Infantile scurvy (Barlow's disease)

CHAPTER XXX INFANTILE SCURVY (BARLOW’S DISEASE) BY ALFRED F. HESS, M.D. In: PEDIATRICS By VARIOUS AUTHORS Edited by ISAAC A. ABT, M.D. Professor of Diseases of Children, Northwestern University Medical School, Chicago; Attending Physician, Sarah Morris Hospital for Children of Michael Reese Hospital, Chicago VOLUME II PHILADELPHIA AND LONDON W. B. SAUNDERS COMPANY 1923 Abt’s “Pediatrics by various authors” published in 1923 (p. 849) is available at: https://archive.org/details/pediatrics0002isaa https://archive.org/details/pediatrics0002isaa/page/848/mode/2up Chapter XXX This book chapter by Alfred Hess was identified in a project to search the early literature on the descriptions of the symptoms of scurvy. Hess appears to be the most important clinical researcher on scurvy in the early part of the 20th century. There was extensive biochemical research related to scurvy which led to the identification of vitamin C and to the Nobel prize to Albert Szent-Györgyi in 1937. However, Szent-Györgyi was not a committed long-term scurvy researcher and not a clinician. Hess wrote over two dozen papers about scurvy. In 1920, he wrote a monograph of scurvy, which is informative about the clinical aspects of scurvy. The most essential parts of the monograph were extracted to a document available at: https://doi.org/10.5281/zenodo.10685194 This current text is restricted mostly to the sections of Chapter XXX that are relevant concerning the symptoms of scurvy. The reference list to the entire Chapter XXX is at the end of this text with links to the references when such were identified. The entire scanned chapter is available together with this document at: https://doi.org/10.5281/zenodo.15465663 Yellow is used to indicate the most relevant parts. This version was prepared by Harri Hemilä, MD, PhD, University of Helsinki, Helsinki, Finland. https://orcid.org/0000-0002-4710-307X https://www.mv.helsinki.fi/home/hemila 1 Portrait of Alfred Fabian Hess: https://dp.la/item/081485fa1faf59ee801a66301939f799 https://siarchives.si.edu/collections/siris_arc_393647 https://www.facebook.com/StrausHistoricalSociety/photos/a.172141832916264/2286596761470750 Biographies about Alfred F Hess: Bass MH. Alfred Fabian Hess (1875-1933). Semin Pediatr Infect Dis. 2005;16(2):144-7. https://doi.org/10.1053/j.spid.2005.01.003 Wiedemann HR. The pioneers of pediatric medicine. Alfred Fabian Hess (1875-1933). Eur J Pediatr. 1993;152(6):461. https://doi.org/10.1007/bf01955048 Rosen G. The case of the consumptive conductor, or public health on a streetcar: A. centennial tribute to Alfred F. Hess, MD. Am J Public Health. 1975;65(9):977-8. https://doi.org/10.2105/ajph.65.9.977 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1775957 Darby WJ, Woodruff CW. Alfred Fabian Hess-a biographical sketch (October 9, 1875–December 5, 1933). J Nutr. 1960;71:3-9. https://doi.org/10.1093/jn/71.1.1 Bass MH. Alfred Fabian Hess (1875-1933). J Pediatr. 1955;46(6):731-7. https://doi.org/10.1016/s0022-3476(55)80182-5 Collected writings. Ann Intern Med 1936;10(4):558. https://doi.org/10.7326/0003-4819-10-4-558 Jobling JW, Park WH, Cohn AE. Alfred Fabian Hess. Bull N Y Acad Med. 1934;10(1):44-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1965595 Gerstenberger HJ. Alfred Fabian Hess, M.D. Am J Dis Child. 