DENTAL INFECTIONSDEGENERATIVE

AND RELATEDDISEASES

SOME STRUCTURAL AND BIOCHEMICAL FACTORS *

WESTON PRICE, D.D.S.CLEVELANf\

M.S F.A.C.D.A.

The relationships between dental infections anddegenerative diseases, if such exist, should be demon-strable by other means than the establishment of simplyan association of the two in the same person, or thedevelopment of such lesions in experimental animalswith cultures taken from focal infections. In this paperI summarize some new data developed in my researcheson the relation of focal infection to systemic disease,with particular consideration of dental focal infectionsand the degenerative diseases, and with especial refer~ence to structural changes that take place in the sup-porting structures about dental focal infections, and toserologic changes in body serums.

In a previous communication 1 I have given a pre-

liminary report, indicating that patients can be dividedinto three groups on the basis of the type of structuralchange that develops in the supporting structures ofinfected teeth, as the result of the presence of a giventype of dental infection, as, for example, that quantityof infection that would be present in a single-rootedtooth with a putrescent pulp, in which there is infectionof the dentin plus infection of the degenerated pulptissue.

In some individuals this condition will produce alarge zone of rarefaction about the apex of the tooth,which will frequently be connected with the externalsurface by a fistula. The medullary structure of thesurrounding bone opens ~uite readily into the periapicalchamber, the trabeculae in the surrounding osseoustissue are approximately normal in size for the age of

*. Read before the.. Section o.n Stomato.l~y at th.e Seventy-Fifth AnnualSess1on of the AmerIcan Medical AsSOcIatIon, Ch,cago. June, 1924.

1. Price, W. A.: Volume I, Denta} Infections, Oral and Systemic,Volume II, Dental Infections and the Degenerative Diseases, Cleveland,P"ntnn P"hli.hing Comnanv.

2

that patient, and the ratio or proportion of medullarymaterial to osseous tissue is as much as, or is more than,50 per cent. of the total mass.

In a second group we find a condition that appea.rsvery similar to the former except that the fistula tendsto be closed and the zone of rarefaction is surroundedby a zone of condensed bone, with a marked reductionin the proportion of medullary tissue and an increase inthe osseous tissue immediately adjoining the chamberthat has been formed in the bone about the apex of theinfected tooth. The thickness of this zone of condensedbone varies in proportion to a time factor, as we shall see.

In a third group we find that this type and quantityof dental infection produces much less of a zone ofrarefaction about the apex of the involved tooth, insome cases amounting to a very slight absorption ascompared with the previous cases. The trabeculae arenot so pronounced in the alveolar bone, and there is evi-dence of more or less diffuse condensation surroundingthe area.

These three general types will frequently be encoun-tered in this clear cut form. However, there will begradations between them, which will make a differen-tiatiOn between either the first or the second, or thesecond and third of these groups, difficult. In otherwords, we seem to be dealing with a combination ofinfluences. This is illustrated in Figure 1, which showsa group of teeth with putrescent canals showing charac-teristic lesions of these types. I 2 have already discussed

this and illustrated it in extensive detail.

Dental Infections, Chapter III.Dental Infections, Chapter IV.

RESISTANCE AND SUSCEPTIBILITY TO RHEUMATICDISTURBANCES

I have made an intensive study of the resistance andsusceptibility factor in individuals with regard to thematter of their developing, during their lifetime, certainof the rheumatic group diseases or affections, and a pre-liminary report of this study has been presented.3 Inthe rheumatic group disturbances I have included thoseaffections which are very frequently caused by, or asso-<;iated with, streptococcal invasions associated withdegenerative processes in organs and tissues, the chiefof which we have included in groups, such as muscles

-2. Price, W. A3. Price. IV. A.

3

and joints, heart, kidrieys, digestive tract, nervoussystem, and special tissues. In these studies I haveundertaken to get the history of the serious breaks inthese groupings in the following individuals: the patientbeing studied" the brothers and sisters of the patient, thefather and mother of the patient, the brothers and sis-ters of the father and mother, and the tour grand-

Fig. 1.-Typical different types of dental apical pathologic changes:A, extensive absorption opening into medulla of bone; B, very littlebone change about apex of putrescent tooth; C, apical rarefaction withbeginning zone of condensation; D, apical rarefaction with extensivezone of condensation.

parents. To secure this information h,a,s required agreat deal of painstaking effort, and, because in manycases it was not possible to get in contact with reliablesources of information, such as family physicians, Ihave eliminated approximately 50 per cent. of therecords as bei!1g inadequate.

