development of scurvy. As the antiscorbutic vitamine is not entirely destroyed by pasteurization, the severity of the disorder will be in inverse ratio to the amount of milk which is consumed.
It has been our experience that milk pasteurized in the home or institution did not lead to scurvy to the same extent as that which was commercially pasteurized. Babies fed on home-pasteurized milk did not develop manifest scurvy. The difference in the two processes consists mainly in the amount of handling during the process of heating and the subsequent aging which the milk undergoes. An interval of forty-eight hours usually elapses between commercial pasteurization and the delivery of the milk to the consumer. In New York city most of the better-grade milk is pasteurized at the farm, so that it is subjected to a longer period of aging than the poorer grade, which is not pasteurized until it reaches the city. Although our results indicated the effect of freshness or staleness on milk which had been heated, they showed also that other factors must be involved, for home-pasteurized milk which is forty-eight hours old is superior to the commercial product of the same age. This difference we believe is due to the handling which the milk undergoes, to the mechanical processes involved in commercial pasteurization.
In considering this aspect of the development of infantile scurvy on a diet of heated milk, it is of interest to refer to the experience of Switzerland and of France. In 1907 Bernheim-Karrer reported nine cases of scurvy which occurred on “homogenized” milk. This milk is forced between rapidly-rotating surfaces at a temperature of 55° to 65° C. at a pressure of 150 atmospheres. This process had been introduced the year previous by a large dairy which was well known for its excellent grade of milk. Before this innovation, milk usually had been boiled for a long while before being fed to infants. In France a similar epidemic of scurvy followed the introduction of the use of homogenized milk (lait fixÉ). Lecornu gives an interesting account of this episode, remarking on the large number of cases of scurvy occurring on this milk compared with sterilized milk, which was employed so much more extensively. These experiences furnish excellent examples of the harmful effect of industrial methods on milk, especially on its antiscorbutic vitamine. Lecornu also emphasized the scorbutic influence of “lait maternisÉ,” which is similar to the German Gaertner milk, and is subjected to dilution, centrifugation, and sterilization.11 He states that before this preparation was introduced scurvy was practically unknown in France. Lecornu attributes the deleterious effect of the “lait maternisÉ” and the “lait fixÉ” to bacterial contamination, as does Bernheim-Karrer. We believe, rather, that its loss of potency is due to the mechanical processes to which it has been subjected.
Boiled and, more particularly, sterilized milk, is regarded as a common cause of infantile scurvy and figures prominently among the foods held accountable for this disorder. It has been pointed out, however, that thousands of infants, especially in Europe, receive milk of this kind, and do not develop scurvy. Statistics such as those of Variot, who has distributed in his out-patient department, during a period of twelve years, 400,000 quarts of sterilized milk (heated in half-litre bottles and hermetically sealed at the farm) without observing a case of scurvy, must be accorded weight in this connection.12 Escherich, some years previously, stated that he did not meet with scurvy in Graz, although he was accustomed to feed babies on sterilized milk. Budin, the celebrated French children’s specialist, writes: “As for the so-called infantile scurvy which is alleged to follow the use of sterilized milk, I have heard a very great deal about it during the last few years, but I am still looking for my first case.” Evidence from such sources cannot be summarily cast aside, but must be given due consideration. It is evident that the mere heating or sterilization of milk, although it reduces the antiscorbutic vitamine, does not do so to a degree sufficient to lead to the production of clinical scurvy. Our experience accords with that of the above observers. Some years ago we fed infants with milk which had been boiled for five minutes, and, at another time, made use of home-made evaporated milk which had been heated for a period of seventeen hours, until it had been reduced to one-eighth its volume. This evaporated milk was well borne for months, although slightly caramelized in the course of heating, and did not lead to any signs of scurvy. Clearly there are other factors involved in this question besides the mere subjection to heat. We believe that every step in the process is important—the freshness of the milk, whether or not it is agitated and exposed to the air, whether it is sealed carefully and used soon after sterilization,13 and, finally, whether the baby receives a sufficient quantity. If this milk, which has certainly lost some of its vitamine content, is given in small amount, it will not supply an adequate amount of the antiscorbutic factor.