1934;47(3):635-9 https://doi.org/10.1001/archpedi.1934.01960100161022 Alfred Fabian Hess. Science 1934;79:70-2. https://doi.org/10.1126/science.79.2039.70 https://www.jstor.org/stable/1660244 https://archive.org/details/sim_science_1934-01-26_79_2039/page/70/mode/2up https://en.wikipedia.org/wiki/Alfred_Fabian_Hess 2 INFANTILE SCURVY (BARLOW’S DISEASE)1 Alfred F. Hess, M.D. History.2—We owe the first description of infantile scurvy to p.849 Glisson,3 who likewise was the first to recognize rickets. Glisson’s description, written in 1668, was entirely lost sight of, however, until the end of the last century. In 1859 Moeller described cases which were evidently scurvy, but which he termed ‘‘acute rickets,” failing to distinguish the distinctive nature of the disorder. Soon after this, Ingerslev4, Jalland1, and Cheadle1 described cases of scurvy, the latter clearly recognizing the disease as the same which occurs in adults. In 1883 Barlow1 furnished anatomical proof that the disorder of infants presented the pathological changes characteristic of adult scurvy. The work of Barlow was accepted remarkably quickly in England and America, but less promptly on the continent, due to the fact that the disorder was far more prevalent in the English speaking countries. An idea of the extent of its recognition may be gained from the fact that in 1894, 106 cases were reported at a medical meeting in New York City,5 and that four years later a comprehensive investigation, based on 379 cases, was published by the American Pediatric Society.1 Infantile scurvy has been reported from almost all parts of the world. Strange to state, in spite of the fact that adult scurvy is endemic in many parts of Russia, reports of infantile scurvy have been remarkably few from this country. Filatow, the great Russian children’s specialist, declared some years ago that he knew of no case of Barlow’s disease described in the Russian literature. During the past few years, as a result of the World War, there has been a great increase of scurvy in Europe, especially in the Central 1 See references with links at the end of this text 2 Summaries of history of infantile scurvy: Still GF. Infantile scurvy: its history. Arch Dis Childhood 1935;10:211-218. https://pmc.ncbi.nlm.nih.gov/articles/PMC1975442 Evans PR. Infantile scurvy: the centenary of Barlow’s disease. Br Med J. 1983;287:1862-3. https://pmc.ncbi.nlm.nih.gov/articles/PMC1550031 Hess AF. Scurvy, Past and Present. 1920:1-22. https://www.gutenberg.org/ebooks/40505 https://digital.library.cornell.edu/catalog/chla2903792 3 Glisson F. Section on scurvy in: A treatise of the rickets. 1651. https://doi.org/10.5281/zenodo.10206723 4 Ingerslev, V. A case of scurvy in a child. Hospitals-Tidende 1874:(Aug 2):121-122. https://doi.org/10.5281/zenodo.15424739 5 Northrup WP, Crandall FM. Scorbutus in infants. NY Med J 1894;(May 26):641-6. https://doi.org/10.5281/zenodo.15463815 Another early report in the USA: Northrup WP. Scorbutus in infants. Archives of Pediatrics. 1892;9:1-22. https://doi.org/10.5281/zenodo.15463670 3 Empires. Erdheim1 recently reported 31 autopsies on infants who had suffered from scurvy. Eric Mueller1 and Brandt have published accounts of scurvy in the foundling asylums of Berlin. Epstein of Prague wrote a paper with the descriptive title ‘‘On a Marked Increase of Barlow’s Disease During the Years of the War 1917-1918.” Vogt reported an outbreak of infantile scurvy in his hospital at Magdeburg. PATHOLOGY As stated, the pathology of infantile scurvy dates back of Barlow’s exposition, the modern milestone in the study of the pathology of this disorder. Until recently attention has been focused exclusively on the bones, all other organs of the body being neglected. This is true of the gross, as well as of the microscopic, anatomy. Lately, however, the p.850 field has been broadened. As a result largely of the interest in experimental scurvy, the heart, endocrine glands and other organs have been subjected to close inquiry. Gross Pathology.