SCURVY

SCURVY (from Polish dziegna-a wasting disease), or scorbutus (from Dutch scheurbuik, skorbek-ulcers in the mouth), an avitaminosis developing from prolonged deficiency or absence of vitamin C in food. Scurvy is characterized by manifestations of general hemorrhagic diathesis. S. affects all ages; among adults S. usually develops in the form of large epidemics, sporadic cases are rare; in children, on the contrary, sporadic cases are common, while mass diseases are the exception. History. The first descriptions of epidemics of S. date to the 13th century. A severe epidemic affected the troops of Louis IX near Cairo in 1250. In the 15th century, epidemics of S. caused much suffering to sailors seeking new countries, for example, Vasco da Gama lost half his crew during his voyage to the East Indies. In the 16th century, S. appeared in Europe and epidemics were observed in Scandinavia and on the Baltic coast. Euricius Cordus in 1534 described an epidemic under the name scharboock (scurvy) from the name of a special kind of cabbage Scharbockskraut, with which patients were successfully treated. Descriptions of S. in subsequent centuries were less definite and only in the first half of the 18th century S. was again strictly differentiated. The practical resolution of the problem of the origin, prevention and treatment of scurvy dates to this time. Kramer (J. Kramer) as early as 1720 pointed out that "even in the best pharmacy there is no remedy against S., that fresh vegetables, orange and lemon juices are the only reliable remedy, and that dried and preserved fruits and vegetables lack antiscorbutic properties". Lind in 1747 conducted the first carefully conducted observations. When scurvy appeared on the ship on which he was sailing, Lind divided the sick into several groups and tested on them the known methods of treatment at that time. Based on his observations, Lind concluded that oranges and lemons have the strongest therapeutic properties*. In 1795, extensive preventive measures were implemented in the English fleet: lemon juice was included in the food ration of sailors; from this time epidemics of S. ceased in the English fleet. In the 19th century, S. in the form of large epidemics was observed during wars in besieged fortresses-in Paris (1871), during the Anglo-Boer war in besieged Ladysmith, in the hungry year 1899 in Russia; during the world war of 1914-1917, epidemics were observed in Russia, Austria, Germany and the Balkans. Epidemics of S. during the world war were little studied, but it can be noted that both in the troops and among the population S. began to spread only at the end of 1916, when mass malnutrition was joined by other predisposing factors-infections and general physical exhaustion. The high mortality noted in epidemics of previous centuries is not observed at present. It must be assumed that the statistics of previous centuries included cases complicated by various infections. With timely recognition and proper treatment, S. proceeds quite benignly, and as reported by Salle and Rosenberg, they did not lose a single patient out of 461 cases observed by them in Germany in 1917. Symptomatology. The picture of S. is different in infants, young children and adults (S. in children-see Barlow's disease). S. in adults is characterized by hemorrhages into the gums, skin and muscles. One can distinguish the prodromal, or latent stage of the disease from the pronounced picture of the illness. The prodromal stage is not always expressed. In this period, complaints of general fatigue, lassitude, drowsiness, mental fatigue and depressed mood are most often noted. The patient's face often has a suffering expression, the eyes lack luster, the visible mucous membranes are cyanotic, the skin is dirty-gray in color, dry and as if sprinkled with flour due to fine peeling. The picture of sharply protruding hair follicles on the skin is very characteristic; various authors described such skin as keratosis pilaris, keratosis superficialis, lichen scorbuticus, "scorbutic skin", "skin resembling a grater", etc. Often in the prodromal stage, patients complain of rheumatic pains in the lower extremities-in the calves, in the shins. These pains depend on small hemorrhages into the thickness of the muscle with damage to the small nerve fibers passing in this area. In the pronounced stage, numerous pinpoint hemorrhages are visible. The size of hemorrhages depends not on the severity of the disease, but on the functional or physical load of the organ: the stronger the subject, the stronger he strains his muscles, the stronger the hemorrhages into the muscles, etc. The location of hemorrhages is determined by the conditions of greatest