Neumann, Czerny, and others state that they have even cured infantile scurvy by giving boiled milk obtained from a different source. In the Berlin epidemic, Neumann laid particular emphasis on the fact that the milk which induced scurvy had been doubly heated, having been pasteurized commercially and later boiled in the home before it was fed to the baby. Plantenga has also laid stress on the influence of two-fold heating, citing an interesting experience with scurvy in his clinic. When the milk was pasteurized one day and boiled for five minutes on the subsequent morning, 23 cases of infantile scurvy developed among the 200 infants attending his dispensary. The following year when the procedure was altered so that the milk was merely pasteurized, no case of this disorder developed. There can be no doubt that milk which has been heated twice must have lost more of its antiscorbutic properties than milk which has been heated but once, and that aging also must contribute to this loss. Whether there is what may be termed a peculiar sensitization of milk following pasteurization, has not been definitely shown.
Up to the present time dried milk has played an insignificant rÔle in the etiology of infantile scurvy. One of the factors which has hindered the general acceptance of dried milk by physicians and laymen has been the fear that its use might lead to the development of Barlow’s disease. It is therefore important to consider this aspect of the subject, especially as dried milk seems destined to be used to an increasing extent. A recent report to the Local Government Board by Coutts states that “Millard and Naisch in England confirmed the testimony of Miele in Belgium, and Gautier and Genevoix in France, that scurvy is not to be feared” from this foodstuff. This coincides with our experience, namely, that dried milk not only does not lead to scurvy, but may contain sufficient antiscorbutic vitamine to cure this disorder. Recently a scorbutic baby was fed with milk which had been dried by the so-called Just-Hatmaker process—whereby it is subjected on a drum for a few seconds to about 230° F.—with the result that the hemorrhages of the gums began to be absorbed in about three days, and all symptoms to disappear shortly thereafter. This infant received dried milk to the equivalent of 24 ounces of fresh milk, and this preparation had been dried and canned somewhat over three months before it was used. Recently two infants, suffering from marked scurvy, were treated with milk which had been dried six months previously. The one received only sixteen ounces a day and the other a quart; both recovered within a few days after this food had been substituted for malt soup. Not long ago, as reported elsewhere in a paper by Unger and myself, after curing a baby of scurvy by means of this milk, it was maintained in health for a subsequent period of three months on a diet which contained no additional source of antiscorbutic vitamine. These results are emphasized as illustrating the peculiar relationship of drying and of the application of heat to the antiscorbutic vitamine, and because recently several reports have appeared, for example, that of Barnes and Hume in England, and of Hart, Steenbock and Smith in this country, to the effect that dried milk is devoid of antiscorbutic value. The difference of opinion is due to the assumption that dried milk is a uniform product and has identical antiscorbutic properties. For milk to retain its antiscorbutic value, notwithstanding drying, it must have been rich in vitamine before desiccation, it must have been dried quickly, and packed within the shortest possible interval in air-tight, preferably hermetically sealed, containers. As in relation to the heating of milk, so in regard to its drying, it is not the degree of heat to which it is subjected which is all important, but rather the associated conditions. The merits of each process will have to be tested individually and perhaps even each particular brand of milk.14
In the foregoing, the dictum has been accepted without comment that fresh milk may be either rich or poor in antiscorbutic vitamine. This point of view has recently gained general acceptance, on the assumption that the milk of the stall-fed cow is markedly deficient in this factor. Recent work by Hart, Steenbock and Ellis gives evidence that “summer pasture milk is much richer in this nutritive factor than dry feed milk or winter produced milk, involving the use in the ration of corn silage or sugar mangels.” In some experiments (unpublished) we have found that dried milk shows similar variations, being a much more potent antiscorbutic when obtained from cows fed on fresh fodder than a similar milk from the same cows on fodder containing a minimum amount of antiscorbutic vitamine. The supposition of a direct quantitative ratio between the antiscorbutic intake in the food and output in the milk needs confirmation, especially as it does not quite coincide with the experience among human beings in countries where adult scurvy is endemic. In such countries—for example, Russia—nursing infants do not develop scurvy to the extent that would be expected, and it is possible that this exemption is due in part to a selective secretion of antiscorbutic vitamine into the milk.
