Studies in Scurvy. Part I: Examination of the antiscorbutic value of some vegetable products

STI]DIES II\ SOI]RYY BY J. ÂXEL HÕJEB X'omer ¡'i¡st ¡.ssistant at the Chil¡hen's Clinic of the Karolinska Institutef, gtockholm. (Chiet: Professo¡ I. Jundeu.) Thi.s worlc l¿as been, carried, out by øid, of gra,nts fronx the l{aroli,nslea Institattet ancl the Stced,ish Soci,ety for Medôcal, Research. UPPSALA 1924 ÀLMQVIST & \ryIKSEL],S BOKTRYCI(ERI-Ä.-B ACTA P.ry,DIATRICA REDÂCTORES: lN DANfA: C. E. BLOCH, xöreNnevN, S. MONRAD, rösnxul.v¡{. IN X'ENNIA: ELIS LöVEGREN, nor,- sINGFoRS, ARVP YLPPö, HELSINGFoRS. IN TIOLLANDIÄ: E. GORTER, LEIDEN, J.ITAVERSCITMIDT, IrrREcHr, CORNELIA DE LANGE, alrsronoau. IN NORVEGIA: TH, F.RöLICH, KRISTIANIA, AXEL JOHANNESSEN, xnrsrrlxr,l, CARL LOOFT, BERcEN. IN SUECIA: I. JUNDELL, srocrnor,nr,.{.. LICHTENSTEIN, srocxHow,WILH.'WERNSTEDT, srocKHoLM. EDrroR: I. JUNDELL, srocKHoLM Yol. III. Supplementum 17:Y. 1924 Almqoist û Witcselts Bolctrgclcer¿-Aktiebolag UPPSAI.A 1924 To Ørofn""or" -Qtn/ 9{o/"t ',/ TÁeodor Tral¡oÁ This worlt is reryectfully insuibed,.bg T.HE AUTHOR CONTENTS Preface Ïntroductory l'Iethods of experimental sc.rvy, from Holst to the lâtesô investigators Part I. Enanzinal,ion of the antiscorbttt'ic aaltte of som,e Desetuble ltroclucts. Survey of experiments Summary; discussion; concltrsions Part If. Hísto -p atho lo gi,c al s tt c d,i, es. Preliminary notes. Introclucúory The macroscopic changes Technique Nomenclatu¡e Classification of scurvy in different st¿ùges Grouping of the material within these stâges Chapter f. The bone formation in scurvy. ?èeth The endosmal ossification The enchontlral ossification. Cartilage * Four cases of infantile scurvy . t Summary ancl conclusions of Chapter I. Chapter II. Museìes. 'Ihe skeleton musculature Hearü Ohapter III. Liver Chapter IV. Spleen . . .. . Chapter V. Kiclney Chapter VI. Atlrenal Chapter VII. Salivary glancls . Chapter VIII. Lung Chapter IX. Blood ancl vessels. Hemorrhages in scurvy Chapüer X. Connective tissue . 8 I 2g 30 31 QO 0Õ so 38 48 50 60 64 18 22 68 79 QÐ 91 96 100 104 107 109 L74 Pørt III. Discussion of some scurug problems. Chapter I. Scurvy and infection Chapter II. Disposition Chapter III. Latent scurvy Chapter IY. The ca'lcium metabolism in scurvy Chapter Y. Scurvy ancl rickets Chapter VI. fnanition anil scurvy Chapter VII. ,t mocliûecl methotl for experimental rating of the antiscorbutic value of a protlucú Chapter VIII. Pathogenesis of scurvy. Relation of scurvy to other 11ó 1.22 r23 726 128 729 130 cleficiency tliseases Summarg a,nd, conclusi,ons of Parts fI and III Part IV. Scuruy and, tuberculos'is. Chapter I. Historical Chapter II. Experimental study on guinea-pig. Technique ancl survey of experiments fnfluence of scurvy on úuberculosis . fnfluence of tube¡culosis on scurvy . . . Chapter III. Experimental stutly on man. Survey of experiment Criticism ancl conclusion , . . Swm,marg and, concltcs'ions of Part IV . Part V. Re)cortls oÍ cases. Cases belonging to Part I . u), ,, Ð ,t oIY, , II ,),),,,IV,,ilI Literature cited: List of authors 94 nicrophotogrâms. 33 curves in the text. 6 colured plates. . t32 139 I40 t64 169 170 748 \64 L62 172 200 206 234 , 265 . 276 Preface. The work which is here presented was begun in July, 7922. rt would have been impracticable to fulfir it without the possibilities of technical aid offered by clinical laborato. ries. To Professors F. Hnrvscn¡w and G. Ificceulsr, who have allowed me to avail myself of these possibilities and, to whom I am also indebterl for much helpful advice, f beg to express my gratitude. My thanks are also due to professors I. ]u¡vopr,r and U. QurNsnr,, to Assistant professor Dr. C. Kr,rrve, Doctors R. Nonocnnr, G^. Vnsrnr:cr, II. D¡.v¡on, A. WlssÉN, S. Srvn, A. IMllr,cnnrv, Å. Årnnr,urvr, the Dental Surgeon Dr. G. \{.usrrrv, and others, for various reasons, some of which I have mentioned more particurarry in my book. speciar thanks are due to Doctor F. \4f^nr,annrv and Fil. Doctor L. G. Ro¡rnr,r, who have kinclly reacl the proofs. My late father, the historian Nrrs J. Ilö.rrn, who during all his life, beside his practical activity as a teacher, d.evoted himself to scientific work for science's sake, has been my model. My wife, Src¡rp Ilörnn, has been my helper. f have allowed myself as a respectful token of ad.mira_ tion to inscribe my work to professors Äxnr, rror,sr ancilrn¡ooon x'nör,rcn in christiania, the first investigators in the fieltt of experimental scuryy, whose work still remains unrivallecl. Even though the exaggeration is evicrent in x'unk's utterance (7922): usince the experiments of Ifoht and FröIich, no real progress has been macle (in.experimental seurvy), in spite of the numerous publications that have appearedr, yet his worcts show how high Holst and. Frölich's works rank among all the rest. Hagalund' sweden' T'ebruary 1924' J. Aret Höjer. IJ. ÄXEL IIöJER lntroductory. .A.fter the strenous research during the last twenty years of a number of distinguished investigators, it has now been proved that scurvy has to be looked. ullon as orze clisease in adults, young chilclren and. infants, in monkeys and guineapigs, with the same etiology, the same unknown pathogenesis, similar clinical symptoms and. patìro-anatomical changes, and identical therapeutics (MacCallun). Scurvy, however, is above aII a diesease of growth, ancl the most profitable stud.ies have been macle in quickly growing organisms, human infants or young monkeys and, guinea-pigs. As surely as the quicker growth is a fund.amentai physiological factor, which principally distinguishes the undeveloped organism of the child from the developed organism of the adult and constitutes pediatrics as a special branch of medical science, as surely the scurvy problem is a central pediatric problem. The pian which from the first f had drawn up for this work rvas the following. I wished 1) in connection with the study of the antiscorbutic substance of some Sweclish wild berriesl to examine the scorbutic