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SOT SETAT Tce gear haw: Gn arene Gn tirtetrerrtee—mal ewan — ee: Fee Te Tenement yeas en Trae ee aot. z coin sa doetspieataiates Bea - ome er error nee ea! ‘ ' ' \ ‘ \ 4 ‘ . ) et ie 4 j the Internet Archive — i in 200¢ with uni from a / '¥ i & ata —— i Se ae ' o er : vga i . e 4 . af / ‘ ‘I + i _ . ; ee NDOCKINOLOGY The BULLETIN of the ASSOCIATION for the STUDY of INTERNAL SECRETIONS Volume Two eee eS 38 /9//9 Published by the Association 1918 TABLE OF CONTENTS ADRENALIN VASODILATOR MECHANISMS. By Frank A. Hartman, STEREO Mee een ee eae eo ee cine reals © cies. ore nonin Rips «i's same ’ A NOTE ON THE USE OF CoRPUS LUTEUM TO PREVENT THE PAINFUL BREASTS OF MENSTRUATION. By H. Lisser, San Francisco.... A StTupy OF THE SYMPTOMS OF EXOPHTHALMIC GOITRE. By F. M. ee ere NIGH ier CU wos 3 -a.c srs wn slam ep mye wars wet Brey ee AINeE INDO GRIN E se ROBIE IM pie 2 Ne ciweiSiaca alttaiae miele Hig old elas aa, sie,=\el6 ENDOCRINOLOGIA, PATOLOGIA E CLINICIA. (Book Review.) By ea ae EE SEE ANID 5 a. ors mas Sip aiphatie Sem civeini mass ations Bin © THE LITERATURE ON THE INTERNAL SECRETIONS..........------- THE THYROID HORMONE AND ITS RELATION TO THE OTHER DUCT- LESS GLANDS. By E. C. Kendall, Rochester, Minn........... _ THE PITUITARY Bopy AND PoLyurIA. By B. A. Houssay, Buenos ANOS aR eae ee ASGi= Moris ce he tales Sea ais othe oateuest sha’ ebara Bak cut oui ON THE SEASONAL VARIATION IN THE IODINE CONTENT OF THE THYROID GLAND. By Frederic Fenger, Chicago............. CONFUSIONAL INSANITY AND THE OVARIES: A CASE History. By Genrverue Hoxie; ManSasn Oty trata teim olelewieie «13h Suet aera, ¥ ce DIABETES INSIPIDUS. By Ketil Motzfeldt, Christiania.......... VASCULAR CHANGES PRODUCED BY ADRENALIN IN VERTEBRATES. By Frank A. Hartman, Leslie G. Kilborn and Ross S. Lang, RD EA ee Dee SR ee ee Res enor ae SUPPURATION OF GOITROUS THYROID FOLLOWING ADMINISTRATION OF THYROID ExTrRAcT: A CASE Report. By Edward A. MUM ESOSLON Saree Toe oors cid cr ieiein onus sls ely Dc ee ab eras A CASE OF PARATHYROID INSUFFICIENCY. By Arthur L. Hertz, De NNR NER Rh Ie os wpa oll MNS brs ivimdotmin < o.8 WS bLCS wee BR 6 THE RELATION OF THE ADRENAL GLANDS TO SUGAR METABOLISM... ‘HYROMLAND) THyMus, “(Book Review):..¢ss0.% 0.05 00s ~ cc wwe THE LITERATURE ON THE INTERNAL SECRETIONS............---- A NEW PLURIGLANDULAR COMPENSATORY SYNDROME. By Walter SiirridyT CoO Wa OT Kee ae eros orerey Merorsiciciese cid. ule eye's wociSiaic sds « «'Se.s © Is THERE A THYMIC HORMONE? By E. R. Hoskins, New York.. ACTIVE COOPERATION BETWEEN THE PHYSIOLOGIST AND THE CLIN- ICIAN AND COMPARATIVE ANALYSIS OF CO-ORDINATED DATA IN THE STUDY OF THE INTERNAL SECRETIONS. By C. E. de M. ey TSS NTL Se ie ered SS at a IODIN AS THE ACTIVE PRINCIPLE OF THE THYROID GLAND. By W. Dee etree CE PINCEb OT. IN. Weer x si5 osc Ws ete Gar ccc ales os tacen THE EFFECT OF THE X-RAY UPON THE RESPONSE OF TADPOLES TO THYROID STIMULATION. By Carey P. McCord and Carlton J. MSIE NIMES ects ie oibrain sw elem ore 6s Lee w nts ment THE USE OF ADRENAL PRODUCTS IN ADDISON’s DISEASE. By Judson rail imc mm eMea LET CMI IAICL marta, he 5s) "state ye fe ict. oa = winds ictslare als Soe THE LITERATURE ON THE INTERNAL SECRETIONS................. 81 258 283 289 CYCLIC CHANGES IN THE INTERSTITIAL CELLS OF THE OVARY AND TESTIS IN THE WoopcHUCK (MARMOTA MONAX). By A. T. Rasmussen: Minneapolis! s. mc. 2eme eres ietareneteierete a oi Mey THE ROLE OF THE THYMUS IN PEDIATRICS. By Murray B. Gordon, Leaqovo) -d hip 0 eee eRM cS tO. oL we rhino. Nike ore Dee a isle ceumissye a Ste 405 THE NEWEST “HoRMONE.” By Swale Vincent, Winnipeg....... 421 A CASE OF MyYXEDEMA WITH TUMOR OF PITUITARY BODY AND LESIONS OF OTHER ENDOCRINE ORGANS. By W. H. Good and AS (Gs cmlhist Philadel phnra s Wrorts\- sc cte< ate, ststate yedsl lees eaekatestte acta 431 SoME POINTS OF CONTACT BETWEEN ENDOCRINOLOGY AND GYNECOL- ogy, ~By-Hmilp Novak; Baltimore’. ).1.'r ites se sere earere 438 HORMONE CONTROL-OF RENAL P'UNCTION:..~ .o- -cs se fe)t re clei eee 447 THESEINDOCRINE ‘GUANDS ENe THE) LINSAINED stale «+ cftie a steisennsicte ee stone 452 EILIOLOGYOOF IGRAVES? MOISHAGE. cle cic suctsee eel oui laaive se clekonensterecie 456 THE ADRENIN TEST FOR THYROID DISORDERS..............-.000- 460 ADRENIN: ANDO ARSPHENAMIND e. o: i 2 \ fees c ~e===—e—e—e—? H ' c “6. c-0 See cae c 6 | iS HH Figure 2 The open ring form of thyroxin as it exists in the body. that thyroxin behaves in this same way, and that it exists within the body, not in the closed ring form such as is present in indol, but in the form COOH NH:. The ability of the indol ring to thus open, furnishes the first concrete conception of how the substance behaves chemically within the body. The fact that both thyroxin and the acetyl derivative exists in open form, suggests that the reason for the inactivity of the acetyl is because of interference with the chemical reaction associated with the NH: group of thyroxin. One is at once struck with the fact that the open and closed forms of thyroxin bear to each other the same relation as does creatin to creatinin, and that the same relation exists between amino acids and the form in which amino acids are united in protein. Establishing these active groups emphasizes the importance of the chemical nucleus CO NH and COOH NH: within the body, which ap- pears to be a necessary structure for the carrying out of chemical changes leading to the production of energy. Patients with complete atrophy of the thyroid have basal metabolic rates approximately 40 per cent below normal. It has been shown that administra- tion of thyroxin alone can bring back and maintain the normal metabolic rate in such patients: But in complete atrophy of the thyroid, the complete or 92 THYROID AND DUCTLESS GLANDS nearly complete absence of thyroxin may be as- sumed. The question arises as to what maintains energy output from 100 per cent below normal, which would be death, up to 40 per cent below normal, the point to which basal metabolism sinks in the ab- sence of thyroxin. May it not be the other chemical substances in the body possessing the same group- ing that occurs in thyroxin? These are amino acids and proteins, creatin and creatinin, and a few other less well-known compounds. It seems probable that on the administration of thyroxin a reaction which has been carried on within the body by other com- pounds is merely increased in rate, but that there is no difference or disturbance of the reactions that have been going on. In regard to the relation of iodin to the activity of thyroxin, the presence of iodin in the compound must exert some influence, and it seems not improb- able that the presence of iodin renders the active groups more reactive. In the absence of iodin it would take a greater working pressure to bring about its reaction. The substitution of the iodin by hydro- gen or chlorine or bromine would undoubtedly be followed by an alteration in the degree of reactivity of the substance, but its gross chemical nature and properties would not be altered thereby. That the iodin breaks off from the molecule and is used as iodin per se for any purpose, seems absolutely im- possible because Plummer has shown that this sub- stance functions for as long as from 15 to 21 days after being administered, and that it acts as a true catalyst, being used over and over, hour after hour, without destruction except at a very low rate. It is finally removed from the body either by actual de- KENDALL 93 struction, or by slow loss in an undestroyed form. Our knowledge of other catalytic agents shows that poisoning of catalysts is common if not universal, so that its slow destruction is to be expected. The exact chemical reactions involved when this substance functions are still unknown, but that the substance possesses the formula as shown above is established by the ultimate chemical analysis of its derivatives. That the active groups present in thy- roxin are a necessary mechanism for the production of energy within the body seems highly probable, and it is of great interest and significance that there exists a close analogy between this substance, whose exact effect on metabolism we know, and other sub- stances, creatin, creatinin, amino acids and proteins, which are also intimately associated with reactions occurring within the animal organism. Are these substances also concerned in the maintenance of the basal metabolic rate? BIBLIOGRAPHY 1. Kendall (KE. C.) Studies of the active constituent, in erys- talline form, of the thyroid. Tr..Assn. Am. Phys., 1916, 31 134-145. 2. Kendall (E. C.) The thyroid hormone. Mayo Clinie Col- lected Papers, 1917, 9, 209-336. 3. Plummer (H. 8S.) The thyroid hormone, and its relation to metabolism. Presented before the Assn. of Am. Phys., May 6, 1918, Atlantic City. THE PITUITARY BODY AND POLYURIA B. A. Houssay, Buenos Aires The following article comprises a summary of var- ious of our observations previously published or re- ported before the Asociacién Médica Argentina (May 3, 1915) and abstracted in La Prensa Médica (1915, p. 451). A concluding report of the entire in- vestigation is shortly to appear. Different immediate effects occur when pituitary extracts are administered to dogs intravenuously. The chemical composition of the gland is very con- stant, as are the physiological effects of the gland ex- tracts, but these effects vary qualitatively according to the methods of preparation. Extracts of the fresh glands produce brief vasodepression followed by aug- mented arterial pressure; during the depressor phase of the reaction the kidney volume is diminished and oliguria occurs, but when the pressure rises a renodi- lation accompanied by more or less marked diuresis is noted. Sometimes we have noted an initial reno- contraction with or without general hypotension which persists for a short time into the hypertensive phase; this mav or may not be followed by renodilata- tion. In other instances, in case of the more strongly hypertensive extracts, kidney dilation and diuresis, together with augmented blood pressure, occur as the primary reaction without initial hypotension. This effect is observed generally in case of extracts prepared by the aid of metalic salts, of decoctions of powder of the posterior lobe desiccated at 37-45° and of preparations from glands extracted with alcohol. It would appear, then, that there occur in pituitary 94 HOUSSAY 95 extracts both renocontractor and renodilator sub- stances, one or the other predominating according to circumstances. The diuretic effects run parallel with the renovascular effects. When we observe the diuresis of twenty-four hours. the effects are not the same and they vary ac- cording to the animals. In rabbits there is con- stantly noted a strong oliguria, but in dogs and in the human beings the effects are extremely variable, and sometimes can be contradictory. In man it 1s com- mon to observe diuresis, especially in oligurics, al- though this action is less than in case of other diu- ‘retic substances. In polyuric men the effect is al- most constantly a depression of urine secretion. In the rabbits a tolerance to the drug develops and the initial diuresis returns at the end of a few weeks, in spite of daily injections. We conclude from the pharmacologic action of _ pituitary extract that it is not permissible to dedu:e an insufficiency of the pituitary body from the suc- cessful use of the extracts in polyuria. We cannot agree that the cerebro-spinal fluid has, as Cushing has claimed, the same effects as pituitary extracts. We have demonstrated, with Giusti in 1911, that the latter retains its actions, in spite of being treated with subacetate of lead, while in case of former the action is lost. In 1913 we proved, as Mackenzie has proved (Quart. Jour. Exp. Physiol., 1911, p. 805), that the cerebro-spinal fluid had not the diuretic action and not even the galactogogue action, which are the most specific tests of pituitary material. For this reason we cannot concur in the opinion that the active components of pituitary extracts pass to the cerebro-spinal fluid. This does 96 PITUITARY-POLYURIA not signify that we deny that the pituitary body has some secretions that pour into the third ventricle (as Hering affirms), but it is not proved that it is the diuretic or hypertensive substance. The operations made for the removal of the pitui- tary gland produce different results in adult dogs and in puppies. In the adults it is very often oliguria, while in puppies it is polyuria that occurs during the first few succeeding days. These results are in agree- ment with those of Cushing and his co-workers. These effects are due merely to the trauma, and it is possible to observe them in animals operated upon without actually removing the gland, or even touch- ing it. The intervention of the pituitary in the polyuria can be excluded, because we have obtained this reaction in cases in which we have removed the whole gland, proved by a series of sections of this region, studied histologically. As we were not able to study directly the injuries of the cerebral basal zone, because the operation to disclose it produced oliguria (adult dogs) or polyuria (puppies), we employed a method similar to that of Camus and Roussy (Presse Médicale, 1914, p. 517). Pricking through the sphenoid with a hot needle or utilizing ivon filings (in which manner it is possible to observe the dogs a very long time, while with the pricking it is necessary to kill them a few days after the puncture because the injury disappears quickly), we obtained in all cases identical results. If the pricking had been in a determined cerebral zone we observed polyuria, and if the pricking had been out- side of this zone the polyuria did not occur. In one case the puncture encountered the pituitary stalk HOUSSAY 97 and penetrated into the third ventricle, without in- jJuring the brain and no polyuria developed. The zone able to generate polyuria in our experi- ments was limited behind, by the peduncle protuber- ance; before, by a line near the anterior limit of the optic chiasma and laterally, as shown in the aeccom- panying drawing. Ventral surface of brain of dog showing zone injury of which produces changes in kidney secretion. Zone outlined by dash line. Finally, we consider that the cerebral basal zone ean generate polyuria. We do not deem it probable that the pituitary constitutes a part of this zone, al- though it is possible that the posterior lobe of the gland participates. It cannot be accepted, now, that polvuria is due toa diuretic hypersecretion of the pituitary gland. ON THE SEASONAL VARIATION IN THE IODINE CONTENT OF THE THYROID GLAND. Frederic Fenger Research Laboratory in Organotherapeutics, Armour & Company, Chicago, Tl. In previous communications on this subject it was shown that a marked seasonal variation exists in the iodine content of the thyroid gland of cattle, hogs and sheep. There is in general from two to three times as much iodine present in the glands in the months be- tween June and November as in the months between December and May. (1) A more or less regular sea- sonal change in the size of the fresh gland exists in the case of cattle and sheep, but not in hogs. A con- sideration of the several causes for the fluctuations leads to the conclusion that the temperature is per- haps the most important of all. (2) These investigations were conducted from Septem- ber, 1911, to December, 1913, during which time sam- ples of fresh glands were collected twice a week and stored at freezing temperature. The glands were trimmed, prepared and analyzed twice a week. The bi-monthly samples represented about ten pounds of fresh glands. During the past four vears, 1914-1917, data have been accumulated on more than one hundred lots of desiccated thvroids from cattle, hogs and sheep which furnish the raw material for medicinal thy- roid preparations. The samples were supplied by the factory and analvzed in this laboratory for con- trol purposes. 98 FENGER 99 Fach of these lots represent many thousand glands and the collection time covered periods of several weeks. The animals furnishing the raw material came from all parts of the United States, with the exception of a few of the Eastern and Southeastern States. It is evident, therefore, that such factors as locality, feed, water, and particularly the consider- able individual variation which is known to exist, have been satisfactorily. eliminated. The fundamen- tal causes for the fluctuations in the iodine content of the thyroid gland consequently must be tempera- ture and weather conditions. In the tabulation below are given the maximum and minimum iodine content of the thyroid glands collected during the two periods mentioned above and the vearly averages for the entire six years. All fig- ures are calculated to a dry fat-free basis. Percent of Iodine in dessicated fat-free glands Entire Period Time 1911-1913 1914-1917 1911-1917 Cattle: PCR NMIUTRIN) eice se walmcies.c ek. Se 0.43% 0.43% CUTEST OO, Gee, en 0.04 0.04 SEPEINY “BVETAR CS io oa sues a eh Be 0.205% Hogs: VES GTS Ser oes eee eee 0.47 0.38 Lifreniiers tie Pee eee eS ee ee ee 0.17 0.15 MieGarliVeaVETAPGre 2.) oo. sa 8st ie 0.300 Sheep: IAEA cee et Bete oe 0.28 0.26 CUD TT ETT ss Oe. cae OIE 0.04 Pie e. is 0.150 It will be seen that the figures obtained during the last four vears are almost identical with the earlier findings, as far as cattle and sheep are concerned. In case of the hog, the differences are more marked. This is in all probability due to the decreased number of hogs slaughtered during hot weather and the ex- tended collection time. The average iodine content of the hog thyroid, 100 IODINE OF THYROID taken vear by year, is considerably above that of cat- tle and sheep. This may be of some significance, since the former is an omnivorous animal, while the latter are strictly herbivorous. The seasonal variation in the size of the thyroid gland of cattle and sheep has been referred to above. Of these, the beef gland particularly is influenced by cold temperatures. It has been noticed year after vear that the onset of severe cold weather is followed in a week or two by a noticeable enlargement of the eattle glands and consequent lowering of iodine con- tent. This enlargment is less prominent or occurs later in mild winters than in severe ones. The glands of sheep are also quite sensitive to temperature changes, but not to the same degree as those of cattle. Fluctuations in the yearly average iodine content of the thyroid gland also exists. These are natur- ally small and vary but a few hundredths of one per cent from year to year. ‘They are undoubtedly due to weather conditions generally. Where due allowances are made for climatic flue- tuations and the differences in the time periods of collection, the last four years’ results, when plotted out on paper, follow closely the curves published in previous reports. SUMMARY Additional evidence has been furnished to show that a distinct seasonal variation exists in the iodine content of the thyroid gland from cattle, hogs and sheep. The temperature factor is the most important of all in producing these fluctuations. BIBLIOGRAPHY 1. Seidell and Fenger. J. Biol. Chem., 1913, 18, 517. 2. Seidell and Fenger. Bull. No, 96, Hygienie Laboratory UlS. PBS 1914, p: 67: CONFUSIONAL INSANITY AND THE OVAR- IES: A CASE HISTORY George Howard Hoxie, A. M., M. D., Kansas City, Mo. In the 1898 Edition of his Psychiatrie, IKvaepelin states (1) that there is a close relation between men- struation and psychic disturbance, but that he in- clined to the view that the relation was not causal. In a symposium on the subject of the relationship between gynecologic and neurologic conditions be- fore the Michigan State Society last spring, Reuben Peterson (2) held that there are four classes of pa- tients to be considered, viz.: “1. Women with neurologic symptoms whose pel- vice organs are anatomically and physiologically nor- mal. 2. Women with neurologic symptoms whose gen- ital organs are anatomically normal but whose fune- tions are abnormal. 3. Women with derangements of the nervous sys- tem whose pelvic organs are unquestionably diseased and where the disease may aggravate but does not necessarily cause the nervous manifestations. 4. Women of naturally good nervous organiza- tions whose nervous manifestations have followed upon and hence apparently are due to true pelvic lesions.’”’ This analysis is very useable, for it puts the crux where it belongs,—namely, in the antecedent condi- tion of the nervous system. And in our study we should make this point our first determination. Bandler (3) outlines a very comprehensive theory 101 102 OVARIES AND INSANITY as to the interaction of the ductless glands in gynecol- ogy. He lays great stress on the influence of the ovary on the pituitary, and seems to believe that definite psychical manifestations may result from ovarian insufficiency. Auer (4) in 1915 expressed the opinion: ‘‘that the occurrence of insanity at puberty and adolescence after severe physical and mental strain and at the time of menopause,—all periods when the metabolic changes of the body are intense,—and the occurrence in syndromes unquestionably the result of disease of the glands of internal secretion of idiocy, imbecility, depression, mania and dementia suggest strongly that the true etiology of the effective psychoses lies in a junctional disturbance of the glands of internal se- eretion.”’ The best statistical study is perhaps that of Carey McCord (5), which he summarizes thus: ‘‘At the Michigan Home and Training School a survey has been made of. 1,134 feeble-zninded inmates for evi- dences of involvement of the internal secretory sys- tem in the defects of growth and development in the feeble-minded. Of the number examined, 240, or 21.16 per cent, presented the characteristics of vari- ous glandular syndromes. From our investigation the following inferences appear justified: “1. Of the glandular cases seen in the feeble- minded, heredity stands out as the foremost factor in the etiology. 2. The demonstration of svndromes in the feeble- minded does not in itself allow any inference that the feeble-mindedness is attributable to the glandular dysfunction. The glandular disease may determine the increasing defect, but more often the co-existing feeble-mindedness and glandular defect are both the outcome of a common cause. HOXIE 103 “3. Promiscuous treatment of the feeble-minded with glandular derivatives is unprofitable and un- warranted. In established glandular types among the feeble-minded, more often glandular treatment is of no distinct and lasting value. ‘4. In borderline cases of glandular disease with trivial mental inadequacy, glandular therapy may prove of special value. More often in these cases no true mental deficiency exists, and all manifestations of mental inadequacy are referable to the glandular mal-function. In such cases glandular treatment persistently carried out may be the factor deciding between normality and increasing defects.”’ In the following case we have some data not usually encountered, and they are given in the hope of mak- ing more definite our concept of the relation between ovarian secretion and neurologic condition. The psychic perturbations are well brought out in the transcription of the patient’s own words. Female, age 25, single, high school teacher. Family History, without definite stigmata. Personal History. Normal childhood. Menses at 12; since 14, painful. The pain is in the left side and begins before flow and lasts into second day. At 19 curetted and lay in hospital for three weeks. She had taken normal, college and university work, graduat- ing with high honors. She had done special work in biologic research and won high commendation from the head of the department. She had taught ina high school two years with egneral satisfaction. Her state- ment of her scholastic life follows: ‘‘I was graduated from advanced course at the normal when I was sev- enteen. I did teach school in our little country school and stayed at home while teaching. When I entered 104 OVARIES AND INSANITY the university I was given Junior credit plus ten hours. I completed both degrees b. A. and M. A. in two and a half vears, graduating in nineteen-ten. The year following my entrance to the university [ taught school at ———-. While here I stayed with my sister, who was married when I was a mere child. When I was graduated from the normal Miss — told me to write, but not to attempt anything for publication until I was 35, but to write, write. She gave me a beautiful picture for having made the best average in the class. Prof. —_—— told me to study seulpturing, Mrs. — wanted me to specialize in music. When I entered the university the zoology people wanted me to specialize in their department. Dr. suggested that I try for the Bryn Mawr scholarship and said he would help me. The spring term of 1910 I assisted in zoology and was invited to join the zool- ogy faculty meetings. That same spring I modeled chromosomes in clay with which to make candy chro- mosomes for the Sigma X banquet.’”’ Her present complaint is of pains in the back of her neck and through the heart, and a backache, dura- tion four or five weeks, but the patient is too confused to state her condition clearly. An aunt’s letter fol- lows: ‘Nov. 29, 1913. ———— was engaged to be married and the date was set several times, but each time there was some excuse; once it was that she must help her brothers, by teaching school, to a profession of some kind. Then her poor health had been a rea- son. The young man has been very patient and I do not suppose realized that her mind had anything to do with putting the date off so many times. But he came to the conclusion it must be she did not love him HOXIE 105 sufficiently and wrote to that effect and we think the engagement is broken. In those spells she says she is ‘broken-hearted,’ and nothing can take the ‘pain out of her heart,’ that ‘no one cares or under- stands,’ that ‘no one belongs to her,’ till it is very dis- tressing, but she never mentions his‘name or tells us her trouble, but wants to make us think her worry is all about the boys’ failure in hfe. My sister can see now that — ’s mind has not been entirely right for several years at times. And I suppose she has been suffering from this trouble since about fif- teen or sixteen years of age. She has always been a great student, graduated from the ——-— Normal and the State University; has taught school for sev- eral years and her pupils love her so much they al- ways want her to come back. She tried it one week this fall but had to resign.”’ Status: 12. VII. 1913. Weight 132 (last year 13014). Nocturia and dysuria present. Neck shows enlarged thyroid (circumference 31.5 and 34 em). Slight rotary nystagmus. BP, 85-109. Pulse, 108. Heart and chest negative. Right hypochrondrium slightly tender. Left groin very tender. Pushing on left leg causes pain in back. Uterus retroflexed, not tender. Bladder very tender. Tongue serrated. Urine: acid, 1028, indicanuria, many bacteria in fresh specimen, much epithelium. Blood: Hb. 80; Rbe. 5,600,000; Whe., 15,300; polys. 64; monos. 25; eosin. 7, (amphophiles 22). 24. VII. 18. Entered hospital for treatment. T. 97.6, 98.4; P. 80-96; R. 20-24. BP. 80-100-110. Dy- suria. Sleep poor. Has been weeping much at home. Twitches arrhythmieally. 25. VII. 18. Under ether, uterus dilated, Naboth- 106 OVARIES AND INSANITY ian cysts opened, erosions curetted, ete. Left hos- pital after 10 days. d. IX. 13. Office consultation. Still nervous. Noe- turia. Pain in left hypochondrium. Neck 31 and 33 em. Weight 131. 21. [X. 13. Patient’s statement of condition: ‘*Pulse varies from 120 to 130. Pain in side—two distinct and separate pains, one a dull ache, the other sharper and feels as if part of my anatomy were con- tracting—brings me up with a start at times. Pain under ribs part of time. Pain in back nearly all the time. Pain in stomach has been very severe for some seven days. The sharp pains extend further down into the abdomen than formerly. My throat bothers me a very great deal—feels as if something were choking me. Red pimples occur all over my body. The shghtest blow makes an ugly black spot. My skin is rough and dry and scales off constantly. * * * I have no ambition or enthusiasm—don’t seem to care about living. It is horrible to feel this way. I am sure I don’t understand why I do.”’ 6. X. 13. From patient’s statement: ‘Condition of tongue—not as badly coated but more highly decorated around the edge. Appetite— none at all, but eat from sense of duty. Digestion is fairly good. Sleep—very restless and am forced usually to resort to sleeping tablets. Bowels act three or four times during day. Kidneys either act very frequently or rarely. In either case, the amount is small. There is always an action during the night and frequently three or four. Pain—not as much in stomach and under ribs. Pain in back and side is much the same. Opposite the heavy pain over my heart, there is a dull pain under the left shoulder HOXIE 107 blade. I have been having a heavy dull ache in my head and when I stand it becomes a throbbing pain accompanied by dizziness. When I was ill last week I suffered very much with pains in my side and back, There was no flow but a discharge.”’ 4, XI. 13. Daily weeping—sobbing—nightmares. Weight 127. Pain in left sacral region most of the time. Coarse tremor of hands and tongue. Pain in left groin when defecating. Neck 30.5 and 32.5, Urine full of bacilli (motile) with pus. 12. XI. 13. From patient’s statement: ‘‘T was so tired and weak when I arrived in ———— that I sank almost at once into a comatose state. The last thing I remembered was vigorously and emphat- ically protesting with the girls not to send for you— I knew I would be all right in the morning. I felt this manifestation of coma enveloping me when I Was in your office—I think it was this condition of mind that made me so stupid. Unele (fictitious— G. H. H.) says you understand why I always exhibit my very worst self when I get nervous and that I must not worry about it, that it will come out all right, when I get less nervous and stronger. He’s such a comforting Uncle. I have been having a little fever each day since coming home. Since beginning the medicine and enemas I have suffered with severe burning pains very low down in the abdomen. The pains are more severe when the kidneys act. They act six or seven times during the night.”’ 30. XI. 13. Mental condition worse rather than better—confused. Visions of father who had died two years before. Indicanuria persists with bacil- luria. Re-enters hospital. 2. XII. 13. Endometritis with profuse secretion. See ee “408. OVARIES AND INSANITY Rectum still inflamed. Renal excretion of phtha- lein 28% in 1 hr., 56% in 2 hrs. Blood: Hb. 90, Whe. 7500, polys. 80, eosin. 5, monos. 22 (amphophiles 22%). Urine eulture, staphylococcus. 8. XII. 13. Hysterical delirium caused by moth- er’s visit. 17. XII. 13. Tenderness in left hip persists; it seems to include both muscles and bones. 29. XII. 13. Cervix practically normal. 1. I. 14. Tenderness in left groin very slight. Patient cannot bring her fore fingers together with eyes shut. 10. [. 14. Still indicanuria. Earthy phosphates. 22. |. 14. Better but cannot collect thoughts or remember recent events. Still visits her father in her dreams. Still has far-away look in her eyes. Pain in side and headache after exercise. 14. Ill. 14. Just returned from spending a month in a sanatorium for mental disease. The contact with the really insane has brought about self-control. She still feels a ‘‘hurt inside’’ which she cannot ex- plain and thinks that it has been there since father’s death. No memory of her last few years. A letter about April 28, 1914, gives her own state- ment of her symptoms thus: ‘‘At night [ am afraid to go to sleep and afraid to remain awake. My heart and soul are so hurt that I don’t feel I can endure it much longer. When I do sleep I dream Miss , mother and you stand around my bed exclaiming in derision, ‘ You are nota truthful person; we don’t trust you; you are not good like your friends,’ and oh! the scorn in your voices. Then, often I plead with you to believe in me and HOXIE 109 show me what to do, you all refuse and desert me. At this point I find myself screaming or sobbing. ““‘T was beginning to feel so much better the last few days I was in Colorado. But nothing seems to help the weight in my head now. I am out doors nearly all dav working inmy garden. I work until I ean endure the feeling of wrong doing no longer, then I have to ery it out and begin over again. I never have a moment’s peace. I am beginning to think I shall never be a normal person again. I have forgot- ten how to smile or be able to bring joy to anyone. I am so wretchedly unhappy—I find myself imagin- ing all kinds of things about myself that would make me different from good people. ‘The last time I menstruated I began to menstru- ate four or five days too soon. The nature of the dis- charge indicated I had taken cold some way. I am so dizzy-headed, have a bad taste in my mouth and _ have very sluggish bowel action and bad stomach.’’ 10. IX. 14. Her mythical uncle still ‘‘writes”’ to her. 4. XII. 14. Menses accompanied by a delirium. Relieved by corpus luteum. Urine negative. Is a pupil nurse in a hospital. 9. IV. 15. Has lost 25 pounds. Now has sore throat and grip. 4. VIII. 15. Pain in left kidney, with frequency and painful micturition. 2. IX. 15. Laparotomy—Hertzler—A fibroma of the round ligament 3.5 cm. in diameter: removed. Left ovary senile. Right only slhghtly better— neither removed. 5. IX. 15. Culture of urine shows a Gram negative bacillus still present. ~110 OVARIES AND INSANITY 25. IX. 15. Constant back and left side ache. Wob- bly on her feet. Troubled by dreams. 10. XII. 15. Left kidney and ureter still tender. 23. Il. 16. Patient requires corpus luteum at every menstrual season. Mental confusion present but can be controlled by this remedy. 30. I. 17. Weight 14414. Still shows nervous weakness at menstrual season, but can do her work Backache and left side ache. 18. IV. 17. Frequent micturition. Sore throat Tired out. Mentally clear. 13. IX. 17. Blood: Hb. 100; Rbe. 4,609,000; Whe. 9000; polvs. 71; eosin. 3; monos 25. Vaccinia with infected arm. Mentally clear. SUMMARY A young, university-bred woman who has always suffered from dysmenorrhea, practically since the onset of puberty, after teaching in a high school for two vears, alarms her friends on account of her men- tal imbalance. Her own account of her condition would place it among the melancholias. But her physical condition is also bad on account of neglected pyelitis and cervicitis and constipation. Treatment for her physical condition, with rest in a convalescent home, slowly brought her out of her melancholia. But not until corpus luteum was given at the men- strual season did she clear up sufficiently to make herself practically useful. The monthly attacks are of the confusional nature—melancholy because con- fused. The young woman is now successfully carry- ing on her chosen work. DISCUSSION In this case the connection between the ovarian dysfunction and the mental confusion was incontro- HOXIE LEE vertible. The other physical conditions—the back- ache, the pvelitis, the vaccinia, ete.,—came and went without disturbing the patient’s mental condition. _ But the ovarian dysfunction produced regularly the mental confusion. The mental confusion seemed to disappear as regularly upon the administration of corpus luteum (either H. W. & D.’s ‘‘lutein,”’ or P. D. & Co.’s ampoules of soluble extract). The patient vrew steadily stronger and the attacks of confusion more fleeting, so that at the end of the story she was: not incapacitated for work at any time during the menstrual cycle. We were rather slow in arriving at this conclusion, and worked first on the hypothesis of its being a base hyperthyroidism. Then, as this syn- drome disappeared, we thought of Freud’s theories; and then, as the mind became clearer, of simple hys- teria. But in the end when all the complicating symptoms subsided it seemed clear that the disease was of the confusional type and due to atrophic ovar- eB: The interesting finding of the very rare fibroma of the round ligament, and its removal, seemed to have very little bearing or influence on the mental condition, although the operation relieved some of the dysmenorrhea. BIBLIOGRAPHY 1. Kraeplin. Psychiatrie, 1898 edition, Vol. I, pp. 60-61. 2. Peterson (R.). Neurologic and gynecologic conditions. Jour. Mich. St. Med. Soe. (Grand Rapids), 1917, 16, 51-2. 3. Bandler (S. W.). Ductless glands in gynecology. Am. J. Obst. (N: Y.), 1917, 76, 644. 4. Auer (EK. M.). The psychical manifestations of dis- eases of the glands of internal secretion. Am. J. Insan. (Balt.), 1914, 71, 405. 5. MeCord (C. P.) and Haynes (H. A.). Frequeney and significance of dysfunction of internal secretory system in fee- bleminded. N. Y. Med. J., 1917, 105, 583. DIABETES INSIPIDUS Ketil Motzfeldt, M. D., University Clinic, Christiania, Norway. Diabetes insipidus has for centuries been recog-— nized as a distinct clinical entity, the main symptom of which is polyuria without pathological content in the urine. The etiology, however, has been obscure. Older writers have distinguished between an “idiopathic”? and a ‘‘symptomatic’’ form, while more recent authors have sought by the functional kidney tests to establish a distinct division between primary polvuria and primary polydipsia. It has also been suggested to reserve the term diabetes insipidus for the ‘‘true”’ cases, that is for the primary polyurias due to an insufficient ability of the kidneys to pro- duce a concentrated urine. During recent years new viewpoints have been advanced of far reaching significance for the con- ception of the etiology and pathology of this disease, — views that have been reflected in the therapy, which at present seems to be more promising than has previously been the case. Although many ob- secure questions remain to be solved, it now appears justifiable to classify the disease as a disorder of the pituitary body. There are many cases in which this cause is beyond doubt, and probably the majority of the ‘‘true’’ diabetes insipidus cases will turn out to be of pituitary origin. It has long been known that polyuria often occurs after traumatic lesions of the skull, and that it is a frequent symptom of certain nervous diseases, or- ganic as well as functional. 112 MOTZFELDT 113 Claude Bernard’s celebrated piqure (1854) threw some light upon these facts, and he believed that he had discovered a ‘‘centre’’ for diabetes insipidus. Later investigations, however, have shown that polyuria will result from lesions of many other parts of the nervous system. These observations gained in importance, as Magnus and Schafer (1901) showed that the pitu- itary extracts had certain diuretic properties. This statement has led to considerable confusion and it has but recently been recognized that the effect really is antidiuretic. Clinically the direct relationship between diabetes insipidus and the pituitary body was first pointed out by Frank (1912), and during the few years that have elapsed since, similar cases have been reported where this relationship is unquestionable. As far as our present, limited knowledge goes, the most frequent pathological findings are tumors, syphilis and tuberculosis. The pituitary adenomas, which are the most fre- quent causes of acromegaly, only exceptionally lead to polyuria, and little is known about the effect of the pituitary cysts. In most of the cases there have been found malignant tumors, either of the neighbor- hood, secondarily involving the pituitary, or in the gland itself. Metastases from cancer are especially prone to locate in the hypophysis. The frequency of a syphilitic history in these cases has long been known. Anatomically the usual finding is syphilitic basal meningitis. This prob- ably in some way interferes with the functional ac- tivity of the hypophysis. In a few instances there were syphilitic lesions of the gland proper. 114 DIABETES INSIPIDUS In many of the cases of diabetes insipidus on record the patients have been suffering from pul- monary tuberculosis, but this fact has not attracted much attention. Of recent years careful anatomical investigations, however, have shown actual tubereu- losis of the pituitary body, sometimes with total de- struction of the gland. These changes are easily overlooked, and in some eases the lesion has not been discovered until the microscope has revealed it. Negative findings, where the hypophysis has not been specially examined, therefore, amount to little. There are, furthermore, as I have reason to be- heve, a certain number of cases due to atrophy or congenital hypoplasia of the gland. It is well known that polyuria often sets in during or after acute in- fectious diseases, and also how apt the ductless glands in general are to be damaged by infections. It is a common experience, gained in experimental as well as in clinical surgery of the hypophysis, that polvuria often occurs after removal or injury to the gland. Most writers on this subject have supported the theory that these conditions have acted as stimuli for the pituitary, in accordance with the views of Mag- nus and Schafer. But as there are some cases where the entire gland has been destroyed, we are obliged to drop this hypothesis and assume a hypo-function of the gland. Some cases have shown a total destrue- tion of the posterior lobe, while the anterior has re- mained intact. During the past four years, or since attention has been directed to the pituitary body as concerned in this disease, there has not been reported a single MOTZFELDT 115 autopsy finding in which this gland has not been in some way involved. These cases are not numerous and they are scat- tered in the literature of many countries, and a pre- sentation of the features common to them has not yet been given. By making retrospective diagnosis in the older diabetes insipidus literature I have been able to add a number of cases where the pituitary origin can be regarded as pretty well established. On this basis I will now outline some features of the clinical picture. It has been surprising to see how relatively clear-cut and uniform this condition is, when facts which were previously considered of minor importance are taken into account. The pic- ture is in general agreement with what the text- books give as the symptoms of diabetes insipidus, without any regard to the pituitary origin. Adi- posity is frequently mentioned, but it seldom reaches any extreme degree. In the few cases where it has been tested, there has been found a high carbohydrate tolerance. Almost as common as adiposity is sexual underdevelopment, the degree of which will be de- pendent as well upon the seriousness of the disease as upon the age at the onset. If the polyuria sets in during childhood, puberty will very likely be delayed or entirely lacking and the patient remain in a more or less pronounced infantile state. When the onset has come in adult age, regressive changes in the sexual organs have sometimes been noted. Im- potency and amenorrhoea are among the most con- stant svmptoms, and usually set in simultaneously with the polyuria which in most instances starts quite suddenly. The secondary sex characteristics show the same changes. The growth of hair in the 116 DIABETES INSIPIDUS armpits and on the pubes is scanty, and even marked loss of hair may come on shortly after the onset, though this is comparatively rare. The growth of the beard is apt to be scanty and slow, while there are usually no changes in the hair on the head, and the eyebrows are also intact. This last mentioned fact is in distinction from hypothyroidism, where the ‘‘eyebrow sign’’ is said to be of value. These patients usually suffer from constant fatigue and are troubled with a never-ceasing lassi- tude; in other words there is a more or less marked asthenia. In many cases psychic alterations also take place, such as somnolence and apathy, some- times accompanied by depression and melancholia. The skin is usually dry and these patients per- spire very little. Another valuable sign is the slightly subnormal temperature. Apart from these general manifestations there are certain symptoms which are directly pointing to. the hypophysis, such as enlargement of the sella turcica and bitemporal hemianopsia. Neither of these findings are very frequent, and negative results do not speak against the pituitary diagnosis. The combination of poly- uria and hemianopsia has long been known, and the visual disturbance is often of a peculiarly short dura- tion, the hemianopsia fugax. All the distressing symptoms of an intracranial tumor may of course be seen in some cases. It could not be expected to find all or even the majority of the above mentioned symptoms and manifestations in each case. However, I believe it will be very rare, in cases of primary polyuria, not to find anything pointing towards the pituitary body. There seem to be two fairly distinct types: the obese, MOTZFELDT 117 indolent; and the lean, infantile type. The family history does not give definite information, although some instances have shown a pronounced hereditary tendency. The complaint, which causes the patient to consult the doctor, is almost invariably polyuria, but when the degree is only shght the most distress- ing feature has been weakness or headache, and very rarely, eye troubles. This varying picture will naturally suggest a dis- ease of different ductless glands, but space will not permit me here to enter into a discussion of the inti- mate relationship between these glands. However, all of these signs can, with apparent probability, be referred to the hypophysis. As mentioned, pathological experience has shown that it is no longer permissible to assume an excess of pituitary secretion. It will therefore be of interest to see how the disease compares with the hypofune- tion of the gland. The picture of this condition has of late been brought out in an admirably clear way,— by Cushing’s work especially. It is sufficient to point out what he regards as the four cardinal symptoms: 1. High carbohydrate tolerance. 2. Subnormal temperature, slow pulse, low blood pressure. 3. Drowsiness and sleepiness. 4. Asthenia. Anhidrosis, scanty growth of hair, sexual hypo- plasia, impotency and amenorrhoea also belong to the picture, and it is now pretty well established. that: Froehlich’s syndrome, the dystropia spec sonee": talis, is due to hypopituitarism. The correspondence is so striking and obyious in- deed, that further comment is unnecessary:. Here T.- 4 118 DIABETES INSIPIDUS wish, however, to emphasize that it is not unusual to see very marked cases of adiposo-genital dystrophy or other cases of hypopituitarism with a normal out- put of urine. The functional activity of the posterior lobe seems to be well specialized. Usually the diagnosis is easy when the conditions just emphasized are taken into consideration. It is doubtful whether a subcutaneous injection with some pituitary extract is of diagnostic value, as the antidiuretic effect seems to be a general physio- logical action, not limited to the cases of pituitary insufficiency. | Psychic treatment or forced restriction of water, sometimes valuable in primary polydipsia, has not proven efficacious in ‘‘true’’ cases. A diet poor in chlorides and nitrogen has been the main treatment and has been able to lower the output to a certain extent. On the whole, however, the treatment has been rather unsatisfactory; none of the drugs recom- mended is of special value. Opium will sometimes decrease the thirst and in that way lower the output without exerting any influence on the concentration. The only remedy which has power to check poly- uria and concentrate the urine is the extract of the posterior lobe of the hypophysis. A subcutaneous injection with an ampoule of some of the usual com- mercial preparauons will probably be sufficient to exert a very marked influence on the output. This effect will usually show in a tew hours and reach its maximum in 4-5 hours. Unfortunately the effect is not lasting and the output will probably be high again the next day. There are, however, cases on record where the diuresis has been checked for weeks afterwards. ‘The injections are well borne; paleness, MOTZFELDT 119 slight headache and ringing in the ears may occur, but only last for a few hours. Intravenous injections are not advisable as they may lead to collapse. As this treatment cannot be kept up for a long period, it would be a great advantage if treatment by mouth might prove of some value. This mode of ad- ministration is far less efficacious, but is without dis- comfort and, as far as our present knowledge goes, is free from danger, even in large doses. Such treat- ment, therefore, can be carried on indefinitely. The sufficient dose has to be tried out in each case, and as a rule very large doses are required, the amount of active material absorbed from the intes- tinal tract being evidently very small. The commer- cial dry preparations will very likely prove ineff- cient. Wherever possible the treatment should be tried with fresh material from the abattoir, as well for economical reasons as for the fact that the dried preparations are less potent. As it is very difficult, at least in pronounced cases, to check the 24 hour amount of urine in this way, it will probably be the best plan to confine the therapeutic aims to securing a hormal output during the night and thus relieve the patient of one of the most distressing features the restless nights. One patient who has been under my care for the past two years has been very much improved by an intermittent pituitary feeding. She has taken from two to seven fresh pituitary bodies from cattle every evening. The output has hereby been checked dur- ing the night,—usually decreasing from nearly 2500 ce. to approximately 300 cc. At the same time the general state of health has improved consider- 120 DIABETES INSIPIDUS ably, adiposity and drowsiness having disappeared, and menses have been re-established. Feeding the anterior lobe alone does not lead to this effect. This patient also shows another interesting feature. At present one hypophysis will have the same effect as, two years ago, could not be obtained by less than seven glands. The most satisfactory explanation of this fact will probably be that the hypophysis of the patient during the functional rest by the extraneous help has gained in secretory ability. This would be analogous to the explanation of the increased sugar tolerance in diabetes mellitus after alimentary rest, and is more in harmony with the laws of general physiology, than the usual assumption that the pitu- itary extracts stimulate the pituitary body. This is an entirely new field for organotherapy, and only the future can tell how many cases will be benefited by treatment along these lines. In the syphilitic cases an energetic antiluetic treatment will often prove of lasting value. The cases due to tumor have to be treated according to general surgical principles. In one case where the patient presented some evidence of brain tumor, the output was checked by a lumbar puncture. As previously mentioned there has been confu- sion as to the effect of the pituitary extracts on the flow of urine. Recent clinical investigations, and among them my own work, have, however, shown quite definitely that the extracts from the posterior lobe physiologically serve to secure a normal concen- tration of the urine. I have gone more deeply into this question experimentally and my results indicate that this action is exerted on the sympathetic nery- ous system, especially on the vaso-motor nerves for MOTZFELDT 121 the renal vessels. These results may lead to a broader view of the polyurias. When the sympa- thetic system does not get its normal stimuli, as is the case in organic lesions with destruction of the posterior lobe of the pituitary body, polyuria will re- sult. In functional disorders of the nervous system polyuria of varying degree and duration is fre- quently seen. The most satisfactory explanation in these cases seems to be to assume a temporary lack of tone of the vasomotor fibres in the sympathetic nervous system. The ‘‘urina spastica’’ of the old observers is probably rather a ‘‘urina atonica,’’ indi- cating a lowered tone of the renal vaso-constrictors. Possibly these pathological polyurias of varying se- verity and of apparently different origin, ranging from the occasional polyuria of the neurotics to the polyurias of extreme degree in diabetes insipidus, can be linked together by the sympathetic nervous: system. Though this field is in urgent need of further in- vestigation, it has become clear that diabetes in- sipidus is merely a symptomatic evidence of disor- dered pituitary function, and that it is due to a deficit of secretion. In consequence, administration of pitu- itary preparations will be the proper therapy. VASCULAR CHANGES PRODUCED BY ADRENALIN IN VERTEBRATES Frank A. Hartman, Leslie G. Kilborn and Ross 8. Lang. (From the Laboratory of Physiology, University of Toronto.) The majority of physiologists still teach that adrenalin is essentially constrictor in its effect upon the blood vessels, ignoring the fact that doses which are probably physiological in their magnitude cause dilatation in a large proportion of vessels. These teachings are founded upon the older experiments in which massive doses of the hormone were used. Such amounts of adrenalin are probably never secreted by the adrenal glands (1, 2, 3). Although in the last few years it has been conclusively proven that small quantities of adrenalin cause vasodilatation and a fall in blood pressure as a result (4, 5, 6, 10) the fact is still ignored. This situation may be easily explained, for, among the common laboratory mam- mals some give evidence of vasodilatation while others consistently fail to do so. These animals which have been found to give positive proof of dila- tation belong to the carnivores, while those that do not belong to the rodents. In face of the experimen- tal facts it was as easy to believe the response of cats and dogs exceptional, as that the effect in rabbits was different from that in other animals. In view of this disagreement, it was perfectly natural to assume that the action of adrenalin in cats and dogs was unusual, since it did not conform to other beliefs such as the absenee of vasodilator fibers in the sympathetic ner- vous system. 122 HARTMAN, KILBORN AND LANG 123 This research was undertaken with the object of determining whether the dilator action of adrenalin was confined to the carnivores. It was conceivable that other groups might give a similar action, al- though none were known to do so; accordingly a sur- vey was made of all the groups available. The re- sults have been sufficient to remove all doubt as to the general occurrence of vasodilatation from adrenalin. : A brief sketch of our present knowledge concern- ing this dilatation is needed as a foundation for this research. The nature of the mechanism on which adrenalin acts was worked out largely by experi- ments upon cats and dogs. Those experiments have proven that a differential effect is produced—dilata- tion in skeletal muscle (5, 6) and intestine, (large doses )—constriction. in skin (6), intestine (small doses), kidney (8, 10), bone (16), thyroid (15) and _spleen (7, 10). With small doses, the vessels in skel- etal muscle more than counteract the constriction in the skin and abdominal viscera, so that a fall in blood pressure results. When the amount of adrenalin is sufficiently large, the constriction of skin and visceral vessels (excepting intestine) becomes great enough to more than compensate for the dilatation in skeletal muscle, thus producing a rise in blood pressure. The dilatation produced by adrenalin has been shown to be brought about by dilator mechanisms located in the sympathetic and dorsal root ganglia (12) as well as in a “‘terminal’’ receptive substance which has been called the myoneural junction (13, 14). The latter, a counterpart of the constrictor myoneural junction, is assumed to be associated with dilator fibers. 124 ADRENALIN IN VERTEBRATES METHODS The methods employed in this research were those already described in work from this laboratory (10, Hy 12): All animals, unless otherwise stated, were anaes- thetized with ether. Blood pressure was taken from the carotid artery, except in the fowl, in which case the sciatic artery was used. Injections were made into the jugular vein. Solutions of adrenalin chloride were made up by diluting the 1:1,000 preparation of Parke, Davis & Co. Volume changes were registered by means of Brodie’s bellows. The plethysmograph for the limb was either of the type which enclosed the paw, or else like a cuff, so that the paw might be excluded (13). It was necessary to use artificial respiration in the fowl when the abdomen was opened. RESULTS Reptilia (Chelydra) A snapping turtie (5.8 kgm.) was employed as representative of the reptiles. Doses of adrenalin as small as 0.2 ¢@.c., 1:1,000,000 were tried with no ef- feet upon the blood pressure. Even 0.5 ¢.¢., 1:100,000 had no effect. 1.0 ¢«., of the latter concentration caused a rise from 46 mm. to 50 mm. 0.4 e.c. 1:10,000 caused a change from 44 to 54mm. 1.0 ¢.c. of the same solution produced about the same effect. Indeed it was found that with large doses, sensitiveness to adrenalin was soon lost. 0.5 ¢.¢., 1:1,000 following the above, increased the pressure only 6 mm. from 51mm. Repetition of this had no effect, nor did twice the dose. Two months later, the blood pressure and intestinal effects were studied in the same animal. The blood pressure responses were similar. The in- HARTMAN, KILBORN AND LANG 125 testine always gave constriction when there was any effect. This was observed with doses ranging from 0.5 ¢@.¢., 1:100,000 to 3.0 ¢.e., 1:10,000. After the latter dose, 1.0 ¢.¢., 1:1,000 produced no intestinal change. Although only tentative conclusions can be drawn from a single animal, they are at least valuable when considered in connection with other vertebrates low in the seale. We have found that the vascular system of the turtle is not very sensitive to adrenalin and that there is evidence of only a constrictor mech- anism. The failure to obtain a fall in blood pressure or a dilatation of the intestine indicate an absence of the dilator mechanisms. Aves (Gallus) The fowl serves as an example of the warm blooded vertebrate other than the mammal. It is much more sensitive to adrenalin than are the cold-blooded ver- tebrates. Moreover it does not easily lose its power to respond to this hormone, even after numerous doses. Constriction is the only effect produced by adrena- lin in the fowl. Both the limb (Fig. 1) and the intes- ) [rrr OY. Nn nan naan RAS [Sra ae Wile S_ A FIG. 1 Effect of 0.5 c.c., 1:100,000 adrenalin upon the limb in the fowl, 1.0 kgm. (Reduced %.) tine (Fig. 2) respond in this way. From a study of 126 ADRENALIN IN VERTEBRATES {atestings non FIG. 2 Prolonged constriction of the intestine in the fowl. (0.92 kgm.) Produced by 0.5 c.c., 1:10,000 adrenalin. (Reduced %). seven animals no evidence of the existence of the adrenalin vasodilator mechanisms (‘T'able 1) has been found. TABLE I. RESPONSE TO ADRENALIN IN THE FOWL — —=— ———— == “$y ae Blood pressure | Weight Dose change in mm.| Limb | Intestine in kgm. of mercury 1.1 | 0.2 ce 1:1,000,000 Slight con- striction 0.5 ee 1:100,000 109-138 Constriction 1.0 ce ss 114-182 Marked con- striction 1.0 | 0.1 ec 1:100,000 | 118-130 | Constriction 0.5 ce : 106-134 | Marked con- | striction 092 | 02 xe | 65- 79 | Constriction | Constriction | 0.5 ee a 95-175 Marked con- striction 0.85 | 0.2 ce 1:1,000,000 | 52- 54 | Constriction | 0.5 ce 1:100.000 | 55- 65 Marked con- Constriction striction | 1.0 ec 80-119 Constriction 0.95 0.5 ee 1:100,000 | Constriction 0.5 ec 1:10,000 | Very raarked | constriction == <<< ————— —— MAMMALIA Marsupialia (Didelphys) A single opossum about two-thirds grown (weight 1.3 kgm.) was used in this research. A fall in blood HARTMAN, KILBORN AND LANG 127 ) pressure (Fig. 3) was easily obtained from adrenalin. Sec. Vt ont a) RT cael TO ey et a ee ae ee FIG. 3 Blood pressure fall in the opossum produced by 0.2 c.c., 1:100,000 adrenalin. (Reduced %.) This was usually preceded by a brief rise. With larger doses pure pressor effects resulted. Although the limb included in the plethysmograph possessed a smaller proportion of muscle than that in most mammals it gave active dilatation (Fig. 4) ex- .e ‘ WoW easy ath ee Snoe 5. eae Ae ie a. 5 Sec. ee ad a ee ee ee ee ee ee a ed OS ea ee ed ees | FIG. 4 Dilatation of limb and intestine in the opossum caused by a depressor dose of adrenalin, 0.2 c.c., 1:10,000. (Reduced %.) cept when large doses were used. The intestine di- lated actively in response to adrenalin (Fig. 5), the dilatation becoming very marked with large doses (Table II). 128 ADRENALIN IN VERTEBRATES ar , aie Wy \ Tis VW), WW ANAKA WV “Wyn WIAD WV Kp JV SIS FIG. 5 Marked dilatation of the intestine in the opossum resulting from the injection of a presser dose of adrenalin 0.5 e.c., 1:10,000. (Reduced 35.) TABLE II. RESPONSE OF-THE OPOSSUM TO ADRENALIN i , Blood pre eect i a tae E a... Dose change in mm. as of Response of of mercury limb Intestine 0.05 cee 1:100,000 140-142-136 Dilatation 0.1 ce rs 138-144-128 Dilatation 0.2 ec és 144-151-135 Slight con- Dilatation striction 0.5 ce *e 118-125-106 Dilatation Constriction and dilatation 0.56 ee 1:10,000 123-180 Smal] dilatation Marked dila- tation 1.0 ce ee 98-215 Small dilatation Marked dila- 2 tation We may conclude then that the opossum and prob- ably all marsupials possess adrenalin vasodilator mechanisms similar to those in the cat and dog. UNGULATA Perissodactyla (Equus) Unfortunately the horse which we used was in such poor condition that it cannot be considered typical. It was anaesthetized with chloroform, and 1:1000 adrenalin was injected in every instance. In no case was there a fall in blood pressure. 5.0 ¢.c., adrenalin changed the pressure from 114 mm. to 162 mm. HARTMAN, KILBORN AND LANG 129 10.0 ¢.c. increased the pressure from 80 to 260 mm. Attempts to produce dilatation of the intestine were successful when 25.0 ¢.c. was injected, there being a strong constriction followed by a dilatation. 20.0 ¢.¢. produced constriction only. Intestinal dilatation was the only indication of the presence of an adrenalin vasodilator mechanism in the horse. Artiodactyla (Capra) In view of the unsatisfactory condition of the horse, it was imperative that another animal belong- ing to the ungulates be tried. An experiment with a goat (weight 13.0 kgm.) removed all doubt as to the existence of adrenalin vasodilator mechanisms in this order. A depressor effect (Fig. 6) as well as FIG. 6 Fall in blood pressure from 0.4 c.c., 1:100,000 adrenalin in the goat, 13.0 kgm. (Reduced 1%.) active dilatation of the limb (Fig. 7) could be ob- tained from the injection of small amounts of adren- alin. However nothing but constriction in the intes- tine (Fig. 8) resulted from even large doses of adren- alin until perfusion was attempted. A loop of intes- tine, with nerves intact, but shut off from the general circulation and perfused with oxygenated Ringer’s solution gave pronounced dilatation both when 130 \alestine anna FIG. 7 ADRENALIN IN VERTEBRATES Dilatation of the limb and constriction of the intestine pro- duced by 0.5 c.c., 1:100,000 adrenalin in the goat. (Reduced %.) Constriction in 1:10,000 adrenalin, goat. the li FIG. 8 mb and intestine caused by 1.0 ec.c., (Reduced %.) TABLE III. ‘HE GOAT TO ADRENALIN Dose | Blood pressure, Change in Limb Change in mm. of mereury y Intestine ce 1:100,000 | 110-128-94 Dilatation ce “ 62- 68-53 | Dilatation Constriction ce S 72- 80-61 |Dilatation and | Constriction |Constriction ce 1:20,000 80- 92-66 Constriction Constriction ce i“ 84-106 |Constriction Constriction ce : 28- 26 Dilatation* cee “ Dilatation* a = *Intestine perfused, HARTMAN, KILBORN AND LANG 131 1.0 ¢.e¢., and when 2.0 @.c., 1:20,000 adrenalin were injected into the jugular vein. (Table LI). Our experiments thus indicate that the mechan- isms for dilatation from adrenalin are found in the ungulates. CARNIVORA Cats and dogs were the only Mammals known to possess adrenalin vasodilator mechanisms before this research was undertaken. We were interested in finding out whether all families in this order reacted to adrenalin in the same way. Two other families were therefore investigated, viz.—the mustelidae and the procyonidae. Mustelide (Putorius) Study of an old ferret (weight 0.6 kgm.) indicated the presence of the vasodilator mechanisms. This evidence was largely limited to depressor effects of adrenalin, 0.2 ¢.e., 1:1,000,000 causing a fall of 6 mm. from 152 mm. In one instance dilatation of the limb was obtained. Procyonide (Procyon) Typical adrenalin vasodilator effects were obtained in the raccoon. A marked fall in blood pressure was produced by small doses. (Fig. 9). Dilatation of See Magee Sse eis FIG. 9 Fall in blood pressure and constriction of the intestine pro- duced by the injection of 0.2 c.c., 1:100,000 adrenalin. Racéoon. (Reduced %.) 132 ADRENALIN IN VERTEBRATES the limb sometimes resulted from depressor doses. Constriction (Fig. 9) or constriction and dilatation (Fig. 10) occurred in the intestine depending upon FIG. 10 Dilatation of the intestine produced by 0.3 c.c., 1:10,000 adren- alin, raccoon. (Reduced 26.) the amount of adrenalin injected, just as in cats and dogs. RODENTIA A reason already given that the cat and the dog have been considered possibly exceptions in their behavior toward adrenalin is the fact that the rabbit does not give the same results. We will show, how- ever, judging from the rat and rabbit that rodents are an exception in their behavior toward adrenalin and that the reaction of the cat and dog is the typical one for most mammals. Muride (Mus) A fall in blood pressure could not be obtained im the white rat. In an animal weighing 0.23 kgm., 0.05 ¢.c., 1:100,000 adrenalin caused a pure rise from 69 to 83 mm. Smaller doses such as 0.3 ¢.e., 1:1,000,- 000 had no effect. Leporide (Lepus) We have never obtained evidence of the presence of adrenalin vasodilator mechanisms in the rabbit. At least twelve rabbits have been examined in this HARTMAN, KILBORN AND LANG 133 connection. It has always been our experience that whenever a dose of adrenalin is large enough to pro- duce any effect, nothing put a pure rise of blood pres- sure results. There might, however, be a differential effect with- out a fall in blood pressure. In one experiment the coeliac, superior mesenteric, inferior mesenteric and renal arteries were tied (5) without changing the re- action to adrenalin. The limb reaction was determined in four animals. With small doses a dilatation which appeared to be passive, sometimes occurred. When the amount of adrenalin was increased constriction was produced. (Fig. 11). The presence of active dilatation was Li by a FIG. 11 Constriction of the hind limb of a rabbit (2.4 kgm.) from 0.4 c.c., 1:100,000 adrenalin. (Reduced %%.) then sought in another way. The hind limb of an animal was perfused with Ringer’s solution, and adrenalin was injected into the jugular vein. If di- lator mechanisms sensitive to adrenalin, exist in the sympathetic and dorsal root gangha, the limb under these conditions should respond. The injection of even large doses of adrenalin into the jugular vein was without effect. Injection into the perfusion fluid as it entered the iliac artery was also without 134 ADRENALIN IN VERTEBRATES effect in one animal, while in a second rabbit the first two doses (0.5 ¢.e. and 0.1 ¢@.¢., 1:100,000) caused con- striction, but later doses had no effect. In one experiment the sciatic and femoral nerves in one limb had been cut seventeen days before. However no evidence of a terminal dilator mechanism could be obtained. In the cat and dog this has been obtained easily by such a method (13, 14). Very small passive dilatations were produced in the denervated limb of the rabbit when adrenalin was injected into the general circulation. This limb was perfused later, doses of adrenalin varying from 1:1,000,000 to 1:10,000 concentration being injected into the fluid, but without result. The reaction of the intestine was observed in four animals. In one, there was small passive dilatation with small doses. The other three constricted with doses of this size. In all there was prolonged con- striction with large doses (Fig. 12). As an illustra- FIG. 12 Constriction of the intestine of a rabbit due to the injection 0.5 e@.c., 1:10,000 adrenalin. (Reduced *.) tion of the amount of constriction; a loop 37 ¢.e. in volume constricted .72 ¢.c. after the injection of 0.5 ¢.