By using 673 cases out of approximately 1,400 andcomparin? the data secured from this number with th()sp

4

secured £rom an earlier group 0£ 250 cases, we find thatthere is a remarkable con£ormity in the two sets 0£studies. In general, it has been £ound, as I have shown,that patients may again be divided into three groups onthe basis of the probable presence or absence in their li£e-time of serious involvements of the so-called rheumaticgroup lesions. These groupings are as follows: First,those persons who during their li£etime have had sohigh a de£ense or have been so £ree from adequatecauses that they have not developed any 0£ this group0£ lesions, nor have the members 0£ their £amilies.Second, a group very similar to the first one, exceptthat while the persons i~ it have been free during themajor part 0£ their lifetime, they have had a recentbreak in the £orm 0£ some 0£ these disturbances. Third,those patients who have had frequent and recurringexpressions of one or several 0£ these rheumatic groupdisturbances throughout their li£etime, which historyis more or less duplicated in various 0£ the members 0£the £amily. I have chosen to call these groups (1)absent susceptibility, ( 2) acquired susceptibility, and( 3) inherited susceptibility.

An analysis 0£ the individuals constituting the mem-bers 0£ each 0£ these groups proves to correspond withthe groupings made OQ the basis 0£ differences in stntc-tural pathology, the association being as £ollows: Group1, absent susceptibility, proves to have the same indi-viduals in it as does tl)e grouping made on the basis ofstructural pathology as having extensive zones 0£ rare-faction £or a given dental in£ection. The individuals ofthe group termed acquired susceptibility prove to be ingeneral the same individuals who were in Group 2 0£the other method, and are frequently, i£ not generally,those showing a zone 0£ condensing osteitis around thezones 0£ rare£ying osteitis; and Group 3, those with aninherited susceptibility, prove to be the individualswith the generally lesser amount of radiolucence andcavitation about the apex 0£ an in£ected tooth, with amarked tendency to fusion and obliteration 0£ trabec-ulae and marked lessening 0£ the medullary matter inthe bone about in£ected teeth. The evidence in support0£ these data is now so abundant as to seem to establishwithout question the association of these structural andclinical phenomena.

When we take fi£teen £amilies as being typical 0£ each0£ these different groups, and then divide the last group-

5

namely, those with an inherited susceptibility-into fourgroupings ( one side mild, two sides mild, one side strong,two sides strong) and use fifteen families for each, weare able to make important observations which suggestelements that are involved factors, if not the fundamen-tal causes, of some of these phenomena. 1~his is illus-trated in Table 1, in which the column headed "suscep-tibility" shows the different classifications as suggested,and the section headed "N umber of Lesions Per Group"shows the incidence of the rheumatic group disturbances ;it will be noted that the total number of severe rheu-matic group lesions (by severe I mean those that haveeithel incapacitated or caused death) is progressivelygreater as the inheritance of the susceptibility increases

T ABLE 1.-Relation of Periodontoclasia to Susceptibility toRheumatic Group Lesions (Fifteen Typical

Families in Each Group),

No. of Lesions per Group Per Cent.' ,. , Per Cent. Periodono

Severe Severe and MIld Caries toclasia

16 81 40 4068 96 80 33

144 201 67 33227 808 93 20258 338 80 20483 754 93 0

SusceptibIlIty

Absent Acquired Inherited:

Onesidemlld.,."

Two sides mIld One side strong.. ,

Two sides strong.

in intensity. There is not opportunity in this text, sincethis is introductory, to review in detail those data whichhave previously been reported.

In the column headed "Severe and Mild" we haveincluded the mild lesi~ns with those that are severe (bymild I mean those that have produced severe incon-venience and discom£ort, but not caused death or inca-pacity) , and here again it will be noted that there ispresented the number 0£ these lesions in the differ-ent £amilies. These data suggest that the mem-bers 0£ the £amilies in the last group-namely, thosewith two sides strong-are subject to a probability forthe development of these lesions £rom twenty to thirtytimes as great as those in the £amilies 0£ the groupsclassed as absent susceptibility. This furnishes a veryimportant £actor in each diagnosis, prognosis and treat-ment, for the £actor 0£ sa£ety 0£ the last 0£ these groupsis very much less than that 0£ the preceding groups.