changes which might be expectecl in liver, muscles ancl teeth, ancl to take up some scuryy problems for discussion; and 2) to stucly the mutual relations of scurvy and tuberculosis. As the result began to show clear- €r, f have wiclened the plan, and especialy f have extênded" the patho-anatomical stuclies a,s far as the material available after the plst-T7u'tenx examinations has allowecl, in ord.er by this means to support the new conception of the pathogenesis of scurvy, which presents itself as the final result of these stuclies. Many orgalls are left out, ancl among those lacking are the thyroid glancls, the sexual org,ans, the hypophysis. Before ì.ong, I am going to publish complementarv investigations, which have been carried on, but are not as yet brought into definitive form. I With "strawber¡iesr are in the following always meant .rviltl wooclstrawberries, Fraga,r,ia uesca L,, ancl not trragaria moscata. ii S'IUDIES IN SCURVY Methods of experimental scurvy from Holst to the latest investigators. In 1907, A. Hor,sr showed that a diet of cerea'l andwater induces scurvy in young guinea-pigs, and together with T. Fnör,rclr he then submitted. clifferent scurvy problems to a resultful exa,mination, using guinea-pigs for the experiments. Their results having been confrrmed from many quarters, the antiscorbutic substance (or group of substances) was rangecl as vitamin C (Dnuuuorcn in 1919) among the vitrimirrs (Fusr<), or the accessory food factors (Horrnrs). Still the guinea-pig is the anirnal most frequently used for scurvy experiments. It is only the introduction of the monkey (Ifunr ancl L¡;ssrnc 1913) that has been a gooit aclctition, but through its quicker growth, easiness to hand.le, and cheapness, the guinea-pig has consiclerable aclvantages as experimental animal. Ilor,sr and Fa,ör,rcn's basal diet,'different kinds of cereal and water, is absolutely free from antiscorbutic factor. ÀlI the later investigators have confirmecl the statement that the pïogress of scurvy in guinea-pigs on such a cliet is very uniform. The nature anil sequence of the symptoms ma,y be studiecl in the works of Hor,sr and Fnör,rcn (1907, 1912), Connr ancl Mnnppr, (1918), Hnss (1920). I give a short extract of their descriptions. After a symptorn-less period of one or two weeks after the animals have been put on absolute diet, the first pathological sign appears, signalling the onset of the disord.er. This first sign may vary, sometimes it is a loss of weight, sometimes a tenclerness of ioint or an inordinate excitability of the animal, which soon changes into inertness. After two or three weelrs the animals show an unwillingness to move which has been ascribecl to the swollen, tendel ìoints, around which there are numerous hemonhages, also in the musculature. Often they try to protect some specially affectecl joint by continually holcling the correspond.ing limb iiftetl, >the scurvy positionu of Crrrcr, Huup and Sxnr,ron. The teeth become loosenecl ancl the incisors.frequently break off. The coat is rough. Very often fractures occur at the o 10 J. ÄXEL IIOJER epiphyseal lines of the long tubular or medullated bones. The hemorrhagic diathesis may be extended to al.l tissues and after three, four or five weelrs the animal succurnbs, after having lost about a thirci of its weight at the beginning of the experiment. The results founcl at the post-,hrcrtem examination may be summarizecl thus: 1) Hemorrhages, most numerous and largest in and. about the epiphyseal ends of the long bones; 2) Atrophy of the bone-system, presenting itself parUy as a general osteoporosis, partly and. principally as a typical d.isturbance of the growth zones of the iong bones. Here the ma,rrow loses its specific elements and gets to resemble a mucoid tissue (>Gerüstmark> or frame-work marrow of ScnonDErr and" Nluwnnr). fn the preparatory calcification zone the osteoblasts are lacking or have taken the appearance of spool-shaped celis of connectiye tissue. There is no trace to be seen of normal new bone. Infractions have often occurred, so that the bone-bridges lie scatterecl about in splinters - the >Trümmerfeld area>. Besicles fragments of bone there are also seen calcified cartilage bridges, recent and older hemorrhages ancl remains of such. fn the cartilage the proli ferating columns a,re in disorder. They are shorter, irregular, and the cartilage cells show degenerative changes in a higher degree than is normal. These changes often cause an enlargement of the epiphyseal line, which is specially evident in the costochondra,l iunctions - a pronounced rosary. If the animals that have scurvy get food. containing antiscorbutic, the symptoms may be ma,cle to subside within a short time. ft is easier still to get an estimation of the antiscorbutic value of an article of food, if from the beginning of the experiment a certain amount of it is given as an addition to the ba,sal cliet. The smaliest quantity which then protects the animal from contracting scurvy, the minim,um, pr"otectir;e dose, is used as a relative standard. of the antiscorbutic value of a substance. The smaller the minimum protective d.ose of a substance is founcl to be, the larger its antiscorbutic value. fn the experirnental methocls of Holst and Frölich, the SÎUDIES IN SCUR\¡Y I7 â,s controls. Half their number iived till they were l<illed after 93 clays, and none of them showed signs of scurvy, tnùctoor microscoPicallY. That the basal cliet described above, and. usecl by me, is free frorn antiscorbutic is shown by series 1 and 26, together cornprising 16 animals, charts fig. 95 ancl 120. All these, with the exception of one who died on the first day of the experiment from an acute infection, developecl typical scurvy and diecl after 18, 19,2+,24, 2+,26,26, 27,28, 30, 3L, 33, 33, 36 ancl 38 da.ys respectively, rvith an average lifetime of 28 days. S¡rnnulx states the ayeraEe life time fol animals of about 300 grarns with totally scorbutic dietary to be 26-34 days, and. other authors also inclicate