ailed study of this aspect of the ia a Tater paper: Coxctsions onable to conclude until more ex- s can be made that, unless he has a tensive stu seuetive lesion of the cord, a transection h thoracie and third lumbar segments exten sive enough to interrupt completely the thoraco- lumbar sympathetic outflow, a patient can and should be potent — that is, he should be able to have erections and 10 ejaculate —and that unless he will be fertile aney. other abnormalities prevent it, and capable of producing p Rurexences Lead Aes, HAR. Sere Takes Chas € Thess 9. Gi Conta of sgney boning aun Far perc trates a, Beal 1 TJ, ci Uris Sead ecm, 15 Many BL Renan of psn ory Grd lo BEB eT bes Mh fi 16 Thompson, C. E, and Witham. 4G Paoeyamal brperenvon in SOUL nla New Be, J, Sea die hon Bw re Peas Wee Sn 8 OBSERVATIONS ON THE BTIOLOGIC RELATIONSHIP OF ACHYLIA GASTRICA TO PERNICIOUS ANEMIA* X. Activity of Vitamin B,, as Food (Extrinsic) Factor Lioset Ber, MD.¢ Wieutaxe B. Caste, MD. Aawoup D. Weer, MD. Rovour Asker, Pu.D.,| asp Marty Bes nosro ‘T HAS been showa that various foods — for ex ample, beef skeletal muscle, milk? and eggs* contain a heat-stable, unidentified substance,! the so-called extrinsie factor. When such # source of extrinsic factor as beef muscle is ingested by a pa- tient with pernicious anemia, untreated or in re- lapse, it produces little or no hematopoietic effect tunless normal human gastric juice is also adminis- tered, either simultaneously or at least within six hours. The very small amount of the gastric seere- tion of the patient with pernicious anemia thus yparently supplies little or none of the heat-labile Memon on Th byte snes dees te aad ieee Ronert W. Heiter, M.D.) eis, M.D MASSACHUSETTS, AND CLEVELAND, O1110 + substance, possibly an enzyme,** that is respon sible for the activity of the so-called intrinsic fac~ tor of normal human gastric juice when adminis- tered with beef muscle. Gastric juice when given without opportunity for contact with beef muscle cor with components of an unrestricted diet possesses, no hematopoietic power.® Despite claims to the contrary,’ incubation of mixtures of beef muscle and gastric juice does not produce the heat-stable, antipernicious-anemia principle of liver in vitro.* Although there is reason to believe that contact between beef muscle and gastric juice at or near a neutral reaction within the intestinal tract is re- quired for hematopoiesis,® attempts to concentrate hematopoietic substances from incubated mixtures of beef muscle and gastric juice have given incon sistent results at best. ‘These observations are com- patible with the theory that the patient with per- hicious anemia requires intrinsic factor to utilize extrinsic factor at some stage in the production of the antipernicious-anemia principle of liver, but that a direct reaction between extrinsic and in- trinsic factors does not necessarily occur, Extrinsic factor is presently recognizable only by: virtue’ of its hematopoietic potency upon oral ad- ministration in pernicious anemia with norson human gastric juice. Consequently, we have as- sumed as a working hypothesis that the greatly increased hematopoietic activity in pernicious an- emia of liver'® and of relatively crude liver ex- ‘tracts when ingested with normal human gastric juice indicated the presence of both the extrinsic factor and the antipernicious-anemia principle. Recently, however, we have found that refined liver extracts when given by mouth are also po- tentiated in their hematopoietic activity by gastric juice, as shown by the following observation, which ‘was conducted according to the methods referred to below. A patient with pernicious anemia and an initial red-cell count of 2,540,000 was given I cc. of solu- tion of liver extract, purified (Lederle), containing Tame Potentiation of Hematopoietic Activity of Orally Cus Tex Der No Pruce, Reo-Cru Cover Rencotoevte Peak ro ise vor se 8 ” tm dn oT wo rpm as ue ne Ms er ws 1212 none ue u iso 3s ve ft 2G 193 one nae i ako seo Susended fo 12 0 WO ce of phy sain lation 15 USP. nits (injectable), daily by mouth for ten days, A reticulogyte peak of 3 per cent a5 at alte ‘on the seventh day. During a second con- WatGve tencday period the simaleaneous adminis {Sstionof normal human gastric juice withthe same noun of liver extract produced a second rtiulo- Um peak of 66 per cent st aa initial red-ell level of Posd 000. In other patients it was shown that hy- Grolybs of liver extents with ditue sulfrie ack, Gch apparendly destroyed most of the anti Foraiiowranemia’ principle, alo. prevented the Perera! fom being potentiated by Hoemal human 7 ‘With’ the isolation" of crystalline vitamin Bu, which behaves so far at is now known like the Tse antipericiour anemia principle of iver" {he effet of normal human gare juice on the ac- tiigy of the pure substance when orally adminis- tered could forthe fet time be tested. Accordingly, FS inicogim. of vitamin But dissolved in 125 oF 150 cc. of physiologic saline solution was siven dally by mouth during 4 frst ten-day period to 4 atiuts with untreated pericious anemia, Tm- Fredatelythereafter_in a second teneday period, the same amount of vitamin By, wns given by mouth Simultancously with 123 or 180 cc. of previously ea st gps Gh of Mask THE NEW ENGLAND JOURNAL OF MEDICINE Dee. 9, 1988 neutralized normal human gastric juice to each patient. The methods of dietary control, of ob- taining normal human gastric juice and of blood study employed in these observations have p: viously been described,” * as has the interpret of successive reticulocyte responses.