6

These data immediately suggest the answer to theparadox that has produced probably more of the differ-ence of opinion than any, if not all, other factor& com-bined: namely, why it is, in our general clinics, thatthose patients who appare11tly have the most dental infec-tion in their mouths, as judged by flowing pus fromfistulas and number of broken down and abscessingroots or suppurating pyorrhea pockets, generally presentthemselves without a history of the rheumatic groupdisturbances, as they appear in general or accident clin-ics ; and, conversely, why it is that the patients who doshow severe or frequent breaks with the rheumaticgroup disturbances are so often those who have verylittle evidence of oral suppurative, infective processes.Whereas in the former group there is a history of recur-ring tenderness of the teeth to make certain that theteeth are infected, in the latter group there is usuallylittle or no history of such inflammatory reactions orpainful disturbances.

RELATION OF CARIES AND PERIODONTOCLASlA

The application of these new principles constitutes anew basis for practice, as I have indicated in the previ-OUS report. I am limiting this discussion to the sig-nificance and nature of some of the structural andbiochemical changes that are associated with these

phenomena.In the column headed "Per Cent. Caries" ( Table 1) I

have shown the incidence of dental caries in relation tothese various factors, and it will be noted that whereasonly 40 per cent. of the patients in the group calledabsent susceptibility ShoW caries, this factor increases to80 per cent. in the next group, those with an acquiredsusceptibility, and progressively increases, as the inten-sity of inherited susceptibility develops, to 93 per cent.This has tremendous meaning _and significance, for itindicates that those patients Who would be in greatestdanger of injury from an apical focal infection (becauseapical infections are the result 0£ loSS 0£ vitality 0£ thepulp, due generally to the approach 0£ caries) , will havemost opportunity £or the in£ection, and, £urther, theseindividuals, Who would be most in danger, would bethe ones Who would have Zones revealed by roent-genograms as small or negative zones, as the local struc-tural expression 0£ tl.e dental £ocal in£ection.

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In the column headed "Per Cent. Periodontoclasia"( Table 1) , I have shown the incidence of periodonto-clasia, or so-called pyorrhea alveolaris, and find ( andthis was a great surprise although it has been abun~dantly verified) that as the tendency to caries increases,not only does the tendency to periodontoclasia decre<lse,but the periodontoclasia tends to decrease as the inten-sity of the inheritance of susceptibility for the rheumaticgroup lesions increases. This has profound importance,since it immediately indicates that the phenomena ofstructural change, whether at the apex of a tooth or ata gingival margin ( for in every case in which we findextensive periodontoclasia our unit quantity of dentalinfection will always produce a large zone of rarefac-tion) are related through their causative factors, eitherdirectly or indirectly, with the forces of defense andresistance. This has led to an effort to analyze theinvolved forces and relate them to these phenomena.

HEREDITY

These studies have thrown an important light on someof the factors that are involved in the relation ofheredity to the type of disturbance from which thepatient suffers. In Table 2 I have arranged a group ofthe relatives of each of ten patients in such a way as toshow the number of instances in all the members of theten families ( approximately sixteen relatives of eachpatient) in which there have appeared rheumatism anddisturbances in the tonsils, heart, neck, nerves, internalorgans, and special tissues. In all, forty patients wereselected, ten of whom were suffering from rheumatism,ten from heart involvement, ten from nervous systemdisturbance, and ten from disturbance of internalorgans. While the patient might be influenced by thehealth of the parents and grandparents, the latter, withthe brothers and sisters of the father and mother :tndthe brothers and sisters of the patient, could not beinfluenced by the patient.

In the section headed "Group," under rheumatism, itwill be noticed that rheumatism was the most frequentlesion that was present. In the section headed "N umberof Lesions in Families," it will be noticed that, in thisgroup of ten patients with rheumatism, all the othermembers of all the ten families gave fifty-nine cases of

,..,

9

rheumatism, only eight instances of infected tonsils ;seven of disease of the heart; nine of the neck; nineteen,of nerves; nineteen, of internal organs, and ten, ofspecial tissues.