about 28 clays. At the post-morten't exarnination of these guinea-pigs, all changes mentioned. as typical for scurvy were present. The first scurvy symptom Ilnss has often been able to iclentify on the 1.21ir'- 14th d.ay. The earliest d.iagnosis was rnade by him on the 8th day. I have also seen Cnrcn's scuïvy position intermediately a,ppea,r on the 8th day, and. in none of these cases the onset of the first symptoms w¿ùs delayed longer than to the 16th day. From this f conclude that a clemonstrable quantity of antiscorbutic has not been present in the basal diet. To believe, like Ro¡s etc. and" How.e, that the first syrnptorn alrvavs presents itself on a fixed clay and. to interpret its coming a day ol two later as proving the presence of antiscorbutic, is contrary to all results gainecl up till now. - As a careful microscopic examination of my animals has been carriecl out (see Records of cases), surely the basal diet fulfilis the two funclamental claims, being quite free from antiscorbutic, ancl in all other respects a cornplete dietary. The 'iuices I have triecl have been given to the animals with a pipet, grad"uated in 0,1 ccm. With patient handling the anirnals soon learn to eat in this manner, and soon they rvill suck the pipet as eagerly as a bottle-fed infant does his bottle, without losing a drop. H¡:ss has opposed the use of weig.ht charts as scurvy charts. He aclmits that they often have a typical course) 2-24125. Acta pød,íatrica. Vot. III. Supplementum. 18 J. Äxnr, HöJErì r'vhen the animal only gets basal diet, with one rising and one sinking part (see Fig. 95 u. o.), but their course does not directly indicate the degree of the scurvy symptoms. Sometimes the scurvy symptoms will appear while the weight is still increasing, sometimes the weight goes down, when the aninral refuses to eat or when an infection is at hand, continually from the beginning of the experiment. Hnss has attempted to clelineate a clinical curve. fn pra,ctice, I have found this impossible. But f appencl the weight charts, as in any case they give much interestinE information. PART T. 'f'he onti,scorbuti,c a(rl,ue of sorne aegetccbl,e produ,cts. Survey of experiments, T}oe nwmber is founcl in the Record"s of cases p. 174. Diet. B. cliet : basal diet (see p. I2). For the aclditions, see Discussion. M. p". cl. : minimum protective close of antiscorbutic (see p. 10). Weight in grams at the beginning of the experiment and. after death. The signs *, -, or ? after the final weight ûgure indicate that the animal was not weighed at the post-mortem exanination ancl that towarcls the end the weight curve was pronounceclly rising (* ), falling (-), o" level (?). Scuruy. For the deffnitions, see pp. 35. Scorbut manifestus graviol' ****. )) )) ¡¡jlig¡ **.. > Iatens gravior (..-4. : ', tt""t"#H.incipie's .. SÎUDIES IN SCURVY Tahl.e 1. Series I250 270 270 260 296 275 270 276 280 2t0 270 100 295 300 320 325 330 345 365 190 190 276 180 195 170 160 200 600 7 í,0 635 710 730 7t0 700 + 580 780 ó60 ? 75b + ilI IV v 1 2 4 ô 6 I I II I 10 11 1,2 13 T4 T5 16 ú 18 19 Basal tliet. 0.0 m. pr. d. ß. diet u'ith srvedes aucl green leaves. > 1 rn. pr. d. Il.dietflccm. recl rvhortleberry juice, 1 year old, ìrought at gtocet's. 0.0 n. pr. d. ts.iliet*óccru. of the srlrne. juice. 0.0 m. pr. <1. B. diet * 10 ccru. of the sarne juice. 0.0 m. pr. d. 20 27 22 23 296 300 280 296 270 23í) 200 280 23í, 290 286 170 200 180 19õ I45 210200 770 24 25 26 27 28 29 30 Weighú in grams o p zDiet initiat I ñnaI Scurvy VI 175 240 140 24 26 38 31 ðð 27 26 24 19 1ìernarl<s Chloroformetl, glavicl , f-prra , f-para (trvins) Infectecl rvith tuberculosis bâcilli on first tlay of experiment. Dietl of pneumonia ac. Diert of septicemia 0 0 0 0 0 0 0 0 0 **-i.:i 142 L42 t42 94 742 142 I42 1,42 742 742 142 32 1.2 74 28 26 28 30 28 28 2S 27 (x,ri.Ë) (?rx-,r n) 20 Series I Y VII VIII IX x XI XII P zDíet B. tlict *ó ccm. of rarv fresh recl rvhortleber:ry juice 7922. 0.0 m. pr. cl. B. cliet t2 ccur. recl whortleberrY juice, pressecl 1922 from berries Preservecl in rtater since 1921. 0.0 m. pr. cl. 13. ctiet *7 ccm. of the same juice. 0.0 m. pr. cl. 2 34 ÐO 36 38 39 40 4T 42 43 44 45 47 48 46 B. cliet *õ ccm juice pressecl 1922 from berries, stirred with sugar 1921 49 0.0 m. pr. cl ó0 B.cliet*1ccm. 51 "¡¡1' juice of fresh blue 'çr'hortleber62 ries 1922 ó3 54 55 0.0 m. pr. d B.tliet*óccm. of the same juice. 0.0 m. pr. tl. ó6 296 366 626 430 400 460 440 2'o0 26í, 270 27r, 230 300 346 290 800 270 236 270 180 230 230 260 240 240 27 í) 230 final inititl .T. ¿\XIìI, HöJEIì Weight in grams Remarks Died of septicemia Suffocation LifeScurvy 210 266 240 260 140 170 220I li) 180 220 206 185 250 320 L55 150 l"ô'o 180 38 35 43 31 30 B1 32 220- (**'Ìr3) Died of enteritis ac. I 27 28 ól 29 26 30 206 1 I Ð170 190 1,.*-+* *tí** :Ì,iti* titr+,Ï ,¡ 22 26 ;10 29 29 28 19 140 tta 185 170 Died of suffocat'ion F .Á Diet initial finnl Weight in gra,ms Series XIV .\VII -\IX XIII Ðð 59 60 61 62 63 64 65 66 87 68 69 70 B. cliet *ó ccm. juice from stewecl blue lvhortleberries 1921. 0.r m. pr. d. SÎUDIES IN SCL]RVY 2l .llernarks In tlying conclition killed with elher Died with lymphaclenitis supp. subment. Died through overlying Died lyith l-vnphadenit. suÞÞ. Died lYitb. lymph¿denit. srrÞÞ. Dietl of bronchopneumonlÍì, ¿to. Diecl of peritonitis ac. Died of pneum.onia, ac. Chloroformed Died through drowning 2t0 27 f' 255 2a\lt 13õ 275195 200 230 150 245 275 340 t¡t¡* 255 260 2í)5 315 406 240 280 2'Ð5 286 160 180 160 250 60 ft2 39 ó7 10 Ðo 4 61 QO 42 46 õ0 B. diet I 10 ccrn. of the same juice. 0.2 m. pr. tl. B. cliet .l5 ccm. juice of fresh sfrarvberries stirrecl rvith sugar. 0.r m. ¡rr. cl. tí -\V XVI 77 72 74 to 76 tó Il.cliet*ãccrn. ûr needle tlecoction. 0.0 m. pr. cl. B. diet *1ccrn. fresh olange juice, vet2rfrc I8/rrother juice. Varied vaìue of m. pr. cl. B. cliet I'ithout oI. jec. Âselli i2 ccm. fresh orange juice. B. diet ¡r.ithout oI. jec. Aselli *4 ccm. fresh orange juice. B. diet *3 ccm. fresh tomato juice 1922. 