¢., 1:10,000 into the general circulation. HARTMAN, KILBORN AND LANG 135 In an unpublished research we have found that there is a dilator mechanism for the kidney located in the aortico-renal ganglion. One of the methods employed has been to apply adrenalin solutions to the ganglion, noting the volume change in the kidney. We did this in a rabbit, but obtained constriction in the kidney instead of dilatation. We conclude from our results that rodents do not possess adrenalin vasodilator mechanisms. PRIMATES ‘Monkey (Pithecus) Adrenalin vasodilator mechanisms are present in the monkey (Table IV). Excellent dilatations of a TABLE IV. RESPONSE OF THE MONKEY TO ADRENALIN Blood pressure Limb Intestine change in mm. Dose of Mercury 0.1 ec 1:100,000 96-101-92 Dilatation Constriction and slight dilatation 0.4 “ so 94- 98-86 Dilatation 19 ca A 80- 98 Very marked dilatation 0.3 “ 1:10,000 86-124 Marked dilata- Marked constric- : tion tion and dila- tation 1 os Sa ny 64-166 Marked dilata- Marked constric- _ tion tion and dila- tation Biber st 64-177 Marked dilata- Marked constric- tion and con- tion and dila- Bteiction tation leg were produced (Figs. 14 and 15) by doses of adrenalin ranging from 0.4 ¢.c¢., 1:100,000 to 0.7 «.e., 1:10,000 (weight of animal 5.2 kgm.) (The foot was not included in the plethysmograph). Indeed, a large dose of adrenalin was required to cause reversal in the limb (Fig. 16). By perfusing the limb and inject- ing adrenalin into the jugular vein we attempted to bring the ganghar mechanism into action, without 136 ADRENALIN IN VERTEBRATES result. We thought this might be due to failure of the adrenalin to reach the ganglia on account of FIG. 13 Fall in blood pressure in the monkey (5.2 kgm.) resulting from 0.4 e@.e., 1:100,000 adrenalin. (Reduced %.) Jalesline A, AAW WW NA NNW NNN FIG. 14 Response to 0.5 c.e., 1:100,000 adrenalin in the monkey. Con- striction followed by dilatation of the intestine. Marked dilata- tion of the limb. (Reduced %.) clamping the aorta too high up, as that has frequently been the case in cats. On the other hand injection of the hormone into the perfusion fluid easily produced dilatation. The explanation, therefore, might be that the vasodilator myoneural junction and not the gan- | HARTMAN, KILBORN AND LANG 137 gliar mechanism was the source of the dilatation. We are inclined to doubt this as being typical, for there is no reason to believe that the monkey is dif- ferent from the cat and dog in which the gangliar mechanism is an important source of adrenalin vaso- dilatation (13). The intestinal mechanism in the monkey worked Naa AAS v¥¥*y * wy \ulesline an we : N FIG. 15 Effect of a larger dose of adrenalin, 0.3 e.c., 1:10,000 in the monkey. (Reduced %.) ee eh N SAW F NAAN NAW Wh nit WWW FIG. 16 Reversal in the limb produced by a large dose of adrenalin, 2.5 ¢.c., 1:10,000 in the monkey. (Reduced %.) 138 ADRENALIN IN VERTEBRATES very well (Figs. 14 and 15) until large doses of adren- alin were used when constriction only was obtained (Fig. 16). A fall in blood pressure was obtained from the in- jection of small doses of adrenalin (Fig. 13), but as sometimes happens in cats or dogs the fall became small or almost disappeared after a few doses had been injected (Fig. 14). | DISCUSSION So far as we know the blood vessels of all verte- brates lower than mammals are constricted by adren- alin. In the frog Burket (17) found that the constrictor effect of succeeding doses of adrenalin rapidly de- clines until there remains only a very small response. He also noted that.the rise in pressure lasts much longer than in the cat. Our observations upon the turtle are somewhat similar, there being a rapid loss in sensitiveness to adrenalin and a prolonged effect when the rise is produced. In addition attention should be called to the fact that the threshold for a blood pressure response is much higher in the rep- tiles than in the mammals. — It is of interest to note also that birds resemble mammals in some respects in their behavior toward adrenalin. The threshold for adrenalin response is about as low and successive doses of adrenalin do not readily decrease the sensitiveness. The percent- age rise in blood pressure that can be produced by adrenalin in the fowl is much greater than that possi- ble in the reptile, although the rise in blood pressure is more prolonged in the fowl than in the mammal. It may be partly due to the absence of dilator mech- anisms which could be affected by adrenalin and thus HARTMAN, KILBORN AND LANG 139 tend to offset the constrictor effect. Dale (22) was able partially to paralyze the constrictor mechanism in the fowl, but he obtained no fall in blood pressure from adrenalin. Besides the carnivores and rodents which have been extensively studied by different investigators, a few observations have been made upon the ungu- lates and primates. Barger and Dale (18) paralyzed the vaso-constrictor mechanism in the pig and the goat with ergotoxin, but failed to obtain a fall in blood pressure when adrenalin was injected. Bar- bour and Prince (19), in experiments with perfused hearts obtained dilatation of coronary vessels in the ox, sheep, pig, and rabbit, but constriction in the monkey. Auer and Meltzer (20) obtained usually a rise, but sometimes also a fall in blood pressure from the intra- spinal injection of large amounts of adrenalin in the monkey. We have been able to show in all orders of mam- mals which we have studied, except the rodents, that both adrenalin vasodilator mechanisms (for skeletal muscle and intestine) are present. On the other hand, we have been unable to prove the presence of such mechanisms in the rodents. Moreover, no one— else (21, 23) has ever been able to produce a fall in blood pressure by the injection of adrenalin in the rabbit. Dale (22) was unable to obtain a reversel by the use of ergot, although he abolished the pressor effect of adrenalin. Dilatation from adrenalin had been observed in the rabbit. The Meltzers (24) obtained dilatation of the ear vessels of the rabbit from the subcutaneous injec- tion of adrenalin. Ogawa (25) produced dilatation 140 ADRENALIN IN VERTEBRATES of the perfused kidney, intestine and hind limbs of the rabbit by adrenalin. However, he usually obtained constriction of the kidney even with dilute solutions. He did not secure a primary dilatation in the limb. We are led to conclude as a result of our experiments that even though adrenalin vasodilatation may occur in the rabbit it is relatively unimportant. In conclusion, we are justified in assuming that the usual vasomotor reaction in skeletal muscle is dilata- tion with moderate doses of adrenalin, rodents being exceptional; and because of the uniform occurrence in other mammalian orders as well as the presence in the monkey we have considerable reason for be- lieving that these mechanisms are also present in man. We wish to thank Lois McPhedran Fraser for as- sistance ina part of this research. SUMMARY 1. Birds and reptiles possess no adrenalin vasodi- lator mechanisms. 2. A small amount of adrenalin produces a fall in blood pressure in marsupials, ungulates, car- nivores and primates. 3. Adrenalin vasodilator mechanisms for the limb and intestine are present in marsupials, ungu- lates, carnivores and primates. 4. Rodents are exceptional in their reaction to ad- renalin, vasodilator mechanisms sensitive to this hormone being absent. Dd. Dilatation in the blood vessels of skeletal muscle is the usual response to adrenalin in mammals. 18. 19. HARTMAN, KILBORN AND LANG 141 BIBLIOGRAPHY Hoskins and McClure. The adrenal glands and blood pressure. Arch. Int. Med., 1912, 10, 343. Stewart, Rogoff and Gibson. The liberation of epinephrin from the adrenal glands by stimulation of the splanchnic nerves and by massage. Jour. Pharm. Exp. Ther., 1916, 8; ZOD. Stewart and Rogoff. The spontaneous liberation of epine- phrin from the adrenals. Tbid, 1916, 8, 479. Cannon and Lyman. The depressor effect of adrenalin on ‘arterial pressure. Am. Jour. Physiol.. 1913, 31, 376. Hartman. The differential effects of adrenin on splanch- nie and peripheral arteries. Ibid, 1915, 38, 488. Hoskins, Gunning and Berry. The effects of adrenin on the distribution of the blood, I. Volume changes and venous discharge in the limb. Ibid. 1916, 41, 513. Hoskins and Gunning. II. Volume changes and venous discharge in the spleen. Tbid, 1917, 43, 298. Hoskins and Gunning. III. Volume changes and venous discharge in the kidney. Thid, 1917, 43, 304. Hoskins and Gunning. V. Volume changes and venous discharge in the intestine. Ibid, 1917, 43, 399. Hartman and MePhedran. Further observations on the differential action of adrenalin. Ibid, 1917, 43, 311. Hartman and Fraser. The mechanism for vasodilatation from adrenalin. Jbid, 1917, 44, 353. Hartman, Kilborn and Fraser. Location of the adrenalin vasodilator mechanisms. Ibid, 1918, 46, 168. Hartman, Kilborn and Fraser. Adrenalin vasodilator mechanisms. Ibid, 1918, 46, 502. Gruber. Further studies on the effect: of adrenalin upon the blood flow in muscles. Ibid, 1918, 45, 312. Gunning, VI. Venous discharge from the thyroid glands. Thid, 1917, 44, 215. Drinker and Drinker. A method for maintaining an artificial circulation through the tibia of the dog, with a demonstration of the vasomotor control of the marrow vessels. Ibid, 1916, 40, 514. Burket. The influence of adrenalin, modified by salt solu- tions, on blood pressure in the frog. Kansas Univ. Sci. Bull Lots: T2214 Barger and Dale. Ergotoxine and some other constituents of ergot. Biochem. Jour., 1907, 2, 250. Barbour and Prince. The influence of epinephrin upon the coronary circulation of the monkey. Jour. Exp. Med., 1915, 21, 330. ADRENALIN IN VERTEBRATES Auer and Meltzer. The characteristic course of the rise of blood pressure caused by an intraspinal injection of adrenalin. Proe. Soe. Exp. Biol. and Med., 1912, 9, 80. Pari. Action locale de l’adrénaline sur les parois des vaisseaux et action des doses minimes d’adrénaline sur le pression du sang. Arch. ital. de biol., 1906, 46, 209. Dale. On some physiological actions of ergot. Jour. Physiol., 1906, 34, 172. Batelli. Présenece d’adrénalin dans le sang d’animaux normaux. Son dosage. C. R. Soe. de Biol., 1902, 54, 1180. Meltzer and Meltzer. On the effects of subeutaneous in- jection of the extract of the suprarenal capsule upon the blood vessels of the rabbit’s ear. Am. Jour. Physiol., 1903, 9, 252. Ogawa. Beitrage zur Gefaszwirkung des Adrenalins. Arch. exp. Path., 1912, 67, 89. SUPPURATION OF GOITROUS THYROID FCLLOWING ADMINISTRATION OF THYROID EXTRACT: A CASE REPORT Edward A. Tracy, M. D., Boston. The patient was a widow, aged 51 vears. When first seen she was melancholic and sleepy in the day- time. She had a moderate-sized goitre. Her mel- ancholy was increased, if not caused, by the fact that her son was in prison. A half grain dessicated thy- roid after each meal was prescribed. After a week’s administration of the material the right lobe of her thyroid became painful. The treat- ment was stopped. After two weeks the painful lobe reddened and a week later ‘‘broke,’’ three days after the patient, on her own volition, had applied a bread and water poultice. It may be remarked here that the mental condition cleared up rapidly after the ad- ministration of the dessicated thyroid. | On seeing her after the poulticing had been done for several days, I was alarmed at. the appearance of the sloughing lobe of thyroid. I had-her apply a sulpho-naphthol poultice every three hours. After a few days I snipped off the dead thyroid tissue pre- senting—about the size of a dime—and had her con- tinue antiseptic treatment until healing occurred— four months later. Healing was delayed because of the necessity of the patient to do household duties. This case illustrates the care with which thyroid extract must be given in such cases. In goitre, with myxedema symptoms, I should commence with half a 143 144 THYROID SUPPURATION grain of dessicated thyroid a day, and watch care- fully for the least sign of trouble, such as slight pain in the thyroid. On its appearance omit the medica- tion. Enough may have been given to awaken the dormant tissue to renewed activity. If not, we can carefully renew our medication, and watch again. A CASE OF PARATHYROID INSUFFICIENCY Arthur f. Hertz, M.A. WM. D.:Oxon., F.C. P. (From the Neurological Department, Guy’s Hospital, London) The following case is remarkable in that it is the only one which I have seen in which the symptoms appeared to be due to a functional insufficiency of the parathyroid glands; and I have not found any record elsewhere of a similar case. Opportunity was afforded to watch this case for over four years, and the result of suitable organo- therapy—the administration of dessicated parathy- roid substance—was so decided that one can hardly believe that the symptoms which will be enumerated could have been produced in any other way. Clinical History—A clerk, aged 47, came under my care late in 1910. When he was 30 years old he first noticed a slight enlargement of the thyroid gland. It gradually became larger and about two years previously—in 1908—it became necessary’ to remove the greater part of it. After this he re- mained perfectly well until four months ago, at which time quite suddenly he became greatly depressed and very nervous and restless. He suffered from an irresistible desire to keep moving, and instead of sleeping spent most of the night walking about. He began to be exceedingly tremulous and found that he had great difficulty in writing. There was a con- tinuous fibrillary twitching of the eyelids, but no tetany was present at any time. The general appearance was not unlike that of a severe case of Graves’ disease, but his eves were 145 146 PARATHYROID INSUFFICIENCY sunken instead of being prominent and the thyroid gland could neither be seen nor felt. When he was taken ill in August (1910) he weighed 191 pounds, but now he weighed only 144 pounds, and despite an increasing appetite—he ate enormously and did not seem to suffer from this—he was losing weight rapidly. At the time I first saw him with Sir Bertrand Dawson he complained of some difficulty in swallow- ing and said that the food seemed to stick in his throat. This was shown by a fluroscopic examina- tion to be the result of irregular spasmodic contrac- tions of the esophagus. He also had some irregular intestinal pains which might be accounted for in a similar manner. While previously he had been ae- customed to open his bowels once a day, he now passed three or four large, but otherwise seemingly normal, stools each day. The urine was somewhat reduced in quantity, but otherwise normal. He was greatly troubled with palpitation and his pulse was constantly about 120. His face and neek were deeply flushed and the secretion of the sweat glands was unaffected. It was noticed that his hair had ceased to grow, though it did not fall out and become thinner. His beard was not growing so fast and while formerly he had his hair eut about every ten days, now six weeks had passed without any no- ticeable increase in its length. In addition to this he had become completely impotent. It seemed obvious that the condition was of en- docrinous origin, and it was thought possible that the condition resulted from injury to the parathy- roid glands during the operation on the thyroid HERTZ 147 gland which was performed more than two vears previously. A definite diagnosis was not made and the treat- ment here outlined was expectant. Treatment—He was put to bed and beside the ordinary full hospital diet, he received four pints of milk a day. His pulse gradually became slower and the abdominal discomfort disappeared. However, his weight continued to fall until it reached 13014 pounds ten days later. The restlessness was not modified and he found it extremely difficult to stay in bed. He was given large doses of opium and bro- mides, which had a favorable effect, and he gained slowly in weight until two months later he weighed 159 pounds. During this time desiccated thyroid gland and later Moebius’s antithyroid serum were tried, but the former aggravated the symptoms and the latter made him sick. In February though the pulse was somewhat slower and the restlessness and tremor less marked, his other symptoms were unaltered. He was allowed to get up and returned to his work. His weight at once began to fall, and in spite of continuing the same diet and both opium and bro- mides, his weight on June 18th was lower than ever —1271% pounds. With difficulty he continued his work, but on that dav he began to take one-tenth grain of dried ox parathyroid glands (Armour) four times daily, and four days later both the opium and the bromides were discontinued. The gain in weight was most remarkable. Dur- ing the first four days he gained 614 pounds, the next five days 12 pounds, five pounds the next four days 148 PARATHYROID INSUFFICIENCY and the same amount during the next six days or a total of 281% pounds in nineteen days. Coincidently he became stronger every day, his sleep was better and more refreshing and the restlessness, tremor and dysphagia disappeared, his hair began to grow, the pulse gradually was slowed until it was less than normal, the amount of feces was reduced and the urine increased. After a month of parathyroid therapy he was almost well, though it was not until he had been tak- ing parathyroid gland for six months that his sexual functions were restored. About seven months after this treatment was instituted—January 11, 1912— his weight was 16T pounds and during that year he gained an additional 14 pounds; and about Christ- mas, 1912, he discontinued taking the parathyroid gland. In August, 1913, he was seen again and though his weight had increased 4 pounds (it was now 179 pounds), he was more restless and his pulse was faster, so he was advised to continue to take one- tenth of a grain of the parathyroid gland daily. This was continued for four months and discontinued in November as, peculiarly enough, his face had as- sumed a brick red color, his throat was somewhat full and the vessels in the neck throbbed. These svmmptoms, however, disappeared ee omitting the parathyroid. T heard from him in February, 1914, at which time his weight was 189 pounds and he felt perfectly well and strong with no trace of nervousness, although he was working quite hard. THE RELATION OF THE ADRENAL GLANDS TO SUGAR METABOLISM Striking effects can be produced by the injection of adrenin. The body contains certain organs, the adrenals, capable of forming adrenin. The actual physiological function of these glands has not been satisfactorily determined. These facts have proven an irresistable stimulus to speculation and theoriz- ing, both upon the part of clinicians and of laboratory investigators. The mysterious etiology of diabetes mellitus has been another potent stimulus to imag- inative activity. Under such conditions it was inev- itable that the possibility of producing glycosuria by the injection of advenin should have led to a theory that the adrenals play an important part in sugar metabolism. The hypothesis is intrinsically attrac- tive and has had many adherents. As tisual in such cases, When the theory had been formulated a con- siderable amount of evidence reveals in many in- stances a partisan attitude,—a conscious or uncon- scious tendency to make the experiments support the preconceived theory. The existence of this atti- tude should at once awaken suspicion. To be suspi- cious of a given theory, however, and to disprove it are two quite different matters. Attractive theories die hard. Many years ago Claude Bernard discovered that an irritative lesion of the floor of the fourth ventricle could give rise to glycosuria. The lesion was pro- duced by a simple puncture through the roof of the ventricle. This is the so-called ‘‘sugar puncture’’ or piqure. 149 ~ 150 ADRENAL GLANDS AND SUGAR METABOLISM When the adrenal glands began to receive prac- tical attention at the hands of investigators an at- tempt was made to correlate the piqure glycosuria with that produced by adrenin. Soon the literature provided the definite ‘proof’? that, in the absence of the adrenal glands, piqure glycosuria could not be produced and that they form, therefore, an essential link in the chain of causation. Without going into a discussion of the technical details of the researches suffice it to say that the experiments cited in proof of the thesis were made upon moribund animals after severe trauma and anesthesia, ail of which factors profoundly effect sugar metabolism. Under such circumstances the presence or absence of glycosuria after piqure could not logically be regarded as either proving or disproving the thesis. Attempts to determine directly the effect of piqure on adrenal discharge were also not lacking. Kahn (1) investigated the matter at some length and concluded that no augmented discharge of adrenin took place after this operation. Later (2) he rein- vestigated the problem employing more adequate technique and concluded that, as a matter of fact, the puncture does cause adrenal discharge. How- ever, as Stewart and Rogoff (3) point out Kahn’s results are not conclusive because he used a colori- metric method not suited to quantitative work or, when he used the delicate frog-perfusion method, took no note of essential conditions in the donor of the blood tested. Moreover, the quantitative factor was ignored, so far as Kahn’s results were regarded as applicable to the problem of glycosuria. Osgood, working in Cannon’s laboratory, has shown that to produce glycosuria it is necessary to inject many ADRENAL GLANDS AND SUGAR METABOLISM 151 times the maximum quantity of adrenin that can be evoked by stimulation of the nerves to the adrenals. Following Kahn’s reports a number of other papers appeared which were mostly of negative tenor and of late years the conviction has been growing that piqure glycosuria is not dependent in any essen- tial way upon adrenal discharge. However, before negative results can be regarded as conclusive it must be shown that all essential conditions of experimental technique have been met. As Stewart and Rogoff maintain this has not hitherto been done. In par- ticular, it must always be proven that the liver con- tains an adequate supply of glycogen before a failure to produce glycosuria or, what is more significant, hyperglycemia, can have any value as evidence. The most recent investigation of the problem has been made by Stewart and Rogoff (8) in the Laboratory of Experimental Medicine at Western Reserve University. Use has been made of the fact that a considerable number of rabbits will survive the skillful extirpation of both adrenals and will afterwards have livers well filled with glycogen. A similar fact can be demonstrated for cats from which one adrenal has been removed and adrenin discharge from the other prevented by cutting its nerve sup- ply. In such animals hyperglycemia can readily be caused by asphyxia, a fact which shows that sugar mobilization is still possible. In such animals piqure results in many cases in marked hyperglycemia. In ease of the rabbit, at any rate, adrenal discharge can clearly be excluded as playing an essential part in the phenomenon and the proof in case of cats is all but absolutely conclusive. It was further shown °152 ADRENAL GLANDS AND SUGAR METABOLISM that, under the conditions of the experiments, in- jected adrenin readily caused hyperglycemia. It may now be definitely asserted that the ad- renal glands do not play any essential role in the production of piqure glycosuria and added doubt is thrown upon the theory that they play an essential part in any type of glycosuria or hyperglycemia. Whatever may be the explanation of the fact that the adrenals have an important influence upon bodily functions the burden of proof now rests heavily upon those who postulate the importance of adrenin dis- charge. Until this proof is forthcoming the elabor- ate superstructures that have been erected upon the pharmacology of advenin have but fragile founda- tions. The assumption that ‘‘hypoadrenia’”’ has any significance as an etiologic factor now needs some- thing more substantial than mere reiteration before it is worthy of the serious consideration of intelli- gent clinicians. BIBLIOGRAPHY Kahn. Arch. f. d. ges. Physiol. (Bonn.) 1912, 144, 251. Kahn. Ibid, 1912, 146,.578. 3. Stewart (G. N.) and Rogoff (J..M.) The relation of the adrenals to piqure hyperglycemia and to the glycogen con- tent of the iver. Am. Jour. Physiol. (Balt.) 1918, 46, 90-116. Doe THYROID AND THYMUS. André Crotti, M.D., F. A. C.8., LL. D. 558 pages. With ninety-six illustrations and thirty-three plates in colors. Lea and Febiger, Philadelphia, 1918. From the general tenor of the book one gathers that the author has set out primarily to write a prac- tical and readable book. If this was the purpose the book may be regarded as a success. The first 60 pages are devoted to the anatomy, physiology and chemistry of the thyroid gland. Of these sections that on physiology is perhaps the least satisfactory of any in the book. ‘Two excellent chapters on path- ology and inflammations occupy the next 60 pages. The next section,—the greater part of the book as a whole,—is devoted to the subject of thyroid diseases. A full discussion of classification, etiology, symptom- atology and treatment of these is included. The last two chapters are devoted to the thymus gland. A noteworthy feature of the book is the illustrat- ing. Many of the colored plates by Marcel Guelin are beautiful examples of anatomical drawing. To a very considerable extent, however, they are super- fluous for any but aesthetic reasons. Many of the points brought out could have been shown as well or better by clean cut line drawings. One can not commend the use of an expensive colored plate to il- lustrate so simple a matter, for instance, as the plac- ing of a subcutaneous ligature (Plate 33.) The book as a whole is one of outstanding exeel- lences as well as defects. The subjects of symptoma- tology and treatment of goitre are especially satis- factory, as is also the discussion of the geographical distribution of endemic goitre. The treatment of the historical aspects of the goitre problem is the best with which the reviewer is familiar; a full account of the Kocher-Reverdin controversy is a case in point. 153 154 THYROID AND THYMUS So much for the author’s efforts as a practical sur- geon dealing with matters of fact. As a scientist, however, dealing with matters still open to investigation, he is less satisfactory. His at- titude is indicated in the prefatory statement: ‘‘I have gathered all I consider of value from the enor- mous amount of French, Italian, German and Eng- lish literature . . . and I have endeavored, in my recital of sources and authorities, to give credit where credit is due.’’ One can but admire the cour- age of a writer assaying the role of dogmatically evaluating the literature of the difficult subject of speculative endocrinology. The author’s lack of suc- cess is perhaps sufficiently indicated by a single quo- tation (page 333.) ‘‘We know that their (adrenal) cortical cells . . . are entrusted with the duty of neu- tralizing the muscular toxins, and that the medulary cells . . . produce adrenalin whose tonie action upon the circulatory and muscular systems is well known. ... We know, too, that the thyroid secretion is an- tagonistic to that of the suprarenal bodies.’’* As a matter of fact none of these things is known. Such confusion of fact and theory is not uncommon throughout the book whenever the author gets out- side the realm of his personal experience. He does not make sufficient distinction between the fanciful conclusions of credulous, amateur experimentalists and the critical conclusions of competent scientists. In several instances a high value is placed upon notably faulty researches. The obsolete viennese ‘“Wechselwirkung”’ theories, for example, are quoted as of current worth. The announced endeavor ‘‘to give credit where credit is due’’ is but poorly carried out. To a serious student the value of the book is greatly restricted by the almost constant failure to include proper biblio- graphic references. The few that are given are *[talics mine. R.G.H. THYROID AND THYMUS 155 mostly in slipshod form. What, with proper atten- tion to this point might have been a valuable book of reference is, in this respect, practically useless. Neither can the attempt to ‘‘include all that is valu- able”’ be regarded as an entire success. Several im- portant recent papers have been missed. Among these are Bensley’s and Goetsch’s work on thyroid eytology, Cannon’s work on the control of thyroid secretion, Marine’s on iodin fixation and that of Nor- ris on thyroid embryology. The author’s use of the English language is some- what remarkable. Some paragraphs might be taken as models of graphic, artistic exposition, while a few might be selected to serve as models of what not to do. Colloquialisms are frequently employed. Ocea- sional unfortunate verbal peculiarities are encoun- tered. Some of these are: ‘‘aspirative needle,’’ ‘‘met- abolistic’’ for metabolic, ‘‘adipositas”’ for adiposity, and ‘‘catheterism’’ for catheterization; reference is also made to a ‘‘thyroidly insufficient patient.’? A lack of familiarity with English scientific idiom is betrayed by the use of such expressons as ‘‘ products of refuse’’ for metabolites, ‘‘anorganic’’ for mor- ganic, ‘‘superficial’’ for swrface tension, ‘‘albumin’’ for protein, ‘‘vasomotry’’ for vasomotor, ‘‘auton- omous’’ for parasympathetic and ‘*‘depoisoning’’ for detoxication. The discussion of the etiology of goitre, and espe- cially of Graves’ disease is, as might be expected, full. The pertinent clinical evidence is skillfully as- sembled. The experimental evidence, however, is less satisfactorily treated. The author believes that ex- perimental Graves’ disease has been successfully pro- duced both in man and animals by feeding thyroid substance. The only properly objective research upon the subject which is known to the reviewer, a research which MceCarrison regards as the most fun- damental on the goitre problem, is ignored. Carlson, 156 THYROID AND THYMUS as a matter of fact, was quite unable to produce any- thing at all closely resembling the disease either in man or animal by thyroid feeding. The problem pro- pounded for discussion is: ‘‘ Is Graves’ disease a true hyperthyroidism ?’’ This problem is soon lost sight of, however, in the consideration of quite a different question,—namely, that of the thyrogenie origin of goitre. The final conelusion is that the malady is es- sentially a toxic thyroiditis. Throughout the book, as a matter of fact, ‘‘Graves’ disease’’ and ‘‘hyper- thyroidism’’ are used interchangably, ignoring the possibility, if not the probability, that Graves’ dis- ease is a dysthyroidism. The two sections that most appeal to the reviewer are those on hypothyroidism in the young and on the water transmission 6f goitre. The latter is especially to be commended as a full, well-balanced exposition of the topie. The two final chapters, on the thymus gland, have in general the same excellences and defects as those on the thyroid. ‘The diagnosis and treatment of thymus hyperplasia are delightfully treated. In the discussion of the experimental pathology of the thymus much stress is laid on the work of Klose and Vogt,—work which various competent scientists have been unable to confirm. Altogether it may be said that the reader who is interested in the thyroid and thymus glands from a ‘practical’? chnical standpoint will find Cotti’s book a rich storehouse of usable and entertaining lore. The reader, on the other hand, who is interested pri- marily as an endocrine biologist will find it unsatis- factory. ‘To such it can be most commended for its excellent illustrations and for its historical material. R. G. Hi ABSTRACTS 80. (ADRENAL) Disparition des enclases, lipocholestériques de la surrénale humaine dans 1’agitation motrice. (Disappear- ance of lipoid-cholesterol bodies of the human adrenal in motor disturbance.) aignel-Lavastine (M:) C. R. Soe. de Biol. (Paris) 1918, 81, 324-325. The adrenals were examined from six cases, each of which had suffered from intense and prolonged motor disturbances before death. The author failed to find lipoid-cholesterol bodies in the adrenal cortex.—F. A. H. 81. (ADRENAL) La teneur en cholestérine des surrénales aux différents stades de la vie foetale (Cholesterol content of the adrenals at different stages of foetal life.) Chauffard (A.), Laroche (G.) and Grigant (A.) C. R. Soe. de Biol. (Paris), 1918, 81, 87-89. As the adrenals increase in size in the foetus the cholesterol content increases until at birth the average amount is 15 grams per kilogram. The cholesterol content of the liver and kidney is about 2.5 grams per kilogram at birth—F. A. H. 82. (ADRENAL) On the liberation of epinephrin from the ardenal glands. Rogoff (J. M.). Jour. Lab. and Clin. Med. (St. Louis), 1918, 3, 209. This article is a review and critique of recent work and theories on the discharge of the adrenal secretion into the blood stream. Nothing essentially new is offered save a tenta- tive theory that certain discharges of adrenal secretion may be due to reflexes involving a definite center located in the spinal cord. At the close of the article the author strongly emphasizes the fact that our present knowledge of the adrenals is not suf- ficient to warrant epinephrectomy as a measure of relief in conditions of arterial hypertonus associated with Bright’s dis- ease, as has been done, on the assumption that this condition is associated with hyperadremia.—H. W. 83. (ADRENAL) The relation of the adrenals to piqure hyperglycemia and to the glycogen content of the liver 157 158 ABSTRACTS Stewart (G. N.) and Rogoff (J. M.) Am. Jour. Physiol. (Balt.) 1918, 44, 90-116. In rabbits which have survived the removal of both adre- nals, and whose livers are well filled with glycogen, piqure causes decided hyperglycemia just as in normal rabbits. This is not compatible with the theory that piqure hyperglycemia is caused in the same way as the hyperglycemia produced by injecting adrenalin, by an increased liberation of epinephrin from the adrenals into the blood. It was frequently noticed also that hyperglycemia was caused by asphyxia in adrenalee- tomized rabbits. The failure of previous observers to obtain piqure hyper- glycemia in rabbits after the extirpation of both adrenals is attributed to the fact that they performed the piqure immedi- ately after the epinephrectomy, or if an interval was allowed to elapse it was too short to permit complete recovery from the adrenal operation and the liver was insufficiently stored with glycogen. Even when a considerable interval is allowed after the adrenal operation, the state of nutrition or the diet is sometimes unfavorable for glycogen accumulation and there- fore a positive result cannot be expected. There is no real evidence that piqure increases the rate of liberation from the adrenals. It is pointed out that the reactions of denervated vaseular regions and of the denervated heart, which have been interp- reted as showing that the rate of liberation of epinephrin is increased by stimulation of afferent nerves and by asphyxia, may have a different significance. The response of these organs may indicate merely an increased rate of blood flow through the denervated regions and therefore an increase in the total quantity of adrenalin reaching them, without any actual change in the rate of adrenalin liberation from the suprarenal glands. The formation and storing of glycogen in the liver is not affected by removal of both adrenals in rabbits, or by removal of one adrenal and section of the nerves of the others in eats with consequent abolition or marked reduction in the rate of liberation of epinephrin. In rats, also, extirpation of the adre- nals produces no essential change in the capacity of the liver to form and store glycogen.—h. G. K. 84. (ADRENAL) Sur le fonctionnement de la capsule sur- rénale humaine dans les gangrénes gazeuses. (On the func- tioning of the human adrenal capsule in gaseous gangrene). Goormagtigh (M.) C. R. Soc. de Biol. (Paris) 1918, 81, 14-17. ABSTRACTS 159 In gaseous gangrene of rapid development the adrenal curtex pours into the blood stream a large proportion of chole- sterol and its ethers. Judging from the histo-chemical charac- teristics these substances undergo important changes at the time of passing into the blood. The elimination of cholesterol is less in sub-acute cases while in chronic cases part of the cholesterol accumulates in the center of the gland. There appeared to be hyperactivity of the medulla.— F. A. H. 85. (ADRENAL) Sur l’origine de la capsule surrénale chez- les chéiroptéres (Upon the origin of the adrenal capsule in the chiropters). Costa (A. GC. da) C. R. Soe. de Biol. (Paris) 1918, 81, 51-53. Although it is generally admitted that the two portions of the adrenal have different origins, Colson thought that in chiropters the two parts had a common origin. The author attempted to verify the work of Colson, but found that chirop- ters agree with other vertebrates—F. A. H. 86. (ADRENALS) Dos casos de hematoma suparrenal. (Two cases of adrenal hematoma.) Deluca (F. A.) Semana Médica (Bs. Aires), 1918, 25, 93. Two eases are discussed. The first was that of a baby who was born asphixiated but was resuscitated and appeared nor- mal for two days. On the third day the mother noted pallor; on the fourth, jaundice developed and the infant eried all day. He was quieted by a bath but later had an attack of clonic convulsions. This was repeated several times during the night and the child died the following morning. - In the second ease the baby was born dead. Autopsy in each case showed hem- orrhages into the adrenal glands. The parents in both cases were syphilitic. Deluca thinks-that syphilis as well as exten- sive burns can produce the condition of adrenal hematoma. G. PG. 87. (ADRENALS) Le role des Surrenales dans 1’action du pneumogastrique sur le coeur. Roger (H.) Jour. de physiol. et de path. gen. (Paris), 1917, 17, 187. Whereas in normal rabbits it is impossible to maintain a prolonged cessation of heart beats by stimulation of the vagus, this is possible after the suprarenals have been removed. The heart may be kept at rest so long that asphyxial convulsions occur. This state can be converted to the normal one by the in- 160 ABSTRACTS jection of adrenin. Accordingly, the so-called escape from the vagus inhibition is regarded as due to central stimulation of nerves to the suprarenals, probably owing to the low blood pressure.—Physiol. Abst. 88. (ADRENALS) Un caso de mal de Addison. (A case of Addison’s disease.) Fonte (C.) Brazil Médico (Rio de Ja- neiro), 1918, 32, 50. Addison’s disease developed in a man fifty-eight years of age,—an alcoholic; nothing of particular interest. GaP. 89. (ADRENALIN) Hemmung der Kochsalzausscheidung im Harn durch Adrenaline. (The infiuence cf adrenalin on the secretion of sodium chloride in the urine.) Frey, Bulcke and Wels. Deutsches Arch. f. klin. Med. (Leipsig) 1917, 128, 163. After subcutaneous injections-of adrenalin the rate of ex- cretion of sodium chloride through the kidney becomes slower. It is the same with the exeretion of nitrogen. Adrenalin acts on the tissue of the kidney; in Brights’ disease the reaction of the body to adrenalin is the same as in health.—J. K. 90. (ADRENALIN) L’action de 1’adrenaline sur le coeur, étudiée par la radioscopie (Action of adrenalin on the heart, studied by the radioscope). Loeper (M.), Dubois (H.) and Wagner (C.) OC. R. Soe. de Biol. (Paris), 1918, 81, 85-86. The authors studied the hearts of a large number of normal and pathological subjects by means of the radioscope before and after giving one milligram of adrenalin. The hearts of normal subjects were found to be unchanged in a majority of cases. There was dilatation in many pathological cases. This was thought to be due to the increased pressure from constric- tion of the arterioles and inability of the heart to recover quickly. This method is suggested as a test for cardiac de- fects —F.: A. H. 91. (ADRENALIN) Location of the adrenalin vasodilator mechanisms. Hartman (F. A.), Kilborn (lL. G.) and Fraser (L.) Am. Jour. Physiol. (Balt.) 1918, 46, 168-185. Adrenalin causes vasodilatation in the skeletal muscle of the hind limb by acting on structures located in the lower lum- bar and sacral sympathetic ganglia and in the dorsal root gan- ABSTRACTS 161 gha of the nerves supplying the limb. Similarly dilatation of the intestine is brought about by adrenalin acting on structures ganglia of the lower thoracic region. It is not probable that in the superior mesenteric ganglion and in the dorsal root the antidromic vasodilator impulses caused by adrenalin are identical with those of Bayliss since there is no evidence that the blood vessels of the skin dilate with adrenalin. These re- sults, however, tend to support the view that the sympathetic system contains vasodilator fibers to the intestine and to he hind limb.—Authers’ Abstract. 92. (ADRENALIN) The combination of local and general anaesthetics and the use of adrenalin. Wishart (D. J.) Can. Pract. and Rev. (Toronto) 1916, 41, 1-4. Includes a discussion of the use of adrenalin in local and general anaesthesia. Cites two cases in which death occurred presumably from the injection of a few drops of adrenalin so- lution during chloroform anaesthesia.—F. A. H. 93. (ADRENALIN) The regulation of renal activity. IV. Regulation of urea excretion by adrenalin. Addis (T.), Bar- nett (G. D.) and Shevky (A. E.) Am. Jour. Physiol. (Balt.) 1918, 46, 39-51. Subentaneous injection of adrenalin in the rabbit is fol- lowed by an increased urea excretion by the kidneys. There is a certain amount of adrenalin which produces the greatest in- crease in funetion, smaller amounts having less and less effect until there is no change from the normal. With larger amounts the augmenting effect on secretion also becomes less until, with relatively large doses, the reverse effect of-a decrease in func- tion is found. Except with these large amounts the rate of urea excretion is more rapid than in animals not given adren- alin, in spite of a lowering of the blood urea concentration. The adrenalin is supposed to influence the secretory activ- ity of the kidney cells through the medium of something in the termination of sympathetic nerve fibers analagous to the re- ceptive substance in the end-plates of muscle fibers.—L. G. K. 94, (ADRENALIN) Untersuchungen iiber die Adrenalinwir- kung auf die weiszen Blutzellen. (The effect of adrenalin on the leucocytes.) Hatigan (J.) Wein. klin Wehnschr. 1917, 30, 1541. The subcutaneous injection of 0.001 gram adrenalin causes a leucotytosis. In the first hour after the injection there is a 162 ABSTRACTS marked inerease of the lymphocytes. The second hour the lymphocytes diminish but there is an increase of the neutrophil leucocytes. It generally takes six hours before the number of leucocytes has become normal again. If a double dose of adren- alin is injected the period of lymphocytosis persists about twice the ordinary time. If atrophine or pilocarpine is pre- | viously injected the reaction to the adrenalin is not changed.— J.K. 95. (ADRENALIN, PITUITRIN) The regulation of renal activity. VI. The effect of adrenalin and pituitrin on the action of the kidney under strain. Addis (T.), Foster (M. G.) and Barnett (G. D.) Am. Jour. Physiol. (Balt.) 1918, 46, 84-89. The condition of ‘‘strain’’ was produced by giving 5 grams of urea at the beginning of the experiment. At high blood urea concentrations the degree of change in the urea exereting activity of the rabbit’s kidney produced by adrenalin and by pituitrin is less than at low blood urea concentrations.—L. G. K. 96. (ADRENIN) Action of adrenin in auriculo-ventricular dissociation. Hardoy (P. J.) and Houssay (B. A.) Revista Assoc. Méd. (Buenos Aires), 1917, 27, 462. In a dog with experimental dissociation and in two patients the injection of adrenin caused a different degree of accelera- tion of the rate of the auricles and of the ventricles. The nor- mal rhythm was not re-established, although at a certain mo- ment there was a false appearance of removal of the block.—B. A. H. 97. (ADRENIN) Adrenin content of the suprarenal glands of cadavers of patients dying from beriberi. Ono (S.) Jikwa Zasshi, 1916, —, 1014. Nine acute cases of beriberi and two dying during preg- nancy were examined as to the post-mortem adrenin content of the suprarenal capsules. The results of the first nine varied from 4.96 to 5.99 mgs. as compared with the normal of 2.82 mgs. and those of the fatal cases were 3.01 and 4.49 mgs. Microscopically the medullary area appeared more fatty than normal and microscopically it was thought to be the seat of a lymphatic infiltration of a mild grade.—Chem. Abst. ABSTRACTS 163 98. (ADRENIN) Azione del l’adrenalina sul l’utero isolato, in riposo e gravido. Quagliarello (G.) Arch. di Ostetricia e Ginecologia (Napoli) Serie II, vol. V, parte I. Abst. La Pediatria, April, 1918. According to the experiments of the author the adrenalin heightens the tone in the isolated pregnant uterus, while in- hibiting the virgin or the non-pregnant uterus.—G. V. 99. (ADRENIN) Carbohydrate metabolism in the surviving dog liver. Abelin (J.) and de Corral (J. M.) Biochem. Ztschr., 1917, 83, 62-73. (Physiol. Abst., 2, 597.). Perfusion of rabbit liver with a peptone solution does not affect glycogen, but in the dog it is diminished. In both ani- mals adrenin perfusion has no effect on the hepatic glycogen. Chem. Abst. 12, 820. 100. (ADRENIN) Ergotoxin and adrenin hyperglycemia. Laurin (E.) Biochem. Ztschr., 1917, 82, 87-95. Stenstrom stated that the hyperglycemia and glycosuria produced by adrenin could not be prevented by injecting pitui- trin. Miculicich reported the same results with ergotoxin. This remarkable similarity of action between an animal and a fungus produet is confirmed. Chem. Abst. 12, 501. 101. (ADRENIN) Location of adrenalin vasodilator mechan- ism. Hartman (F. A.). Proce. Am. Physiol. Soc., Am. Jour. Physiol. (Balt.), 1918, 45, 555. See. Endoerin, 1918, 2, 1. 102. (ADRENIN) Relation between chemical constitution and physiclogical action. Pyman (F. L.) Jour. Chem. Soe., 1917, 111, 1103-28. A lecture dealing principally with work of the past ten years on adrenin and various esters, anesthetics, ete. Refer- ences are given and conclusions summarized. Chem. Abst. 12, 593. 103 (ADRENIN) The combined digitalis-adrenin therapy. Frey (W.) Deutsche med. Wehnschr. (Berlin), 1917, 48, 872-3. This combination method is not recommended. Chem. Abst. 12, 951. Se 164 ABSTRACTS 104 ADRENIN, the effects of on the urine flow of anesthe- tized and unesthetized dogs. Gunning (R. E. L.). Am. Jour. Physiol. (Balt.), 1918, 45, 528. Adrenin in all effective dosages administered intravenously inhibits the urine flow in both anesthetized and unanesthetized dogs. The threshold of the reaction is shightly lowered in un- anesthetized animals. Small injections and infusions merely decrease the flow of urine while larger doses produce a com- plete cessation of flow. The inhibition usually persists until shortly after the blood pressure reaction is complete. Diuresis succeeding the inhibition was not observed. The rapid return of the flow to normal after.prolonged in- fusions suggest that the drug exercises its inhibition on the kidney function in a way other than by the ischemia produced. During the administration of ether the urine flow is com- pletely checked and recovery under the anesthetic takes place slowly.—T. C. B. 105. (ADRENIN, VI) Further studies on the effect of adren- alin upon the blood flow in muscles. Gruber (C. M.). Am. Jour. Physiol. (Balt.), 1918, 45, 302. The present research was carried out to determine whether or not adrenalin acted centrally or peripherally in producing vasodilation in muscles. The conclusion reached is, that ‘‘ Vasodilation in muscles caused by small amounts of adrenalin is dependent upon the tonicity of the vessel wall.’’ Small doses of adrenalin (0.5 ee 1:100,000) bring about vasodilation by their action on the peripheral vasodilator mech- anism.—T. C. B. 106. (DIABETES) Treatment of diabetes from the general practitioner’s standpoint. Janney (N. W.) Jour. A. M. A. (Chgo.) 1918, 70, 1282-87. Of no direct endocrine interest.—R. G. H. 107. (ENDOCRINE GLANDS) Changes in the relative weights of the various parts, systems and organs of young albino rats underfed for various periods. Stewart (C. A.) Jour. Exp. Zool. (Phila.) 1918, Vol. 25. In rats underfed from birth to 3, 6, and 10 weeks, the spinal . cord, eyeballs, liver, and stomach and intestines (empty) in- crease considerably in weight. A less marked inerease occurs = os, ABSTRACTS 165 in the brain (at three weeks especially), spleen and intestinal contents (at 6 and 10 weeks, loss earlier), suprarenals and heart (progressive increase), kidneys, testes, epididymi (at 3 and 6 weeks, loss later), ovaries and hypophysis. There is no marked change in the weights of the thyroid and pineal glands, whereas the lungs and especially the thymus lose markedly. In young rats underfed for very long periods (up to 428 days), the marked increase is maintained in the weight of the spinal cord, eyeballs, suprarenals (usually), and brain (slightly). There is but slight change in the weights of the intestinal con- tents, kidneys, ovaries, testes(?) and pineal body. The thyroid, thymus, heart, liver (variable), spleen (variable), alimentary canal (empty) epididymi, and hypophysis (in males) usually suffer a loss.—E. R. H. 108. (ENDOCRINE GLANDS) El sistema nervioso y las glandulas endocrinas en un caso de myopathia. (The nervous system and the endocrine glands in a case of myopathy.) Navarro (J. C.) and Correas (C. A.) Soc. Med. Argent., 1917 (June 29). Histological examination of the nervous centers, peripheral nerves, thyroid, hypophysis, suprarenals, ete., disclosed no demonstrable lesions.—B. A. H. 109. (ENDOCRINE GLANDS) Excretion of uric acid in sev- eral cases of disease of the blood glands. Nowaczynski (J.) Deutsche med. Wehnschr. (Berlin), 1916, 42, 1478-80. (Physiol. Abst. 2, 132.) Although purin metabolism is frequently upset in diseases of the blood glands the changes are most variable. The injec- tion of extracts also causes varying results, though ovarin and pituitrin produce a rise in the excretion of exogenous urie acid. Chem. Abst. 12, 941. 110. (ENDOCRINE GLANDS) The glands of internal secre- tion. Crispin (A. M.) La Prensa méd. Argentina (Buenos Aires) 1917, 27, 279. Nothing new.—B. A. H. 111. (ENDOCRINE GLANDS) The origin of progressive muscular dystrophy. Editorial, Jour. A. M. A. (Chgo.) 1918, 70, 1376. ; Diseusses late work on the subject, including the possible relation of the endocrine glands to that malady.—R. G. H. 166 ABSTRACTS 112. (ENDOCRINE GLANDS) The effect of the administra- tion of various substances on the blood diastase of rabbits. Watanabe (C. K.) Am. Jour. Physiol. (Balto.), 1917, 45, 30-43. The dextrose content of the blood was increased without any change in diastase content by the administration of ad- renin. Pitruitrin injections and thyroid feeding had no effect on either diastase or dextrose content. 113. (ENDOCRINE GLANDS LACTATION) Preliminary research on the effect of extracts of certain endocrine glands on the amount of milk produced by cows and goats. D’AI- fonso (C.) Ind. latt. e. zootec., 1916, 14, 215-6, 234-5, 253-4, 268-9, 286-7, 302-5, 316, 350-1; 1917, 15, 7-9. This is a repetition of previous studies of the effeet of the injection of extracts of ovaries, testes, adrenals, thyroids, hypo- physis and mammary glands on milk production. Chem. Abst. 12, 592. 114. (GASTRIN) Gastric secretin. Maydell (E.) Diss. Kiev, 1917. (Physiol. Abst., 2, 415-6.) Gastrin prepared from the mucous membrane of the pyloric part of the stomach with 0.4% HCl was injected into dogs with chronic gastric fistula and esophagotomy. A rather ener- gvetic secretion of gastric Juice was obtained under such condi- tions; its acidity was equal to that of the juice obtained by means of sham feeding, but its digestive power was less. The immediate introduction of the gastrin into the blood acts more feebly than upon subcutaneous injection, and in the former case a decrease of blood pressure occurs, but not in the latter. If the gastrin is treated with alcohol and ether, it is possible to separate two component parts, one of which evokes secretion and the other dilates blood vessels. Gastrin is absorbed neither by the duodenum nor by the large or small intestine. The gastrin prepared from the fundie region is inactive. Atro- pine diminishes the secretory effect of gastrin. Chem. Ast. 12, 718. 115. GLAND EXTRACTS, the bacteriolytic action of, on tu- bercle bacilli. Porter (A. E.) J. Hygiene (Lond.), 1917, 16, The results obtained point to a consistent relationship be- tween lipolytic activity and bacteriolytic power on tubercle zi fi yf) ABSTRACTS 167 bacilli. The least bactericidal extract was lung extract and the most powerful was pancreatic extract. Liver, thymus and lymphatic glands were strongly bactericidal. Other organs, suprarenal glands, pig and cat spleen, human and eat kidney, human and ox brain, ox thyroid, cat lung, ox bone marrow, and ox pituitary glands were found to be bactericidal to a lesser degree. Human skin extract was fatty and cloudy in appear- ance and exceptionally rich in esterases. This sample of skin bears out the relationship between lipolysis and bacteriolysis of tubercle bacilli in a striking way, as it was extremely bac- tericidal. No difference was observed between human and bovine tubercle bacilli in susceptibility to any gland extract examined. Other acid-fast bacilli, though on the whole less susceptible to the influence of these extracts, were bacteriolyzed by them. They were also killed by one lung extract (pig) which contained an unusual amount of olein hpase and which had no effect on tubercle bacillimChem. Abst. 116. (GONADS) Kérpertemperatur und Pubertitsdriisen. (Bodily temperature and the sex glands.) Lipschiitz (A.) Arch. f. d. ges. Physiol. (Pfliiger’s) (Bonn) 1917, 168, 177. The temperature of female animals is about 0.6-0.7° C. higher than that of males. After castration the temperature becomes about 0.4° lower. When after this operation a testicle is implanted the temper rature becomes still lower. In male animals, however, castration has no scntieites on temperature. When after castration an ovary is implanted the temperature rises until it reaches that of normal female animals.—J. K. 117. (GONADS) Microrchidie et gynecomastie consécutives a4 une orchite double. [Laignel-Lavastine (M.) and Courbon (P.) Presse Méd. (Paris) 1917, 25, 492. Before the Sociétié Medicale des Hopitaux (July 20, 1917) the case of a soldier of 22 was presented, who after suffering from mumps last December, which was complicated by a double orchitis, began to present retrogressive evolution in the repro- ductive organs. Virility was lost and there was a remarkable transformation of the secondary sex characteristics and the establishment of those of the opposite sex. Little by little these changes were accentuated and the mammae attained a marked degree of hypertrophy with atrophy of the testes and penis. The authors consider this of the plastic type of hermaphro- ditism.—H. R. H. a ABSTRACTS 118. (GONADS) Spontane Geschlechtswandlung beim Hunde in Verbindung mit Morbus Basedowii. (Spontaneous change of sexuality in a dog suffering from Graves’ disease.) Heil- born. Deutsche med Wehnschr. (Berlin) 1918, 44, 213. A very remarkable case is described. A male dog becomes very nervous and thin and shows an exophthalmos; there is a large goitre and tachycardia; in the last two years the testes have become atrophic and the mammary glands larger. The most typical symptom, however, was an absolute homosexu- ality. The author does not discuss whether the changes in the thyroid have anything to do with the homosexuality.—J. K. 119. (GONADS) The effects of inanition upon the develop- ment of the germ glands and germ cells of frog larvae. Swingle (W. W.) Jour. Exp. Zool. (Phila.) 1918, Vol. 24. Immature frog laryae were starved from the time of their emergence from the egg capsule for over one hundred days. During this interval the tadpoles were fed a few filaments of algae at odd times to prolong the experiment. No growth oe- curred, nor were there any indications of metamorphic changes. The control animals developed normally and underwent meta- morphosis at the usual time. Microscopic examination of the gonads and germ cells showed that in the starved animals growth and development of these structures had, like somatic development, been completely inhibited. In one or two of the oldest animals of the starved series, germ cells were observed which appeared to be in the early maturation stages. Drawings and photographs are given illustrating these points.—E. R. H. 120. (GONADS) Vorherbestimung der Geschlechts. (Is it possible to prophesy the sex of the child during pregnancy?) Konigstein (R.) Zentralbl f. Gyn. (Leipsig) 1917, 41, 1097. Theoretically it would be quite logical when if the child in pregnancy is a boy, the serum of the mother would contain ‘protective ferments’’ against testicle. The experiments by Konigstein in this direction gave from time to time a positive result, but not regularly enough to be of clinical value. he results, however, were remarkably better when, instead of or- dinary testicle, that of an embryo or a calf was used. 121, (HYPOPHYSIS ADRENAL) The relation of the glands of internal secretion to milk production. Hammond (J.) and Hawk (J. C.) Jour. Agr. Sci., 1917, 8, 147-53. "5 ABSTRACTS, 169 The flow of milk produced by an injection of pituitary extract varies with the state of nutrition of the injected ani- mal. The ratio of morning yield to pituitary yield rises with the fall of nutrition and falls as the nutrition rises again. Therefore the yield obtained as a result of pituitary injections tends to be more constant than the morning or daily yield. The fat percentage of the pituitary milk is increased by the state of lowered nutrition in the same way as with normal milk. Injeetions of adrenin give results similar to those of pituitary extract in causing hyperglycemia, but different in having no immediate action on milk secretion. The secondary effeet on milk secretion is a decrease in the amount of milk produced for a period of a day following the injection. The fat percentage in the milk from the period following an adrenin injection is above normal but the absolute amount obtained is decreased. The rate of blood flow is very susceptible to changes in the sugar metabolism of the animal. Chem. Abst. 12, 822. 122. (HYPOPHYSIS) Acromegaly. Castex (M. R.) La Presna méd. Argentina (Buenos Aires), 1918, Supplement 25 (Feb. 10). Although the subject (evidently acromegalic) presented an appearance of the sella turcica on the X-ray plate of an ad- vanced stage of the disease and showed certain visual disturb- ances, the author believes that the symptoms, even headache and vomiting, are due to syphilis. He thinks the symptoms could all be ascribed to a functional defect of the pituitary secretion and doubts the existence of a tumor.—B. A. H. 123. (HYPOPHYSIS) Cirurgia da hypophyse. (Surgery of the hypophysis.) Novaes (J.) Brazil Médico (Rio de Janeiro), 1917, 31, 431. Novaes in a review of an article by Segura criticises the latter for leaving the accessory hypophysis. GePuGy 124. (HYPOPHYSIS) Control of polyuria in a case of dia- betes insipidus by means of hypophyseal extract. Rosen- bloom (J.) Jour. A. M. A. (Chgo.), 1918, 70, 1292. The case of .a boy of 1214 years is deseribed in which polyuria of 9 years’ duration existed. Thyroid tablets, 6 grains a day, were without effect, as were also pituitary tab- lets. Pituitary solution, however, injected subcutaneously brought about an almost three-fold reduction of the urine. The effect lasted about 24 hours.—R. G. H. 170 ABSTRACTS 125. (HYPOPHYSIS) Beitrage zur Pathologie der Hypophyse. (Pathology of the hypophysis.) Fahr (T.) Deutsche Med. Wehnsehr. (Berlin) 1918, 44, 206. A woman of 50 years suffered from convulsions; the Argyll-Robertson symptom was positive; the Wassermann re- action negative; the blood pressure was normal and the skin showed a brown pigmentation as in Addison’s disease. The postmorten examination showed atrophy of both suprarenal bodies; medulla and cortex were both affected. Macroscopi- cally the pituitary body showed no changes; microscopically, however, nearly the whole organ was changed to a mass of eon- nective tissues, except the pars posterior, which showed no pathological changes.—J. K. 126. (HYPOPHYSIS) Further studies upon amphibian larvae from which the anterior lobe of the hypophysis had been removed. Allen (B. M.) Anat. Ree. (Phila.) 1918, Vol. 14. The anterior lobe of the hypophysis was removed from larvae of Rana pipiens and Bufo lentiginosus as described in an earlier paper. The observations previously published were verified and much extended because of greater success in rear- ing the operated tadpoles. Several are still alive. Limb development in both species is greatly retarded, run- ning parallel with the condition in tadpoles from which the thyroid gland has been extirpated. In Bufo there is a color change to a light yellow-brown, and contrary to the case in Rana there is little retardation of bodily growth. The pars nervosa of the hypophysis forms normally in tadpoles, both Rana and Bufo, from which the anlage of the anterior lobe has been removed. There is, of course, no pars intermedia formed. Gonads of operated Rana tadpoles were compared with normal controls of the same size killed several months before. They showed the same features as to size, structure, and germ- cell development as seen in the controls. The same correspond- ence in the gonads was noted when comparison was made with some small thyroidless tadpoles of the same size killed at the same time. The retardation of bodily growth in Rana prevented the gonads from reaching the size attained in the controls at meta- morphosis three months before. In Bufo, however, the oper- ated tadpoles reached a bulk double that at metamorphosis. Correspondingly, the gonads and germ cells developed far be- yond the condition attained at the time of metamorphosis in the controls.—E. R. H. ee on ie ¢ ABSTRACTS 171 127. (HYPOPHYSIS) Pituitary disturbance in its relation to the psychoses of adolescence. (Abstract.) Tucker (B. R.) A general description of the functions of the pituitary gland and of its anterior and posterior lobes is given. Remarks are made upon the period of adolescence and the physiological disturbances of the pituitary secretion occurring at this time. The pathological disturbances of the pituitary secretion causing the psychoses are then taken up. Pituitary adolescent psychoses are divided into four groups: Ist—Those with a pre-adolescent history of hypersecre- tion, in which during adolescence the secretion is apparently still further inecréased ; 2nd—Those in which there is a history of pre-adolescent hypersecretion, in which during adolescence this secretion is markedly diminished ; 3-a—Apparently normal pre-adolescent cases in which the secretion during adolescence is increased. 3-b—Those with an approximately normal pre-adoleseent pituitary history, in which during adolescence the secretion is diminished ; . 4th—Those cases with a history of pre-adolescent de- creased secretion, in which during adolescence the secretion is apparently still further decreased. Cases are cited with radiographic findings to illustrate these groups and a description of their psychoses given Author’s abstract. Read before neurological section, Amer- ican Medical Association, Chicago, June, 1918. 128. (HYPOPHYSIS) Poliuria no hipofisiaria en un cancer de la mama con metastasis. (Non-hypophyseal polyuria in mammary cancer with metastasis.) Houssay (B. A.) — Re- union de Médicos del Hospital Alvear, 1917 (June 29). The author remarked that according to his experimental studies the so-called hypophyseal polyuria does not depend upon the hypophysis.. In a clinical case studied a polyuria of 3-4 litres was not influenced by injections of pituitary material. At autopsy metastases were found in the frontal and bacilar sinuses and in the meninges, but the hypophysis and adjacent cerebral zone were not affected.—B. A. H. 129. (HYPOPHYSIS) Sobre o tratamento dos tumores da hypophyse e, especialmente, da acromegalia. (Treatment of hypophyseal tumors and especially of acromegaly.) De 172 ABSTRACTS Castro (A.), Souza (O. de) and Novaes (J.) Brazil Médico (Rio de Janeiro), 1917, 31, 415. _ De Castro reviewed favorably the work of Segura, who was the first in South America to undertake the surgical treat- ment of pituitary tumors. Souza agreed with de Castro that attention should be paid to the parahypophysis. Novaes re- viewed the Austrian statistics and concluded that both the nasal and frontal approaches to the hypophysis are very dan- gerous. G. P. G. 130. (HYPOPHYSIS) Sobre un caso de poliuria esencial, de aparicion a los 3 anos de dad. (A case of polyuria appearing at the age of three.) Deluca (F. A.) Semana Médica (Bs. Aires), 1918, 25, 422. Deluca discusses the theories of polyuria including the hypophyseal variety. He reviews the experimental work of Camus and Roussy and of the Houssay, which indicates that the condition is produced by injuries of a certain basal zone rather than of the gland proper. (See Houssay, Endoerin., 1918, 2, 94.) A complete review of the Argentine hterature on the subject is included. A ease is discussed of a boy three years of age who complained of marked thirst and who passed four litres of urine daily. A detailed study of the case was not permitted. . GPG: 131. (HYPOPHYSIS) Su un infermo con sindrome psichica e femminilismo hipofisario, guarito con l’asportazione di veg- etazioni adenoidi. Caliceti (P.) La Pediatria (Napoli) 1918, 26, 233. The author refers to one of three cases of hypophyseal feminism with psychic syndrome, caused by adenoids, accord- ing to Prof. Citelli’s opinion and his own. The patient has been seen eight months after the removal of the adenoids and showed a wonderful change from his previous conditions. Physically stronger, with a much better color, lively and quick, he was not showing dullness or apathy as before. His hair on the face and on the pubis is now practically normal; and the sleep as well as his psychic behavior do not now longer show any abnormality. Such an effect hardly eight months after the removal of the adenoids points—Ist, to the hypophyseal nature of his pre- vious feminism, asthenia and psychic syndrome; 2nd, to the right surmise of Prof. Citelli, that the adenoids may be the cause and not the effect (according to Poppi’s theory) of hypo- psyseal alterations; 3rd, to the efficacy of intervention, even + < =) ABSTRACTS 173 late, whenever the hypophyseal alterations are not grossly ana- tomical.—G. V. 132. (HYPOPHYSIS) The action of hypophysis extracts on gastric juice secretion and gland secretions in general. Pal (J.) Deutsche med. Wehnschr. (Bérlin), 1916, 42, 1030. This paper concerns the action of the extract of the in- fundibular portion of the hypophysis on gastric secretion, on the action of the kidneys and other exocrine glands, as well as on the thyroid. In summary, the extracts act inhibitingly on certain glands. This action is demonstrable in man in cases of hypersecretion (on the kidneys in diabetes insipidus, on the thyroid in hyperthyroidism, and on the stomach mucosa in hyperacidity). On the other hand, it promotes the secretion of the mammary gland and the excretion into the follicles of the thyroid, but only when there is hyperfunction of these glands. The secretion of the innervated glandular apparatus (stomach glands, kidneys, ete.) is not only dependent on the irritability of the secretory nerves, but also of the inhibitory nerves. The depressant action of the infundibular extract on the secretion depends on the action of the extract on the irritability of these nerves, which are located in the sympathetic. The stimulating action can be traced to a direct action on the cells——Chem. Abst. 133. (HYPOPHYSIS) The arterial supply of the human hypophysis. Anat. Ree. (Phila.) 1918, Vol. 14. Three methods are being used: (a) Injection with thin _celloidin and corrosion by artificial gastric juice—somewhat unsatisfactory because of difficulty of injecting finer vessels, and beeause relations of arteries to tissues are not preserved ; (b) wax reconstructions of thick colloidin sections of foetal specimens—sections not yet studied; (¢) dissection under binocular of gelatin-injected vessels. Brains for dissection are injected through the common earotid, with contra-lateral carotid, both vertebrals and ex- ternal and internal jugular veins hgatured. Robin’s Prussian blue and carmin have been used. The base of the brain in the region of the sella tursica and the underlying bone are re- moved and preserved in formalin. The brain and meninges are carefully freed from the underlying bone, dehydrated and cleared in cedar oil. They may then best be dissected under oil of wintergreen with a binocular. The brains are dissected through their underlying meninges successively upon two planes: (1) an intradural 174 ABSTRACTS plane, comprising the internal carotids and their branches within the cavernous sinus; (2) a subdural plane comprising the circle of Willis and its branches. Four brains only in the intradural plane have thus far been dissected. In each of these four brains there are found, arising from each internal carotid at. its first and superiorly convex flexure in the cavernous sinus, an artery of approximately one to two millimeters in diameter which quickly breaks up into several somewhat variable branches. These branches, together with an inconstant artery which may arise from the carotid in the sinus cavernosus more anteriorly, supply the semilunar gan- glion, the third, fourth, fifth and sixth nerves in this region and the contiguous dura mater. One of the branches on each side, ramifying, courses between the layers of the dura across the posterior lobe; twigs are sent also to the dura and may even be sent to the anterior lobe. The branch described is probably sufficient to supply the posterior lobe, but apparently does not form a considerable element in the supply of the highly vascular anterior lobe.— K. R. H. 134. (HYPOPHYSIS) The development of the pars tuberalis of the rabbit’s hypophysis. Atwell (W. J.) Anat. Ree. (Phila.) 1918, Vol. 14. For the rabbit it has been possible to trace the development of the paired anlagen of the pars tuberalis of the hypophysis from an earlier stage than that given by Tilney (713) for the chick and the eat, or by Miller (716) for the pig. From the thickened epithelium which early lies in front of Rathke’s pocket two thickened ridges are developed. These ridge-like eminences may be ealled the latral lobes, and are evident in em- bryos of 10 days. At 14 days these lobes have begun to grow out laterally and are more sharply constricted from the body of the hypophysis. The lateral lobes are the anlagen of the pars tuberalis of the adult hypophysis. They begin to be in relation with the brain wall at 16 days of development, and by 19 days a con- siderable portion lies spread out under the diencephalic floor. There are present at this stage two blunt nasal horns extending toward the optic chiasm and two sharper caudal horns extend- ing backward to surround the neck of the neural lobe. The caudal horns have completely surrounded the infundibulum, and have met in the mid-line by the end of the twenty-eighth day. The nasal horns fuse with each other a day or so later. Since the lateral lobes of the mammalian hypophysis may be seen early in development, it is now easier to consider them ABSTRACTS 175 homologous with the lateral lobes of the reptilian hypophysis. Because of its paired origin, the anterior part of the pars tuberalis cannot be homologized with the ‘‘Vorraum’’ of the reptiles, as is done by Woerdeman (’14).