In the ten patients with heart involvement, the mem-bers of their families showed fifty-se:ven cases of heartdi-Sease, and only twelve cases of diseased tonsils ;twenty-four cases of rheumatism; six of involvement ofthe neck, twenty-five, of nerves; thirteen, of internalorgans, and nineteen, of special tissues.

In the ten patients suffering from involvement of thenervous system, all the other members of their familiescombined showed 142 instances of nervous affections;ten cases of diseased tonsils; fifteen instances of rheu-matism; ten of affections of the neck; twenty-eight, ofinternal organs; and nineteen, of special tissues.

In the group of ten patients with involvements ofinternal organs, all the other members of their familiesshowed ninety cases of involvements of internal organs ;six cases of diseased tonsils; thirteen cases of rheuma-tism ; nine of affections of the heart; ten, of the neck ;thirty, of the nerves, and twelve, of special tissues.

This seems strongly to indicate not only a familycharacteristic, but also that it is a factor which relates toindividual organs and tissues quite independently ofother types of tissue.

Whe"t1 this problem is approached from another angle,it has given another type of data, which is also verysuggestive. When we take the number of childrenaffected in the case in which the patient being studiedis the parent of the child, we find in the selected familiesin which both parents belong to the group that there isa marked increase in the prevalence of the total rheu-matic group lesi<?ns in the group classed as having aninherited susceptibility, as compared with each ofthe two groups, absent susceptibility and acquiredsusceptibility.

This is shown in Table 3, in which A represents thepatient with an absent susceptibility, B the patient withacquired susceptibility, and C, strongly inherited sus-ceptibility. Eight families in which the patients haveabsent susceptibility are combined in a group with anaverage number of children of 7.3. The average numberof children per family who were affected was 0.63, or 9

10

per cent. of the total number of children. In the group offamilies of patients classed as having acquired suscep~tibility, 17 per cent. of the children were recorded ashaving involvements; whereas, in the strongly inheritedsusceptibility group the percentage of children affectedjumps to 44, or approximately five times as many as inthe group with the absent susceptibility.

When we realize that so many of these degenerativediseases develop beyond the age of 40, and that most ofthe children being studied were well under that age, itappears that, if 44 per cent. were already affected at thetime the record was made ( for these were cases in whichthe parent involved was still living ) , a much higher per-centage should be expected to present involvements laterin life.

TABLE 3.-Mendelian Factors

-= --.ji;Relative number of children affected In familIes when 0,;,

A Patient has absent susceptibilItyB Patient has aCQuired susceptibilityC Patient has strongly Inherited susceptibility

Average No. PercentageAverage No. of Children of

No. of of C'hildren per Family Children Susceptl-Cases per Family Affected Affected bility

A 8 7.3 0.& 9 AbsentB 8 7.2 1.2 17 AcquIred0 8 9.0 4.0 44 InherIted

CHANGES IN THE BLOOD

We naturally look to the blood as being one of theearliest disturbed tissues, and as it is studied in largemeasure to determine the presence or absence of infec-tion by its hematologic, serologic and bacteriologicchanges, we have undertaken to compare these. Ingeneral, we find that chronic dental infections do notproduce the blood picture of acute infections. Insteadof there being a marked leukocytosis, there is frequentlya marked leukopenia. The polymorphonuclears, insteadof being increased, tend to be decreased in percentage,and the lymphocytes increased. When, however, a den-tal infection is producing an acute reaction, as an acuteabscess, it then produces the marked leukocytosis andincrease of polymorphonuclears. This is particularlytrue of the persons in Group 1, and these patients tendto develop a marked rise in temperature, and extensiveswellin~. severe pain and physical depression, usually

1

terminating in rupture of the abscess from its pressure,and rapid fall of fever and return to normal. In thosewith low defehse, this process is much less acute, andmost frequently absent. The condition tends to takeon a chronic state with slight tenderness or no localtenderness, and a tendency to the development ofsubnormal temperature.

When non virulent green-producing streptococci,under which grouping approximately. 99 per cent. ofthe strains taken from chronically infected teeeth willclassify, generally spoken of as Streptococcus viridans,are inoculated into the marginal ear vein of rabbits, orwhen an infected tooth is placed beneath the skin 0£ arabbit, we frequently do not get the acute inflammatoryreactions that we do from many other types, such ashemolyzing strains. There is often at first a slight risein polymorphonuclears, and then a general depressionof this cell, with a marked increase in both the actualnumber as well as the percentage of lymphocytes.