physical exertion, for example, during marches in soldiers, the strongest hemorrhages most often appear in the calf muscles (Aschoff and Koch). In frequency of localization, hemorrhages are arranged in the following order: 1) gums, 2) muscles, 3) subcutaneous tissue, 4) skin. Hemorrhages into the periosteum, internal organs and joints are rare. Changes in the gums belong to almost obligatory manifestations of S.; in abortive cases they are often the only symptom of the disease. Due to capillary bleeding into the thickness of the gums, their mucous membrane swells, becomes cyanotic and loose. With infection, usually originating from carious teeth, the mucous membrane ulcerates, is covered with blue-red granulations and a dirty-gray discharge appears. Swelling of the gums begins with the papillae of the mucous membrane between the incisors at their anterior surface and from there spreads in a roller around the entire circumference of the tooth. Gradually the changes spread to the mucous membrane around other teeth, and only where there are no teeth, the gums remain unchanged. As a result of secondary infection from carious teeth, the mucous membrane around them sometimes undergoes disintegration and ulcers form (stomatitis ulcerosa). Often with S., teeth become loose and fall out. Hemorrhages into other parts of the oral mucosa and the soft palate have been described, but they are rare. The gums heal quickly with proper treatment, and usually no visible traces remain, only with significant hemorrhages can sclerotic changes remain.-Hemorrhages into the muscles often occur suddenly. With significant hemorrhages, a soft tumor is noted at first, which later becomes dense due to the development of connective tissue-scorbutic sclerosis, which sometimes leads to contractures. As a final result, even in moderately severe cases, muscle atrophy develops, edema due to local circulatory disturbance and cyanosis. With hemorrhages into the muscles, patients complain of pain and have a characteristic gait with knees turned inward and feet rotated inward or an old person's gait with bent knees and a forward-leaning body. Sometimes hemorrhages can be palpated in the muscles in the form of a dense and painful cord. The most common site of hemorrhages is the calf muscles, but hemorrhages into any muscle group are possible. Hemorrhages into the rectus abdominis muscles have often been observed.-Hemorrhages into the subcutaneous tissue can be extensive and occur more often where the skin is subjected to strong tension or pressure, for example, the popliteal fossa, buttocks, ankle area, on the heel, etc.-Hemorrhages into the skin have a petechial character and are localized around the hair follicles. The stronger the hairiness, the more petechiae; the most can be found on the hands and feet, less on the trunk; petechiae usually do not occur on the face. Fresh hemorrhages into the hair follicles look like bright red spots, later they turn into blue-black nodules, from the middle of which a broken hair sometimes sticks out; often the hairs fall out. Subsequently, the nodule resolves and a pigmented spot remains. As a result of the different timing of bleeding, the skin gets a motley spotted appearance; the blue-black, blue-red and rainbow colors depend on the change in blood pigment at sites of hemorrhages of different duration. Bones and joints. In children, bones are often affected at the junction of the epiphyses with the diaphysis. In adults, bone lesions are rare, but if they occur, they are identical to the changes in children. Changes are more often found on the ribs at the junction of the bone with the costal cartilage, where growth continues longer than in other parts of the skeleton. Here, as with S. in childhood, swelling, crepitation and fractures have been described, leading to the complete separation of the sternum from the ribs, which can lead to disruption of the mechanism of breathing (see Barlow's disease). This severe form has been described in young individuals and does not occur in the elderly. Joints are affected more often than bones; hemorrhages into the periarticular tissue of the knee joints are most often observed, as a result of which large deformations sometimes occur. Effusions into the joints are more often serous than hemorrhagic. Gastric, intestinal, pulmonary, pleural and renal bleeding are also observed, either independently or in combination of scurvy with infections: typhoid, dysentery, tuberculosis, etc.-Nosebleeds in scurvy are often observed and are often difficult to stop. In the eye, subconjunctival hemorrhages, into the anterior chamber of the eye, the vascular membrane and hemorrhages into the retina are often observed.