—The skin is pale and dotted with numerous petechiæ or echymoses of moderate size. Generally there is some edema about the ankles. The emaciation is not extreme unless the picture has been complicated by starvation or by general infection. Enlargement of the long bones, especially of the femur and tibia, may be noted, due to subperiosteal hemorrhage, and may be associated with fracture and crepitation. Another bony alteration which is readily palpable is “beading” of the ribs, the counterpart of the rachitic rosary. On incision, one of the striking phenomena is the anasarca of the soft parts. In one of the first cases with postmortem examination Barlow1 described this condition as follows: “The muscular walls of the thorax were pale yellow and watery, as though they had been bathed in serum.” Any or all of the serous cavities may be involved in this hydrops, the order of frequency being the pericardium, pleura, peritoneum and joints, especially the knee. On opening the thorax the heart will be noted frequently as enlarged— an alteration overlooked until recently. In the article referred to above entitled ‘‘Das Barlowherz,’’ Erdheim1 described enlargement of the heart, especially of the right ventricle, in 21 of the 31 necropsies of infants who died of scurvy in Vienna during the World War. In view of these protocols and of the clinical demonstration of cardiac enlargement by means of roentgenograms (Hess), and of the pathological reports in adult scurvy, enlargement of the heart must be regarded as a true scorbutic lesion. The lungs are almost always congested. The main lesion of the gastro-intestinal tract is an intense congestion of the duodenum, frequently found in the upper part, and ulcers of the large intestine, especially where secondary infection has occurred. The liver and spleen usually are of normal size. 4 SYMPTOMATOLOGY p.863 Infantile scurvy must be considered as presenting three types of symptoms, which will be grouped as acute, subacute and latent. The stereotyped picture, and the one which this designation suggests, is that of the acute type of the disease. I have described this elsewhere as follows:6,p.183 ‘‘We have to do generally with a poorly nourished, pale infant with a peculiarly alert and worried expression. As we approach its bed it whimpers or cries out in terror. Frequently its posture is characteristic, as it lies quietly on its back with one thigh everted and flexed on the abdomen. Examination shows that one or even both thighs are swollen and exquisitely tender, or that there is merely tenderness, the baby shrieking at the slightest pressure upon the lower end of the femur. If teeth are present, the adjacent gums are red, swollen and bleed readily. This is the syndrome which the medical student is taught to carry away to guide him in his everyday practice.” This is a striking picture and one which impresses itself in the memory, but it is not the common form of the disorder, which should be diagnosed before this stage is reached. Subacute Infantile Scurvy.—The commoner form, which we have termed ‘‘subacute infantile scurvy,’’ comprises a large number of symptoms which are inconclusive individually, and frequently escape correct interpretation. The affected baby is usually in the second half of the first year of life, and does not gain in weight or gains but slightly for weeks. It may be fairly well nourished, but is pale, or sallow, with perhaps slight edema of the upper eyelids. The mother or nurse complains that the child is irritable and peevish, and that the appetite is poor or capricious. The gums show a lividity or slight peridental hemorrhage, which on subsequent examination may be no longer visible, and may have consisted merely of a rim of crimson edging the borders of the upper gum. Attention may be called to tenderness of the lower thighs, which in some instances is definite, in others so ill-defined and fleeting that it is impossible to convince oneself of its significance or even reality. There may be slight edema over the crests of the tibia, of a kind which does not pit on pressure. The knee-jerks are almost always markedly exaggerated. The urine is diminished in volume but is generally normal or contains a trace of albumen and red and white blood-cells. The pulse is frequently rapid, and becomes markedly rapid and irregular on the slightest excitement. The respirations are also rapid. 