A typical group of such cases is shown in Table 4,in which will be seen the effect of tooth implantationsin nine rabbits. From this it will be noted that therewas a progressive decrease in the polymorphonuclears,with a progressive increase in small lymphocytes, whichdo not follow the changes in the total leukocytes. Thedecrease 0£ polymorphonuclears for the nine rabbits isan average of 17 per cent., and the increase of smalllymphocytes £or the nine rabbits, an average of 17per cent.

In our study of the chemical changes in the blood ofrabbits and patients we have included sugar, nonproteinnitrogen, urid acid, urea, ionic calcium, pathologicallycombined calcium, ionic calcium plus pathologically com-bined calcium, total calcium of all forms, and alkalinityindex. These have been run as a routine, and othe.relements have been made subject of special studies. Ofthese various factors, two that we have found to be ofparticular importance in connection with dental infec-tions are the ionic calcium of the blood and the alkalinityindex. Since the pathologically combined calcium plusthe ionic frequently makes a total calcium up to orabove normal, the determination of the total calciumis very inadequate and of much less value as anexpression of the picture than is the ionic calcium.

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When we relate ionic calcium to the three fundamen-tal groups of patients, as I have classified them, we finda very striking difference which doubtless has greatsignificance. In the group with an absent susceptibility,the ionic calcium is usually normal to high, with a rangefrom 10.5 to 12 mg. per hundred cubic centimeters; inthe group with an acquired susceptibility, usually from9.5 to 11, and in the group with the strongly inheritedsusceptibility, already breaking, usually from 7 to 10.

In many instances, after the removal of dental infec-tions, the ionic calcium of the patient rises from 10 to15 per cent. in a few days or weeks, which is a greatdeal, since this difference makes a great change in thefunctioning of practically all the organs and tissues ofthe body. Normal circulating blood should containfrom 10 to 11 mg. of calcium per hundred cubic centi-meters. As it is in circulation, approximately 4 mg. iscarried in combination with the thrombin, a little lessthan 1 mg. in the blood cells, and about 6 mg. as plasmaionic calcium. In the process of clotting, the 4 mg. incombination with fibrinogen will be released in theprocess of the formation of fibrin, and will appear asfreshly released ionic calcium in the serum. When,therefore, there is a depression of say 2 mg. in the ioniccalcium of the blood, it must largely be lost from thecirculating plasma, since that, in combination with thethrombin, remains relatively constant; therefore, a lossof 2 mg., while it may mean a depression of only 20 percent. of the total, may be one third of the plasma ioniccalcium.

Of several methods that we have used for studyingthe effect of the type of culture which we have foundin infected teeth on experimental animals, one that hasbeen very instructive has been the placing of freshlyextracted infected teeth beneath the skins of animalsfor the stu9y of the changes in the blood picture. Few,if any, of these changes have been more striking andregular than the depression of the ionic calcium in allcases in which the animal was being seriously affectedby the presence of the tooth. In practically everyinstance, when the infected tooth is so placed under theskin of an animal, if the animal does not becomeseriously injured by the presence of the tooth, it buildsabout it a fibrous capsule, highly vascularized, whichfor a time at least apparently quite successfully protects~

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the animal from the toxic products of the bacteria andfrom the invasion of the animal by the organisms ofthe tooth.

In every instance in which an animal does notbuild such a membrane, and that promptly, it tendsto lose in weight, there is a formation of an abscess,more or less pronounced, and there are very importantand quite uniform changes in the blood picture, followedby death. One of the most important of these is theprogressive depression of the polymorphonuclears andprogressive increase of the small lymphocytes, whichprocess is quite regularly paralleled and accompanied bya depression of the ionic calcium of the blood.

A typical illustration is shown in Table 5, in whichit will be seen that the polymorphonuclears, starting at57 at first, increased to 70 and then decreased to 31(26 per cent.), while the small lymphocytes, starting at34, increased to 62 ( 28 per cent. ) .Parallel with thesechanges, the ionic calcium decreased from 11.53 to 8.05,or 3.5 per cent., which was about half of the plasmaionic calcium. The depression in ionic calcium is prac-tically always accompanied by a loss in weight of theanimal. These two factors are shown in comparison ina group of animals in Table 6. In the first of theserabbits, it will be noted that the ionic calcium wasreduced 50 per cent., while the actual body weight wasreduced 17 per cent. In the next, the weight reductionwas 34 per cent., the ionic calcium loss 12 per cent. ; thenext, weight loss, 24 per cent., calcium loss, 28 per cent. ;next, weight loss, 6 per cent., calcium loss, 17 per cent. ;next, weight loss, 9 per cent., calcium loss, 21 per cent. ;and the last, weight loss, 19 per cent., calcium loss,10 per cent.