# Particular attention was paid to administering the gast juice at times as widely separated as possible fro meals to minimize possible contact between the patient’s food and the gastric juice. As an addi- tional control on any hematopoietic effect of the gastric juice on the food, 3 patients (Cases 102, 103 and 104) received gastrie juice during the first period twelve hours before each dose of vitamin B: ‘As shown in Table I, in each case a reticulocyte response was observed during Period I. Except in Admininered Pitemin Buby Normal Haman Gastric Jui Diver Paearet 5 ranma of iain Bat 5 p.m Sammut viamio Band 1Decn gure le SP Case 104, this was accompanied by a signifi crease of red cells and indicates the greater poietic effect of vitamin By, given simul with normal human gastric juice, The reticulocyte peaks were not marked in Period IL of Cases 103 and 104, However, no hematopoietic effect what ever was noted during Period I, and significant clinical improvement did not begin until the ret locyte response appeared in Period IT of the ob: tions on these 2 patients. In Case 104, ds Period TIL, 5 gamma of vitamin By was given intra~ muscularly daily. ‘This resulted in a striking second reticulocyte response. Coxctusioxs "These observations indicate that the hematopo! etic activity in pemicious anemia of orally adminis- tered vitamin B,- is potentiated by the simultaneous administration of normal human gastric juice but. as with liver extracts, is not so great as the activity of the vitamin By, when given parenterally. It is suggested, therefore, that the food (extrins factor may be identical with or closely chemically to. the antipernicious-anemia rine of liver, which is itself presumably identical vitamin B,, It is further suggested that theVol 259 No. 24 ry for the optimal utile zation of the relatively small amounts of vitamin Bu of of chemically related substances present in various foods. Prelininary microbiologic findings with the use of Lactobacillus leichwanii (A-T.C.C. 4797) in an un- treated patient with pernicious anemia suggest that the fecal elimination of vitamin By is of such niagnitude that either the vitamin derived from the food, or more probably that eynthesized by in- testinal ‘bacteria, i not absorbed insufficient amounts to abolish the deficiency. (Since this manu- script was submitted for publication Bethell and his associates have reported the results of microbio- logic observations demonstrating large daily fecal excretions of vitamin Bin 4 cases of untreated per- nicious anemia, and from this fact have drawn simi- lar conclusions.) [Other observations suggest that material "soluble in 70 per cent alco- hoolie extracts of beef muscle, a classic source of extrinsic factor, when prepared in a form suitable for parenteral administration, possesses both micro- Biologie activity as vitamin By, and hematopoietic activity upon intravenous injection in_ pernicious anemia. It is therefore possible that the funetion of the intrinsie factor of normal human gastric juice is to facilitate the absorption by the intestine of vitamin By, oF of chemically related compounds in the food, rather than to react with the extrinsic factor as hitherto assumed. Rerzaexces WG Oh {intsinsie) factor is neces ite Pies Sey Se, DIPHTHERITIC MYOCARDITIS — BOYER AND WEINSTEIN 913 2 Mier, Fa iat Bah Bat aha BERS SE gata amberai der soa), Batin a pernicious anemia: nee cat Po eRaer ee fergie emule Pode Md MOP1AS61403, 1938. * ae at ngs aa ea is 9% Ris ds aug ab Iino Hn leat gtaenemne pence of ery ela af thermo Agbiie hacmopoletin om beck. Biochem. J. 28:1681-1692, 1934 ouch FD Wiser er Le EEQTRSE Ke tins, Zeke BR Mad 8: 1, Fou PJs Helin 0 My an Zan fe © Quetta Bont eihen’ nce Fem Tac Med wo, Bas, Ea Bah N. Gy Resioay, FR, Wend Ra and Git: Grate’ sac oh HE Bik "desp fronin Baa Alon pen ea erextracin New Eng J Med, 30% mle tagis A Gera LP DIPHTHERITIC MYOCARDITIS* Norwax H. Bover, M.D,f axp Louis Weiwsrer, M.D UBINERIA bes showa 2 siking, se in incidence over the entire world in the last five years. Although the rate of occurrence in the United States a¢ a whole has remained at a static level during this period, some parts of the country have experienced a disturbing increase. In Massa~ chusetts, for example, the number of cases has risen from 123 in 1941 to 439 in 1946 and 440 in 1947. ‘This change, together with the prevalence of the disease in the armed forces in various areas of the world during the war, has aroused again an interest in the study of this infection. ‘The purpose of this report is to re-emphasize the important effects of diphtheria on the heart as determined by electro- cardiographic examination. “rion the Hayres Merial and she Eva Meno Mvachontte eee Heats SNPS shee IPgiisuehtees ienosst Hexic nosToN ‘The eases of diphtheria reported below occurred mainly in 1946 and 1947; some patients observed receding two years and a few admitted in the carly part of 1948 are included. During this period 140 patients with diphtheria were admitted to the Haynes Memorial Hospital (the Infectious Disease Department of the Massachusetts Mem- rial Hospitals); electrocardiograms were taken at periodic intervals in all cases. Casual electro- cardiographic examination through the course of the disease was shown to be wholly inadequate because it was observed that changes might occur im the first few days of the disease or not until after several weeks and were not infrequently very tran- sient. It became evident that, to demonstrate short-lived variations from the normal, eleetro- cardiograms had to be made almost daily from the time of admission to the hospital until con- valescence was well established. This point deserves special emphasis because without fre~ in the