similarity of the other symptoms to those produced by removal of the parathyreoids which follow the administration of guanidin and its methyl compounds seems to show that they play a part in the maintenance of that tone. 3. The fact that these substances are increased in the blood and urine after parathyreoidectomy, and in the urine in idiopathic tetany, suggests that their metabolism is controlled by the parathyreoids and that it is through them that muscular tone is regulated. 4. The immediate action of these substances in one adequate dose is undoubtedly to stimulate the efferent neurons of the spinal cord, and in a moderate dose to increase the excitability of the neuro-myons. But with repeated doses they apparently become anchored upon these structures to produce a condition of facilitated activity, and this is probably their chief mode of action in tetany. 5. That a decrease in the calcium of the blood is not the primary factor in the causation of the symptoms is shown by the effect of bleeding and transfusing a calcium-free solution, and further by the fact that a decrease in the calcium of the blood may occur without tetany, e.g., in uræmia, and that tetany may occur without a marked fall in the calcium. 6. There is no conclusive evidence to show whether this fall, when it occurs, is a result of the increase in the methyl-guanidin or a concomitant of it. 7. No satisfactory explanation of the rise in the phosphates has been given, although the results of Greenwald and György indicate that there may be a decreased excretion. 8. There is no indication that the increase in the phosphates plays a direct part in the production of symptoms. 9. Accepting the evidence that the parathyreoids influence the tone of muscles, they seem to do so by controlling the metabolism—production or destruction, or both-of the methyl guanidins. 10. Evidence has been adduced that the methyl-guanidins and creatin may be derived from the cholin of the lecithin molecule. 11. There is some indication that an excess of guanidins may be detoxicated by conversion to creatin. 12. There seems to be no doubt that the precursors of the methyl-guanidins are endogenous, although possibly the products of the digestion of meat, etc., may also furnish precursors. Since this paper was written an article by W. G. MacCollum on "The Pathogenesis of Tetany" (Medicine, 1924, iii., 137) has reached me. D. N. P. REFERENCES. 1 Quart. Journ. of Exp. Phys., 1916, x., p. 315. 2 Biedl, Innere Sekretion, 4th Aufl., 1922, Bd. iii. 3 Boothby, Endocrinology, 1921, V., p. 403. 3a György, Zentralb. f. die ges Kinderh., 1922-23, xiv., p. 1. 4 Luckhardt and Rosenblom, Proc. Soc. Exp. Biol. and Med., 1921, xiv., p. 129. Salvesen, Suppl. 6 to the Acta Medica Scandinavica, 1923. 6 Koch, Journ. of Biol. Chem., pp. 12-313 and 15-437. 7 Findlay and Sharpe, Quart. Journ. Med., 1920, xiii., p. 433. 8 Nattrass and Sharpe, Brit. Med. Journ., 1921, ii,, p. 238. 9 Sharpe, Quart. Journ. of Med., 1920, xiii., p. 433. 10 Greenwald, Journ. of Biol. Chem., 1924, lix., p. 328. 11 Komarow, Bioch. Ztsch., 1924, cxlvii., p. 221. 12 Frank, Stern, and Notthmann, Ztsch. f. ges. exp. Med., 1921, xxiv., p. 341. 13 Vines, Parathyroid Gland in Relation to Disease, Arnold, 1924. 14 Farner and Klinger, Mitt. Grenzgeb. Med. u. Chir., 1920, xxxii., p. 469. 15 Nicholas and Swingle, Proc. Soc. Exp. Biol. and Med., 1923, xxi., p. 1607. 16 Watanabe, Journ. of Biol. Chem., 1913, xxxvi., p. 531. 17 György and Vollmer, Arch. of exp. Path. u. Pharm., 1922, xcv., p. 200. 18 Wilson, Stearns, and Janny, Journ. of Biol. Chem., 1915, xxiii., p. 123. 19 Greenwald, Proc. Soc. Exp. Biol. Med., 1921, xviii., p. 228. 20 Cruickshank, Proc. Soc. Exp. Biol. and Med., 1923, xxi., p. 115. 21 Bayer, Ztsch. f. ges. exp. Med., 1922, xxvii., p. 119. 22 Trendelenberg, Arch. f. exp. Path. u. Pharm., 1921, p. 89. 23 György, Jahrb. f. Kinderheilk, 1922, xcix., p. 104. 