Another very striking phenomenon is the effect ofplacing some pieces of patients' infected teeth into someof the serum of that patient's blood for from twentyminutes to a half hour. This often produces a verymarked reduction in the ionic calcium of that bloodserum, with a marked increase of the pathologicallycombined calcium. In Table 7, a group of blood sam-ples from patients so tested with their own teeth areshown, in which the total decrease in ionic calcium hasbeen from 10 to 76 per cent., and the total increase inpathologically combined calcium from 15 to 83 per cent.

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The methods used for making our calcium determina-tions have been chiefly those suggested by West 4 and

Vines.5EFFECT OF CALCIUM LACTATE

In many instances we have found it very helpful, inaddition to the removal of the dent~ focal infection, toadminister to the patient calcium lactate, from 10 to 15grains (0.65 to 1 gm.), with each meal, which may bekept up for several weeks without any unfavorableeffects, and in cases of marked pathologically combinedcalcium to administer parathyroid extract, one-tenthgrain (0.006 gm.) daily, usually for only a few days.In some cases, we have found additional assistance inthe use of thyroid extract, particularly in patients suf-

TABLE 8.-Effect of Treatment on Ionic Calcium of Blood

Patbo- IoniclogIcally plus

Ionic CombIned Com-Oa.Jcium Calcium biDed

7.5 2.2 9.77.9 1.9 9.98.1 1.~ 9.58.2 1.2 9.~

10.6 0.3 11.09.2 1.8 11.19.4 0.5 \ 9.9

HourA.M.

9:0010:0011:0011:0011:00

Treatment for

Ioruc Calcium

Began.. Continued. Continued.. ContInued. DIscontinued. ...

Resumed.. Continued

Date

8/31/229/ 6/229/13/229/26/221124123

2/16/Zj4/25/23

fering from marked depression, for whom the adminis-tration of from one-eighth to one-fourth grain (0.008 to0.016 gm. ) daily for a few days is very helpful.

An illustration of the change in ionic calcium withthe administration of calcium lactate and parathyroid issh<?wn in Table 8, which represents the changes in thepatient from one of complete incapacity for work,extreme lassitude and persistent discharge from surgi-cally drained glands of the neck, which had becomeinvolved following the extraction of a tooth somemonths previously, accompanied by a general cellulitis,all of which latter promptly disappeared with the changeof ionic calcium content of the blood from 7.5 to 10.6mg. For approximately one and one-half years thispatient has carried on his work very efficiently at the

4. West, Fred: A New Method for the Determination of Calcium andThrombin in Serum, ]. A. M. A. 78: 1042 (April 8) 1922.

5. Vines, H. W. C. : Coagulation of Blood I, Role of Calcium,]. PhysioL 56: 86 (May) 1921; 11, C1otting Complex, ibid. 56: 287(Aug.) 1921.

'017

19

age of 65, when previously he had been an invalid fortwo or three years. It will be noted that, Jan. 24, 1923,when the ionic calcium was up to 10.6, the calciumlactate and parathyroid were discontinued; in aboutthree weeks the ionic calcium dropped back to 9.2, atwhich time treatment was resumed, and by its resump-tion from time to time this man has kept in workingcondition. He had had several extensive zones of dentalinfection removed, which apparently had been largelycontributary to bringing about his serious condition.