6Hess AF. Scurvy, Past and Present. (1920). https://doi.org/10.5281/zenodo.10685195 Extraction of the most important sections. https://www.gutenberg.org/ebooks/40505 https://digital.library.cornell.edu/catalog/chla2903792 https://archive.org/search?query=creator%3A%22Hess%22+scurvy https://openlibrary.org/books/OL6631267M 5 Happily, infantile scurvy now-a-days rarely progresses any further, because treatment is instituted and a quick recovery brought about. However, before the true nature of infantile scurvy was understood, the case progressed even to the point of death, and this happens occasionally at the present time. The gums become markedly hemorrhagic and even necrotic, leading to the foul odor of putrefaction. p.864 Hemorrhages of greater or less extent develop in various parts of the body. There are separations of the epiphyses of the long bones, accompanied by exquisite tenderness and swelling. The general condition of the infant becomes worse, the appetite fails, and the general nutrition is so greatly impaired that intercurrent infection comes about7 and leads to death, unless the condition is alleviated by giving large amounts of some antiscorbutic food. Some have stressed the importance of roentgenograms in the diagnosis of scurvy, especially of “the white line of Fraenkel,” which is seen at the epiphysis of the long bones, usually of the femora. Reliance cannot, however, be placed on this sign, as it is frequently absent when the diagnosis is otherwise clear. As has been previously stated, scurvy takes about six months to develop. It is therefore evident that there must be, from a clinical standpoint, a pre-scorbutic stage leading to what may be called latent scurvy. This form of infantile scurvy necessarily must be the most common type. It is, however, frequently impossible to diagnose at this stage. Indeed, there is need for some means of diagnosing scurvy and other nutritional disorders before they have brought about such marked alterations that they are apparent to ordinary clinical observation. Latent scurvy is characterized by pallor, or rather a peculiar sallow or muddy complexion, by a lack of gain in weight, fretfulness, leading to frequent whining and crying, a loss or capriciousness of appetite. The knee-jerks may be increased, and the respirations and pulse rapid (“cardio-respiratory syndrome’’).6,8 The symptoms are suggestive and do not enable an absolute diagnosis to be made. The diagnosis is established in part by an investigation of the 7 HH added: Recent reviews on vitamin C and infections: https://pubmed.ncbi.nlm.nih.gov/39803741 https://pubmed.ncbi.nlm.nih.gov/38082300 https://pubmed.ncbi.nlm.nih.gov/28353648 https://pubmed.ncbi.nlm.nih.gov/23440782 https://doi.org/10.5281/zenodo.14717360 8Hess AF. Subacute and latent infantile seurvy, the cardiorespiratory syndrome (a new sign). JAMA. lxviii (1917) p. 235. https://doi.org/10.5281/zenodo.10102042 https://doi.org/10.1001/jama.1917.04270010235001 HH added: Recent papers on vitamin C and heart function: https://pubmed.ncbi.nlm.nih.gov/38504249 https://pubmed.ncbi.nlm.nih.gov/35282368 https://pubmed.ncbi.nlm.nih.gov/28143406 6 diet of the infant—whether it was rich or poor in the antiscorbutic vitamin. Most of the instances of latent scurvy which I have seen have developed on pasteurized milk, which contains some vitamin, but an insufficient quantity. The diagnosis is furthermore established by giving an antiscorbutic food, for example, orange juice or tomato juice, and noting the prompt disappearance of the above symptoms. As stated, hemorrhages dominate the picture of scurvy. The commonest manifestation are the hemorrhages of the gums. These do not appear