As is well known, a diet of condensed milk leads to scurvy. This is not surprising, considering the prolonged heating to which this milk has been subjected. It is probable that many cases of mild scurvy developing on this food and characterized by beading of the ribs (rosary) and other indefinite manifestations, have been erroneously diagnosed as rickets.
It is hardly necessary to discuss separately the various kinds of milk which have led to scurvy in the course of infant feeding.15 The principles laid down in the preceding discussion hold good for milk of all kinds. Heat will destroy a certain amount of vitamine, and, if the heating is followed by aging, still more will be lost. If an interval elapses and a second heating ensues, there will be further loss of vitamine. It should never be forgotten in considering foods in their relation to the causation of scurvy, that the amount of food given must not be overlooked. For example, a pint of ordinary pasteurized milk will lead to scurvy, whereas a quart in most cases will be sufficient to tide the baby over until the period of mixed feeding. No general rule can be laid down, however, as may be judged from the fact that dried milk which has been subjected to almost all the influences which are deleterious to the antiscorbutic vitamine—heating, drying, aging, all carried out in a neutral medium—nevertheless retains its specific potency.
Infantile scurvy has always been far more prevalent in England and in America than in Europe, notwithstanding the fact that on the continent practically all milk for babies is boiled or sterilized. This has been ascribed, and probably rightly so, to the widespread usage of proprietary foods in the English-speaking countries. Among the cases reported by the American Pediatric Society about 60 per cent. had been given foods of this description. How is this relationship to be explained? These preparations in general may be stated to consist of cereals, sugar, with occasionally a small amount of dried milk; they are mixed with varying proportions of water and milk and then cooked. It is evident that two important causative factors of scurvy are thus furnished, namely, a small and inadequate quota of milk and the application of heat. In most instances not more than sixteen to twenty ounces of milk are used to make up the day’s feeding, and frequently this has been previously pasteurized. But there is an additional factor which comes into play in this connection, one to which we have recently drawn attention in treating of “The Deleterious Effect of the Alkalization of Infants’ Food.” It has been shown that the antiscorbutic vitamine is peculiarly sensitive to the faintest alkaline reaction, in which medium it rapidly undergoes deterioration, and even total destruction if heat is applied. Proprietary foods, with but few exceptions, are alkaline, having been rendered so by the addition of potassium carbonate or bicarbonate, in order to prevent acid fermentation of the fat and to counterbalance the relative poverty of potassium in cow’s milk. Little or no regard has been paid to this reaction; the textbooks on children’s diseases give this point no consideration whatsoever, expressing the salt content merely in terms of total ash. By this means ideal conditions are furnished for the destruction of a large part of the vitamine, and if this factor is not present in excess, scurvy will readily develop. It is to these various circumstances—the deficiency of milk, the alkalinity and the heating—that the scorbutic quality of proprietary foods is to be ascribed.
The most flagrant example of an infant’s food leading to scurvy is “malt soup”—an alkaline preparation of malt, which is prepared with flour and a small amount of milk.16 This food brings about scurvy almost invariably unless an antiscorbutic is added to the dietary. That this effect is due to the alkaline potassium carbonate was shown by a recent test which is illustrated in chart. (Fig. 2). Here we see that in a case of scurvy, when the food was altered and prepared with the same amount of milk and alkali, the disorder did not abate (although the carbohydrate had been discontinued), but when the potassium carbonate was omitted a gain in weight ensued, and, we may add, the symptoms disappeared.
A test of this kind once more raises the question whether carbohydrates lead to the development of scurvy. As previously stated, there are many who believe that the carbohydrates, especially starch, have this harmful effect by requiring a large amount of the various vitamines for their metabolism. This relationship was first brought forward by Bradden and Cooper in regard to beriberi. It is a suggestion which cannot be disregarded in view of the great amount of scurvy which comes about on diets rich in carbohydrates, especially those containing malt sugar. We do not believe, however, that the harmful effect which this foodstuff exerts can be explained on the above hypothesis, as experience has shown that infants may receive for many months equally large amounts of carbohydrates—cane sugar, flour, or a combination of both—and nevertheless not manifest a similar tendency to develop scurvy.