DEFENSE A(;AINST BACTERIAL INFECTION

I have referred to the fact that, when an infectedtooth is planted beneath the skin of a rabbit, oneof two things will generally, if not always happen :either the animal will build about the tooth an encap-sulating, highly vascularized structure, which protects itfrom the toxic and bacterial elements of the tooth, andthe animal lives with very little change in weight, bloodchemistry, or general health, or else there is formedabout the tooth a local abscess which mayor may notbe accompanied by a considerable exudate or pus, with-out the formation of the closely adapted encapsulationtissue, and the animal loses in weight, suffers a redt1c-ti on in ionic calcium of blood, and ultimately dies, fre-quently without much local destruction of tissue, all ofwhich may occur in from two days to a few weeks.(We have had one tooth transferred to a series of thirtyrabbits in succession, which killed all but one in fromtwo to six days, one living ten days. )

Rats have a relatively high defense for streptococcalinfections such as occur in teeth, and not only build thecapsule quickly, but, when on a normal diet, exfoliate thetooth in an average time of nine days; on a deficiencydiet, it may take over forty days. This quality of highdefense is not found in rabbits, which in this regardbehave more nearly like human beings. However ,many, if not most, human beings have a higher defensefor this type of infection than do rabbits that have nothad their resistance raised and their immunity estab-lished by previous inoculations.

Human beings, as they come under observation, havevery great difference with regaro to the capacity of theirblood, both plasma and whole blood, to destroy serophy-tic micro-organisms, which are chiefly streptococci and

20

staphylococci. This is well illustrated by the methodof Wright 6 for testing the bactericidal property of the

blood. In Figure 2 will be seen tests made from thebloods of two patients seen within an hour of eachother, one with an exceeding1y high defense, the otherwith a very low defense. A shows control cultures,approximately 1,000 streptococci placed in Petri dishes,and their profuse growth is noted. B shows the resultof taking a similar quantity-namely, 1,000--of thisstrain of streptococci, and placing them for ten minutesin 0.3 c.c. of the patient's blood, after which they weretransferred to similar Petri dishes, and except for the

.Fig. 2.-Bactericidal properties of bloods: at left, from girl with

low defense with heart involvement; at right, from man with high.defense, physically excellent.

effect of the blood, should show the same growth as inA. The cultures on the left are from a girl, aged 15years, suffering frolil a partial nervous breakdown andheart involvement, probably contributed to by the over-load of stren4ous college. The cultures on the rightare from a man, aged 56, with extensive periodon-toclasia (pyorrhea) with much suppuration, never sicka day in his life. It will be noted that with this test, asshown in B, this man killed off a very large proportionof the streptococci, and the girl a little more than half.

6. Wrightl. A. E.; Colebrook, L., and Storer, E. I.: TherapeuticInoculation, Lancet 1.: 365-373 (Feb. 24), 417-430 (March 3), 473-478(March 10) 1923; Ann. de l'Inst. Pasteur 37: 107-182 (Feb.) 1923.

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21

But the plasma of the circulating bloqd does not con-tain all the available defensive properties that it may,if the individual is suffering from an invasion. There-fore, the placing of some dead organisms in the blood( in this case 100 for twenty minutes) , to call out fromthe leukocytes additional defensive factors, resulted ininducing the blood of the man to kill off practically allthe organisms, whereas, when this was done with theblood of the girl, the def~nsive mechanism not onlydid not kill off as many as before the dead organism~were introduced, as shown in B, but the blood was verymuch less efficient, suggesting that an additional over-load had been provided. Similarly, when 1,000 deadorganisms were added to this quantity of blood (0.3 c.c. )for twenty minutes, prior to the adding of 100 liveorganisms, the blood of the man, with its high defense,was not only able to devitalize practically all the liveorganisms in ten minutes, but could do that in the pres-ence of so large a quantity of toxic material as wasadded with the 1,000 dead organisms. The blood of thegirl, however, was not so efficient as with either 100dead organisms or with no dead organisms. For herblood, it seems that there had been simply the additionof supplemental toxic material. She, apparently, wasalready utilizing all her available reserve forces forfighting this infection. With the removal of the dentalinfections, one of which was a badly infected first per-manent molar, which, incidentally, showed very littlerarefaction roentgenographically and had not been inthe least tender, she gained 15 pounds (7 kg.). Theacute heart irritation disappeared, as did also thenervous symptoms, and she returned to practically nor-mal health. By inherit(lnce she had a marked suscer;Jti-bility for heart and nervous system.