0.t m. pr. tl. 270 240 250 250 370 380 445 360 IIealiDg 0 0 to 29 28 27 66 ob 66 30 470 | 260 I 39õ i 390 + 346 ',435+ 320 360+ 390 280 400 - 510 - 200 280 230 226 46 19 Chloroformetl VIIIX7c 80 81 QO 83 84 85 86 265 420 480 340 400 270 30õ 60 60 43 39 39 ,13 Scurvy Lifetime clays initiali final Weight in grâms Diet 22 xxr 87 88 89 90 õ0 46 J. Á,XEI, HOJTIì o P z Selies Iì,ern¿rks Lyrnphatlenitis supp C¿use of tleath tloul¡tfui Dietl ¡t the lìrst pipet feeding, XX Oats and bran, 200 ccm. milk, r'&r1'ând fresh, for them all together'. 0.t m. pr. t'i. B. cliet -l 2 ccm. raspberry juice, preservecl. 0.0 n. pr'. cl. 320 345 340 350 260 220 200 220 91 92 365 280 23-o 200 270 220 28 27 6 XIII 9tl 94 XIII C'o 96 ì B. diet * 2 ccm. I blackculmntjuice, I preservetl. | 0.0 m. pr. d. I -8. ¿iet * sn'etles t f ancl green lelves J > 1 nf m. ¡rr.. tl. 470 250 24 200 220 220 0o 0 8 0 Summary and discussion. Recl øuhortleberries (Vaccinium vitis ic[æa, L.). Of the antiscorbutic value of these berries there is onlv one investigation in the iiterature, by Fûnsr. Seven guinea-pigs were giverl a basal tliet of oats, yellow peas and. rice meal, ancl with this d,iet in all 100 ccm. red whortleberry juice (t.".p. 1'48; on p. 128 the quantity of juice for each animal is inclicated as 25 ccm.). The animals died after 18-28 days and a,ll showecl scurvy in a higher or lower degree. IMe are not told whether atl the juice was consumecl, and in a,ny case it is impossible to know how much the different animals have had-. Fürst believes he can conclu¿le a certain protective effect. The conclusion is d.oubtful. 29 of my animals have been used for testing red whortleberries. So-callecl natural juice, bought at a grocer's and for the composition of rvhich there has been no guarantee, has been tested in doses of 1, ó and 10 ccm. Further the 'iuice STUDIDS IN SCURVY 23 of ra,w berries bought in the ma,rket-place was testecl in a dose of 5 ccm.; the iuice of whortleberries, which iuice since 1921 had been lrept in closecl bottles with water pourecl over them, in doses of 2 anð, 7 ccm.; and the iuice of crushed. whortleberries, preparecl in 1921 by stirring raw berries together with the same quantity of sugar cluring an hour. All tlne 2g animals showed manifest signs of scurvy; six, who cliecl of intercurrent infection, less pronounced, the rest very markecl, and diecl, countecl in groups (the six animals mentionecl are left out), a,fíer 28, 28, 31, 37,31,28 artð,34 days, respectively. The group that had got the iuice of fresh, raw berries, Iived longest, which might be supposed to be due to a certain amount of antiscorbutic; but the lifetime,37 days, is too shortto allorv any such conclusion. Thus, f have not been able to prove the presence of an antiscorbutic substance in red whortleberry ìuice prepared in different ways. This does not preclude the possibility that a small amount may exist and.und ercertain circumstances be demonstrated. P¡.nsolvs pointed out in 1920 that the guinea-pig, who requires a comparatively large d.ose of antiscorbutic, is not a very suitable animal for testing food-stuffs of lorv antiscorbutic value. I.L mary be mentioned that the peasants are said. of olcl to have regardecl the recl whortleberries as possessing a certain antiscorbutic vàlue. Blue uhot"tleben",ies (Vaccinium rnyrtillus). Not tested earlier'. First fresh, raw iuice of the year L922 was testecl in doses of 1 and 5 ccm., then juice of berries from 1921, which hatl been boiled and stirred, for half an hour in an open pan, and. afterwarcls kept in a closecl bottle for a year, in d.oses of 5 and 10 ccm. The raøu juice of L922 sltooued no ptotectiue efect øultateuet". The animals in both series cliecl after 29 ancl 27 ó[ays, respectively, in pronounced" scurvy. The boilect juíce of 792L, 01x the othet" hønd,, shor,ued, a, cet"taon protectiae effect, which for the doses given - 5 and 10 ccm. - corresponded, to 0.1-0.2 of the minimum protective dose. An animal from 24 J. Äxnr HöJER the first g'ïoup' that had 5 ccm., died of intercurr.ent i'fectio' a-fter 39 clays without showing the highest degree of ,À"oy; the other three died of severe scurvy uft"" u' J_ru"ug. fii"U_" of 56 days. Of the five animals who had 10 ccm.,"4 died of infections, two very soon, two after 2g anð. 82 days with slight scurvy symptoms. The fifth clied with pronounced scurvy after 61 days. This juice of Ig2L had undergone a treatment which must be supposed to have reduced its antiscorbutic value in a high d.egree. as it nevertheress had provecr itserf so far valuable, these øuhortlebe*ies of Lgp,, øahin fresh, ntust haue possessed quote a h,igh øntiscorbutic actlue. Stra.oaberr,íes. Not tested earlier. The juice of fresh berries rvas given for three weeks, ancl sub-sequently the juice of berries which at the end of august had been stirred with like quantity of sugar during halfan hour and then kept in a dosãd jar a month. The itrawbø-ry juice showed ø certøon protectiae e,fect, in a close of 5 ccm. corresponcling to about 0.r of the minimum protective dose. One animai rlied with less highly marked scurvy after 42 days, the three others with pronoorr"ãd scurvy after an average of ó0 days. Decoction of fi" needles. Not earlier tested experimentally on animals. The army_ surgeon of charles xrr, Ennnwrus, is said to have cured. >soldier epidemics, with it. Toslpn states, without indicating his d.ose, that he has cured scurvy in children bv this *"rrr*l the same thing is reported by Ulrnnn, whereas tr'r*"r"srrr¡r mentions that he has seen no clinical effect; perhaps, he ad.cls, because the ¡.eedles were not sufficiently fresh. f triecl a decoction of fir needles, prepared in the following rvay. The tops of fir sprigs *""" pi"k.d in July Ig22 und kept in a cellar for six weeks; 0.s kg. was soaked for an hour in 2 litres of water nearly 100' C. Then the decoction 1ryas strained ofi and boi,ed. 5 ccm,. of this clecoctooto shoøuecl ,o antoscorbutic efect oulzateae,in four an,mctls. They died after 2'o 28 d.ays. Tor the pr.esent it is irnpossible to clecide whether this depenclecl on the scanty sunshine in 1922, of rvhich more below, or on the needles not being fresh, as -t'inkelstein suggests for his cases, or perhaps picked. too late in the year, or whether the dose was too weak to show any effect in the guinea-pia.s. 