The symptoms of guinea pig scurvy have been very carefully noted by various observers. A full description is given by Cohen and Mendel16 who remark as follows:

In the guinea pig this is a disease the onset of which is usually characterised first by a tenderness of the joints; and the wrists, ankles and knees become involved in the order named, though there are many exceptions. There follows in a day or so, a gradual swelling of the affected joints, often to twice or three times the original diameter of the bone. Sometimes in the younger animals a joint will fracture spontaneously, - the wrist being most susceptible in this regard. The older animals develop a difficulty in using their hind legs, which seem to become stiffened or paralysed. In order to relieve the pain in the affected member, the animals will lie on their side or back and assume the scurvy position described by Chick and Hume." If curative measures are instituted early enough, the swelling disappears entirely; if not, these knobs harden into exostoses that can be felt through the skin. The disease appears also to affect the junctions of the ribs with the cartilages, and in advanced cases it is possible to palpate these oostoohondral enlargements described by Jackson and Moore.18

14 Parsons, J. Biol. Ghem. 44, 687, 1920.

15 Plimmer, Biochem. J. 14, 570, 1920.

16 Cohen and Mendel, J. Biol. Ghem. 35, 426, 1918. 8ee also Oivcns and Cohen, lb. 36, 132, 1918.

17 Tr. Soc. Trop. Med. Hyg. 10, 141, 1917.

Accompanying the joint enlargement, one notices a marked hypersensitive-ness that is succeeded by a dullness or lethargy. The symptoms described may appear while the animals eat well and gain in weight steadily. Then follows a loss in appetite with a resulting decline in weight to death.

Hemorrhage of the gums in scorbutio guinea pigs has been reported by Mc-Colhttn and Pitx, and Jackson and Moore have found it in a few of their animals. However, Givens and Cohen, in common with Hoist and Frttlich, and with Gerstenberger, never observed this feature. Very rarely (in four cases) there was an appearance of submucous hemorrhage at the base of the lower incisors. Oftener (in ten or fifteen cases), there was observed a hyperemia or congestion at the same site.

Loosening of the teeth was quite a common occurrence in the animals with scurvy. Occasionally during life, the lower incisors were shown to be loose. Sometimes they could break off, though never in normal pigs or in animals with scurvy that was recently developed. At autopsy the lower molars were nearly always loose, - at times to such a degree as to permit the teeth to be removed easily with forceps. The upper molars on the contrary were not so often affected in this manner.

The X-ray picture of the affected joints is reported to be characteristic of the disease. As first shown by Fraenkel, there appears at the junction of the epiphysis and diaphysis of the long bones a white line which recedes very slowly after other symptoms have gone.

At autopsy the two most noticeable conditions are hemorrhage and fragility of the bones. The viscera often were normal in appearance; though now and then the stomach, intestines, or cecum showed congestion, hemorrhage or ulceration. These would occur usually on the oat and water or oat and milk diet, and less frequently on the soy bean diet.

The similarity between the symptoms thus described and those of human scurvy leave no room for doubt as to the identity of the disease in both species.

Hess and Unger 19 point out that all work on this subject should be checked by careful histological examination of the bones. Changes occur in the epiphyseal ends of the bones which are typical of scurvy and differ from those which occur in other diseases of the bony system. It is, therefore, imperative that such lesions be found before we take it for granted that we are really dealing with scurvy. Hess and Unger have encountered microscopic lesions at autopsy which were considered characteristic of true guinea pig scurvy (hemorrhages in to the costochondral junctions of the ribs and swelling of the joints) but which later microscopic examination proved to resemble rickets. The bones of the animals referred to in this study showed the typical "frame work" marrow at the epiphyseal junction, a marrow poor in cells and rich in connective tissue; it did not show the osteoid tissue always associated with rickets.

18 Jackson and Moore, J. Infec. Dis. 19, 478, 1916; J. Am. Med. Ass. 67, 1931, 1916.

19 Hess and Unger, J. Biol. Ghem. 35, 473; 36, 479, 1918.

Zilva and Wells20 have described the changes observed in the structure of the teeth of scorbutic guinea pigs. Even where no microscopic signs of the disease had been detected during the life-time and only the faintest traces could be discovered with the naked eye at post-mortem, well-defined microscopic changes were invariably detected in the structure of the teeth. In advanced cases of scurvy the teeth were found to be apparently sound but useless, inasmuch as they had been loosened by the gradual absorption of the cement membrane of the alveolar sockets, leaving the portion below the neck exposed. Probably pereostitic pain accompanies this condition as is the case with human patients. In addition, the teeth presented all the appearance of senile change.11

The condition in young guinea pigs was precisely the same as in the older animals, and the same changes have been observed in monkeys.

The circumstances under which scurvy makes its appearance points as indicated, to a dietetic origin for this disease, a hypothesis which is further supported by the beneficial effects of fresh foods or certain preserved fruit juices. Nevertheless certain other theories have been advanced from time to time.

Wright22 claimed that the symptoms of scurvy were caused by acidosis, a theory which has never found much acceptance23 and which is entirely disproved, so far at least as guinea pig scurvy is concerned, by the study of the alkaline reserve of the blood in scurvy made by McClendon, Cole, Engstrand, and Middlekauf.24

20 Zilvm and Wells, Proc. Roy. Soc. 90B, 506, 1919.

21 Talbot (Dental Cosmos, 63, 796, 1921) considers interstitial gingivitis (pyorrhea alveolaris), its oocurrenoe as a deficiency disease, and its relationship to scurvy.

22 Wright, Army Med. Dep. Rep. 37, 394, 1895.

23 See Pint, Norsk. Mag. Lag. 1912, 1; Hoist and Frdlich, Z. Hyg. 72, 1, 1912; Funk, J. Biol. Chem. 25, 409, 1916; Labbe, Haguenea, and Nepveux, Bull, mem. soc. me. Hop. 44, 1094, 1920, Chem. Abe. 1920, 3267.

24 McClendon, Cole, Engstrand, and Middlekauf, J. Biol. Chem. 40, 243, 1919.