From the cardiovascular system, one can often note muffled heart tones, anemic murmurs, and a soft, compressible pulse. No specific changes for scurvy are noted in the lungs. In severe cases, Aschoff and Koch found fatty infiltration of the liver. In cases of scurvy not complicated by infection, the spleen is not palpable and is not even enlarged on percussion. Hemorrhages into nervous tissue occur very rarely. Usually, hemorrhages are localized not in the substance itself but in the nerve sheath and lead to severe neuritis and paresthesias. The sciatic nerve is most frequently affected; Feigenbaum and Noorden described two cases of paralysis of the lower extremities; in one of these patients, a subdural hematoma was found on autopsy. The blood often shows deviations from normal, but these changes are not specific for scurvy. Secondary anemia with a decrease in the amount of hemoglobin and the number of red blood cells is most commonly observed. The color index is equal to or less than one. The number of leukocytes may be normal, but leukopenia with relative lymphocytosis is more common. Sedimentation of red blood cells is often slowed. Despite such pronounced hemorrhagic symptoms in scurvy, the number of platelets, blood coagulability, and resistance of red blood cells show no characteristic changes. Subfebrile temperature is often observed in scurvy. The temperature curve is completely characteristic. Some authors suggest that increases in temperature are due to absorption of blood, but increases in temperature do not always coincide with the appearance of new hemorrhages. In many cases, complications with infections play a major role. It is characteristic that with successful treatment, normal temperature is quickly restored, as well as the normal blood picture. Course of the disease. With a prolonged deficiency of vitamin C, the disease drags on for months. Gradually, symptoms of increasing weakness develop. The color of the patient's face takes on a pale-yellow tint, appetite disappears. Hemorrhages usually develop in the form of a series of rashes, and they appear significantly later than the first manifestations of malaise, weakness, and anemia. More rarely, the disease begins suddenly with a single symptom—a hemorrhage into the calf muscles, etc. If one examines the population in which scurvy develops, it is possible to fairly early detect changes in the gums and small petechiae in the hair follicles. In untreated cases, after several months, severe hemorrhages, strong weakness, anemia, and cachexia with a fatal outcome develop. Complications in the form of pneumonia or some other infection hasten the sad outcome. In mild cases with proper treatment, complete recovery occurs in 15-20 days, in severe cases—usually in 35-40 days. Complications. Scurvy often develops among starving populations and is often combined with hunger protein-free edema. Krehl speaks of hydrops scorbuticus, Buquoy—of general inanition, Aschoff and Koch—of impaired water metabolism. Zalle and Rosenberg also point to the frequent combination of scurvy with edematous disease, which is a consequence of nutrition with incomplete proteins. A number of authors have indicated that night blindness is often a precursor of scurvy, which depends on a deficiency of fats (vitamins A and D) in the diet (see Hemeralopia). In the old literature, there are many indications that scurvy develops on the basis of epidemic diseases. It is undoubtedly true that infection in a scurvy patient runs especially severely, but on the other hand, infections often serve as a trigger for the development of scurvy and the transformation of a latent form into an obvious one. It must be taken into account that during infection, the body's need for vitamin C is significantly higher than normal. The absence of vitamin C during infection leads to severe hemorrhagic effusions and hemorrhages into internal organs. According to Zalle, cases of scurvy complicated by tuberculosis always end fatally, and Klinkovshteyn. Pathological anatomy. The pathological anatomical picture found on autopsy of scurvy patients usually represents a combination of changes of three kinds: 1) hemorrhagic diathesis, 2) general exhaustion, and 3) complications of the main disease with various secondary pathological processes. Sometimes to this are added characteristic changes in the bone system. Hemorrhagic diathesis in scurvy corpses manifests in hemorrhages of different types. Cutaneous petechiae and deeper purpura scorbutica are hemorrhages into the connective tissue of the skin, especially around the hair follicles. Microscopic examination of hemorrhages reveals nothing specific, in