unless the teeth are present or in the process of eruption.9 Very rarely small gingival hemorrhages have been noted where scurvy has not been present and the nutrition is normal. The gums may merely be bluish red or show a hemorrhagic rim above the teeth, or in severe cases may be deep red and pouting and even necrotic, similar to the lesion found in adults. The other characteristic sign of scurvy due to hemorrhage is the subperiosteal hemorrhage (Fig. 144)10. This involves most frequently the lower end of the femur but is not infrequently encountered in relation to the tibia and may occur in bones of the upper extremity. The hemorrhage usually manifests itself by a sudden swelling at the lower end of the femur or femora. The swelling is very tender and may be barely perceptible or so large that it renders the leg twice its normal size. p.865 It persists long after the gums have become normal and becomes harder and less tender, and may develop a consistency of bone. In this stage such swellings have been diagnosed as new growths and have led to incision or even to amputation of the leg. The subperiosteal hemorrhages may be clearly seen by means of the Roentgen-ray. The shaft of the bone appears surmounted by an elongated blood-clot. Fig. 144.—Subperiosteal hemorrhage at epiphysis of femur; beginning calcification of periosteum.10 The periosteum frequently undergoes calcification, which renders its outline clear. Other forms or other manifestations of hemorrhage are the bleedings of the skin, which lead either to small petechial spots in various parts of the body, or to echymoses seen especially about the joints or on the forehead, following trauma. A form of hemorrhage 9 HH added: The American Pediatric Society’s collective investigation draw a different conclusion (p.490): “This is a proof that affection of the gums may occur equally well when there are no teeth as when teeth have developed. The fact that in the great majority of cases of infantile scurvy the presence of teeth and the affection of the gums is associated, depends merely on the fact that the disease generally develops at an age when teeth naturally have been cut.” https://doi.org/10.5281/zenodo.15282390 10 A scanned Figure 144: https://archive.org/details/pediatrics0002isaa/page/864/mode/2up p.865. 7 which has always excited the interest of physicians, although it is uncommon, is the proptosis of the eyeball11, which results from subperiosteal hemorrhage into the orbit. In general, it may be said that every organ has been described as being the site of hemorrhage—the pleura, p.866 pericardium, peritoneum, meninges; the glandular organs of the abdomen may at times show hemorrhages, depending largely on the occurrence of trauma or intercurrent infection. A typical symptom of infantile scurvy is the separation of the epiphyses, which occurs most often in infants, but may be seen even in young adults (Fig. 145)12. It is most frequent at the lower end of the femur and upper end of the tibia. These epiphyseal hemorrhages are Fig. 145.—Separation of lower end of femur. Calcification of periosteum, appearing as “periosteal tags.”12 usually termed fractures or infractions. The union is remarkably perfect, even when no treatment has been employed and the cure has been effected by nature. We have referred to the use of roentgenograms in connection with subperiosteal hemorrhages; it is also of value, as may be supposed, in substantiating the diagnosis of the separation of the epiphyses. The x-ray has been given particular prominence in this disorder in connection with the so-called white line of Fraenkel. By this is meant a transverse somewhat irregular band which is seen near the lower end of the epiphyses of the long bones, especially of the radius and the 11 HH added: Zilva SS, Still GF. Orbital hæmorrhage with proptosis in experimental