—E. R. H. 135. (HYPOPHYSIS) Trastornos hipofisiarios en Gineco- logia. (Hypophyseal disorders in gynecology.) Guardado (J.) Revista de la Asociacion Medica Argentina (Buenos Aires) 1918, p. 256, (March). Certain cases of amenorrhea in which ovarian opotherapy had been unsuccessful were treated with posterior lobe pitu- itary extract with favorable results. In other cases the treat- ment failed. The author thinks that the pituitary extract stim ulated the ovaries.—B. A. H. 136. (HYPOPHYSIS) Veranderung in der Hypophysis ce- rebri bei Kretinismus und Myxoedem. (Changes in the pitu- itary body in cretinism and myxodema). LEichhorst. Deutsches Arch. f. klin. Med. (Leipzig) 1916, 124, 207. In ecretinism and myxodema a hyperfunction of the pitu- itary body is observed. The organ becomes larger and shows an enormous hyperemia. Often hemorrhages are observed. The glandular cells grow; the chromophil cells degenerate and are replaced by cells which show the same structure as the preg- naney cells of Erdheim and Stumme. Later on a growth of the connective tissue is to be seen; then the glandular tissue be- comes atrophic ; in the connective tissue necrosis and the forma- tion of cysts is observed. At the end of the disease the pitu- uitary body becomes smaller and smaller.—J. K. 137. (HYPOPHYSIS-SYMPATHETIC SYSTEM) Diabetes insipidus in pregnancy. Novak (J.) Berlin. klin. Wehnschr. (Berlin), 1917, 54, 107-9. This condition is due to stimulation of the sympathetic system. A study of cases in which the hypophysis enlarges in pregnancy shows that the regulating centre is not altogether in the bulb but partly in the mid-brain. Chem. Abst. 12, 914. 138. (INTERNAL SECRETION) Adiposis dolorosa Der cumsche Krankheit mit Beteiligung der optischen Leitungs- bahnen. (Dercum’s disease with ocular symptoms.) Behr. (C.) Klin Monatsbl. f. Augenheilk. (Berlin) 1917, 59, No. 728. 176 ABSTRACTS A case of adiposis dolorosa with amblyopia was treated with thyroidine without success. Pituitary extract (‘‘Hypo- physin’’) raised the vision to 7/15.—J. K. 139. (INTERNAL SECRETION) Is the course of experi- mental cramp modified by disturbance of the internal secre- tions? Fischer (J.) Sitz. nat. Ges. Rostock, 1914, 6, 1-2. Fischer believes that the course of experimental cramp is modified by disturbances of the internal secretions. The ab- sence of the thyroid and epithelium increases the cramp-pro- ducing component of the amyl nitrate action, while the ab- sence of the suprarenals decreases it—Chem. Abst. 140. INTERNAL SECRETIONS. Collip (J. B.) J. Can. Med. Assn. (Toronto), 1916, 6, 1063-1069. Nothing new.—F. A. H. 141. (INTERNAL SECRETIONS) Lidodystrophia Pro- gressiva ina male. Weber (F. P.), Brit. J. Chil. Dis. (Lond.) 1917, 14, 179. The author presents a table of all of the cases of this condi- tion in males reported in the literature, and describes a case in a boy of 13 years. This boy was moderately fat in the face and body until the age of 8 years. He then began to look thinner in the face, although in all other respects he continued to appear and feel perfectly well. The loss of fat gradually progressed and for the last three years there has been prae- ticallv no fat left on the face and neck, except in the orbits. The fat covering on the gluteal regions and on the lower ex- tremities, however, is fairly normal.—M. B. G. 149, (INTERNAL SECRETIONS) Results observed in a further study of prenatal causes of dentofacial deformities. Weinberger (B. W.) Dental Items of Interest, 1918, 40, 6-31. A discussion of the factors influencing the growth of the bones of the face and the teeth, with special stress on the role of the internal secretions. Chem. Abst. 12, 933. 143. (INTERNAL SECRETIONS) Sexual precocity in the male. Strauch (A.) Amer. J. Dis. Chil. (Chgo.) 1918, 15, 132. The author makes an exhaustive study of the literature on this subject, quoting freely from several sourees and attempts to sum up our present knowledge of the condition. In a few ABSTRACTS 177 observations premature sexual development has been ascribed to such early and excessive practices as masturbation and co- habitation due to seduetion. Where such pathological factors are absent, what may he the cause of the prematurity of the impulses for the somatic changes remains a problem. Though the nature of the primary stimuli that control these changes is not known, it is established that the endocrine glands in their interlocked and mutually affecting functions are of the greatest importance for the normal growth of the body and for sexual maturity, among them especially the genital glands, the adrenals, the pituitary body, the thyroid and the so-called “puberty glands,’’ the thymus and the pineal. The author quotes several cases in the literature in which the etiological factor was a tumor of the generative glands. He thinks that these tumors suggest that the irritation of the gonads causes an excessive and premature increase of the fune- tion of the interstitial tissue of Leydig, hastening the develop- ment of the secondary sexual characteristics. Where the causes were tumors of the adrenals, he ascribes to these merely a has- tening influence on the development of the secondary sexual characteristics, causing also an excessive growth of the body, since other recognizable sexual functions, such as menstruation or ejaculation, are not mentioned in the reported cases. The relation between genital hypertrophy and the pineal gland is perhaps to be interpreted as due to a premature decrease of the funetiorating glandular tissue, which otherwise under nor- mal conditions undergoes degeneration, beginning with the seventh year of life. The trophic disturbances, that is, the premature development, may be considered as a manifestation of the insufficiency of the epiphyseal gland.—M. B. G. 144. (INTERNAL SECRETIONS) Studies of internal secre- tions in their relation to the development and condition of the teeth. V. Summary of miscellaneous findings. Gies (W. J.) Dental Cosmos, 1917, 59, 1238. Thyro-parathyroidectomy has no influence on the dentition of young white rats., Parathyroidectomy, without material dis- turbance of the thyroid, almost invariably produces deficient calcification, but has no influence on the general conditions or dimensions of the teeth. ‘‘Possibly the thyroids normally tend to induce deficient (subnormal) calcification of the teeth and the parathyroids normally tend to induce correspondingly ex- cessive (supernormal) dental calcification.’’ Physiological variation in the composition of the teeth, in rats, is relatively slight. Chemieal changes in developing enamel occur under the influence of substances that originate outside of, and enter 178 ABSTRACTS or superficially affect, the cells involved in the production of enamel.—Chem. Abst. 145. LYPODYSTROPHIA PROGRESSIVA. Spear (I. J.). Arch. Int. Med. (Chgo.), 1918, 21, 39. Case report of lypodystrophia progressiva occurring in a school girl 15 years of age who otherwise showed no pathologi- cal findings. The case has progressed continuously for the past six years. Thyroid extract failed to retard the progress of the disease. The author does not accept the view that the condi- tion is due to abnormal function of the endocrine glands, but considers it closely related to the muscular dystrophies; one factor having to do with dystrophy of fatty tissue, the other with muscular tissues. There were no indications of altered functioning of the ductless glands.—H. W. 146. (MENSTRUATION) Sindroma apendicular en la men- struacién. (Appendiceal symptoms in menstruation.) Plat- ero (H.) Rev. Méd. del Uruguay (Montevideo), 1918, 21, 71. Three cases are described in which virgins without evi- dence of genital injury or infection had pain at MeBurney’s point for three or four days preceding menstruation. At oper- ation swelling of both appendix and ovaries was noted. In one case pus was found in the peritoneal eavity. G. PG: 147. MONGOLISM associated with congenital cataract. Weber (F. P.) Brit. J. Chil. Dis. (Lond.) 1917, 14, 267. According to Weber, the only other published case of asso- ciation of mongolism with congenital cataract was that of W. B. Hill, reported a few years ago. The author reports a case of a boy of 13 months with a typical mongolian facies, protruding tongue, rhacitis, and con- genital eataract. The thumbs and little fingers were rather short in proportion to the other fingers, the little fingers pre- sented a slight lateral curvature with the coneavity of the curve toward the other finger. The mother of the boy gave a negative Wasserman re- action.—M. B. G. . 148. (MONGOLISM) Congenital heart disease in a mentally defective child with a negroid-mongoloid facies. Weber (F. P.) Brit. J. Chil. Dis. (Lond.) 1917, 14, 269. ABSTRACTS 179 The author reports a case of a girl of 4 years with a brachycephalie head, upward slant of palpebral fissure, broad nose with low flat bridge, lips and cheek and soft parts above eyes thick and coarse, hair scant and curly, no hair on eye- brows, no lower and hardly any upper eyelashes. The face was highly colored at times. The thyroid could be felt but was not enlarged. There was dry skin and xeroderma, but no signs of rickets. The heart showed a definite systolic murmur, was always present, especially well marked over the base to the left of the sternum (perhaps a congenital pulmonary sten- osis) ; X-ray examination showed a shadow on that side. The Wassermann reaction of the mother was negative. W. B. Hill has stated that 10 to 20 per cent of all cases of Mongolian type have congenital heart disease.—M. B. G. ~ 149. (MUSCULAR DYSTROPHY) Chemical changes in the blood and urine in progressive muscular dystrophy, progres- sive muscular atrophy and myasthenia gravis. McCrudden (F. H.), Sargent (C.S.). Arch. Int. Med., 1918, 21, 252. In three cases of progressive muscular dystrophy were found museular weakness, hypoglycemia, hypocholesterinemia, ereatinuria and normal excretion of ammonia. Treated patients demonstrated a rise in blood sugar with a parallel increase in strength. Blood sugar was found low in one ease each of progressive muscular dystrophy and myasthenia gravis and normal in -pro- gressive muscular atrophy. Creatinuria was present in the cases of progressive muscular atrophy and dystrophy and ab- sent in myasthenia gravis.—H. W. 150. MUSCULAR DYSTROPHY, the endocrine origin of. Janney (N. W.) and Goodhart (S. P.). Arch. Int. Med. (Chgo.), 1918, 21, 189. The authors diseuss the clinical and laboratory findings in a representative series of cases (9) of museular dystrophy in ehildren and adults. Metabolism experiments on these cases gave the following results: marked decrease in preformed creatinin in the urine; abnormal presence of creatin in the urine; low percentage of creatinin in the blood; normal amounts of creatin in the blood; hypoglycemia; delayed utili- zation of glucose. Distinct osseous changes accompany muscu- lar dystrophy in most cases which resemble closely those condi- tions found in cases of disturbed function of the organs of in- ternal secretion. Other changes indicative of general endocrine disturbance found in these cases were dryness and abnormal 180 ABSTRACTS pigmentation of the skin, brittleness of the hair, hypertrichosis. trophic changes in the nails, unusual distribution of fat and both hypertrophy and underdevelopment of the genitaha. Re- tardation of growth, a symptom indicative of endocrine hypo- function, was characteristic also of several of these cases. After an extensive comparison of conditions found in museu- lar dystrophy with altered endocrine function the authors point out the possibility of muscular dystrophy and perhaps other so- called myopathies being in reality nothing more than symptom complexes caused by deficient function, not of one, but of var- ious endocrine organs affected separately or coincidently. This attitude appears reasonable in view of the fact that the symptoms which are known to represent dysfunction of one ductless gland are often very similar to or identical with manifestations of the affection of another. For instanee, stop- page of erowth. adiposity and defective bone formation are known to result from lesions of either the pituitary, the thyroid or the sex glands. Hence, if these svmptoms are associated with such widely different organs, it seems probable that mus- eular dystrophy may likewise represent a symptom complex which may he caused by dysfunction of various ductless glands singly or collectively. Therefore, muscular dystrophy cannot he ascribed to hypothyroidism. as the results of former investi- vations might seem to indicate. The fact that the hypophysis was unquestionably affected in one case and possibly the pineal body in two others, illustrates how diffienlt it would be to ex- plain the present series of cases on a basis of hypothyroidism or disturbanees of the hypophysis.—H. W. 151. MUSCULAR DYSTROPHY, progressive. McCrudden (F.H.) Jour. A. M. A. (Chgo.) 1918, 70, 1216. ‘In progressive muscular dystrophy, we find low blood sugar, and, following treatment which increases the blood sugar, an improvement in muscular strength. ‘‘Blood sugar is the source of energy for muscular contrae- tion. Active muscle rapidly uses up glucose. As the supply becomes exhausted, muscular strength diminishes and can be restored only by glucose. Agencies such as Addison’s dis- ease, diphtheria toxin, and phosphorus and hydrazin poison- ing, which reduce the blood sugar, cause profound myasthenia, the severity of which is proportional to the fall in blood sugar. Hypoglycemia, then, sufficiently accounts for the myasthenia, the most striking symptom of progressive muscular dystrophy. ‘As the glucose of the blood is used up by the muscles, the loss is rapidly and quantitatively made good from the store of ABSTRACTS 181 glycogen in the liver, the blood sugar being thereby main- tained at a fixed level. Hypoglycemia can result only from a failure of replenishment to keep pace with the needs, that is, from a loss of balance between supply and demand. Greater needs, such as increased utilization of sugar, or loss through the kidneys, can be ruled out in progressive muscular dys- trophy. There is no rise in heat formation such as would ac- company increased sugar catabolism, and the urine is free from sugar. A rapid fall in blood sugar during the first twenty- four hours of starvation—in health, the normal blood sugar level is maintained during starvation—testifies that in pro- gressive muscular dystrophy, as in all forms of experimental hypoglycemia, there is a decreased rate of replenishment re- sulting from a diminished reserve of glycogen. ‘““The diminished glycogen reserve in experimental hypo- glycemia results from impaired glycogen formation. The car- bohydrate ingested is not converted into glycogen, but remains a long time in the blood, after which it is probably changed to fat. The deposition of fat in the museles points to a similar impairment of glycogenesis in progressive museular dystrophy. ‘*Impaired glycogenesis may result from damage either to the liver or to the suprarenals, the organs that control the process or other endocrine glands. If the fault is with the suprarenals, administration of epinephrin restores normal ely- cogenesis. If the fault is with the liver, epinephrin has no effect. A prompt and marked rise in blood sugar following the administration of epimephrin in progressive muscular dystrophy testifies to the efficiency of the liver in this disease and points to a deficiency in epinephrin.’’—Abbreviated from original. 152. (OVARIES) Hernias conjenitas tubo-ovaricas. (Con- genital tubo-ovarian hernia.) Lugones (C.) Soc. Med. Argent., 1917 (June 29). Among fifteen cases observed in little girls there were two in which the ovaries were removed on account of hermorrhagic cysts. Microscopic examination confirmed the presence of hermorrhagic cystic cavities —B. A. H. 153. (OVARY) Effect of hysterectomy on ovarian function. Richardson (E. H.) Proc. Am. Gyn. Soc., Jour. A. M. A. (Chgo.) 1918, 70, 1885. ; ‘The uterus is not essential to a continuation of ovarian function, except as regards menstruation and reproduction. The disturbances of ovarian function attributed to hysterec- 182 ABSTRACTS tomy are partly those associated with normal menstruation and partly those arising from damage to the ovary through operative trauma or disease. The weight of evidence fur- nished by anatomic, experimental and clinical investigations is overwhelmingly in favor of retention of sound ovaries both before and after the menopause age.’’ 154. (OVARY) End results of the conserved ovary. Polak (J. O.) Proe. Am. Gyn. Soc., Jour.-A. M. A. (Chgo.) 1918, 70; 1975. ‘From a study of seventy-three reoperations on patients in whom one or both ovaries were conserved, we must draw the following conelusions: 1. Routine conservation without due consideration of the ovarian and contiguous pathologic condition as it exists in the individual case, is not good teach- ing. 2. Regeneration of the conserved ovary depends largely on the type and duration of the existing infection and the con- dition of the tunica of the individual ovary. 3. Even when the most detailed technie is observed, the ovarian cireulation is impaired. 4. The retained ovary, without the uterus, is always a focus for possible trouble. 5. The hfe history of the retained ovary is of short duration, and the trophie influence of the diseased ovary has been overestimated. Finally, a cured patient has few nervous symptoms. ’’ 155. (OVARIES) Evidence of toxic action of ovaries of Gar. Greene (C. W.), Nelson (E. W.) and Baskett (E. D.). Proe. Am. Physiol. Soc., Am. Jour. Physiol. (Balt.), 1918, 45, 558. 156. (OVARY) La funcion endocrinica del ovario y la secre- cin mamaria. (The endocrine function of the ovary and mammary secretion.) (oni Bazan (F. A.) Semana Médiea (Bs. Aires), 1918, 25, 570. In 1915 Coni Bazan published with Berutti an article upon mammary deficiency in lactating women treated with ovarian opotherapy, corroborating various observations first recorded by Gonalons in 1914. The latter reported the successful use of corpus luteum in the treatment of these cases, adducing numer- ous clinical and experimental observations. Gonalons has dis- cussed the matter also in a paper in Surg. Gyn. and Obst. In his earlier article Coni Bazan stated that all cases of mammary insufficiency are preceded by menstrual disorders of hypovarian origin. The later paper is based upon a more careful study of cases in which corpus luteum or ovarian treat- ment influenced favorably the scanty milk secretion. As the ABSTRACTS 183 latter condition improved other symptoms of ovarian deficiency decreased. It is stated that these cases, called by pediatricians ‘essential hypogalactia’’ are actually hypovarian hypogalactia. 157. (OVARY) Oogenesis in the white mouse. Kingery (H. M.), Jour. Morph. (Phila.) 1917. Vol. 30. In the development of the ovary of the mouse there are two proliferations of cells from the germinal epithelium. The first, occurring before birth, gives rise to ‘‘primitive’ germ eells’’ and their follicle cells; the second, extending from about birth, or a few days after nearly to sexual maturity, forms the ‘definite ova’’ and their follicle cells. The primitive oocytes undergo synizesis (contraction of the chromatin) and then pass through the stages pachytene, diplotene, and dictye (of v. Winiwarter), after which they all degenerate. In the defini- tive oocytes there is no evidence of synizesis nor of synapsis (conjugation of the chromosomes), but the chromatin network, very delicate at first, becomes heavier, and then becomes attenu- ated as the cell grows in size. The definitive ova develop after birth by a process of differentiation from the cells of the germ- inal epithelium. Stages were seen transitional between meso- thelial cells and primary. These are fated to degenerate. The suggestion is repeated that this is a stage in degeneration in which the normal relations of nucleus and cytoplasm are dis- turbed. The fact that similar stages have been found in somatic cells militates against the attributing of any special genetic significance to this condition in the germ cells.—E. R. H. 158. (OVARY) Seniladad prematura y atrofia genital. (Pre- mature senility and genital atrophy.) Turenne (A.) Revista Médiea del Uruguay (Montevideo), 1917, 20, 742. Turenne reports a very interesting study of the pathogeny of some of the genital atrophies. He obtained in four cases a history of puerperal infection which was followed in a short time by amenorrhea, whiteness of the hair, senile appearance of the skin and loss of the teeth without caries. The patients were observed from two to three years after the puerperal in- fection. A characteristic genital atrophy developed. The uterus diminished in size,—in case of one 6-para having a length of but 6 em.,—and the vagina and labia majora also showed atrophy. In one patient obesity preceded the genital atrophy and early senility appeared; the mammae, however, remained normal in appearance. GsPr&. 184 ABSTRACTS 159. (OVARY) Sex Studies. X. The corpus luteum in the ovary of the domestic fowl. Pearl (R.), and Boring (A. M.), Am. Jour. Anat. (Phila.) 1918, 28, 1. Evidence is presented in this study which is believed suf- ficient to demonstrate that there is normally found in eonnee- tion with the discharge or degeneration of the ovarian follicle in the domestic fowl a structure which is homologous to the corpus luteum of the mammalian ovary. The origin of this structure in the bird is plainly simply from the theea interna. The course of development of the bird’s corpus luteum is an abbreviation of that in the mammal.—E. R. H. 160. (OVARY) Sex studies. XI. Hermaphrodite birds. Boring (A. M.) and Pearl (R.) Jour. Exp. Zool. (Phila.) 1918, Vol, 25. This paper is a-detailed study of the external characters, behavior, anatomy, and cytology of a series of hermaphroditie fowls and guinea-chicken hybrids. The more significant gen- eral results obtained are as follows: The eight hermaphroditie fowls studied were all basally females with ovaries in various stages of embryonic arrest of development or degeneration. Three of the lot were demonstrably changing from the female to the male condition in respect of the structure of the gonads, secondary characters, and behavior. The assumption of male behavior (treading) by an otherwise normal female has no demonstrable basis in changed structure of the gonad. The sex or degree of activity of the gonad has no direct causal re- lation to the development of comb, spurs, and wattles. Body shape and earriage have a general relation to the sex of the gonad. The interstitial cells have, in this material, no causal relation to the secondary sex characters. The amount of lutear cells or pigment is in precise correlation with the degree of external somatic femaleness exhibited by the individual.— H. R. H. 161. (OVARY) The formation and structure of the zona pellucida in the ovarian eggs of turtles. Thing (Alice) Am. Jour; Anat. (Phila.), Vol. 23. The ovarian eggs of .the various forms studied are sur- rounded by a single layer of prismatic epithelial cells, which are separated from each other at the surface by a special ee- ment, the terminal bars. The zona pellucida is to be looked upon as a cuticular formation, taking origin in large part from these terminal bars. It varies in thickness from 1 to 22 miera, ABSTRACTS 185 depending on the stage, and early (3 micra) may be divided into an outer denser and thicker and an inner thinner, clearer, and striated layer. Later growth and differentiation occur mainly in the outer layer. The zona is made up of a homo- geneous fundamental substance traversed by numerous fine canals, in which are contained filaments or prolongations of the epithelial cells outside, connecting these cells with the surface of the yolk beneath the zona. These prolongations vary in length with the thickness of the zona and end in knob-like en- largements on the yolk. The fundamental substance of the zona arises in part from a delicate secondary network within the primary network of the terminal bars which is apparently produced by the superficial cytoplasm of the cells and which gives rise at its surface to a cuticular substance similar to that derived from the terminal bars. From these networks are de- rived, as the thickness of the zona increases, the fundamental substance and its enclosed canals, thus presenting a structure well adapted to the conveyance of nutritive material from the maternal blood to the growing yolk.—k. R. H. 162. (OVARY) The winter cycle of egg-production. Good- ale (H. D.) Anat. Ree. (Phila.) 1918, Vol. 14. Of no direct endocrine interest. 163. (OVARY) Tubal and ovarian hemorrhage; its etiologic relation to pelvic hematocele and extra- uterine pregnancy. Bovee(J. W.) Proc. Am. Gyn. Soc., Jour. A. M. A. (Chgo.) 1918, 70, 1975. “Trauma plays a part in producing these hemorrhages. Hemorrhage from the fallopian tube may occur from general conditions that similarly affect othe rtissues. Venous stasis from circulatory disturbances or pressure from tumors may reasonably be included in a list of its causes. Ovarian hemor- rhage may be confined within the ovary, constituting one or more hematomas, or it may take place into the peritoneal cav- ity, producing, if abundant, a hematocele. No other organ of the body is so frequently the seat of hemorrhage as is the ovary. Stromal hemorrhage is commonly preceded by infee- tion of the ovary. In but few cases have correct diagnoses been made before operation or necropsy. As to treatment, in the milder forms of the condition rest and anodynes may meet all indications. In the severer forms the same rules apply as are employed in the treatment of ectopic pregnancy.’’ 186 ABSTRACTS 164. (PANCREAS) Pancreatic diabetes. Hardoy (P. J.) Re- vista Assoc. med. Argentina (Buenos Aires), 1917, 27, 123. A man 21 years of age with positive Wasserman, consider- able glycosuria, marked polyuria and emaciation (20 kg. lost in 3 mos.) was considered to have pancreatic diabetes. Fune- tional tests indicated that the external secretion of the pan- creas was normal. The author believed that the condition was due to relative over-activity of the sympathetic nervous sys- tem, the vagus being depressed. Accordingly he administered pilocarpine and the glycosuria disappeared. Allowing the pa- tient the use of carbohydrate caused a return of the glycosuria which again yielded to pilocarpine treatment.—B. A. H. 165. (PANCREAS) Sugar absorption and the pancreas. v. Korsky (K.) Ztschr. F. physiol. Chem., 1916, 98, 37-48. Experiments on dogs are described which indicate that when the blood is prevented from circulating through the organs of the body, including the pancreas, the introduction of a large quantity of dextrose solution into the intestine leads to an increase in the amount of dextrose in the blood; while, if the pancreas is left in the.cireulation, under otherwise nor- mal conditions, a decrease in the amount of dextrose in the blood is observed. Chem. Abst. 12, 497. 166. (PANCREAS) The site of formation of fibrinogen. Wohlgemuth (J.) Berlin, klin. Wehnschr. (Berlin), 1917, 54, 87-90. The influence of the pancreas on the liver is not limited to carbohydrate metabolism, but is also related to protein meta- bolism, one effect being the liberation of fibrinogen into the blood. - Chem. Abst. 12, 933. 167. (PANCREAS) Morphine hyperglycemia in dogs with ex- perimental pancreatic deficiency. Auer (J.) and Kleiner (I. S.). Jour. Exp. Med. (N. Y.), 1918, 27, 49. The authors contend that any factor causing hypergly- cemia will probably call forth a greater response in animals with a pancreatic deficiency than in normal animals. This conclusion was substantiated by injecting morphine, 2 mg per kilo body weight, into the subcutaneous tissue of dogs that had previously sustained partial removal of the pancreas. In these animals it was found that morphine produced a rise in the gly- cemia about four times greater than the same amount of mor +04 ern eemains). L Ge-Bine: Aah tg ABSTRACTS 187 phine calls forth in normal dogs. Animals with pancreatic deficiency may be considered to be in a prediabetic state, hence, inasmuch as morphine causes hyperglycemia in these experi- mental animals, the inference is drawn that this test should be of value in detecting a weakened carbohydrate metabolism in the human subject. The data presented afford additional cor- roboration of the view that the responses of a normal and of a pathologically altered organism to the same drug in the same dosage may show very large quantitative differences.—H. W. 168. (PARATHYROID) Action of the serum of normal dog's and of those in tetany on the muscles of toads and frogs. Houssay (B. A.) Revista Assoc. Méd. Argentina (Buenos Aires), 1917, 27, 641. The muscles of the frog, Leptodactylus ocellatus, were not influenced by the serum of either normal or tetanic dogs. The muscles of some toads, Bufo marinus, submerged in the serum of a dog in tetany showed contractions, but these were pro- duced also by the serum of normal dogs.—B. A. H. 169. (PARATHYROID) The present day therapeutics of spasmophilia. Cozzolino (O.) La Pediatra (Napoli) 1916, 24, 292. Abstr. Brit. J. Chil. Dis. (Lond.) 1917, 14, 238. Parathyroid opotherapy is discussed and attention drawn to the probable divergence in therapeutic value of preparations from too old or. too young animals as not containing sufficient quantity of the active principle. The author considers that opotherapy in spasmophilia may, in the future, tend toward a pluriglandular or at least a parathyroid-thymic opotherapy. He lays stress on the value of proper feeding and care of slight ailments which may favor the development of convulsive mani- festations.—M. B. G. 170. (PINEAL) Calcification in the pineal gland. Boas (E. P.) and Seholz (T.). Arch. Int. Med. (Chgo.), 1918, 21, 66. Case report of extensive calcification of the pineal gland in an individual 74 years of age. No symptoms referable to a dis- eased condition of the pineal body were demonstrable during the period of observation. At necropsy (death caused by a strangulated sliding hernia) areas of softening were found in the brain involving the external capsule and island of Reil on the right side, primary contracted kidneys, cholelithiasis, and extreme arteriosclerosis and calcification of the coronary arter- 188 ABSTRACTS ‘es, with calfication of a large part of the myocardium of the left ventricle. The pineal gland showed slight enlargement and marked calcification. Pineal calcification is now known to be a not unusual find- ing in roentgenograms of the skull. In the majority of cases this calcification is only an exaggeration of the deposits of brain sand normally found in the glands of adults. Inasmuch as calcification occurs normally in the course of involution of the pineal gland such changes are insignificant save in pre- adolescent individuals. Calcification of the gland occurring at the period when the gland is normally physiologically active may result in symptoms due to insufficiency of pineal secre- tion.—H. W. 171. (PITUITARY) Effect of tethelin on experimental tu- berculosis. Corper (H. J.) J. Infect. Dis. (Chgo.), 1917, 21, 269. Tethelin, a substance precipitated from the anterior lobe of the ox pituitary, has been shown by Robertson to have a stimulating action on growth in mice and rats. Because of this action, Corper suggests that tethelin might be used in the in- direct therapy of tuberculosis by stimulating the resistance of the host to tuberele bacilli. Guinea pigs were infected with virulent human tuberele bacilli and injected on alternate days subeutaneously with 25 me. doses of tethelin for 18 days, before and during the infection. Such procedure had no appreciable effect on the progress of the tuberculosis or on the duration of life of these animals. Tethelin administered in 25 mg. doses daily to guinea pigs sensitized to tuberculosis by dead and living human tubercle bacilli had no appreciable effect on the development, recession or rupture of intracutaneous tubercles produced by dead human tubercle bacilli, nor on deep puncture wounds of the skin in these animals.—Chem. Abst. 172. (PITUITARY) The influence of pituitary extracts on the daily output of urine. Rees (M. H.). Am. Jour, Physiol. (Balt.), 1918, 45, 471. c An attempt to ascertain ‘‘ whether the subeutaneous injee- tion of pituitary extract will cause any quantitive variation in the daily output of urine’’ and ‘‘ whether such injection will in any way affect the quantity of urine excreted, and, if so, to find out if possible, the factor involved.”’ The methods of Motzfeldt were followed, except that the ABSTRACTS 189 observations extended over longer periods of time. The con- clusions reached are: 1. Subeutaneous injections of pituitary extract do not alter quantitatively the daily output of urine in eats and rab- bits, nor do they cause any marked variation in the specific gravity of the urine. 2. The subeutaneous injection of pituitary extracts causes a delay of seven to eight hours before the beginning of the diuresis which follows the ingestion of large amounts of water. 3. The delay in diuresis which is produced by subeutan- eous injection of pituitary extract is due in part at least to a delayed absorption from the alimentary canal. 4. The subcutaneous injection of pituitary extract has no influence on the diuresis induced by the continuous intraven- ous injection of isotonic salt solution.—T. C. B. 173. PITUITRIN, its value in post-operative treatment. Davis (N.) and Owens (R.). New Orleans Med. and Surg. Jour., 1918, 70, 712. The authors present an enthusiastic account of their ex- perience with pituitrin in 126 laparotomies. Although they regard it as of little use in obstetrical practice. they believe that it has an important place in surgery. They conclude: “That pituitrin is a valuable drug in stimulating the muscular coats of the intestine after abdominal section in non-septic cases. It is of decided assistance in preventing post-operative shock. It has very little if any effect upon cases complicated with septic peritonitis, but our results are inconclusive on ac- count of the small number of cases. It stimulates the seecre- tory section of the kidneys in cases of eclampsia. It materially reduces the amount of post-operative suffering.’’—R. G. H. 174. (PITUITRIN) The regulation of renal activity. V. Regulation of urea excretion by pituitrin. Addis (T.), Bar- nett (G. D.) and Shevky (A. E.) Am. Jour. Physiol. (Balt.) 1918, 46, 52-62. The subcutaneous injection of pituitrin in the rabbit is followed in all effective amounts by a decrease in the urea excreting activity of the kidney. The rate of urea excretion is slower than in animals not given pituitrin, although the blood urea concentration is higher.—L. G. K. 175. (PITUITRIN) The value of pituitary extract in incom- plete abortion and placenta previa. Lipkis (A.) Northwest Med. (Seattle), 1918, 17, 74. 190 ABSTRACTS Pituitary extract in 0.5 ¢.e. doses will do away with the curette or pack in most, if not all, cases of incomplete abortion. It controls hemorrhage, and the paleenta usually comes away within three days. In some few cases it may take longer—6 or 7 days. As a rule the longer the pregnancy and the larger the placenta the less time it will take for the uterus to empty itself and the more likely the placenta will come away as one piece. The advantage of this treatment over the prevailing method of cureting or packing is that it is simple, and by avoiding local manipulations, lessens the danger of infection. In one case the author sueceeded in delivering a placenta previa marginalis with one-fourth ¢.e. doses of pituitary ex- tract.—Author’s Abstract. 176. REPRODUCTIVE GLANDS, internal secretion of. Steinach, Foges, and Lode, Ztsehr. f. Sexnalwissensch. (Leipzig), August, 1917. It is stated that after castration the sexual disposition of young mammals may be reversed by implanting a testis into females, or an ovary into males. The reproductive hormones are regarded as antagonistic, and the erotising effect does not occur if castration has not been performed. The ‘‘Lancet’’ n an annotation from which this is taken maintains a cautious attitude in reference to these results.—Physiol. Abst. 177. (SECRETIN) A new plant secretin. Bickel (A.) Berl. klin. Wehnsehr. (Berlin), 1917, 552-3; Eisenhardt (W.) Ibid., 553-4; Djenab (K.) Ibid., 24-5. (Physiol. Abst., 2, 605. ) Spinach contains a secretin which acts both on the stomach and the pancreas. In the fresh vegetable it is firmly united, but can be boiled out by water or liberated by hydrolysis with HCl. It resists this action, but is destroyed at 140°. It is an organic substance with an activity about equal to that of pilo- earpine. Its action is shown better by intravenous injection than by administration by mouth. The relation of secretins and vitamines is discussed. Confirmatory experiments by Eisenhardt on dogs with Pavlov stomachs are recorded. The stimulating substance is the arginine-histidine fraction. Its relation to vitamines is also considered. Djenab determined that when injected into a femoral vein it lowers blood pressure and causes secretion from the panereas. Injected into the mesenteri¢ vein, the fall of pressure is less and does not last as long; there is no effect upon the pancreas. The conclusion is drawn that it is neutralized in its passage through the liver, ABSTRACTS 191 and to some extent, through the muscular tissues. The same effect is produced on the true pancreatic secretin ; examination of the various levels of the intestinal mucosa shows that secre- tin is most abundantly obtained in the deeper layers of the duodenal lining. Chem. Abst. 12, 1069. 178. (SECRETIN, II) Its influence on the number of white corpuscles in the circulating blood. Downs (A. W.) and Eddy (N. B.). Am. Jour. Physiol. (Balt.), 1918, 45, 294. It is possible to produce an increase in the number of white corpuscles per cubic millimeter of blood by the administration of secretin, even in small doses and by subcutaneous injection. The most efficient dose is 1 ce. of secretin solution per kilo- gram of body weight. It is suggested that the effects described are due to a direct stimulating action of secretin on both the bone marrow and the lymphatic tissues in general.—T. C. B. 179. (SPLEEN) The elimination of iron and its distribution in the liver and spleen in experimental anemia. Dubin (H.), Pearce (R. M.) Jour. Exp. Med. (N. Y.), 1918, 27, 479. No increased elimination of iron was observed in the feces of dogs showing an essentially chronic experimental anemia produced by infecting the animals with Trypanosoma equiper- dum. The storage of iron in the liver and spleen was slightly increased in amount, but of the same general character as in transient experimental anemia. Splenectomy before and after infection influenced neither the elimination of iron in the feces nor its storage in the liver. Retardation of the course of the trypanosome infection likewise failed to affect iron storage. In the presence of a bile duct-ureter fistula the iron content of the mixture of urine and bile was not appreciably greater than that of normal urine alone. Therefore, the elimination of iron in the bile does not seem to be an important factor in the dog. However, when bile is excluded from the intestine an unusual storage of iron occurs in the spleen. No explanation of the latter condition is offered.—H. W. 180. (SPLEEN LIVER) Hematogenous icterus, hemoglobin and iron metabolism. Lepehne (G.) Beitr. z. path. Anat., 1917, 64, 55-126. (Physiol. Abst., 2, 25.) Clinical work on jaundice and experiments on animals show that there is an inter-relationship of liver and spleen in reference to hemoglobin and iron metabolism. After the spleen 192 | ABSTRACTS is extirpated in rats and mice the Kupffer cells of the liver be- come active, and phagocytosis and accumulation of iron occur in that organ. Differences in that respect oceur in different animals: the guinea pig, for example, does not show the same effect as that manifested in rats and mice. Chem. Abst. 12, 939. 181. SPLENOMEGALY, Familial, a clinical study. De Lange (C.) and Schippers (J. C.) Amer. J. Dis. Child. (Chgo.), 1918, 15, 249. The authors report the clinical history of seven children in one family, at least two of whom, in their opinion, presented the clinical picture of Gaucher’s type of splenomegaly. Case 1. The first child in the family died at the age of two years of ‘‘hepatitis.’’ Case 2. The second child, 11 years old, had en- largement of both spleen and liver; skin was slightly yellow tinted; death occurred suddenly after a serious hematemesis. Case 3. The third child died at the age of 17 days from an um- bilical infection. Case 4. The fourth child looked healthy ; his spleen was palpable beneath the costal margin. Case 5. The fifth child did not show any enlargement of either spleen or liver. Case 6. The sixth child, a girl of 71% years of age, had a dis- tended abdomen. The spleen was felt one-half inch above the anterior superior spine; the right border was 214 inches from the median line. The liver extended 3 inches below the costal margin. The Wassermann reaction was negative, as in the previous cases, and the Von Pirquet, positive. The others were negative except Case 4. The blood showed leucopenia with increase, however, in the number of mononuclear lymphocytes. There was no marked anemia. Splenectomy was performed. Case 7. The seventh child, a girl, 514 years old, showed a few pigmented spots on the abdomen, but no jaundice. The spleen extended 1 inch above the anterior iliac spine; the right border was 214 inches from the navel. Splenic dullness was heard in the axillary line at the ninth rib. The liver was en- larged, the Wassermann reaction negative, and Von Pirquet, positive. Blood examination showed a leucopenia varying from 4200 to 8500, hemoglobin in very large amount, and a high count of erythrocytes. Splenectomy was done. The mother said that the enlargement of the hver and spleen was already noticed in this case at the age of two and in Case 6, at the age of four. Examination of the father did not show any abnormalities ; no enlargement of the spleen or liver. While his blood exam- ination was practically normal on three tests, there was a con- ABSTRACTS 193 vlycogen in the liver, the blood sugar being thereby main- stant relative lymphocytosis. The authors emphasize this latter point, although they do not venture to state that the disease in the children can be traced back to the father. Clinical and blood examinations of .the mother, maternal and paternal grandmother and maternal grandfather were all negative. After the operation the blood of both children showed an increase in leucocytes. The liver in one decreased somewhat in size and then remained stationary, while in the other, it in- ereased slightly and then returned to the size preceding the operation. Both children were in good health a year after the operation. Microscopic examinations did not show the accepted path- ological picture of Gaucher’s disease. The authors think, how- ever, that they are dealing with a familiar progressive disease of the spleen which produces, sooner or later, an increasing vachexia and in the course of which a hemorrhagic diathesis occurs ante-mortem.—M. B. G. 182. SUGAR METABOLISM AND DIABETES. McGuigan (H.). Jour. Lab. and Clin. Med. (St. Louis), 1918, 3, 219. An interesting paper dealing with the history of diabetes and the various chemical tests used in the determination of sugar.—H. W. 183. (TESTES) Cases showing remote results of testicle im- plantation. Lydston (G. F.) Jour. A. M. A. (Chgo.) 1918, 70, 907-8. Two cases are described in which testes of boys 14-15 were implanted in the scrota of men lacking these organs. A marked development of virility followed. The author con- cludes that when technie and material are right and the re- cipient is properly selected, continuity of hormone production by the implanted gland for at least a prolonged period is certain and that permanent beneficial results are prob- able.—R. G. H. 184. (TESTIS) Chrondriosomes in the testicle cells of Fun- dulus. Duesberg (J.) Am. Jour. Anat. (Phila.) 1918, 23, 133. In the cells lining the proximal part of the excretory ducts in the testicle of Fundulus the chondriosomes are represented by long chondrioconts, whose disposition reminds one of the Heidenhain’s or of the Pfliiger’s rods. In the latter part of the excretory ducts the chondriosomes are replaced by granules of pigment. The connective tissue of the testicle holds a num 194 ABSTRACTS ber of cells with special characters (bacilli-shaped chondrio- conts, secretion granules) ; these cells are probably interstitial cells. Chondriosomes are found in all generations of germ cells and transmitted during mitosis from one generation to the fol- lowing one.—E. R. H. ; 185. (TESTIS) The influence of excessive sexual activity of male rabbits. I. On the nature of the seminal discharge. Lloyd-Jones (O.) and Hays (F. A.) Jour. Exp. Zool., (Phila.) 1918, Vol. 25. Of no direct endocrine interest. 186. (TESTIS) II. The influence of excessive sexual activity of male rabbits on the nature of their offspring. Hays (F. A-) Jour. Exp. Zool. (Phila.) 1918, Vol. 25. Of no direct endocrine interest. 187. (TESTIS) The relations between the interstitial gland of the testicle, seminiferous tubules and secondary sexual characters. Loeb (L.) Biol. Bull. (Woods Hole) 1918, Vol. 34. The author found that a guinea pig with certain female secondary sex characters was an abnormal male. The testes were small, had not descended and were made up of interstitial cells, and typical tubules which lacked spermatogonia. The interstitial cells were abnormal containing vacuoles and eosino- philic bodies. The mammary gland was female in character.— E. R. H. 188. THYMUS and dwarf growth. Krabbe (K. H.) Ugeskrift. f. Laeger (Kobenhavn), 1917, 79, 1329. A ease of pronounced dwarf growth is deseribed and it is suggested that the thymus is responsible for the condition. There were no symptoms indicating abnormal functions of the thyroid. parathyroids, pituitary, suprarenals, ovaries or pan- cereas.—Physiol. Abst. 189. (THYMUS) Extirpation of the thymus gland in Rana pipiens larvae. Allen (B. M. )Anat. Ree. (Phila.) 1918, Vol. 14. The thymus gland anlagen were removed at their very in- ception from 8 mm. to 9 mm. tadpoles. This was accom- plished by eutting into each side of the head with a cataract ABSTRACTS 195 needle. Although the severity of the operation retarded de- velopment for a time, recovery was rapid and complete. Seven specimens were reared to the time of metamorphosis, attaining normal size and appearance. All died or were killed at this time. It is impossible from the material at hand to determine whether the high mortality at this time was due to the absence of the thymus gland or to other causes. It was in sharp con- trast to the fate of the controls. Further experiments will be made upon this point next year. They appeared to be strue- turally normal in every regard. The characteristic features of metamorphosis occurred. A careful study of the thymus gland region of each specimen showed that the glands had in each case been successfully removed. Five out of the seven were males. Sexual differentiation was complete, and measure- ments showed the gonads to be altogether normal in size as compared with metamorphosed controls. A comparison of sec- tions of the gonads of operated and control specimens showed those of both to be identical in structure and in the develop- mental stage reached by the germ cells.—E. R. H. 190. (THYMUS) Is the influence unon development, meta- morphosis. and growth of thymus. when taken as food, due to a specific action cf that gland? Uhlenhuth (E.) Jour. Exp. Zool. (Phila.) 1918, Vol. 25. The differences in the rate of growth between thymus-fed and worm-fed larvae of Amblvstoma opacum and A. punctatum are not the result of a specific growth-promoting influence of the thymus. but are due to the circumstance that animals which are better fed grow more rapidly. In order to make this point clear, quantitative feeding experiments were introduced in the study of the effect of the thymus. The meaning of the results regarding the effect of the thymus on development and meta- morphosis will not become entirely clear before extensive ex- periments are available concerning the relation between size, rate of growth, differentiation, age, and metamorphosis in ani- mals which have been fed on only one kind of food. When thymus-fed larvae of A. opacum and punctatum metamorphose, they are smaller than worm-fed animals at the time of meta- morphosis. Larvae of A. opacum develop more rapidly when fed on thymus than do the controls; but only some thymus-fed individuals metamorphose earlier, while the development of others ceases (except development of the skin). when they reach the stage preceding metamorphosis, and either metamor- phose only after a relatively long time or die as larvae after a certain period. Thymus-fed A. punctatum behave similarly. Two of these species, kept in low temperature, remained larvae 196 ABSTRACTS for about fifteen months, and died after they had commenced to metamorphose. Similar cases, however, are found even among worm-fed animals. It seems that the thymus does not interfere with those factors necessary for differentiation dur- ing the larval period ; when metamorphosis begins, a new factor seems to become indispensable to further differentiation, and the thymus diet apparently often disturbs in some way the de- velopment of this factor. After a thymus-fed larva has once metamorphosed, it may live on exclusive thymus diet to at least eighteen months of age.—E. R. H. 191. (THYMUS) Klinische Bedentung der Thymusdriise. (The clinical significance of the thymus.) von Haberer ( H.) Arch. f. klin. Chirurgie (Berlin) 1917, 109, 193. In every case of partial thyreodectomy in Graves’ disease it is necessary to look for the thymus and to enucleate it. The results of this combined operation are much better than when only a part of the thyroid is removed. There are classical cases of Graves’ disease in which the thyroid is small, the thymus, however, being very large. In these cases complete recovery is observed after resection of the thymus. The author operated on 40 cases in this way; he never ob- served a relapse. In young children the growth continued per- feetly normally after removal of the thymus—J. K. 192. (THYMUS) Physiologie der Driisen. Asher (L.). XXXIII. Hine neve Funktion des inneren Sekretes der Thy- musdrise. Miiller (H.) Ztschr. f. Biol. (Miinchen), 1917, 67, 489. In frogs nareotised with urethane the triceps was fatigued by the method of Kornecker. In eight experiments Thyro- glandol (La Roche) and in fifteen experiments a fresh watery extract of thymus was injected into the abdominal cavity and the effect on the height of the successive contractions was noted. The normal muscle fatigue curve descends gradually in a straight line. Provided fatigue were not too pronounced, both preparations caused its temporary disappearance in spite of continued stimulation, the height of the contractions (1) remaining stationary or (2) showing a slight inerease; eventu- ally the typical curve of fatigue reappeared. The action of thyroglandol was characterised by a latent period of twenty minutes, and was less marked than that of the fresh extract. Nucleoprotein, Ringer’s solution and pituglandol, had no effect on the fatigue curve, and the author coneludes that the bene- ficial action of thymus is specific. The physiological and patho- ABSTRACTS 197 logical significance of this new function of the internal secre- tion of the thymus is evident. Rabbit sermm had a distinetly beneficial action on muscle fatigue, whereas plasma was in- active.—Physiol. Abst. 193. (THYMUS) Transplantation of the thymus in rabbits. Relation of the thymus to sexual maturity. Marine (D.) and Manley (O. T.). Jour. Lab. and Clin. Med. (St Louis), 1917 3, 48. Transplants of thymus tissue in the subcutaneous tissues of the abdomen survive in sexually immature rabbits. Only auto-transplants persisted. The present experiments conform with the result of others and demonstrate that removal of the thymus hastens sexual maturity. Utilization of rabbits for breeding purposes hastens not only normal involution of the thymus but also the auto-transplants as well. This condition suggests that a specific nerve influence is not essential for these involutionary changes.—H. W. 194. (THYMUS) Report of nineteen cases of hyperphasia of the thymus gland, treated by the X-ray. Benjamin (J. E.) and Lange (S.) Arch. Ped. (N. Y.) 1918, 35, 70. The authors found that out of 225 cases of all sorts seen in their children’s clinic, 19, or 8.47 per cent, showed undisputed evidences of enlarged thymus. The chief complaint is nearly always a history of a cough in a child who does not show the prodromal symptoms of a cold but is apparently well. The cough is generally present at night and may be accompanied- by a choking sensation. The ‘‘threshold method of percussion’’ was used to outline the thymus. The child is placed on the mother’s lap on his baek. Pereussion is begun well out in the chest, with such light strokes that when the ear is within a few inches of the area pereussed only faintest possible resonance is heard. When sound disappears, dulness begins. Some observers outline the border of dullness by the tactile sense of resistance rather than sound. The outer borders are determined more easily than the lower boundary; the latter may be obtained by auscultatory percussion and is relatively less important. The writers found that the percussion outlines determined in this way correspond remarkably closely to the Roentgenogram. A clinical diag- nosis of thymic enlargement is never absolutely positive with- out X-ray confirmation. X-ray diagnosis is based upon an enlargement (usually lateral) of the thymus shadow, which normally rests upon and 198 ABSTRACTS is continuous with the heart shadow, which may, however, be contused with the shadow of congenital heart enlargement. In all cases where the diagnosis by the X-ray was doubtful, a therapeutic test of an X-ray exposure was given and found to be very reliable. Many symptomless and supposedly healthy children may show an apparently enlarged thymus upon the X-ray plate. An enlarged thymus in an apparently healthy child may be abnormal although its ill effects may not be mani- fest until some added strain be put upon the heart or respi- ratory organs or until the resisting powers of the child be called upon to overcome an acute infection. Three treatments were the usual number given at intervals of one week, unless the urgency of the symptoms suggested more frequent applications, when a second dose was given in a day or two. In the average case the improvement was noted in 24 to 48 hours after the treatment. The X-ray therapy in these cases was carried out as fol- lows: A Coolidge tube backing up a 91% inch spark was em- ployed. The rays were filtered through 4 millimeters of alum- inum and a piece of thick leather. The target skin distance Was approximately nine inches. The routine exposure was 25 milliampere-minutes. In mild cases a single dose over the an- terior surtace of the chest proved sufficient. In more urgent eases 50 milliampere-minutes were administered at the first treatment, 25 anteriorly and 25 posteriorly. During the treat- ment the child was kept quiet by four sandbags, one placed across each arm and one across each leg. In order to get re- sults it is essential that the treatments be comparatively heavy and that they be repeated at sufficiently short intervals. The exposure varied from one-sixtieth to one-thirtieth of a second.—M. B. G. 195. (THYROID) Akuter Morbus Badedowi. (Acute Graves’ disease.) Boir (C.) Klin. Monatsbl. f. Augenheilk (Berlin) 1917, 59, No. 728. Three cases are described, in which soldiers after a great fright, showed a classical picture of Graves’ disease.—J. K. 196. (THYROID) Blutzuckerbestimmungen bei einem Fall von infantilen Myxodem. Nilsson (N.) Deutsche med. Wehnschr. (Berlin), 1917, 48, 41. Hypothyroidism is associated with a raising of the assim- ilation limit for glucose; hyperthyroidism with the opposite. In the present case (a boy aged seventeen) there was an in- crease of the blood sugar after giving either thyroid tablets or ABSTRACTS 198 adrenin. The effect on the blood picture is also described.— Physiol. Abst. 197. (THYROID) Effects of the extirpation of the thyroid gland upon ossification in Rana pipiens. Terry (G. 8.) Jour. Exp. Zool. (Phila.) 1918, Vol. 24. Examination of the vertebral column of thyroidless and control tadpoles shows that the removal of the thyroid gland produces a marked retardation in the process of ossification which almost amounts to a cessation of the process. Up until the period when the hind legs begin to grow in length there is little difference in the process of ossification between the thy- roidless and control specimens, but after this period the re- tardation becomes markedly noticeable in the thyroidless ani- mals. In comparing the thyroidless and control specimens of the same age, calcification of the cartilage seems to take place at about the same time in both, but the erosion of calcified car- tilage preliminary to ossification takes place very slowly in the thyroidless tadpoles. As a result of this, the vertebrae in older specimens appear more uniform than in the controls of the same age when studied from whole-mount preparations. The outline of the centrum is very regular and the ealecification appears uniform in all specimens studied. There is a heavy deposition of calcium salts in the end of the rib, not present in control specimens. There is a complete absence of spinous pro- cesses upon the vertebrae of the largest thyroidless specimen (43 mm. body length from anterior tip of head to cloaca). Comparison of the hind legs of the control with much older thyroidless specimens with the same leg length shows that the removal of the thyroid gland has greatly retarded if not com- pletely stopped both the processes of growth and ossification.— E. R. H. 198. (THYROID) Effects of external temperature and certain drugs on thyroid activity. Mills (C. A.). Proc. Am. Physiol. Soc., Am. Jour. Physiol. (Balt.), 1918, 45, 557. 199. (THYROID) Forma congestiva del hipotiroidismo. (Congestive form of hypothyroidism.) Mussio Fournier (J. C.) La Prensa Medica Argent. (Buenos Aires) 1918, 4, 463. A patient 53 years old had suffered from attacks of pul- monary congestion . . . anuria and hematuria and hemiplegia which had become ameliorated. The congestions had been treated repeatedly and the kidneys had twice been decapsu- 200 ABSTRACTS lated. As there were falling out of the hair, headache, insomnia. transitory edema of the lmbs, ete., and the Wasserman reac- tion was negative and antiluetic treatment was always followed by symptoms of intoxication, it was decided to institute thy- roid treatment. The results were gratifying; many of the symp. toms gradually improved. Prof. Kocher introduced three thy- roid grafts from a Basedow patient. An impovement of the symptoms, but also glycosuria, followed. Anginal attacks from which the patient had previously suffered reappeared, the arterial blood pressure reaching 220 mm. The author at- tributes these untoward results to the hyperthyroidism.— B. A. H. 200. (THYROID) Influence of thyroidin on standard meta- bolism. Krogh (M.) Ugeskrift for Laeger, 1916, No. 52. Determinations were made of the oxygen consumption by urethanized frogs before and after the administration of thy- roidin: also with and without division of the nerve trunks for the four limbs. Thyroidin caused a much smaller rise in meta- bolism after the nerves were cut. It is accordingly provision- ally coneluded that thyroidin acts chiefly by increasing the tonus of striated muscle. Chem. Abst. 12, 719. 201. (THYROID) Headache from thyroid deficiency. Giaco- bini (G.) Semana Médiea (Bs. Aires.), 1918, 25, 516. A short paper, containing nothing new. G. P. @ 202. (THYROID) Sarcoma of the thyroid gland. Jorge (J. M.) and Arrillaga (F. C.) Revista Asoc. Méd. Argentina (Buenos Aires) (Dic.) 1917, 27, 932. A malignant sarcoma was observed in a woman 24 years of age. The case came to autopsy. Of the metastases pres- ent one especially worthy of interest had penetrated the veins Of the neck and was prolonged to the interior of the heart.—B. A. H. 203. (THYROID) The acceleration of metamorphosis in frog larvae by thyroid feeding, and the effects upon the alimen- tary tract and sex glands. Swingle (W. W.) Jour. Exp. Zool. (Phila.) 1918, Vol. 24. Very great acceleration of metamorphosis occurs in frog larvae when they are fed extract of thyroid gland. It is pos- sible by judicious administration of thyroid to stimulate very immature tadpoles to complete metamorphosis, assuming all of ABSTRACTS 201 the adult characteristics except size. Examination of the gonads and germ cells reveals no observable changes, either gross or histological, from those of the control larvae of the same age and size; this despite the fact that from the stand- point of somatic development the thyroid-fed animals are months ahead of the controls. The alimentary tract of tadpoles is a long, cylindrical, much-coiled structure, with little or no differentiation into stomach, small and large intestine. When the animals are placed upon thyroid diet the alimentary tract undergoes an extremely rapid differentiation to a well-marked stomach, small and large intestine. These changes occur within a few days. By thyroid feeding differentiation of the alimentary tract into its three characteristic divisions can be brought about in starved larvae in which all growth and development have ceased for months. Drawings and photographs are given illustrating these points.—E. R. H. 204. (THYROID) The effect of the extirpation of the thyroid upon the thymus and the pituitary glands of Rana pipiens. Rogers (J. B.) Jour. Exp. Zool. (Phila.) 1918. Vol. 24. The pituitary gland continues to develop when the thyroid gland is extirpated, the anterior lobe reaching a larger size in proportion to body length than it does in the pituitary gland in normal.specimens. This is true in all stages up to young sexually mature normal frogs. In most cases the pituitary gland of the thyroidless tadpole is larger than that of the cor- responding control without reference to body length. The pituitary gland is largest in proportion to body length in thy- roidless tadpoles of the same age as young sexually mature frogs. The thymus glands continue to develop when the thy- roid is extirpated. In metamorphosing controls they are much larger than those from thyroidless tadpoles of the same age. The thymus glands of the thyroidless tadpoles do not suffer degeneration like those of normal controls, but continue to grow; consequently those of thyroidless tadpoles do not mi- grate to the position in which the glands are found in adult frogs. The thymus glands of the thyroidless tadpoles grow to large size in later stages, but in early stages do not undergo the sudden increase in size that the controls do at metamor- phosis.—E. R. H. 205. (THYROID) The effects of thyroid secretin on the ex- citability of the endings of the cardiac vagus. Levy (L.). Arch. Int. Med. (Chgo.), 1918, 21, 263. ee 202 ABSTRACTS The author’s experiments were designed to determine whether or not the secretion of the thyroid gland increases the responsiveness of the vagus nerve terminations to electrical stimulation. If it does, as certain investigators maintain, thy- roid secretion must be regarded as having a sensitizing effect on true sympathetic as well as on parasympathetic (vagus) end- ings. In cats pithed to the mid-thorax it was found that re- peated stimulations of either vagus with a given strength of stimulus resulted in a uniform series of responses, both as to degree of depressor effect and duration of cardiae inhibition. After inducing secretory activity of the thyroid through far- adic stimulations of the central end of the cut cervical sympa- chetic, even at a time when increased pressor responses to a xiven dose of adrenin gave evidence that there had been a pouring out of thyroid secretion, there was no significant alter- ation in the depressor effect or duration of eardiae inhibition following stimulation of the vagus nerves. Therefore, it ap- pears evident that after the thyroid gland has lberated its secretion in sufficient quantity to sensitize the sympathetic structures acted upon by adrenin in raising arterial pressure, there is no demonstrable effect on the excitability of the end- ings of the cardiac vagus.—H. W. 206. (THYROID) The aetiology and treatment of exophthal- mic goitre with special reference to the use of radium. Aikins (W. H. B.) Can. Pract. and Rev. (Toronto), 1916, 41, 323. A review of the etiology of exophthalmic goitre followed by a brief account of the various forms of treatment. "A brief summary is given of the treatment by medicaments, organotherapy, and Roentgen rays, and hydro-therapy, but many cases do not respond to any of these. Seven cases are discussed in which radium treatment, usually combined with the administration of hydrobromate of quinine and ergotin and the application of ice-bags to the praecordia was very effective. In all cases a very great improvement or a complete cure was recorded.—h. G. K. 207. (THYROID) The fate of the ultimobranchial bodies in the pig (Sus scrofa). Badertscher (J. A.) Am. Jour. Anat. (Phila.), 1918, Vol. 22. The ultimobranchial bodies in the pig participate in the formation of thyroid follicles. The portion of the gland in full term embryos that is derived from these structures is small in ABSTRACTS 203 comparison to the part derived from the median thyroid anlage. Colloid first appears in the follicles of the thyroid gland in embryos 75 m.m. long. Colloid first appears in the follicles of the ultimobranchial bodies in embryos 125 m.m. long. The cephalo-caudal extent of the ultimobranchial bodies is equal to or nearly equal to that of the thyroid gland in em- bryos up to about 33 mm. long. In stages from about 50 mm. length to full term they usually lie in the posterior half of the thyroid gland, but may be found in the middle third or in the middle two-fourths of the gland. In the majority of late stages they are entirely imbedded. The ultimobranchial bodies in a thyroid gland may vary in size, in shape, in the degree of their transformation, and in their location in the lateral halves of the thyroid gland. The developmental stages in which the ultimobranchial bodies can no longer be recognized structurally from the median thyroid anlage vary greatly. The transformation of their greater part may take place as early as in a 35 mm. embryo, but in the majority of stages examined it takes place in later stages. Even in full term embryos an entire ultimo- branchial body may not be completely transformed.—kE. R. H. 208. (THYROID) The influence of large doses of thyroid ex- tract on the total metabolism and heart in a case of heart block. Aub (J. C.) and Stern (N. 8.). Arch. Int. ‘Med. (Chgo.), 1918, 21, 130. A ease report of a woman 24 years of age showing auricu- loventricular dissociation together with a systolic murmur and slow heart. The thyroid gland was not palpable. Thyroid ex- tract was administered in increasing doses over a period of four months during which time the patient ingested a total of over 2,000 grains. During the last month the doses amounted to 28 grains per day. The basal metabolism was increased 47 per cent above normal and a rapid auricular rate, 120 per minute, followed the administration of the large doses of extract. With- in 12 days after withdrawal of the extract the basal meta- bolism dropped to normal and within 19 days the auricular rate dropped to 71, which rate was thereafter maintained. The administration of thyroid extract had apparently no effect on the respiratory quotient or the blood sugar. Because of the in- crease in auricular rate without alterations in the ventricular rate it is suggested that thyroid extract does not increase the heart beat by direct action on the muscles, but through nervous elements.—H. W. =~ 204 ABSTRACTS 209. (THYROID) The infiuence of the thyroid of anastomosis of the phrenic and cervical sympathetic nerves. Marine (D.), Rogoff (J. M.) and Stewart (G. N.). Am. Jour. Physiol. (Balt.), 1918, 45, 268. A repetition of the experiments of Cannon, Binger and Fitz. In none of the animals were there any symptoms of Graves’ disease. No respiratory hippus, and no exophthalmos. No histological difference between the two sides of the thyroid. No study of the metabolism seems to have been made.—T. C. B. 210. (THYROID) The isolation and identification of the thy- roid hormone, etc. Kendall (E. C.). Proce. of Am. Physiol. Soc., Am. Jour. Physiol. (Balt.), 1918, 45, 540. The iodin-containing compound of the thyroid has the em- pirical formula C,, H,, O, N L, and is shown to be tri-hydro, tri- iodo oxy-indol proprionic acid. Physiological testing has shown that this substance will relieve all the symptoms of cretinism and myxedema to the same extent as desiccated thyroid. (It is assumed that a full report will appear later.)