particular no noticeable changes are found in the skin vessels; the fatty degeneration of vessel walls described by some researchers is rejected by most authors, ruptures of vessel walls are a very rare phenomenon (E. MSH-1eg). The main mass of hemorrhages occurs per diapedesin. In late cases, deposition of blood pigment—hemosiderin—is found in the skin, located in the elements of histiocytic infiltrate that appears in these cases along the vessels. Hemorrhages are also found in the area of fasciae and aponeuroses, in adipose tissue, in connective tissue along the course of nerves and vessels. Of the mucous membranes, hemorrhages are most constantly found in the gums, where they are located near the necks of the teeth; on the corpse, these hemorrhages take on a dirty-gray color from the action of hydrogen sulfide. Further, hemorrhages are often found in the intestine, where they usually form a rim around the follicles, often ulcerated at the same time (see below). Hemorrhages in the lungs (their posterior parts), in lymph glands, in the heart coverings (especially in the epicardium) are by no means as constantly found. Hemorrhages in muscles and in the periosteum are found with great constancy only in the corpses of young scurvy patients (up to 25 years old); at a later age they are rare. The most affected are the muscles of the lower extremities, and among them the gastrocnemius, peronaeus, soleus; however, hemorrhages can occur in all other muscles. Usually, hemorrhages arise in the parts of the muscle closest to the tendon or to the place of attachment to the bone, and from there spread along the connective tissue along the bundles of muscle fibers. Periosteal hemorrhages in scurvy most often occur in the area of the epiphyses of long bones. Hemorrhages can also occur in joints, where they are localized in the synovial membrane, and sometimes give a collection of blood in the joint cavity. Hemorrhages in scurvy usually give blood impregnation of tissues, spreading along the connective tissue layers. Sometimes hematomas of one volume or another form, pushing apart muscles, detaching the periosteum, etc. During recovery, in the places where hemorrhages occurred, proliferation of connective tissue occurs, leading to hardening and limited mobility of the corresponding part (scurvy sclerosis). It should also be noted that hemorrhage from scurvy easily occurs in places of various inflammatory processes; thus, almost any inflammation in a scurvy patient takes on a hemorrhagic character. It is interesting that during endemics of scurvy, the hemorrhagic character of a banal inflammatory process (pneumonia, pleurisy, suppuration) can be observed even before the obvious signs of scurvy are revealed, which testifies, as it were, to a hidden scurvy state, revealed in places of inflammation. Manifestations of general exhaustion are naturally expressed more strongly on the corpse the further the disease has progressed. These include: general emaciation, the original feature of which is the lag in loss from the side of adipose tissue compared to the loss of muscle tissue and atrophy of internal organs; general anemia with relatively weak regenerative manifestations in the bone marrow; atrophic changes in muscles, brown atrophy of the heart, liver, atrophy of the thyroid gland; in the adrenal glands, weakness or absence of chromaffin reaction from the medulla; a wide, edematous, yet preserving lipoids cortical layer. To this can be added marantic edemas and dropsy of serous cavities. Among the complications, various manifestations of secondary infection are encountered. The most constant is infection of the affected gums with subsequent decay, formation of ulcerative stomatitis, with the spread of suppuration and ulcerative process to the mucous membrane adjacent to the gums, to the dental cells, etc. The mentioned ulcerative-gangrenous stomatitis can be a source of phlegmonous angina, aspiration pneumonia, and gangrene of the lung. Among other complications, very frequent are lesions of the intestine in the form of catarrhal enteritis, follicular and follicular-ulcerative enteritis and colitis and finally diphtheritic colitis of the dysentery type. In some cases, marantic thrombosis of veins with its consequences is observed. Exacerbation of the pulmonary tuberculosis process is a fairly frequent complication of scurvy, and in these cases the tuberculosis process takes on a sharply expressed exudative character and malignant course. Changes in the bone system, as is known, are very characteristic for scurvy in children (infantile scurvy), in which they manifest in the picture of Barlow's disease (see Barlow's disease).