scurvy. Lancet 1920;195:1008. https://doi.org/10.1016/S0140-6736(01)08066-7 “Out of 64 [human] cases 6 showed orbital haemorrhage, and in 5 of these there was proptosis … During experiments on [mangabey] monkeys… a similar occurrence was recently observed… [on a scorbutic diet] there was some exophthalmos and haemorrhage in the eyelids… [with antiscorbutic treatment] the eye symptoms had almost disappeared… [on a second scorbutic diet] there was marked exophthalmos of the left eye, with such extreme eversion and bulging of the conjunctiva as completely to hide the cornea; the everted conjunctiva was covered with blood. The right eye showed no exophthalmos. [with a new antiscorbutic treatment] next day there was much less exophthalmos… [with larger doses antiscrobutic treatment] the proptosis of the left eye was greatly diminished, and subsequently disappeared in a few days.” “Dr. A. Harden and Dr. S. S. Zilva have recorded an experiment on another monkey (Macacus rhesus) in which the scorbutic exophthalmos affected the right eye.” The Harden and Zilva (1919) report stated: https://doi.org/10.1002/path.1700220305 “scorbutic condition in the monkey… exophthalmus of the right eye was noted, which disappeared after a few days, leaving the upper eyelid and orbit of the eye hæmorrhaged. A more pronounced condition of exophthalmus was again observed in the right eye… which disappeared after about two days, again leaving the orbit hæmorrhaged…” 12 A scanned Figure 145: https://archive.org/details/pediatrics0002isaa/page/866/mode/2up p.866. 8 femur (Fig. 146)13. Its diagnostic value has been greatly exaggerated. We have found it frequently missing when the disorder is advanced and it persists for months after a cure has been effected. Among the signs of infantile scurvy involving the bones beading p.867 of the ribs must be mentioned. Hess and Unger14 have recently described this sign, which has been considered as pathognomonic for rickets. It is important for us to realize that there is scorbutic as well as rachitic beading, and that the diagnosis of rickets cannot be based merely on the presence of a ‘‘rosary.” The beading is somewhat different from that found in rickets, being more angular and less knobby. Fig. 146.—“White line” at epiphyses of femur and tibia.13 The cardiovascular system is frequently involved in infantile scurvy.6,8 The heart is enlarged, as may be elicited by means of percussion and roentgenologic examination. The pulse is often rapid and unstable, increasing inordinately on the slightest exertion or rise of temperature. The respirations are also rapid. This symptom complex has been termed “the cardiorespiratory syndrome.” 6,8 The urinary system is frequently involved in the course of scurvy. Hematuria may occur as the first symptom. This fact is emphasized in many descriptions of the disease. It is an exceptionally rare sign, however, just as is hemorrhage into the orbit. Microscopic hemorrhage leading to the appearance of red blood-cells in the urine is, however, a frequent symptom, having been found by Still in 89 per p.868 cent. of his cases.15 Quite apart from or in combination with these hemorrhages there may be a true nephritis, accompanied by albumen and casts and irregular fever. This nephritis generally subsides quickly with the disappearance of other scorbutic symptoms. Oliguria is a symptom common to both adult and infant scurvy, but has been overlooked until attention was directed to it recently by Gerstenberger and by Hess and Unger. It gains an added interest in view of the fact that this symptom is common to both adult and infantile beriberi. 13 A scanned Figure 146: https://archive.org/details/pediatrics0002isaa/page/866/mode/2up p.867. 