'f'ont atoes. The iuice of tomatoes, both fresh a,nd sterilizecl, is by common consent stated to be highly antiscorbutic. A daity dose of 3 ccm. will protect a guinea-piE from scurvy. It has been proved that fully ripe red. tomatoes have greater antiscorbutic value than those which are unripe ancl green. For my tests I used tomatoes, that hacl ripenecl late in the season of 1922. They were full.y ripe but not so intensely red in colour as tomatoes may become. The juice was pressecl out and was given immediately in a dose of 3 ccm. to each animal. The animals clied in the most seyere scurvy after an ayeïa,g.e of 41 days, rvhich possibly may be counted as proving c(, certain q,tztíscorbutoc ualue, but uz any ccße uery stight (cu. 0.t min. protective dose). fn the Literature I have only found one sta,tement of failing clinical antiscorbutic effect of ripe tornatoes, and. that by FrNrinr,srnrn. ;|nÌk. 200 ccm. of fresh raw milk rvere given cì.uring October" ancl l[ovember 1922 to four animals, who consumecl it ioinily; they may haye drunk different quantities. They died after 37, 37, 46 and 59 days, with pronounce¿l scurvy. 1 litre of this miII< at the least can be reckoned. necessary to protect these four anima,ls. This agrees with the experience of different investigators that milk, in itself a 'r,eak a rtiscorbutic, is especiaily weak when the cows are kept in the shed (Durcnrn etc., Ilnss, UNe¡:n a,nd. Sunrlnr, B¿nxns and llulrr, IfEnr). The essentially clifferent lifetime of the animals also emphasizes the necessity stated by Curcn and ÏIuun of a quantitative closage for each anirnal of the substance to be testecl. STUDIES IN SCURVY 26 J. AXI'I, i{OJI'Iì llaspberry jwí.ce. According to Ilor,sr and Fnör,rcn 10 ccm. of raspberry juice, boiled. as well as ray¡, have a complete protective effect. I founcl no protective effect whatever in a liquid, bought a,t a pharmaceutical chemist's as uraspberry juice 1922, a,nd given to two anirnals in a dose of 5 ccm. ßlack cun"ant jwøce. Bought and tested uncler the same circurnstances as the preceding, it showed no protective effect. No conclusions must be drarvn from these last experiments about the antiscorbutic value of the bemies, no more than from the series with ,naturalu red whortleberry ìuice from a grocer's. But they show that it is very unsafe to rel¡' up6n berry juices and syrups bought in shops as a,ntiscorbutic. Oratrye ,juice. According to various experiments (Hnss), guinea-pigs require 3 ccm. of fresh raw juice to protect them completely frorn scurvy, while 1.s ccm. is enough to prevent the manifestation of clinical signs (Davey). I gave 2 ccm. and 4 ccm. of fresh raw juice ancl stated for the latter close complete protection. (Series 18.) Series 17 is interesting. First the animals had" 1 ccm. of raw fresh orange juice. This was pressetl out of oranges that looked dry and" gave but little juice; it was in October and the season rva,s drawing to its close. The weight charts of the four anirnals were alread.y declining when the oranges disappeared from the market, ancl therefore the anima,ls hacl a, dose of preservetl orange juice. As this ha,s been prepa,real through stirring in an.open pan for nearly an hour and" the antiscorbutic in the iuice might thus be supposed to have lost its potency, the preserved. juice was given in a dose (8 ccm.), twice as large as the one calculated to be equivalent to 1 ccm. of fresh iuice. Nevertheless the animais lost weight very quickly and got worse ancl worse. When, after 20 clays of this preserved juice, new fresh oranges were again to be had", in the month of December, 1 ccm. of fresh juice rvas again aclministered. STUDIES IN SCUR\/Y 269 --: rlhe scurvy of guinea-pigs. Journ. Biol. Chem., 3ã, 1918, pp. 479, 487. --' Sãot"y of guinea-pigs. III. Journ.Biol. Chem., 38, 1919, p. 293' Hnss, Ar,nnDD, IINGEIì, LnstER, anct Suppr,pn, G. C.: Relation of foclcler to the antiscorbutic potency of rnillr. Journ. Biol. Chem., 45, 1920, p. 229. HrueNnn, O.: Ûber clie Barlowsche Krankheit. B. kl. W., 1903, p. 285. HonnlreNN, W.: Untersuchung eines Falles von Barlowscller Krankheit. Zieglers Beitr., Suppl. 7, 1905, p702. HollrcnnN, E.: Histoiogi. Stockholm 1920. Hotslr, Axnr,: Shipberiberi ancl scurvy. Journ' Hyg., 7, 1907, p.619. Holsr, Axnl, ancl Fnör,icn, Ttloolon: SÌrip-beriberi and scurv¡'. Journ. Hyg., 7, p. 634. --, ÜL,et experimentellen Scorbut. Z. Hyg., P,d" 72, 1912, p' 1' --, Übet experimentellen Scorbut. Z.Hyg., Bc1. 7õ, 1913, p. 334' --: Fortsatte unclersøkelser om skørbuk etc. N. Mag. f. Lv., 1916, p. 1009. Horr<rÑs, Golvl,rtNo: On the 'resent position of vitami¡s in clinical meclicine; with cliscussion' Br. Mecl. Journ., 1920, p. I47. -'--: Lancet 200, 1921, P' l. Holann, C. P., ancl lxçt¡,tl,psnw, T.: The mineral rnetabolism of experimental scurvy of the monkey. Johns llopkins Hosp. Bnll., 28, 1917, p. 222. Ho1'vn, P. R.: Effects of scorbutic cliets upon the teeth. Dental Cosrnos, Bcl.62, 1920, P.586. --: f)ental caries. Ibid., P. 921. --: The effect of vitamin cleflcient cliet upon the teeth. I)ental Cosmos,1921, p.1086. --: Effect of cliet upon the teeth ancl bones. Journ. Am' Dent' Ass., No. 3, 1923, p. 201. --: Fooc-l âccessory factors in relat'ion to teet]r. Journ. Dent' Research, March 1921. Hörnn, .A.., Fall av levercirrhos. Hygiæa 1919, p. 955. --' Öveïsikt av vitaminforskningarna. Hygiæa 1920, p. 449. Ioo, T.: Gefässveränclerungen bei iler Möller-Barlowschen Krankheit. Z. 1. Khk., 32, 1922, P. 165. INcten, Ar,nxaNnR¡: Beiträge zur Kenntniss cler Barlowschen Krankheit. Frankfurt. Ztsclnr. f. Path., 14: l, 1913. --: A study on Barlow's c-lisease, experimentally proclucecl in fetal ancl newborn guinea-pigs. Journ. Exp. Mec-[., 2], 1915, p. 52ó' ItvAeucnr, T. : Über Nebennierênveränderungen bei experimentellem Scorbut. Beitu. z. Path' Anat., Bal. 70, L922, p. 440. 