Changes similar to the manifestations of Barlow's disease in children can sometimes also occur in adults (more often up to 25 years of age), however with the difference that these changes affect not the epiphyses of the long bones of the limbs, but the anterior epiphyses of the ribs, i.e., the places where the bony and cartilaginous parts of the ribs connect. In the part of the rib adjacent to the cartilage, first there occurs the disappearance of bone marrow cells, and the bone marrow acquires a reticular character, osteoblasts atrophy and disappear, the bony trabeculae thin out and break; at the same time, in the bone marrow space and under the periosteum, exudation of fibrin and hemorrhages occur. As a result of such changes in the ribs near their transition into cartilage, thickenings appear, and subsequently mobility arises, culminating in the complete detachment of the cartilaginous part of the rib from the bony part. When several ribs are affected, especially when such detachment of cartilage from ribs occurs on both sides, the sternum together with the cartilaginous parts of the ribs sinks in, falls inward into the chest cavity (see fig.). A further complication may be that the sharp edges of the anterior ends of the ribs, by their pressure on the inner surface

Changes in the ribs of the type of Barlow's disease in adult scurvy; separation of the bony and cartilaginous parts of the ribs with sinking of the sternum; V the right rib has pierced through the skin.

ness of the skin cause bedsores in it, which open the gates for secondary infection. If this process at one stage or another of its development subsides, then regenerative bone neoplasm occurs. In addition to the above changes, in severe cases of scurvy, one can find in various spongy bones the disappearance of bone marrow cells, a reticular appearance of the bone marrow, atrophy of osteoblasts, and thinning of bone trabeculae. Because of this, spongy bones in S. are often porous, deprived of their usual density, and can be cut with a knife. Scurvy patients die relatively rarely from pure S. with marasmus, anemia, and dropsy. More often, the immediate cause of death are complications in the form of sepsis, pneumonia, gangrene of the lung, dysentery, and tuberculosis. A. Abricosov. Etiology and pathogenesis. Although the problem of the origin, prevention, and treatment of S. was correctly resolved by doctors of the first half of the 18th century, in the 19th century there were attempts to explain the occurrence of S. by the lack of organic salts in the diet, poisoning by ptomaines of canned meat, and with the flourishing of bacteriology - infection by microbes. With their classic experiments, Holst and Frolich in 1912 put an end to all doubts and finally established that S. is avitaminosis C. Holst and Frolich achieved the development of experimental S. in guinea pigs by feeding them a special diet consisting of hay and various grains (wheat, barley, rice, oats, rye). Since this diet was insufficient in terms of its content of lipovitamins and led to the development of polyavitaminosis, it was later modified and to the diet of water, bran, and oats was added egg yolk, containing vitamins A and B but lacking vitamin C. Although such a diet is inadequate in terms of calories, the phenomena of developing S. are so predominant over all others that the researcher sees a pure picture of omno-avitaminosis. When feeding the guinea pig the specified diet, it soon loses its appetite, and its weight progressively falls. Usually after two weeks the animal becomes listless and due to pain in the joints becomes less mobile. After 3 weeks the joints become painful and swell, and the animal assumes the characteristic 'scurvy position' - it lies on its side, stretching out its painful limbs in front of it and somewhat upward (Chick, Hume and Skelton). Further, the fur loses its luster, becomes ruffled, the teeth become loose, and due to pain in the jaws and gums the animals lay one side of their head on the bottom of the cage (scurvy face-ache position). The gums in experimental animals are sharply hyperemic, ulcerative processes are rare, spontaneous fractures of the ribs are often observed, and finally with increasing exhaustion on the 25th-40th day the experimental animals die (Holst-Frolich, Tozer). The