24 Greenwald, Journ. of Biol. Chem., 1913, xiv., p. 363. 31 Pearl Henderson, Journ. of Physiol., 1918, lii., p. 1. 32 Wishart, Journ. of Physiol., 1920, liii., p. 440. 33 Frank, Notthmann, and Gottmann, Pflug. Arch., 1923, cci., p. 519. 34 Freudenberg and György, Jahr. f. Kinderheilk, 1921, xcvi., p. 5. 35 Morris, Brit. Journ. Exp. Pathol., 1922, iii., p. 101. 36 Grant and Goldman, Am. Journ. of Phys., 1920, lii., p. 209. 37 M'Cann, Journ. of Biol. Chem., 1918, xxxv., p. 553. 38 Anderson and Graham, Quart. Journ. of Med., 1924. 39 Scheer and Salmon, Jahr. f. Kinderh., 1924, civ., p. 65. 40 Kishi, Mitt. a.d. med. Fac. d. Kais. Univ. zu Tokayo, 1622, xxx., p. 91. Abstracted Berichte u. ges. Phys., 1924, xxiv., p. 364. 41 Salvesen and Linder, Journ. of Biol. Chem., 1923, lviii., p. 625. 45 Morel, Les parathyreoïdes, Paris, 1912. +6 Dragstedt, Amer. Journ. Phys., 1923, lxiv., p. 424. Dragstedt, Am. Journ. of Phys., 1923, lxv., p. 503. 48 Hammet, Amer. Journ. of Phys., 1922-23, lxiii., p. 151. 49 Luckhardt and Goldberg, Journ. Amer. Med. Assoc., 1922, lxxx., p. 79. 50 Dragstedt, Phillip, and Sudan, Am. Journ. of Phys., 1923, lxv., p. 503. 51 Reisser, Ztsch. f. physiol. Chem., 1913, lxxxvi., p. 413. Baumann, Hines, and Marken, Journ. of Biol. Chem., 1916, x., p. 263. Shanks, Journ. of Phys., 1921, lv., p. 8. Burns, Biochem. Journ., 1916, x., p. 263. Sharpe, Biochem. Journ., 1924, xviii., p. 151. 56 Shanks, Journ. of Phys., 1923, lviii., p. 230. Shanks, Journ. of Phys., 1924, lviii., p. 466. Wishart, Journ. of Phys., 1920, liii., p. 440. Burns and Sharpe, Quart. Journ. Exp. Phys., 1916, x., p. 343 HYPERTELORISM.* A hitherto undifferentiated congenital cranio-facial deformity. By DAVID M. GREIG, C.M., F.R.C.S.E., Conservator of the Museum.† Any event in this world—any human being for that matter—that seems to wear even the faintest cast or warp of strangeness, is apt to leave a disproportionately sharp impression on one's senses.-Walter de la Mare. I DEEPLY appreciate the honour that has been conferred upon me in asking me to deliver the Struthers' lecture. Sir John Struthers was a life-long friend of my father, and as Professor Struthers he formed one of the earliest recollections of my childhood and remained thereafter a paradigm and an incentive. It was an admirable characteristic of Sir John Struthers' anatomical studies, a characteristic thoroughly appreciated by surgeons, that they so frequently presented a clinical vein. No one knew better than he that the study of anatomy necessarily entails the study of abnormalities, that an understanding of growth is interwoven with appreciation of congenital defects, that the so-called normal is but the average among variations, and that the abnormal is merely a departure from a somewhat arbitrarily chosen type. I am not able to follow Professor Struthers' example by making the anatomical aspect the primary one, but I hope to present a clinical study in which I believe anatomical considerations do not form the least important feature. The outstanding peculiarity of the cranial deformity for which I propose the name ocular hypertelorism, or briefly, hypertelorism, is the great breadth between the the eyes. Hypertelorism (ὑπέρ = too much, τηλε = apart, ὁρίξω separate) preceded by the adjective ocular, accurately, concisely, and suggestively describes the salient and constant feature observable during life. = to Great breadth of nasal bridge sometimes with hypertrophy of bones, interocular hyper-rhinoplaty, to coin another name, may exist without an undue distance between the eyes. The eyes may be far apart in cases of frontal meningocele or encephalocele, or in cases of congenital facial or nasal cleft, * The fourth Sir John Struthers' lecture delivered in the Hall of the Royal College of Surgeons of Edinburgh, 1st February 1924. I desire to thank the Carnegie Universities Trust for a grant towards the cost of reproducing the illustrations of this paper. |