270 J. AXÌII, ITöJER Iwenucnt, J.: Uber Organanalysen bei experimentellem Scorbut. Z. f. d.. ges. exp. Mecl. 30, 1922, p. 76. JacIcsoN, L., ancl Moono, J. J.: Studies on experimental scurvy in guinea-pigs. Journ. Inf. I)is., 19, 1916, p. 511. Jrtcoestuel, H.: Zur Pathologie cler Knochenerkrankungen bei BarÌowscher Krankheit. Beitr. z. Path. Anat. XXVII, 1900, p. 173. JeNsnn, W. II.: Die Oclemkrankheit. D. Arch. f. klin. Med., Bd. 131, 1919-20, p. 144. Joos'r, 8., uncl EuunoFÌr, E.: Stuclien äber clie Histogenese c'[es Lymphclrüsentuberkels. Virschows Aich., 210, 1912, p. 188. Josr.ts: Traitement cle la tuberculose pulmonaire chez les enfants par le suc nusculaire et la viancle crue. Revue cl'hygiène et d.e méclec. infant., No. 1. 1902. Josr¡s ancl Roux: Idem. Gaz. méc1.. cle Strasbourg, 10, 1903. Kencz¿ç: Über clie känstliche Beeinflussung cler AlÌergie bei Tuberkulose. Beifi. z. klin. cì. Tuberk., 41, 1919, p. 1. Krprpn: Statistische uncl klinische Beiträge zur Lungentuberkulose mit besonclerer Berticksichtigung cler Kriegseinflüsse. Z. Tbk., 32, 1920. p. 65. Kr,rNc, C.: Untersuchungen äber die bakterientötentlen Eigenschaften etc. Jena 1910. Kocu, -W.: Die Bluterkrankheit in ihren Varianten. Stuttgart1889. Kocn, W.: Der jetzige Stancl cler Pathologie uncl Pathogenese cler Barlou'schen Krankheit uncl cles Skorbuts. D. M. W., 30. Juni 1921, p. 749. Kour,snüsco: Gärungskrankheiten. C. f. Bakt., 8d. 60, 1911, p. 223. KonnNcHnvsxv, \r., ancl Cenn, M.; Biochem. Journ. 17, 192:1, p.187. Kossr,nn: Kl. W., I, 1922, p. 195. Le Men, Yrcton, âncl C¡\.MeBELr,, If. L.: Changes in organ weight producetl by cliets cleffcient in antiscorbutic vitamine. Proc. Soc. Biol. ancl Mecl., Vol. 18, No. 1, 192I, p.32. LlnDeu, M.: Die Nebennierenrinde. Jena 1915. LeNcs'rntN, L.: Welche Aufgaben stellen die Infektionen im Säuglingsalter cter Diätetik? .2. f. Kh., 7, 1913, p. 193. LrLsÈcun, Cu. ancl L¡cnoux, -4.: L'epidémie cle scorbut dans la Prison cle la Seine et à I'Hôpital de la Pitié. Arch. gén. de Méd., Vol. Il, 1871, p. 5; p. 680. LucrrrnNrRrrr, 8., ancl Zrnr,esr<or,vsnr, M.: Der Gehalt des kindlichen Serums an trypanozider Substanz: Jhrb. Khk., Bd. 98, 1922, p. 310. Lntrupn: W. kl. W., No. 3i, 1917. LDSAGn, A. : Matadies cìu nouïrisson. 191 1. STUDIES IN SCUR\¡Y 27I Luvnx, M.: Une epiclémie cle scorbut, observée à I'Hôpital Militaire cl' Ivry pendant le siège cle Paris 1871, Gaz. mécl. de Pa,ris, 187 1, p. 430, 469 elc. Lrcsrpxsrplx, A.: Pseudoleukämie uncl Tuberkulose. Virch. Ärch., 202, 1910, p. 222. --' Untelsuchungen äber clie Ätiologie d.er Lymphogranulomatosis. Frankf. Z. f. Path., Bd. 24, Flg. Hft, 1921, p.529. v. LrNNÉ, C,q.nr,: Collegium cliæteticum. 1742. (Printecl in: Upsala Universitets Åt*"ktift, 47: 3, 1907.) --'De effectu et cura vitiorum cliæteticorum. Uppsala 1766. f,onwv, O.: Scorbut mit Xerose uncl Hemeralopie. W. mecl. 'W., No. 42, 1921, p. 1816. Loospn: Jhrb. f. Kh., 62, 1905, p. 743. Loppz-Lou¡., M., ancl ReNlotn, M:me: Production de scorbut chez le cobaye au moyen d.'un nouveau régime complet. C. Rend. cte I'Acacl. d.e Sc., 176, 1923, p. 1003. Lueenscu, O.: Beitr'äge zur pathol. Anatomie cler Unterernährungsuncl Erschöpfungskrankheiten. Zieglers Beitr. 69, 1921, p.242. -'-: Handbuch cler ärztlichen Erfahrungen im Weltkriege, Bcl. 8, 7921, p. 73. Lusr, !-., anal KLocMÄNN, L.: Stoffwechse]versuche an Barlow's Krankheit. Jhrb. cl. Kh., 75, p. 663. LöwpivsrerN: Tuberkuloseimmunität. Kolle-Wassermann's Hanclb, cl. path. Mikoorga,nismen. Bcl. 5, 1913. M.rcC¡r,r,uu: Textbook of pathology. 1922. Manttus, Fn.: Disposition uncl inc'tivicluelle Prophylaxe. BrauerSchröd.er-Blumenfeìtl IIb., Bd. 1, 1915, p. 395. MAssr,ow, M.: Zerrüttung c-[es Knochensystems durch phosphorarme Ernährung. Biochem. 2., 64, 1914. Mc CennrsoN, R. I.: The pathogenesis of cleffciency clisease. Journ. Med. Res., Yol. 2, 1919, p. 167. --: Effect of a scorbutic cliet on the adrenalin glanals. Brit. MecÌ. Journ., 1919, p. 200. McCr,pNtoN, CoLE, ENcstnlnt, a,ncl Mrtor,pI(AUt'F: The effect of malt antl ma,ltextract on scurvy ancl the alkaline reserve of the bioocl. Journ. Biol. Chem., 40, 1919, p. 243. Mr:Cor,r,ulr, E. V., SrulroNns, N., and Prrz, W.: The nature of the clietary cleffciencies of the wheat embryo. Journ. Biol. Chem., 25, 1916, p. 105. MEDIN, O.: 15 tilfaelcle av Morbus Barlowi. N. mag. f. laegevicl., 59,1898, p.1016. --: Om beharrcllingen af mjöÌk mecl vätesuperoxicl. Hygiæa, Bcì. 70, 1908. Mnvon, Ao. H.: Barlows sygclom. København 1901. 272 J. ,,\XEL HöJER Mevnn, L. F.: Die Scorbutische Diathese. Mo. f. Khk. 25, 1923, p. 454. Moven, L. F., anil Nlsseu, E.: Über icliopathische Blutungen in Haut etc. Jhrb. Khk., Bcl. 94, 1921, p. 341. Monnl, ,{.., MounrquÄND, G., Mtcrrnr,, P., ancl THÉYENoN, L': C. Rend. Soc. Biol., Bcl. 85, 1921, p. 469. MounrqurlNn, G.: Scorbut typique avec oeclèmes. Lyon Mecl. 131, L922, p. 448. Mounreu¡un, G.. ancl Mrcnol, P.: Ac'tjuvants non antiscorbutiques cle ia substance antiscorbutique. C. Rend. Soc. Biol. Dec. 1922, p. 1404. -_-: Scorbut expérimental. C. Rencl. Soc' Biol., Bcl. 84, 1921, p. 736. --: C. Rend. Soc. Biol., Bcl. 84, 1921, p. 43; p. 734. --' De I'action cle certains alirnents gras sur le métabolism osseux. C. Renc-l.. Soc. Biol., tsd. 86, 1922. Mounrqulxl, G., Mrcunr,, P., and Bnntov: Evolution d.u scorbut expérimental chez le cobaye tuberculisé. Lyon Mecl' 131, 1922, p.689. Mounreu.lNt, G., Mrcntrr,, P.,,anc[ SeNv,ls, R.: Huile cle foie cle morue et lésions clu type scorbutique. Lyon Mecl. 132, 1923, p.360. MucH, H,tiss: Die Immunität. Brauer Schröcler-Blumenfelcl Hb., Bd. 1, 1915, p. 300. Nrncor,r, O. (senior) : Corresp. BI. f. Schweiz. lLrzt'e. 1. Okt' I 897. --, (junior): Zrr pathologischen Anatomie uncl zurn-Wesen cles Morbus Barlow. Z. f. allg. Path. uncl path. Anat., No. 17, I 897. Nessau, 8., ancl Snccpn, M. J.: Zur Kentniss cles Vorstacliums cl,er Barlowscheu