— T. C-B. 211. (THYROID) The physiological action of the thyroid secretion and a method for its demonstration. Asher (IL.) Deutsche med. Wehnschr. (Berlin), 1916, 42, 1028. By stimulating the nerves of the thyroid, it is shown that certain biological reactions are obtained which occur when thyroid preparations are given. For practical purposes the most useful reaction to demonstrate the thyroid secretion is the strengthening of the adrenin action with the Laewen- Trendelenburg preparation. By this method it is possible to demonstrate the presence of an increased thyroid secretion in the blood of cases with Basedow’s disease. It can further be shown that by feeding rats with thyroid tablets an inereased formation of thyroid secretion occurs. The most important biological reaction is obtained not only by thyroid gland ex- tract but aiso by the protein and iodine free ‘‘thyreo-glandol’’ prepared by Hoffman-LaRoche, Basel. It produces the same action on metabolism as the whole gland.—Chem. Abst. 212. (THYROID) The prevention of simple goiter in man. Marine (D.) and Kimball (O. P.). Jour. Lab. and Clin. Med. (St. Louis), 1917, 3, 40. ABSTRACTS 205 From a complete census of the condition of the thyroid gland in 3872 girls from the 5th to the 12th grades of the school population of a large community in the Great Lakes goiter district, it was found that 1,688, or 43.59 per cent, had normal thyroids; 2,184, or 56.41 per cent, had enlarged thy- roids; and 594, or 13.4 per cent, had well defined, persistent thyroglossal stalks. From the results of experimental work and general con- clusions a method of prophylaxis has been developed and put into practice. This consists of the administration of small doses of the iodides.—H. W. 213. (THYROID) The relation of normal thyroid-gland de- velopment to bodily growth and differentiation in Rana, Bufo, and Amblystoma. Allen (B. M.) Anat. Ree. (Phila.) 1918, Vol. 14. In Amblystoma both fore and hind limbs begin to grow before any colloid is formed in the thyroid gland. In Bufo it appears almost immediately after limbs have begun to grow, while in Rana pipiens it appears practically simultaneously with anlage of the hind limbs. In all three forms there is a rapid growth of the gland and this corresponds closely with limb development. In all three forms the thyroid gland is well developed and contains a large amount of colloid long before metamorphosis is completed. In axolotls of 140-160 mm. length the thyroid gland was found to be approximately of equal size and structurally sim- ilar to that of adult Amblystoma tigrinum. Colloid was pres- ent in large amount in both, but the axolotls were not well enough preserved to enable one to judge of its density. Although the thyroid gland of Bufo is actually smaller at metamorphosis than that of Rana or Amblystoma its pro- portion to body size is greater than in either Amblystoma or Rana. This is probably correlated with the shortness of its larval life and the greater rapidity of its metamorphosis. There is a clear correspondence between the normal devel- opment of the thyroid gland and normal progress toward meta- mophosis, although limb development may be partly independ- ent of it—HE. R. H. 214. (THYROID) The relation of the thyroid gland to re- generation in Rana pipiens. Allen (B. M.) Anat. Ree. (Phila.) 1918. Vol. 14. These experiments involved three classes of tadpoles: 1. Tadpoles from which the thyroid gland had been extirpated 206 ABSTRACTS —absence of thyroid secretion. 2. Normal control tadpoles. 3. Tadpoles to which thyroid extracts were fed—excess of thy- roid materials. In each case approximately the terminal half of the tail was removed. Regeneration proceeded normally in quantity and in quality in all three groups. There was a certain amount of individual variation in the degree of regeneration, dependent upon the amount of material removed, the age, and upon indi- vidual factors, but the range in amount of regeneration was proportional to that in corresponding controls, in spite of the total length from 16.7 mm. to 58 mm. Class 3 was composed of tadpoles of intermediate size, ranging from 32.8 mm. to 45.1mm. The amount of regeneration in this group was nearly proprotional to that in corresponding controls, in spite of the fact that the thyroid feeding had caused a marked shrinkage in body leneth and had caused one-half of the specimens to develop to the stage where one or both of the fore limbs had broken through the skin. We conclude from these experiments that the thvroid eland does not influence the process of regen- eration.—K. R. H. : 215. (THYROID) The results of thyroid removal in the larvae of Rana pipiens. Allen (B. M.) Jour. Exp. Zool. (Phila.) 1918, Vol. 24. Removal of the thyroid gland anlage was accomplished when the tadpoles were from 6 to 7 mm. in leneth. Develop- ment proceeded normally until the hind limb buds appeared. From that time the tadpoles underwent structural development very slowly. but continued to increase in size until they at- tained a length of trunk of from 30 to 43 mm. measured from the anterior tip of the body to the cloaca. The hind legs reached a leneth of 5 mm. The fore limbs did not break throuch the skin. The controls underwent metamorphosis normally while kept under identical conditions. The brains of the thyroidless tadpoles remained approximately in the structural form found in normal tadpoles in a corresponding stage of development. In the length of the intestine, the char- acter of the mouth, the persistence of the gills and in all other somatic features studied. the tadpoles retained the structural characteristics that had been attained at the time when meta- morphosis was arrested. The gonads behaved in sharp contrast to the soma in that they continued in the normal course of development to a con- dition far beyond that found at metamorphosis and comparable to that of normal young frogs killed at the same time (Feb- ruary following the operation). This was true of both ovary << eccetlg E ABSTRACTS 207 and testis as regards form, structural development and relative size. In the thyroidless tadpoles ripe spermatozoa developed in large numbers and oocytes grew to twice the size found in young frogs at the time of metamorphosis.—E. R. H. 216. (THYROID) The thyroid gland and the oxidative fer- ments. Goldenberg (L.) La Semana Méd. (Buenos Aires), 1917, No. 50. Thyroid extract added to iodin decolorized by zine in an alkaline medium restored its reddish color. Sodium citrate prevented the reaction.—B. A. H. 217. (THYROID) Tratamiento del bocio exoftalmico por inyecciones de agua hirviendo. (Treatment of exophthalmic goitre by injections of boiling water.) Olivieri (E. M.), Ronchi (P.) Ceballos (A.) and se Seca (G.) Soe. Med. Argent., 1917, (June 29). Olivieri and Ronchi presented four cases subjectively and objectively improv ed by the treatment. They had less tachy- cardia, increase in weight (2 to 13 and 4.5 to 6 kg.) and di- arrhea and vomiting ceased. Ceballos and Bacigalupo reported six cases, some of which improved gradually and some rapidly with no treatment other than the boiling water injections.— A. H. 218. (THYROID) Un caso de acondroplasis con antecedentes familiares de hipotiroidismo. (A case of achrondoplasia with family history of hypothyroidism.) Mussio (F.) Rev. Méd. Uruguay (Montevideo), 1917, 20, 768. — Describes the case of a boy 15 years old, three of whose uncles had shown symptoms of hypothyroidism. The boy early developed signs of sexual maturity, including hirsuitism, adult genitalia and deep voice. Mussio thinks that the case is one of hypergenitalism associated with thyroid-pituitary insuf- ficiency. G. P. G. 219. (THYROID AND THYMUS) Pharyngeal derivatives of amblystoma. Baldwin (F. M. ) Jour. Morph. (Phila.) 1918, Vol. 30. This paper deals with the morphogenesis of the thyroid and thymus glands, and postbranchial and epithelial bodies of Amblystoma, beginning with larvae 5 m.m. long, and inelud- ing stages in a metamorphosis and adult. The thyreoid gland 208 ABSTRACTS arises as a solid outgrowth from the pharyngeal floor and breaks up into seattered cells, which, by mitotic division, give rise to the thyreoid follicles, in which colloid appears in late larvae. There is no evidence of the formation of accessory thyroids. Venous twigs form a rete mirabile around the fol- licles, but the jugular vein does not participate in this. There is no thyroid artery. The thymus gland arises from five pairs of anlagen, derived from the dorsal margins of the correspond- ing gill pouches. The anterior two degenerate, the other three form the definitive organ. There are no ectodermal contribu- tions to the gland. The adult gland is three-lobed and is in- nervated by the ninth and tenth nerves. The postbranchial body arises from a thickening of the pharyngeal fioor behind the last gill pouch. In all cases, with one exception, it was asymmetrical. In the adult it hes medial to the additus laryngeus muscle. It never contains colloid. The carotid gland has no connection with cells of the pharyngeal wall or those of the degenerating gill pouches. At the time of metamorphosis two pairs of epithelial bodies arise from the ventral parts of the last two gill pouches. In the adult they he just helow the thymus and are supplied with blood from the second affer ent and external carotid arteries and are innervated by the vagus. They are the homologues of the parathyroids of the mammals.—KE. R. H. This issue has been prepared with the collaboration of: G. P. Gonalons, Buenos Aires, Argentine. F. A. Hartman, Toronto University. E. R. Hoskins, University and Bellevue Medical College, New York. L. 8S. Kilborn, Toronto University. H. Wheelon, St. Louis University Medieal School. PNBOCERINOIIEOG Y : Ghe BULLETIN of the ASSOCIATION for the STUDY of INTERNAL SECRETIONS JULY—SEPTEMBER, 1918 A NEW PLURIGLANDULAR COMPEN- SATORY SYNDROME* Walter Timme Associate Physician, Neurological Institute, New York City, N. Y. INTRODUCTION For the past six years there have come to my notice in my service at the Neurological Institute, New York City, as well as in private work, a fairly large number of cases in early adolescence whose chief complaint was great muscular fatigability. Usually combined with this outstanding symptom was headache referred to the frontal region and midway between the temples. Included in the history was frequently a statement of recent or concurrent rapid growth in height as well as of the extremities. Frequent repetition of these complaints in various individuals led me to go deeply into their antecedent history, their family history, and to follow the cases as carefully as possible during their course. Their clinical examinations also showed many character- “Read in abstract at the second annual meeting of the Association for the Study of the Internal Secretions, Chicago, June 10, 1918. a 210 PLURIGLANDULAR SYNDROME istics In common, as did their laboratory and X-ray findings. Finally, one case, observed for six years, went through various stages to recovery at the age of thirty-two years. From his early history we recog- nized symptoms that are presented by cases observed from time to time in the beginning stages of this syndrome, notably the fatigability, the headaches, and the skeletal growth. ‘‘Cross Sections’’ at various stages of his further progress also resembled clinical pictures in different patients that had heretofore been somewhat puzzling to analyze. In the past three years so many cases of the kind have been observed that from our past experience we have been enabled to foretell, to a degree, the progress that such cases would undergo in the future. To add to this assurance, of late it has been my privilege to see many individuals admitted to hospital for divers complaints of middle age, in whom were recognized the final compensatory stages of the syndrome here to be presented. Upon close questioning, their ante- cedent history bore out to surprising detail the facts that our studied clinical types presented to us im various stages of the syndrome. They were com- pletely compensated cases and their presence in the hospital was for some entirely adventitious cause. So that our observation has netted us: (1) clinical types presented by single cases at various ages and stages of the syndrome; (2) progressive cases, observed over periods of from one to six years, show- ing the changing and probably compensatory nature of the disturbance; (8) completed cases in which the disturbance had come to a definite stop, in which the antecedent history bore out the close relationship to our isolated cases which were still in active progress ; TIMME 211 (4) uncompleted cases in which the condition, after going through the several preliminary — stages, remained indefinitely progressive. Manifestly, to complete the chain, it is necessary to observe at least one case from the beginning to the end of the disorder —a period varying from ten to twenty years. Until this can be done, we must fill in the gaps as best we can. GENERAL DESCRIPTION The syndrome, pieced together as above presented, may be generally described as beginning in youth some years before puberty and going through its varying stages in about two decades. In its incipiency (first stage) it presents largely the characteristics of the so-ealled status thymico-lymphaticus, or status hypoplasticus of Bartels. There is complaint of muscular fatigability as a subjective sign. Objec- tively the case presents frequently, though not inva- riably, (for exception see case Bryan, fig. 6) an insufficient genital development, with perhaps inver- sion of sex type with a penis that emerges from scrotal folds of labial type, or erytorchism or both. In the female, the menses are usually delayed, the uterus and ovaries remain infantile and there is scarcity of pubic hair. Blood pressure is usually low, and blood sugar content low. Enuresis is common. There is usually present, the white line of adrenal insufficiency of Sergent. In the second stage, that beginning at puberty, we find a continuance of the muscular fatigability or even an increase. The genitals may remain backward in development, the pubic hair is sparse and has the distribution of the opposite sex, the male showing a horizontal demareation, Axillary hair is. absent 212 PLURIGLANDULAR SYNDROME and chin and lip show no signs of hair in the boy. Blood sugar is low, usually below .070%, and blood pressure below the normal. The white adrenal line may be elicited, especially marked after fatiguing exercise. Roentgenograms of the skull usually show a sella turcica which is small or which may appar- ently be even enclosed by the clinoid processes. This is an important point to determine, for the later progress of the disorder presumably depends upon the capacity of the pituitary gland to become hyper- plasic. This excessive function of the pituitary later on dominates the picture and is conducive to com- pensatory cure. The thymus gland frequently is seen in the X-ray quite enlarged. In some cases of extreme fatigability, | have also seen pineal shadows. During the second stage, rapid growth in length begins to become manifest,—not ordinary normal erowth,—but rapid in the extreme so that 5 or 6 inches in height a year is frequent. With this growth, fatigability increases, and it is on this account that the case is first brought to our attention. In the third stage, we begin to see the results of some of the compensatory activities. It is usually ushered in about the 20th year of life. Growth has continued until the patient is 6 feet high or over; his weakness, even though his musculature seems splen- did, is his prominent symptom. He shaves rarely or never. Pubic and axillary hair remain as before. Now he begins to notice an enlargement of his hands and feet, and a frontal headache or rather an intra- temporal headache comes on. Blood pressure remains low (90 to 100 millimetres systolic), blood sugar usually remains low, but now frequently rises as com- pensation progresses. Our patient shows decided TIMME 213 ragotonic symptoms. An X-ray of the skull at this stage, or during this stage, if the case progresses favorably, shows a sella turcica which, while small, may show erosion of the clinoids and a deepening of the cavity. This tendency of the pituitary to become hyperactive produces the headache (if the sella is contracted ), the increase in blood sugar content, the erowth of hands and feet, and a gradually rising blood pressure. The fourth stage now comes on, from three to ten years later. This is the stage in which either com- plete compensation is produced or else the untreated ‘ase takes on the varying and various attributes produced by an enlarged pituitary body engrafted upon the earler manifestations of a thymic state. That is, we have in the completely compensated case, features of acromegaly, although the blood-pressure and blood sugar are normal and the headaches have gone. The sella on X-ray seems large. In the uncom- pensated cases we usually see a sella which is still small and bridged, with headaches of increasing severity, perhaps attacks of petit or grand mal, mental torpor, increase of weight with constantly increasing fatigue and a final lethal termination in intercurrent disease. A brief resume of the characteristic symptoms and findings in the different stages is here succinctly put forth: First Stage. The bony structure shows various endocrine anomalies and defects; disproportion of various skeletal units; teeth late and epiphyses slow in joining shafts of bones; hyperextension of joints; hair growth late and sparse, distribution of invert type; cramps in muscles; tendency to hemophilia 214 PLURIGLANDULAR SYNDROME and spasmophilia; enlarged thymus; tonsils large and adenoids; low blood pressure; low sugar content of blood; epistaxis; cyanosis of extremities; fatiga- bility; small sella turcica; enuresis; low CO: coeffi- cient of blood. Second Stage. At about age of puberty; rapid skeletal growth begins; late menses and small or infantile uterus; great fatigability with all evidences of low adrenal supply—low blood sugar; low carbon dioxide combining power of the blood; white line of adrenal insufficiency ; pubic hair of invert type; lack of hair on face and chin and axilla; smooth soft skin of child; genitals of invert type or else retarded; vagotonia; symptoms of hyperacidity and gastric ulcer; enuresis; undue length of long bones; low blood pressure ; little stamina. Third Stage. 20th to 30th year; beginning giant- ism; headaches pituitary in character; drowsiness; acromegalic beginnings or other pituitary stigmata; fatigability may continue or improve; mental confu- sion and hebetude; epileptiform attacks—uncinate in type; sella turcica enlarges or else erosion of sella or clinoids takes place; blood sugar gradually increases if cure established. In uncompensated cases mental symptoms, moral and intellectual def- ciencies and delinquencies arise. Fourth Stage. Either complete compensation— so that patient may live comfortably within limits of exertion or else progress to end of life as pituitary ease. The various external manifestations of the pituitary disturbance remain even if physiological cure is complete. Blood pressure rises; headaches cease; fatigability vanishes. DISCUSSION OF SYMPTOMATOLOGY The bony structure in the first and second stages usually shows anomalies in proportionate skeletal orowth, i. e., legs too long for thorax or vice versa; the joints usually are hyperextensible and frequently TIMME 215 the ligaments are so relaxed that dislocations are easily produced. The extremities can be thrown about like flails; while the teeth are usually delayed in their appearance they also show certain character- istics. The lateral incisors, especially in girls, are fre- quently greatly underdeveloped. The canines, like- wise, are either underdeveloped or else take on the flat appearance of incisors, losing their fang-like appear- ance. With the cyanosis of the extremities we occa- sionally get a pustular-like eruption about the nails. The symptoms during the second stage may need some elucidation. The so-called ‘‘white lne’’ of adrenal insufficiency was first desciibed by Sergent. It has not been proven to be due to the deficiency, but in my experience it invariably accompanies low blood pressures, and may be made to disappear very quickly after a hypodermatie injection of adrenalin. Previous emotional disturbance, even so slight as that produced by standing before a camera to be photo- eraphed, will make its appearance impossible to obtain. It is obtained best by having the patient lying quietly in bed for a short while and then strok- ing the skin, preferably of the abdomen or thigh, hghtly, with the palmar surface of the index finger. In 10 to 20 seconds, there will be a blanching of the skin thus stimulated. (See Sergent’s article, Endo- erinology, 1917, 1, 18, for the explanation of this phenomenon.) The low carbon dioxide combining power of the blood plasma diminishes the so-called ‘buffer’? property of the blood and leads to acidosis on slight provocation. The smooth soft skin of these cases, even 1n the third decade of life, with little or no secondary hair on the face, a faint suspicion of lanugo on the hp and chin, and a ‘* peaches and cream’’ com- 216 PLURIGLANDULAR SYNDROME plexion, frequently stamps these cases at sight. The headaches, produced as will be discussed in the patho- genesis, are of a specific type. They are invariably stated to be between the temples, the patient indicat- ing the locality by putting one index finger on each temple, directed mesially. We have come to call them ‘‘nituitary headaches.’’ The vagotonia present in many of the cases frequently takes on the character of hyperacidity of the gastric Juice with frequently symptoms of gastric ulcer, spastic constipation and eosinophilia. In the third stage, the symptoms of ereat interest are the mental ones. In many years’ observation of pituitary disorders, we have been fre- quently struck with the mental quips of the hypopi- tuitaric. He exhibits lack of inhibition of the emotions, becomes highly excitable on little cause, alternating with sluggishness ; frequently has phobias and compulsions—(one case was a true kleptoma- niac)—shows frequently moral and sexual obliqui- ties; and exhibition of pituitary feeding often modifies these characteristics. The symptoms of the uncompensated cases usually merge into those of a frankly dyspituitary syndrome which it is not my province to discuss here. AETIOLOGY In practically all our cases, there have been family histories of importance as regards endocrin- opathies. Frequently, parents or grandparents have shown such disturbances as diabetes, goitre or acro- megaly. A very common complaint is giantism. Col- lateral branches, too, show similar disturbances. Thus, W. W. (fig. 10) the fully compensated case, has four cousins all afflicted with Graves’ disease. There appeared in our cases no particular antecedent TIMME 217 disabling disease or injury. One case, now in the second stage, had two brothers, both dying suddenly after exertion without known cause, in youth— possibly a so-called thymie death. DISCUSSION OF PATHOGENESIS During the first stage, we see a clinical picture which is dominated by the characteristics of the status hypoplasticus of Bartels. The anomalies have been variously credited to hypofunction of the indi- vidual endocrine glands, excepting the thymus, which is supposedly hyperactive. Thus, Tandler and Gross aud Tandler have described many of the features of such a condition due to deficiency of the gonads. Wiesel, Schur, and Schmorls and Ingiers have given both clinical descriptions and histological and patho- logical findings in such hypoplastic conditions refer- able to underactive or inhibited adrenal glands. Many observers have described the smallness of the sella turcica. My own observations agree with these. All of our cases show the smallness of the sella turcica in the early stages and in addition many of them have the bridging over by the clinoid processes, evident on X-ray examination. With these deficiencies of glandular structure and their diminished physiolog- ical activity ab initio, the organism would of necessity come to early grief if some corrective were not forth- coming. Many cases do succumb early. Undue exer- cise, sudden excitement, narcosis, are all critical moments for such organizations, many of which cannot survive them. After puberty should have been reached (the second stage) the deficiency of the gonadal inhibition to growth (Tandler and Gross) is responsible for the extreme height rapidly reached ee 218 PLURIGLANDULAR SYNDROME by our cases. One of our cases (Private B.) however rather opposes this theory in that the gonadal system early became hyperplasic and still the growth in body took place. This excessive genital development may be due in his case to an early involution of the pineal gland, for in the X-ray, calcification of the pineal is seen. (Some authors hold that the overactive thymus with disturbed calcium metabolism is the cause of such *‘thymic giantism.’’) The deficient adrenal-chro- maffin system is to be credited with the great fatiga- bility, the low blood sugar content, the low blood pres- sure and the white line. Now comes the third stage, the all-important one. It isin this period that the out- come of the syndrome is determined. In our judg- ment it is the pituitary gland which is here the erit- ical factor. As we have seen, it is invariably enclosed in a small sella tureica and possibly even hemmed in by the clinoids. Among its functions we have as all important, a blood pressor principle and a sugar mobilization factor. Both of these are deficient in our patient. If the pituitary possibly could become hyperplasie and hyperactive with an intensification of these important properties, compensation might be accomplished. Such tendency to hyperplasia ia a small cavity would of necessity through pressure produce headaches—an invariable symptom in the third stage of the compensated cases. And such headache would continue until the enlarged gland through erosion of its bony capsule or through push- ing apart the clinoids made sufficient room for itself. As will be seen, these headaches continued for two to three years in some of our cases. Synehronously with these headaches, other incidental features of an enlarged pituitary gland became manifest ;— (a) TIMME 219 acvomegaly—lasting until the headaches ceased and the process then likewise ceasing; (b) a higher blood sugar content; (¢) a higher blood pressure; (d) a diminished sugar tolerance. To make this view of the nature of the process of Compensation more ten- able, many of the sellae turcicae of our patients in the second and third stages show erosion of anterior or posterior clinoid processes; and in the final stage, an enlarged sella with practically no clinoid processes left at all. In the cases in which no compensation was effected, i. e., in which fatigability, et cetera, remained and progressed, the sella showed no enlargement (notably that of T. R., fig. 12). In these cases, we had headaches, periodical in type, adiposity, mental and moral deficiencies, petit mal and other manifestations. Curiously enough in al/ our cases, the feeding of the pituitary gland in fairly large quantity, disposed of many and at times of all of these symptoms. but if the feeding were diminished or stopped, the symptoms reappeared. It seemed analo- gous to thyroid feeding in myxoedema. One case, which gave a typical early history and seems uncom- pensated today at the age of 44, still shows the very small sella turcica with a clinical picture of abnormal bony structure much resembling Paget’s Disease. On pituitary feeding, this case is improving mark- edly in its features of fatigability, headaches and heaviness of extremities. It is too early to state whether in her case the cancellous condition of the bones will be restored. Finally, the fourth stage is ushered in by a gradual cessation of the fatigue, amelioration of the headaches, restoration of a normal blood pressure and normal sugar content of the blood. But the adventitious signs of the disturb- 220 PLURIGLANDULAR SYNDROME ance of the pituitary gland remain. Thus the fully compensated cases may show acromegaly more or less marked; and this acromegaly is not to be taken as a diseased condition needing treatment, but simply as the hallmark of a process that has come to a stop— a self-curative process. It is analogous to the hyper- trophied heart become so through the deficieney of the cardiac valves and making up for such deficiency by its enlargement. And that condition likewise, per se, needs no treatment. A case that presents acromegale features, therefore, need not necessarily be a case that calls for therapeutic intervention. It may well be a ‘‘finished’’ case. (W. W. fig. 10) isa good representation of this type. These ‘‘finished’’ cases, must always, however, live within certain limits of exertion and stress. The cases that in the fourth stage do not spontaneously go to full compensation, are those in which we either find a sella turcica which did not enlarge (perhaps because there was no spon- taneous effort of the pituitary to become hyperactive ) or in which an enlargement of the sella did take place and the pituitary even in its hyperactive condition was not sufficient to compensate. These uncompen- sated cases go right on with progressive symptoms of fatigability, asthenia, headaches and so forth, mak- ing of them easy prey to intercurrent affections. TREATMENT The treatment of these cases in any stage is extremely satisfactory. The great point to remember is the probable nature of the process of compensation which the organism is endeavoring to carry out. That would make one believe that suprarenal gland therapy is indicated throughout on account of the patent deficiency of this organ in these cases. And TIMME 221 yet in our hands its administration is disappointing. The whole gland perhaps has given better results than adrenalin, although the latter, either hypoder- matically or (even against the dictum of the physiol- ogist that it is inert when administered per os) by mouth in larger doses is good to tide over exception- ally bad days of fatigué and exhaustion. But the prime agent—almost a specific one—is_ pituitary gland in some one of its varied forms. Whole gland feeding in fairly large doses, gr. 11 to gr. 111 t. 1. d. may be given in appropriate cases. Occasionally, pituitrin hypodermically 0.50 to 1.00 ¢.c. per day or alternate days for one or at most two weeks at a time is excel- lent as supplementing the feeding of pituitary gland. Occasionally in cases with pronounced genital delay, anterior lobe pituitary gland gives fair results. In those cases with vagotonic symptoms, hyperacidity and conditions resembling gastric ulcer, atropine in doses to physiologic tolerance is indicated, and gives results. But the pituitary feeding in itself, alone, produces highly satisfactory improvement in almost every case. Under its use, the headaches disappear, the fatigability diminishes, the blood pressure and blood sugar content increase, and the case goes on to cure. Gradually the pituitary feeding can be diminshed and finally discontinued. In the older cases, In which the sella persists in remaining small (T. R. fig. 12) and (J. 8. fig. 11) constant feeding would seem to be necessary; at all events, the patients relapse as soon as treatment is stopped. Indeed, the patients themselves reach that point of accuracy of judgment in feeding the gland to themselves that they can determine the size and frequency of the dosage necessary to maintain them comfortably. 222 PLURIGLANDULAR SYNDROME The following case histories are cited as a few among many which show characteristics of the differ- ent stages of the syndrome. Only facts having direct bearing are introduced into the case histories. 1G eal Fig. 1. J. M. Casel. Shows abnormal length of thorax compared with legs. Thighs especially short compared with lower leg. Small genitals. Has large thymus and enclosed sella turcica. Case 1. J. M. (fig. 1). Ten years; mentally backward; no hair on body anywhere; genitals unde- veloped; elongated thorax; spasms in muscles; great TIMME 223 fatigability; is a bed wetter; joimts ave hyperexten- sible; has nose bleeds. X-ray of chest shows thymus (fig. 3); skull shows small sella turcica, entirely bridged over (fig. 2). Blood pressure 85; white advenal line. id 3 pees | FIG. 2 Fig. 2. J. M. Casel. Sella turcica small and entirely enclosed and “roofed in.”’ Discussion. This case is presented simply to show the type from which arise the cases presenting the later features of the syndrome and hence may be classed under stage 1. Case 2. Master F. J. Age, 133 years; height, 615 inches. He was brought to the Neurological Institute on account of his predeliction for lying and further for his rapid fatigability. He had been discharged from several schools on account of his incorrigibility. The climax was reached when he 224 PLURIGLANDULAR SYNDROME appeared as a material witness in a murder trial, his evidence being of the greatest importance in the con- viction of the accused. Apart from these facts, he also complained of spasms in the muscles, especially FIG. 3 Fig. 3. J. M. Casel. Shows thymic enlargement. of the calves, which occasionally awakened him by the pain caused thereby. He had frequently also had nocturnal enuresis. Upon stripping him (fig. 4) the examination revealed the following: the body was perfectly hairless, no trace of pubic or axillary hair bo bo Ov TIMME being evident. The genitals were small—infantile in fact—but both testicles were descended and the serotum surrounded the penis likea labial fold. Upon eliciting the cremasteric reflex, however, the testicles FIG. 4 Fig. ae F.J. Case2. Age 13% years. Shows hypoplasia of genitals and a scrotal fold surrounding base of penis. Absence of hair. Bruise on raised arm from slight pressure. were drawn up out of the scrotal sac into the inguinal canal where they could not be palpated. He bruises very easily, the dark patch on the left raised arm 226 PLURIGLANDULAR SYNDROME being produced by the simple pressure of the exam- iner’s thumb in raising the arm. Hands and feet are somewhat larger than they should be. Stroking the skin of the abdomen produced a marked white line of reaction, which persisted for a rather long time. FIG. 5 Fig. 5. F.J. Case 2. Pituitary fossa shut in extremely by large cli- noids. His blood pressure was low, 80mm. Mentally he was well up to his chronological age according to the Binet-Simon scale. Upon close questioning he admitted that he had frequent headaches referable to a point midway between the temples and deep- seated. TIMME 227 The neurological examination was negative. Laboratory examination showed the sugar content of the blood to be .070%. Otherwise blood and urine were negative and the Wassermann was negative. X-ray examination: The sella turcica (fig. 5) was small and encroached upon by large clinoids; the upper thorax showed a thymus shadow. Discussion. This case is presumably a type of the beginning of the second stage of the syndrome. It presents many of the well marked features of a status hypoplasticus:—small sella, enlarged thymus, low blood pressure, low blood sugar, marked fatiga- bility, spasmophiliae and hemophihae attributes in uddition to the obvious externals. The mental attri- butes are those which we frequently see in small and enclosed sellae turcicae. This case is presented sim- ply as a living present example of the early begin- nings of the second stage of the syndrome. Case 3. Private B. (fig.6). Age 20 years; height 6 feet 1 inch. This case was sent to the Institute by Capt. Reed, stationed at Fort Wood, to determine whether or not the man was a malingerer. His one complaint was that of excessive fatigability after moderate exertion. Asa result he could not perform the military duties required of him. His muscula- ture and his whole bearing and appearance when stripped were that of a powerfully and symmetrically built young giant, and seemed to belie his statement of rapid fatigue. His early history could not be obtained with any degree of reliability for, coming from a mountainous district of the South, he was extremely uncommunicative. In early adolescence he was a rover, traveling over many states in divers 228 PLURIGLANDULAR SYNDROME occupations, but never steadily at any one. He did say that for the past three years he had been rapidly and steadily growing in height, that this growth was still continuing and with it his fatigability was FIG. 6 Fig. 6. Private B. Case 3. Feminine distribution of pubic hair; large genitals; height 6 feet, 1 inch; no hair on face. Seems well-proportioned. increasing. Stripped, he showed a splendid make-up muscularly. Of note was the fact that he had prac- tically no hair on his lip or chin, no hair in the axillae, pubic hair of the feminine type and rather largely TIMME 229 developed genitals. Stroking the skin produced a white persisting reaction. His blood pressure was between 95 and 100 mm. systolic, 80 diastolic. Blood sugar was 0.062%. X-ray examination showed a FIG. 7 Fig. 7. Private B. Case 3. Complete closing in of pituitary fossa. sella turcica (fig. 7) which was extremely small, with thickened anterior and posterior clinoid processes completely roofing in the cavity. A shadow in the pineal region also was evident. The thorax showed a thymic shadow. Neurological examination was negative. Viscera appeared normal. Discussion. This young man is going through the transition period from the second stage to the third. His low blood pressure, low blood sugar per- centage (extreme normal low limit should be at least 075% ), white skin reaction line, all go to prove his statement of fatigability. In addition he shows a crowded pituitary fossa and a pineal shadow. We 230 PLURIGLANDULAR SYNDROME have found in the past two years ina large percentage of muscular dystrophies, pineal shadows; and in extreme cases of muscle fatigue in the adolescent, short of dystrophy, there were shadows in the pineal region. This parallelism between the myasthenic types and early involution of the pineal gland will be the subject of a future paper. ‘This feature of the case is an example of many similar ones. but pre- sumably early pineal involution also produced his enlarged genitals. He is undergoing the rapid growth incident to the second stage of the syndrome in spite of the fact of the enlarged genitals. Some authors (especially Tandler and Gross) have main- tained that the hypoplasia of the genitals accounts for the continuance of the skeletal growth. That is certainly disproved here as a universality. Upon feeding of pituitary gland, this youth improved suffi- ciently to go back to army life. After the lapse of a few months, he discontinued this feeding and shortly thereafter returned with his old complaint of fatig- ability. He is again improving on treatment. No white line can now be elicited, and his blood pressure is usually at 120 mm. Case 4. G. H.R. (fig. 8). Age 22 years; height 6 feet 34 inches; single; stenographer. Came to the Neurological Institute complaining of loss of memory and lack of sleep; feeling stuporous and extremely fatigued. Has headaches intratemporal in location. Not able to do much manual work on this account and hence took a position as stenographer. Is exempt from military duty, being the sole support of his nother. Past History. While a child, he was never strong; he took a long time to develop and on account of his TIMME 201 was always known as ‘‘sissy’’ to ways—feminine his playmates. He realized this appellation to be more or less just. Would easily cry if deprived of his FIG. 8 Fig. 8. G. E.R. Case4. Height 6 feet, 3% inches; feminine pubic hair; no hair on face; musculature seems flabby; feminine attributes. way and still does so. Always was a bed-wetter, and this weakness persisted to his 19th year. Realizing his feminine attributes, he endeavored to compen- sate for them by indulging in the most manly of sports—boxing and football. But he was too slow 32 PLURIGLANDULAR SYNDROME to amount to anything here. He gave up this conflict and sank to his own recognized levyel—became a stenographer. He began to get headaches at 17 years of age, at which time his excessive growth started. Examination. A man powerfully set-up, 6 feet 34 inches high and proportionately built. (fig. 8.) No hair on face or body except in the pubic region, where it is of feminine distribution. The scrotum also is divided above the penis into typical labial folds. He shaves once in two weeks. His appearance is really FIG. 9 Fig. 9. G. E. R. Case 4. Sella turcica with anterior cavity eroded and a deepening of posterior fossa. pugnacious, but is not borne out by his mental atti- tude. He eries when questioned about the simplest difficulties. His blood pressure is 100 mm., systolic. He has the white line reaction of the skin, and his blood sugar was low. The X-ray of the skull shows TIMME 233 a sella in which erosion of the anterior clinoid is evi- dent and an excavation of the posterior portion of the floor. (fig. 9.) The X-ray of the thorax shows a possible enlargement and persistence of the thymus. Neurological examination is negative. Discussion. The early history is that of a thy- mus state. The further progress, especially the headache concomitant with the growth is suggestive of pituitary enlargement. This is partly borne out by the picture of the sella. His headaches are now much less prominent than they were, but his fatig- ability is marked. His growth seems to have ceased. This case belongs in the third stage—with the giant- ism gradually reaching its acme, with the stuporous and drowsy mental condition of a dyspituitarie still present, great fatigability, low blood pressure and low blood sugar content. The enlargement of the sella turcica however gives promise of a gradual efficient compensation taking place. Feeding of whole gland pituitary extract within two weeks measurably improved all his symptoms. It is still being continued. Case 5. W. W., 32 years; machinist; married; several children; height 6 feet 43 inches; acromegaly in slight degree. This case has been under our ob- servation since 1912. At first the complaint was one of utter exhaustion to the exclusion of all minor ills. He could not stand at his work, he could hardly walk without becoming exhausted. At 19 he had severe headaches referred to the intratemporal re- gion which persisted in spite of all measures. These headaches he deseribed as ‘‘crushing.’’ At the same time his hands enlarged while under our observa- 234 PLURIGLANDULAR SYNDROME tion. The fatigability was so great that he would have to take to his bed and remain there. His past history was typical of the thymic. Nose bleeds, gen- eral weakness, enuresis, over-extensibility of the FIG. 10 Fig. 10. W.W. Case5. Six feet, 44% inches. Fully compensated case. Great length of leg compared with length of thorax. Feminine waist; fem- inine pubic hair; acromegalic hands; no hair on face. joints. His family history was a typically endocrine one. On his mother’s side four members of direct and collateral branches had goitre, two with exoph- TIMME 239 thalmos. His father never shaved until the age of 28. Puberty in this patient was reached at 19. Hairy evowth in the axilla and on the face remained absent. T'o this day he has never shaved. During the period of intense headaches and growth, he had various vagotonic symptoms: hyperacidity; excessive per- spiration; precordial distress; nausea and vomiting ; marked pallor; lack of libido. His gastric distress became so acute that operation was advised at an- other hospital for gastric ulcer. At this time an X-ray of the skull was taken and showed a large sella turcica, with practically no clnoids present at all and erosion at the edges. His photograph (fig. 10) has some interesting points. The extreme length of leg compared with thorax is noteworthy. The feminine distribution of pubic hair and femi- nine waist are present. His extremely large hands and generally deficient masculature attract notice. This photograph was taken about a year ago when he was just completing his cure. Today he has gained 30 pounds in weight and is feeling practically well, working constantly as machinist and support- ing his family of wife and two children. During the last three years, his blood pressure had gradu- ally risen to 130 mm. systolic from an initial 90 to 100 systolic; his gastric symptoms have abated, the white line of adrenal deficiency is disappearing ; his fatigability has passed; libido has returned, and he is to all purposes cured of his malady. His fatig- ability and headaches in the past three years could always be improved with the administration of whole gland pituitary extract and gradually it became pos- sible to diminish the dose and to allow the compen- sation to proceed unaided. He has now been with- 236 PLURIGLANDULAR SYNDROME out treatment for practically six months. He seems to be a fully compensated ease. Discussion. The history and progress of this case is typical of all cases passing through the complete syndrome and is presented as a type of which I have now seen at least ten examples. It must not be for- gotten that he now shows giantism plus acromegaly. That does not mean that his clinical picture indi- cates treatment. Far from it. He is a finished case. The giantism and acromegaly are incidents merely of the compensatory process—they themselves do not necessarily indicate present disease. This is a point well worth remembering. Many cases show- ing endocrinopathic features come under our notice and it should be our first aim to determine whether or not they represent processes that have come to a stop through compensatory efforts of which they are the indices. Under such conditions of course no treatment is called for. An interesting case of this nature was seen at Mt. Sinai Hospital, New York, in the service of Dr. Goldenberg, through the kind- ness of Dr. I. Strauss. A woman, 53 years of age, with typical acromegaly—hands, feet and skull ab- normalities, was admitted for some minor ailment. Her history showed that she began to menstruate at 19 years, had intense headaches at 25 years which for three years resisted all attempts to alleviate, and during whose persistence she began to grow acrome- galic. When the headaches spontaneously ceased, the abnormal growth ceased, and she passed an un- eventful life to the time of the present slight ail- ment. Her childhood and adolescence were like those described in the first two stages of this syndrome— fatigability, being the prominent symptom. Her TIMME 237 acromegaly then, was completed at about the twen- ty-ninth year, did not further increase, and she re- mained well for twenty-three years longer. This was also a ‘‘finished’’ case as far as the syndrome of thymus, adrenal and pituitary was concerned. This case might be many times duplicated. UNCOMPENSATED CASES I desire to give rapidly the salient features only of several uncompensated cases belonging to the syn- drome, FIG. 11 Fig. 11. J.S. Uncompensated case 6. Shows pituitary fossa completely enclosed. Stereoscopic plates confirm this. Age 22 years; height 6 feet. Case 6. Miss J. S. Referred by Dr. Robert T. Morris. Height 6 feet, large hands and feet, ex- treme fatigability, headaches, vagotonia, rapid growth in past two years with a past history of status thymico-lymphaticus; comes for rehef of her headaches and fatigability. Blood pressure 95 sys- tolic; blood sugar .065% ; fatigue so great that she must remain prone the greater part of the day. In- 238 PLURIGLANDULAR SYNDROME tense white line. Her sella turcica (fig. 11) shows a roofing in by the clinoids. Pituitary feeding gave gratifying results, but must be continuously carried out. Case7. T.R. Age 35 years; height 6 feet, 1 inch. Obese (220 Ibs.). Early fatigability. Late puberty. Feminine pubic hair. Unmoral. Intense intratem- poral headaches. Although wealthy, and of excel- lent family, commits sexual and other excesses. Frequently in jail. Fatigability and headaches per- FIG. 12 Fig. 12. T.R. Uncompensated case 7. Age 35 years; height 6 feet, 1 inch. Sella turcica completely shut in and extremely small. Confirmed by stereoscopic plates. sist. With beginning of headaches growth began. Blood pressure 95 mm. Sella turcica small and closed in by the elinoids (fig. 12); polyuria. Pitui- tary feeding helped not only his headaches and fatig- ability, but strangely and unexpectedly his moral sense is elevated and his excesses are no longer in- Culged in. But the pituitary feeding must be con- stantly kept up. A few weeks of discontinuance TIMME 239 leads rapidly to the old condition. He has been now practically free of his troubles for two years. CONCLUSION The syndrome of thymus—adrenal—pituitary combination is one frequently met with and its va- rious stages are easy of recognition. The main characteristics of fatigability, low pressure, head- ache and growth are invariable components of the syndrome and depend upon mal-adjustments of en- docrine interactivity. Stabilization of the balance may be spontaneously produced providing the sella turcica may be made to accommodate a hyperactive hyperplastic pituitary gland. This is done presum- abby by erosion of the bony capsule of the gland. In eases of inability of such enlargement of the sella, the syndrome persists, but the symptoms may be alleviated by the feeding of pituitary extract contin- uously. In the course of the syndrome other glands may be brought into the complex and alter the pic- turé somewhat, but these are vagaries and seemingly have no great determining effect upon the course of events. Once recognized in any of the early stages, the further general progress of these cases ean be prognosticated with a great degree of accuracy; and intervention, if necessary, can be undertaken with a large degree of success in the amelioration of the distressing symptoms. BIBLIOGRAPHY Maranon. Insuffisance plurigland. (Atrophie testiculaire acro- megalique.) Rey. clin. de Madrid, 1909, p. 330. Marie, Pierre. Persistance du thymus chez un acromegalique. Soc. med. des Hopit., 1893, 2, 17. Wiesel. Zur pathologie d. Chromaffin Systems. Virchow’s Arch., 1904, 176, 103. 240 PLURIGLANDULAR SYNDROME Tandler. Ub. d. Einfluss. d. innersekret. Anteile d. Gesch- leschtdrtisen auf. d. aussere Erchein. d. Menschen... Wien Klin. Wochenschr., 1910, 23, 459. Tandler und Gross. Uber d. Einfluss d. Kastration a. d. Organ- isms, u. s. w. Arch. f. d. Entwicklungsmechanik., 1909, 27, 35. Cushing. The Pituitary Body and its Disorders. Especially case XXxli—giant Turner; this case seems to fit into the above syndrome almost perfectly; lack of hair; small gen- itals; low temperature ; minute adrenals; intense muscular fatigability ; growth beginning to be excessive at age of 15 accompanied by intense headaches. Cushing himself states that ‘‘the patient is not an acromegalic giant’’ in the true sense. (p. 168.) Bartel. Status thymico-lymphaticus and status hypoplasticus. Vienna, 1912. M. Lucien and J. Parisot. ‘‘Contribution 4 1’étude des fone- tions du thymus.’’ (Arch. de med. experiment., 1910, 22, 98. Muller. Fall von Akromegalie, Osteomalacia, Tetanie und Struma. Wiener Klin. Wochensehr., 1909, 22, 76. Ingiers und Schmorls. Uber d. Adrenalingehalt d. Neben- nieren. Deutsch Archiv. f. klin. Med., 1911, 104, 125. Schur und Wiesel. Uber d. Verhalten d. Chromaffin.. Gewebes bei d. Narkose. Wien. Klin. Woch. 1908, 21, 247. Renon, Arthur Delille et Monier-Vinard. Syndrome _ poly- gland, (thyreo-testiculaire-hypophys). Soc. med. des hopits- 1909"2) 75: . Massalongo. Sull’ acromegalia. Riforma med., 1892, 8, 157, et seq. Hoskins, R. G. ‘‘ Relation of the adrenal glands to the cireula- tion of the blood.’’ Endocrinology, 1917, 1, 292. IS THERE A THYMIC HORMONE? EK. R. Hoskins Department of Anatomy, University and Bellevue Hospital Medical College, N. Y. From the frequency with which reference is made to the internal secretion of the thymus, and the various influences which this organ is commonly declared to exert over other parts of the body, it would seem superfluous to question the existence of a thymic hormone. But as a matter of fact, it has never been definitely proven that this organ produces any internal secretion at all. For some time it has been the practice of work- ers in biology and medicine to declare that this or that organ or tissue of unknown function has an in-. ternal secretion, with little or no valid evidence to support their theories. Recent literature contains several ‘‘new ductless glands.”’ Morphologists having pointed out the fact that in the human species the thymus ‘‘usually’’ begins to undergo involution at ‘‘about’’ the time of pub- erty, experimentalists seized the faet and built upon this slender foundation various theories of control of sexual development by the thymus. Later it was pointed out that this correlation between the time of thymus involution and sexual differentiation does not exist generally among animals, but varies with- in wide limits, and also it was pointed out that in the human the thymus in many cases reaches its greatest size before puberty and in many other cases much later than puberty, but the theory had already been firmly established in the minds of many peo- ple, and it still persists. Below we shall point out 242 THYMIC HORMONE that the thymus is relatively larger at birth than ever after that time. Another theory of thymic function arose from the fact that during the greater part of the involution of the thymus, the skeleton is growing rapidly. This theory stated that the thymus controls skeleton erowth. In regard to the theory of the thymus-skeleton relationship it may be pointed out that another lym- phoid organ, the pharyngeal tonsil, ‘‘usually’’ be- gins its involution during infancy. If it so happened that some other striking phenomenon occurred at the same time, there would doubtless have arisen one or more theories on the inter-relationship of the two. The fact that the thymus and thyreoid both have their anlagen in the pharynx gave rise to various theories of the relationship between these two or- gans. Whenever in the life of an animal two phenomena occur together, and especially if they are not well understood, there has been a tendency to evolve theories associating the two functionally. Dancha- koff (718) in discussing another subject has well said, ‘‘The infinite complexity of developmental pro- cesses requires special caution in the attempt to es- tablish a direct causality in the relations between two invariably concomitant phenomena.’’ In no field of biology has such caution been disregarded more frequently than in endocrinology. Most of the experiments with thymus can_ be placed under the headings, extirpation and admin- istration of thymic tissue or extracts. In the lower animals there is relatively little lymphoid tissue other than the spleen and thymus and experiments HOSKINS 245 with the thymus in these forms should therefore be very instructive because of the relative sim- plicity of the problem. Removal of the thymus from frogs apparently is not fatal (Vincent, ’04), but the animals seem less resistant to infections (Verenke, ’99). Allen (718) has recently shown that frogs will develop without the presence of the thymus. He removed the anlagen of this organ from young frog-larvae before it could possibly have functioned, and yet the larvae grew normally and metamorphosed at the normal time. Allen has not as yet, however, published any obervations on the effect the experiment may have had upon the spleen, but he showed conclusively that the thymus is quite un- necessary for the proper development of frogs. The same is probably true for other amphibia. In feeding experiments with these forms, Guder- natsch (714) found that thymus fed to larvae de- layed their metamorphosis although the animals grew on this diet. Romeis (715) and Abderhalden (715) were able to verify these results in part, but Swingle recently (716) states that such larvae kept by him on a diet of thymus were able to grow and metamorphose normally. Uhlenhuth (717) feeding thymus to another amphibian (Amblystoma), ob- tained in general, negative results. This author be- lieved that the delay in metamorphosis obtained by thymus feeding is due simply to the fact that thy- mus is not a sufficient food. He obtained delay in metamorphosis also by a diet of worms. The very numerous recent papers of Osborn and Mendel and others, show that many diets, although fed in abundance, lack certain constituents necessary for growth. 244 THYMIC HORMONE Metamorphosis in amphibia is probably initiated by skeletal changes which in turn depend upon the calcium metabolism. This metabolism is probably dependent upon the thyroid or hypophysis, or both, since removal of either of these two glands will delay if not entirely prevent metamorphosis. In this interference with metamorphosis which is caused by thyreoid removal (see Hoskins (718), the thymus appears to be in no way affected, either in size or structure. Gudernatsch’s results were obtained by feeding thymus-tissue from mammals, which of course have no need for a ‘‘metamorphosis- preventing’? hormone, and hence are unlikely to have developed one. In extirpation experiments with higher animals, the results are conflicting. Klose and Vogt (710), Lucien and Parisot (710), Paton (711), Friedleben (758), Matti (712), Soli (710), and other authors report that following thymus removal in birds and mammals various effects are produced, such as in- terference with skeletal growth, including rachitic changes, adiposity, emaciation, injury to the thy- reoid, no effect on thyreoid, degeneration of testes, no effect on testes, ete. Pappenheimer (714), Park (717), and others, state that if the experiments are carefully performed and carefully controlled, the thymus can be removed without producing any harmful effects whatever. Paton and Goodall (714) noted a decrease in the number of cireulating leu- coeytes after thymus extirpation, and this seems to indicate that the thymus produces leucocytes as in- deed is obvious from its microscopical appearance. Hewer (716) reports that injury to the thymus by X-ray irradiation results in injury to the function HOSKINS 245 of the testes. Since complete destruction (removal) of the thymus has no such effect and since unhealthy animals never breed well, Hewer must prove that her treatment did more than injure the health of her animals. In feeding thymus to animals, Hewer (14) claimed that the treatment injures the testes, a re- sult not consistent with her report just mentioned. Hoskins (716) feeding thymus to mammals obtained negative results on the growth of the body and all organs. R. G. Hoskins (710) states that feeding thyreoid causes hypertrophy of the thymus, but E. R. Hos- kins (716) obtained negative results with similar experiments. Calzolari (798), Henderson (’04), Hatai (715), and others found that gonadectomy delays involu- tion of the thymus and may even cause hypertrophy. There are also other changes produced by this op- eration, such as deposition of fat throughout the body, hypertrophy of the suprarenals and hypo- physis in the male and decrease in the size of these two glands in the female. The changes that occur in the thymus may be secondary and not show a direct relationship between the thymus and gonads, especially since changes other than that of mere size may occur in organs other than those mentioned. The subject needs further investigation, particu- larly on the microscopical side. A possible cause of the delay in thymus involution after gonadec- tomy will be discussed below. Clinically many functions and diseases are at- tributed to the thymus. Many of these theories are 246 THYMIC HORMONE based upon the concomitant phenomena already mentioned. ‘‘ Hyperactivity’? of the thymus is frequently de- scribed where percussing indicates a dullness in the region of the sternum or a shadow is shown there by X-ray. This condition is described in cases of “mors thymica’’ and exophthalmic goitre. As a matter of fact it is questionable without an autopsy whether such enlargement of the thymus is not due simply to an unusually large deposit of fat. Often the size of the thymus is maintained in this man- ner, although relatively little thymic tissue is pres- ent. Moreover, the variability of the thymus is so great that the gland often persists normally until late in life, as is disclosed by autopsies of accident cases. Anatomists make an allowance of from one hundred to seven hundred per cent in the normal weight of the thymus at different ages. Whenever in clinical cases there is an actual overgrowth of thymic tissue (or an early atrophy) this change may be brought about by the factors ‘ausing the disease in question, or still other and independent factors may be the cause, rather than that the thymus itself produces the clinical condi- tion under consideration. We may be dealing with concomitant phenomena not directly related. In many cases where the disease is attributed to thymic changes, no autopsy is or can be performed, and the diagnostician does not really know whether or not the thymus is even pathological. Hammar (716), who has investigated scientific- ally the subject of ‘‘mors thymica,’’ in a large number of cases, has found that the thymus is often HOSKINS 247 perfectly normal as compared with that seen in children killed by accident. Melchior (717) has pointed out the facet often disregarded, that although an ‘‘enlarged’’ thymus is frequently found in exophthalmic goitre, the symptoms are not different when the thymus is not enlarged. In inanition and in wasting diseases, the thymus tends to atrophy. This fact is used in the theory of the relation of the thymus to general metabolism. Jackson (715, 716), Stewart (718), and others have recently investigated experimentally the subject of inanition. They find that in young starving animals there is a decrease in the size of the thymus, but the same is true of other organs and tissues. Cer- tain tissues, especially the connective tissues, have a very strong growth tendency and where nourish- ment is insufficient in amount for all bodily needs these tissues grow or maintain themselves at the expense of other tissues and organs with a weaker erowth tendency. Among these latter are included the thymus, thyreoid, heart, liver, spleen, alimen- tary canal (including the pancreas), lungs, and other soft parts. In older animals suffering from acute or chronie inanition, there is a marked loss in weight of the spleen, liver, and alimentary canal (including the pancreas), and a less extensive loss in weight of the kidneys, heart, lungs, hypophysis and testes. The thymus in these animals had al- ready undergone ‘‘age involution,’’ and hence was not affected. From these experiments it would ap- pear that the loss suffered by the thymus in inani- tion does not indicate that this organ is affected differently from many other organs and does not 248 THYMIC HORMONE add any definite proof that the thymus has any con- trol over metabolism. Difficulty in breathing is often attributed to pres- sure by an ‘‘enlarged’’ thymus against the trachea and bronchi, but an anatomical study would show that these organs are the most unyielding structure within the thorax, and are separated from the thy- mus by a mass of yielding soft tissues in the medi- astinum. It would also be very difficult for the thymus to exert sufficient pressure on the lungs to interfere with breathing on account of the fact that one ordinarily uses much less than the entire ex- pansion of the lungs during respiration. Even with a considerable portion of the thoracic cavity filled with abnoimal tissue there would still be left suf- ficient room for breathing. The theory that rachitic changes in children are caused -by the thymus cannot be proven by any known facts. The theory is based upon the fact al- ready referred to that the skeleton and thymus grow at the same time; upon the changes in the skeleton ‘ thought to result from extirpation of the thymus; and upon changes thought to be noted in the thymus of rachitie children. The concomitant growth of the thymus and of the skeleton may not be caus- ally related, the extirpation experiments have been lately discredited, and unless the children are suf- fering from inanition the thymus is as often normal as not. The faulty metabolism which causes the rachitie condition is sufficient in itself to explain the atrophy of the thymus. There are theories of thymus function other than those noted above, which rest upon still weaker foundations. For example, Kaplan (717) assocei- HOSKINS 249 ates a certain dental condition with the thymus by the term ‘‘thymodontia.’’ His theory is dependent upon the facts that children have thin teeth and a thymus. They also possess other organs such as ton- sils, the pharyngeal, one of which normally begins to disappear in infancy. The dental condition Kaplan describes might as well be called ‘‘tonsildontia.”’ Pighini (716) states that following vagotomy in chickens there results an atrophy of the thymus. There are also other changes including respiratory and circulatory difficulties which affect the meta- bolism and may in that way injure the thymus and other tissues easily affected by inanition. Further- more, the question of thymic involution in chickens has never been adequately worked out. Haneborg (716) blames the thymus for chorea minor because this disease occurs between the ages of two and sixteen years, during which time the thy- mus is normally growing to its maximum size and because thymus administration seemed to be bene- ficial to his patients. He weakens his argument by the statement that there is much to sustain the as- sumption that an infection is the primary factor, perhaps an encephalitis. The latter condition alone might well account for the increased irritability of the nervous system in his cases. ‘“‘Hyperactivity”’ of the thymus is described even without determining whether the ‘‘enlargement”’ of the thymus is due to fat, to pathological tissue or to normal tissue. 2 eae 276 COORDINATED DATA, ADRENALS comes arterial. Once at the air cells, the adrenal product should be destroyed and remain so through- out all arterial channcls and the whole venous tree (unless resupphed, so to say, in the subsidiary adre- nal tissues) until the adrenals per se are again reached. The concentration in the adrenal veins is 1 part in one million, according to several investi- gators quoted by Barger (59). The venous channels between these veins and the air-cells being, of course, much larger, it is probable that Battelli’s concentra- tion 1 part to 10 or 20 millions (60) is the correct one for caval blood 1.e., one thousand times greater than Trendelenberg’s. On the whole, the actual minuteness of circulating adrenin in arterial blood cannot justly be cited to con- trovert the many concordant data submitted in favor of the respiration theory. The great quantity of adrenin needed to produce the effects recorded would kill by paralyzing the al- mentary canal. The invalidity of this objection is emphasized by the teaching of physiologists that ‘‘adrenin circulating in the blood is rapidly de- stroyed’’ by oxidation. Such being the case the adre- nal secretion would meet its doom on reaching the alveoh, thus preventing any action either on the stomach or intestines. Abundant clinical experience also shows that such an action is not produced either when adrenalin or the adrenal gland are given by the mouth or adrenalin is injected hypodermically, endomuscularly or ree- tally during short or prolonged periods in therapeutic doses. This apphes also to children. I could produce a large number of cases in which 3 to 7 minims given orally several weeks served only to act as tonic, and SAJOUS 217 to increase the appetite. In keeping with the obser- vations of Loeper and Verpy (61), it often promoted the secretion of HCl where hypochlorydria existed. A medical patient suffering from asthma wrote re- cently, requesting my opinion concerning the con- tinued use of adrenalin: ‘‘I have employed it for several months once a day, sometimes twice a day, hypodermically in doses of 10 minims of the 1-1000 solution.’’ His blood pressure rose from 130 to 180, he lost flesh and feared a permanent rise. Not a gas- tric symptom occurs, however, in the history of this ‘ase. If inhibition of the rhythmic contractions of the intestine occurs in the lower animals, as shown by Ott, Magnus and others, even when injected in very low concentrations (1 to 20 millions, Magnus) (62), no appreciable effect of this sort is observable when adrenin is given in the therapeutic doses used in man. Possibly it occurs as an ephemeral effect of the con- striction of the arterioles of the intestines similar to that caused by adrenalin throughout the body. INVESTIGATIONS NEEDED TO DETERMINE THE VALID- ITY OF THE OXIDATION THEORY Some physiologists hold that the adrenals ‘‘in some way influence the metabolism of contractile tis- sues.’’ If the word ‘‘metabolism’’ is actually meant here, it would seem as if the word ‘‘destruction”’ (of _ the adrenal secretion in the blood) should be replaced by its conversion into something else that is not sub- ject to destruction by oxidation. I have long held that it entered the hemoglobin, and endowed it with its power to become oxyhemoglobin; we have seen that Menten found that the adrenal product actually becomes converted into that body. ee 278 COORDINATED DATA, ADRENALS If then it does become converted into oxvyhemo- globin, the adrenal secretion or principle must be taken up by the red corpuscles. Mulon (63) has found that the latter gave some of the reactions of adrenalin. Again, Traube, in 1853, concluded that hemoglobin could not fulfill the functions attributed to it without the aid of a catalyst, a substance capable of hoarding oxygen and crowding it, as it were, on the tissues as an ‘‘accelerator.’’ Poehl (64) found that the adrenal principle was a catalyst, while Jolles (65) pointed out that the activity of a given volume of blood as a catalyst corresponded with the number of red corpuscles it contained. This suggests that the adrenal secretion (not necessarily adrenin, which does not represent the secretion in toto) is the corpuscular catalyst which supplies the tissues with oxygen. In this connection, and possibly accounting for the small proportion of secretion produced excepting under stress, such as fright, excitement (Cannon), hard labor, disease, ete., its active principle may be an oxidizing enzyme—‘adrenoxidase,’’ as I onee termed it. As Bayliss (66) states, ‘‘enzymes are merely a particular class of catalysts, considered for convenience apart, owing to the fact that they are produced by living organisms and are for the most part of unknown chemical composition.’ As an enzyme, adrenoxidase could act as an oxidizing cata- lyst without itself being destroyed. Now the oxidiz- ing ferment of Bunge and Schmiedeberg (67), Jaquet (68), Abelous and Biarnés (69) and adrenin give heat reactions very similar to those of adrenin; while Menten (70) also refers to the influence of tempera- ture on the activities of adrenin within fixed limits, a peculiarity of enzymes. SAJOUS 279 The adrenals or other chromaffine tissues would thus only be required to replace actual losses of the enzyme, the residual body asset of which would be conserved as the oxygen carrier and accelerator of the hemoglobin and constantly be re-used, while hav- ing lost its identity as adrenin. This would afford a legitimate nidus for the ‘‘function’’ suggested by MacMunn (71), who, having found haemochromogen in the adrenals, concluded that these organs served to break down worn out hemoglobin and histohaema- tins. From my viewpoint, this process would serve to extract from them what constituents might serve for the elaboration of the adrenal secretory product. Finally, much might be learned by trying to ex- plain all the respiratory phenomena that have been attributed by as many physiologists and clinicians to adrenin in the foregoing pages to a function other than that of pulmonary and tissue respiration. Need I urge in the presence of all these facts that a systematic cooperation between the physiologist and the clinician, each seeking to aid the other through the special knowledge he possesses, would greatly hasten our knowledge of the endocrine glands? Need I urge that all recorded data, physio- logical and clinical—of which the foregoing are but a few on the question treated—carefully tabulated and checked, then coordinated logically, irrespective of any preconceived theory, might open new fields which we would all, working in harmony, cultivate ? The respiration theory is only submitted here as one of the many fields of this kind. It may die a nor- mal death; if it does, we shall at least have learned that the soil in that one area is sterile, and that an- other coordination of data of the many available 280 COORDINATED DATA, ADRENALS may prove more fruitful. Many lines of thought may thus have to be dropped by the wayside, but the day must finally come when success will reward honest effort. Of course, the coordination of all available data is no small task; but it is one to which I hope to de- vote my remaining days, with financial help the nucleus of which is available. All our members will be asked to criticize to their hearts’ content and to contribute from their store of observation or special knowledge, and if the true scientific spirit is shown in suggesting possible criticisms, our Association and its journal ‘‘ Endocrinology,’’ will, I feel confident, prove a blessing to mankind in its far-reaching influ- ence upon our knowledge of disease. REFERENCES Pawlow: ‘‘The Work of the Digestive Glands,’’ Thomp- son’s trans., 1902, p. 46. Josué: Paris méd., 1917, 7, 13. Goormaghtigh: Arch. méd. belges, 1917, Aug. Moltschanow: Rev. del Cire. Med. Argentino, 1912, Nov.- Dee. 5. Paisseau and Lemaire: Presse méd., 1916, 24, 545. 6. Remlinger and Dumas: Annales de méd. de Paris, 1915, 2, 605. 7. Steiger: Cor-Bl. f. schweizer Aerzte, 1917, Apr. 8. Kolsko: Vierteljahresb. f. gerichtl. med., 1914, 47, Suppl. 217. 9. Richards: Guy’s Hospital Reports, 1905, 59, 217. 10. Parhon and Golstein: ‘‘Les Seerétions Internes,’’ 1909, p. 294. 11. Jump, Beates and Babeoek: Arch. Pediat. 1913, 30, 556. 12. Bra: cited by Adams: Practitioner, 1903, 71, 472. 13. Jaboulay: Lyon méd., 1897, 84, 399. 14. Courmont: Congrés de Méd. Interne, Montpellier, 1898. 15. Bohr: Skand. Arch. f. Physiol., 1891, 2, 236. 16. Haldane and Lorraine Smith: Jour. Physiol., 1897, 22, 231. 17. Vaughan Harley: Ibid., 1899, 25, 33. 18. Pembrey: ‘‘Recent Advances in Physiol. and Bioehem- istry,’’ 1906, p. 549. — eats SAJOUS 281 19. Bohr and Henriques: Arch. de Physiol., 1897, 9, 459, 819. 20. Menten: Amer. Jour. of Physiol., 1917, 44, 176. 21. Bohr: Skand. Arch. f. Physiol., 1909, 22, 261. 22. Stoerk and Haberer: Arch. f. mikr. Anat., 1908, 72, 481. 23. Elhott: Quarterly Jour. of-Med., 1914, 8, 47. 24. Gottschau: Arch. f. Anat. u. Physiol., Anat. Abth., 1883, p. 412. 25. Manasse: Arch. f. Path. u. Physiol., 1894, 135, 263. 26. Aulde: Brit. Med. Jour., ae i aes a BF 27. Stilling: Arch. f. path. Anat., 1887, 109, 324. 28. Pfaundler: Sitzungsber. d. k. ‘Akad. d. Wissensch. Mathem., 1892, 150, 3. 29. Cybulski and Szymonowiez: Gazeta Lekarska, 1895, 2nd Ser, 15, 299; Arch. f. d. ges. Physiol., 1896, 64, 97. 30. Biedl: Arch. f. d. ges. Physiol., 1897, 67, 445. 31. Langlois: Arch. de Physiol. norm. et ‘pathol., 1897, 5 série, 9, 152. 32. Dreyer: Am. Jour. Physiol., 1899, 2, 203. 33. Salvioli and Pezzolini: Gaz. degh osped., 1902, Mar. 23. 34, Bert: C. r. de l’Acad. des Sci., 1878, 87, 628. 35. Setschenow and Holmgren: cited by Ludwig: Wiener med. Jahrb., 1865, 21 (i) 145. 36. Zuntz: Hermann’s Handbuch der Physiol., 1882, iv, part 2,.p. 43. 31. ‘Vulpian : C. r. de l’Acad. des sci., 1856, 43, 663. 38. Cybulski: Gazeta Lekarsha, 1895, ‘ond series, 15, 299. 39. Langlois: Arch. de physiol. norm. et path., 1898, 10, 124. 40. Battelli; C. r. Soe. de Biol., 1902, 54, 1435. 41. Abel: Bull. Johns Hopkins Hosp., 1898, 9, 215. 42. Takamine: Therap. Gaz., 1901, 17, 221. 43. Menten: Loe. cit. 44. Jackson: Jour. Pharm. and Exper. Therap., 1913, 4, 291. 45. Januschke and Pollak: Arch. f. exper. Path. u. Pharm., 1911, 64, 205 46. Nice, Rock and Courtright: Am. Jour. Physiol., 1914, 34, 326. | 47. Byelaventz: Russkii Vratch, 1903, ii, No. 7. 48. Bernstein and Falta: Verhandl. d. deut. Kongr. f. inn. Med., 1912, 29, 536. 49. Oliver and Schaefer: Jour. of Physiol., 1895, 18, 230. 50. Reichert: Univ. of Penna. Med. Bull., 1901, Apr. 51. Morel: Le Progrés méd., 1903, 32, 81. 52. Lépine: La Semaine méd., 1903, 23, 53. 53. Menten and Crile: Am. Jour. Physiol., 1915, 38, 225. 54. Menten: Loe. cit. 59. Senator: Charité Ann., 1897, 22, 235. 282 COORDINATED DATA, ADRENALS Addis, Barnett and Shevky: Am. Jour. Physiol., 1918, 46, 39. Trendelenberg: cited by Hoskins: Endocrinology, 1917, 1, 151. Menten: Loe. eit. Barger: ‘‘Biochemistry,’’ 1914, p. 98, cited by Menten: Loe. cit. Battelli: C. r. Soe. de Biol., 1902, 54, 1179. Loeper and Verpy: C. r. Soe. de Biol., 1917, 80, 703. Magnus: cited by Ott and Seott: Jour. of Pharm. and Exper. Therap., 1912, 3, 625. Mulon: Personal Communication. Poehl: J. med. khim. 1 organoterap., 1903, 9, 1-20. Jolles: Minch. med. Woch., 1904, 51, 2083. Bayliss: ‘‘The Nature of Enzyme Action,’’ 1914, p. 139. Bunge and Schmiedeberg: Archiy. f. exper. Path. u. Pharm., 1876, 6, 233. Jaquet: Archiv f. exper. Path., 1892, 29, 386. Abelous and Biarnés: Arch. de physiol. norm. et pathol., 1895, 5 série, 7, 195, 239. Menten: Loe. cit. MacMunn: Brit. Med. Jour., 1888, 1, 233. . ae e C3 4 | i] IODIN AS THE ACTIVE PRINCIPLE OF THE THYROID GLAND W. W. Swingle Department of Biology, Princeton University The relation of iodin to the thyroid gland has been for many years a matter of great interest to clinicians and experimentalists, and it has long been recognized that this substance holds an important place among the constituents of the gland. For several years the writer has been engaged in research on problems involving the thyroid, and this last spring obtained some results in the course of a series of iodin-feeding experiments which should prove of interest to. clinicians and other readers of this magazine. he complete account of these experiments has appeared elsewhere (Jour. of Exp. Zoology, Abstracts, Endocrin, 1918, 2, 200, hence only a summary will be given here. | The problem briefly stated was to test the rela- tion of iodin to the physiological activity of the thy- roid and the general problem of. amphibian meta- morphosis, by feeding this substance and various of its compounds to normal and thyroidless frog larvae. Most of the investigators who have dealt with the problem of the relation of iodin and its compounds to the thyroid, have used mammals as experimental material, forms, which in the author’s opinion, offer no such sure and certain criteria for judging the effects of iodin administration and thyroid activity upon the organism as do frog larvae. The investi- gations of Gudernatsch (since followed by those of Morse, of Lenhart and of Swingle) showed that any ee a 284 IODINE AND THYROID GLAND increased stimulation of thyroid activity, as for in- stance feeding extract of the gland, is at once indi- cated by metamorphic changes in the tadpoles. The idea was to utilize such somatic changes as an index of the effect of iodin feeding upon the physiological activity of the thyroid in the normal animals, and to see if animals whose thyroids had been removed very early in embryonic life would react to iodin. For the experimental work, the larvae of the common leopard frog, Rana pipiens, and the toad, Bufo lentiginosus were used. The animals of all cultures came originally from the same batch of eggs, hence were of the same age. lodin and two of its compounds were used in the original work: iodin crystals, iodoform, and potassium iodide. Since the publication of the original work, an experiment was tried in which potassium iodate was fed. The iodin crystals were ground exceedingly fine and mixed with wheat flour in the proportion of one to one- hundred, enough water was added to make a thin paste; this was allowed to dry at room temperature, and when dry finely crumbled and fed to the larvae. The normal animals with thyroid glands intact, were started upon the iodin, KI, and iodoform diet when they were ten mm. in length; none showed in- dications of limb-buds. Within a few days of the first administration, the larvae fed iodin crystals showed all of the characteristic symptoms of hyper- thyroidism. They had developed limb-buds, growth had ceased, bodies were emaciated, eyes bulged out, and the tails of the larvae showed signs of resorp- tion. The control animals for this culture showed none of these body changes. ~~ ay SWINGLE 285 Shortly afterwards the larvae to which iodoform ras fed showed marked metamorphic changes. Still later, the animals of the KI-fed culture revealed these metamorphic changes, though to a less degree than the animals of the other cultures. The reac- tion was much slower in regard to the time of ap- pearance. Within two weeks of the first feeding of iodin crystals the larvae of the iodin-fed culture had completely metamorphosed. This was true of both toad and frog larvae. The animals used as controls for all of these cultures revealed no indications whatever of metamorphic changes. This same ex- periment with slight modifications in the method of administering iodin and its compounds was carried out with four sets of larvae. The results obtained were the same in all cases. In the meantime, cultures of larvae, the thyroid glands of which had been removed at the four mm. stage, were started on the iodin crystal diet. These animals when first fed were ten mm. in length, and were controlled by other thyroidless and normal larvae of the same age. In a remarkably short time —five to six days,—all of the thyroidless animals showed marked signs of ‘‘hyperthyroidism.’’ The hind legs of the animals had appeared, growth had ceased, bodies were emaciated and eyes bulgy. Within two weeks’ time these thyroidless animals had come to complete metamorphosis. The controls, on the other hand, showed no indications whatever of metamorphic change. Microscopic examination of the thyroidectomized animals failed to show any vestiges of the thyroids, nor were there any signs of accessory glands. PSE PTE Tet. Ee el 286 IODINE AND THYROID GLAND The writer was under the impression at first that perhaps the mixture of flour, iodin and water had produced a substance which simulated the physio- logical action of thyroid secretion. This erroneous idea was duc to the fact that in some previous ex- periments it had been observed that frog larvae are very soon killed when iodin crystals are placed in the container. In order to test the point, whether it was iodin itself or the mixture of flour, iodin and water that accelerated metamorphosis, cultures of normal and thyroidless larvae were placed in weak aqueous so- Jutions of iodin. The solutions were made by plac- ing quantities of iodin in a few cubic centimeters of water and mixing thoroughly. Two ¢c¢. of such a solution added to 500 ¢.c. of water was sufficient to bring about metamorphosis in the experimental an- imals. Normal and thyroidless animals living in such solutions of iodin undergo transformation from the larval to the adult form as rapidly as those fed upon. the flour-iodin mixture. Tests were also made regarding the rapidity of action of the various iodin compounds in accelerat- ing metamorphosis. The results show that iodin crystals bring about the reaction quicker than any of the compounds used; iodoform is slightly less potent than the iodin crystals; potassium iodide is much slower than iodoform, and potassium iodate has practically no effect. Microscopic examination of the thyroid glands of larvae reared in iodin solutions or fed on the iodin-flour mixture from the earliest feeding stage to the time of metamorphosis, shows that the thy- SWINGLE 287 roids of such animals are very much smaller than those of control larvae of the same age and held at the same size by under-feeding. Discussion. The results of the experiments just cited appear to indicate very strongly that iodin is the active principle of the thyroid gland, and that this substance functions within the organism as a hormone itself without the intermediation of the eland. It has been shown by investigators that frog larvae whose thyroid glands have been removed early never develop into frogs, but permanently retain their larval characters. Yet iodin feeding brings about metamorphosis in these thyroidectomized an- imals in an abnormally short time. The fact, too, that the thyroid glands of animals fed iodin from the free feeding stage until metamorphosis, are much smaller and less developed than those of normal an- imals of the same age and size, is further evidence that iodin is the active principle. The function of the thyroid, then, appears to be chiefly that of extracting and storing the physio- logically active iodin, rather than elaborating an active hormone itself. That the tissues of animals are capable of utilizing iodin directly without the mediation of the gland, is shown by the results of feeding iodin to thyroidless larvae. In this connec- tion the results of a series of experiments as yet un- published, may be of interest. The writer has been able to demonstrate that normal blood serum acts as a solvent for iodin crystals to the extent of .00075 ems. per ¢.¢. All of the active substances so far extracted from thyroid tissue contain iodin, the more active they are 288 IODINE AND THYROID GLAND the more iodin they contain. ‘This is clearly shown by Kendall’s Alpha substance reported in a previous issue of this journal. The same principle holds true of goiters. The higher the iodin content of such glands, the greater their physiological activity when fed to lower animals. The work of Hunt and Seidell and of Lenhart is of interest in this connection. The fact that iodin is capable of functioning within the organism without the gland tissue, should prove of interest to clinicians because of its bearing upon iodin therapy in the treatment of toxie goiter. If all of the symptoms of ‘‘hyperthyroidism’’ can be produced in thyroidless frog larvae by over-feed- ing with iodin, it is logical to suppose that the symp- toms of ‘‘hyperthyroidism’’ in man are due to the same cause. BIBLOGRAPHY Kendall, E. C. On the erystalline compound containing iodin which occurs in the thyroid. -Endocrinology, 1917, 1, 153. Swingle, W. W. Experiments with feeding thymus glands to frog larvae. Biol. Bull., 1917, 33, 116. Swingle, W. W. The acceleration of metamorphosis in frog larvae by thyroid feeding and the effects upon the ali- mentary tract and sex glands. Jour. of Exp. Zoology, 1918, 24, 521. Swingle, W. W. The effects of inanition upon the development of the germ glands and germ eells of frog larvae. Jour. of Exp. Zoology, 1918, 24, 545. Swingle, W. W. Studies on the relation of iodin to the thyroid. Part One. (In press.) THE EFFECT OF THE X-RAY UPON THE RESPONSE OF TADPOLES TO THYROID STIMULATION* Carey P. McCord and Carlton J. Marinus Detroit, Michigan INTRODUCTION The experiments carried out by Gudernatsch (1), in 1912 upon the growth of tadpoles after thyroid gland feeding, have been repeated in this laboratory during four summer seasons. In short, Gudernatsch observed that tadpoles whose normal metamorphosis into frogs occupied from three to six months, com- pleted this metamorphosis in five to ten days when small quantities of thyroid gland substance was added one or more times to the living water of the tadpoles. This induced early differentiation into frogs, including all the gross changes normally dis- tributed over several months. The miniature frogs so produced, although apparently anatomically per- feet, were unstable and regularly died after a few days. Tn all essential respects our findings have been in accord with Gudernatsch’s reports. The experiments of this laboratory were extended to include low life forms other than tadpoles and also tadpoles of cer- tain frog species whose metamorphosis normally ex- tends over two or more years. An effort was made to determine the influence of thyroid feedings upon the growth and differentiation of tadpoles whose nat- ural development had been deviated by diverse procedures. *From the Research Taboratories, Parke, Davis & Co., Detroit, Mich. 290 X-RAY THYROID STIMULATION The present report concerns itself with observa- tions made as to the development of thyroid fed tadpoles which had been exposed to the action of the X-ray. Three distinct theories have been advanced to explain the action of the Roentgen ray upon normal tissue cells. One of these adhered to by O. Hertwig (2), and his coworkers (1912), is that the rays exert a specific destructive action upon the chromatin of the cells. Opposed to Hertwig’s hypothesis is the older theory proposed by Schwartz (3), (1903), who concludes from the observation of the destructive action of the Roentgen ray upon the lecithin of egg volk, that the injury to the cells is due to the destrue- tion of the lecithin which they contain. Richards (4), (1914-15), has shown that the activity of various enzymes or ferments, of both ani- mal and vegetable origin, is susceptible to change through the influence of Roentgen rays. He con- cludes from his experiments that, ‘‘a short radiation has the effect of accelerating the activity of these enzymes (diastase and pepsin), while longer radia- tion is inhibitive. Between these strengths les a point at which the radiation is non-effective.’? His observations on pepsin and diastase have since been extended to include other enzymes, the results all tending to confirm his original conclusions. He ad- vances the theory, therefore, that, ‘‘life processes are subject to marked change under the influence of radiation, a slight exposure being accelerative in most cases, while a more intense treatment is inhibitive or destructive. As a causal factor in these effects, the demonstrable injury to the chromatin of the cell is undoubtedly important; but there are also good evi- MeCORD AND MARINUS 291 dences that the modifiability of enzymes under the action of the rays likewise plays a considerable part either directly or indirectly in the resulting injury.”’ MATERIALS AND METHODS The tadpoles collected to participate in these experiments conformed within the acceptable lmits in weight, length and in stage of development. These were maintained in large shallow trays under good condition as to light, air and aeration of living water. The food, apart from thyroid gland materials, consisted of green algae supplemented at intervals with small quantities of desiccated beef liver. Tadpoles of the species Rana eantesbiana (bull- frog) exclusively were used. The individuals of this species normally live for at least two years in the larval state. This fact permitted the use of larvae representing two widely different stages of develop- ment. The younger group (Experiment A) was composed of tadpoles approximately one year old. At this stage the individuals exhibited no signs of differentiation into the adult form. The second group (Experiment P) was composed of tadpoles not quite two years old. These tadpoles would under the nat- ural conditions have completed their metamorphosis before the end of the summer. The controls in this experiment actually did complete their metamorpho- sis, but long after the conelusion of the experiment. In both experiments (1st and 2nd year groups) the tadpoles were divided into four equal and similar lots. Two lots in each experiment were then subjected to the rays from a Coolidge tube according to the following standardized formula :* *The tadpoles were irradiated by Dr. George C. Chene, Detroit. Our thanks are due him for his courtesy. 292 X-RAY THYROID STIMULATION Experiment A, Experiment D. CUEDent a ey eyecantstotpe eee trste iene receess 6 milliamperes 12 milliamperes Spawls Galpenert Page a oters: «ke ates 8 inches 7 inches Distance from Anode......--.:... 12. inches 12 inches FEIT ea ee Sie, 2-8 oe eee Cee 2, minutes 4 minutes Tadpoles of Experiment A were irradiated a second time one week later, under identical conditions except that the current was doubled. In each experiment one irradiated group and one untreated group were placed on thyroid feedings while the second irradiated group and the second control group were kept on the desiccated liver and algae diet. The thyroid was administered by secat- tering 100 mgms. of the commercial desiccated prod- uct in the living water. After the death or complete metamorphosis of all the thyroid-fed tadpoles of Experiment A, and tabu- lation of the accrued data, the two remaining control groups were again divided. Half of each group was placed on thyroid treatment identical with that deseribed above. This second feeding was started one month after the irradiation of the tadpoles. The alterations in size and shape of the tadpoles incident to their development were recorded by means of a method of ‘‘shadow photography.’’ This procedure afforded a permanent and relatively accu- rate record of the growth. For the purposes of carry- ing out this photographic mensuration a temporary dark room was constructed near the tables containing » trays of tadpoles. In this dark room was placed a small shallow rectangular glass container (2”x4’’) with a smooth flat bottom. Photographie printing paper was cut in such size as to fit exactly into the rectangular container. One piece of this paper was placed in this container sensitive side up. Super- imposed upon the sensitive paper was a mask of MeCORD AND MARINUS 293 transparent celluloid upon which had been printed lines at millimeter intervals. Representative tadpoles to be measured were taken from their trays, placed in small beakers in a constant quantity of clear water. To this was added a few drops of chloroform (two to ten, depending upon the size of the tadpoles) to pre- vent their moving while being photographed. As soon as the tadpoles were motionless they, together with the water, were poured into the rectangular chamber previously prepared. Directly above the chamber, at. about the height of 18 inches, a high power nitrogen electric lamp was placed to whose light exposure was made for two or three seconds. The motionless tadpoles resting on the millimetered mask served as a negative and the linear dimensions were directly printed out on the sensitive paper. The chloroform was found to be harmless for all except very young tadpoles. It is necessary however that immediately after being photographed the tadpoles be removed from the chloroform water. This method of recording dimensions is much less tedious than actual photography and is more rapid and less irk- some than the actual measurement with dividers at frequent intervals of many hundreds of tadpoles. TECHNICAL DATA AND COMMENTS The effects of thyroid feeding on normal tadpoles varies with the age of the individuals. This is to be expected in view of the nature of the changes induced. In our experiments with two-year-old tadpoles (Rana cantesbiana ) which had reached the stage in develop. ment immediately preceding the initiation of meta- morphosis, thyroid feeding served simply to induce a premature and accelerated differentiation. Thyroid- treated tadpoles differentiated into normal frogs, 294 X-RAY THYROID STIMULATION wholly indistinguishable from the controls. In the case of one-year-old tadpoles, thyroid feed- ing was invariably followed by the death of the indi- viduals. Certain somatic changes occurred before death, which were obviously similar to those changes which take place in the metamorphosis of older indi- viduals. The alterations which were macroscopically observable occurred in approximately the following order: 1. Marked diminution in general size. 2. Alteration in the shape of the body, the rounded, well-fed larval shape giving way to the slen- der, trim adult form. 3. Elevation-of the eye-balls above the dorsal surface. 4. Increase in width and size of the mouth. 5. Acceleration of growth of hind legs. 6. Thinning and eventual breaking through of the ventral body wall at points corresponding to the future site of the fore legs. 7. Noticeable growth of the fore leg buds. 8. Disappearance of the ‘‘fin’’ from the tail. 9. Shortening of the tail. It was observed that the tadpoles all reached a certain stage in this abnormal metamorphosis, at which point death occurred. The examination of a large number of specimens preserved shortly after death demonstrated that all were very similar in the extent to which the changes outlined above had occurred, and that the date of death affords a valuable criterion as to the reaction of the tadpole to thyroid treatment. This fact has been noted before and other workers have taken the time of death of the treated tadpoles as the end-point in the quantitative estima- rare MeCORD AND MARINUS 295 tion of thyroid activity. (Marine and Rogoff, 1916, C. H. Lenhart, 1915.) The following table indicates that in experiment A (one-year old tadpoles) the irradiated tadpoles reacted earlier than did those that were unexposed. At the outset of the experiment equal numbers (17) of tadpoles composed each of the four lots to be compared. Under thyroid stimulation both the nor- mal tadpoles (A) and X-rayed tadpoles (A:X_) which were thyroid fed responded to thyroid stimulation and died upon attaining to a certain phase of meta- morphosis, however, the X-rayed tadpoles earler attained to this point. TABLE I. A,X A,X DATE A Thyroid iN Control Thyroid plus X-Ray Control plus X-Ray 5-20 17 17 17 ily¢ 5-21 Vi 11 17 li 5-24 (17) 14* 8 17 17 5-25 11 + 17 17 5-26 4 il 17 17 5-29 4 0 17 17 5-31 3 0 17 17 6-1 2 0 17 17 6-5 0 0 wy 17 *Three killed for photographing. The first death in the non-rayed (A) group occurred four days after the first death in the irra- diated group, or when the irradiated tadpoles had been reduced to a fourth of their original number. So also the last survivor in the non-rayed group lived five days longer than did the last of the irradiated group. The exposure of tadpoles to the action of X-rays in some unknown manner determined an increase in the rapidity of their reaction to thyroid stimulation. This conclusion is supported by photographic evidence. In figure I are shown views of average individuals from groups A: and A-X. (Thyroid-fed 296 X-RAY THYROID STIMULATION and thyroid fed, X-rayed, respectively.) These pho- tographs were made on the same day and under identical conditions of focus, and of distance of the object from the lens. FTG al Figure I. Photographs (made at the same time) of average tadpoles from group AsX: (thyroid-fed and X-rayed) and from group Ai, (thyroid-fed but not exposed to X-rays). The relative size of the tadpoles may be esti- mated from the millimeter lines included in the one photograph. The metamorphosis of the individuals in A.X is obviously further advanced than those in A;. This is indicated by the following points: 1. Smaller size. 2. More triangular shape. 3. More prominent eye balls. 4. Larger mouth. o. Shorter tail. 6. Presence of fore-leg buds (discernible as MeCORD AND MARINUS 297 small white spots in the center of the dark area of skin rarefaction). Under the binocular microscope fore leg buds were also discernible on the tadpoles of A. They were much smaller, however, than on the other tadpoles. FIG. 2 Figure II. Drawings three times natural size of average tadpoles, illus- trating the differences in the degree of metamorphosis attained at a certain iime by members of groups A; and AoX, respectively. Groups A; and A:X, which had not been thyroid- fed and which had exhibited none of the phenomena of metamorphosis were now divided and half of each group placed on thyroid feedings. As before, the 298 X-RAY THYROID STIMULATION X-rayed tadpoles began to differentiate before’ the unexposed individuals showed any signs of change. The difference was not so marked in this case, undoubtedly because of the time (30 days) which had elapsed since exposure to the X-rays. It is significant that the irradiation was, in some measure, effective after such an inteival of time. It might be maintained that the changes induced in young tadpoles by thyroid feedings are so abnor- mal as to furnish no dependable index to their reac- tivity. For this reason tadpoles which would normally metamorphose within the space of a few months, were subjected to the same treatment. Table II gives the relative condition of the tad- poles July 2nd, at which time the thyroid-fed tadpoles were in the midst of the metamorphosis process. The results are in accord with those already outlined. TABLE II. ae P, P; Py State of Metamorphosis Thyroid X-Ray X-Ray Thyroid Number of tapoles(//2)i--. .->..--- - 12 5 1] 19 Number of tadpoles with 4 legs...... 3 3 0 0 Number of tadpoles with 3 legs...... 2 ] 0 0 Number of tadpoles with 2 legs. ..... 7 ] 1] 19 Per cent of tadpoles with 4 legs...... 25% 60% 0% 0% Per cent of tadpoles with 3 legs...... 16.7% 20% 0% 0% Per cent of tadpoles with hind legstonl yer \as- cere ee ee oe oe 58.3% 20% 100% 100% In the tadpoles entering into this experiment, no developmental differences were detectable in group P., which had been X-rayed, and in group P:, which were normal. That is, the X-raying of the tadpoles brought about no demonstrable alteration in growth- differentiation processes. Both the X-rayed and normal tadpoles completed their metamorphosis at the anticipated time. Also, no differences were observable in the rate of response to thyroid feeding in the X-rayed tadpoles, group P., and the non-rayed MeCORD AND MARINUS 299 thyroid-fed tadpoles, group P:. The metamorphosis of both groups was hastened, but, equally so, indi- viduals composing both groups completed their meta- morphosis and survived. In so far as the results of observation on this small number of test animals permits, it is inferred that the exposure to the X-ray exerts no gross effect upon the process of metamor- phosis, either in normal tadpoles or in thyroid-fed tadpoles. The observation that the irradiation is: without demonstrable effect upon normal tadpoles is impor- tant in considering the mechanism of the reaction produced upon thyroid-fed tadpoles. Several observ- ers have shown that following intensive exposure to X-rays there may be found a slight increase in nitrogen metabolism of normal animals. (Baermann and Linser (5), 1904, Benjamin and Van Reuss (6), 1906.) If the results recorded in tliis paper are due to the direct action of the rays upon metabolism, the same phenomenon also occurs in those tadpoles which received no thyroid material. The occurrence of changes in the metamorphosis of the thyroid-fed groups only, is an indication that these changes are due to an altered susceptibility on the part of the tadpoles to the thyroid hormone. This interpretation is apparently in keeping with Richard’s theory of the mode of action of the Roent- gen rays. He states that a small dose of the rays serves to increase the activity of certain, and presum- ably of all, enzymes, while large doses produce the opposite effect. In our experiments, weak irradia- tion of the tadpole increased the activity of a normal hormone (thyroid), administered subsequent to the irradiation. According to Richard’s theory, strong 300 X-RAY THYROID STIMULATION irradiation should decrease the activity of the hor- mone when given under identical conditions. In the event that further experiments prove that large doses of X-rays produce an effect opposite to the results here recorded, it may be inferred that the thyroid hormone normally acts in conjunction with the intiacellular enzymes to produce the phenomena commonly associated with thyroid activity. Such an interaction has often been postulated by writers on the thyroid gland, but experimental evidence has hitherto been lacking. SUMMARY Selected tadpoles were subjected to the action of Roentgen rays in small amounts. Certain individuals were then treated with preparations of thyroid gland and the rate of their metamorphosis compared with the metamorphosis rate of (1) normal tadpoles, of (2) thyroid-fed tadpoles which had not been irradi- ated, and of (3) irradiated but not thyroid-fed tad- poles. The results of our experiments indicate that irradiation is without apparent effect upon normal tadpoles, but determines a slight but distinct increase in the susceptibility of young tadpoles to thyroid stimulation. REFERENCES TO LITERATURE CITED (1) Gudernatseh (J. F.) Areh. f. Entwickmech. d. Organ- ismen., 1912, 35, 457. (2)~ Hertwig(O:.G.)- and .GP.) -Arch.-£ Makers Anat.) 19a Tl, 2.. Abt., 1-95, 4 pl. (3) Sehwarz (G.) Arch. f. Physiol., 1903, 100, 532. (4) Richards (A.) Am. Jour. Roent., 1915, 2, 908. Am. Jour. Phys., 1914, 35, 224. Ibid, 1915, 36, 400. (5) Baermann (G.) and lLinser (P.) #=Miinchen. Med. Wehnschr., 1904, 51, 996. (6) Benjamin (E.) and v. Reuss (A.) Miinehen. Med. Wehnschr., 1906, 8, 1862. a THE USE OF ADRENAL PRODUCTS __IN ADDISON’S DISEASE* Judson Daland, Philadelphia Lieut. Commander M. C.,U.S. Navy Male, aged 40, American, married, was admitted to the Medico Chirurgical Hospital in October, 1911, complaining of extreme weakness, almost like that of approaching death, attacks of dangerous collapse, dyspnoea, loss of weight and marked constipation. The family history was negative. He had a mild attack of smallpox at the age of 26; diphtheria at the age of 10 and pneumonia at the age of 27 years. Prior to 1911 brownish spots were noted on the skin of the face, neck and hands, which grad- ually increased in size and depth of color. In July, 1911, weakness was first observed which gradually increased, and during the preceding five years there had been a gradual loss of flesh. During 1911 he lost weight rapidly and weighed slightly less than 100 pounds when admitted to the hospital; whereas im 1906 he weighed 135 pounds. In August, 1911, while at work in his office he suf- fered a collapse, which recurred in five minutes. From time to time chills followed by fever were complained of, the temperature occasionally rising to 103° F. From the age of 11 to 14 he worked in the coal mines as a breaker boy and later in the switch yard. From the age of 34 to 43 he was a street car conductor, and is now an official in the Street Carmen’s Union. For many years he chewed daily from two to three ounces of tobacco and smoked two or three cigars; *Read before the Association for the Study of Internal Secretions, Chicago, June 10, 1918. 302 OPOTHERAPY, ADDISON’S DISEASE drank coffee to excess but avoided alcohol. Habits of eating and sleeping were markedly irregular. Physical examination revealed emaciation; visi- ble carotid and epigastric pulsations; diffuse apex beat and prolongation of the first sound of the heart; pulse slow, very weak and easily extinguished by slight pressure; radial and temporal arteries scle- rosed; marked spinal curvature to the left from the first to the fifth dorsal, and to the right from the fifth dorsal to the second lumbar vertebra, and a roent- genogram showed the signs of ostitis, rather than tuberculosis. There was increased fremitus and impaired resonance over the apices of the lunes cor- roborated by an X-ray examination and interpreted as indicating healed tuberculosis. The von Pirquet test was positive. The right kidney was movable and slightly tender on pressure. The renal efficiency test showed the first hour 52%, the second hour 28%, total 80%. There were pigmented areas of the skin varying in color from hght to dark brown, more marked on exposed surfaces, particularly the neck and face, also on the thighs, about the nipples and umbillicus and the scapula where the suspenders exerted pressure. The pigmented areas of skin dis- tributed over the forearms and hands were of mahoeg- any or bronze color, but pigmentation was absent over the spinal region which was subject to the pres- sure of the weight of the body while lying in bed. There were areas of leucoderma over various parts of the body, especially over the right temple, where the hair had turned white, and these areas seemed dryer than the surrounding skin. There were marked pruritis and numerous seratch lesions. The muscles were markedly flabby, relaxed and atrophied. There ee a DALAND.- 303 was a negative history of venereal disease and a nega- tive Wasserman reaction. The temperature was continuously subnormal, at times 96°F. The pulse varied between 56 and 98 per minute; the heart was overacting. Examination of the blood revealed 69% erythrocytes, 74% hemaglobin and 11,200 leucocytes, of which there were 65.5% poly- morphonuclears, 21.8% large lymphocytes and 8% small lymphocytes. Later a mild eosinophilia occurred which was non-parasitic and toxic in origin. October 21st in the recumbent posture the pulse was 60 per minute, systolic pressure 80 mm. and dias- tolic 60 mm. Numerous urinalyses gave negative results. | The following day 1 drop of a 1 to 1000 adrenalin chlorid solution was given thrice daily.* After the third dose no change was noted in the blood pressure. After four doses of two drops each had been given, the systolic pressure was 90 mm., the diastolic 60 mm. and the patient volunteered the information that he felt somewhat stronger. On October 25th three drops of adrenalin chlorid solution were given four times daily, and the systolic pressure rose to 110 mm. and the disastolic remained 60 mm. From October 25th to November 1st, 1911, five drops of adrenalin chlorid solution were administered three times daily, after which the systole pressure was but 100 mm. and the diastolic 70 mm. Then followed an interval of five days during which no medication was given, at the end of which time the systolic pressure was 90 mi. On November 13th, 1911, 8c.c. of an infusion of digi- talis was given four times a day. After ten doses had been administered the systolic pressure was 110 mm. *The adrenalin in all cases was administered hypodermatically. Tt EAE ae SS I ES SEL NS 304 OPOTHERAPY, ADDISON’S DISEASE and the diastolic 80 mm.; the first sound of the heart was somewhat blurred and the second sound at the apex was reduplicated. The digitalis was withdrawn and four days later the systolic pressure was 98 mm. and the diastolic 70 mm. On November 24th, 1911, adrenalin chlorid was given in gradually increasing doses and on December 2nd, 11 drops thrice daily were administered, causing the heart to beat violently, shaking the entire chest, and a faint, soft, mitral sys- tolic murmur became audible. The systolic pressure was 112 mm. and the diastolic 88 mm. Adrenalin chlorid was discontinued, and four days later the murmur had disappeared, but there was marked reduplication of the second sound at the base of the heart; the systolie pressure was 110 mm. and the diastolic 90 mm. The administration of adrenalin chlorid slightly raised the blood pressure, when therapeutic - doses were given, but toxie doses were dangerous, causing cardiac dilatation. Digitalis only slightly increased the blood pressure. In January, 1912, 15 grains of adrenal gland (B. W. & Co.) were administered three times daily. January 15th, the systolic pressure was 110 mm., the diastolic 88 mm. and the blood examination revealed a marked increase in red cells, and a disappearance of the leucocytosis and eosinophilia, possibly due to adrenal extract. Until discharged from the hospital in January, 1912, the systolic blood pressure varied from 102 to 110 mm., while the diastolic remained constant at 80mm. Upon leaving the hospital he had. gained 10 pounds in weight, strength was greatly increased, and the profound malaise, dyspnoea, and syncopal attacks had disappeared. Soon after re- DALAND 305 turning home he endured a serious mental strain in conducting a carmen’s strike, apparently with no ill effect, and believing himself cured and contrary to advice discontinued the adrenal gland extract. Soon thereafter profound weakness, dyspnoea, and one attack of collapse occurred. He consulted Dr. Mar- tin T. O’Malley of Scranton, Penna., who as a student happened to attend the clinic when this patient was presented to the class, and remembering the patient advised the prompt use of adrenal gland extract in 15 grain doses thrice daily. Marked improvement was soon observed. Later the patient returned to his physician complaining of tachycardia, painful cramps in the muscles of the extremities, pain in the chest, dyspnoea, pulse from 110 to 140 per minute, occasional shght rises in tem- perature, Insomnia, ocular fullness and staring eyes. At this time the patient was supposed to be taking one dram of adrenal extract thrice daily, but investiga- tion revealed that the druggist had dispensed thyroid extract instead of suprarenal extract. Improvement promptly followed the omission of the thyroid extract and the substitution of adrenal extract. Experi- mentally, toxic doses of adrenal extract ers. 90 t. i. d. were administered, which caused mental and physical weakness, irritability and insomnia, which disap- peared when the dose was diminished. Maximum benefit was secured from 35 grains of adrenal extract thrice daily. During 1914 he was able to perform work with no discomfort except when the use of adrenal extract was discontinued. In January, 1914, an attack of pheumonia supervened, and for a long time the patient complained of general weakness, exhaustion 306 OPOTHERAPY, ADDISON’S DISEASE after light exertion and coldness of the hands and feet even on the hottest days. During 1915 an attack of pleurisy occurred; otherwise he felt well while taking the adrenal extract; but if it was omitted he began to lose energy, was unable to work, complained of subjective and objective coldness of the extremi- ties, profound weakness and recurring collapse. Physical examination in January, 1915 and 1917, gave the same results as when first examined, except that strength had greatly increased. On January 15th, 1917, the systolic blood pressure was 95 mm. and the diastohc 60 mm. Blood examination showed the erythrocytes 64% , hemaglobin 60%, leucocytes 6,800; polymorphonuclears 61.6%, large lymphocytes 7.3%, small lymphocytes 25.6%, eosinophiles 3.6% baso- philes 1.6%. | In October, 1917, the patient died of asthenia, following neglect, and unfortunately an autopsy could not be secured. BLOOD PRESSURE OBSERVATION Date Pulse Sys. Dias. Remarks: 10-21-11 60 80 60 10-22 56 80 50 3 doses adrenalin each gtts. i. Blood 10-23 64 90 60 pressure recorded one hour after 10-24 64 110 60 third dose. 10-25 60 90 60 4 doses gtts. il. 10-27 60 110 60 At bedside; 4 doses gtts. iil. 10-30 72 100 70 Adrenalin etts. iv. 11-1-11 68 100 70 11-16 76 110 80 Adrenalin gtts. v. Left hospital for a few days. 11-17 76 110 80 10 doses of infusion of digitalis dr. iv. 11-19 78 98 65 Reduplication. 11-20 76 98 70 No digitalis for 24 hours. 11-24 72 105 90 11-25 84 110 90 11-26 12 100 80 Adrenalin gtts. ii. and iii. 11-27 [ve 106 $2 Adrenalin 2 doses, gtts. iv. 11-28 12 98 78 Adrenalin 2 doses, gtts. v. 11-29 72 104 80 Adrenalin 2 doses, gtts. vi. 11-30 72 104 84 12-1-11 76 108 90 Adrenalin gtts. viii. 12-2 68 112 88 12-3 Adrenalin gtts. ix. DALAND 307 Date Pulse Sys. Dias. Remarks: 12-4 84 110 86 Adrenalin gtts. xi. Faint mitral systolic murmur. Pulse irregular; distinct mitral sys- 12-5 88 96 76 tolic murmur; reduplication; ad- 12-6 80 108 84 renalin omitted. 12-7 96 110 82 12-8 88 110 90 Heart regular; murumur less marked. 12-10 84 106 82 12-11 54 110 84 No murmur; reduplication. 12-12 54 122 90 12-13 76 108 86 teduplication. 12-14 92 106 86 Faint mitral systolic murmur; marked reduplication. 1-15-12 60 95 60 1-16 72 95 70 Returned home for one month. [=17 90 80 No murmur or reduplication, 1-18 90 70 1-19 85 70 1-20 85 70 1-21 78 85 72 1-23 87 75 ]-24 95 - 79 1-25 95 75 1-29 95 80 1-30 95 80 1915. 1-5-15 74 110 85 1-11 64 160 70 1-15 70 110 80 1-16 74 105 80. 1-17 70 105 80 1-18-15 70 105 80 1-20 72 100 80 1917, 1-5-17 92 70 1-15 76 95 60 EXAMINATIONS OF THE BLOOD 1911. Erythrocytes Hemoglobin Leucocytes Oct. 26. 69% 74% 11,200 Nov. 13. 76% 64% 10,600 Polymorphonuclear 66.5% Large Lymphocytes 21.3% Small Lymphocytes 8.0% Eosinophiles 4.0% Basophiles 0.5 Noy. 20, 17% 75% 11,000 E ; 1912. Jan. 16 85% 98% 6,800 1915. Jan. 5 82% 86% 8,000 1917. Jan. 15. 64% 60% 6,800 Polymorphonuclear 61.6% Large Lymphocytes 7.3% Small Lymphoeytes 25.6% Eosinophiles 3.6% Basophiles 1.6% 308 OPOTHERAPY, ADDISON’S DISEASE In view of the existence of the classic symptoms of terminal Addison’s disease it is probable that the suprarenal gland had almost entirely disappeared probably due to the advancing tuberculosis as this is the most common of all causes; and further- more the apices of the lungs showed evidence of healed tuberculosis and the von Pirquet test was positive. The tender right kidney and the ankylosis of the vertebral joints may have been due to tuber- culosis. When first seen in October, 1911, it was believed that he was in danger of death from collapse at any time; and under the best circumstances he was expected to die within a year, whereas he did not die until six years after treatment was begun. It is fair to assume that the prolongation of life was secured by the administration of appropriate doses of the suprarenal gland extract. It is interesting to note that the adrenalin was only slightly beneficial and in toxic doses produced cardiac dilatation; that divitalis in therapeutic doses produced only slight benetit and in full therapeutic doses was detrimental. It would appear that toxic substances manufactured im the course of Addison’s disease may produce leucocytosis or eosinophilia, which disappeared apparently due to the influence of adrenal extract. The influence of toxic doses of thyroid extract in one suffering from Addison’s disease was an interesting involuntary experiment. This case illustrates that marked increase in vitality and strength may be secured by suprarenal extract without as great an increase in the blood pres- sure as would be expected. ABSTRACTS 220. (ADRENAL) Two cases of suprarenal disease. Osborne (O. T.), Am. J. Med. Se. (Phila.), 1918, 156, 202-5. Two cases are described. In the first pigmentation and circulatory weakness were unusually pronounced. Under treatment with adrenal and pituitary tablets the circulation temporarily improved and the pigmentation greatly decreased. The patient died shortly after. Autopsy showed complete de- struction of the adrenals. In the second case pigmentation also was very marked. Under treatment with adrenal tablets and iron the pigmentation largely disappeared and the circulation and weight improved. The prognosis was regarded, however, as bad. The author considers that the poor circulation did not alone account for the marked asthenia present in both cases, . but that the weakness was partly intrinsic in the muscles. —R. G. H. 221. (ADRENALS) Antibody production after partial adren- alectomy in guinea pigs. Gates (KF. L.), Jour. Exp. Med. (Balt.) 1918, 27, 725. Experimentally it is possible to remove from three-fourths to seven-eighths of the adrenal tissue of guinea pigs without causing symptoms of adrenal insufficiency. In order to deter- mine antibody production after partial. adrenalectomy guinea pigs were immunized to bacillus typhosus or to hen corpuscles at varying intervals before or after operation, and the curves of antibody formation traced for two to three months after immunization. Comparisons with antibody curves of control animals similarly immunized failed to show that adrenalectomy had any influence upon the rise or persistence of antibodies in the blood. Acute adrenal deficiency was not deemed necessary. If the adrenal glands were the site of antibody formation or played an essential part in immunity processes, it does not seem probable that the small remainder of adrenal tissue would effect quantitatively the antibody response to a given antigen infection as do the entire normal glands. Therefore, not only are the adrenal glands not one of the important sources of typhoid agglutinins, or of hemoagglutinins or hemolysins, but they play no essential part in the mechanism by which these antibodies are produced and maintained in the body.—H. W. 310 ABSTRACTS 222. (ADRENALS) ‘‘Le role des surrénales dans l’action du pneumogastrique sur le coeur.’’ (The role of the suprarenals on the action of the vagus nerve on the heart). Roger (H.) Jour. de physiol. et de path. gen. (Paris), 1917, 17, 187. Roger removed both suprarenal glands of the rabbit by laparotomy, then after an interval of about one-half hour stimu- lated the peripheral stump of one divided vagus nerve. Elee- trical stimulation produced a more pronounced vagal inhibition of the heart and lowering of the blood pressure than is pro- duced in controls from which the suprarenals have not been excised. The cardiac escape from vagal inhibition was later than normal and without the usual secondary rise of blood pressure above the normal level. On the slow and continuous intravenous injection of epinephrin, in a concentration and rate so adjusted as to produce no change in blood pressure or heart rate, vagal stimulation in the depsulated rabbit produced typi- cally normal responses: The author believes that the interven- tion of the suprarenal glands in the normal animal is respon- sible for the progressively diminishing effects of repeated vagal stimulations on the heart rate and blood pressure and for the secondary rise in blood pressure following vagal inhibition.— AS Se Te 223. (ADRENALS) Sulla funzione delle capsule surrenali. (On the function of the adrenals.) Pisani, from an article of Roger. Presse méd. Nov. 22, 1917, Rivista crit. di clin. med. (Firenze) 1918, 19, 19. Under the influence of a violent nervous impression a sud- den hyperfunction of the adrenal medulla is found with con- sequent increased blood pressure. If the adrenals were previ- . ously removed there is marked and steady hypotension. The excitation of the vagus, which determines a sudden, but tem- porary bradycardia in normal rabbits, causes a severe and durable bradycardia if the adrenals are previously removed. This would signify a reaction against the action of the vagus determined by the adrenals, which would bring forth a pre- dominating action of the sympathetic. The problem though is not always so simple, since the same author found out that the black pigment of the adrenals is antagonistic to the action of the adrenalin.—G. V. 224. (ADRENALS) The influence of certain conditions on the rate at which epinephrin is liberated from the adrenals into the blood. Stewart (G. N.) and Rogoff (J. M.). Am. Jour. Physiol... (Balt.), 1917, 42, 585-86. ABSTRACTS 311 Data elsewhere reported. See abstracts in this journal, 1917, 1, 348; 1917, 1, 508; 1918, 2, 54; and 1918, 2, 157.—L. G. K. 225. (ADRENALS) The physiology of the melanophores of the horned toad, Phrynosoma. Redfield (A. C.) Jour. Exp. Zool. (Phila.), 1918, 26, 275. Stimuli from the thoracic cord are carried to the adrenals and eause the secretion of adrenin which is carried: by the cir- culation to the melanophores in the skin. This adrenin helps control the movement of pigment granules of the melanophores in the changes of color which the animal undergoes at various times.—E. R. H. 226. (ADRENALS) Uber die nach zentraler Reizung zur Storung des Kohlehydratstoffwechsels fihrenden Vorgange. Eine kritische Studie zur Frage: Zuckerstich und Neben- nieren. (Disturbances of carbohydrate metabolism produced by central lesions.) Kahn (R. H.) Pfliiger’s Archiv (Bonn), 1917, 196, 326-394. Experiments dealing with the disturbances of carbohy- drate metabolism produced by central lesions—diabetie pune- ture, ete.—may be grouped in 4 elasses, wrth the following main results: (1) Extirpation of both adrenals. Rabbits sur- vived many months, and subsequent diabetic puncture was not followed by glycosuria, although the glycogen content of the liver was ‘normal. Hyperglycaemia is not produced in such animals by CO poisoning or by diuretin, nor do they exhibit emotional or salt glycosuria. Salt glycosuria is diminished in dogs and unaffected in cats. (2) Chromaffin and adrenaline content of the suprarenals. The adrenal gland extirpated after diabetic puncture exhibits distinct loss of chromaffin substance and adrenaline compared with the control adrenal removed be- fore the puncture. Previous section of the corresponding splanehnic nerve in the above experiment protects the adrenal from the effect of diabetic puncture. The same phenomena after diabetic puncture are seen in the eat, ape, and dog. Cats and dogs exhibit loss of chromaffin tissue and adrenaline in the suprarenals after asphyxia and CO poisoning. The above changes persist for a considerable time after diabetic puncture and CO poisoning in rabbits and birds. The chrome affinity of the paraganglia of the abdominal aorta is diminished for a con- siderable time after diabetic puncture. (3) Nervous isolation of the liver. Section of the nerves and vessels to the liver, with the exception of the portal vein, is still followed by hyper- 312 ABSTRACTS glycaemia in half the cases, although the conditions are ex- tremely unfavorable for its occurrence. Isolation of the liver and the right adrenal from the central nervous system, leaving the connections of the left adrenal intact, was almost always followed by pronounced hyperglycaemia. (4) Adrenaline con- tent of the blood. Adrenaline cannot be detected by the biolog- ical method in blood vessels remote from the suprarenal veins after diabetic puncture and other central nervous excitants or after active (1.e., which produce glycosuria) subeutaneous in- jections of adrenaline. Blood from the vena cava opposite the suprarenal veins has an increased adrenaline content after diabetic puncture, asphyxia, ete. There is no definite increase of blood-pressure after active subcutaneous injection of adrena- line or diabetic puncture. A eritical survey of all the facts suggests that certain ele- ments in the brain maintain a continual tonus in the liver cells via the splanchnies and the peripheral ganglia in the abdomen. This neurogenic tonus is increased by central stimulation (diabetic puncture, ete.). Other elements in the brain near to the above are to be regarded as secretory nerve centres for the chromaffin tissue and particularly for the adrenals. Their stimulation leads to an increased output of adrenaline, which reaches the liver cells by the portal vein and hepatie artery. Excitation travels via the splanchnic and peripheral sympa- thetic ganglia or direct. Stimulation of the central nervous elements causes simultaneous increase in the neurogenic tone of the liver cells on the one hand, and an increased inner secre- tion of the chromaffin tissue on the other. Both together cause glycogen mobilisation with hyperglycaemia and glycosuria. Increased tonus of the liver cells is not a sine qua non for the disturbanees of carbohydrate metabolism, however, and simi- larly under favorable conditions increased tonus alone is suffi- cient to produce abnormal glycogen cleavage in the liver and shght hyperglyecaemia.—Physiol. Abst., 1918, 3, 130-31. 227. (ADRENIN) Adrenalin content of suprarenals after death from beriberi. Ono (S.) Tokyo Igakukai Zasshi, 1917, 31, 1-10. Jap. Med. Lit. (Seoul), 1918, 3, 26. On the basis of the post-mortem examination of ten acute beriberi cases, and of two which occurred during pregnaney, the author finds a medullary hypertrophy of the suprarenal and an inereased adrenalin content. The chemical examination was made by the Comessatti method and the average for the left gland was 14.96 me. It is as yet unknown what relation exists between the clinical manifestations of beriberi, especially ABSTRACTS 313 of the acute type, and this adrenalin-hyperfunction.—Quoted. See No. 97, p. 162, Vol. I] Endocrinol. 228. (ADRENIN) Adrenalin injections, and their effect upon the viscosity of the blood. Yamada (S.), Chugai Iji Shimpo, 1917, No. 893, pp. 669-75. Jap. Med. Lit. (Seoul), 1918, 3, 23. A rise in the viscosity of the blood was noted about 10 to 30 minutes after the injection of adrenin, which gradually de- creased again in a few minutes. After a second injection the reaction occurred more slowly, in 50 to 80 minutes. The re- action was not constant in all the persons examined.—Quoted. 229. (ADRENIN) A method for maintaining an artificial cir- culation through the tibia of the dog, with a demonstration of the vasomotor control of the marrow vessels. Drinker (C. K.) and Drinker (K. R.). Am. Jour. Physiol. (Balt.), 1916, 40, 514-521. A method of perfusing bone marrow is described, and the existence of vasomotor nerves to the marrow is demonstrated. Electrical stimulation of these nerves or the injection of epine- phrin into the perfusion fluid causes vaso-constriction. In one case after the administration of ergotoxin phosphate ‘‘a slight but rather doubtful degree of active dilatation was secured.”’ The authors do not consider this reliable evidence for the ex- istence of an active dilator mechanism.—lL. G. K. 230. (ADRENIN) Constriction from adrenalin acting upon sympathetic and dorsal root ganglia. Hartman (F. A.), Kil- born (L. G.) and Fraser (L.), Am. Jour. Physiol. (Balt.), 1918, 46, 521-525. It was shown by the methods used in previous researches (see abstracts in Endocrinol., 1917, 1, 510, and 1918, 2, 160, abst. 91) that adrenalin not only causes dilatation, but occasionally can produce constriction also in the hind limb by acting upon the sympathetic and dorsal root ganglia, and in the small intestine by acting upon the superior mesenteric and dorsal root ganglia.—lL. G. K. 231. (ADRENIN) Die Hemmung der Kochsalzausscheidung im Harn durch Adrenalin. (Inhibition of sodium chlorid ex- cretion through the kidney by adrenin). Bulcke (\W.), and Weis (P.), Deutsches Arch. f. klin. Med. (Leipzig), 1917, 123, 163-203. 314 ABSTRACTS Adrenin given subcutaneously in man and rabbits inhibits the NaCl output in the urine. The same occurs on intraven- ously injecting Ringer’s solution to which adrenaline has been added. This leads to retention of salt. The urinary nitrogen runs parallel to the NaCl in rabbits, and in man depends on the amount of urine formed. The kidney itself is the point of at- tack. It does not appear to be a purely vascular effect, but the kidney cells are affected, and in disease they are more sen- sitive to the action of adrenaline than they are normally.— Physiol. Abst., 1918, 3, 1380. 232. (ADRENIN) Disappearance of the pigment in the melano- phore of Philippine house lizards. Ruth (KE. S.) and Gibson (R. B.) Philippine Jour. Sci. (Manila), 1917, 12B, 181-188. These pigment cells neither contract nor expand. The color is discharged by adrenaline, both in vivo and in vitro. Bleaching occurs when the lizard is in white surroundings, and it is assumed that the pigment varies during life owing to the action of a hormone (probably adrenaline ).—C hem. Abit’ 233. (ADRENIN) L’azione dell’iodio e dell’adrenalina studiata su cellule viventi fuori dell’organismo. (Effect of iodin and of adrenin in tissue cultures.) Cervello (V.) and Levi (G.), Arch. di fisiol. (Firenze), 1917, 15, 219-228. Tissues from embryo chicks grow well in iodised plasma. Adrenaline is not favorable to such growth.—Physiol. Abst., 1918, 3, 55. 234. (ADRENIN) On the adrenalin in the blood of one who is suffering from a primary glaucoma. Kusama (K.) Mitt. a. d. med. Fakult. d. k. Univ. zu Tokyo 1917, 17, 137-157. The author employed Trendelenburg’s test for comparing the amount of adrenin present in the blood of healthy persons (ten eases) with that in the blood of thirteen patients suffering from glaucoma. The adrenin content was found to be de- creased in the blood of the latter, and therefore, contrary to the belief of some investigators, the rise in blood pressure in elaucoma is not due to an increased output of adrenin. A more marked reduction was found to occur in cases of chronie inflammatory than in acute inflammatory or absolute glaucoma. —L. G. K. 235. (ADRENIN) The action of the autonomic drugs on the surviving stomach. Smith (M.J.) Am. Jour. Physiol. (Balt.), 1918, 46, 232-43. ABSTRACTS 315 These experiments were carried out on strips of the surviv- ing stomach suspended in Tyrode’s solution. The drugs were added in definite amounts to the solution containing the strip. Strips were taken from the following regions of the stomach— antrum, perantrum, body and fundus. Longitudinal, cireular and oblique strips were used. Pilocarpine was found to cause a contraction of all regions of the surviving stomach of the guinea-pig, rabbit, cat, dog and human subject. Atropine antagonizes the action of pilocarpine and produces a relaxation. Nicotine produces a similar effect to pilocarpine, except that the fundus and cardiae sphincter of the cat’s stomach may relax, and the antrum and body of the rabbit’s stomach may slightly relax before contracting. The reaction of the different parts of the stomach to epinephrin may be relaxation (cat and human), or relaxation of some parts and contraction of others (guinea-pig, rabbit, dog). The reaction of the sphincters to epinephrin is always that of contraction. After ergotoxine those regions of the dog’s stomach that contract from epinephrin may relax from admin- istration of adrenin. The author concludes that the sympathetie innervation of the stomach is inhibitory in the cat and in man, but inhibitory in certain regions only while predominantly augmentory in other regions of the stomach of the guinea-pig, rabbit and dog. —L. G. K. 236. (ADRENIN) The effect of adrenalin on the irritability and contractility of mammalian nerve muscle preparations after death. Gruber (C. M.) and Fellows (A. P.) Am. Jour. Physiol. (Balt.), 1918, 46, 472-477. The tibialis anticus muscles of the cat were perfused with warm Ringer’s solution containing only the oxygen absorbed from the air. The animal was killed with ether at the com- mencement of the perfusion. The nerve was stimulated by means of a Sherrington shielded electrode. The author found that the addition of adrenin to the perfusion fluid at varying intervals after the death of the animal increased both the mus- cular activity (height of contraction) and the irritability (de- creased threshold of stimulus) of the nerve muscle preparation to electrical excitation. Adrenin therefore affects dying mus- cles in a similar manner to fatigued muscles. Three possible points of action of the adrenin are men- tioned: (a) It may assist or hasten the conversion of glycogen into sugar. (b) It may help to transform fatigue products by hastening the reconversion of lactic acid into sugar. (c) It 316 ABSTRACTS may assist in the destruction of fatigue products by increasing the rapidity of the oxidation of lactic acid into carbon dioxide and water.—L. G. K. 237. (ADRENIN) The effects of adrenin on the distribution of the blood. VII. Venous discharge from the adrenal glands. Gunning (R. E. L.) Am. Jour. Physiol. (Balt.), 1918, 46, 362-365. The author found that the intravenous injection of adrenin produced no active changes in the venous outflow of the adrenal elands, and therefore concludes that the splanchnic nerves carry no vasomotor fibres to the adrenals.—L. G. K. 238. (ADRENIN) The inhibitory effect of adrenalin upon the spinchter muscle of the iri8. Joseph (D. R.), Am. Jour. Physiol. (Balt.), 1917, 42, 608. Adrenalin solutions of various concentrations when ap- plied to the spinchter pupillae after either partial or complete excision of the muscle cause a prompt and unmistakable relax- ation. The relaxation is maximal with stronger solutions. (1:1000 to 1:100,000), but only partial with very dilute solu- tions (1:10,000,000). The duration of the effect varies directly with the concentration. The spinchter muscles of the bovine, swine, sheep, goat and human irises were tested. In its re- sponse to adrenalin the spinchter of the iris resembles the in- testinal strip.—lL. G. K. 239. (ADRENIN) Uber der Adrenalingehalt der Nebenniere des Menschen bei verschiedenen Todeursachen. (Adrenin content of human adrenals after death by various causes.) Lueksch (F.), Virchow’s Archiv (Berlin), 1917, 223, 290-300. The normal amount of adrenaline is 4 mg. per gr. of dry adrenal weight. This figure falls in infectious and other dis- eases, and may reach 0.35 mg. or in infants 0.13. In Addison’s disease the figure is lowest, in nephritis the highest.—Physiol. Abst.;. 1918,.3, 130. 240. (ADRENIN, PITUITRIN) The regulation of renal activ- ity. VII. The balance between the regulation by adrenalin and by pituitrin. Addis (T.), Shevky (A. E.) and Bevier (G.) Am. Jour. Physiol. (Balt.), 1918, 46, 129-146. See previous abstracts in Endocrinology, 1918, 2, 161, 162, 189. ABSTRACTS 317 The subcutaneous injection of amounts of adrenalin which increase the urea excreting activity of the kidney, and of amounts of pituitrin which depress that activity, have no effect when they are injected together in a certain balanced propor- tion. All grades of stimulation or depression may be induced by the injection of mixtures of adrenalin and pituitrin in which this halance is deflected by a preponderance of one or the other. In the rabbit the removal of both suprarenal glands is followed by a depression of the urea excreting activity of the kidney, which is greater than that which follows control opera- tions in which the suprarenals are not removed. The authors conclude that under physiological conditions the urea exereting activity of the kidney is determined by two main factors. There is a fixed and mechanical regulation through the urea concentration of the blood, but there is also another and overruling type of regulation which acts through the medium of the central nervous system. It is suggested that variations in the balance between the rates of secretion of the active principles of the adrenal and pituitary glands may play a part in regulating this nervous mechanism.—L. G. K. 241. (ADRENIN PITUITRIN) Azione di varie sostanze, e specialmente della pilocarpina e della atropina sopra alcuni organi muscolari lisci. (Action of various substances on smooth muscle) Bottazzi (F.), Atti d. r. ace. medico-chir. (Napoli), 1917, reprint, pp. 33. Pilocarpine increases the tone of various intestinal prepara- tions, most of all the dog’s small intestine, but the effect is always completely annulled by atropine. The effects of these alkaloids on the retractor penis muscle are very uncertain and inconstant (in contrast to de Zilva’s experiments, which could not be reproduced). Their effect on the uterus is likewise ir- regular. On the other hand, the uterus is affected in a con- stant manner by adrenaline, p-hydroxyphenylethylamine, B-iminazolylethylamine, and hypophysine. The first two caused relaxation of the non-pregnant, and contraction of the pregnant uterus of the bitch. In the cat they always caused contraction, which is not in agreement with the results of Cushny and others. Speculating on the adrenaline-ergotoxine vasomotor reversal, and the fact that adrenaline always causes contraction of the pregnant uterus, the author suggests that the inhibitory inner- vation of the organ may in pregnancy be paralysed by sub- stances as yet unknown.—Physiol. Abst., 1918, 3, 103. 242. (AUTONOMIC NERV. SYST.) Asthma considered in its relation to the vegetative nervous system. Pottenger (F. M.) Am. J. Med. Se. (Phila.), 1918, 155, 417-24. 318 ABSTRACTS A general discussion of the etiology of asthma relating the malady particularly to reflexes mediated through the vagus nerves.—R. G. 243. (AUTONOMIC N. §.) Le azioni antagonistiche autonomi. (The action of antagonistic autonomics.) Spadolini (1.), Arch. di. fisiol. (Firenze), 1917, 15, 1-167. : Rather more than one-half of the paper is devoted to a critical review of earlier work, the remainder to observations on the autonomic innervation of the urinary bladder and of the small intestine. Excitation of the hypogastric nerves in dog and cat may lead either to inhibition or to augmentation of the vesical contractions according as the stimulus is weak or is strong respectively. Similarly, adrenaline in small doses may inhibit, whilst in larger’ doses its effect may be the converse. The nervi erigentes are motor in function. Analogous effects were observed on the small intestine, when the vagi or the splanchnies were stimulated. Excitation of either of these nerves may produce either inhibition or the converse, accord- ing to the intensity of the stimulus. The writer regards the parasympathetic fibres (of vagi and nervi erigentes) as being responsible for relatively rapid contractions, and the sympa- thetic fibres as being pre-eminently-tonic in function. The re- sponse to a given stimulus is in any ease a function of the con- dition of the musecle.