Age Incidence.—Scurvy may occur at any age if the diet does not furnish sufficient antiscorbutic factors. As a matter of fact, it is encountered most often among infants and adults, not because these two age-groups are particularly susceptible, but because there are peculiar attendant circumstances. In the case of the infant, it is due to the fact that for almost the entire first year of its life it is dependent entirely upon milk, a foodstuff poor in antiscorbutic vitamine, and containing, under favorable conditions, barely enough to meet its requirement. If, therefore, the potency of the milk is weakened, or if an insufficient quantity is fed, and more particularly when both of these factors are involved, a scorbutic condition will ensue. The reason why older children, those over one and a half or two years of age, do not develop scurvy is largely due to their varied and liberal diet, which is amply provided by the mother or guardian, so that even in times of want they receive more than their due share of the available food supply.17
From a clinical standpoint scurvy may be said to occur in infants during the second half year of their lives. There is general agreement on this point; it is borne out by the investigation of the American Pediatric Society and by the statistics of various individuals. On the basis of a large experience, Still states that nearly eighty per cent. of the cases appear between the ages of six and ten months, and that in no case did the disorder occur before the age of five months. It is of importance from both the etiologic and the therapeutic standpoint to distinguish clearly between the age when infantile scurvy is commonly diagnosed, and the earlier stage when it appears as a general nutritional disorder. We must remember that scurvy generally takes from six to nine months to become manifest, this developmental period varying mainly in proportion to the degree of the dietary deficiency. It is evident, therefore, that there must be a prolonged period of nutritional failure which precedes the diagnosis. This stage consists of two early phases, the first months where the faulty diet causes no apparent change and seems to have no deleterious effect on the infant, and the second, of latent and subacute scurvy. The “latent” condition is one merely of unsatisfactory nutrition and retarded growth, which it is not possible to interpret; “subacute scurvy,” which develops subsequently, is distinguished by characteristic signs and symptoms. We shall not review their symptomatology, as it is given in the chapter devoted to this topic. The subject is brought forward in this connection to emphasize the fact that the scorbutic condition occurs far earlier than is generally realized, and furthermore, that if the earlier and more subtle symptoms of scurvy were comprehended, the age incidence would fall earlier than the current figures indicate. The earliest instance of this disorder which we have seen occurred in a baby four and a half months of age.
Age does not seem to play a definite rÔle in regard to the incidence among adults. Scurvy frequently has been encountered among old men, and is of common occurrence among the most vigorous of the nation, the young soldiers and sailors. Some have stated that it takes place less often among soldiers in the twenties than among those in the thirties, but this has not been demonstrated. The fewest cases have been reported among children over two years of age. It was due to the apparent immunity of this age-group that, until very recently, German writers doubted the identity of infantile and adult scurvy. The exclusion of children of this age is merely fortuitous and, moreover, is by no means absolute. One of the earliest cases of scurvy in children, reported by Montfalcon, occurred in a child six years old. Bateman in America described a case in a child of about this age. Barlow, in one of his first articles, reported scurvy in a small group of older children. The case so frequently quoted by German authors in this connection is that of Fraenkel, who described both clinically and pathologically a case of scurvy in a boy eight years of age. These cases by no means exhaust the number which are reported. Recently, Tobler has given us an account of scurvy, occurring during the war, in a Viennese foundling asylum which harbored children between the ages of two and fourteen.
Season and Climate.—Many of the older writers laid great stress on the influence of season on the occurrence of scurvy, which they believed broke out particularly in the cold and damp months of the fall, winter and early spring. It is true that most of the epidemics have occurred at these seasons of the year. This is merely what should be expected, considering that the disease depends mainly upon the supply of fresh fruits and vegetables. Where conditions are abnormal, as in war, there have been notable exceptions to this seasonal incidence. In the “Report of the War of the Rebellion” there is an instructive graph illustrating the occurrence of scurvy in our Civil War and in the Crimean War, which shows that this disease prevailed to the greatest extent during the winter months in the former, whereas in Crimea, the season of greatest frequency was the summer time. One of the severest outbreaks of scurvy on record is that which occurred at the siege of Thorn in Germany in the year 1703. During the months of July and August, when the weather was excessively hot, scurvy ravaged the besieged army. There are, furthermore, many reports of scurvy in the tropics during the dry season. In the island of Aruba, in the Dutch West Indies, which has been visited by scurvy year after year, and which is referred to elsewhere, the disease is endemic during the dry, hot season. Formerly it broke out on the men-of-war and vessels of the mercantile marine while they were in southern waters. As regards infantile scurvy, it has always seemed to us that season played a slight rÔle; that cases which occurred in the summer tended to be less severe and to be characterized by periods of intermission rarely observed in the winter time.