picture of experimental C-avitaminosis in monkeys is even closer to S. in humans: among the symptoms in them, edema, bleeding, loosening of the gums, and loosening of the teeth are observed. Hart and Lessing as early as 1912-13 managed to induce a state in young monkeys that was indistinguishable from Barlow's disease. Thus there is a complete analogy between experimental S. and S. in humans. After obtaining experimental S., it remained to clarify the chemical nature of the substances, the absence of which causes the development of S. Szent-Gyorgyi in 1928 isolated from the adrenal glands of bulls, from cabbage, and from oranges a crystalline substance of composition C₆H₈O₆, which according to further research turned out to be vitamin C. In 1933 Hirst and Haworth, in 1934 Reichstein, synthesized this substance, which received the name ascorbic acid, and thereby finally established its structure as the 1-isomer of the enol form of the lactone of 3-keto-gulonic acid: I HO-CH₂-C(OH)=C(OH)-COOH. II HO----------°------ Ascorbic acid melts at 190°, [α] = 49° (in methyl alcohol). Ascorbic acid is very easily oxidized, and this oxidation reaction is reversible, which allows one to assume the participation of ascorbic acid, similar to glutathione, in the oxidation-reduction processes of the body. There are indications of the activating effect of ascorbic acid on some proteolytic enzymes (cathepsin, papain, arginase). The human body's need for ascorbic acid (about 30-60 mg per day) is easily covered due to the wide distribution of ascorbic acid in nature. There is especially much ascorbic acid in the fruits of Capsicum annuum, oranges, and lemons. Although the action of vitamin C in the body is not yet fully known, on the basis of available experimental data it can be assumed that vitamin C affects the function of the protoplasm of cells throughout the body, and not of any one organ. As clinical data shows, in avitaminosis C, the formation of dentin associated with the function of odontoblasts, the formation of bones, and the endothelium of capillaries are affected - in short, there are disturbances in the vital activity of various organs and their functions, and from this it is clear that vitamin C is a substance without which life is impossible. The amount of vitamin C necessary for an adult pro die is about 50 mg. In newborns it is very high, not less than 25 mg. Observations by Kramar established that in premature infants who received large doses of pure vitamin, no side effects were observed, and thus it was established that there can be no talk of the harm of hypervitaminosis C (Harris, Ray, Ward). Excess vitamin C is excreted by the kidneys. It has also been established that the action of the synthetic preparation of vitamin C is identical to the vitamin contained in fruit juices. The diagnosis of S. is not difficult with a clearly expressed symptom complex. In differentiation from other hemorrhagic diatheses and leukemia, it must be borne in mind that the changes in the blood in S. are not characteristic. For S. is characteristic the localization of hemorrhages in the area of hair follicles and changes in the gum mucosa only around the teeth. A detailed questioning of the patient's diet and the result of the effect on the disease diet ex juvantibus help in diagnosis. Difficulties arise in cases when there are only insignificant invisible hemorrhages in the muscles and in the nerve sheaths, but here too a careful anamnesis helps; sometimes it is necessary to differentiate scurvy from rheumatism, tumor, and sciatica - in these cases the appearance of hemorrhages after applying a tourniquet has diagnostic value. Prevention. The usual picture of S. is a terminal manifestation of C-avitaminosis, initial changes are difficult to detect. Data from the experiment showed that primary phenomena begin soon after deprivation of vitamin C. Already by the end of the 5th day with C-avitaminous food, the guinea pig's body loses all its reserves, and Gyorgyi and Sverbelli, Hojer and Westin already on the 5th day of avitaminous diet histologically established the disappearance of odontoblasts. This disappearance of odontoblasts is a manifestation of a deep disturbance in the vital activity of the protoplasm of the entire body, and not only of the teeth. Such