—Physiol. Abst., 1918, 3, 18. 244. (AUTONOMIC NERV. SYST.) Pharmacodynamic ex- amination of the vegetative nervous system in typhoid fever. Matsuo (I.) and Murakami (J.). Areh. Int. Med. (Chgo.) 1918, 21, 399-410. : A study was made of the reactions of typhoid patients to pilocarpine, atropine and adrenin. In 38 cases 14 showed ab- normal irritability of the parasympathetic system and 11 cases showed hyperirritability of the sympatheties. Three cases were sensitive to all drugs, 7 cases were sensitive to pilocarpine and adrenin and 3 only to piloecarpine. 245. BONE MARROW, Internal secretion of. Ord. (G. W.), Laneet (Lond.), 1918 1, 385. The suggestion is made that marrow does something more than minister to bone nutrition. Some bones have little or no marrow, and the way it is so safely housed, and the serious re- sults (shock, death, ete.) that follow extensive bone removal, are considered to support this view.—Physiol. Abst., 1918, 3, 132. ABSTRACTS 319 246. (CORPUS LUTEUM) The non-effect of corpus luteum preparations on the ovulation cycle of the rat. Corner (G. . W.) and Hurni (F. H.) Am. Jour. Physiol. (Balt.), 1918, 46, 483-486. On each of the four days following littering a benzidine compound, staining the corpora lutea blue, was injected intra- abdominally into rats. This was followed by the intra-abdom- inal administration of dessicated corpus luteum substance in normal saline, given every other day for twenty days. The rats were then killed and the ovaries examined in serial see- tions, the number of stained and unstained corpora lutea being compared. It was found that in all cases ovulation had con- tinued unchecked, showing that the intra-peritoneal injection of mammalian corpus luteum substance does not inhibit ovula- tion in the rat.—lL. G. K. 247. (DERCUM’S DISEASE-ADRENIN) Istografia, Isto- chimica e Patogenesi dei lipomi di Dercum. (Histology, histo-chemistry and pathogenesis of Dercum’s lipomata.) Martelli (C.) Tumori (Rome) 1918, 6, 1. The author begins with an accurate description of the severe symptoms determined by the formation of such lipo- mata, and insists on the good effects brought about by adrena- lin therapy during the following asthenic period. Upon examination of one of | these tumors the author found it histologically like the common lipoma, made of adult fatty cells. There are, besides, hyperaemiec zones with perivascular micro-cellular infiltrations, due to inflammatory processes. He finds also mononeuritis of the few nervous fibres, and an elas- tic, pre-colloid hypertrophy of the tumor, which makes its consistency more dense than that of the surrounding fatty tissue. The chemical composition of the lpomatous cells is chiefly that of neutral fat mixed (in 2 to 3 per cent of said cells) with fatty acids, which show also a granular appearance in the interstitial tissue. Common lipoids are found in greater amount either as cuticle and lipoid grains, or spread in the subeuticular stratum at the periphery of the adipose vesicle. Very scanty, if present, are the special lipoids as lecitine, lipo- ehromes and cholesterine. There is no calcium. Compared with the common lpomata, Dereum’s lipoma does not show either embryonal elements or lecithinic cells, or phenomena of atrophy. It appears like an accumulation of adult fatty vesicles (at rest), quite like those of the normal subcutaneous adipose tissue, only a little smaller, pressed to- 320 ABSTRACTS gether and rich in lipoids with hyperemic foci and micro- cellular infiltrations inserted. As for the pathogenesis the author claims that such lipomata are the expression of disturbed equilibrium of lipo- genesis (connected with multiple endocrine-sympathetic dis- funetions—mostly suprarenal) which forms in the subeutaneous connective tissue in parts rich in elastic tissue. This forma- tion may be either slow, as in the indolent lHpomata, or (very seldom) sudden and painful—in form of an anaphylactic dis- charge (Dereum’s)—almost as if the organism were to free itself of a toxie product (probably lpoid and very likely in connection with suprarenal insufficiency) and were to localize such product under form of lHpomata in the subcutaneous tissue.—G. V. 248. (DIABETES) Diabetic polyneuritis. Pitres (A.) and Marchand (L.) Prog. méd. (Paris), 1917, 32, 295. A case is described at length. The prognosis is usually favorable. 249. (DIABETES) The application of the Auer-Kleiner mor- phine test in human diabetes. Epstein (A. A.) Proc. Soe. Exp. Biol. and Med. (N. Y.), 1918, 15, 89-90. An attempt was made to utilize as a clinical test for latent diabetes the fact that morphine in dogs eauses a rise in the blood-sugar. Within the practicable limits of dosage no un- equivocal effect was produced in man.—R. G. H. 250. (DIABETES) The rate of dialysis of diabetic blood-sugar. Kleiner (I. 8.), Proe. Soc. Exp. Biol. and Med. (N. Y.), 1918, 15, 81-2. ; The fact that the sugar of diabetic blood was found to dif- fuse less readily than a similar concentration of sugar in normal blood is thought to indieate that the diabetic blood-sugar is held in some sort of loose combination.—R. G. H. 251. DIABETES, Salt metabolism in. Beard (A. H.) Arch. Int. Med. (Chgo.) 1918, 21, 716-39. This paper is a report of an elaborate study of the problem. Two points of general interest were brought out: 1. Increase of weight on unrestricted chlorids is invariably associated with their retention. The edema usually disappears following the disappearance of the glycosuria. 2. Sodium bicarbonate ad- ‘ ‘, > ~ & LS eee ABSTRACTS 321 ministration has no constant influence on carbohydrate toler- ance in diabetes.—R. G. H. 252. (DIABETES) Uber die Kchlenhydratverwertung des nor- malen und diabetischen Muskel. (Carbohydrate content of normal and diabetic muscle)—I. Forschbach (J.) and Schaffer (H.), Arch. exp. Path. Pharm. (Leipzig), 1918. 82, 344-367. It is generally supposed that the tissues in diabetes are sugar-laden, and this is regarded as an explanation of their lessened resistance towards infective agents. This view is dis- puted. In the muscles the sugar content is not increased in diabetes.—Physiol. Abst., 1918, 3, 119. 253. DIABETES INSIPIDUS, A case of, as sequel to gunshot wound of the head. Graham (EK. A.) Ann. Surg. (Phila.), 1917, 66, 529. Additional support that diabetes insipidus is an expression” of a disturbed funetion of the hypophysis, or neighboring tissue. 254. DIABETES INSIPIDUS, Control of symptoms of by subcutaneous injections of extracts of hypophysis cerebri. Barker (L. F.) and Mosenthal (H. O.), Jour. Urol. (Balt.), 1917, 1, 449. A most. favorable effect was obtained by this method. Tethelin and adrenaline were of no value. ; 255. DIABETES INSIPIDUS from hemorrhage in the neuro- hypophysis and peduncle. Luzzatto. Lo Sperimentale, Nos. V-VI, 1917. Rivista crit. di clin. med. (Firenze) 1918, 19, 91. A case of polydipsia and polyuria with progressive cachexia is reported by Luzzato, who at the post-mortem examination found an old hemorrhage destroying the pos- terior lobe of the hyophysis and cutting the peduncle at its entrance into the posterior lobe. The surrounding parts of the brain do not show any abnormality, so that the author brings out such a finding as a severe objection against Camus and Roussy’s theory (Lesions of the optopeduncular basilar region as a cause of Diabetes insipidus).—G. V. 256. DIABETES MELLITUS, Influence of the war on. vy. Noorden (C.) Med. Klinik (Berlin), 1916, 12, 991. 322 ABSTRACTS Nervous stress alone does not elicit diabetes, but it aggra- vates the condition, prohakly by whipping up the adrenals.— \ Chem. Abstr. 257. DUCTLESS GLANDS and War. The Medical Research Committee call attention to over- activity of the endocrine organs in times of intense stimulation. In the siege of Paris (1871) Graves’ disease was common. So far in the present war its frequent sequela, myxcedema, has not had time to oceur. Alexander (Med. Klinik, 1917, 13, 994-996), notes a ease of Graves’ disease following a bomb explosion. Reference is also drawn to the following paper in relation to the adrenal glands: Ramond and Francois (Bull. et mém. soe. méd. des hop. de Paris, 1917 [3], 41, 1001-1003), who have noted the frequeney of Addison’s disease ; here adrenal exhaustion in- ereases liability to tubercular infection. Among other points noted is that in war eases the blood-pressure is well sustained until near the end.—Physiol. Abst., 1918, 3, 50. 258. (ENDOCRINE GLANDS) Animal diastases. II. Blood diastase of rabbits. Watanabe (C. K.), Am. Jour. Physiol. (Balt.), 1917, 45, 30-48. This is increased by the intravenous injection of human saliva, parenteral administration of starch (slightly, amylase also appearing in the urine), intravenous or intraperitoneal in- jection of NaHCO, in large doses. The latter also causes hyper- glycemia. Ether anaesthesia and adrenaline cause hypergly- eaemia, but no change in the diastase of the blood. Pituitrin, ingestion of HCl, small doses of Na,CO,, and thyroid feeding have no appreciable effect on blood-sugar or diastase. 259. (ENDOCRINE GLANDS) Azione degli estratti di ghian- dole endocrine sui processi di regenerazione. (Effect of en- docrine gland extracts on regeneration).- Piccoli (G.), Arch. di fisiol. (Firenze), 1917, 15, 199-208. The tails of newts were amputated a week before injecting gland extracts. Taking the number of dividing nuclei as the criterion, an increase was noted with pituitary and adrenal (small dose) extracts; a diminution occurred with thyroid and a large dose of adrenal extract, and no change with extract of testis. Taking the rate of growth of the stump as the eriterion, adrenal, thyroid, and testicular extracts all caused a diminu- tion; a small dose of pituitary produced no change, but a large dose caused an increase.—Physiol. Abst., 1918, 3, 52. ABSTRACTS 323 260. GLYCOSURIA, renal. Beard (A. H.) and Grave (F.) Arch. Int. Med. (Chgo.) 1918, 21, 705-15. The continued presence of any considerable amount of sugar in the urine is nearly always indicative of insuffi- ciency of the endocrine function of the pancreas. Beard and Grave present a detailed study of a case of glycosuria, however, of renal origin. In order to differentiate a renal from a pan- creatic glycosuria it is necessary to demonstrate: 1. A urine containing dextrose in amount unchanged to any great extent by fluctuations of carbohydrate intake. 2. A blood sugar of normal percentage. Cases of true renal diabetes are very rare. —R...G. Fi. 261. (HORMONES). The destruction of hormones, pro- enzymes, and enzymes, by ultra-violet radiation. Burge (W. E.). Am. Jour. Physiol. (Balt.), 1916, 40, 137-138. Data elsewhere reported. See abstract in this Journal, 1917, 1, 66—L. G. K. 262. HYPERNEPHROMA, Vaginal metastases of. Gellhorn (G.) Am. J. M. Se. (Phila.), 1918, 156, 94-104. Metastases of hypernephromata in the vaginal wall are rare, the author having found only nine eases in the literature. A tenth case is reported.—R. G. H. 263. (HYPOPHYSIS) Abuso de la pituitrina (Abuse of pitu- itrin) Artega (J. F.), Rev. Med. y Ciruj. (Havana), 1916, 21, 71-2. Two cases are described in which reckless use of pituitary injections led to unhappy results—in one ease a barely averted rupture of the uterus and in one to a tear of an old sear in the cervix, causing profuse hemorrhage. The author thinks that none but competent specialists should be allowed to use medica- ments of such potency.—R. G. H. 264. (HYPOPHYSIS) An improved apparatus for testing the activity of drugs on the isolated uterus. Pittenger (P. S.), Jour. Am. Pharm. Assoc. (Easton, Pa.), 1918, 7, 512. A detailed description of the author’s apparatus and method for testing pituitary preparations on the isolated uterus. —F.F. 265. HYPOPHYSIS cerebri: its structure and development. Parker (K. M.), Sci. Progress (Lond.), 1918, No. 47, 450-464. 324 ABSTRACTS A review of recent work. The physiological side of the subject is only cursorily mentioned.—Physiol. Abst., 1918, 3, 52. 266. (HYPOPHYSIS) Hypophyseal tumors through the intra- dural approach. Adson (A. W.), Jour. A. M. A., 1918, 71, 721-26. The technique of this operation is described and illustrated. The results of six cases are reported and the advantages of this method of operation pointed out.—R. G. H. 267. (HYPOPHYSIS) Physiological assay method of the U. S. P. IX. Pittenger (P.S.), Jour. Am. Pharm. Assoc. (Easton. Par) 1907-6: STA. Pittenger states that more concordant results are obtained, in the standardization of liquor hypophysis, by employing the whole one horn of the uterus of a 350 to 425 gram guinea pig, instead of only a segment of the one horn from a 250 eram guinea pig. The author suggests improvements in the lever ar- rangement by means of which the uterine contractions are re- corded on the kymograph.—F. F. 268. (HYPOPHYSIS) Pituitary disturbance in its relation to the psychoses of adolesence. Tucker (B. R.), Jour. A. M. A., LOTS cid, aou-oe. Author’s abstract previously published as No. 127, Endoe- rinology, 1918, 2, 171. 269. (HYPOPHYSIS) Preliminary note on the value of beta- iminazolylethylamin hydrochloride as a standard for testing pituitary extracts. Pittenger (P. S.) and Vanderkleed (C. E.) Jour. Am. Pharm. Assoe. (Easton, Pa.), 1917, 6, 131. A criticism of the standard adopted by the U. S. Pharma- copela, ninth revision, for iquor hypophysis.—F. F. 270. (HYPOPHYSIS) Production of transplantable growth. Erdmann (Rhoda), Proce. Soe. Exp. Biol. and Med. (N. Y.) 1918, 15, 96. The stimulating effect of tethelin upon new growths was shown by the author in the following manner: Embryonic heart tissue of the chicken is cultivated after twelve days’ ineu- bation, for three days in a plasma medium. Then pieces 1 mm. square are implanted subcutaneously in a fowl. After ten days small protuberances develop which upon section appear as ABSTRACTS 325 cystic formations. If one of these protuberances is treated with injections of tethelin it becomes three times as large as its un- treated neighbor.—R. G. H. 271. (HYPOPHYSIS) Recherches experimentales sur l’hypo- physe de la grenouille. (Experimental researches on the hypophysis of the frog). Houssay (B. A.) Jour. de physiol. et de path. gen. (Paris), 1917, 17, 406. The hypophysis of the frog (Leptodactylus ocellatus) is made up of the three parts: glandular, intermediary and nervous portions. The glandular part contains both acidophil and chromophil cells. Hypophysectomy was performed by aii incision through the palate, leaving a flap of bone and mem- branes with which to close the wound after the operation is completed. Total hypophysectomy frequently, but not invar- iably is fatal within a few days. Occasionally animals survive for many weeks. The same operative manipulations without removal of the gland is not fatal. A previous grafting of the hypophysis appeared to lessen the mortality. Reflex excit- ability is not diminished. Hypophyseal extract from the frog exerts a pressor effect, increases cardiac systole, acts as a gal- actagogue, dilates renal vessels and produces diuresis, being thus analogous to the action of hypophyseal extract of higher vertebrates.—A. L. T. 272. (HYPOPHYSIS) The pituitary in relation to loss of memory. and inability to concentrate the attention. Dasile (G.) Polelinico (Rome), 1917, 24, 458. Certain cases showed more or less loss of memory, insomnia and an inability to concentrate the attention in association with diseased sphenoidal sinus or tumors in the nasopharynx. It is regarded as probable that such lesions involved the pituitary body, giving rise to the mental symptoms.—Physiol. Abst., 1918, 3. 132. 273. (HYPOPHYSIS) Uber das Vorkommen von Reisenzellen in der Hypophyse. (Giant cells in the hypophysis.) Sim- monds (H.) Virchow’s Archiv. (Berlin), 1917, 223, 281-90. True giant cells were noted in certain conditions, mainly in elderly women.—Physiol. Abst., 1913, 3, 132. 274. HYPOPHYSIS, THYROID AND PARATHYROIDS, Studies of. Kamo (K.) Kyoto Igaku Zasshi, 1917, 14, 1-39. Jap. Med. Lit. (Seoul), 1918, 3, 33-34. 326 ABSTRACTS The hypophyses of puppies thyroidectomized 1% to 5 months previously were always found to be hypertrophied even to 214 times the usual size, the anterior lobe being chiefly af- fected. Marked histological changes also occurred, among which may be mentioned the appearance of enlarged eosin-staining granular cells. These were not present in adult animals simi- larly treated, although the hypophyses were enlarged. No spe- cial alteration took place in the middle lobe. The hypophyses of parathyroidectomized dogs and puppies were not particularly changed in the anterior lobe, but the middle lobe showed an increase in volume in puppies and an increase in colloid substance in full-grown dogs. The parathyroids remaining after thyroidectomy were al- ways hypertrophied, but exhibited no cellular changes. A thyroid rest, overlooked in total thyroid-parathyroidectomy, underwent great hypertrophy; the follicles were very unequal in size and contained a thin fluid. Adrenalin glycosuria was greatly decreased by total thy- roidectomy in dogs, and adrenalin had no toxie action on these animals when given in reasonable doses. It was, however, quite toxie for parathyroidectomized dogs, and the violent symptoms of tetany were suppressed by the administration of thyroid ex- tract. The histological and physiological independence of the thyroid and parathyroids was considered proven, even though at times there may seem to be antagonism and at other times a complimentary action between them.—L. G. K. 275. INTERNAL SECRETIONS, General physiological rela- tion of. Sewall (H.) Col. Med. (Denver), 1918, 15, 45-47. A general discussion of well-known data.—R. G. H. 276. (INTERNAL SECRETIONS) Internal Secretion in learn- ing. Dunlap (K.), Psychobiology (Balt.), 1917, 1, 61-64. The author suggests as a hypothesis that the direct influ- ence of emotion on action and particularly the influence of pleasure (or satisfaction) and pain (or dissatisfaction) on the formation of habits are due to the ‘‘fixing effects’’ of a hor- mone. The nervous discharge is supposed to leave an are or certain important points in the are in such a condition chemi- cally that this unknown hormone, which is discharged into the blood during pleasure, may a few moments later ‘‘fix’’ it. The effects of pain in preventing the fixing of the reaction may likewise be due to a negativing agent (perhaps adrenalin). The theory is entirely speculative and as yet unsupported by experimental evidence.—L. G. K. ABSTRACTS 327 277. INTERNAL SECRETIONS, Progress of the year in the study of, with report of five cases. Ruggles (A. H.) Rhode Island Med. Jour. (Providence), 1917, 1, 170-75. A brief review of some of the recent literature. Five cases are reported with a few superficial details. They are: (1) Thy- roid intoxication with mental symptoms; (2) Hyperthyroidism following extirpation of ovaries, treated with ovarian sub- stance; (3) Adrenal insufficiency (?); (4) Adrenal insufficieney treated with suprarenal tablets; (5) Anemia with adrenal in- sufficiency. The diagnosis of adrenal insufficiency was appar- ently made largely on the presence of Sergent’s ‘‘ White ne? ——h, G..H. 278. INTERNAL SECRETIONS, Some relations between the emotions and glands of. Cannon (W. B.) Jour. Lancet (Minneapolis) 1916, 36, 685-88. An address detailing the well-known work of Cannon and his collaborators on the relation of the emotions to adrenal and thyroid discharge.—R. G. H. 279. INTERNAL SECRETIONS, The. Guenther (A. C.) Nebr. State M. J. (Norfolk, Nebr.) 1918, 3, 15-19. A general review of the more important literature. Noth- ing new.—R. G. H. 280. (INTERNAL SECRETIONS) The defective child from the standpoint of the internal secretions. Harrower (H. R.) So. Cal. Pract. (Los Angeles) 1917, 32, 101-106. An enthusiastic general discussion of the topie—R. G. H.-: 281. (INTERNAL SECRETIONS) The diagnosis of the in- ternal secretory disorders. Harrower (H. R.) Med. Herald (St. Joseph, Mo.), 1916, 35, 186-88, 217-19, 257-60, 295-98, 333-37, 361-65. Also published in Western Med. Times (Den--: ver) 1916, 35, 502-4, 558-61, 36, 9. Preliminary serial publication of material which after- ward appeared in book form.—R. G. H. 282. INTERNAL SECRETIONS, The relations of, to neur- ology and psychiatry. Hammes (E. M.) Jour. Lancet (Min- neapolis), 1916, 36, 449-52. 328 ABSTRACTS An interesting general discussion of the topic with de- scription of three cases illustrating respectively: hypothy- roidism; hyperthyroidism, associated with insanity (melan- cholia), and partial gonadectomy with hypogenital symptoms benefited by testicular extract.—R. G. H. 283. (INTERNAL SECRETIONS) The activation of muscle catalase by liver. Burnett (T. C.) Am. Jour. Physiol. (Balt.), 1918, 46, 63-66. In these experiments the liver and leg muscles of the rat were used as being at the two ends of the seale of catalytic activity, the liver being the most active and muscle the least (excepting the brain). Both were perfused till free from blood by saline solution introduced through the aorta. The tissues were then passed through a meat grinder and the pulpy mass obtained was used in weighed quantities. It was found that when a small amount of liver was added to a much larger quantity of muscle in either neutral or acid hydrogen peroxide the catalytic activity of the combined mass was much greater than the total activity of the two taken sep- arately, as measured by the volume of oxygen produced in a given time. Blood was also found to have a similar marked accelerating effect on muscle catalase, while thyroid, spleen and kidney produced only a small amount of acceleration. Pan- creas and testes appeared to cause a slight retardation. The suggestion is made that this accelerating action may be due to an internal secretion of the liver. Its presence in the blood would also account for its effect in producing accelera- tion.—hL. G. K. 284. (MONGOLISM) Ricambio azotato nell’ idiozia mongo- loide e nella mixo-idiozia ed infiuneza su di esso della Tiroi- dina. (On the mongoloid idiocy and on the mixo-idiocy and of the influence on them of the thyroid treatment.) Caronia (G.) La Pediatria (Naples) 1918, 26, 336. The author emphasizes the difference of effect of the thy- roid treatment on these two forms of idiocy, as found from personal research. The children to be examined were first kept ten days on a diet chiefly of milk, eggs, bread and cereals, so that the nitrogenous dosage was rendered very easy. Then, keeping on with the same diet, for six days the food was exam- ined as well as the urine and the faeces. After an interval of ten more days, while the thyroid treatment was begun, there was a period of six other days, during which analysis of food, urine and faeces was made, without dropping the treatment. /_ ABSTRACTS 329 For the determination of the total nitrogen Kjeldahl’s method has been used for food, urine and faeces. For the urea, Morner-Syoovist’s; for uric acid, Folin-Shaffer’s; for ammonia, Folin-Spiro’s; for the amino-acids, Henriquez-Sorensen’s. The residual nitrogen (creatinine and purini¢ bases) was not deter- mined. Conclusions: (a) The nitrogenous metabolism (in the microcephalic mongoloid idiocy) is normal as regards the total retention of nitrogen, but irregular in regard to the various nitrogenous elements of the urine. There is a conspicuous re- tention of nitrogen and increased elimination of amino-acids. Under the influence of the thyroid the metabolism comes ‘soon to a negative balance at the expense of the tissues, about as we find it in hyperthyroidism. (b) In mixo-idioey the metabolism is also irregular as regards the relations between the various elements of the urine (increased elimination of amino-acids). Under the thy- roid treatment, though, the metabolism improves, showing better oxidation by diminished elimination of amino-acids and giving normal amount of the residual nitrogen and of uric acid.—G. V. 285. (ORGAN EXTRACTS.) The effects upon the gastric secre- tion of organic extracts. Rogers (J.), Rahe (J. M.), Faweett (G.-C), and Hackett (G. S8.). Am. Jour: Physiol. (Balt.), 1916, 39, 345-353. The authors were of the opinion that the equivalent of a specifie gastric hormone is to be found in some substance com- mon to many extracts which favorably affects the nutrition and consequently the activity of the gastric epithelial cells, and has some relation to their nerve supply. They accordingly tested the effects of the subcutaneous injection of organ ex- tracts on the gastric juice of dogs in which the Pavloff isolated stomach pouch and fistula had been established. The thyroid, or only the non-coagulable portion of an aqueous extract of the thyroid, was found to contain a sub- stance which is an active stimulant of both gastric secretion and gastric motility. Only the ‘‘residue,’’ or non-coagulable portions, of aqueous extracts of the parathyroid, thymus, spleen and liver were found to have a similar effect.. Both the coag- ulable and non-coagulable portions of an aqueous extract of the pancreas are vigorous stimulants of gastric secretion. The pituitary and adrenal residues inhibit the flow of gastric secre- tion. All the stimulating residues seem to act upon a periphe- ral gastric mechanism of which the nervous system is an essen- tial part. Injection of other organ extracts gave entirely nega- tive results.—L. G. K. 330 ABSTRACTS 286. (PANCREAS) Role of the pancreas in glycolysis. Lepine (R.) Rev. de méd. (Paris), 1917, 35, 289. A protest against incriminating the pancreas alone. Cer- tain other glands with an internal secretion are unmistakably involved in glycolysis. 287. (PANCREAS) The effects of painting the pancreas with adrenalin upon hyperglycemia and glycosuria. Kleiner (I. 8.) and Meltzer (S. J.) Jour. Exp. Med. (Balt.) 1918, 27, 647. The authors in repeating experiments of earlier workers find that in the majority of cases painting the pancreas with adrenalin is followed by glycosuria which varies in different animals. The results of earlier experiments lead to the infer- ence, first, that painting the pancreas with adrenalin caused a marked glycosuria and hyperglycemia, and second, that the glycosuria and hyperglycemia produced by intraperitoneal in- jections were of pancreatic origin. To decide this point the authors performed experiments in which the pancreas was isolated from the rest of the peritoneal cavity and found that the glycosuria produced was about one-third, and the rise in blood sugar about two-thirds that obtained by painting the unisolated pancreas. They therefore conclude, first, that the painting of the isolated pancreas produces only mild glycosuria and hyperglycemia; second, that the greater production of sugar observed after painting the unisolated pancreas cannot be of pancreatic origin, but due to the escape of adrenalin to the peritoneum. As evidence of this conclusion experiments were performed in which the adrenals were painted. The ef- fects on sugar production was apparently as intense as that obtained by painting the unisolated pancreas. Whether the production of sugar after painting the unisolated pancreas is due to the escape of adrenalin to some definite organ covered by the peritoneum or whether the peritoneum as a whole is re- sponsible for sugar production, it appears that, when sugar production follows intraperitoneal injections of adrenalin, it is not of pancreatic origin.—H. W. 288. (PANCREAS) Uber die Bedeutung der Langerhansschen Inseln fiir den Kohlehydratstoffwechsel. I. Mitteilung. Das Verhalten des Blutzuckers nach Unterbindung des Ductus Pancreaticus bei Kaninchen. (The significance of the islands of Langerhans in carbohydrate metabolism. I. The retention of the blood sugar after ligation of the pancreatic duct in rabbits.) Kamimura (N.) Mitt. a. d. med. Fakult. d. k. Univ. zu Tokyo 1917, 17, 95-126. Ne ABSTRACTS 331 The author found that ligation of the pancreatic duct in rabbits resulted in complete atrophy of the parenchyma of the ‘pancreas with the exception of the islands of Langerhans, which did not appear to show any change. No digestive dis- turbaneces resulted, and no lasting hyperglycemia or glycos- uria occurred. Artificial hyperglycemias were produced in various ways (injection of adrenin and diuretine, hemorrhage and the intravenous introduction of sugar), but the animals showed no difference in their behavior towards these factors than did other normal rabbits. These facts support the accepted belef that as long as the islands of Langerhans remain normal the carbohydrate metabolism is not interfered with in disturbances of the pan- creas.—L. G. K. 289. (PANCREAS) Uber die Bedeutung der Langerhansschen Inseln fur den Kohlehydratstoffwechsel. II. Mitteilung. Zytolytisches Immunserum der Pancreas inseln. (The sig- nificance of the islands of Langerhans in carbohydrate meta- bolism. II. Cytolytic immune serum of the islands of Langer- hans.) Kamimura (N.) Mitt. a. d. med. Fakult. d. k. Univ. gu Tokyo 1917, 17, 127-136. A serum, supposedly cytolytic to the islands of Langer- hans, was prepared as follows: Saline extracts of rabbits’ pancreas, the ducts of which had been previously ligatured so that only the islands of Langerhans remained in an un- atrophied condition, were injected into the peritoneal cavity of a young dog. After several injections, at intervals of five to ten days, the dog was bled and the serum so obtained was injected into rabbits, some of which had previously had the pancreatic duct lgatured. Glycosuria was not produced in these animals, thus confirming the earlier work of Ssobolew and Klimenko. In some cases there was a slight increase in the blood sugar content, but the author did not attribute this to the action of a specific serum. The serum produced no noticeable pathological changes in the islands of Langerhans. —L. G. K. 290. (PARATHYROIDS) Guanidine hydrochloride and blood- sugar. Watanabe (C. K.), J. Biol. Chem. (N. Y.), 1918, 33, 253-265. Paton’s views on the relationship of guanidine to tetany are confirmed. It is further shown that hypoglycaemia is pro- duced both by guanidine and removal of the parathyroids (rab- bits). 332 ABSTRACTS 291. (PARATHYROIDS) Uber todlich verlaufende Tetanie. (Fatal tetany). Stankovie (R.), Wien. klin. Woch. (Wien.), 1917, 80, 1107-1108. Five fatal cases in soldiers on active service are recorded. They had been exposed to privations mental and bodily. The condition is attributed to parathyroid insufficiency, and there was no evidence of compensatory action in other endocrine organs. (Med. Research Committee.)—Physiol. Abst., 1918, 3, 130. 292. (PITUITARY) Dystrophia adiposogenitalis (Frohlich’s syndrome). Madigan (J. J.) and Moore (T. V.) Jour. A. M. A. (Chgo.), 1918, 70, 669. Clinical report of a case of dystrophia adiposogenitalis in a boy 10 years of age. The author believes the condition had a prenatal origin because of a hereditary taint upon the ma- ternal side, blindness from birth, nystagmus at three or four months of age, very small optic disks and a genital aplasia of such a nature that it must have dated well back into the prenatal history of ‘the child.—H. W. 293. (PITUITARY) The pituitary gland in epileptics. The conformation of the sella turcica (2nd paper). Munson (JJ. F.) Arch. Int. Med. (Chgo.), 1918, 21, 531. The sellas from a series of unselected epileptic subjects present a wide variation in type. The average size seems a trifle smaller than figures given for normals and the contained eland seems to weigh less. Roofing of the fossa can be seen in Roentgenograms, but contrary to impressions given by the statements of other writers, the author believes that the gland in reality is well exposed and pressure seems a remote possi- bility. Bony changes are present but seem to be the anomalies which might well be present in a similar series of nonepileptic cases. The author concludes that there is no characteristie change to be seen in epileptic sellas——H. W. 294. (PITUITRIN) Uterine inertia. Titus (P.) Jour. A. M. A. (Chgo.) 1918, 71, 890-93. The author regards pituitrin as of relatively httle use in the practice of obstetrics. Its use in the first stage of labor is regarded as indefensible. Having had three cases of hour- glass contraction of the uterus with retained placenta as a result of its use in the second stage, he has come to the con- clusion that its safest use is in the third stage to control uterine ABSTRACTS 333 relaxation and hemorrhage. He comments ironically on the free use of pituitrin by mid-wives.—R. G. H. 295. RICKETS, The modern views on the nature of. Rivista erit. de clin. med. (Firenze) by ‘‘Y’’ 1918, 19, 189: Rickets is considered as a disease of development, deter- mined usually by dysfunction, first of one and then of all the elands of the thyro-parathyro-thymie group. The thymus lesions would alter the metabolism of ealcium and cause a diminished specific activity of the cartilage cells; the para- thyroids would be the cause of the spasmophilic symptoms ; the exophthalmus and the lymphocytosis would be charged to a dysfunction of the thyroid.—G. V. 296. SECRETIN, Its mode of action in producing an increase in the number of corpuscles in the circulating blood. Downs (A. W.) and Eddy (N. B.). Am. Jour. Physiol. (Balt.), 1918, . 46, 209-221. The authors have previously shown that the injection of secretin is capable of producing a marked increase in the num- ber of erythrocytes and leucocytes in the circulating blood. Be- heving this inerease to be due to direct stimulation of the bone marrow and lymph glands, the authors investigated the changes in the blood picture and the histological appearances of these organs after prolonged administration (8 weeks) of secretin to two rabbits. The results were compared with those obtained from two controls. A marked increase in the leueoeyte count was obtained (146.7 per cent in the third week), and a less pronounced in- crease in the erythrocyte count (18.5 per cent in the eighth week). At autopsy the thyroids and spleen of each of the secretin rabbits were much heavier, and the liver was slightly heavier than the same organs in the control animals. Smears and sections of the bone marrow showed that cells of all types ‘were much more numerous in the treated rabbits. The lymph olands of the secretin animals also showed evidence of increased activity. The enlargement of the liver and spleen was at- tributed to the rapid accumulation in them of the debris of broken down immature erythrocytes produced by the over- active bone marrow. Alterations in the relative proportions of the different varieties of leucocytes was also found to take place and nucleated red corpuscles appeared in the blood of the secretin rabbits.—L. G. K. 334 ABSTRACTS 297. (SEX) A demonstrtaion of the origin of two pairs of fe- male identical twins from two ova of high storage metabolism. Riddle (O.), Jour. Exp. Zool. (Phila.), 1918, 26, 227. The author advances further data for a theory of sex dif- ferentiation to which he still adheres despite all cytological op- position. He states that he obtained two pairs of identical fe- male twin doves, each pair of which was’produced from a single ovum. The two yolks were of very large size, and were pro- duced under conditions known to favor the production of fe- males. The author claims that the fact that these two cases of identical twins were from ova of high storage metabolism and were of the female sex lends support to his theory that germinal differentiation of sex is a differential metabolism. Practically all other biologists believe that sex is determined by the chromosomes of the germinal cells.—E. R. H. 298. (SEX) A microscopic study of the reproductive system of foetal free-martins. Chapin (C. L.) Jour. Exp. Zool. (Phila.), 1917, 28, 453. A microscopical study of the material de- scribed by Lillie in the same Journal. In early stages the free-martin resembles the normal female embryo but it gradually comes to resemble the male in many ways. Such changes occur in the gonad in which the sex cords may resemble either the primary cords of the ovary or the seminiferous tubules of the testis. Other organs which in the sterile free-martin tend to resemble those of the male are the rete, Wolffian body and duct and the Mullerian ducts which normally form the uterus. The changes in these organs vary greatly and are believed to depend upon the amount of male internal secretions which get into the female, and upon the stage of development at which this introduction oceurs.— EK. R. H. 299. (SEX) Another case of gynandromorphism. Harman (M. T.) Anat. Ree. (Phila.), 1917, 13, 425. The author deseribes very briefly a cat in which the sex organs on right side consisted of an ovo-testis, uterine tube and uterus, while on the left side they were of the normal male type. The subject of gynandromorphism is diseussed.—RE. R. H. 300. (SEX) Studies on sex in the hermaphrodite Mollusk crepidula plana. II. Influence of environment on sex. Gould (H. N.) Jour. Exp. Zool. (Phila.), 1917, 23, 225. ABSTRACTS 335 The author has shown that in a certain mollusk the colony both in natural and under experimental conditions develops all female animals until one of these reaches a point where fertiliz- ation is needed and then males develop. The males never de- velop under any other conditions. If the large females are removed, development of males ceases, and on the other hand males will develop from animals which have already begun to differentiate into females if the conditions are proper.—E. R. H. 301. (SEX) The free-martin; a study of the action of sex hormones in the foetal life of cattle. Lillie (F. R.) Jour. Exp. Zool. (Phila.) 1917, 28, 371. In eattle twins the sterile free-martin and its mate are rarely if ever monozygotic. The female zygote contains factors for both sexes. The quantitative difference between the male and female factors of the female zygote necessary for the differ- entiation of female characters are reduced in the free-martin by internal secretions from the male twin, and the free-martin therefore becomes a sex intergrade. In these cases the author - found that the two animals receive blood from the same chorion. This permits the internal secretions from the male to be carried into the female and interfere with her normal sexual differen- tiation, thus producing the sterile free-martin. Different de- grees of intersexuality may be produced in these free-martins. Absence of normal ovarian tissue may influence their later de- velopment by the absence of certain inhibitions normally brought about by the ovary. Sex differentiation is controllable within variable limits in certain groups of animals including mammals. The paper is well illustrated.—E. R. H. 302. (SPLEEN) Histological examination of the spleen in various infectious diseases. Kozumi (K.), Tokyo Igakkwai Zasshi, 1916, 30, 1-30. Jap. Med. Lit. (Seoul) .1917, 2, 2. Contains nothing new.—L. G. K. 303. (SPLEEN) The spleen during hibernation. Mann (E. C.) and Drips (D.) Jour. Exp. Zool. (Phila.), 1917, 28, 277. The spleen of the gopher is congested early in hibernation. Spleenectomy does not interfere with hibernation, hence the spleen is not primarily directly concerned with hibernation.— HK. R. H. 304. (TESTIS) The effects of testicular transplants upon vaso- motor irritability. Wheelon (H.) and Shipley (J. L.) Am. Jour. Physiol. (Balt.); 1916, 40, 394-400. Previously published 1917, 1, 482, but not included in index. 336 ABSTRACTS .305. (THYMUS) Enlarged, in infancy. Herrick (J. F.), Surg. Gyn. and Obst. (Chgo.), 1916, 22, 332; abstr. Arch. Ped. 1916, 33, 792. Enlargement of the thymus gland often causes death di- rectly or indirectly. It is a question whether the pressure is exerted solely on the trachea or on other organs as well. The chief symptom of a thymic enlargement is a respiratory dis- turbance which simulates a foreign body in the trachea. This is in the form of a mild stridor both at inspiration and expira- tion, or it may be a very severe dyspnea with fatal termination. After fits of vomiting, coughing or crying there seems to be a few minutes of relief. Pressure on the trachea, on the vagi, and on the heart are assigned as causes of death. The diagnosis of the stridor caused by a foreign body and that caused by an enlarged thymus may be made from the gradual onset, slowly increasing difficulty, absence of foreign body in the skiagram, dullness to the side of the sternum and an enlarged gland in the X-ray shadow. It is nearly impossible to differentiate an enlargement of the mediastinal glands from one of the thymus. In an enlarged thymus, dullness is usually higher up. The thymus patient is usually well nourished, although pale and pasty looking, and without a history of tuberculosis. Slight cachexia and elevation of temperature often suggest tubereu- losis in a thymus case. The author reports 6 cases, ranging in age from 4 weeks to 3 years. The X-ray treatment seems to be the most satisfactory and safest method. Extirpation is both dangerous and uncertain.—M. B. G. 306. (THYMUS) Persistence of thymus gland in relation to sudden death of adults. Taguchi (K.), Kyoto Igaku Zasshi, 1917, 14, 1-14. Jap. Med. Lit. (Seoul) 1917, 2, 2. The author in a review of three cases of sudden death dis- cusses the findings of the post-mortem examinations in their relation to forensic medicine. The first, a woman of 23, died during anaesthesia for a curettage during which less than 15 ee. of chloroform was given. The autopsy revealed a large thymus, a mild grade of hyper- trophy and fatty degeneration of the heart, and nephritis. A 14-year-old boy was drowned and the verdict, based upon the post-mortem examination, was that the accident had occurred as a result of heart failure incident to an enlarged thymus. A strong and well nourished man, aged 57 years, died within an hour after the administration of 1 ce. of typhoid vac- cine, with symptoms of chilliness, exhaustion, headache, 4 ABSTRACTS 337 dyspnoea, vomiting ete. The status thymicus was evident with. characteristic findings, such as definite persistent thymus, lymphoid hypertrophy, hypogenesis of the papillary muscles of the heart, narrowing of the aorta, imperfect calcification of the xyphoid process, and costal cartilages, and a general de- ficiency as compared with what would be expected of a man of that age.—L. G. K. 307. (THYMUS) Status lymphaticus. Symmers (D.) Am. J. M. Se. (Phila.), 1918, 156, 40-58. The paper comprises a discussion of the definition, clinical aspects and elinical signs of status lymphaticus, followed by an analysis of 249 cases seen at autopsy at Bellevue Hospital. There were 212 males and 37 females in the series. There were 118 cases which were well marked, 89 recessive and 42, border line, tending, however, toward recessive. In the 118 eases the thymus was hyperplastic in every instance. In 70 cases desig- nated recessive the gland was ‘‘practically invisible.”? The — only noteworthy histological change in the thymus was hyper- trophy of the lymphoid follicles, but the lymph nodes often had peculiar necrotic germinal areas, especially in the subjects that had met sudden death from trivial causes. In later stages the necrotic areas were replaced by characteristic whorls of con- nective tissue cells. The author believes that the sudden death that is frequent in status lymphaticus is due to anaphylaxis, the sensitizing substance being derived from the necrotic lymphoid tissue. The blood vessels in a considerable number of the cases showed gelatinous alterations or hypoplasia,—a condition predisposing to cerebral hemorrhage. A high inei- dence of status lymphaticus was noted in cases showing emo- tional instability and chlorosis. For many interesting details the original should be consulted.—R. G. H. 308. (THYMUS) Uther Beziehungen zwischen Thymus und Carcinom (Relationship between the thymus and carcinoma) II. Kaminer (G) and Morgenstern (O.), Biochem, Zeitsch. (Berlin), 1917, 84, 281-331. The authors claim to have proved that there is a close rela- tionship between the destructive action of serum upon cancer cells and the condition of the thymus.—Physiol. Abst., 1918, 3, 140. 309. (THYROID) A case of complete cretinism with normal mentality as the result of thyroid therapy. Hoag (W. B.). Arch. Ped. 1916, 33, 308. 338 ABSTRACTS Hoag presented a girl 514 years old, who first came under his care at the age of 34% months. At that time, she presented the appearance of a typical cretin. At the time of reporting, she was 40 inches in height and weighed 43 pounds; she talks and plays like any other child and the mother stated that she did not then show any abnormality. Thyroid treatment had been begun at the time he first saw the child, with one quarter of a grain of thyroid extract twice daily, this being gradually increased, until for a time, when she was 4 years old, she showed signs of excessive dose, when getting 5 grains a day. She has now been getting 3 grains a day for the past few months. The case showed the results possible with thyroid medication if the case is seen early enough.—M. B. G. 310. (THYROID) Cerebral manifestations in a case of exoph- thalmic goitre. Heuer (G. J.) Am. J. Med. Se. (Phila.) 1916, 151, 339. Heuer reports the cerebral manifestations in a ease of exoph- thalmiec goitre. This is of special interest and statistical value in that it is the first -of the grave cases to be operated upon. His case is that of a man, 23 years of age. Family history un- important. The illness was at intervals of six years’ duration. The symptoms of nausea, asthenia, dyspnea, dysphagia and diplopia gradually became worse. Examination revealed the presence of a bilateral thyroid enlargement, bilateral ptosis, fixation of the globes, exophthalmos, tachycardia and extreme nervousness. Summary of Cranial Nerve Examination: Olfactory un- disturbed; diplopia; complete ophthalmoplegia externa. The pupils reacted to ight. The sensory fifth nerve was unaffected, the motor markedly involved. Involvement of the seventh was shown by the mask-like face. Involvement of the remain- ing cramials was shown by the symptoms of dyspnea, dys- phagia and dysphonia. Marked hyperesthesia was also noted. Symptoms suggesting involvement of other glands like adrenal, hypophysis and thymus are discussed. After opera- tion temporary improvement was noticed. Patient died from acute respiratory failure. No postmortem. 336. — 1914 The correlation between the cyclic changes in the uterus and ovaries in the guinea pig. Biol. Bull., vol. 2A ee tT — 1917 The relation of the ovary to the uterus and mam- mary gland from the experimental aspect. Surg., Gynec. and Obst., vol. 25, p. 300. —— 1918 The relations between the interstitial gland of the testicle, seminiferous tubules and the secondary sexual characters. Biol. Bull., vol. 34, p. 33. M’Ilroy, Louise 1917 Physiology of the female reproductive organs. New System of Gynecology, edited by Eden and Lockyer, London, vol. 1, p. 39. MacLeod, M. J. 1880 Contribution a ]’étude de la structure de l’ovaire des mammiféres. Arch. d. Biol., T. 1, p. 241. Mann, F. C. 1916 The duetless glands and hibernation. Am. Jour. Physiol., vol. 41, p. 173. Meyer, R. 1913 Ueber die Beziehung der Eizelle und des be- — fruchteten Eies zum Follikel-apparat, sowie des Corpus luteum zur Menstruation. Arch. f. Gynaek., Bd. 100, me 4. Montuoro, F. 1903 Sulle cellule midollari dell’ovaio del coniglio. Con tavola IV. Arch. Ital. d. Anat. ed. Embr.., vol. 2, p. 45. Mulon, P. 1910 Sur une séerétion lipoide nouvelle de la glande interstitielle ovarienne. Compt. Rend. Soe. Biol., T. 69, p. 423. Nussbaum, M. 1880 Zur Differenzierung des Gesehlechts in Thierreich. Arch. f. mikr. Anat., Bd. 18, p. 1. O'Donoghue, C. H. 1916 On the corpora lutea and intersti- tial tissue of the ovary in the Marsupialia. Quart. Jour. Mier. Sci., vol. 61, p. 483. RASMUSSEN 401 Paladino, G. 1887 Ulteriori ricerche sulla distruzione e rin- novamento continuo del parenchima ovarico nei mam- miferi. Napoli. (230 pp., 9 pl.). —— 1888 La destruction et le renouvellement continuel du parenchyme ovarique des mammiféres. Arch. Ital. de |r el lps ily © a a Pardi, U. 1914a Sur la fonction endocrine de |’ovaire durant la gestation. Lo Sperimentale, p. 183; Arch. Ital. d. Biol. EOL, te Lee. —— 1914b Sur les cellules interstitielles ovariques de la la- pine et sur les éléments de la théque interne de l’ovaire humain hors de la gestation et durant celle-ci. Lo Speri- mentale, p. 409; Arch. Ital. d. Biol., T. 62, p. 353. Pearl, R., and Boring, A. M., 1918 Sex studies. X. The corpus luteum in the ovary of the domestie fowl. Am. Jour. Anat., vol. 23, p. 1. Pinto, C. 1905 Note istologiche sulle modificazioni delle ovaia in gravidanza. Ann. di Ostet. e Ginec., vol. 27, p. 476; Boll. d. Soe. med.-chir. di Pavia, p. 146. Plato, J. 1897 Zur Kenntniss der Anatomie und Physiologie der Geschlechtsorgane. Arch. f. mikr. Anat., Bd. 50, p. 640. Popoff, N. 1911 Le tissue interstitiel et les corps jannes de l’ovaire. Arch. de Biol., T. 26, p. 483. Pottet, M. 1910 Contribution a 1’étude du corps jaune pend- ant la grossesse. Thése, Paris. Rabl, H. 1898 Beitrag zur Histologie des Eierstocks des Menschen und der Siugetiere nebst Bemerkungen iiber die Bildung von Hyalin und Pigment. Anat. Hefte, Bd. At, p- 109. Rasmussen,-A. T. 1915 The oxygen and carbon dioxide con- tent of the blood during hibernation in the woodchuck (Marmota monax). Am. Jour. Physiol., vol. 39, p. 20. —— 1917 Seasonal changes in the interstitial cells of the testis in the woodchuck (Marmota monax). Am. Jour. Anat., vol. 22, p. 475. Regaud, C. et Dubreuil G. 1906 Richerches sur les cellules interstitielles de l’ovaire chez le lapin. Bibliogr. Anat., Ta t5, py. 169. — 1907 Variations macroscopiques de la glande intersti- tielle de l’ovaire chez la lapine. Compt. Rend. Soe. Biol., Paris, T. 63, p. 780. — 1908 Parallélisme des variations macroscopiques et micro- scopiques de la glande interstitielle dans l’ovaire de la lapine. Compt. Rend. Soc. Biol., T. 64, p. 901. 402 INTERSTITIAL CELLS — 1909 Nouvelles recherches sur les modifications de la glande interstitielle de l’ovaire consécutives a 1|’isole- ment et a la cohabitation avec le male. Compt. Rend. Soe. Biol., Paris, T. 67, p. 348. (An analysis of the work of Regaud and Dubreuil has been made by Pottet in Ann. d. Gynéecol. et D’Obstét., 1910, Série 2, T. 7, p. 363. ) Regaud, C. et Policard A. 1901 Notes histologiques sur Vovaire des mammiféeres. Compt. Rend. Assoc. des Anat., Session 3, Lyon, p. 45. Saimont, G. 1905 Recherches relatives a l’organogenése du testicule et de l’ovaire chez le chat. Arch. de Biol., T: 22, Poe Schaffer, A. 1911 Vergleichende histologische Untersuch- ungen tiber die interstitielle Eierstochsdriise. Arch. f. Gynaek., Bd. 74, p. 491. Schottlander, J. 1891 Beitrage zur Kenntniss der Follikel- atresie nebst einigen Bemerkungen tiber die unver- anderten Follikel in den Eierstocken der Saugetiere. Arch. & mikrs Amat. Bd. :3T, px 92. —— 1893 Uber den Graafschen Follikel, seine Entstehung beim Menschen und seine Schicksale beim Menschen und Saugetieren. Arch. f. mikr. Anat., Bd. 41, p. 219. —— 1914 Zur Theorie der Abderhalden’schen Sehwanger- schaftsreaktion, sowie Anmerkungen iiber die innere Sekretion des weiblichen Genitales. Erwaigungen auf morphologischer Grundlage. Zentralbl. f. Gynaek., Jahrgang 38, p. 425. Sehulin, K. 1881 Zur Morphologie des Ovariums. Arch. f. mikr. Anat., Bd. 19, p. 442. Scott, W. J. M. 1916 Experimental mitochondrial changes in the panereas in phosphorus poisoning. Am. Jour. Anat., vol. 20, p. 237. Seitz, L. 1906 Die Follikelatresie wahrend der Schwanger- schaft, insbesondere die Hypertrophie und Hyperplasie der Theea-interna-Zellen (Theea-lutein-Zellen) und ihre Beziehungen zur Corpus luteumbildung. Arch. f. Gynaek., Bd. 77, p. 203. De Sinety, L. 1877 De l’ovaire pendant la grossesse. Compt. Rend. de 1’Aead. d. Sci., Paris, T. 85, p. 345. Tandler, J. und Grosz, S. 1911 Uber den Saisondimorphismus des Maulwufhodens. Arch. f. Entw. der Organ, Bd. 33, p. 297, —— 1913 Die biologischen Grundlagen der sekundiren Ge- schlechtscharaktere. Berlin. Tourneux, G. 1879 Des cellules interstitielles de l’ovaire. Journ. de 1’Anat. et de la Physiol., T. 15, p. 305. RASMUSSEN 403 Van der Stricht, O. 1901 L’atrésie ovulaire et l’atrésie fol- lieulaire du follicule de Graaf, dans l’ovaire du chauve- souris. Verh. d. Anat. Gesell. zu Bonn, p. 108. —— 1912 Sur le processus de l’exerétion des glandes endo- erines: Le corps jaune et la glande interstitielle de Vovaire. Arch. de Biol., T. 27, p. 585. Wagener, G. R. 1879 Bemerkungen iiber den Eierstock und den gelben Korper. Arch. f. Anat. u. Entw. (Reichert’s Archiv), p. 175. Wallart. -'. 1907 Untersuchungen iiber die interstitielle Eier- steeksdriise beim Menschen. Arch. f. Gynaek., Bd. 81, pera ee —— 1902 Untersuchungen iiber das Corpus luteum und die interstitielle Eierstockdriise wihrend der Schwanger- sebaft. Zeitschr. f. Geburtsh. u. Gynaek., Bd. 63. p. 520. Wheelon. H. 1917 The internal secretion of the testis. Inter- state Med. Jour. (St. Louis), vol. 24, p. 1089. Whitehead, R. H. 1912 On the chemical nature of certain granules in the interstitial cells of the testis. Am. Jour. Anat., vol. 14, p. 63. Von Winiwarter, H. 1908 Das_ interstitielle Gewebe der menschlichen Ovarien. Anat. Anz., Bd. 33, p. 1. —— 1912 Observations cytologiques sur les cellules intersti- tielles du testicule humain. Anat. Anz., Bd. 41. p. 309. Von Winiwarter, H. et Sainmont, G. 1908 ttber die ausschliess- lich postfetale Bildung der definitiven Eier bei der Katze. Anat. Anz., Bd. 32, p. 613. Wolz, Elisabeth 1912 Untersuchungen zur Morphologie der interstitiellen Eierstocksdriise.des Menschen. Arch. f. Gynaek., Bd. 97, p. 131. Zalla, M. 1907 Ricerche sopra la struttura e l’istogenesi della sostasnza midollare dell’ovaia. Arch. Ital. d. Anat. e d. Embr., vol. 6, p. 706. 404 ~ INTERSTITIAL CELLS Plate 1 EXPLANATION OF FIGURES 1. Photograph of longitudinal section of ovary of active adult wood- chuck; just before hibernation (Oct. 26). Meves’ acetic-osmic-chromic fixer, 10 micra, no stain, no cover. X 7. Shows distribution of interstitial cells, which are co-extensive with the blackened lipoid, which is unusually abundant for this time of the year. 2. Photograph of adult ovary, comparable to figure 1 in thickness, plane of section and technique. X 7. Animal taken from normal habitat while dormant. Typical ovary of late hibernation (Feb. 25). Shows an in- crease in interstitial tissue as judged from the amount of lipoid. 3. Photograph, comparablé to figures 1 and 2, showing extreme hyper- trophy of interstitial cells as met with late in the rutting season (last of April and first of May). X 7. Somewhat greater development than nor- mally occurs at the beginning of pregnancy earlier in the season. CL are young corpora lutea. CL’ are corpora lutea of earlier ovulation not fol- lowed by pregnancy. 4. Photograph of area outlined in white in figure 3 under higher mag- nification. X 30. Shows the extent of lipoid-laden interstitial cells in the stroma. 5. Photograph comparable in every way to figures 1, 2 and 3, showing in black the characteristic interstitial cell content of late pregnancy and early lactation (May 8). X 7. 6. Photograph of typical ovary of midsummer (July 28) after inter- stitial cells have nearly reached a minimum. Shows characteristic fatty content of corpora lutea just before they commence rapidly to disappear. Same technique as in figures 1, 2,3 and 5. X 7. 7. Photograph of typical ovary of late summer when interstitial cells are minimal in size and number and almost free from lipoid. The single dark area is the remains of a corpus luteum which has not yet entirely disappeared. Same technique as other general views in this plate. Aug. 30. X.7. 8. Photograph of ovary of adult animal isolated in captivity till May 18, showing the small size of the ovary and the relative amount of inter- stitial tissue in females kept in captivity during the spring. Comparable to other general views in this plate. X 7. 9. Photograph showing migration of interstitial cells (identifiable by their black lipoid content and indicated by the arrow, which also shows the direction of movement) with neighboring stroma into a portion of a young corpus luteum. A portion of the corpus hemorrhagicum (CH) is present. Same technique as in preceding figures. X 60. 10. Photograph showing relation of interstitial cells (dark areas) to vascular channels, which appear as prominent light areas because the blood has been washed out. In the center of each interstitial cell mass is usually a medullary cord. Zenker’s with only 4 drops of acetic acid per 100 c.c., 5 micra, copper hematoxylin. X 45. Plate 2 EXPLANATION OF FIGURES 11. Photograph of ovary of pregnant woodchuck (foetuses 40 mm. to 45 mm. in length). Shot in the field April 17. Zenker’s, 10 micra, iron hematoxylin. X 67. Shows general view of cortex where cells appear to enter the ovary from the germinal epithelium. 12. Photograph of portion of figure 11 under higher magnification. X 333. : 13. Photograph of peripheral portion of section of ovary of old adult showing cells leaving germinal epithelium. Early autumn (Sept. 5). The uninterrupted portion of the tunica albuginea is marked T. Carnoy’s, 4 micra, iron hematoxylin. X 333. i4. Photograph of another portion of same section as figure 13 showing tunica albuginea apparently interrupted by cells from the germinal epithe- lium passing through it. A mitotic figure is seen at M. X 333. 15. Photograph of portion of adult ovary, in which the corpora lutea are rapidly being absorbed and many follicles are developing (Aug. 16), showing close relation of cells with oval and hyperchromatic nucleus to voung follicles. Carnoy’s, 3 micra, iron hematoxylin. X 333. 16. Photograph of medullary stroma of adult ovary as it appears in early autumn, showing relatively few cells with round vesicular nuclei. Carnoy’s 4 micra, iron hematoxylin. X 200, 17. Photograph of medullary stroma of adult ovary as it appears at the close of hibernation (Mar. 18). Animal sacrificed within 48 hours after waking up. To be compared with figure 16. Shows a noticeable increase in size and number of round nuclei (nuclei of interstitial cells). Carnoy’s, 4 micra, iron hematoxylin. X 200. 18. Photograph of medullary stroma of adult ovary when interstitial cells are maximal. Note large size of cells and vesticular nuclei. Carnoy’s, 4 micra, iron hematoxylin. X 200. Plate 3 EXPLANATION OF FIGURES 19. Camera lucida drawing of stroma of adult ovary showing transi- tional stages between elongated cells (free from fatty globules, with hyper- cromatie nucleus and with but little cytoplasm which is difficult to demon- strate) and typical interstitial cells with lipoid-laden cytoplasm (indicated as vacuoles) and round vesicular nucleus. Zenker’s with only 4 drops of acetic acid per 100 cc., 4 micra, iron hematoxylin. X 800. a, early indica- tions of cytoplasmic increase. Solid stained nuclei are lymphocytes. 20. Photograph of a corpus luteum-like structure still containing an ovum (QO). Early pregnancy (uterine enlargements 8 mm. to 9 mm. in diameter, April 27). Zenker’s, 10 micra, iron hematoxylin. X 30. 21. Camera lucida drawing of portion of adult ovary during mid- summer when corpora lutea (CL) are degenerating, showing characteristic down growths of germinal epithelium, giving rise to the irregular masses and cords of cells shown in the region marked C. Tunica albuginea is dark. X 500. 22. Photograph of atretic follicle and adjacent stroma when intersti- tial cells (IC) are maximal. M indicates the basement membrane of the granulosa and T the theca interna. Lipoid is black. Acetic-osmic-chromic fixer, 5 micra, acid fuchsin, no cover. X 44. 23. Camera lucida drawings, showing certain nuclear characteristics. Carnoy’s, 5 micra, iron hematoxylin. a and b are from the germinal epithe- lium of pregnant female and show what might be regarded as indications of direct cell division, but which is believed to be merely a folding. X 1000. ec is a section through cell cord newly derived from the germinal epithe- lium, showing the tendency for the nuclei to fold and twist. X 1000. d, e, f, g, h and i are cells encountered in the stroma especially in mid- summer, showing a variety of forms they may assume. Nucleus is gran- ular and hyperchromatic. Appear to have been derived from the germinal epithelium and may transform into typical interstitial cells. X 1500. Plate 4 EXPLANATION OF FIGURES All figures in this plate X 1000. Acetic-osmic-chromic or neutral forma- lin-dichromate fixation, 3 micra, acid fuchsin and methyl green stain. Large fatty globules appear black or as vacuoles. Mitrochondria and larger (secretion ’) granules are red. Nucleolus either blue or red. 24. Types of interstitial cells of ovary in autumn before hibernation, a and ¢ are transitional stages between elongated cells in the stroma and typical interstitial cells. Red granules are mitochondria. 25. Largest interstitial cells of ovary found immediately after wak- ing up from hibernation. a is an intermediate stage between cells of figure 24 and of figure 26. Note appearance of a few red granules distinctly larger than mitochondria. - 26, Interstitial cells of ovary at maximum hypertrophy during spring. a is a group of four cells with indistinct boundaries. Note numerous large and intermediate fuchsinophil granules. 27. Successive stages in atrophy of interstitial cells of ovary (late spring and early summer). 28. Interstitial cell (of ovary) that has survived atrophy (midsummer). 29. Lutein cell for comparison with interstitial cells. Shows typical granular cytoplasm. 30. Intermediate stages between ordinary stroma cells and interstitial cells of ovary. 31. Stages in degeneration of lutein cells for comparison with inter- stitial cells. 32. Interstitial cells of testis as they are in autumn. b contains three pigment granules, one yellow (natural color), one red and one blue. Pigment in ¢ is blue. p is a “pigment cell,” showing nucleus crowded to lower border of cell and cytoplasm filled with pigment granules, which are mostly blue, four red, one orange and four yellow (natural color) stained red only on the surface. Shows coalescence of smaller granules to form larger ones. Mito- chondria appear as small red granules. 33. a is an interstitial cell of testis in early stage of spring hyper- trophy. p is a pigment cell of this stage. Fatty globules appear as vacuoles, pigment blue, mitochondria red. 34. a is an interstitial cell of testis during maximum hypertrophy in spring and early summer. Pigment (blue) nearly absent. There are many fuchsinophil granules (red) and large fatty globules (vacuoles). The group arrangement often seen is indicated. p is a pigment cell of this time of the year just before complete atrophy. Mitochondria red. Pigment blue. 39. Interstitial cells of testis during midsummer atrophy. b is des- tined to become a pigment cell as p of next figure. Newly formed pigment is blue. Small red granules are mitochondria. 36. Interstitial cells of testis just after atrophy (Aug. 5). a repre- sents the majority and contains some pigment (blue) and mitochondria (red). p is a newly formed pigment cell. Mitochondria are red and pig- ment is blue or vellow (natural color) stained only on the surface. Forma- tion of larger granules from coalescence of smaller ones is evident. on y - ~ , A wt <' > - oAS & a ¥ Mf ihe THE ROLE OF THE THYMUS IN PEDIATRICS Murray B. Gordon, M. D. Assistant Clinical Professor of Pediatrics, Long Island College Hospital, Brooklyn, N. Y. (From the Department of Pediatrics, Long Island College Hospital) This paper is offered as a review of the literature of the past few years on the subject of the thymus. The study of this gland, both from an experimental and clinical viewpoint, has given the various inves- tigators contradictory results and has therefore given rise to opposing opinions as to its role in the general body metabolism. An attempt is made here to give an unprejudiced review. The thymus is susceptible to all infections and con- ditions affecting the general nutrition of the body. Pathological involution often results. In acute dis: eases like starvation, pneumonia, acute nephritis and acute infectious diseases, this change is usually fol- lowed by’ a return of the organ to the normal. In chronic disorders, however, a return to the normal does not take place, the gland instead undergoing a permanent sclerosis with resulting permanent involu- tion. Hereditary syphilis, tuberculosis and diphtheria produce atrophy and degeneration. Respiratory dis- eases (according to Charkowski) if not tubercular, do not interfere with the development of the thymus. In the course of an acute disease the thymus may be decreased to one-fifth or one-sixth of its normal weight. Function—The function of the thymus is still an open question. There is a tendency among investi- 405 ———————————___eee 406 THYMUS IN PEDIATRICS gators lately to question the former findings of Klose, Vogt and Matti that it is an organ of internal secre- tion and to give it now the same or similar function as that possessed by other hematopoietic organs like the spleen and lymph glands. Sajous thinks that it is not the source of an inter- nal secretion. He considers that the ‘‘ function of the thymus is to supply, through the agency of the lymphocytes, the excess of nucleins which the body, particularly the osseous, nervous and genital systems, requires during infancy, childhood or even later, if need be, to construct the nuclei of its cells.’’ He thinks that the thymus, due to its richness in nucleins, takes part in the oxidation and auto-protective pro- cesses of the body, and that it has some important re- lation with metabolism as regards the role of phos- phorus in the body. Conclusive evidence on these points, however, is lacking. The experiments of Klose and Vogt seemed to in- dieate that the thymus is essential to life, has a pro- found influence on growth and development of the body and presides especially over calcium metabolism of bone. They found that the removal of the thymus in animals was followed by marked disturbances in erowth, that the animals developed a condition re- sembling rickets and showed well-marked changes in the adrenals and thyroid. The thymus was re- moved in ten days’ old puppies. This was followed by a latent period of two to three weeks, then by a condition of adiposity lasting about two to three months, this in turn giving way to a cachexia and an impaired mentality resembling idiocy and finally eul- minating in death in about four months. It was claimed that extirpation of the thymus in children is GORDON -— 407 followed by the same results. Klose and Vogt con- sidered that the bone and other changes were due to an acid intoxication and that one of the functions of the thymus is either to inhibit the formation of nucleic acid or else to neutralize its excessive forma- tion. They also claimed that the total removal of the thymus in the young resulted in rickets, but that in adults extirpation was followed by osteoporosis and osteomalacia. Basch, Matti, Gudernatch, Rochford and others have reported substantiating observations. Considerable experimental study in the labora- tories of other careful investigators has failed to con- firm these results. Park assails the work of Matti, Klose and their followers on the ground that the changes found in the animals were due to poor hygienic surroundings in the kennels. Some of the results were obtained by extirpation of the thymus in guinea pigs. Park made a careful study of serial sections through the neck region of this animal and showed that a guinea pig has so much accessory thymus tissue as to render complete thymectomy im- possible. Earlier reports of results following thymec- tomy in this animal must therefore be interpreted as partial only. Pappenheimer claims that removal of the thymus does not produce disturbances in growth or devel- opment and that no pathological changes are found after thymectomy anywhere in the body. He arrived at the following conclusions: ‘*1. In some species of animals, complete re- moval of the thymus arrests growth, especially the proper development of the skeletal system. ‘*2. We have no data as to results of removal in human beings. 408 THYMUS IN PEDIATRICS ‘*3. We have no experimental work which gives us a clue as to the effects of an excessive or perverted secretion. ‘4. We are not yet justified in assigning to the thymus a definite role in the causation of any known disease.”’ E. R. Hoskins, using albino rats, found that thymus feeding resulted in no constant effects on body weight or on that of individual organs. Park extirpated the thymus in animals and found that no difference could be detected between the ex- perimental animals and the controls, either as to pro- creative activities, growth or conditions in endocrine glands. He did. not obtain rickets in any of his_ thymectomized animals. Swingle fed fresh thymus and powdered commer- cial thymus to 150 frog larvae and found that it had no effect on growth or on the gonads. Inter-relationship between thymus and organs of internal secretion. Investigators are divided as to the relationship be- tween the thymus and the organs of internal secre- tion, depending upon their belief as to whether or not the thymus itself has an internal secretion. Basch, Matti, Gudernatch, Paton, Henderson, Rachford and others claim that they have demonstrated this rela- tionship and believe that the thymus has an inhib- itory action on the thyroid, adrenals, gonads, spleen and pancreas. Halnan and Marshall, however, ob- served no pathological changes following thymec- tomy; their experimental animals did not show any abnormalities of growth or development after the re- moval of the thymus, nor did removal of both testes GORDON 409 and thymus in young guinea pigs alter the growth of the animals up to the time of sexual maturity. Park, Swingle and others also found that the thymus per- sists after castration. Heidinger found seven cases of enlarged thyroid in twelve cases of thymic death in the new born. Garre and Capelle found 95 per cent of fatal cases of exop- thalmie goitre to have enlarged thymuses. ‘There have been many other reports of a combination of exopthalmic goitre and thymus hyperplasia. (Vir- chow, Crotti, Hart, Weber, Gluck and others). Mac- kenzie noted that in 36 post mortem examinations of cases of exopthalmic goitre, the most constant feature next to thyroid enlargement was the pres- ence of an enlarged or persistent thymus. Hart be- lieves that there is a pure thymogenic form of ex- opthalmic goitre. Behlow makes the statement that he has looked for thymic enlargement in all cases of glandular dyscrasia and that he has found it in several in- stances. He also thinks that X-Ray examination of the chest in cases of Addison’s disease will show an enlarged thymus. Myesthenia gravis, while not properly a disease met with in children, will be considered here, as it. may be the result of a condition which has its incep- tion during childhood or even in utero. Bell quotes Starr, who had reviewed 250 cases of this condition and had noted a pathological state of the thymus in 28 of the cases that came to autopsy. Of 56 autopsies published since then, the thymus was found to be enlarged in 17 and contained a tumor in 10. Hart thinks that in this disease the affected individual has a ‘‘lymphatie constitution’’; in other words, is 410 THYMUS IN PEDIATRICS constitutionally inferior and therefore predisposed from birth to the development of such a condition. He also believes that the thymus in myesthenia gravis exerts a pathological function and is frequently, if not always, the cause of the disease. He states that the removal of the thymus produces a cure, but ad- mits that there are cases without thymus hyperplasia. His theory has not been substantiated. Absence or deficient activity of the thymus, ac- cording to several observers, produces mental dis- orders in children. Bourneville found that in 28 mentally defective children, the thymus was absent. He has shown, based upon the findings of a large number of autopsies, that in over 70 per cent of men- tally defective and epileptic children, the thymus was absent. Katz found that there was a normal thymus in every case of 61 normally mental children from 1 month to 13 years old, as shown by autopsy. Sajous believes that, while no type of idiocy can be referred to deficiency of any one gland, still, ‘‘de- ficient activity of the thymus results in deficiency of nucleins supphed to the brain through lympho- cytes, causing idiocy.’’ Harrower makes the state- ment that thymus hyperplasia is accompanied by defectiveness and by the hypoplastic type of indi- vidual. Status Thymo-Lymphaticus Post mortem examinations of cases of sudden death have in several instances revealed an enlarged thymus as the only pathological finding, with or with- out an accompanying hyperplasia of the lymphoid tissue of the body.. This has led-many to accept the thymus as the causative factor of the death, explain- GORDON 411 ing it on the basis of physical compression of the trachea or of the great vessels in keeping with the anatomical arrangement of the thymus. Antero-posterior diameter of the superior opening of the thorax is 2 to 3 centimeters. A finger placed behind the episternal notch can feel the impact of the rising thymus. The thymus follows the up and down movements of the trachea and larynx during acts of coughing, swallowing and hyper-extension of the head. Grawitz believed that it was possible for the thymus to become wedged in between the upper part of the sternum and the vertebral column in such a way as to compress the trachea at that point, caus- ing death from asphyxiation; this space is now known as the ‘‘eritical space of Grawitz.’’ Another place taken as a critical space where the trachea may be compressed is at the crossing of the innominate (Klose, Matti). Death may also bé caused by direct pressure on the base of the heart. Herrick suggests that the respiratory symptoms are probably caused by pressure on other organs, for how can one explain the fact that the trachea, which is cartilaginous, should suffer compression and the neighboring veins and arteries should not? Classification of thymus cases by various observers ean be summed up in the following grouping: A. Status Thymus (No changes in lymphatics). 1. Simple hyperplasia with clinical and anatom- ical evidences of compression. © 2. Simple hyperplasia without any symptoms. 3. With an accompanying increased activity of the thyroid which may cause clinical symptoms of exopthalmie goitre. 412 THYMUS IN PEDIATRICS B. Status Thymo-Lymphaticus. 1. Enlarged thymus associated with general en- largement of lymph tissue like adenoids, tonsils, spleen and mesenteric glands. To both groups may be added congenital enlarge- ment of the thymus and lymph glands. Cases of con- genital thymus enlargement have been reported by Heidinger, Kayser, Somma and others, but the ques- tion has been raised by some as to their being true cases of this condition. Crotti suggests that asphyxia neonatorum may possibly be due to congenital thymus hyperplasia. Hammar has done pioneer work in disproving the old ideas as to thymic death. His has been the most reliable work performed, as all his experiments, ob- servations and deductions were carried out with mathematical accuracy and precision. He claims that thymic death is not of thymus origin and he seems to have proved his case. The thymus in cases of sudden death from internal causes differ in no respects from thymus in healthy children. He com- pared the microscopic findings in 16 children from 3 weeks to 15 months old and analyzed and compared them with an equal number from apparently well children killed by accident or dying from external causes. He arrived at the following conclusions: (1) The two so-called critical spaces are so near to- gether that they can be considered as one, particu- larly in the new born. (2) The statement that the trachea is greatly compressed immediately before the bifurcation where the innominate artery crosses is erroneous, for the innominate artery lies above the bifurcation. If the trachea was actually compressed at that point by the thymus, that part of the thymus GORDON 413 lying immediately opposite, just above the base of the heart, must have been responsible. (3) Since the thickest portion of the thymus lies at the level of the base of the heart, just below the critical point, draw- ing the thymus upward would intensify dyspnea, since it would bring the thicker mass of the thymus between the top of the sternum and the spine. It would not relieve dyspnea produced by pressure of the thymus on the trachea. (4) If ascent of the thymus relieved inspiratory dyspnea, it was proof that the point of compression of the trachea did not lie above the thickest part of the thymus, but at, or below the thickest portion in the neighborhood of the bifurcation. The thymus is not forced upward into the neck with each inspiration but recedes into the thorax; it is forced up into the base of the neck during expiration, so that if it produced dyspnea by compression of the trachea, it would produce it during expiration and not during inspiration. Hammar proved that the notions of mechanical compression of the trachea by the enlarged thymus are largely false. His anatomical preparations show that an enlarged thymus may exert pressure close to the bifurcation or on the bronchi, particularly in the new born, but he does not say that it actually does. He also disproved that enlargement of the thymus is constant in thymic death. He showed that it was not possible to distinguish any fixed type; in fact, in the majority of glands, variations were within the normal limits. He studied 14 cases, 13 of which were in children (ranging in age from 9 days to 16 years). He estimated the exact amount of paren- chyma, minus the fat and connective tissue, by serial 414 THYMUS IN PEDIATRICS sections and reconstruction and in the same manner determined the exact relation of the medullary to the cortical substance. He counted the number of Has- sal’s corpuscles. He found that of the 13 children, the thymuses of only two were enlarged, while the others showed amounts of parenchyma that were within the normal limits. The cortical medullary in- ~ dex was high (normal). He arrived at the conclu- sion that no morphological ground exists on which to rest a theory of hypofunction or dysfunction. Other theories of thymus death. Tracy advances the view that there is a super- abundance of ‘‘ Hormone X”’ in the blood stream and insufficiency of adrenin. The existence of Hor- mone X has not been substantiated. N. Paton believes that thymus death is a pluri- glandular syndrome and that in the absence of secre- tions of these glands and because of general imper- fect development, death is more easily produced by trauma which would otherwise be ineffectual. MeNeil says that ‘‘status lymphaticus is an abnor- mal condition in the body in which if anaphylactic phenomena occur, they do so in an exaggerated way.”’ He advances the theory that it is an intensified anaphylactic condition but produces no proof. Wooley, with others, thinks that the clinical phe- nomena are due to over-functioning of the thymus. There has not been any supporting evidence to war- rant this conclusion. Another theory that has not been substantiated is one that tries to explain the symptoms as end results of an intoxication from the products of a faulty metabolism. GORDON 415 Symptoms of enlarged thymus Enlargement of the thymus may cause no symp- toms at all and the first warning of the presence of the condition may be a sudden paroxysm of severe dyspnea which may or may not terminate fatally, or else there is a sudden death from some slight cause or following a trivial operation. The chief complaint ‘is nearly always a cough or attacks of choking which come and go, frequently in paroxysms. Friedlander calls attention to three definite symptoms, Le., dyspnea, stridor and suffocative attacks with cyano- sis. The dyspnea is the most striking sign and may be constant or intermittent with or without par- oxysms. The stridor is inspiratory in character, and may be aggravated by fits of anger, exertion or sudden retraction of the head; it is more marked in sleep because of the position of dorsal decubitus as- sumed. Diagnosis of enlarged thymus Diagnosis of this condition depends upon physical examination and X-ray examination. While some elinicians question the possibility of making a posi- tive diagnosis of a normal thymus by means of per- cussion, there have been many who have been able to demonstrate an enlargement by this method. A fa- vorite with many is the so-called ‘‘threshold method.”’ The child is placed on his back in the mother’s lap. Percussion is begun well out in the chest, with such light strokes that when the ear is within a few inches of the area under percussion only the faintest pos- sible resonance is heard. When sound disappears, dullness begins. Some observers outline the borders of- dullness by the tactile sense of resistence rather 416 THYMUS IN PEDIATRICS than sound. The outer limits are determined much more easily than the lower boundary. This latter, which may be obtained by auscultatory percussion, is relatively less important. The percussion outlines, determined in this way, according to Benjamin and Lange, correspond remarkably closely to the Roent- genograms. A clinical diagnosis of thymic enlarge- ment is never absolutely positive without X-ray con-: firmation. Friedlander was the first to treat this condition fully by the X-rays. His first case has since had an anesthetic and has been operated without any bad results. He summarizes the treatment as follows: (1) In the X-ray we have an agent which is at the same time safe and efficacious in the treatment of en- larged thymus and status lymphaticus. (2) It is possible to induce not only an involution of the thymus, but also in cases of status lymphaticus, to re- duce the size of the spleen, of the lymph nodes and to change the lymphatic picture to a normal one. (3) The dosage of the X-ray can be regulated according to the necessities of the case. Where the symptoms of thymic asthma are urgent, the exposures can be given on successive days. A thymus partially invo- luted by the X-rays is capable of regeneration. The shadow of the normal thymus occupies a V-shaped area which scarcely extends beyond the limits of the median bony structures. An enlarged thymus gives a wide median shadow above the heart, appearing like a broad cap superimposed on the shadow of the heart and great vessels. This shadow is suggestive of thymic enlargement when it extends for some dis- tance on either side of the bony structure, above the heart shadow and continuous with it. GORDON 417 Cook advises that children with retarded mental development, if suspicion is directed toward the thymus, should have the thymus rayed. In the so- called lymphatic type of children, he suggests thymus raying as a pre-operative procedure. Operative Procedures Immediate operation should be performed in chil- dren if the mechanical symptoms are alarming. Tracheotomy may be of avail. The operation most frequently done now is that of thymectomy, the earlier ones of exothymopexy and resection of the upper part of the sternum having been to a great measure discarded. Organotherapy. Rational organotherapy is at present impossible owing to very unsatisfactory knowledge of the gland and its functions. None of the diseases in which thymus treatment has been tried has been shown to be related to either thymus hypo-function or dys- function. As Sajous has shown, if any results at- tend its administration, they are probably due to the high nucleic content of the thymus. It has been used for cretinism and hypothyroidism in conjunc- tion with thyroid for the possible effect on the osseous development. This relationship between the bony system and the thymus must be cleared up before this empiric treatment can be given a scientific basis. It is used also in rickets, Addison’s disease, infant- ilism and osteoarthritis. Sajous advises it in the condition known as progeria, a premature senility in which the child attains senility in a few years; he thinks the condition is due to deficient activity of the thymus. 418 THYMUS IN PEDIATRICS Hanaborg recently advocated its use in chorea, having obtained good results in 16 cases of this dis- ease. He thinks it plausible to assume that acute articular rheumatism may so affect the thymus that the secreting function is impaired and the unstable nervous system of the child feels the lack of the nor- mal restraining influence of the thymus. Thymus extract seems to have a sedative effect on the nervous system. It controls convulsions, these recurring when the treatment was suspended. Thymus insuf- ficiency, in his opinion, may be an added factor to the infection, but he gives salicylates in addition. Hanaborg’s work awaits confirmation. BIBLIOGRAPHY Bell (EK. T.) Tumors of the thymus in myasthenia gravis. Jour. Nerv. and Ment. Dis. (Lancaster, Pa.) 1917, 45, 130. Abst. Endoerin. 1917, 1, 368. Benjamin (J. E.) and Lange (S.) Report of nineteen cases of hyperphasia of the thymus gland, treated by the X-rays. Arch. Ped. (N. Y.) 1918, 35, 70-76. Crotti (A.) The Thyroid and Thymus. Philadelphia, 1918. Carlson (A. J.) in Supplement to Forchheimer Therapeusis of Internal Diseases. N. Y. and London, 1917, D. Appleton & Co., pp. 56-60. Charkowski (V.) Sull’ anatomia pathologica e normale del timo nei lattanti. La Pediatria, 1917, 25, 433. Abst. En- doeerin, 1917-1, 480, Cook (P. H.) Thymus hypertrophy, Roentgen therapy. Boston M. and §. Jour., 1916, 175, 483. Abst. Endoerin. 1917, 1, 106. Dunn (C. H.) Pediatries. The Hygiene and Medical Treatment of Children. Troy, N.Y., 1917, Southworth Co., vol. 3, pp. 357-364. Endocrinology editorial, 1917, 1, 282-285. Friedlander (A.) Enlargement of the thymus treated by the Roentgen ray. Am. Jour. Dis. Child. (Chgo.) 1917, 14, 41. Abst. Endoerin. 1917, 1, 519. Forchheimer (F.) Therapeusis of Internal Diseases. N. Y. and London, D. Appleton & Co., vol. 3, pp. 911-915. 1916, 22, 712-719. GORDON 419 Hoskins (E. R.) Growth as affected by feeding thyroid, thymus, hypophysis and pineal substances. Jour. Exp. Zool. (Phila.) 1916, 21, 295. Abst. Endoerin. 1917, 1, 69. Hammar (J. A.) Histology in so-called ‘‘Morsthymica.’’ Svenska Likares. Handl. (Stockholm) 1916, 42, 867. Abst. Endoerin. 1917, 1, 88. Haneborg (A. O.) Corea minor. Aetiologie og pathogenese. Norsk Mag. f. Loegevid. (Christiania) 1916, 77, 1040. Abst. Endoerin. 1917, 1, 113. Herrick (J. F.) Enlarged thymus in infancy. Surg. Gyn. and Obst. (Chgo.) 1916, 22, 333. Mackenzie (H.) Exophthalmie goitre. Lancet (Lond.) 1916, 191, 815. Abst. Endoerin. 1917, 1, 251. Pappenheimer (A. M.) American Medicine, 1914, New Series, 9, 212. Park (E. A.) Thymus extirpation in the guinea pig. Jour. Exp. Med. (N. Y.) 1917, 25, 129. Abst. Endoerin. 1917, i, 240. Park (E. A.) A review of the advances in our knowledge of internal secretions during the last two years. Am. Jour. Dis. Child. (Chgo.) 1916, 12, 477. Pfaundler and Schlossman. Diseases of Children, 1912, 3, 437. Renton (J. M.) Thymus extirpation and transplantation. Glas- gow Med. Jour. 1916, 86, 14. Abst. Endoerin. 1917, 1, 69. Swingle (W. W.) Experiments with feeding thymus glands to frog larvae. Biol. Bull. (Woods Hole) 1917, 33, 116. Sajous (C. E. de M.) Hemadenology: A new specialty. N. Y. Med. Jour., 1915, 101, 471, 586, 587, 694, 802, 1234; 102, 102, 206, 313, 419, 723, 916. Sheffield (H. B.) Thymus disease in children with report of a ease of thymus hypertrophy. Pediatrics 1917, 29, 5. Abst. Endoerin. 1917, 1, 532. Tracy (KE. A.) A contribution to vegetative neurology : touching upon heart action, status lymphaticus and so-called vago- tonia and sympathicotonia. Boston M. and S. Jour. 1917, 176, 538. Abst. Endoerin. 1917, 1, 336. The abstract department of Endocrinology has been freely consulted and utilized in the compilation of this review. 4402 Twelfth Avenue, Brooklyn, N. Y. THE NEWEST ‘“HORMONE”’ Swale Vincent, Winnipeg In the ‘‘Archives Italiennes de Biologie’’ for August, 1918, appears a résumé of a paper by Pro- fessor Marfori entitled ‘‘Sur la fonction hormonique des ganglions lymphatiques’’ (10). The original paper was published in Italian in 1916 (9). The author of this communication has performed some experiments with extracts made from lymphatic glands, and has arrived at the conclusion that these organs furnish an internal secretion, which he calls ‘‘lymphogangline.’? The methods by which he has reached this conelusion, and the grounds upon which he bases it, will be referred to later on. For the present it will be essential to give some account of the history of investigations upon tissue and organ extracts. The account which I am about to give may possibly save future workers from wasting time and paper upon a careful description of phenomena which are either well known or the presumption of which might follow directly from those already re- corded. The study of the effects of intravenous injections of organ extracts came into prominence after the publication in 1894 by Oliver and Schafer (11, 12, 13) of their important discovery of the extraordinary pharmacodynamical effects produced by extracts made from the chromaphil tissue included in the ad- renal body. Since that time observers have worked with extracts from every organ and tissue in the body, with the hope of discovering some remarkable 420 VINCENT 421 physiological action which might rank in importance with that of adrenin from the chromaphil tissues. The result of all these labors, as far at any rate as the action upon the blood-pressure is concerned, can be very readily and simply stated. One other tissue besides the chromaphil, namely, the nervous portion of the pituitary body, contains a pressor substance. All other organs and tissues furnish a depressor sub- stance or depressor substances. Oliver and Schafer noted, in addition to the ef- fects of adrenal extracts, that pituitary preparations also produce a rise of blood-pressure. Schafer and the present writer (19, 20) found that a depressor principle is also present in pituitary extracts, and recorded ‘‘a certain similarity of physiological action between nervous matter and the infundibular part of the pituitary.’’ Schafer and Moore (18) had previ- ously noted, in a casual manner, a lowering of blood- pressure on injection of brain extracts. . Professor W. A. Osborne and the present writer (14, 15, 16) found that extracts made from all parts of the nervous system produce.a marked fall of the blood-pressure, which occurs after section of both vagi and after the administration of atropine. ‘The question at once arose as to the chemical nature of the active substance, and our experiments led us to the conclusion that this could not be choline (as had _ been suggested by Mott and Halliburton) because this substance, when administered to an animal under the influence of atropine, produces a rise of blood-pressure, while our extracts of tissues, on the contrary, always produced a fall. Halliburton (6) maintained that the active substance was choline; in other respects his results were the same as ours. — 422 NEWEST HORMONE The present writer, working in conjunction with Mr. Sheen (25, 26), confirmed the statements of Os- borne and Vincent, and added some new facts. They reported that depressor principles can be extracted, not only from nervous tissues, but also from all kinds of muscular tissue, kidney, liver, spleen, testis, ovary, pancreas, and lung. They note also that others had extracted a depressor substance from thyroid and thymus. By this time it was clear to most observers that tissues generally impart to extracts a substance or substances the most striking action of which, when tested physiologically, is a lowering of the blood- pressure. There are of course other actions also, as for example, that on the pupil. This was not noticed by the present writer until recently, and with the strength of the extracts employed, was only shght. It was also clear that in most of these cases at any rate there is no reason to regard the presence of such substances as evidence that the tissues in ques- tion furnish an internal secretion. It would for ex- ample be nothing short of preposterous to assert that the presence of depressor substances in brain ex- tracts has any direct bearing upon the problems of brain physiology. I believe that no one up to the present time has suggested that the depressor action of brain extracts points to an internally secreting function of the higher nerve centers. Again, the present writer, working in conjune- tion with Dr. Cramer (23, 24), made a further at- tempt to isolate the depressor principle or principles in nervous tissue extracts. We found, it is true. a choline-like body in these preparations, but from physiological and chemical considerations, were con- VINCENT 423 vinced that this could not be the actual active sub- stance. The tests for choline employed by previous observers were unreliable. This was confirmed by Webster (27), who worked under my direction. Vin- cent and Cramer pointed out that normal blood con- tains a depressor substance. Popielski (17) has ventured to give a name to the unknown depressor substance discovered through its physiological action by my co-workers and my- self. He calls it ‘‘vaso-dilatine.’’ Schwartz and Lederer (21) arrived at the same conclusions as Vin- cent and Cramer; so also other observers. Although the chemical nature of the depressor substance is not certainly known, it is probable that it is B-Iminazolylethylamine [Dale and Laidlaw (3), Barger and Dale (1)]. This probability seems to apply at any rate to the principle found in the intestinal mucous membrane. ‘There may of course _be other active substances present in organ extracts. An account of this literature is given in my book on internal secretion (22) published in 1812. Biedl (2), whom Marfori quotes, warns investigators against assuming that a physiological activity shown by an extract of an organ is in itself any proof of an internally secreting function. The manner in which these results have been in- terpreted has not always displayed a proper critical attitude. Thus Livon (7, 8) divides the glands of the body into two groups, ‘‘hypertensive’’ and ‘*hy- potensive,’’ according as their extracts cause a rise or a fall of blood-pressure. If we insist upon such a division, we have to place the chromaphil tissues and the nervous portion of the pituitary body in the first, and all the other organs and tissues of the body 424 NEWEST HORMONE in the second group. Gautrelet (4, 5) holds views similar to those of Livon, and thinks that the ‘‘hypo- tensive’’ glands owe their activity to the presence ef choline. The point of view of these two observers is fairly typical of those who believe that the normal blood-pressure is maintained by a series of antag- onistic chemical messages arriving from the differ- ent glands and tissues of the body. This point will be referred to again later on. It will thus be seen that considerable attention has been paid already to the depressor action of tis- sue extracts, and the chemicai nature of the active substance. I have for some years taught my students that organs and tissues of the body yield to extracts a substance or substances which lower the blood- pressure. But I have warned them not to assume that this fact bears any direct interpretation in the direction of internal secretion. The fact is at this time perhaps largely of historical interest. I have also urged my laboratory workers not to write papers describing in detail the physiological action of ex- tracts of the vermiform appendix, of the vocal cords, or of the fingernails, beeause nowadays no one would accept the theory that these structures are to be classed with the endocrine glands. But now Professor Marfori appears on the scene and gives a careful account of the physiological action of extracts of lymphatic glands! It is remark- able that he makes no reference to any of the litera- ture quoted above. Surely he cannot imagine that it is irrelevant to his subject. He describes the action of lymphatic gland extracts on the heart, on the blood-vessels, on the pupil, on adrenalin glycosuria, and lays stress on the antagonism between the active VINCENT 425 principle and adrenin, and finally, with a great flour- ish of trumpets, announces a new hormone—‘‘lymph- ogangline.’’ His results, although they occupy four- teen pages of the ‘‘ Archives,’’ can be stated in a very few words. Extracts of lymphatic glands reduce the frequency of the heart beats (after the administra- tion of atropine), lower the blood-pressure by vaso- dilatation, contract the pupil, and hinder glycosuria of adrenal origin. Now this last action is only men- tioned in his ‘‘conelusions.’’ It is not referred to in the body of the paper, and no evidence in support of the statement is put forward. It is possible that this evidence is given in the original paper in Ital- ian, but I have not been able to consult this. Most if not all of these actions are the same as those ob- tained by the use of extracts of brain, spleen, or any other organ or tissue (with the possible exception of the constriction of the coronary vessels, which point I have not tested). The effect on the pupil is cer- tainly seen with other extracts than those of lymph gland, though I have not tried it with a large number. With the preparations of the strength I have usually employed (one in three or four parts of saline) the effect is not very marked, though quite distinct, but Marfori uses very concentrated decoctions (one gram of the gland to one cubic centimeter of normal saline solution) and no doubt obtained a greater contrac- tion. There is no reason to believe that the effect is a specific one. The reduction in frequency of the heart beat, especially after the administration of atropine, is by no means peculiar to extracts from lymphatic glands. Vincent and Sheen did not test this point very carefully, though one of their trac- ings shows the effect very clearly, even in an animal 426 NEWEST HORMONE without atropine. I have recently found that brain and spleen extracts reduce the heart frequency, espe- cially after atropine. The state of affairs, then, seems to be this, that extracts of chromaphil tissues stimluate sympathetic nerve-endings, extracts of the posterior lobe of the pituitary body have an action which is in some re- spects of the same character, while extracts of other tissues have an effect directly opposite. But surely this does not justify us in assuming an internally secreting function for all parts of the body. If such were justified, then observers might have already named a whole series of ‘‘hormones’’—‘nervine,”’ ‘“musculine,’’ ‘‘jecorine,’’ ‘‘testine,’’ ‘‘ovarine,’’ and so on. It may possibly save some labor on the part of future workers if I announce in this place that extracts of the haemolymph glands, of the corpora lutea, of the lining membrane of the arteries, of parathyroid, of the pineal body, and of different kinds of bone-marrow all have the same or very similar activities. If it is still possible to find some organ or tissue which has not up to the present time been extracted and tested, we shall not be anxious to hear about it, unless it should happen to contain a pressor and not a depressor substance, or should re- veal in other directions the presence of some new and remarkable active principle. Current views on the whole subject of intemal secretion demand a severely critical investigation. There is no branch of physiology littered with so many vague, unproved, and in many cases unprov- able hypotheses. The terminology is becoming in- ordinately complicated, and one meets with a newly coined word every few months. The term ‘‘hormone’’ VINCENT 427 iS in everybody’s mouth, yet how little do we know about these bodies! Only one alleged hormone has been chemically identified, and this has not been proved tobe a hormone at all. It is perhaps not alto- gether a matter for rejoicing that the word was ever introduced. The term ‘‘internal secretion”’ is better in many ways and is at any rate sufficiently definite to describe the little-known substances derived from organs which are admittedly organs of internal se- cretion. It seems to be established that the thyroid gland, the parathyroid bodies, the adrenal body (‘‘cortex’’), the pancreas (possibly the ‘‘islets of Langerhans’’), the duodenal mucous membrane, the reproductive organs (possibly the ‘‘interstitial’’ cells) and the pituitary body' furnish internal secre- tions which are of great importance in the economy. Yet in none of these cases has the chemical nature of the active secretion been ascertained.” Adrenin, the substance isolated by Takamine from chromaphil tissues, has not yet justified its. claim to constitute an internal secretion. | There has been for some years a tendency among the members of a certain school of physiologists, especially in France, to attribute an internally se- ereting function to all the organs and tissues of the body. This is exemplified by the views of Livon and Gautrelet quoted above. I imagine that the ten- dency has been derived, at any rate in part, from theories of the activity of adrenin in the animal body. It has been assumed that this substance is secreted by the adrenal bodies (or rather, by the chromaphil *The pineal gland ought probably to be included in this list. *Kendall’s work on the thyroid principles may point to an exception in the case of this gland. 428 NEWEST HORMONE -° tissues) in order to help to maintain the normal blood-pressure, and to preserve the tone of other sympathetically innervated structures. This matter cannot be discussed here, but it is not going too far to say that there is ne satisfactory evidence that the secretion of the chromaphil tissues is of any use whatever in the normal state of the animal. More- over, it is not clear that the circulating blood con- tains any adrenin. If we have to admit all this in the case of the chromaphil tissues which undoubtedly contain an extraordinarily powerful drug found in no other tissue,’ how much more must we recognize that there is no evidence that a lymph gland furnishes an internal secretion. The function of a lymph gland is to manufacture lymphocytes, and, although it may perform other functions in addition, we have no right to allocate rashly extra duties to an organ which has already, as we may imagine, sufficient labor to accomplish. We have not here as in the case of the adrenal bodies, a gland of unknown function, for which we seek to find some raison d’etre. The lym- phatie glands are not in the ordinary acceptance of the term, secreting glands. They are not formed of a highly specialized epithelium, and their structure does not suggest any kind of secretory activity. The substance yielded to extracts by a lymphatic gland is not powerful, and is not specific, but common to all organs and tissues. Reviewing the whole matter, it seems abundantly clear that there is not the shghtest reason for beheving that these bodies carry out any endocrine function. It follows that the term ‘‘lymph- ogangline’’ as apphed to the active principle in the ‘That is to say in the mammal. We must of course bear in mind the occurrence of adrenin in the “parotoid” gland of Bufo agua (Abel). VINCENT 429 extracts, is both useless and dangerous, and it is to be hoped that it will not find any place in the litera- ture. BIBLIOGRAPHY 1. Barger (G.) and Dale (H. H.) B-aminazolylethylamine a depressor constituent of intestinal mucosa. Jour. Physiol. (Lond.) 1911, 41, 499-503. 2. Biedl (A.) Innere Sekretion. 2te Aufi. Berlin, 1913. 3. Dale (H. H.) and Laidlaw (P. P.) The physiological action of B-aminazolylethylamine. Jour. Physiol. (Lond.) 1911, 41, 318-344. 4. Gautrelet (J.) Contribution 4 1’étude de la, choline dans l’organisme. C. r. Soe. d. Biol. (Paris) 1910, 68, 86-88. 5. Gautrelet (J.) La choline; son rédle hypotenseur dans l’organisme; contributions 4 ]’étude des coordinations fonetionnelles. Jour. d. Physiol. et d. Path. Gén. 1909, AL, 227: 6. BeiiGartn (W. D.) The physiological effects of extracts of nervous tissues. Jour. Physiol. (Lond.) 1901, 25, 229- 243. 7. Livon (C.) Séerétions internes: glandes hypertensives. C. r. Soe. d. Biol. (Paris) 1898, 5 (10se) 98-99. 8. Livon (C.) Séerétions internes. Glandes hypotensives. Tbid., 1898, 5 (10se), 135-146. 9. Marfori (P.) Atti d. R. Acad. Med. Chir. di Napoli, 1916, 70. See also: Sull’azione biologica dell’estratto di gangli linfatici e sulla funzione ormonica degle stessa. Arch. di fisiol. 1916, 14, 285. 10. Marfori (P.) Sur la fonction hormonique des ganglions lymphatiques. Arch. Ital. d. Biol. (Pisa) 1918, 68, 113- 127. 11. Oliver (G.) and Schafer (E. A.) On the physiological ac- tion of extracts of the suprarenal capsules. Proce. Phys- iol. Soe. Mar. 10, 1894. Jour. Physiol. (Lond.) 1894, 16, 1-iv. 12. Oliver (G.) and Sehafer (E. A.) Ibid. Proe. Physiol Soe. Mar. 16, 1895, Jour. Physiol. (Lond.) 1895, 17, ix-xiv. 13. Oliver (G.) and Schafer (E. A.) Ibid. Jour. Physiol. (Lond.) 1895, 18, 230-276. 14. Osborne (W. A.) ‘and Vincent (S.) Proe. Physiol. Soe. Feb. 17, 1900. Jour. Physiol. (Lond.) 1899- 1900, 25, 000. 15. Osborne (Ww. A.) and Vineent (S.) The phy siological ef- fects of extracts of nervous tissue. Jour. Physiol. (Lond.) 1899-1900, 25, 283-294. 430 NEWEST HORMONE 16. Osborne (W. A.) and Vineent (S.) : 385. BANTI’S DISEASE in children, progress and treatment of. Graham (EK. E.) Am. Jour. Obst. (N. Y.) 1916, 74, 548. Of no direct endocrine interest. 386. (CORPORA LUTEA) Etiopatogenia del embarazo extrau- terino. (Pathogeny of ectopic PREGNANCY.) Piccardo (T.), Semana Méd. (Bs. Aires), 1918, 26, 90. Piceardo has found that in many women operated upon for ectopic pregnancy, the tubes show no injuries of the mucosa (macroscopically). He believes in accordance with Ancel and Bouin, Moreaux and Katz and other observers that the smooth ABSTRACTS 483 muscle of the tubes brings about fixation of the ovule, fecon- dated or unfecondated, under the influence of the corpus lu- teum, and that ectopic pregnancy is due to early formation of the trophoblast. This in turn is occasioned by physical or anatomo-pathological disturbances of the corpus luteum. This theory is subject to much criticism. In fifteen pages no histologic evidence is offered to prove that the mucosa is normal, The nearness of the intestines renders infection prob- able. To conclude that the corpus luteum is responsible for the ectopic pregnancy without histological or macroscopic study of the structure is scarcely permissable. And finally, it is not inherently probable that the muscularis plays such a relatively large part and the ovum itself such a small one.—G. P. G. 387. CORPUS LUTEUM and the periodicity in the sexual cycle. Loeb (Leo) Science (N. Y.) 1918, n. s. 48, 273-277. A discussion of the author’s previous work on this sub- ject. —F¥. A. H. 388. (CORPUS LUTEUM) Etiopatogenia del embarazo extra- uterino (Etiopathogeny of extra-uterine gestation.) Picardo (T.) Semana Méd. (Buenos Aires) 1918, 25, 91. The author thinks that the premature fixation of the ovum is due to the ability it possesses to develop precocious tropho- blasts. It is probable that this capacity is derived not merely from the ovary but that the corpus luteum also contributes. —B. A. H. 389. CORPUS LUTEUM, Soluble extract of. Beach (L. E.) Maryland M. Jour. (Balt.) 1916, 59, 198-200. A superficial report of six cases of menstrual disorders treated by a soluble extract of corpus Iiteum. The results were favorable. The corpus luteum preparation was not identi- fied. —R. G. H. 390. CORPUS LUTEUM, The therapeutic use of the extract of. Happel (H. E.) Med. Ree. (N. Y.) 1917, 91, 848. After describing the origin, development, appearance and structure of the corpus luteum, Happel takes into considera- tion function, indications, and reports of cases in which the extract has been employed. The corpus luteum elaborates an internal secretion which (a) determines the development of the secondary sex characteristics, as growth of the breasts; (b) eontrols menstruation; (c) is essential to the uterine 484 ABSTRACTS changes connected with implantation of the ovum and its maintenance during the early stages of pregnancy; (d) retards ovulation during pregnancy; (e) aids in maintaining the nerv- ous equilibrium and normal metabolism. The extract obtained from pregnant animals is more potent than that from the non-pregnant. It is useful in the treatment of functional dysmenorrhea and amenorrhea, scanty or irregu- lar menstruation of young girls. Thyroid extract and extract of corpus luteum are exceedingly valuable in the treatment of the seanty or irregular menstruation of young women who have a tendency toward obesity. It is useful in some cases in nausea and vomiting of pregnancy. The neuroses of the natural, arti- ficial, and premature menopause are relieved by its administra- tion in adequate doses. The extract should be prescribed soon after operative removal of the ovaries. Asthenia, inability to concentrate, nervousness, scanty or irregular menstruation, the symptom complex of ovarian insufficiency are alleviated by the extract. It has also been recommended in the treatment of hyperemesis gravidarum, sexual asthenia sterility, and repeated abortion not due to pathological lesion. The dosage must be adapted to the needs of the patient, increased until the effect is produced, and the treatment con- tinued for a sufficient length of time. If the symptoms recur, it should be preseribed again.—W. H. 391. DIABETES and INFANTILISM, Case of. Parkinson (J. P.) Proe. Roy. Soe. Med., See. Dis. Children. 1917, 10, 2627. The author deseribes briefly a typical ease of diabetes in a 10 year old girl. She has grown very little for the past five years during which period the diabetic symptoms have con- tinued. There is no specific evidence of endocrine gland de- fects except the diabetes. The infantilism is of the Lorain type.—R. G. H. 392. (DIABETES) Besteht beim Diabetes mellitus eine Stei- gerung der Zuckerbildung oder eine Storung des Zuckerver- brauches? (Is sugar destruction diminished or sugar forma- tion increased in diabetes mellitus?) Bernstein and Falta. Deutsches Arch. f. klin. Med. (Leipsie) 1918, 127, 1. In light cases the fraction CO./O, (respiratory quotient) . is often normal. When a patient is kept on a ecarbohydrate- free diet and this is followed by one high in carbohydrate the fraction at first does not undergo a change because glycogen is formed; after a time in light eases the fraction increases on ABSTRACTS 485 account of oxidation of the sugar. Normally an intravenous injection of sugar causes an increase in the respiratory quo- tient; in diabetes such an injection is followed by glycosuria but not by an increase in the quotient. Injection of adrenalin or pituitrin has in diabetes no influence on this quotient. In serious cases of diabetes it is impossible to increase the quo- tient ; in cases the prognosis of which is fatal the quotient even diminishes and glycosuria increases. Although it is not pos- sible to prove that in diabetes more sugar is formed it is, ac- eording to the authors, certain that the oxidation of sugar is largely diminished.—J. K. 393. (DIABETES BLOOD GLYCOLYSIS.) Het suikersplit- send vermogen van het bloed in zyn beteekenis voor het wezen der suikerziekte onderzocht. (The glycolytic power of the blood and its significance in diabetes). Hekman (J.) and Van Heeteren (A.) Nederlandsch Tijdschrift voor Genees- kunde. (Haarlem) 1918, 62, 497. The authors have worked out a new, exact method for de- termining the glycolytic power of the blood. Contrary to pre- vious workers the authors always found the glycolytic power increased. They always used, however, the whole blood instead of only the serum, which procedure permitted a comparison of their values with those reported in the literature. In diabetes the results are not always uniform. In serious cases the glyco- lytic power was very low, but in other cases it was often in- creased. Lépine has previously reported a marked reduction after experimental pancreatectomy, but the authors, on the contrary, found a marked augmentation of glycolyic activity after this operation. Similar results were obtained from the blood in acute pancreatitis. In hyperthyroidism the glycolytic power was found often to be slightly diminished, in myxedema, often increased, in Addison’s disease, absolutely normal and in acromegaly markedly diminished.—J. K. 394. DIABETES, Pathogeny of, and fecal disinfection. Pala- cios (G. D.) Med. Ree. (N. Y.) 1916,89, 543-51. Develops a theory that ‘‘the primitive phenomenon of the pathogenic mechanism, of diabetes mellitus is to be found in an excess of ammoniacal and acid fermentatien of the large intestinal contents.’? The starvation treatment, according to this theory acts by relieving the intestine of its fermenting content.—R. G. H. 486 ABSTRACTS 395. DIABETES, The dietetic treatment of, complicated by nephritis. Stark (H. 8.) Med. Rec. (N. Y.) 1916, 89, 987-91. Of technical interest.—R. G. H. 396. DIABETES INSIPIDUS in children. Moffett (R. D.) and Greenberger (M.) Med. Ree. (N. Y.) 1917, 92, 487-95. This article comprises a detailed report of a case together with an excellent review of the literature. (IN. .Y.) 2907, 92: 357 ; A brief report of a case which developed and ended fatally within a period of three days.—R. G. H. 398. DIABETES MELLITUS, The diet in, as modified by con- siderations of nitrogenous metabolism. Cornwall (E. E.) Med. Ree. (N. Y.) 1916, 89, 907-10. Cornwall emphasizes the benefit to be secured by regulat- ing the quality and quantity of protein food to favor protein metabolism.—R. G. H. 399. DIABETES MELLITUS, The present treatment of, Moses (H. M.) Med. Ree. (N. Y.) 1916, 90, 1069-72. A readable general review of the most approved modern therapeutie practices useful to any reader desiring an epitome of these.—R. G. H. 400. DIABETES MELLITUS, The relation of prognostic fac- tors to treatment in. Foster (N. B.) Med. Press and Cire. (Lond.) 1916, 101, 193-95. The author emphasizes that every case demands eareful study not only of the diabetie state but of all conditions influ- encing health. Infections must be kept in mind as a constant danger. Early cases should be kent sugar-free to augment resistance and avoid acidosis. Restrieted low diets are the means of accomplishing this. In advanced eases glycosuria ABSTRACTS 487 must be controlled to regain normal weight and vigor. The chief difficulty is the necessity of long-continued constant Vigi- lance.—R. G. H. 401. DIABETES MELLITUS, Syzygium jambolanum in the treatment of. Kramer (A. 8.) J. Am. Inst. Homeopathy (N. Y.) 1918, 10, 1489-95. From experiments in vitro and on dogs, and humans, it was concluded that Syzygium retards diastatie activity, stimu- _ lates the pancreas to increase the oxidation of glucose in the muscles, and decreases the amount of glucose in the urine of diabetics unless the blood has been greatly dealkalinized. In the latter case, prior to administration of Syzygium, NaHCo, (contained in a double gelatin capsule to prevent its neutraliza- tion by the gastric HCl) should be given, or else calcium lactate if the urinary phosphates are excessively high. Syzygium is less efficient in glucosuria of renal (phlorphizin) origin and in that due to purely nervous conditions, and is not indicated in glucosuria produced by pituitary overactivity. Chem. Abst. 18, 2003.:- 402. DUCTLESS GLANDS, Diseases that can, with assurance, be referred to absence of, or derangement with function of. Root (A. S.), Arch. Ped. (N. Y.), 1918, 35, 401. The writer thinks that the only diseases which ‘ean, with assurance, be attributed to an absence of, or derangement of function of the ductless glands are those referrable to the thy - roid, i.e. myxedema, hyperthyroidism and exopthalmie goiter. There is some evidence to support the view that Frélich’s syndrome is due to a derangement of function of the pituitary gland. The clinical evidence in favor of giving pituitary gland in cases of diabetes insipidus is sufficient to warrant its admin- istration. Prescribing preparations of the endocrine glands for obscure disorders cannot be too strongly condemned. A plea is made for the early recognition of cretinism, in order that the best end results may be obtained, i.e., from early thyroid treatment.—M. B. G. 403. (DUODENUM) Extirpation of the duodenum. Drag- stedt (L. R.), Dragstedt (C. A.), MeClintock (J. T.) and Chase (C. 8.) Am. Jour. Physiol. (Balt.). 1918, 46, 584-590. As a result of the controversy as te whether the complete extirpation of the duodenum is fatal or not the authors per- formed a series of experiments in which the duedenum or vary- ing lengths of the jejunum or ileum were removed. Several 488 ABSTRACTS dogs so treated survived from one to three weeks, and one lived for three months without a duodenum None of them exhibited any symptoms which could not be explained by the loss of the bile, panereatic and duodenal juices, and death was really due to starvation from inability to digest food. The upper intestinal tract then can not be classed wtih the adrenals or parathyroids as essential to life. It was also found that when the intestinal juice was al- lowed to empty into the abdomnial cavity no toxic effects were produced. When bacteria were excluded from the lumen of the intestine, various pathological changes even to complete occlusion of the blood supply to an isolated piece of intestine with resulting autolysis and reabsorption, occurred without the elaboration of sufficient toxic substances in the cells them- selves or in their secretions to kill the animal. Nor was the duodenal juice found to contain any substance (hormone) nee- essary to the life or the function of the intestine lower down, since animals survived for as long as twelve days when a fistula was made which drained all the duodenal and pancreatic juice as well as the bile to the exterior.—h. G. K. 404. (ENDOCRINE GLANDS A case of pluriglandular dis- turbance; Organotherapy; Cure. Timme (W.) Arch. of Ped. (Ne Y=); 1917, 24, 901. A boy of 74% years had the nee of both hands and feet, erythematous and pustular; great fatigability; slowness in physical growth, sluggish mentality and uneven temperament were noted. The condition had continued a year and was steadily growing worse. A very complete history of the case, past and present, pointed to an endocrine disturbance, the hereditary factors pointing in the same direction. Pituitary medication was begun at once in the form of whole gland cap- sules administered twice a day, one hour after meals. To- gether with these, three drops of adrenalin in salt solution were given by the mouth three times daily, after meals. During the next two weeks the patient slowly improved, blood pres- sure rising to 92 mm. He had more initiative, was less irritable and more amenable to direction; weight remained stationary, extremities about the same, but less painful. At one time during the pituitary treatment, the patient complained severely of frontal headaches, a symptom frequently attending pituitary treatment. The headaches in this case promptly ceased when the administration of the gland was stopped. They did not return, even after beginning again with the gland. The quantity was diminished thereafter, the inter- vals between doses being inereased to whole days and even to two days.—W. H. ABSTRACTS 489 405. (ENDOCRINE GLANDS) A new syndrome. Block (S.) Med. Ree. (N. Y.) 1916, 90, 984-86. The author sets off one group of the border line endocrine- neurotic cases as presenting a new symptom-complex. The procedure appears to the reviewer as being merely verbalism. R. G. H. 406. (ENDOCRINE GLANDS) Dementia precox. Ernst (J. R.) Med. Ree. (N. Y.) 1917, 91, 942-3. In a general article the author points out the pancity of reliable data on the relation of the endocrine glands to this condition and emphasizes the need of extensive systematic re- searches on the problem.—R. G. H. 407. (ENDOCRINE GLANDS) Dysmenorrhea. Shaw (.J. C.) Internat. J. Surg. (N. Y.) 1916, 29, 321-24. An interesting general discussion of the etiology of this condition. Endocrine dysfunction is regarded as an important factor.—R. G. H. 408. (ENDOCRINE GLANDS) Fibromas del ttera (Uterine fibromas). Castafo (C. A.) Semana Méd. (Buenos Aires) 1918, 25, 69. Castafio believes that uterine fibroma is due to depressed thyroid and augmented ovarian and hypophyseal functions. He thinks that endocrine disorders are often produced by syphilis. No definite proof of the assertions is offered.—B. A. H. 409. (ENDOCRINE GLANDS) PEPTIC ULCER, The probable endocrine origin of. Friedman (G. A.) Jour. A. M. A. (Chgo.) 1918, 71, 1543-48. A somewhat uncritical review of the literature is offered. The reliable data as well as some dubious physiology and pathology are treated. The conclusion is reached that the endocrine glands play a predominant role.—R. G. H. 410. (ENDOCRINE GLANDS) Precocity. Cautley (E.) Med. Press and Cire. (Lond.) 1917, 103, 141-43. An interesting general discussion of this topic and of the part played by the endocrine glands. No new data are offered. 6..G; 2s 490 ABSTRACTS 411. (ENDOCRINE GLANDS) The ductless glands in de- mentia praecox. Dercum (F. X.) Arch. of Diag. (N. Y.) 1917, 10, 38-45. The various glands of internal secretion of patients with dementia praecox suffer in the course of the development of the organism so that their functions are subsequently imper- fectly performed. It is probable that the entire ductless gland chain is involved in most eases. Certain glands, especially the sex glands, may dominate the picture ; in some patients it is the thymus, in others the system of pituitary, thyroid and adrenals. The symptoms which would point to thymus involvement are considered in detail.—L. F. W. 412. ENDOCRINE GLANDS, Some observations upon the. Cobb (I. G.) Med. Press and Cire. (Lond.) 1916, 101, 466-69. A vigorous general article of interest particularly from a standpoint of practical endocrine therapeuties.—R. G. H. 413. (ENDOCRINE GLANDS) The bone changes occurring in Von Recklinghausen’s disease. Gould (E. P.) (Based upon an investigation carried out in the Laboratory of Prof. Lud- wig Pick, Friedrichshain, Berlin.) Quart. J. Med. (Lond.), 1918, 11; 221-27, Von Recklinghausen’s disease is more than a disease of peripheral nerves and skin. A frequent symptom is softening of the skeleton. This softening is microscopically and maecro- . scopically the same as osteomalacia. Osteomalacia beg prob- ably a disease of the glands of internal secretion, these glands must be studied in von Reeklinghausen’s disease.—Chem. Abst., 12, 2213 J ——s . 414, (ENDOCRINE GLANDS) The causation and cure of cer- tain forms of insanity. Farrant (R.) Brit. M. J. (Lond.) 1916, 1, 882-3. Reviewed elsewhere in this issue under the caption ‘‘The endocrine glands in the insane,’’ page 452. 415. (ENDOCRINE GLANDS) Relationship of the ductless glands to arterial disease. Daland (J.) Arch. of Diag. (N. Y.) 1917, 10, 32-38. Experimentation and accumulated evidence secured at the bedside clearly prove that overfunectioning thyroid and adren- als produce arteriosclerosis, more especially when the hyper- ABSTRACTS 491 function is long continued or recurs frequently. The method whereby sclerosis is produced is not known. It is probably a secondary process and no doubt varies in different patients. Overwork, mental or physical, throws an added strain on the duetless glands. Daland believes that worry, fear, and ‘‘stren- uous living’’ account for the great increase of this condition in recent years.—L. F. W. 416. (ENDOCRINE GLANDS) The ductless glands in gynecology. Bandler (S. W.) Am. Jour. Obstet. (N. Y.) 1917, 76, 644-673. ‘} 1916,.9, 66-7. This case is of interest in that selerodermia is often ascribed to thyroid deficiency whereas this patient showed marked evidence of ‘‘hyperthyroidism.’’ It might serve as an example of ‘‘hypothyroid manifestation’’ in Graves’ disease and cast some further doubt upon the theory that this disease is actually due to hyperthyroidism proper.—R. G. H. 597. (THYROID) Sobre atireosis. (Congenital myxedema). Strada (F.) Rev. Universidad de Cérdoba, 1917, 4, No. 6. ——_—S eer ABSTRACTS 541 Strada reports the result of a detailed postmortem exam- ination of a four-year-old myxedematous ecretin girl who had died of bronchopneumonia. Complete absence of the thyroid, cystic tumor at the base of the tongue and four parathyroids of normal structure were noted. In the hypophysis (Wt. 0.8 gm.) the intermediate cleft was filled with colloid. Microsecop- ically no alterations were seen in the neurohypophysis, which, however, was large. In the pars intermedia a colloid cyst was found. There were some chromophile cells in the anterior lobe of which the mass was made up of voluminous cells with clear protoplasm, sometimes slightly granular, pale in color, with vesicular nuclei lightly stained and round or oval in shape. The cell outlines were not sharp. Their appearance suggested the so-called ‘‘gravidic’’ cells. Skiograms of the bones showed an obscure line below that of the epiphysis. This, however, had not hindered growth when thyroid was administered.—B. A. H. 598. (THYROID) Sul morbo di Flajani—Basedow (Graves’ dis- ease). Mantella (G.) Pensiero Med. (Milan) 1916, 6, 221-23. A general discussion of the symptomatology and treatment is followed by a brief report of four cases treated with anti- thyroid serum. In three of these the results were favorable. —R. G. H. 599. THYROID, Surgery of. Gatch (W. D.) Jour. Indiana S. Med. Assn., 1918, 9, 13-17. Discusses the surgical treatment of goiter and emphasizes the importance of a careful study of each case. The Goetsch test (Adrenin cutaneous reaction) is especially valuable to de- termine the degree of toxicity. Operation should be discour- aged in the presence of pulmonary tuberculosis, edema of the feet, ascites or mania.—L. F. W. 600. (THYROID) Surgery of the thyroid gland.. Porter (C. A.) Boston M. and 8. Jour. 1916, 175, 551-557. An interesting discussion of the technique of thyroid- ectomy together with indications for and results of the opera- tion. Several instructive cases are discussed. The article does not lend itself to abstracting.—R. G. H. 601. THYROID, SYPHILIS of the. Thompson (L.) Am. Jour. Syphilis (St. Louis), 1917, 1, 179. Review of the literature and report of a case. This is a rare condition but would probably be more frequently recog- 542 ABSTRACTS nized if looked for more systematically. It appears to be more common in women than in men, and may occur at any age. It may accompany either congenital or acquired syphilis. The histologic picture of early stages has not been described; later stages closely resemble tuberculosis of the gland. The clinical picture may present nothing but tumefaction of the gland, or there may be tachycardia and exopthalmos.—J. P. 8S. 602. THYROID, The alleged detoxicating power of. Bassinger (H. R.) Jour. Infeet. Dis. (Chgo.), 1917, 20, 131. Bassinger injected diphtheria and tetanus toxins directly into the thyroid gland. He was unable by this procedure to demonstrate any detoxicating action on the part of the thyroid. —J. P.S. 603. (THYROID) The differential diagnosis of mild thyroid toxemia and incipient pulmonary tuberculosis. Jennings (C. G.) Med. Press and. Cire. (Lond.) 1916, 101, 423-24. A general discussion. No new data.—R. G. H. 604. (THYROID) The etiology of the exophthalmos in hyper- thyroid goitre. O’Day (J. C.) Internat. J. Surg. 1916, 29, ate-b3. A theory is offered that the exophthalmos is dne to stasis in the ophthalmic veins, due in turn to ‘‘tetany of the ven- tricles.’’ No new evidence is offered.—R. G. H. 605. (THYROID) The hypothyroidic eye. With some notes on Napoleon’s myxedema. Jacobson (A. C.) Med. Times (N. Y.) 1916, 44, 207-209. The author believes that such a term is desirable to de- scribe the somewhat inconspicuous appearance of the eye in myxedema and cretinism as contrasted with the prominent eye in Graves’ disease.—R. G. H 606. (THYROID) The influence of certain factors on the inci- dence of endemic goiter. Mackay (N. D.) Caledonian Med. J. (Glasgow) 1916, 10, 254-63. A general discussion of the relative importance of geologi- cal conditions, species, race, heredity. age, sex, occupation and social state as factors in the incidence of endemie goiter. —R.G.H. ABSTRACTS 543 607. (THYROID) The irritable heart of soldiers. Wilson (R. MeN.) Brit. Med. Jour. 1916, (i), 119-20. The author is somewhat skeptical of the theery that the thyroid plays a significant role in this condition.—R. G. H. 608. (THYROID) The isolation in crystalline form of the com- pound containing iodin, which occurs in the thyroid: its chemical nature and physiological activity. Kendall (KE. C.) Tran. As. Am. Physicians (Phila.) 1916, 30, 420-49. Data published elsewhere. See abstracts Endoerin., 1917, 7, 18, also 1918, 2, 81-93. 609. (THYROID) The life history of the thyroid apparatus. MecCarrison (R.) Med. Press and Cire. (Lond.} 1917, 108, 307-9. The article being itself a summary of existing knowl- edge—and probable hypotheses—is impossible to abstract sat- isfactorily. Among the points emphasized is that the human infant is dependent during the normal suckling period upon the mother’s milk for its elaborated thyroid hormone, a fact which is not true of the calf, hence artificial feeding of infants with cow’s milk necessarily leaves a thyroid deficit. If Me- Carrison’s point is well taken, the addition of minute quanti- ties of thyroid material to the milk of such infants should be made as a routine measure. The close relation of the thyroid with all phases of sex life is emphasized.—R. G. H. 610. (THYROID) The relation of the thyroid gland to epi- lepsy. Harrower (H. R.). Lancet-Clinie (Cineimnati) 1916, 116, 100-104. The author believes that the thyroid gland because of its intimate relation to detoxication and to metabolism in general should be considered as a possible factor in the etiology of epilepsy. In eases in which evidence of thyroid defiicency is noted thyroid therapy can be expected to act as an effective adjuvant to other measures directed toward the epilepsy. —R. G. H. 611. (THYROID) ‘‘The soldier’s heart’’ and its relation to thy- roidism. Barr (J.) Brit. M. Jour. (Lond.) 1916, (i), 544-46. Barr regards the thyroid as being largely at fault in this condition. The influence of the gland is exerted primarily upon the calcium metabolism which in turn affects the action 544 ~ ABSTRACTS of the heart. The condition first appearing is likely to be ‘‘hyperthyroidism’’ followed by hypothyroidism. Calcium preparations together with iodin and thyroid tablets are fa- vored by way of treatment.—R. G. H. 612. THYROID, The relation of the to the other ductless glands. Kendall (EK. C.) Jour. Lancet (Minneapolis) 1917, 37, 768. Data reported elsewhere. See Endoerin. 1918, 2, 81-93. 613. (THYROID) Tiroides aberrantes. Jorge (J. M.) Semana Méd. (Bs. Aires), 1918, 25, 542. Jorge presents two cases: (1) A woman having an aberrant thyroid at the base of the tongue between the muscles of the floor of mouth; (2) a girl having a similar gland in the muscles, between the lingual V and the epiglotis. The glands were ex- tirpated.—G. P. G. 614. (THYROID) Treatment of certain types of goiter with quinine and urea injections. Watson (lL. F.) Texas M. J. (Austin) 1916, 82, 153-158. Data reported elsewhere. See Endocrin. 1917, 1, 178, 376. 615, (THYROID) Trichomonose intestinal: cura pelos en- teroclymas iodicosi Myxedema consecutivo; cura pelos thy- roidina. (Trichomoniasis intestinalis cured by iodin entero- clysis, followed by myxedema cured by thyroid medication). Ribeiro da Silva, Brazil Medico (Rio de Janeiro), 1917, 31, 24. The first treatment was given successfully to eure a severe diarrhoea due to trichomoniasis, but it was followed by marked facial edema. This was ascribed to hypothyroidism. Upon in- stituting thyroid medication the edema in the course of a month cleared up.—B. A. H. 616. THYROID tumor, An intrathoracic. Report of a case with autopsy findings. Moses (H. M.) Med. Ree. (N. Y.) 1917, 92, 1025-26. The tumor measured 14x8x6.5 em. The patient had gen- eralized arteriosclerosis, dying from a rupturcd blood vessel of the colon. The thyroid played no apparent part in the symptomatology except as possibly interfering with the aetion of a poorly nourished heart.—R. Gui. ABSTRACTS 545 617. (THYROID). Zur Joddarreichung bei Kropf. Crumme. Correspondenzbl. f. Schweiz. Aerzte (Bern), 1916, 46, 494. Crumme claims that the administration of iodin benefits patients with endemie goiter, but does harm to those with Base- dow’s disease. Regions in which goiter is endemic are usually free from exophthalmic goiter. Crumme therefore believes that endemic goiter is due to a lack of iodin in the food. He recommends that Switzerland import sea-fish in abundance so that it may become generally used as a food. He believes that the rich iodin-content of this food would greatly reduce the incidence of goiter in Switzerland. The ancient Greeks recom- mended sponge charcoal, which is rich in iodin, in the treatment of goiter. Crumme warns against the use of iodin in those patients who show a tendency to Basedow’s disease. Even eat- ing sea-fish aggravates exophthalmie goiter.—J. P.S. 618. THYROIDECTOMY, Partial. An operation for trans- planting and anchoring the remaining lobes of the thyroid gland. Hubbard (EK. V.) Med. Ree. (N. Y.) 1917, 92, 842-47. Of technical surgical interest.—R. G. H. 619. (TONUS) Some attempts to produce experimentally con- ditions of sympatheticotonus, vagotonus and hyperthyroid- ism. Troel! (A.) Surg. Gyn. & Obst. (Chgo.) 1916, 22, 81-92. With certain modifications, Troell repeated the experiments of Cannon (1914), who reported that it was possible to obtain. through a ‘‘hyperstimulation’’ of one sympathetic brought about by fusion of the anterior root of the phrenic of a eat, with the cervical sympathetic nerve, the same symptoms that characterize Graves’ disease in human beings. ‘Troell united in the neck the proximal end of tke phrenic nerve with the sympathetic or vagus. In order to escape the disturbing influ- ence of the vagus fibres on the heart he made the anastomosis of the nerves in the thorax near the diaphragm. In several individuals phrenic and one sympathetic were severed and then sewed together, so that proximal end of the former was connected with the distal end of the latter, imme- diately under or at the superior cervical ganglion; phrenic im- pulses of central origin would then influence chiefly the smooth muscles of the orbit of the eye. A second series of operations in the thorax consisted in cutting off the proper nerve-trunks and uniting the proximal end of the phrenic with the distal end of the sympathetic or vagus. 546 ABSTRACTS No unquestionable symptoms indicative of sympathetico- tonus, vagotonus or hyperthyroidism were found. Loewi’s adrenalin test was negative in the five cases in which it was made. In the eyes no other symptoms were found than the customary effects (paralysis) on the operated side. Equally unsatisfactory were the macroscopic and micro- scopic findings in the organs on autopsy. Numerous firm adhe- sions and strands of connective tissue were present; the intes- tines showed occasional saclike extensions and the mesentrie¢ glands were enlarged, indurated and pigmented.—W. H. 620. VAGATONIA. Tonus problem und Vagatonie. Schmidt (R.) Ztschr. f. kin. Med. (Berlin) 1918, 84, 89. The author contributes a critique on the theory of vaga- tonia. If one is to believe in the theory of Eppinger and Hess, it is concluded, he should not know too much of clinical medi- cine, physiology and pharmacology. Most of their principles have never been demonstrated and some are demonstrably not valid.—J. K. ; The abstracts in this number have been prepared by the staff assisted by: W. E. Blatz, University of Toronto. W. Harrison, Detroit. L. G. Kilborn, University of Toronto. V.J. Pollina, Boston. Hector Rosello, Montevideo, Uruguay. J. P. Simonds, Northwestern University, Chicago. A. L. Tatum, Chicago. L. F. Watson, Chicago. With the permission of the editors, certain abstracts have been quoted from ‘‘Physiological Abstracts’? and ‘‘Chemical Abstracts. ”’ INDEX GE sets, CE UMCOIRS) . cece cise sss 500 PATO RUSS tela. tee cei teen fe sia Sistets eis eis 15 = 66 eye Oop el oF 9 Ih SP Oe lo 163 Abortion, incomplete, pituitary PEPSI TO] "3 0 6 TR Te Re eras oka a 189 Aberrant thyroid......... soa Meira age ee Abrahamson, Q. (Climenko)....417 Acetonitrile test for thyroid..... 460 Achrondoplasia with history of HypPotByroidisny —s..5.:.:.- 207 Acrocyanosis, Vincent’s syndrome.350 Acromegaly....... 48, 169, 216, 218 —and diabetes insipidus....... . 64 — ORO ROT MEV PICAL 2 ».< «els oneke ovens 236 see EROERISETRUCN Nats fe cl cae alte Aotrata) bw neh 3 494 TAINAN “ANG ces age feels eles ns 236 — hallmark of a stopped process.220 ap OAL MICU Os ere asin lars) asd lores a(n Addis, T. (Barnett and Shevsiey)) so: . cece ss 161, 189 — (Foster and Barnett)....... 162 — (Shevsky and Bevier)....... 316 LNGVIINSET DS 3, a La Sea ee 63 Addison’s disease, adrenal prod- AUGUST AUN meaner eels) < Sua, ‘ois 301, 308 —-—and Basedow’s disease... .470 — —w— deficient tissue oxida- ELON SR. Sera ce aate e b ones 272 — —— exophthalmic goitre...475 — — — the “respiration theory’’.264 SS (GSE 0) Ra eA a 160 — — history of case.......... -.301 — -— low adrenin content of ad- renals after death...... 316 —-—ssuprarenal gland in termi- TEU reer ee eyo ates aeons 308 = SVNOTOMEG! eacralals sraleen sok cis 49, 471 PMC eN OLAS ae eases) eae sie wih os 214 —cause of hypophyseal femin- ISTE rater ie See weaves FS 172 AGiposis “dolorosa. so. k. ashes eee Lid ——report of case...........502 ITO STUY art hemes ech cae, oer ~.s sce 219 —and scanty menstruation..... 439 — in diabetes insipidus........ yas Adiposo-genital dystrophy and normal urine output....... 118 — ——endocrine origin of....439 —-—-—in women............502 —-—-— metabolism in......... 500 Adiposo-genitalis of syphilitic ori- gin Adolescence, pituitary disturb- PAYICONATY Ga oe os ooo Caio hd RR Pa ee eee — psychoses of, and pituitary GisiiTVAtCes §~.. s/- = ) a6 aia ke! — constrictor effect of succeeding GOSCS: $i-5.4 : settle Yincaeee 138 — ‘content of -blood:.:.........\. sae 312 —-—of suprarenals........... pale — —-— — after death by beri- beri, <2. ie See 312 —ilatation, brief sketch of knowledge. Of...... =. =e 123 — -— methods of research...... 124 — dilatator mechanisms........ 123 — effect on blood fiow in muscles.164 —— —— pressure ......... 2 etd: — — — vessels 4.05 722 122 — — — fatigue .............. 480 = —— — irritability 22.2252 eee S15 — — — leucocytes .........2.3 161 — glycosuria and hyperglycemia. 55 —in Addison’s disease........ 5 iors Aa Ee 301, 303, 304, 308 — — blood of one suffering from glaucoma. 2>-ene. ae 314 —-—diabetes insipidus.......- 321 — influence of on blood distribu- tion. in-man.: . "4 >. eee 482 —— — —— urine ...8...:..+25 160 — inhibitory effect of......... 316 — injection and white line of ad- renal insuficiency. 9... 215 —-— causing constriction...... 479 — — effect upon blood=.2---e. Stils: —'-— jn ~asthma......%: 2% 5.0 - = eee 270 — injections and metabolism.... 88 — mydriasis ana dementia DraAceCOk. 2 cs Te eee 476 — painting of pancreas, effect of .330 —pituitrin and in asthma...... 517 — produces diuresis. ...--.s.5- 449 —relation of urea excretion. ...161 —regulation of renal activity MPR Pee AE bars 161, 162 —response in birds........... 140 — —— carnivores ........-..-- 140 — —— ferret <2... 2s sce ee gis Fit — ——the fowl........ <<: ss 125 — — — poat ... 8. 