The effect of climate has been accorded a variable place in the etiology of scurvy. Lind believed that a damp, cold climate, such as that of the Low Countries, was conducive to scurvy. On the other hand, since it is realized that diet is the essential element, all other factors have been regarded as of no moment whatsoever. It is difficult to pass judgment on this question, since scurvy is now endemic in such a limited area of the world. It seems quite possible that a damp, cold climate, which depresses the various functions of the body, may exert an influence where the quota of antiscorbutic foodstuff is not quite adequate. Exposure to infection is also greater under such climatic conditions.
Economic status has to be considered in connection with infantile scurvy. Numerous writers have drawn attention to the fact that scurvy is seen relatively more frequently among the infants of the well-to-do and the rich than among those of the poor. This curious and paradoxical situation is due to the zealous care which the former receive—the extreme precautions in sterilizing the milk, the addition to the formulas of expensive proprietary foods, the watchfulness to avoid the child’s obtaining a chance bit of fruit or vegetable. Since the popularization of commercially-pasteurized milk in the larger municipalities, and the advertising propaganda for the sale of “baby foods” which has extended their use among the masses, this distinction in the social status has been largely obliterated.
Sex seems to play no part in the etiology of scurvy. Several writers have claimed, however, that there is a certain degree of racial immunity. For example, Sheppard reports that the Zhob Kakai seldom develops scurvy, although he naturally excludes vegetables from his diet, and Boerich noted among the prisoners of war that the Slavs, especially the White Russians, were more susceptible.18 Of course a lack of susceptibility of this nature can be merely relative. Such a racial distinction may seem far-fetched, but if we admit that disposition and habits of life can play a rÔle, it is quite possible for races to vary in their predisposition to this disorder. Moreover, we shall see that individuals differ markedly in this respect. Lind and others repeatedly emphasize the fact that the indolent and slothful sailor was stricken with scurvy far oftener than the one who was active, and claimed that physical exercise even tended to bring about a cure.19 Those who have had a large experience with scurvy in adults are almost unanimous in believing that a psychic element enters into its etiology. In this way, in a measure, they account for the frequency of scurvy among defeated troops, in besieged armies, and among men depressed by homesickness, fatigue, and discouragement. This point of view cannot be lightly disregarded, bearing in mind that depressed mental states alter the functions of the organs and markedly affect secretion. The many cases and epidemics in institutions for the insane cannot, however, be attributed to this cause, but are probably almost entirely due to a want of supervision of the dietary. Among infants, the question of the influence of race and of the mental state needs but little consideration.20 For some time we have carefully observed the course of scurvy among happy and contented infants compared with those of an unhappy and fretful disposition; in some instances the former, although the diet was similar, seemed to develop scurvy less readily than the latter.
There can be no doubt that there is predisposition to scurvy, as there is, probably, to every nutritional disorder. Among soldiers and sailors a certain number develop scurvy on the same ration which does not harm others. Some years ago when scurvy developed among a group of infants fed on pasteurized milk, this idiosyncrasy was noted. The distinction, however, is rarely sharply defined. Careful clinical investigation will generally show that the infants which seem to be spared are not thriving quite normally; they are somewhat pale, and do not gain in weight as they should, and their appetite is poor. The most interesting experience of this kind is the following which is frequently cited: In a family where the first child developed scurvy, Finkelstein took the precaution, in the case of the second child, to have the milk boiled for as short a time as possible, and to begin mixed feeding early. In spite of these precautions this boy also developed scurvy. Finkelstein states that once before he had met with a similar mishap. An experience which he relates, regarding a foster-mother, an excellent nurse, who had three infants in succession develop scurvy in spite of preventive measures, is also of interest in this connection. The latter occurrence evidently cannot be attributed to hereditary or family predisposition, and serves to emphasize the inherent difficulties of the subject. v. Starck’s report of an instance where twins were fed on similar milk mixtures and one developed scurvy, whereas the other thrived satisfactorily, is a striking illustration of the rÔle of idiosyncrasy. This case, as well as many others, fails to be absolutely convincing in view of the fact that the daily intake of milk is not recorded.
