On the other hand, one must not forget that marked soorbutio symptoms have been induced in guinea pigs on laxative diets. Infantile scurvy has also been found to occur quite as often in connection with diarrhea as with constipation.35 It seems clear, therefore, from the foregoing facts that constipation is not the causative factor in scurvy. Undoubtedly the vital resistance of a scorbutic animal is lowered, thus rendering it more susceptible to unfavorable conditions like infections and toxemias.

Fig. 15.

Fig. 16. - Adequate protection against scurvy was offered by these milk powders containing, respectively, 12 per cent and 26 per cent of fat. The powders were made by a roll drying process.

Courtesy of Messrs. E. B. Hart, H. Steenbock, N. R. Ellis and Journal of Biological Chemistry (46, 315, 1921).

Gerstenberger 36 sought for a connection between scurvy and derangement of calcium metabolism.

35 Cf. American Pediatric Society Committee, Arch. Pediat. 1898, 15, 481. 36 Gerttenberger, Amer. J. Med. So. 145, 253, 1918.

In view of the known data regarding the pathology, chemistry, and symptomatology of scurvy on the one hand, and regarding the important function played by calcium in bone growth, nerve conduction, vessel sealing, and cell permeability on the other, Gerstenberger considered that all of these different system symptoms might be explained on the common basis of an interference with one or more of the normal functions of calcium and its physiological anion in the osseous system, vascular system, nervous system and probably other systems. That scurvy is not a calcium deficiency d indicated by the increase in the calcification at Frankel's line but while there is an excess of calcium deposited at one part of the bone there is nevertheless in all probability not so much calcium in the bone as a whole in advanced stages of scurvy as there would be in the normal bone, because the rate of growth of the bone is much less rapid than under normal conditions, while the normal process of resorption is going on, producing a rarefication and brittleness with consequent loss of material.

He fed cod liver oil containing tricaloium phosphate to scorbutic animals, but without result.Similar ill-success attended the administration of calcium in different forms by Hoist and FrBlich.37

Pitz 38 was able to protect guinea pigs against scurvy for 18 weeks by addition of meat and tricalcium phosphate to a ration of rolled oats and milk. He found some beneficial effect from the ingestion of tricalcium phosphate alone, but not so pronounced as when meat was introduced. Calcium chloride was more effective than tricalcium phosphate, showing that the phosphorus is not of prime importance. When sodium chloride was added to the oats, milk, meat, and tricalcium phosphate ration the onset of scurvy was delayed still further. Pitz concludes from this that the chlorine metabolism is deranged in scurvy as well as the calcium metabolism, and that the added calcium salts afford a certain amount of protection by controlling the permeability of the tissues of the animal and thereby affording protection against invading agents.

Pugliese 39 asserts that the conditions produced in animals by a ration of dried grain are not dependent upon the absence of the antiscorbutic vitamin, but are caused by a change in the reaction of the organic fluids, and a resultant demineralization of the organism, especially with respect to phosphorus and calcium.39a.

37 Hoist and Frolich, Zeitsch. Hyg. Infekt. 72, 1, 1912.

Young guinea pigs weighing 250-300 g., fed on a diet deficient in water-soluble C, show at death a pronounced increase in weight of the adrenal glands; this may indicate a compensatory response to the decreased adrenaline production known to exist in the scorbutic animal. The heart and kidneys appear to be increased in weight on scorbutic diets, while the liver shows no effect, LaMcr and Campbell (Proc. Soc. Ezptl. Biol. Med. 18, 32, 1920).

38 Pitz, J. Biol. Ghem. 36, 439, 1918.

39 Pugliese, Rend. r. Inst. Lomb. Sci. Lett. 52, 723, 1919; Physiol, Abstracts 5, 92, 1920.

39a Findlay (Biochem. J. 15, 355, 1921) claims that lack of vitamin A is in no way responsible for the lesions that occur in experimental scurvy.

Howard and Ingvaldsen 40 studied the mineral metabolism of the monkey during experimental scurvy, but without significant result. They state that the changes in the mineral excretion of the monkey during the scorbutic period are not sufficiently significant to admit of easy interpretation. The marked loss of the various mineral substances encountered in previous experiments with man and guinea pigs not having been observed in the present series. These investigators are of the opinion that a study of the intake and output of the inorganic elements in human adult scurvy and the experimental scurvy of the guinea pig and the monkey does not yield sufficiently decisive information to warrant an explanation of the pathogenesis of scurvy.

Robb41 found that guinea pigs subsisting on a diet of dried plants 14 or 21 days before the experimental period, eliminated twice as much calcium as those that had been on a green diet. Scurvy appeared in all animals.

While there is either lack of confirmation of or positive evidence against each theory of the origin of scurvy except that of deficiency in diet, there is convincing evidence in favor of this in the history of the disease and its treatment. As early as the middle of the Eighteenth Century Lind published an account of the disease showing the remarkable curative power of orange and lemon juice.41 This quaint report is of interest from a historical standpoint:

On the 20th of May, 1747, I took twelve patients in the scurvy, on board the "Salisbury" at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of their knees. They lay together in one place, being a proper apartment for the sick in the fore-hold; and had one diet common to all, vis. water-gruel sweetened with sugar in the morning, fresh mutton-broth oftentimes for dinner; at other times light puddings; boiled biscuit with sugar, etc, and for supper, barley and raisins, rice and currants, sago and wine, or the like.