Krankheit. Jhrb. f. Khk., Bc't. 98, 1922, p. 44. Nonnt, E.: Zur Barìowfrage. Z' f,. Khk., 28, 1921. OnnÄN, B.: Das gegenwzi,rtige Stancl cler Lehre von clen Vitaminen 'unc-[ clie Becleritung cler ]etzteren fär clas Gebiss. Z. f. Stomat., H. 7, 7923, P. 420' Oseontln, T. 8., ancl MnNou, L. B.: The incitlence of phosphatic urinary calculi in rats fecl on experirnental rations. Journ. Am. Mecl. Ass., 69, 1917, P. 32. --: The vitamins in green foocl. Journ. Biol. Chem., 37, 1919, p. 187; p. 223. --: Skimmecl milk as supplement to corn in feecìing. Journ' Biol. Chem., 44, 1920, P' I' PrrnsoNs, Hpr,pN: The antiscorbutic content of certain bocly-tissues of the rat. Journ. Biol. Chem. , 44, 1920. SîUDIES IN SCURYY Plcrporì, H.: Uber clen Lipoiclgehalt cler Nebennierenrinc-le des Meerschweinchens bei experimentellem Scorbut. Klin. W. I, No. 25, 1922, p. 1263. Pntl,tr,, R. W.: On raw meat alimentation in tuberculosis. Lancet, 23 Dec. 1905. --: Tuberculosis of hrng. Encycl. Mecl., Bcl. 8, i922, p. 463. \'. PrrìeuEr: Die Aufgaben cler Küche. Z. f. Kh., 18, 1918, p.225. Prrz: Stutlies of experimental scurvy III. Influence of meats ancl sâlts. Journ. Bioi. Chem., 36, 1918, p. 439. Poconscrrnr.sKy, H. : Zar Frage cles Auftretens von Scorbut beim tsrustkincle. Z. t. K.h. 35, 1923, p. 244. PRvu, P. : Allgemeine Atrophie, Oclemkrankheit uncl Ruhr. Frankf. Z. f. Palh., Bcl. 22, 1919-20, p. 1. Qutrxsnr,, U.: Bid.rag till känneclomen om clen späcla barnålclerns patologi. Bit. 7 till AIlm. Barnhusets årsberättelse år 1898. Rr\ItBrGER, H.: Das Meerschweinchen. Hannover 1923. Rarsox¡*uut: La Zomothérapie. Thése de Paris. 1902. Rr,;Nor,t: Buil. gén. cle thér., 168, 30 Juillet 1914, p. 91. RnnrNoonn by Tûcnr,nn: lTber Scorbut. Mecl. Klin., No. 5, 1918. Rone, E. F., MnDns, Gnecn, McClnNtoN, J. tr'., Gnenln{, MaRG., anal Muneuv, I. J.: A stucly of scurvy ancl its bearing on the preservation of the teeth. Journ. l)ent. Res., March 1921, p. 39. Iìönnn, P., ancl Josnen, K.: ExperimentelÌes Tuberkulosestuclium. Ziegler:s Beitr. klin. Tub., 17, 1910. RoNroNr, P., ancl MoNrlcnenr, M., quotecl after FuNn. RosnNsuNp. F.: Allgemeinschädigungen im Rahmen cles Säuglingsscorbuts. Z. f. Khk., Bcl. 34, 1923, p. 333. Sr\r,LE, V., uncl RosnxnRnc, M. : Über Scorbut. Erg. cl. inn. Mecl. u. Khk., Bd. 19, 1921, p. 31. Se,to, T., uncl Nalrnu, K.: Zur Palhologie un¿l Anatomie c-[es Scorbuts. Virch. Arch., Bd. 194, p. 151. S,\XL, R., unc'[ Mpr,rrr, J.: Über clen Scorbut. Mecl. Klin., No. 37,1919, Scttltonr,, G.: p. û¡886. er clie Pathogenese cler bei Möller-Barlo¡¡¡scher Krankheit auftretencÌen Knochenveränclerungen. Jhrb. f. Khk., 35, 1902. --: Die pathologische Anatomie cler rachitischen Knochenerkrankung. Erg. cl. inn. Mecl. u. Khk., Bc-[.4, 1909, p,403. --: Zur pathologischen Anatomie cler Rarlowschen Krankheit. Zieglers Beiträge z. path. *Anat. 30, 1901, p. 215. Scuononl, J., ancl Neuwencr, C.: Untersuchungen äber cìie MöilerBarlowsche Krankheit. Jena 1900. Scuut,z, -t.: Über clie Chromotrophie des Gefässbinclegewebes. Virch. Arch. Bd. 239, H. 3. 18-24125, Actø pæd,í,atrì,ca. Vo]. III. Supplementum. 274 .T. ÀX1.)L HöJI,IR Snr,rnn, H., ancl Nnumuç: Einfluss cler Ernährung auf clie Tu berkulosesterblichkeit. Z. f. Tuberk.,8c1.34, 1921, p' 1' Snnnlre,u, H. C., Le. Mnn, V' K., ancl C,rlnrnl,r,, H. L': Quantitative cletermination of the antiscorbutic vitamin' Journ' Am. Chem. Soc., 44, 1922, P. 165. SunnlrÀN, H. C., ancl Surrrl: The vitamins. Am' Chem' Soc' Mon. Ser., New York 1922' Sl,Itrtl, M.: Am.. Rev. of tuberculosis. 7, 1923, p. 33' S,rRrNlrz, F.: Über clen Einfluss von Ernâhr*'gsstörungen a.f clie chemische Zusammensetzung des Säuglingskörpers''Thrb' f. Khk. 59, 1904, P. 449. S.rnrNrrz, F., ancl Wnlçnnr: Über Demineralisation 'ncl Fleischtherapie bei Tuberkulose' Jhrb' f. Khk., 61, 1905' Srrll,, G. F.; Brit. Med. Journ., July 31, 1920, p. 156' sronr,tzNnn, w.: Zur ctiätetischen Behantllung cler Tuberkulose. B. ki. W., 1920, P. 981' Tnoues, E.: Biochem. 2., 57, 1913, p. 456' THOll^s, E.: Über die Beziehung chronischer Unterernährung z.r Infektion. Z. IKin., 11, 1914, P' 317. Torr,nn, W.: Der Scorbut im Kindesalter. Z' f' Kh', Bd" 18, Orig., 1918, P.63. Tovnnul,-G.: Caries clentis. Norsk tancllaegefol' ticì', Dec' 1923' Journ. ,{.m. Dent. Ass., No. 3, 1923, p' 207' Toznø, F. M.: The effect on the guinea-pig of cleprivation-of vitamin Ä. Journ. Path. and tsact., Bc[' 24, I92L, p' 306' IJnepn: Mecl. Klin., Bd. 18, 1922, p. 851. VocT : Säuglingsscorbut. Jhrb. f. Kh. 91, 1920, p' 278' W.o,r,l,cnnn, A.: Acta Pædiatrica. Vol. II, 1923, pp' 376' --: wahi cler versuchstiere fär experimentelleTuberkulosestuclien. Braners Bei1or. z. Klinik tl' Tuberk., Bù. 47, 1921, s' 42'o' --' Z\r Symptomatologie unct Pathogenese iter oectema scorbuticum invisibile' Z. 1. Klnk., 1922, p. 35' 'WDIL, E., ancl MoumQUAND, G': Journ. physiol' path', 17, 1918' p. 849. Wr*Nfn.r, A.: Ilber phtisische Infectionen. Hclb. cl. ârztl. Erfahr. im Weltkriege., Bd. 8. wInr,enp: Bruning & Schwalbe, Hdb. cl. allg' Path' cl' Kinclesalters. 2: 1, 1913, P. 281' wIDNennçnR: Möller-Barlowsche Erkrankung. Klin. wochellscht., I, No. 4, L922, P. 119. Zrt,yt, S. S.: Influence of deficient nutrition on the prociuction of agglutinin etc. Biochem. Jl. 13, 1919, p' 172' --: Influence of aëration etc. Lancet 1921, I, p' 478' --: Conclitions of inactivation etc. Biochem. JI' 16, 1922, p' 42' SîUDIES IN SCU1ìVY Zu,vl^, S. S., ancl Wor,LS, F. M.: Changes in the teeth etc. Roy. Soc. London. B. 90, p. b0ó. List of authors. '¿to Proc. The olcl liúerature, not mentioned here, may be founcl in the books of W. Kocn (tSSg) arrcl Ao. Mpypn (tOOt). A. Abderhalden 83, 1:14, 158, 265. Abels 118, 719, 265. Àdams 145, 265. Àndersson 12, 266. Aron 32, 725,266. Aschoff 67, 63, 64, 66, 66, 67, 58, 59, 66, 87, 70, 77, 76, 77,79, go, 92, 93, 01, 92, 96, 100, 110, 111, 113, 176, 732, 144,266. B. Ilaginsky 49, 26'0. tsardin 265. Rahr<lt 6í,,727,265. Barlorv 49, 69, 111, 779, 112, 26-Ð. Barnes 25, 265. Rartenstein 138, 26õ. Baumann 83,265. Baumgarten 