14 Hess AF, Unger LJ. Scorbutic beading of the ribs. Am J Dis Child. xix (1920), p.331. https://doi.org/10.5281/zenodo.10102674 https://doi.org/10.1001/archpedi.1920.01910230001001 https://babel.hathitrust.org/cgi/pt?id=uc1.b3845616&seq=347 https://babel.hathitrust.org/cgi/pt?id=uva.3470086176&seq=343 15 HH added: Still wrote (p.115) that “the proportion of cases showing some urinary change was 89 per cent., and the proportion showing haematuria was 60 per cent.” Still G. Common Disorders and Diseases of Childhood. (1915), p.115 https://doi.org/10.5281/zenodo.15342856 [section on scurvy] https://archive.org/details/b29929465/page/114/mode/2up (1915) 9 10. Erdheim, J., Ueber das Barlowherz, Wien. klin. Woch. (1918), p. 1293. https://doi.org/10.5281/zenodo.7756493 [English translation] Recent papers on vitamin C and cardiac pathology: https://pubmed.ncbi.nlm.nih.gov/38504249 https://pubmed.ncbi.nlm.nih.gov/35282368 https://pubmed.ncbi.nlm.nih.gov/28143406 11. Filatow, Cited by M. Schubert, Beriberi, und Skorbut, Deutsch. Arch. f. klin. Med., lxxxvi (1905), p. 79. 12. Gerstenberger, H. J., Pathogenesis of infantile scurvy, an hypothesis, Am. Jour. Med. Sci., clv (1918), p. 253. https://zenodo.org/records/1607154 https://oce.ovid.com/article/00000441-191802000-00008 https://archive.org/details/paper-doi-10_1097_00000441-191802000-00008 13. Glisson, F., ‘Treatise on the Rickets,’’ London (1651). https://doi.org/10.5281/zenodo.10206723 [section on scurvy] https://archive.org/details/b30335693/page/248/mode/2up https://archive.org/details/b30327246/page/248/mode/2up https://archive.org/details/b30329589/page/248/mode/2up https://wellcomecollection.org/works/qn24bpgf/items?canvas=265 https://quod.lib.umich.edu/e/eebo/A86032.0001.001 https://archive.org/details/bim_early-english-books-1641-1700_a-treatise-of-the-ricke_glisson-francis_1668/page/n251/mode/2up Biographies: https://pmc.ncbi.nlm.nih.gov/articles/PMC1720777 https://history.rcp.ac.uk/inspiring-physicians/francis-glisson https://en.wikipedia.org/wiki/Francis_Glisson 14. Harden, A., and Zilva, S. S., The differential behavior of the antineuritic and antiscorbutic factors towards absorbents, Biochem. Jour., xii (1918), p. 93. https://doi.org/10.1042/bj0120093 https://pmc.ncbi.nlm.nih.gov/articles/PMC1263881 Hess, A. F., and Unger, L. J., The destructive effect of oxidation on antiscorbutic vitamine, Proc. Soc. Exper. Biol. & Med., 1921, xviii, 143, https://doi.org/10.3181/00379727-18-68 https://www.biodiversitylibrary.org/item/156421#page/153/mode/1up also: Brit. Med. Jour., 1920, ii, 147. Hopkins FG. The present position of vitamins in clinical medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC2337987 Hess, A. F., and Unger, L. J., The destruction of the antiscorbutic vitamin in milk by the catalytic action of minute amounts of copper. Proc. Soc. Exper. Biol. & Med., 1921, xix, 119. https://doi.org/10.3181/00379727-19-57 https://www.biodiversitylibrary.org/item/156400#page/129/mode/1up Report in JAMA 1924;82(12):952-956. https://doi.org/10.1001/jama.1924.02650380020007 Van der Walle, N., The presence of the antineuritic and antiscorbutic vitamins in urine. Bioch. Jour., 1922, xvi, 47. 16 https://doi.org/10.1042/bj0160713 https://pmc.ncbi.nlm.nih.gov/articles/PMC1259131 Vedder, E. B., The Etiology of Scurvy. Military Surgeon, 1921, xlix, November. https://babel.hathitrust.org/cgi/pt?id=hvd.32044103092334&seq=522 15. Hess, A. F., “Scurvy, Past and Present,” J. B. Lippincott (1920). https://doi.org/10.5281/zenodo.10685194 [sections that are most relevant] https://www.gutenberg.org/ebooks/40505 https://digital.library.cornell.edu/catalog/chla2903792 https://archive.org/search?query=creator%3A%22Hess%22+scurvy https://openlibrary.org/books/OL6631267M 16. Hess, A. F., Subacute and latent infantile seurvy, the cardiorespiratory syndrome (a new sign), Jour. Am. Med. Assn., lxviii (1917) p. 235. https://doi.org/10.5281/zenodo.10102042 https://doi.org/10.1001/jama.1917.04270010235001 17. Hess, A. F., and