early changes show that between complete C-avitaminosis - scurvy - and health there is a wide range of hypoavitaminosis, which easily yields to medical intervention, and therefore for the prevention of mass diseases it is necessary to care for the proper supply of the population with fresh vegetables and fruits, as well as for the dissemination of information about their importance. It is absolutely necessary to specially care for the inclusion of products containing vitamin C in the diet of all patients limited by special diets due to the nature of the disease, this is especially important in all infections, fractures of bones, and in stomach ulcer. Prevention is especially important for the prevention of scurvy in children, because when milk is boiled, a significant part of vitamin C is destroyed. Children, starting from the third month, should be given fruit juices. Up to three months, children usually do not tolerate fruit juices, and the use of pure vitamin C at this time opens up wide possibilities in the struggle for the correct development of the child. Treatment. The specific therapeutic agent against S. is a diet containing a sufficient amount of vitamin C. The best source of vitamin is orange juice: 1 cm³ of it contains 0.5 mg of vitamin C, almost as much vitamin in tomato juice. A lot of vitamin is contained in cabbage, young carrots, spinach, green salad, potatoes, green onions and rhubarb, apples, strawberries, raspberries, black currants, and especially in the juice of lemons growing on the coast of the Mediterranean Sea. It is necessary that some of the mentioned vegetables and fruits be served in raw form, because during cooking some vitamins are destroyed. Vitamin C is very unstable and easily decomposes when heated above 60°, especially in an alkaline environment and in the presence of salts of copper (copper utensils), it is also very sensitive to oxidation. The activity of vegetables decreases when stored in the open air and when dried. A good source of vitamin C is raw liver and kidneys, and according to McCollum, fresh meat.

Raw milk from animals receiving green fodder contains vitamin C; during pasteurization and brief boiling in a well-sealed vessel, the milk loses little of the vitamin, but with prolonged boiling the vitamin is lost. Medicinal treatment has little importance. With gum soreness and bleeding, it is useful to apply a solution of potassium permanganate or a mixture of Tinctura Myrrhae, Rathan., and Gallarum aa, as well as rinsing the mouth with sage and chamomile. For hemorrhages into the muscles, warm compresses are beneficial, and to prevent contractures, timely prescribed massage.

I. Klinkovshtein. Lit.: Abricosov A., Changes in bones of the type of Barlow's disease in adults with scurvy, Voen.-vrach. san. sbornik, vol. I, M., 19(6; Krivusha V., On the question of pathological-anatomical changes in hematopoietic organs in scurvy, diss., SPB, 1888; Lavrov B., Scurvy, M.-L, 1933; Levitsky A., On the question of scurvy, diss., SPB, 1888; Novodvorsky V., Experience in determining the mechanism of spontaneous hemorrhages in scurvy, Klinich. med., 1928, no. 13; Osinsky N., Scurvy in children, M., 1927 (lit.); Palladin A. and Savron E., The influence of scurvy and starvation on the chemical composition of the brain, Zhurn. exper. biol. i med., 1927, no. 15; Pashutin, Course of general and experimental pathology, vol. II, SPB, 1902; Pletnev D., Clinic of scurvy, M., 1921; Scurvy and the fight against it in the north, ed. by A. Schmidt, M.-L, 1935; Scurvy, ed. NKZdr., M., 1921; Cherkes L., Vitamins and avitaminoses, M.-L, 1928 (lit.); Aschoff L. u. Kosp. W., Skorbut, eine pathologisch-anatomische Studie, Jena, 1919; Funk C., Die Vitamine, München-Wiesbaden, 1924; Hoist A. u. Frolich T., Uber experimentellen Skorbut, Zentralbl. f. Hyg. u. Infektionskr., B. LXXII, 1912, B. LXXV, 1913; Meyer A. u. Mc Cormick L., Studies on scurvy, Stanford Univ., 1928; Miiller E., Skorbut und haemorrhagische Diathese, Zentralbl. f. allg. Pathol. u. path. Anat., B. LVIII, 1933; Stepp W. u. Gyorgy P., Avitaminosen, B., 1927; Szent-Gyorgy A., Vitamin C, Adrenalin und Nebenniere, Deutsche med. Wochenschr., 1932, no. 22; ibid., Die medizinische Bedeutung des Vitamins C., ibid., p. 556, 1934; Tournay R., Le scorbut aux armées, P., 1921.