1õ7. Betlson 108, 109, ll0, 265. Bergheim 13, 268. Bettoy 747, 272. Beitzke 744, 265. Berg 132, 265. Bezssonoff 14, 265. Bierich 100, 109, 116, 123, !'36,747, 266. Bolle 138, 266. Branclt 108, 266. Broderich 132. c. Campbell 11, 130, 270, 274. Carr 1.2, 270. Carrell 115, 266. Chick 9, 17, 13, 17 , 25, I23, 124, 739, 266. Cohen 9, 76,129,266. Cole 15, 271. Cordier 125, 266. Cornet 140, 266. Cowarcl 27. Cramer 92, 136,266, D. Dahle 12, 266. Dalyell I24,739, 286. Darling 737, 266. Davey 26, 266, DeIf 12, I3,27,33,36, 66, 266. I)rummoncl 9, 266, Dutcher 72,25, 265, 266. E. llckles 12, 26-Ð, 266. Edelstein 66, I27, 26í, Ellis 12, 267, 268. Emhoff 75I, 270. Engstrand 15, 271. Epstein 700, 124, 267. Erclheim 7Ð, 267. F. Faber 13, 267. Finrllay 80, 101, 109, 112, 713,267. Finkelstein 24, 25, 26, 777 , I22, I24, 267. Fortenato 121. Fraenkel 48, 49, 50,55,66,60,65, 109, 111, 712, 126, 729, 730, 267. Frank, H., 124, 267. !-rank, M., 60, I27, 267. Freise 267. Freudenberg 734, 267. Frölich 9, I0, 12, I3, 76, 25, 29, 67, 69, 64, 69, 77, 76, 778, I17, I29, 131, 138, 267, 269. Ftrnk 9, 27, 99, 267. Ftrst 22, 267. G. Geoghegan 746,267. Gerhartz I43, 748, 756, 267 Gerstenberger 127, 267. Givens 13, 267. Gocllevski 33, 268. 276 .I. AXI.]I, H('.TFJR Gougerot 158. Graham 17, 39, 46, 49, 129, 273. Grüner 16L, 268. György 134,778,268. H. }Iall 25, 266. Hamburger 151, 268. Hamilton 745, 265. Happ 147, 268. H¿lrden 268. Hart, C., 9, 30, 48, 49, 60, 53, 57 , 68, 69, 76, 78, 79, 80, 93, 100, 109, 110, 111, i24, 136, r47, 266, 268. Hart, E., 3, 72, 25, 268. Hausmann 83, 109, 268. Hawl< 13, 268, l{ayern 65, 76,79, 82, 96, 268. Héricourt 741, 268. Hersharv 25, 266. Herxheimer 77, 268. Herzog 64, 7I, l0S, 726, 268. Hess 9, 11, 13, 16, 77,18, 26,26, 29, 30, 33, 39, 64, 64, 6ó,68, 70, gg, 91, 92, 96,109, 109, 110, 116, 120, L22, r24,1,26, 126,729,732, r33, 136, 137, 146, 163, 268. Heubner 724, 269. Hirschsprung 91. Iloffman 729, 269. Holmgren 77,269. Holsú 9, 10, 12, I3, 14, 16, 25, 26, 29, 30, ó7, 59, 64, 6Ð, 71, 76, 176, r77, 129, 131, 138, 269. Horne 13, 265. Hopkins 9,72,73, 269. Holvartl 83, 128, 265, 269. Horve 17, 36, 40, 46, 49, 726. Hume 9, 77, I3, 26, t23, 266. Iläggquisô 47. Höjer 158, 160, 269. t. Ide 113, 269. Ingier 53, 56, ó7,70,100, 110, 111, II2, 1,47,269. Ingvaltìsen 128,269. Irvabuchi 54, 65, 67, 83, 101, 103, 109, 110, 128,737,269, 270. J. Jackson 39, 69, 112, II7,270. .Tacobsthal 51, ó3, 69, 100, 111, 270 Jansen 137, 270. Joest 1õ1, 270. Joseph 159, 273. Josias 141, 270. K. I(aiserling 145. I{arczag I42, 270. I(assor"itz 147. I{iefer 143, 2?0. l{irch 108. I(Iing 1ó8, 270. l(Iocnrann 96,127, 728; 271. Koclr, \Y., 6-L, 53, 64, 55, 56, 57, ó8, 59, 66, 6?, 70,77,76,77, 79, 80, 82, 83, 9I, 92, 96,100, 110, 111, I12, L16, 732, 744, 265, 270. l{och, W., 33, 79, 82, 709, 7L7, I72, 779, 124, 270. l{ohlbrägge 270. I{orenchevsky 12, 270. Kossel 140, 266. I{ossler 12-Ð, 270. t-. La }Ier 11, 130, 270, 273. Lanilau 70I,270. Langstein 270. Lasègue 65, 270. Legroux 69,270. Leichtentritt 116, 119, 121, 270. Leitner 709, 270. Lesage 33, 270. Lessing 9, 30, 38, 48, 49, 50, ó3,57, 58, 69, 76, 79, 79, 80,83, 100, 109, 110, 111, 724, 736,147, 268. Leven 69, 79, 82, 271. Lichtenstein L58, 160, 271. v. Linné 82, 136, 740, 277. Loeb 136. Loervy 138,271. Looser ?0, l7'1., 772, 179, 271. Lopez Loma 1L, I3,277. Luba,rsch 733, 137, 271. Lukin 82, 91. Lust 96, I27. I28,27I. Lön'enstein 740, 277. M. I{ac Callum 8, 66, 271. Martinotti 703, 271". Martius t4L, 277. Masslow 74, 27I. l\{cOarrison 89, 100, 101, 104, 110, 725, 733, 737 , 271. i\lcClerrclorr 7ú, 17, 39, 16, 49, 27 7, 27 3 lfcCluggage I3, 267, 268. McCollnnr 1"I, 33, 723, 271. lfead 12, 266. n'Iectes 17, 39, 46, 49, 725, 278. ùIeclin 12, 67, 63, 27I. Nlelka 113, 273. Mellanby Il3, 132. Menclel 9, 16, 99, 12C, 266, 272. ÙIengering 136. lVleyer, Ad., 7C, 27I, 274. Nleyer, L. F., 124, 272. lficlrel 13, L1,128,129, 180, 147,162, 272. Midcllekauff 76, 27I. Monrail 12. n[ontagnani 100, 101, 27:]. Moore 39, 69,772, I77, 270. NIorel 128, 272. Ìfottranr 92, 738, 266. Monricluancl 1.3, 14, 128, l2g, IJ}, 147, 162, 272,274. Iluch 141, 2?2. Ilrirphy 77, 39, 46, 19, I2g, 278. N. l{aegeli I09, 141, 272. Nanrbn 60, 79, 80, 82,97,278. Nassau 779, 272. Nauwerk 10, 100, 273. Nehring 744,273. Nobel 137, I38, 740,272. Noeggerath 137. 0. Or)st"l 732, 272.. Osborne 99, 272. P. Paclua 99. Parsons 23, 89, 272. Peiper 13, I01, 273. Pìrilip 141, 273. v. Pirquet 138, 13C, 273. Pitz L7, 123, 128,277,27à. Prym 737, 273. 0. Qnensel 6I, 62, 63, 730, 2î8. R. ßaebiger 76, 273, Raissonnier 741, 273. U. Uurber 24, 108, 109, 7I0, 274 Unger 13, 2ó,268,269. Urizio 82. STUDJÐS IN SCUR\¡Y 277 Ilandoin 17, 73, 271. Iìeinert 01. Iìenon 27;1. ! Iìheinclorf 108, 113, 278. Ilichet 141, 268. l(obb 17, 31, 46, 49, 728, 27:1. Iìondoni 100, 101, 273. Iìosenberg 109, 110, 116, 186, 146, 763,273. lìosenbuncl 74, 273. Iloux 141, 270. Iìünrer' 159, 273. s. Salle 109, 110, 116, 736,146,16ts,2?8. Sato 69, 79, 82, 97, 273. Saxl 113, 273. Sclrnrorl 49, 50, 66, 777, 772, I47, 27 B. Schoedél 10, 49, 5I, 52, 55, rÒ6, bZ, 63, 69, 100, ltl, I24, I30, 747, 273. Sclrntz 32, 80, 107, 108, 278. Selter 744, 274. Shaefer 72,266. Sher¡rran 11, 13, 16, 17, 130, ItsL,271. Sinrnroncls 17, 271. Singer 119, 272. Skelton 9, 266. Snith 16, 747, 149, 268, 274. Sonnenburg 56. Steinitz I37, 147, 271. Stéenbocli 72, 27, 266, 268. Sternberg 168. sLilt 27,274. Stoeltzner 743, 274. Stoerk 1õ8. Snpplee 25,269. Srvitle¡ski 771, 712. T. 'Iailor 132. 'Ihévenon, L, 728, 272. l'homas I42, 274. 'Iobler 24, 108, 100, 274 Tovernd ¿0, ió,-id,' +q-àr, ro+, roo, 107, 109, 726, 274, 'Iozet 72,13, 33, 36, 66, 266,.274. 278 v. Variot 82. Virchow 136. Yogt L16,274. W. 'Wagner 82, 147, 288. 'Wailgren 116, 137, 148, L60, 274. Wassermann 108. 'Weigert !4L, L42, 144;274. 'Weil 274. J. AXEI, göJER 'Weinert L44, 214, 'Wells 39, 46, 46, L47,274. Wertheimer 83, L84, 266. 'VÍieland L4, L22, 274. 'Wienberger 68, 274, Wilbut L2, 2;ß6. Zielaskowsky Zilva L2, 73 274, 216. z. 116, 119, tzt,270, , 89, 46, 46,12L, 268,