A predisposition to scurvy cannot be ascribed to a condition of general malnutrition. For example, among infants it has never seemed that those suffering from marasmus or atrophy were particularly prone to develop scurvy. Whether syphilis, tuberculosis or malaria tends to precipitate the onset of this disorder cannot be stated.21 In view of the fact that prematurity is such an important factor in the pathogenesis of rickets, it would be of interest to know whether a similar relationship exists between infantile scurvy and prematurity. The only clinical condition which we have found predisposing to scurvy is the “exudative diathesis” of Czerny, a term which implies a tendency to develop exudations of the skin or of the mucous membranes. Probably it is not without significance that in this diathesis the blood-vessels may evince a decided weakness, an increased permeability, as demonstrated by the “capillary resistance test.” (See Symptomatology.)
Nothing whatsoever is known regarding the possible influence of the fat, protein, carbohydrate and salt content of the diet on the development of scurvy. Is it entirely immaterial whether one or another food element largely predominates, or is the antiscorbutic factor to some extent modified by other components of the food? Influences of this kind, which at most are secondary, cannot be ascertained by the biologic test which at present has to be relied on to measure the development of scurvy and the potency of antiscorbutics. It is quite possible that the course of scurvy may be affected by the character of gastric and intestinal digestion, by the activity of the glands which pour their secretions into these organs, by the destruction or elimination of the antiscorbutic factor in the food. The frequent association of dysentery and scurvy noted during the recent war and referred to by many previous writers, shows the effect of intestinal disorders. These hypotheses are tentatively advanced because it is evident that some factor exists, apart from the mere antiscorbutic value of the diet, which at times exerts a potent influence on the development of scurvy. Cases developing in spite of a moderate amount of antiscorbutic food, and others not responding to the addition of vegetables or fruit to the diet—although not numerous—have occurred too frequently and have been reported by too experienced observers to be brusquely disregarded. For example, Neumann, one of the keenest clinical students of scurvy, stated that he had met with four instances of this nature. Hess and Fish reported two similar experiences.
The secondary etiologic factors are mainly predisposing; a few words, however, must be added concerning what may be termed exciting factors. Infection is the most important condition which may suddenly and precipitously induce scurvy. This fact was brought to our attention in 1912 in connection with the outbreak of scurvy among infants receiving pasteurized milk. Its explanation was not clear at the time, but was elucidated by subsequent experience, and was described in 1917 as follows: “Latent scurvy was prematurely changed to florid scurvy by the presence of a ward infection; an epidemic of ‘grippe’ precipitated an epidemic of scurvy exceptional in its hemorrhagic tendency.” The association of scurvy and infection has been recently emphasized by McCarrison and others, and seems to hold good for the other so-called deficiency diseases. In this connection one other exciting cause of scurvy may be mentioned, namely, trauma. The older writers noticed that following a fall or an accident, a sailor frequently developed scurvy, and Barlow in 1894 remarked on the influence of trauma in connection with infantile scurvy. As might be inferred, its effect is mainly to induce premature rupture of the weakened blood-vessels; in infants we have seen this occasioned by pressure exerted on the lower end of the thigh to ascertain the presence of tenderness. Viewing the situation broadly, it must be acknowledged that except for the realization that scurvy is due to a new food factor—a vitamine—our fundamental understanding of its pathogenesis has advanced but little, in spite of the employment of experimental methods and the availability of modern technic.
It is doubtful whether mere clinical studies will contribute in a large measure to the solution of the pathogenesis of scurvy. Much may, however, be learned by investigations of the metabolism in human scurvy—an aspect of the problem which, as will be brought out in a subsequent chapter, hardly has been explored. By this means may be acquired a clearer understanding of the effect of an antiscorbutic deficiency on the tissues and on cellular activity. Much may be expected from physiologic and pharmacologic studies of the specific vitamine, although it is not yet available in a pure state. Finally, it is probable that the solution of similar questions relating to the pathogenesis of cognate disorders—a study which is engaging the best efforts of so many workers throughout the world—will shed light on this particular disease.