2. oe ee 129 Adrenalin response in horse....128 — — — Mammals .:......<6... 140 ——-— marsupials ........... 140 ——— —— OPOSAUHE ee cy eles te soe ae 126 — — — primates ......6...060. 140 — —-—- TACOON ..........0000 U3 — ——rabbit............ 132; 135 ——— reptiles .............. 140 —— —- rodents .....0...0500. 140 ——w— turtle ............... 124 ——w— ungulates ............ 140 —— — white rat............. 132 — sensitiveness to, following thy- MOLUOCLONN Ye bate of eles ce 2 Re Ge ele 5 — stimulation of sympathetic ter- MVM ALOT A Ge, ac. pest a eee ee ats 449 — treatment of nephritis....... 480 — use of in anaesthesia........ 161 — vascular changes produced by ie Verte DTaAtes: . 2c ale tatla ce a0 122 — vasodilation in skeletal muscle 10 — — location of intestinal mech- SUMIUSINN Ae See cece es 6 =— ——— limb mechanism..... 6 — vasodilator mechanism....1, 476 — — — absent in reptiles, birds and, rodentses «. $2 0%.. 9 — —-— animals found in...... — — — location of..... 6,160; 163 — —-—not in central nervous SYSLCIO Ox Noe ssrererd sc % 4 — — — occurrence of.......... 8 sAG UAE INOOT se) oI Ae, Ale ae Aeneas Wa .538, 55, 162, 163, 164, 476-482 SS OEE hs) ee 278 ———AECELOM Ol: es ots. we es Ab. 162) 35 EIA MInIstrabON: Ofc se ... oe s 273 — affects oxygen exchange in EDO ere PT aS Aon ote vue ene Seah & 270 —and autonomic nervoussystem.477 —-—arsphenamine ........... 467 —-—blood sugar increase.....198 — -— cardiac resistamce......... 478 —w— digitalis therapy......... 163 —-—neo-arsenobenzol ........ 477 ———neoSalvarsam ...:......:. 54 — — pituitrin in bronchi, antag- ONIStIGTEHeCE.] 16.6 eet 478 — character of toxic action of. .479 — circulating, minute quantity CLE RNs eta a eee oo PATS —GONGENEVAtION 22 .\) ck ns 6 ee es 276 — constriction produced by..... 2s —content of human adrenals 0 oy emo Pet Fl os aie re 316 — —— suprarenals in death by DETIDETI ES. Se ee 2 — “conversion”’ rather than “‘de- SURMGULOM Crete arctel gs eee ele 2TT — destruction by oxidation..275, 276 — effect on blood pressure...... 273 — —— distribution of blood. ..316 Adrenin effect on dying and fa- tigued muscles 54.229. 56 315 — — — irritability ........... 315 — — — isolated pregnant uterus.163 —-—-——muscle .............. 65 — —— non-pregnant uterus....163 — — — tissue cultures......... 314 — —w— urine flow............ 163 —— hyperglycemia, ergotoxin and.163 — in Addison’s disease.,...... PO ae Se 301, 303, 304, 308 — influence of causing exanthema 54 ——of temperature on activity DPRsr ovine oy Se nee eee 278 — inhibits excretion of sodium ehianide 2. Us: ois Waa eee — injections, effect upon blood. .313 ——in red corpuscles......7.9.. 278 — liberation from adrenal glands.157 —neutralization of in normal blood — pituitrin, action of on muscle..317 — — treatment of asthma.....: 479 — quantity required to produce recorded effects........... 276 — rate of liberation into blood. — reaction of in typhoid patients. 318 ————Stomach to..:....5.6.; 315 —relation of to experimental nyperslycemias-<. <2). Maes 54 — some actions of on liver...... 53 — study of action on heart by ra- GIiOSCOPE! 26 2. HS Ae ss oe ee 478 — test for thyroid disorders... .460 NdPenGgxidasr® “04 25 woot Se oe 278 Adsons +A a W ss) os. Soke Se 324 OMA TSTMS. so lets cs ete orate 49 Aikins, W. H. B.. oe BOD ee Albumoses in hypophy sealextract. 500 Alfred HOON Y 3.6.0 Sos oe eee Alimentary glycosuria........29, 50 —-—absence of.............. 28 —rest in treatment of diabetes mellitust atess...0 ats oe .514 — tract, effect of thyroid feeding WMpOnS eset eew ea ae ee 200 Allen, B. M..170, 194, 205, 206, 351 Alveolar abscesses and hyperthy- POMUSTHS soe. Foe sia» cS lee rere 2 Amblyopia treated with pituitary CRUNACH OE fol Se ela Stak eR ere 175 Amblystoma, pharyngeal deriva- TAVOSOE. ir eres x a a ee Ambulatory types of thyroid dis- CABS ois ke hws hea ee a spe Amenorroiea se. 20 oi! ts eee 438 — corpus luteum in........... ile ——OVATICN IRs ei. oak ks ee 52 Amnesia following thyroidectomy.525 Amentia, atrophy of glands in. .453 AINOPEELE, Misses soa alereral aio aan 537 Amphibian larvae, studies upon.170 Anaesthetics combined with ad- Tenalin®: +... cakiseAe belek Beer OM: Anatomy of parathyroids....... 516 Anemia, adrenal insufficiency WGI: becca ieereeete yee lane Ub ches sau 327 Animo acids, relation to thy- TO XAT oes lie ioe n'y jeiwges sis be 92, 93 Anorchidism, congenital, case of. 68 Antibody production following ad- TEN AIECTOMLY: 225\o ae ees Be eee 309 Antidiuresis as a normal pituitary TUN CEIOMW\ caer eartens ee eke 448, 449 ““Anti-toxic action’’ of endocrine lands. crcayeyn cece stor. erp 42 — functions of adrenals.......: 274 Aorta, dilatation of in exophthal- MIC: GLOWS are see erseena 342 Aortic insufficiency in exophthal- MICU COMEC LS ope 0 silo ee aawera the 343 Apameneadtismiry, 2.5 cect feist a chckexe 49 ADATATHYROVGISING fetes o oe saeeeeeee tr 48 ATI e ais, tails < veNehend a qeiceler ate fabs powstes 50 ADUEUICAT TSIM ieee aeiss alan ay oh -i ‘oom es 48 Apparatus for testing shi of drugs on isolated uterus...323 Appendix and menstruation..... 178 Arrillaca, hen. s(SOrZe,)) ..ms aee 200 Arsphenamine, adrennin and... .467 ARTO D AE de ee a's acs 2~o0.-e- a fsyshauw tors a2e Arterial disease, relationship of ductless: slands: to... 2... 4s 490 — pressure in exanthematous ty- DAES 4 ofcne Smee fs. se pa Manas ois 479 — supply of human hypophysis.173 Arteries, constriction, caused by GOMES AM » Sess ees ke) Hee eee 1 Artificial circulation, method of DVAMMGATMITNE See sie sis) dues! eye 313 Asher, L. (XXXIII)....75, 196, 204 Association for Study of Internal Secretions, purpose of.258, 280 ABCHECT Tae POTIOGIGS). cy... emete 49 — in diabetis insipidus........ ncaleye — neurocirculatory ........... 535 Asthma, adrenin-pituitrin treat- TCE LO fee rens ce ioewcusteresels 479 —and vegetative nervous system.317 —pituitrin and adrenalin in....517 —=-, TreatMEDE (OL. a. so Wiesner 65, bil7 ABUPTATen Bsa oe asco ae wicks le 48 Arthritis with pyorrhea alveolaris, endocrine etilogoy of......529 AThymismrsielss cae. ee icas dee iets pal so 49 Athyroigismiis 2 2s: bniere\r.e ele ee 48 Atrophine: “action “ots... tase. Ty —-—on surviving stomach.... wie — pilocarpine and, action of. wT — reaction of in typhoid patients. od 8 — use and dosage.............22 21 Atrophy of nerve cells......... 18 Atwell, Weide. =. Satins steer he epee 174 Aub, de Gs (Stern) eis cats oe 203 Auer, J. -CKlemer) -2eciee PS ieena nasi 186 (Meltzer)~ <.. «gee 479 Auer-Kleiner test in human dia- PORES esi stan ajar 5 ic Pahokee Re Re 320 Auriculo-ventricular dissociation, ATC MAN TN... %s,<:3. 5s vole eee 162 ITER COLDS fave 2 ona, 2) a rote kh 2 oucee eee ome Bi Autonomic drugs, action of on SUrVivine, stomachi.. . 4.4: on 314 —nervous system........ 317, 318 —-—— —— AOTECNMIN | esl Sethe eee 477 Autonomics, action of antagon- TSEIC. Us 0-'s\ye Bove, poo eeee 318 Babonniex, L. (Celos)......... 529 Bacigalupo, G. (Olivieri, Ronchi, and. Ceballos) icin. :skise nae 207 Backman, Be... 257.4% sD oye ‘Badertscher,. J. Au. 3 224.558 Bee 202 Bainbridge, F. A. (Trevan)..... 53 Baldwin, “Bh. Mi 233s eee 20:7 Bandler,. S:°W..02.2% 2-4. oe 491 Banti’s disease in children, prog- ress and treatment of..... 482 Rarnett, G. D. (Addis and Fos- : t6r) |... esha Ae eee 162 — (Addis and Shevky)....161, 189 Barker, Le Ps...0 lc ac 6 ee eee 343 (Mosenthal) 3... < 2c.) eee o2L Bart, JsccacisGiusn tee 543 Barros, Fis. 4 a0, toe eee 497 Basal metabolic rate in body.... 86 Basedow’'s disease, see Exoph- thalmic goitre. Basedow’s disease ........ 204, 541 — wand Addison’s disease..... 470 —-—typical ecase.....5...e- ote Basile, iGes ovis eaten eee BAS Baskett, E. D. (Greene and Nel- SOM)... tae. oe 182 Bassinger,, H. R.. «.:....> « Sap Bandoin,, Mi oc °...56% Sos ee Bauer eis... tens bos 3 os el 473 Beachy Ti. H:.. . 3. 03d «hoe 483 Beard, Av H.. «0. ...dsheeeeeeeee 320 — (Gravie)t..: ss ...04 2 eee 32m Beck, Hi G@:.,:....2.k es eee 492 Beck, (GG i 6) 0 Beclere, «Ass. ai ci ka oe oie ee Beebe, SS! Pie. oo. see eee Behr, (O22 oes nats Re 175 Bell. Bo Bs Sach 2.83 ee 516 Benjamin, J. E. (Lange)....... 197 Benzonanhthol in endemic goitre.532 Benoit, BH. P. ... .:.0 2. 4c ae Bensaude, R. (Hallion)........ 479 Beriberi, adrenin content of ad- renals in death by....162, 312 Bernstein (Falta) :..4.-c2 Soar —nmethod of maintaining artifi- Glial...) . 2. SER eS eee Sle: Circulatory phenomena in exoph- thalmic “goltres ....21.eceeees 22 Olatsen;S.{ We): 2:3: Si eee 496, 504 Climenko, H. (Abrahamson)... .417 Clinical investigation of thyroid hormone’ .!: =. ¢: Se ec 345 —picture of diabetes insipidus.115 — possibilities of pharyngeal pit- uitary.. 2 i.2s.. «+ 2h eee 504 — significance of thymus. .-....- 196 Clinician, physiologist and, co- operation between....258, 279 Clinostatic bradycardia... :... 555 350 Clinoid processes..... 212) 2a 2a Clogs; SHO Sis: &. .es Se eee 493 OobbL.. Gin) ane are 490, 525, 529 Coccigeal land. .... >. 2.5 45 Cockayne, +E... A... . ...:> eee 540 Collip;.- JoeB... «05.52 8-5 5 eee 176 Compensatory syndrome, a new pluriglandulary <2 24-1 209 Complexion, “‘peaches and cream’’.215 Concentration of attention, effect of pituitary (on.2 5... eee 325 Confusional insanity and the ova- Ties .42%:. 7.244050 101 — -—history of case.......... 103 Congenital anorchidism... .... 68 — cataract with mongolism..... 178 — heart disease with mongolism.178 — myxedema’ ..%. . Samm. skeen 540 ———Case + leash. ers Sigal eee 535 —sclerodermia and _ sclerodac- tylia’ 4. $65.44 45 540 ComipBbozamn’, Wie Age saseie sane atasc-o 182 Constipation, SPaStiCu.<.., cis . 0.2. 216 Constitution, chemical and physi- MOPICAL ACHON. a gis. d aetdia a « 163 — relation between endocrine or- Te ees ne aaa oh angles eurak oes 59 Constriction by adrenalin injec- ELOVTN Aaa ole iad Sachigcaiicl athens 479 —from adrenin acting on sym- pathetic and dorsal _ root- fora ted hit ees ee ee ere 313 — produced by adrenin........ 210 Constrictor myoneural junction. .123 Control, vasomotor, of marrow Ay elsts tel EV 3 rel ee en ee 313 ComeraG.oWe (EMULE) =< 2s. oe 319 KECET SOV ATEDLLUES O 1 D8 aa ee 486 COUP EIS Use es eit tas sw bye le ataln< 188 Me mC Ort aly en PMs e. -.<,6 3 ccousmnere a DLA de Corral, J. M. (Abelin)...... 163 GWorreas;-G; A. (Navarro) . 2... 165 Corpus luteum and menstruation. 438 —-w—aand periodicity in sexual (e\itel FE eet ain Sr oe Cte eater 483 —— effect of feeding......... 495 — -— in amenorrhea........... 12 ——— asthma ..:........... 65 —-— — confusional insanity....110 —-——dysmenorrhea ........ | —— — guinea pig............ 56 eee eet ULC OMA USCS teria oath evel < 12 = SS = TNS CIA REE os oer 15 — —-— ovary of fowl......... 184 — — —painful breasts of men- SEUUATUONS A t.. -tovs ayeno.< s 12 —— — sterility ............. 12 — — — vomiting in pregnancy.. 12 — — preparations, noneffect of.319 —-— soluble extract of........ 483 — —therapeutic use of extract Din ag Yah PE ee re eee 483 Cramp, experimental, and inter- nal secretory disturbance. .176 GuOOSEAS Aa tO erecta «oie Soecclsas 159 Courbon, P. (Laignel-Lavastine) .167 OUTVOISIOIS lng ec 5.5 on 5806 ayers ess 347 WIOZZONMMO LOL peste he seus bale 2 abo ice oes 187 Cramps) ane IMUSCIES) cose veie . ny6-2,010.> 213 Creatin, relation to thyroxin. .92, 93 Creatinin, relation to thyroxin. 92, 93 Cretin, energy of metabolism of.347 (Caveintelisiaiee ©) ele cee ener’ 83 SSRIS (Cee eee ree Bio —and Chagas’ disease......... 79 =A Sore here a a Migr aba, 62 «Diet, — metabolism and blood picture Tied” L2 Ak DO eae an Se aa ee eee es 348 — pituitary body changes in. SA AS DY OTL LCM gaye rche aS) Gon Pyete eaten Sam (hr retin’) (ater. Ob 3.4 ¢ a si.n.n0 40, 347 COrefaenice, os VS! eee a ec 165 “Critical space of Grawitz”’ CRORE: SAME yous obs: «0 phase cee 153 MORURTINNRG Ooo cet hee: x auie ile clark, Te CET COTO UNNI ticks veo s are neers eles 211 Cutaneous disease, relation of in- ternal secretions to....509, 510 Cyanosis of extremities....214, 215 Cyclic changes in interstitial cells Of WOOGCDUCES..< «2.050606 353 Cystic goitre, case of..........926 Cytolytic immune serum of is- lands of Langerhans........ 331 DCO At ha =: Gis sz) s «ccs ass oe 342 DSI ATIO Ck ss ciata: ake tro ae 301, 490 Dale. Hy WH: (Richards)> 2. 4-ss5 480 DY PONSO} Mleac< a oreisia <.c1eieav rele 166 Dalrymple’s sign in Graves’ dis- GAS Cerchatee oun 1 Sent cheh2, aes 24, 28 Danielopolu, D. (Simice)....... 479 Davenport, C. B. (Preiser).....: 520 Davis) 2 Mie. i orth ale ches eee 525 Davis. :-N. (Owens)icu<: .¢ 227 189 De Castro, A. (Souza and Novaes).172 Death of adults, persistent thy- WNTS AUG Nt oe we ee ees 336 — from adrenal hemorrhage... .494 Defective child and internal se- GTLELONS. Uw. nes Se eee De Lange, C. (Schippers)...... 192 Del _Campo,, Byer ..-iciele ase. 2 pete Deluca. Hh Ae ns tener 159, 172 Dementia. praccox . ffs: «sec as 489 — adrenalin mydriasis with. .476 ei hitcisKszfimeiearvek phils, Sle ree 490 — — endocrine organs in...59, 492 Dentofacial deformities, results observed in prenatal causes See aE SSE) Sg Pe ne So Si a er, 176 Depressor effects of extracts....422 —nerve, increased irritability of 33 Werewm. Hh. cee cae 6.5 dos 6 silt ade 490 Dercum’s disease with ocular SVN LOANS eee, ao 5 eraus eeeie ees a be 35 — — histology, histochemistry and pathogenesis of....319 DeHStelantOwiSseu Gs sheen teks «eh eee 62 De Quervain’s goitre operation. .532 DHA GLEB ics «..suskoieeo enone 2116; s207 32k —and fecal disinfection....... 485 = —— NAN tlLuism., CASC OL. <% +b). 484 — —sgsugar metabolism........ 193 = HIGOUSPLYGCOLYSIS: ID... n= <.o8- se. 485 —= iCtetic-treanmMent OL. \....3 5 = 486 — human, Auer-Kleiner test in.320 SET OALINETEMOL shoe ~ 20%) «1s face ese 164 PSM SI DUS ars aie (seeks | Rae eed ——a sequel to gunshot wound Glen OaGe sn 2 a desccin obser 21 SS ANG AGI DOSILS == >. «250.2 ee 145 — ———— disturbed functions of DY PODLVSIS: »..0% siekeeeie BPA | Diabetes insipidus and pituitary BS MLN ota Sete ee LD2, 2S were at — -—carbohydrate tolerance in.115 ——— cage Of) open? eee 495 — ——‘'centre™ fOr tects... ss eles — -— clinical picture........... 5 ta ss — -— due to insufficient pituitary SOCTCCONGee es see iat 121 — — effect of injection of pitui- tary solution on urinary OUEPUEL . oe ee ee 496 — —— of pituitrin in......... 496 ete OETING OL. coer ashevrsirn shies eakdemeas UD, ——— four cardinal symptoms...117 ——— from hemorrhage in neuro- hypophysis and peduncle.321 — — hypophyseal extract in con- trol of Symptoms of... 7321 — -—hypophysis and........... 495 —=-——n) Childrens, . .6 6 ex< gee 486 —-—-—pregnancy ........... aby Ass ——new theory of........... 56 —-—pituitary feeding in...... 119 —-— pituitary therapy in...... 121 — — sexual underdevelopment WA eT er ka cetie Pay on otarteh Gast ren 115 —-— treatment ........ ene bn 118 — — treatment ofsyphiliticcases.120 => == tYDES cui oe.) eee Ss 116 Diabetes mellitus, acute........ 486 —-—and acromegaly.......... 64 === dicta .. «teas eer eee 486 — — influence of war on....... Seal: — -— pancreas in relation to....515 — — present treatment of...... 486 —-w—relation of prognosis to EC CALNICNE 7. ito. Da Sony 486 Ss SUPP AT oo sstcara ies, Site) ws, See ae 484 — — syzygium in treatment of. .487 — -— treatment of by alimentary NEStielerar. osc eee obras 514 —— PATI CTOAGIC: wales: |S lget alent coe 186 — salt metabolism in.......... 320 — blood sugar, rate of dialysis.320 — muscle, carbohydrate content OS aeRO oes a0 TRIN Shea —— PUNGEUNE). esse es wee ile: i) OL YAVETITUC IS ba ere 255k" 4 Kinet 320 Diarrhoea in Graves’ disease.24, 28 Diet..ot Cretins twee oe oe 346, 347 Dietetic investigation of thyroid NOTIMOUEC ce sere eee hs oh) ley teh 345 — treatment of diabetes....... 486 Dietrich, ci4s - shew cere te 475 Digitalis-adrenin therapy....... 163 — infusion of, administration of A @. i ene EM: Mate es Scr aOs Disease, ‘‘pathological physiol- ORY Osa o ee 259 — pituitary, study of 100 cases.517 — thyroid function in......... 345 — ductless glandular.......... 487 Disease infection, spleen in..... 335 Diuretic effects of pituitary ex- tract ‘fis. Cees: 4 95 Diviak, R. (Wagner von Jaur- 628) or oo. SIRS eee 527 Djenab;; B.2h. Ss2cs 1niece eee 190 Doolin Wi b.t i . eeeeeee 522 Dorsal root ganglia, vasodilator mechanisnis: iN... S15. .s see Dover; ‘HE “(Stein): 2)... 2 ee 518 Downey, H. (Mandlebaum)..... 61 Downs, A. W. (Eddy)...... 192.335 Dragstedt, C. A. (Dragstedt and Ghase)) 2... Are sche 10 — (Dragstedt, McClintock and Chasey 5. 322 eae 487 —L. R. (Dragstedt and Chase) .519 — (Dragsteda, McClintock and Chase) 9..2%5.2 620... 2 eee 487 Drips;:-D.. (Mann): 22-5 = eee 335 Drinker; CC: K. (Drinker). 2.25. Ba is) — K; ‘R.~ (Drinker)... ee 313 Drowsiness: ©.) .\..2) j.c02 ant eee 214 —and sleepiness in diabetes in- sipidus: .. 0.4 <1 eae 117 Drugs, autonomic, action on sur- Vivine stomachs... 2. .a.-e 314 Dubin; -H. (Pearce). 2 2. eee 191 DuBois-Roquebert, H. (Loeper and Wa2ner.). ; =). sce eee 478 —H. (Loeper and Wagner)....160 == Meee Se 24 OPEC See * The Ductless glands, see endocrine glands. — = ‘cell control...” eee 493 — -— extracts, indiscriminate use Of .3:2.. wy. 3) Mook ee eee —-— is the thymus a.......... 250 —— =—and “War. 2A. 3215 eee 322 — — effects of on development of flesh flies oo + eee Rib —-— in dementia praecox...... 490 —-in gynecology....... 102, 491 —-—and infections..,........ 114 —+—-— relation of thyroid hormone ton. Sak eee 81, 88 — — relation of thvroid to other.544 —-—-—to gynecology and ob- stetrics 1 2. ene 491 — — relationship to arterial dis- ease! . 0 ae ee 490 — -—role of regarding thyroxin. 88 —eglandular diseases.......... 487 — — disturbances and reproduc- tion and menstruation. .438 Duesherg. J....\. - ¢. “Sees 193 Dunlap, Ke 2s 3s inc. SS 326 Duodenum, extirpation of...... 487 Dwarf growth, thymus and...... 194 Dysmenorrhea.. <)c-scine oe ee 443, 489 — corpus: luteum in. - seo. ee 12) SS — organotherapy in........... 444 Dyspepsia, adrenal..< Jin. sseeee 469 PV ADURITLEAT ISIN Ma Otte ye he ue ate ov 216 — case of in girlof15......... 64 — metabolism study of case of. .500 Dysthyroidism, familial and her- CUILATY Ae ete ee os cep. DLS Dystrophia adiposogenitalis..... 332 — genitalis, a case of..........506 —adiposa genitalis, case with eongenital’ dues. 2.2.05. 495 Dystrophy adiposa genitalis in WOHDOONTT ree tds, ws eee ts COZ Ectopic pregnancy, pathogeny of Meret Me ee de lnc Sheal heh < hd 482, 483 Eczema due to deficient thyroid BCOTAUION Mere secs Wi cavce A009) : Eddy, N. B. (Downs)...... HOW 33 OPUS STE a BE en ee ae 339 LGAs: S10 E. ea eee 61 Egg-production, winter cycle of.185 LURE eee! als ee ey ae ae 491 LTO AUD RSE See ae ean ey bo: ean aa 175 LOTS es ee, ee Toye ho VOR STELALCE TCG |, a 190 MAYES RNa a ns, 6 Sw 0 as ee) TROL. St (Covers ee ee 431 ING WON. As Ste AS Sood % 486 LN are en ORs ar pee a eee 77 Emotions, relations between and glands of internal secretion. 327 Endemic goitre, etiology of.....532 — — influence of certain factors ida! 1 2 See A at eh aS 7 —— thyroid extract in........545 — -— treatment of............. baz Endocrine condition in eunuch- Gua STET Wo Gels ye Ra eke eee oe PA — etiology of anthritis......... 529 —function of ovary and mam- Mary, SCcrelvion.2... sess. 182 — gland extracts and lactation. .166 effect on regeneration. .322 p= AVE RALS Sete eetets etc le sce. o)s sees DEL Endocrine glands, see also duct- less glands. ——....... 165, 166, 322, 488-489 —w—a new syndrome......... 489 — — alteration in following vag- CURRIER oo ete ee a ree 3) —-w-—and nervous system...... 165 — — “‘anti-toxic action’’ of...... 42 ——-—— Changes im. id. os. coe ue. 165 — -— hypofunction of.......... UY —— iT) SES INSANE... fos hale eects 452 — -— knowledge of ........... 279 —w—relation to exophthalmic POLED GM Sede sb oteets a Se 26 — -—some observations upon...490 —-— Studies on............... 57 = IILCTACULVIGY sire. ats See elas wo ole LNG 239 —— HEULASCHENTIAN .. 4.3 ss are fa 0 bss 491 Endocrine organs, see Ductless glands. —-— in dementia praecox...... 492 — —function of..............2638 —-—in dementia praecox...... ag —-+—-lesions of............... 43 —-—relation between constitu- on Andis s. Jevisweke 459 — disturbances in gynecology. ..438 —equilibruim at menopause and DELDOULY: stb + ls eae eee ee 441 — origin of Froelichs’ syndrome. 439 —— of muscular dystrophy....179 ——— peptic ulcer........... 489 ——PT ORIG (Ess ks. 4s 4 cs we wale 40 =~ SPHCOUL Ces «we Ncae ene Ob eee 42 — — observations on..........537 —sympathetic balance......... 43 ——-=— TOIATIONS “Fe )0a ocd Sees 43 Endocrinologia, Patologia E Clin- HCL A ee 5a oo TS eel See eee 42 Endocrinology and clinical find- MISS Sete ae a... Se 260 “and £YRSCGLOLY fof. ts e See 445 —-—-—some points of contact betweelr * s.\)/ as: bee 438 — clinical, in general practice... 60 == HOTA GL. | eked te mors bla o Oe one 445 Endocrinous origin of fat dys- ETO DHICS ok. oe ens hele an 492 Energy production influenced by thyroxin ~; 2 o\.ceee . Rae 88 ba oho Uys's5 (siS EN eee a + ee 214- 23s Environment, influence of on sex.334 Enzymes, changes in by X-ray. .290 —destruction by ultra. violet TAR eee rel ow a, a: oe 323 HORIMOD DMA (2.0 trols cere s oe 216 —jin Graves’ disease........ 24, 28 Epinevhrin, see adrenin. ——TANGe TACISUGs © =.» silo se eB oo ee 479 —conditions effecting liberation DOE-in bo plod). 6 ASt-ss 310 — hyperglycemia and hepatic dis- turbances q — liberation from adrenal glands.15 — pituitrin and, in hay fever and ASUMIN Ae Ye bor o's tee eee ene 57% —reaction of stomach to......315 — supposed physiclogic role of. .473 Epilepsy, relation of thyroid PVA LO die 3s xd Kien MS ie SOO Epileptics, pituitary gland in...332 Epilepvtiform attacks...:....... 214 Epiphora in Graves’ disease. .24, 28 Priphyses, Slow? . Ya. sere see 213 WING URIBs € he SE aca ey eee MSC eke es ake eS Se 320 Ergotoxin and adrenin hyper- SIVCGmig «hari v~ ate oe 163 HTMWCGLOINM . os coats bs a ee eae 49 —endocrine condition in......521 Exanthema, caused by neosalvar- Sam and Aarenini,- ree: 54 LS ed Shae SO rhuo Gg gcc ooo 500 Hrdman, Rhoda a... soe ais es 324 POPNSU, Ad oy EO cins teaver ees 489 HiGiennes, (Gis his sesenaeiaiy ustedes 5510.00 470 Eyes ine. eRe Nes Fes nistig tO Exanthematous typhus, adrenal MU SUGHCLOTIG VAT. «1s. 2) a.fe Yee ‘abe 479 WIXETCISE: SUIMdWeee. + sie 2 sw eue) tye twe 217 Excessive sweating in Graves’ GUISCASGMIE .. iuccchsdemenchoterste 24, 28 Excitement followed by exoph- PADLMIC SOTO an hadieusus oo cece 529 (STC Re on Sto ccm SC 217 Exophthalmic goitre, see hyper- thyroidism. ono osu eae 529, 530 — -— Addison’s disease and..... 475 ——and thymus hyperactivity Pena ern CE Rene or 246, 247 ——and tuberculosis of thyroid 79 — -— atrophy of nerve cells in.. 18 — -— boiling water treatment... .207 —-—cerebral manifestations in.338 —— i @hTOMALOly SiS Mes so «+ ee 18 —-— circulatory phenomena in.. 22 — — dilatation of aorta in..... 3842 —-—early diagnosis of........530 — -— etiology and treatment, spe- cial reference to use of TAG’ < ern 32 — in hyperthyroid goitre...... 542 — postmortem findings in case.537 Extirpation of duodenum....... 487 — -— pituitary in dog.......... 497 — thymus gland in tadpoles.194 — — thyroid, effect of......... 199 — —— and ‘Spleens ...\;i-4as.eecee 13 Extracts, depressor effects of....422 — organ, effects on gastric secre- TION), 4.0.0.04-08 Les ee 329 Eye, development and _ internal Secretlons syd eee 64 —relation to cervical sympa- thetic) eanieliia.ce.-cse eee 18 “Eyebrow: sign’? <<, ..ucc-1. Sy.0; 08%) 166 —w— effects of organic extracts REOTE icivs Sayan & Bel deeis 6. < 329 —— SOCERHMOTLL +, seducereenee t «dh ave «Sieve 166 ee yeh cn boyanentee a false ac 'dvar's 216 — -—hyperacidity and......... 214 Sarah. Sl Ce ee eee 166 Gastro-intestinal syndrome of hy- porenitaligmy ... 6. ig. cad2T Gana Wie. Pe reves eee cece wine ah OF Speen OE. tm ato aie y MAvsiens 309 Gaucher's) disGas@ sce. < che capi Ss 61 —-—report of two cases...... 60 Gehl Grn ite. ferry eas Bt eo es 323 Generative organs, female, func- LLCS Of eee. oe cic Es tae & 438 Genital atrophy and premature BEDUIU | x cia nis ws olelaicue eel 183 — development, excessive.......218 — — insufficient ............. 211 — dystrophy, case of.......... 506 — hypoplasia and skeletal growth 230 — internal secretions.......... 44 =e CORN FIs. Se knew is. ol arte a 49 Os eo ake: yall Gel ai eee En tT CIR he! gs sa ge idk ube in hei ome 225 eet POLLINA GOL 5 uhh e fot iy wueieenoas ie eh xen eee 214 Giant cells.in pitnitarys <.inwts sles 325 CASON | otk... cnidvdtn:cigtdoasater irae 200 RVG AST ais as, ye xin oh oe a 216, 218, -23% —and acromegaly............. 236 a OPA UEINE Ss 6 in daa a. 3.6 wool a 214 ETT TUE Gl wis an 3.3 ars. arbhdreee KREation 48 GEDSOM Ric aay CECUUI ) i.) calla aleneaghe 314 CIOS PUK snake cose + we ee 177, 508 Gicantism:, . Case. Of .-. <= ... See 74 sOnMRIne, OR: Bede... ae 164, 316 Guthrie, "D:.....)3 0... eee 344 Gynandromorphism, another case OL Ae nis 3's PO 2s We 334 Gynecologic and neurolgic con- ditions, relation between. .101 Gynecological operation followed - by: ‘tetany .’.'¢.. 4.4 Sie eee 516 Gynecologist, broadness of range Of vision . oss. 2a See 445 Gynecology, ductless glands INy eo. SN 3 ie oe ee 102, — pituitary disorders in........505 — relation of ductless glands to..491 — some points of contact between endocrinology and......... 438 — thyroid. in. o.«issn. ja Yee Gynecomastia, hyperthyroidosis associated | with. 226.002... eis: Worl ELADOLCN Elsie cs os aie chert os 196 Hackett, G. S. (Rogers, Rahe, and WA WGALE Ye et ne a ican oie 329 Hair, growth and distribution. ..213 —— ON 1aeOy MACK Ob ne. oa je x ores 214 _— pubic, distribution. .211, 228, 232 Hairless pigs, cause and preven- : PIO) Ofek Ot se mien ao, a LD Hallion, L. (BenSaude)........ 479 TRIER, YAR ta 8 RS nee ees are ee 535 12 ONE ed OS a2T 49733—Endocrinoiogy.. . . NINE Tima monds oo) ( LHaAWE) cs oe whet As 168 Matsa eMlareed os... etie. ie leletes 233 — and feet, enlargement of.212, 226 URAPR GE me Eley Morir. 0h she vans Poke, « whe, S90res 483 Sg So. 2 Ss wea g 2 186, 521 EL OIESS ALY). a: a Where came Bee rec che 162 Harrower, H. R....60, 327, 520, 543 CE Mt fates os a fe) eu pis Sid ww « £80 LES 0 Bd Ne ee ce eee ee 334 PAPE acs. estan tes Las O0l, Dae TELS ETT alps Gere ne eee eng io als: = CST oy gi ge ee ae ee 52 — (Kilborn and Fraser) UGOS SLs 476 — (Kilborn and Lang)........ 122 BASSUS. COFDUSCleS 25... 2 2. acrereae 2D0 LEENA Ts 3 ee a re 161 Hawk, J. C. (Hammond)....... 168 Hay fever, treatment of......... 9 REPS GE CLE Seal USA aia tsk ae LE COLS Eon Teta a a 194 Ovi TOROS) “i... ss eisla a o's se 194 Headache. .209, 226, 230, 233, 230% oleae oseeg ——SEOINEMNOE «sf Geare stale. < ake AL Sei2ks —from thyroid deficiency..... 200 — frontal or intratemporal..... 212 —— PICMICAr ye eke etd es 214> 216 ——-—— duration Of. .3...:.20%..... 218 —-— extract in........2... 235, 238 Heart, action of adrenalin on...160 — -—in Addison’s disease...... 303 —— ——on Hervous control. of -.:: :352 —adrenals and action of vagus REEVEIUOM Nereis 2 oad LO — beat, acceleration of in tuber- CORI ee ee els Pas ee — block, influence of thyroid ex- EEACE «Gc eer okt eer a 203 — disease, congenital, with mon- POEM, erase eave a SY 178 —effect of thyropara thyroid- BEROEIys ‘ORS SER. co ek eo ee Sink — irritable, of soldiers..... 2 oa —relation to cervical sympa- Bhehicr Sansa! see. 2b 18 Heart resistance, use of adrenin Fou determine...) ied. cee 478 OURS gets 21S sos) 5 ave ree 304 Health, thyroid function in.....345 PADMOUEGC ocr od gy ons cde ose 214 ECP EBOVIRIEE (550.00 5. 6b ons Coheed oan 168 Hekman, J. (Van Heeteren)....485 mina Wises.) 2s. 5 2 -D08 Hematoma, adrenal, two cases of.159 Hemoglobin and iron metabolism.191 Henrophilia, tendency to....... pop Hemorrhage, tubal and ovarian.185 Hemorrhagic adrenals in the VOUS. oy ese eae e ctera ss bie 474 Hereditary dysthyroidism......528 Heredity and feeble mindedness. 102 Hermaprodite. birds. 3.22. -9.88 184 Hermaphroditism:,) 2. :.2%5. ) eee 49 —— HlIAStIG PER DOG As a. 2%, Sso eee 167 Hernia, congenital tubo-ovarian..181 1a Pad to eee a DR eee c= 336 Herring eats. 65 ack «eee f (hee Herrman Geo 2 - «lee eee fir( HMert7, Athi. 2. eee ee 145 Heteroplastic grafts with thyroid 342 Mener,. Go dic. . 2s. - Aa rae gk $y 338 Hibernation, spleen during..... 335 High carbohydrate tolerance in diabetes insipidus......... 1B ivi Histamine, vasodilator action of .480 History of thyroid apparatus... .543 GAS OW Boek Sc. canter. cle ola ae 3o1 Hormone control of renal func- Lat en ee ee 447 —equation of psychoses....... 493 7 BOWOSE lots s. one c 5 2 eels elapse se ata 420 aa STLG Sd gc Gc thea PN ok BO 241 ——— EVE OLGUNS ig.6 era phe inte eciels 81 t= CITOCCES s JOLE sien oO she oss eee EFOR MONG 2X Sets. st cers 39, 414 EGEINOMES ) sence 6 2 vies als 62, 493 — destruction by ultra violet PAYS RAT. ae. oie oie Dee ——— MP EPASTANGUWIAT: 2.2 6 oben eek Ss 43 Hormonology, practical applica- Ah ON te ee 2s A oe 62 HI ORESTIS- 1 Brats. fet. c li.2 ss A ELC TES Ve oy ots oo, Ss aes aro es 340 — Margaret M. (Hoskins)...... 340 Houssay, B. A.. .64, 94, 171, 187, 32D, “£is, 250 —— (Hardoy) (0.5. .4..: PEP eon 162 Howland, J. (Marriott)........515 PORT Moe MGs 272 2.5/5, stan) et a ees 101 RUMEN! WAS te 0. Sra Ss eee Sad SE PRETEEN» Mice, Wa ose alc 2 3. ee PeaEM ARCO. MENS. ost Gicrs a cyt oie aeete SS Hurny FF . B- (Corner). 3.)\. 3! 62; 319 Hyperacidity and gastric ulcer. .214 —in Graves’ disease....... 24, 28 Hyperchromatization in exophthal- BTC A OITED Coches eats ne eee 18 Hypercenitalismi ys 5 ac wells ee -iete 49 — with thyroid-pituitary insuffi- GICHCY nS oP it eee 207 Hyperglycemia and adrenalin gly- GCOSULIA® Aico usbaade stele le st — — pancreatic deficiency..... 186 —effect of painting pancreas Wit LoOnenalin’..-.<.. et lesieste 330 —— Ore QUO RIT AIIG, oy eca) se 2/5 = ale tee 163 — experimental and adrenin.... 54 — piqure, relation to adrenals. .157 —role of adrenal glands in....152 Hypernephroma =)... -6. 22s... = 265 vaginal metastases of....... 3a Fy pero OPMORISM var eek a = chet = eee ie 442 Hyperpigmentation in exophthal- MIG, KOLETE eee. ole seek 18 FLY PEED UITATISTI geass rel oe esse 48 Hyperplasia of pineal body..... 516 —of thymus glands, treatment Ofer Hes hoc tte sane Ute eae 197 EUV OIG!, ucucy-tece) dental» eee eaeeies 78 Eypentuhym smi. epee or) <-)- Sapte Bass 49 Horse, response to adrenalin in.128 Human adrenal, lipoid choleste- TOL apOGLESA UME ssc olay asia sees iT hg a thyroid . extract Hyperthyroid goitre, etiology of exophthalmos in... ..i9.-.- 542 Hyperthyroidism, see exophthal- mic goitre. Hyperthyroidism... 20, 48, 525, Bin pee clinical -Shudiesean << -is(ak-be 533 — diagnosis and treatment of...343 Ox Debi CUba le coats i) s «es 285, 288 — following extirpation of ova- ia Ae Spee ee ee 321 ———_ intestinaly toxemia........ 32 —goitre and, in Vosges region. .531 a athe CaS OL; seit eee 288 ASTI hse ee a See 62 = jRLECLIONS > PrOGUCiINe. .. .s < ar 32 — quinine and urea injectionsin 74 TLC (CHEAP Y:, 1M. .s ivi: «= ieee ont — some attempts to produce ex- jn) Stel POS) O21! bh wets Ae Bi Gna o 545 SS ia RO eg il Gein Aes Oc ace 343 Hyperthyroidosis associated with SVRGEOMIASLIA, ene chs) e ste 3 OOS Hypoactivity of thymus........ 249 SE VIDOAGTEMIAT ie s'sis exe « 8s eee = 152 Hiynozenitalism, .. 2. -<)...\. 49, 521 —— UG PLA CLLIR I cries iois te) 2 het s 493 Liypopancreatisny 0. cee a yess s 50 Hypoparathyroigism .°..2-f6 = 48 Hypopituitarism and adiposo-gen- italis of syphliitic origin. ...498 Hypophyseal disorders in gynecol- OLY a ee a eis ee 175, 505 — extract, see pituitary extract. Hypophyseal extract, active prin- CIDIC'OL cf cic sul Dee ee ee 64 — -— from frog, action of...... 325 — — jin diabetes insipidus...... 169 —— fentinism”: ==. 23 > eee . 48 —-—+ —adenoids’ fo... ss Fs ewe 172 -——infantilism™ 4 925.5 +. — TORE: «i. ss os ee T1 —-—-— thymus .......,.. 241, 255 — — —— new function of... .523 — -— keratoconus and.........537 -—— secretions ...176,-177,,326, 337, 427, 509, one —-— and development of ‘teeth . me Urs — — — uremia — — Association for Study Ol shi i6ce hoe eID eee — -— coordinated data in study OX 5 Batali Take is era ee 258, — — defective child from stand- OID OL... 6 a..as eee 327 — —in development of skin and eyes — — — physiology, pathology and therapeutics ........509 —-— progress of year in study Oleg teer > Ss eae 327 — — physiological relation of. .32 —-—relations of to neurology and psychiatry —-—some relations between the emotions and glands of.327 Internal secretory disorders, diag- HOSIS (Ol isch ie ee ee 327 —-—disturbance and mental crampe. ...) se 176 — — glands, see ductless glands. —-—-—and milk production. ..168 — -—-— insanity due to disturb- ANCE OL oe eee 102 ——-OTrlans and eiymiys... 2. 408 — —system in feeble minded. .102 Interstitial cells and enlarging of OVAL eee Cueede eeo 357 —-—of ovary, after hibernation duningsrutting... 005... 371 — — —— captivity and isolation during spring.....375 ———_— —_iCOnaition. Guring all— LEAT G 12 a en RR 367 —— —— cyclic changes in...356 — — — — during pregnancy and IACEAiOn. «sins Te pa S's: Mokiwen, Ba bis. cs 26 scicane Gt SD McKenzie, J. (Wilson, Poynton ANG” ‘SEGUIGY)). ~ cicccletate aust sbeaes 527 MACAUHINCG Ui aioe. 5) oc < samesians suse 531 Machead: 5) -.ieeit. <. ((Murakam)) <>. c0 318 Wawel sor Bis in .ctarcterc toes 8-5 -0-1.5 he 166 May OW rcs coset ioe patos o- . : sees 103 Mentally defective child, congen- ital heart disease with..... 178 Merkilen,. PB... ..°..::.<Seeee 511 Messerli, F......... 0... «05 ce eee Metabolic (basal) rate increased. 86 — -— influenced by thyroid 86, 88 — investigation of thyroid hor- MONG) |. 2 LF se eee 3845 Metabolism, adrenin in........ 272 —and the endocrine glands.... 42 — and rachitic changes........ 248 — — rise of temperature....... 28 —calcium, dependent upon thy- roid or hypophysis. 5-- 22s. 244 — carbohydrate, disturbances of.311 _—in surviving dog liver....... 163 — — islands of Langerhans INR eee oe eee 330,, oo i — direct action of X-ray upon. .299 — disturbances of... . i... 272 — effect of castration upon.... 57 —-— — parathyroidectomy upon 57 — — — parathyroid feeding UPON! |.) .. sA) eee ee eee Sy — —-—thyroidectomy upon.... 57 — — — —feeding upon....... 57 —in Graves disease........... aig —-— myxedema and Graves dis- Case ov 2s: ki she eee 347 — influence of thyroid on...... fe — — —thyroid hyperactivity on 35 — -— —thyroidin on.......... 200 — iron, hemoglobin and....... 191 — of contractile tissue......... 20% —-—cretin, energy of......... 347 — protein, influence of thyroidec- tomy On... =.=. .. eee 345 — ‘salt, in diabetes... ...: “ose 320 — stimulated by thyroid feeding.352 —stimulation not associated with protein... ... o>. See 75 Metamorphosis in amphibia..... 244 —iodin compounds and...286, 287 —of tadpoles, influence of X-ray UPOR, -o Sao hs ows 296 Metastases, hypernephroma, in Varina. ss sa... co 323 Microsplanic type of development 43 Mikhailow,s N. As... ose wee ee 501 Milk, endocrine gland extracts in production. Of ..2/2. we <. ie 166 — production, relation of inter- nal secretory glands to....168 Mills? Giraee on aC a ere 199, 340 Mineral metabolism in Graves’ MISEOSC) «Cede ett ce ee os DOL Minvielle (Remond)...:....... 65 Mitotchondria, presence and be- Haw iter iemree = tcc. os cs se 387 Mixo-idiocy, influence of thyroid PLC ARTMEM TOTS che sk ace a c's 3 328 ii tirei rl Mies 1p ol CR Ree eee ie ae 493 Moffett, R. D. (Greenberger)....486 PRMRTIDIE at tote fa ose soso sive eas > oe O20 RUIPAPRE PINGING enc chcl ccc cta se eee E78; 328 -Mongoloid idiocy, influence of thy- roid treatment OW)... 5.2). « 328 Monkey, response to adrenalin Lys eee eee creme arse ace ey ee 3b Mono-glandular endocrine syn- dromes, classification of.... 48 MGOnGlOl so 4) ke eee cc hee DAO a = ONO AN) 2S. cc ee e's o Bey a ADTET Pie. LDS 3G (Ca a aes ea eR 494 Moral deficiencies and delinquen- GIES te a, foc Fe dee 214, 219 TU TIRDIIS? et RRS SORE ree a A cena 237 —and pituitary feeding....... 238 Mongrane hoot. (BOLI). 2.2%... 519 Morgenstern, O. (Kaminer)....337 Morphine, effect on thyroid activ- LAO See Sue ne ee ee eee 340 — hyperglycemia with pancreatic Genciencyer cae = vows wars 186 — test in human diabetes...... 320 NMIGEPIS wien. os cs tee es ee DOS SOM Se ERMC, as te ee ee oe AO Moschcawitz. Vin... ss ccs ec oe 472 Mosenthal, H. O. (Barker).....321 DDS eae 2 EA ees 486, 544 LET re al DS |, I ee eee Wt, B06 BS mCEOESEOT)) cine ccc aes tle se ene 51/2 MotiarOsende. Co. 52's... wc. ose 470 NOUREN GES eS sw cre 0 8055 ee ee 112 Mouth infection, relation to STE SB aig ere Sn 532 LOU ress § 0 ee nO ee 196 TSO) pe Ree RUS oa ne 332 Murakami, J. (Matsuo) ...5..:. 318 Muscular fatigability...... 209, 211 Muscle contraction and organ ex- CHRZC IS; Saat oh ae re 65 — diabetic, carbohydrate content Dib 2: Weed Bie ree 321 — normal, carbohydrate content Ti 2 + otha A See eee 321 — preparations, effect of adren- DUC oa. a Seen ee 315 — smooth, action of various sub- SURAINGSS) 0) 0S Se ae BEY Muscles, action of serum of dogs Ma Le HUNG Ola... six vis 0.056 «'s 187 — blood flow in, effect of adren- Uy Soke Re eee oe 164 SAVES SE e100 he ee ee 224 Muscular dystrophy....... 179, 180 Muscular dystrophy, progressive.180 —w— origin of progressive..... 165 — — progressive cre dice Re 180 Musser, J. H. (Krumbhaar)..... 70 — (Krumbhaar-Peet) ......... 69 WIRES i rr 207 Mussio-.Fournier, J. C.199, 526, 536 Myasthenia gravis, chemical changes in blood and urine.179 Myatonia congenita, report of CARES Gs heroine eit ae is DLS Myoneural junction... > 2cltee ez. . 123 Myopathy, nervous system and endocrine glands in....... 165 Myxedema and sex functions in WOTMGIE 5 3°s°s \ ave oon tet ee 79 —'bleod, picture: in... .... 72055 348 ——COnLenItal. .72 5s... ae J ae ————— 0), CABG Of. ... 25.2. tk oe eee ——— TT LAID EL Eo ahs, «cat atcha Saree ane 198 — influence of thyroid prepara- TIRTIS Weis 9s, ska) 4 nic, at ole ala eee 47 — metabolism in.........347, 348 — microscopic findings in case Bi eet. 6 ere ee eee 436 — Napoleon’s, notes on........542 — pathological findings in case Clee eis ee Gare ee 435 — pituitary body changes in....175 — sclerodermia with, treatment.526 — thyroid feeding in.......... 219 — thyroid medication in.......544 EN YTOSIN IN. 2 Sa. piste a aw Moo 85 — treatment of a case....432, 433 — with tumor of pituitary body.431 8) A ee es ee ee oe Napoleon’s myxedema, notes on.542 Nausea of pregnancy, ovarian ex- TRACE Meir is sk. + cas 5.2 ie RN, Navarro, J. C. (Correas)....... 165 Nelson, E. W. (Greene and Bas- Bec siete < seg Ae eee wins alee 182 Neosalvarsan and adrenin...... 54 — treatment of Graves’ disease combined with syphilis. ...535 Nephritis, high adrenin content of adrenals after death.......316 Nerve cells, disturbance of equil- THEM eis o 5 5.08 sa Signe ete 25 Nervous isolation of liver...... ore symptoms in goitre......... 343 PRCRIMEGONIGET © DUlircncs ath ais 2.2... 518 — thyroid, recurrence after..... 536 Operative procedures in thymic CnlarTeeMeniven sc sie side ee 417 Opossum, response to adrenalin TEES 2 cs, Senet Paacs Acai earns 2 126 Orchitis, double, case of..~.... 167 Ord as: WW iceicie eke! o3.crs Maeariek native 318 Organ extracts, active substances LTD tee tee stouers es. oreiaie oc Stee eae ae 423 en OIPOCTS TOL sun cat Os en sates 65 —-— —on gastric secretion... .329 Organs, internal secretory and DMV IISA oh tos en, eee 408 Organotherapeutic measures in SUGKULICY.» et a. cast ee 445 Organotherapy, a new field for. .120 — development of............. 12 —in dysmenorrhea............ 444 Organotherapy and pluriglandu- lar disturbance’ i... chee 488 —w-—thymus enlargement...... 417 Orrico, Stee s Mics Bes See 507 Osborne; (ORD, ct oe ee 309 Ossification, effects of thyroid ex- TIT PALTONO OD. = sic. 22 cee cee 199 Ostwald AA. oie crests chee i3 Ovarian extract in nausea of preg- DANCY. eh ane ut: ce Pee eee ete 513 —function, effect of hysterec- CODLY. OMS... i2% a! Se eee 181 — insufficiency, physical mani- festations >... >. eee 189 Ox pituitary, extract of..o.. ee 493 Oxyhemoglobin, adrenal product ANG ee canoer 272, 215.) ean — conversion of adrenin into. ..278 Oxidation theory, investigation of.277 Paget's disease.....20. 2.)S eee 219 Painful breasts of menstruation, CGOrpus. huteum) in. >. eee — — — — thyroid extract in... 14 Paisseau (G.) (Lemaire)...471, 476 Palo Gis ooo ke oie ee Oe Lis Palacios; .G. (Dies. a2 ee eee 485 PancTegs. mae meee ee 47, 186, bala —and sugar absorption.....:<. 186 — effect of painting with adren- alin 4.8 vers 0). 6S. eee 330 — jin relation to diabetes mel- LUC «Maden sche Sees cee a 515 — relation between thyroid and parathyroids:;.... ..<'t). cena 57 — role of in-glycolysis. .<% 225" 330 Pathology, internal secretions in.509 PetEPOTOE GIG. 1.2) s de clese aya ela sen asses is 49 —‘'deficiency, experimental in (IO RS Se iaa atts rene ayia os: ag 186 TA DOLCR ete eis at eietain oa eas wes 186 — duct, retention of blood sugar Aten lis aelOm Of. 6 Ic ols c/s 330 — endosecretion, infiuence' of nervous system on...«.....514 —extract, effects on gastric se- GTEEIOT Mert eee eaters) alla ee ies, es 329 Sesh ee ee oe cee ee Pee SS=Hol ofc Vy Ae AP on oe eee ae 50 Paereahitis.: AGL a os)... tl. sats DLS Paralysis agitans, treatment of. .515 Papanicolacu, G. N. (Stockard). 56 Paralysis in a hypothyroid......536 Parasympathetic nervous system, relation to exophthalmic goi- NVIGMNP Ste sehr ey cs Rae a dich cnet 23 — organs, physio-pathology of.. 44 Paravinynoigs .'. >. see 2s Bal hin bl Gy “187 = OTOCt ON MiUSGle. . ...ecce.enais 65 — extract, effects on gastric se- SISO es ee 329 — feeding, effect on metabolism. 57 — gland in paralysis agitans. a sya iss ETT CLOM GW Weleye 2.2! ep sue. ace,s 6 145 ——and fatal tetany..........: 332 — — functional, treatment of...147 — glands, a function of........ 89 ——-—— thyroid and ............525 erry and. SOME! «ccs. 0 eo ss ie PIU EG ADVE ic aie aoe Jatres Sus .s, «cesses 148 —thymus and, antagonism be- tween ..... eae eee Js. 3 524 —MOTUERL ENT andes <2 Ss cxreh ave, areitel’saleie © 516 BaraciyroidectOmy 2... 5 << ..c. 26 5) — effect on metabolism........ Bil Paravhiyroids: ..i.<-. AG 48 sal, soe Sn) jiGish 1) er 66 —w-—thyroid, relation between DAM CUCAS eee lc wre. ss a ue —-——relation between pitui- WANS VE MEA ca. coals Sit —hypophysis and thyroid, stud- NCS OtaMEsteet Ged . oes cha BAG === Th CLO ee, Ree oe 333 — normal and pathological anat- (ONT, (Clue) Guat eae oi eee 516 LES RoIne Us a hee eee eer 78 TEESTATETT OU | Fikes), re 70 een erat elo tewer a ais ies «eves o20 Teped gris raed Bo] ee 484 Pars tuberalis, development of, in rabbit’s hypophysis........ 174 ——— i ORETAGE OF < cis oes ce wee 493 Pathology of menopause........511 PGRECE; es i GE UDIN ) 25.2055... 8s» 191 PCAN ge Ruse wero. sieteie te wie ed uci 495 i (Borin ins. eieeoicier sn «fas 68, 184 PewIAtricSssth ymiisedee ke Si, ease 405 Peet, M. M. (Krumbhaar and Mus- BODY Note et 2/5 che cee 69 PCRMGNG Ge bo n> ce bit be ee Pellecrink koe, vaares we eee 506 Pendens Sa aae ene ae te eee 42 Peptic ulcer, probable endocrine Orig Ot 4. > eee ae 489 Perithelioma of hypophysis.....500 Per Ba oss x 0's bo bee ee ee eee Pharyngeal pituitary, clinical pes- Sibilities \ofi. 245A. 26k) oe. Oe Ligivt by 2eh' et | Se ite amr ember es ey Phiogiston- theory... seal 82 PmOCINnP ae. St. ase be ee eee 55 Phrenic and cervical sympathetic nerves, influence of thyroid ORAS. Bydk-on scsi oe wee Physics, mechanics, hydrolics and chemistry, their application.8&2, 86 Physiolcgical action and chem- 164 “GCONSEIEULION. <0. « y-s tee ee 163 Physiologist and clinician, co- operation between.... .25 Physiology, internal secretions in.509 — of melanphoresof horned toad.311 —of menopause...........,..511 ——— NOLO SICAL acs ar aay chara sec eee oer PiCCaARGOs he SS i. 3 ote se Gas, oo 482, 483 Piceolt (Gere see ee «cree eee one Pishimil iGe.3 eo. ests ser = ase 59 Pigmentation, adrenin control of.311 — disappearance of............314 Pigment granules, source of....390 Pigs, hairless, cause and preven- TOM ORM Se oe Sree ee aie ae 526 Pilocarpine; action of: 235 ..2.5 -- Sit —-—on surviving stomach..... = BS —and atrophine, action of..... 477 — reaction of in typhoid patients.318 EAUHGHINI 2h Osa ss. «ci oncia ee ee eee 495 Pircols, MEO. CA bel)... or Oe Pingaie. <1. . ok he ns OU, eee — body, hyperlasia of..........516 =f CAGE RUA see euave. a0 a atone a Sr erateys 50 — development in mammals.... 67 senna 12526 | PPT eee Rea ear Ae 67, 230 —— calcification of........... 187 —-w-——and hypophysis.......... 45 —— early involution of.......218 — —jin mental disorders....... 452 — — secretory phenomena in...516 — malfunction in insanity...... 453 = SODESINVE Da ele as as leiw, « erudene eae 50 = EIPACUW lols cts 22) Sisnucee ewe eee Piqure, effect on adrenal dis- GCRATRSE isk an ways «4 Somes 150 —geglycosuria and the adrenal DAA oe ee Mose 150, 152 — so-called ‘“‘sugar puncture”. ..149 Passe aah ee a s OP oes 310, 343 Pitres, A. (Marchand)~ 2... 22% 320 Pittenserehs Sil 2 ee cee 323, 324 Pittenger, P. S. (Vanderkleed) . .324 Pituitary, see hypophysis....... Pitiitary ocr ©) os ee 48, 332 —adenomos causes of acromeg- EUV be backed eho eke: =: = a, shone Sereeee gals — and compensative cure....:.212 —-—pineal gland in compensa- ERVOT (CULT C. 6! of) 5 adewtacte seers og br —— SIG NECCLN . .).006 4 @ ga dae oe eee 500 ——thymus gland in compensa- tive. CULCse oe ae ee ee 212 — associated with thymus per- SISteENCE © .c.c usdeudiecie. eee 434 — body and female sex glands, interrelationship «.. 5:.; << 499 ——— polyuria ............. 94 — — -—retropharyngeal tumor. 63 — — atrophy of and diabetes in- SIP UMS riences als Werke, setae 114 —-changes in cretinism and IY RECCOMA, Fo ee cee bas —-— effect of feeding.......... 495 — -— hyperplasia of and diabetes INSIDIGUS Cosh. EER. oe eee 114 —-—special examination of in diabetes insipidus...... 114 — — syphilitic lesions of....... ie? — -—tuberculosis of........... 114 — pony Gapsule~Ofs os ..< d2s.% Sune 239 — cell changes in, following cas- TEA DEOTUIORS «... casper oe eee ieee 63 ——/ CY StECASG. OL. sea ee 494 — disease, study of 100 cases. ..517 — disorders in gynecology...... Wess ——I@ISTUEDAN COSt a =,- Sac s,s heleians 214 —-—and adolescence...... abpeates yr) —-w—and metabolic rate....... 88 — diuresis, cause of....... 447, 448 —effect of thyroid extirpation OT en SNS << SES casa 201 — effect on memory and concen- ETALION: Fes eeeeee <:. Me or eee 325 ON LAT ZGMeNG wee ..« <).+ 4c iene 233 — extirpation in dog.......... 497 Biguitany, CXtTaee «<0 clomeee ~o0x — — — reducing polyuria of dia- betes insipidus...... 449 —w-—of posterior lobe......... 504 —function, relation of thyroid LOCIW: COrw ooh. sets vk ee Se ee 6 —-—physiological effects con- Stanit. <. ..-3 32 218 —-— effect of removal......... 96 ——feeding........ 221, ZeO wie =—— functions Of 2-7. s. + eee 218 —— “headaches” ............ 216 — —w— duration of........... 218 — — hyperactive, hyperplastic.. .239 — —jin epileptics............. 332 — hemangio-endothelomia of....435 — hyperactive .23..... 402 oe 220 — hyperactivity of, causing head- aCchee oY. a ledi- ae 189 Placenta previa, pituitary extract LENNON dt oe hae ee danas éutee, ahs 189 Placental extract, tissue stimulat- Imeeirect Obs, n. Liss stesso OLS TIC Un Se eee 178 Pluriglandular compensatory syn- PBOMOR ahah ate eel eases ae 209 — — — first stage....211, 213, 223 — —-— second stage.......... ates ee beds, Lae 227. 229 ———third stage........... a See 22 24. 229... 233 — — — fourth stage..213, 214, 236 — — — aetiology ............. 216 —— — — description of......... 211 — — — pathogenesis of........ ALT —-——symptomatology ...... 214 — —— treatment of.......... 220 — — — uncompensated cases...237 — disturbance, organotherapy, GUE MM Pe Sistas = ones tls seus, 22% 88 —endocrine syndromes......... 47 — syndrome, thymus death a...414 —syndromes in infectious and enronie diseases)... 0. 0.65. 470 LTT ed 0 ee ee eee 182 LPO ei: Gee Oe ee 166 ICIMA EEA reenter CAS al Aids cad) a Ges es SLO = IME CCUONAE. atk ct cs 114 — — lesions of nervous system.113 — -— pituitary body........... 94 —— pituitary extract......... 95 —w— sympathetic nervous sys- SIT abies oe cee cay MEP he's 5s 1200828 = | CASPRA UNTO iy. fib lac alee 2cc0 os 172 —non-hypophyseal in mammary (EIDE Ose ira ae are ee gL ge —not due to hypersecretion of TOUTES 2 lee a i UT foe | iv. A ee oe 470 TOS dei es Ge. 2: te 541 PE ORUGCAMS A eo. ck ic.) Ha es 469 imottenger. BMS. oie ws ass my eed Oy ¢ Poynton, F. J. (McKenzie, Wil- SOME ANG I OLONECY) oss isis 163 Quantitative analysis in investiga- HOGI SS ieee oan ae 82 Quimby, -A.. J. (Quimby)... ..:..52D —— AW oo ee CUIMOID >)! oa ot sw ec oe toe DO Quinine and urea injections in PETE ones a petcce oy vn gas 74, 342, 544 — effect on thyroid activity..... 340 Quinquaud, A. (Gley).......... 73 Rabbit, response to adrenalin in.132 Rabbits, blood diastase of...... 322 Rachitic changes and faulty met- SavoOlIsmy Woes Sh ooo coe 248 — — in children and thymus... .248 Racoon, response to adrenalin in.131 Radiation, ultra violet, effect of .323 Radioscope used in studying ac- tion of adrenalin on heart. .160 Radiotherapy treatment of testic- ular, neoplasmato. Gest 6 SUE Radium treatment of exophithal- MUCOUS docs eee eee oe 202 Rahe, J. M. (Rogers, Fawcett and ackett)iinieee ecole sce oases 329 Ramond-F.--(F'rancois)’.’.. ec: 475 RUASMUSSEM SO a! str cee ler ke Tile Sis CSTMPSON)” cis ote as eee ieee 35) CoG ts Ge 0 ee er ie a Age SU ig eS a 132 Reaction to adrenin in thyroid CABROB Sh. dere caemanes 462, 463, 464 Reaheld;: Axle Teese ee 311 Reede; BH ioe ron oe Oe ow Reesi MeSH See oe eee ee ae 188 Reisman; Dawe loactisate oe ers 343 Regeneration, effect of endocrine eland:extracts#ons. 25.5. a: ees Remond, A. (Minvielle)........ 65 Renal activity, adrenalin and pit- uitrin in regulation of...... 162 —— regulation of.161, 162, 189, 316 —and adrenal extracts, toxicity Of: (se ai le ee alee ete oes 469 — function, hormone control of .447 —— S1VCOSUTIAg so siete eae) el ats o> = py Sate: Renocontractor substances in pit- itary extractive... .'.7 ae 2s 94 Renodilator substances in pitui- tary extract Reproduction influenced by duct- less glandular disturbances. 438 Reproductive glands, internal se- GReHOn Of. 2% pees oe eee 190 —system of foetal free-martins. 33 Reptiles and birds, adrenalin re- Spouse: lve Aen ses wk ween 140 Respiration, diffusion doctrine of.267 ——"TITGOLY:.. cre %6 be ote oe eve stele ate 264 ————— VAIUC: Of. Sates oes oe ee MOD —— weak points of.......... 275 —-— quantity of circulating ad- TEU aera: foe.c hee ere eae 275 Rheumatism, chronic thyrogenic.538 Bibeiro sda Silwanw-s... cic eis oe oo ee PCAC OMT OAS poe ete ash cn sor sl eS Richards: A. N.accpale): ..: 2, c= 480 RICHArGson- rs ables ae ts a 181 RAChtery Gwe ters feo es ee Ola Rickets and spasms nutans...... 350 — modern views of nature of...333 —=——if{reatMenbh. OL ache ohare eee le eels 2 350 RIGGS, Os oe eee eee ede tel ee 334 Ringer's solmtionimc wwe ek) eee 33 Ritter: 2B: CwWeilland)\.. een. 80 Robertson: ULB tie eek 02 Robey, (W. Hz.(Boas)) 25 a ee 5 Rodents, adrenalin response in. .140 Roger; \Hieils ee eee ee 159, 310 Rogers, J. (Rahe, Fawcett and Hackett) Rogers;..J.° Buck eaters cles 207 Rovoli,.. J. Mise 2 tins ne eee een — (Marine and Stewart)....... 204 — (Stewart)... 2.4 54; 158; 3.10 Ronchi, P. (Olivieri, Ceballos and Bacizalupo). 88} a ates 207 Rontgen rays, see X-ray. —— as stimulant to sex glands. 69 Root ASS. fos ein ios ae Re 487 Rosenbloomyiws-+2 2 ote eas 169, 500 Hosenbush, 'T. (Kraus) = 3-26 79 Rosenow, (Gil dacdsis. Pe Se eee 481 Roux. cok aie eee Sfp yi kamera ys iff Rugvles A.B. ook eee see Be Ruth, ES. (Gibson) .s2s..2e 314 Ryftel, J. H. (Leyton, Spriggs, Brown and Cammidge)....514 Sajousy ©. Hy der Vins te. ores 258 Salt metabolism in diabetes..... 320 Sandelin.. Ts .:.4-. s868. oe 2 eee 75 Sarcoma of hypophysis cerebri. .495 —-thyroid gland ........... 200 Sargent, C. S. (McCrudden).....179 SARC Acs oo oho Sask hts a hek omen setae 470 == (Gros) Ss t...2t5a. DeLee 474 Saupheks ....:..2/)/2- «0 eke tee 477 Schaffer, H. (Forschbach)...... ook Schippers, J. C. (De Lange)....192 Schlenker, Ms :As.)s 2.0m ae eee oe Ee i} Schmeisser, H. C. (Knox and SW DD) ea eisai: sis cece keg eye nee ae 60 Schmidt, Rave 225... 4 ee eee Scholtz, "TE. (CBoas)):.. #. 2 ~eucsaeneee 187 Schumann, HevAS< 2.25 oe 502 Schwertzer,; .... cS. ae 506 Sclerodactylia, sclerodermia and.540 Sclerodermia and hypothyroidism.527 —and sclerodactylia...........540 — case of edematous........... 540 —in case of myxedema under thyroid treatment... ao ae 540 — with Graves’ disease, treat- ment..-/...% }. 66 .. 2 Re Oe Sclerodermic trophoneurosis of the lower extremities...... 495 Scrotum, divided ..2. 2.3 .e.sse2 cone Seasonal variation of iodine in thyroid. eet eee 98, 100 Secondary sex characters....... 194 Secretin, a new plant.......... 190 — and corpuscles in circulating blood), 232.2% SA no eee 333 == Pastri¢w. i. . <.keue ae ae 166 —— effects of organic extracts WPOW oo... idee 329 — influence on number of white corpuscles? ...)2 Nepean 191 Secretory activity of organs, dem- onstration“ of . . 2s 2 Ae 250 Sélla .turclicas + cepa 212; Sella turcica, enlargement of....214 , <, « ne lie — extract, effects in gastric secre- ELON eigenen «2 ince che. so ake 329 — — therapeutic value of......520 — in infectious diseases........ Sees —relation of, to blood destruc- IGT Ah, ayes tery Me RRS pNP 69, 70 Splenectomy, study of effects of.. 69 Splenic blood diverted from liver Dit WolOaki= See Lee ere 70 — diseases, atypical form of.... 79 Splenitis, report of case........ Th Splenomegaly, blood dyscrasias in 70 — familial, clinical study...... 192 OP SCL VALIONS) OV) «s. 22 «) xj aive.eolenere 7 Sporadic, CreLinism. . -2~ .. a, :.0b et. (a Spriggs, E. I. (Leyton, Ryffel, Brown and Cammidge).....514 Siamina- lack Os 2 sa sus. 2 3 sete GAMO. Pie's) c eos s io a toe mere ieee By Stanton, Bb; MacD: 2 0... ete ee 348 Starks “HES S25 oboe oho ee eee 486 Starvation. -thy muss. «oc ee eee 72 Status hypoplasticus...211, 217, 227 Status siymphaticus’....+-.. oe ee 337 — — cause of sudden death.....524 —w—military aspects of....... 520 Status thymico-lymphaticus..... See eiee sacstek 211; 237, 441, 520 Status thymicus of youth and AMIS: «oda eee ts oe peas 49 STOISPOCR fo.5 sien steer cent’ «<<, oye. + pegeiens 64 Stem-slA Seer. Seon eee ————i COVED. <.s eave eters eksvenehes 518 Steinach (Foges and Lode)..... 190 Steinach’s experiments on trans- plantation of sex glands.... 68 Stephenson; Six 4 spend fees eae 64 SSPOIUUCY .cs te wae cee ee 444 — corpus luteum in........... 12 — organotherapeutic treatment Of ea Eee Lae aan 445 Stern; No Sey (AUD) eee ves ee 203 Stewart, -C.* Aloe see cs ators ot a: GSN Sonia lnk ee oe riewee Ball ——— (AOL OI) a aks oie oes tone 54, 158, 310 — (Marine and Rogoff)........ 204 Stiles WELtGe sees eee eee a ee woe SOOO Stockard, C. R. (Papanicolaou). 56 Stomach, action of autonomic CUS S EL lls cack hehe: cialis cae ataieae 314 Stoney, Florence A. (McKenzie, Wilson and Poynton).....:527 Strada, Shes ie ee Le ra Stranchyaen 2 hee ee ee 176 Structural formula of active con- Shiinent Gk thyroid 2.oct aes. 90 Strychnine, effect on thyroid ac- USLVIUURYINE 7 cre cae cae Loe ee 340 Stumpkey oGencc ys ete so. ese ID. Subnormal temperature in dia- betes insipidust: .-. 5 or. e oy, — temperature in soldiers......511 Sugar absorption and the pan- OL SY We bie ee ina 9, el i 186 — blood, guanidine hydrochloride LOY hte ei ann aso, oo a 331 — —retention of, after ligation On PANCTEAUG GUCtS -... 0-006 330 —= IM diabetes. Mellitus: 4205... 484 “sugar DuNnctire, -pidure..-..<.< 149 igneds4.. = 2s. 219 Suprarenal, see adrenal. hepatic insufficiency, fol- lowing chloroform poisoning.469 — gland therapy: *'.. 3: 27. 3.2220 — glands in nephritis.......... 470 — — pre-existing lesions of....469 — insufficiency in recurrent fever.469 Suprarenals, enlarged and_ sud- den death in an infant..... 472 Surgery of hypophysis......... 169 Surgery. of thyroid: teen oe 541 ——= LhyFoid ,“prineiples-@is. er) Hone Surgical treatment of exophthal- WMNCUuSOibre:< 22. ae eee 79 Swingle, W. W....-.... 168, 200, 283 Switzerland, ‘zoitre: in. 7 5-. jon * Syinmers! D2. hak 337, 349, 524 Sympathetic ganglia, vasodilator mechanisms 4nJ.!.. . cae ee 9 —nervous system and polyuria Sy oe eee eke. eae rae 120, Lan — — —relation to exophthalmic SOItTC® .. .°.. 25 ls eee LT — stimulation and adrenal hyper- — SCCrebiOn. . ;°.-2s'2 teste 45 — system, hypopnysis in....... LTS. Sympathicectomy, Graves’ disease ONG 590 al 2 5 i awe eee iss Sympathicotonic disposition, in- fluence! Of.) See oe eee 26 —type of exophthalmic goitre, characteristics “OL... aoe 28 Sympathicotonus, vagotonus and hyperthyroidism, experi- mentale... Ae ie 545 Syndrome, a New = <..c-: «Spee 489 Syphilis, acromegalic symptoms — combined with Graves’ disease, treated with neosalvarsan. .535 — congenital* 2.5... See 495 — Of thyroid]! 32... 2 >. eee 541 Syphilitic basal meningitis...... 113 —cases of diabetes insipidus, treatment; of. 2.245 eee 120 — hypopituitarism, case........ 495 — lesions of pituitary.......... 113 Syzygium in treatment of diabetes mellitus a < 2.¢ —role of thymus in........... 524 Tethelin, effect on experimental ERC MLO SIS. Lyitce es < touen ots 188 — in diabetes insipidus...:....321 — in production of growth..... 324 — some properties and actions of.502 ‘Therapeutics, internal secretions RTigoe eae ete ci ees eo ke are 509 —present day, of spasmophilia . 187 AyLOn ee ees Wit fe 2 ee ha ee 184 AM IVOECE UST 9 OBS Seedy aed 541 IMI@AITTO. (Vs nen eee 49 —cells, small character....... 250 Sts iy “te ee 217 <= (ili siiilig 122) 0 oa a ee re 234 — extracts, administration of...242 pa RTATE DUST 7 § ee dis, bess so alas 218 SSN Ciciiciil: ee ie el ae re 241 — tissue, administration of..... 242 —w— cells, vascular........... 250 BAAR TRIG OT DIA | coe Sees, os es eee. 249 Sverre POTEET Ch... ssi. s 8 61 Thymotoxic serum and growth... 71 Thymic eniarzement .:. 0. 6.".. 522 ———AGInenOsiS Of... 0... oS. ee 415 — — operative procedures...... 417 Thymic enlargement, organother- ETSY AW tee nena cpl ale ace ae cae we 417 —-— symptoms of............. 415 — -— treatment of............. 416 — persistence and thyroid, pitui- tary and gonad involvement.434 PH PIOUS 25:42 47,194, 195. 196, ALOT oo Oecd al. Ores eee —- adrenal- -pituitary syndrome. : Petes ats o. Sul a ene evetere me Ren —a ductless gland (?)........250 —a lymphoid organ........... PASS —a misplaced tonsil..........254 ——and chorea minor...........249 —— dwarf growth............ 194 — and organs of internal secre- tion, inter-relationship be- WOT Birr ie oe Scrat St once eke ee 408 —-—pparathyroid ............524 — — post-operative death in Graves’, dis@ase. ........ 12 ———— VAP OLOTLY: .\5 @ & <\'si.0!3:2layeiene 59 ee PAT OTE, |. xs. 20k ate aos So alee 242 — — — feeding ..............245 — atrophy and vagotomy....... 249 — cases, classification of....... 411 — change of position of........253 CHAM CR MEN Sw. o cake an oe oe ee — clinical significance of....... 196 — control of skeleton growth...242 ee) at rl ol eee gy MOE on Mie a 522 — — other theories of......... 414 —— st MOOTICS OLS «cakes =. ciatcun eee 412 — effect of thyroid extirpation OU ats ot irene neta ete: «! eee 201 ——— (OMIAR OCW ios. steele 5 Bete oe cme 214 ——aand difficult breathing... .248 == —— Fs INEANCY. «2-6 s Serene 2 as = 336 —-a possible cause......... 246 — — treatment of............. 336 at WO GASES, OL 4 <4 a cs ERP VT ALONE. © fine», ois, shies ot ont aes 242 — extract and fatigue......... 196 — extract, effects on gastric se- CUCELOMMeeESe ><: = se aude Mexeee eS 329 — feeding to frogs............ 243 — -—to animals, results of..... 245 =A TUOCVOTIG ORG sce cies oh sty 405, 522. — gland, extirpation of........ 194 —— hyperplasia of, treatment. .197 —-— specific action of......... 195 Thymus gland, tetany-producing SMS UA MCet, MN etocciet tenis Sao oe ee —— eT PCTACTLVICY © oe stereo. 0,2 2 mic o,s 246 — hypertrophy, therapy of.....522 EMD OACELVEUY = Foes) snc eate dew asap 249 — ina case of starvation....... 12 — influence on skeletal growth. .253 —-— upon development and PPOWLENOE A> ccna ce erie 195 ——Ingiry, TESUIES.OF .. <2 2). /. 2 =< 245 Pat PI COTRELECS 20-02 ssn suche woe Epes 405 \ Thymus internal secretion. .241, 255 ==), PICK OCU. 2. 2 ous cdereisieeenene nets 333 ——INVOMNLELON .6, o.com x ee 241 —-— gonadectomy and......... 245 —jin wasting diseases......... 247 — new function of internal secre- (ALOT Cy eS, 55+ RR Wie ayrA33 = NELHISEANGE <. .. .\s a8 sik oe eee Aion ——of and sudden death of SOLU LCS Siar oe eee ae 336 —rachitic changes in children. .248 — relation of sexual maturity. ..197 — relation to general metabolism TS ene ae Pee 247, 248 —relationship between, and car- CUNOMUA 2 sien weeds 3 eee —vrelative size at birth and pu- DOUGY. erie le be core Sanece en uae 252 — removal, effects of.......... 244 ——=— {TOM TTOLS <5..— sone Sores ens 243 —— results following. 406, 407, 408 — resembles tomnsils.......253, 254 — role of in producing tetany. ..524 — sclerosis of, with grave osteo- DOLOBIG..0 15 tenes sre Skee 523 — secretory activity (?)....... 250 —— SACO Wiiecce. 2 he rats, = 6 OO —— STP miftCANGe Ol: o> oc so sce ee 254 — skeleton relationship........ 242 — susceptibility to infections... .405 — temporary and permanent ehaneesaam'. 2 cescchci ea US etree 405 ——— tHYTOLUSAR. . 6 Se .cie eo Pie, 20 — transplantation in rabbits.... Thyrogenic rheumatism, chronic.538 Thyreoglandol-Roche...75, 196, 204 TRhyroOld= set. 7 ho 46, 48, 58, 198 JtOma0l, Soo tO eo, D206. aos —— AN CLPANE wo: spatter sae se cnc: — action of, upon growth....... (2 — active constituent of........ 344 — activity, effect of certain drugs OT Re es sso eng ee 3 see oe 199 — -— effect of temperature on.. SR rea 2 5 aera 199, 340 — and parathyroid, effect of thy- BOM,s OXUTACL Ge. ons <.c Srs,cue ees Hi — — — effects of partial removal ihe O00 01 ee eli early» Ae ee 9 ie SH ——w—glands.............. a2 —--—relation between pan- CRGAS Sate veal eases ous Sacre 57 ——— tetany ............... 105) — —— EICALY occ lsieys) whe waren) nisl 76 — — — extracts, effect on blood DTERSUTG yeche thes) reise oe 76 — — —relation between in rat. 57 — -— resistance to infection.... 87 ———— EhYMUS’ ~ Re wv sis suenes se Lbs, 207 — — — enlargement, X-ray treat- MICNE On =: seis was ee nae S20 — — VAZOtoMy ...- i ecserceewve 59 Thyroid, alleged detoxicating DOWEL. OL x «cise 542 — apparatus, life history of... .543 — associated with thymus per- SISCENCO =4ceet- ae oe eae ee 434 — atrophy of and basal metabolic TALE ss ci pete Eb ae ee Bee — blood (siearenitiee -ccic se ics 344 — changes in caused by pituitary @Xthact hots. 2 oe ee 78 — deficiency, headache from... .200 — -—relation of chronic infec- TIONG y cuetels Gyeusicats eee 527 —development of malignant tu- MOLES! Ol cps eee 338 — disease, action of thyroid prep- aratiGns iN=jc% fs -- ee ered (i: — — effect on thymus and pitui- TATE coor = Secaptey sym, in loot taco — extract, action on parathyroid- ectomized. dogs: .* +=. aa 326 — -and blood sugar increase. .198 —-—-—hydrocephalus ........ 77 —=— G0SALE =... es 3 ee ee 434 —w— effect of administering to PUTA | cc toveacys tree eee aH — -—-—of substitution for ad- renal extract). -..305-scun —-—-——on muscle............ 65 —-—-on regeneration....... 322 —.=——n. eretinism:., 35.5 -neee 347 — —w— endemic goitre........ 545 — —— painful breasts of men- Struation 34... 14 — — — Myedema following ‘ SETUMECEOMY, sce iG; ———spasmus nutans ....... ou Ue — — — treatment of rickets. ...350 — —jinfluence of on metabolism and heart... = <= aes 203 —-— specific for eczema....... 339 —-—suppuration following ad- ministration: Of:<... a2 143 — feeding causing hypertrophy of LEVIS Se oes anno os fore deute Oe oe 245 — — effect on metabolism...... 5 — —jin goitre in children...... 341 —-—-— myxedema ........... 219 — -— of tadpoles, alterations fol- LOWINE: «>. sexe chem ee 294 — — eo adana cd 242 — toxemia and incipient tubercu- WOSTS HP sce ens ik sun ovata eee — treatment, influence on mon- PIOUISTNN wee cieunas Gye. sake acti rere oo ——of Vincent’s syndrome... .350 — tuberculosis of and exophthal- IMAC OMT Coho cod eet nee tae 76 — tumor, an intrathoracic, report Ol CASS... 2 citi twa scone 5 eee Thyroid-pituitary insufficiency. ..207 TR VFOUUECTOMIN:, 3.2002 «lence eee 15 —amnesia following........../.525 — effect-on metabolism........ aT —in amphibia, further experi- MUCUS D sce. sas oeeee a 340 — influence on protein metabo- List, 10% Sane eer tre oe 345 = Narvialle ool 2. oc ate Bie ic: o's Sees 545 — temporary loss of voice follow- RIVES eas. Pith nc Site ce Oe mn eee oes 344 Thyroidin influence on standard metabolism. 2... or eee 2 Thyroidism, relation of soldier’s CATE WhOmecs. s.48 2. she io others ee Thyroiditis, case of recurrent AiGUEG peewee) 2 See sir s leven ane 525 Thyroparathyroidectomy, action on nervous control of heart.351 — effect on blood coagulation in HOR eer HL erences ne ereuct s bes oaks 354 — effect on heart and circulation.351 7 Thyronucleoprotein, influence on TCT AMI OMSINI a5. 6c) oun erceueh ones 347 Thyrotoxie Cardiopathy ......-...- 349 SUNT RANI tas oper soot es 3 /sna p> pel ay wlan 85 —2etlOn! 1 Why XCOCMA. «ss. - «pels 85 SS HTC oa Oa Ke) ne See cen 90 —— energy production........-.- 88 ODE rine. TOL 1 WpOd ys... a. 91 —relation to creatin, creatinin animo acids and protein.... 92 MDG sak Mice she hia, sense > enage ion 4.... eee 121 “VWrina: -Spastica’: - 5 nc) oe 121 Urine flow, effect of adrenin on. .164 — influence of adrenalin on se- cretion of sodium chloride | «ener e eRe eemre ee nirr ecelsee: ~~ 160 — — — pituitary extract on flow Of. 2S a ae eee 120 —.— — —— output ...... ave ee Uterinie ibleediney sss. seen 441 == fibromas <2. .-sie x. 2 4 oe eee 489 — inertia, pituitary extract in. ..332 Uterus and ovaries remaining in- fantile ...< S55 Sas Dee 211 — isolated, apparatus for testing activity of druesson, eee 320 — small. or infantile: o. Ses 214 — ovaries and, tumors of...... 512 Vaginal metastases of hyperne- DHTOMA s.r. ee ee 323 Vagotomy and the _ endocrine PLAN GS? v2 6 ese. oe sk pace 59 —-—thymus atrophy.......... 249 Vaeotoniainas.. 42 214, 216, 235.237 —tonus problem and.....7.. 3. 545 Vagotonic disposition, influence of 26 — Symptoms’ <5 5.05 cae oe Zito —type of exophthalmic goitre, characteristics. of..-noee 28 Vagotonus, attempt to produce ex- perimientally.” ......:.. eee 545 Vagus nerve, action of on heart, adrenialsya:... {.Ac6n eee 310 Vanderkleed, C. E. (Pittenger) .324 Van Heeteren, A. (Hekman)....485 Vanneman, A. S. : 68 Variation, seasonal, of iodine in thyroid... oon eee 98, 100 Vascular changes produced by ad- renalin in vertebrates...... 122 “Vaso-dilatine’: =... 6. eee 423 Vasodilation in intestine, location Of mechanism. cen oh cee Vasodilator action of histamine. 480 — mechanisms, adrenalin.....1, 476 — —w— location of............ 163 Vasodilator mechanisms in sym- pathetic ganglia ......... —— — cat at different ages... 52 Vasomotor changes following ad- TENN PA VTOIG ULES. «ce esses s 464 — control of marrow vessels... .313 — irritability, effects of testicular LVANSDIANESS UDOM2:, 2... ... « 335 Vegetative nervous system in ty- POLO WOp (Ca Le ay Rta te ae ae 318 — —— relation of asthma to. .317 — — — relation to exophthalmic POILTE Sate cydere * 2825 Gs alee RIOTS MWA) ner tater Maier Lencn ev of seals; 79 Venous discharge from adrenal FeAl Waite (8 Vos cone Aa ease 316 Acer Vay HAL OR sre aes vc cele DOU Worce causes Of IGSS Of: 22. 2. 3.6% 344 —— loss of treatment...0.5.. 6... 344 —temporary loss of, following EMMY TOU SETONIY, = iiiene coe sche 5 os 344 Von Graef’s sign in Graves’ dis- GENE: oo he ee OIG SR eee 24, 28 von Recklinghausen’s disease. . .520 — -—— bone changes in....... 490 Wagener, C. (Loeper and Dubois) .160 — (Loeper and DuBois-Roque- [DETTE hate Seen Cee e Conn Ree 478 Wagner (Loeper and Benzard)..469 Wagener von Jauregg, J. (Diviak) .527 Wahl, H. R. (Knox and Schmeis- Se) ook Se) Shee 60 War, ductless glands and....... B22 — hypoepinephric syndrome of. .474 — influence of on diabetes mel- MUU ENS} Ses. SiG engiio 5.0 eee 321 ANE VaR d hol ogo he Oo 0 67 Wasting diseases, thymus in... .248 Watanabe, C. K........ UGGrmsiod tole Watson, A. MclL. (Burns)...... SHyAl BRS US 5 aes nae cee (4, 342, 533, 544 Weber, Pe oe Gee hTS8, 494) 5L0 Weight, loss of, in tuberculosis. 16 Weiland awe (Ritter) 22. .i..... 80 Wembersericis-g Wa... 06. ees 176 SS Ubon os SR 920 527 em NIL ECHO) a as Voc ct wo oie > eos ae WU CIC lan Acta & piciea one eet ae 526 Wels, (Frey and Bulcke)....... 160 Wheeler, L. (Gillett and Yates). .511 WHRGCION Dio. Chic piss eee 71 —— (SULDLOV)" o.c 05 oo sTh Slee s a eee W hite-vadrenal. Tine! 2.5.23... <3. .4 470 — corpuscles, influence of secre- PLOURG OTS dy nctate Pate toh eaten ee 191 —line of adrenal insufficiency A Naisaicna eka eA vaniy. yin Ade AOU, Aon, Bed. ae sae —rat, response to adrenalin in. 132 NOU L CC Ua oe Rea ee ee ees 68 WOR AYNIA a Wee Ws otc eckc se os. ee, Dae =o DO ee noes eS 491 VERMIN Heatran: Sys robe eEYe ao ee eR SMS OM eM iwess 20)..2% ao tod ee eo — R. M. (McKenzie, Poynton and SLONGY:) ste ec see eee 527 LGN a= oat sd oes acer aud coe ote A SE ee see tenes oe eh th Suede ee = ere (pat Witherspoon, J. A... ...<.<...-580 Washaré2DsJ...235-4 eee 161 Wohivemuth., Jic..44o1 2 eee 186 Women, material lost in menstru- AULON ako kets oc eee re, = RE ee Woodchuck, cyclic changes in in- terstitial cells. of........~- 353 X-ray, see ROntgen ray. — action on normal tissue cells. .290 — and thyroid stimulation in tad- poless.c.J fs hae ee 2 99 S00 —in thymus hypertrophy...... War — radiation, effect of......290, 300 — -— influence on life processes eA Aare axe DO eg — treatment of enlarged thy mus SEA So. Ee eee 336, 416 — — — exophthalmie goitre....538 — — — hyperplasia of thymus. .197 — —-—thyroid and thymus en- laneement 4252. 1... 25 —as Stimulant to sex glands 69 EAU Ee Ss St Se err ne tt Yates, A. (Gillett and Wheeler) .511 Zona pellucida, structure and POTIMALONR eG... -< 008 .9--< ule Se 184 MMC CESUGIN. | Sscn . ~ s «ste a ls 55 ATG CUT 9 OA ee ene een ee Pe IS seme TS / . 4 ee aS, =. 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