Fish, M., Infantile scurvy: The blood, the blood-vessels, and the diet, Am. Jour. Dis. Child., viii (1914), p. 386. https://doi.org/10.5281/zenodo.10207276 https://doi.org/10.1001/archpedi.1914.02180010395001 See also: Proc Soc Exp Biol Med. 1914;11(5):130-2. https://doi.org/10.3181/00379727-11-80 https://www.biodiversitylibrary.org/item/156416#page/140/mode/1up 18. Hess, A. F., and Unger, L. J., Scurvy: viii, Factors affecting the antiscorbutic value of foods, Am. Jour. Dis. Child., xvii (1919), p. 221. https://doi.org/10.5281/zenodo.15210367 https://doi.org/10.1001/archpedi.1919.04110280002001 https://babel.hathitrust.org/cgi/pt?id=uc1.b3845614&seq=239 https://babel.hathitrust.org/cgi/pt?id=uva.3470086174&seq=233 https://scispace.com/pdf/scurvy-viii-factors-affecting-the-antiscorbutic-value-of-1pzkzbzo88.pdf 19. Hess, A. F., and Unger, L. J., Scorbutic beading of the ribs, Am. Jour. Dis. Child., xix (1920), p. 331. https://doi.org/10.5281/zenodo.10102674 https://doi.org/10.1001/archpedi.1920.01910230001001 https://babel.hathitrust.org/cgi/pt?id=uc1.b3845616&seq=347 https://babel.hathitrust.org/cgi/pt?id=uva.3470086176&seq=343 20. Holst, H., and Froelich, T., Ueber experimentallen Skorbut, Ztschr. f. Hyg. u. Infektionskrankh., lxxii (1912), p.1. https://doi.org/10.1007/BF02216486 https://doi.org/10.5281/zenodo.8410010 In English: https://pmc.ncbi.nlm.nih.gov/articles/PMC5548395 https://doi.org/10.1017/s0022172400033611 https://pmc.ncbi.nlm.nih.gov/articles/PMC2236198 https://doi.org/10.1017/s0022172400033623 https://pmc.ncbi.nlm.nih.gov/articles/PMC2236195 17 21. Holt, L. E., “Diseases of Infancy and Childhood,” New York and London Appleton (1919). https://doi.org/10.5281/zenodo.15343352 [section on infantile scurvy] https://archive.org/details/diseasesofinfanc00holtiala/page/232/mode/2up (1911) https://archive.org/details/diseasesofinfanc0000unse_s8n0/page/230/mode/2up (1916) https://archive.org/details/cu31924003491127/page/230/mode/2up (1919) https://archive.org/search?query=holt+%22diseases+of+infancy%22 https://wellcomecollection.org/search/works?query=emmett+holt+diseases+infancy Biographies: https://en.wikipedia.org/wiki/Luther_Emmett_Holt https://doi.org/10.1126/science.59.1534.452 https://pmc.ncbi.nlm.nih.gov/articles/PMC1721179 https://doi.org/10.1001/archpedi.1941.02000110207020 https://pmc.ncbi.nlm.nih.gov/articles/PMC1531204 https://pmc.ncbi.nlm.nih.gov/articles/PMC7937145 https://wtty.webstermuseum.org/biographies/dr-l-emmett-holt 22. Jackson, L., and Moore, J. J., Studies of experimental scurvy in guinea pigs, Jour. Infect. 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Related: https://pmc.ncbi.nlm.nih.gov/articles/PMC2099764 Biographies: https://doi.org/10.1093/clinids/10.5.1061a https://doi.org/10.1093/clinids/9.3.636 https://doi.org/10.1093/clinids/9.3.625 https://pmc.ncbi.nlm.nih.gov/articles/PMC2634653 https://pmc.ncbi.nlm.nih.gov/articles/PMC2446360 https://pmc.ncbi.nlm.nih.gov/articles/PMC1559041 https://pmc.ncbi.nlm.nih.gov/articles/PMC1525488 https://pmc.ncbi.nlm.nih.gov/articles/PMC1372771 https://pmc.ncbi.nlm.nih.gov/articles/PMC543631 https://www.nal.usda.gov/exhibits/speccoll/items/show/8205 https://www.njmicrobe.org/who-was-tss https://en.wikipedia.org/wiki/Theobald_Smith 28. Still, G., “Common Disorders and Diseases of Childhood,” 3d Ed. London (1915). https://doi.org/10.5281/zenodo.15342856 [section on infantile scurvy] https://archive.org/details/b29929465/page/108/mode/2up (1915) https://archive.org/search?query=creator%3A%22Still%2C+G%22+disorders https://wellcomecollection.org/search/works?query=Common+disorders+george+still See also: Still GF. Infantile scurvy: its history. Arch Dis Childhood 1935;10:211-218. https://pmc.ncbi.nlm.nih.gov/articles/PMC1975442 Still GF. The treatment of infantile scurvy. 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