IMMUNITY VERSUS SUSCEPTIBILITY

One of the most important values of these new datais the light they throw on some of those fundamentalforces which are at work in determining not only thelocal and systemic expressions of disease but also thenature of some of the factors involved in immunity anddefense, in contrast with susceptibility. I have pre-viously shown data demonstrating that individuals witha tendency to tearing down of bone, whether at the necks

22

of teeth or at the apexes, tend as a group to have a highdefense against systemic involvements of streptococcalorigin; in other words, they tend to be quite free fromso-called rheumatic group, degenerative diseases. Ihave also stated that these individuals tend to have ahigher ionic calcium content of the -blood than do per-sons with a mild or marked susceptibility to rheumaticgroup disturbances, where they are suffering from such ;and these factors obtain in the presence of even con-siderable dental infection, and that dental infectiontends in all individuals to depress the ionic calcium, butin proportion to the factor of lack of ability to maintainthe body without systemic involvements. When, there-fore, individuals are studied on the basis of the signifi-cance of the type of reaction in bone about suchinfections as dental infections, very important light isthrown on the types of disease which tend to developin individuals in accordance with this factor of thedevelopment of rarefaction on the one hand, or itsabsence, and a tendency to condensation of involvedcalcified structures. This is graphically brought out inTable 9. in which are arranged the various d1stltrbancesand types of disease on the basis of the factor of whetherbone will go into solution or be deposited.

Under the caption, Type of Local Reaction in Bone. Irefer to the structural change in the alveolar bone aboutinfected pulpless teeth and teeth with periodontoc\asi~or pyorrhea. I have divided these changes into threegroups: first, rarefying osteitis with extensive decalcifi-cation; second, condensing osteitis about extensiverarefying osteitis; and third, condensing osteitis, or veryslight rarefying osteitis, or both; and have related eachof the following factors to these groupings: namely,susceptibility group ( absent, acquir~d or inherited) ,blood ionic calcium ( serum calcium) , bactericidal effi-ciency of the blood for streptococci; and, finally, to allthese I have related certain of the systemic disturbancesor involvements, both streptococcal and n()nstreptococcal;

There is doubtless a great significance in these asso-ciations of data, which, so far as I am aware, are largelynew. Clinicians, particularly dental, have 1ong observedthat the mouths with active pyorrhea have little or nocaries. We have not, however, associated these withparticular types of systemic susceptibility. Patientswith periodontoclasia or pyorrhea in an active stageseem always to develop lar~e areas of cavitation and

31

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radiolucence about the apexes of infected pulplessteeth, typifying a good reaction to an irritant. Theseindividuals tend to keep themselves free from rheumaticgroup disease involvements, such as arthritis, and henceclass as absent susceptibility, have a normal or highionic blood calcium, and have a high bactericidal effi-ciency of the blood for streptococci, as well as for mostother organisms. They do not develop the rheumaticgroup, degenerative diseases while in this state, but thepersons who develop progressively fatal miliary pul-monary tuberculosis are largely in this group, as arealso those who develop cancer. This is easily verifiedin many ways. For example, how often have any ofus seen patients with deforming proliferative arthritisdevelop either tuberculosis or cancer ? It should also benoted how constantly cancer patients are free from therecurring rheumatic group symptoms and how fre~quently, if not almost constantly, they report that theyhave never been sick a day before in their lives.

In the second general grouping, namely, condensingosteitis about extensive rarefying osteitis, we find thepersons who formerly had a high defense but have lostit as the result of infection and physical overloads.They are therefore in the acquired susceptibility group.Their blood calcium is usually below their normal, asis also the bactericidal efficiency of their blood. Pre-viously, while in the preceding group, they had littleor no caries, but now they have it in active form. Theirsystemic breaks tend to appear in the nervous system.One type of arthritis, the degenerative, which is asso-ciated with a normal or above normal ionic calciumcontent of the blood, may develop, but not the prolifera-tive type. Since they tend to return to their normal,which is high, the prognosis for recovery from systemicinvolvements arising in streptococcal focal infections isgood. This is the group which, according to our tabula-tion, we find developing the sensitizations, such as skinirritations, asthma, hypertrophic rhinitis, and hay-fever ,all but the last coming frequently from the antigen ofdental infections. The development of these phenom-ena seems to be related to the long continued presenceof the antigen in an individual with normally a highdefense or a high capacity for developing antibodies.The sensitizations frequently completely disappear withthe elimination of the dental focal infection. There isevidence that many disturbances are fundamentally

~~

25

related to, or have involved in them, antigen-antibodyreactions.

In the third group, we have as the typical local bonereaction about dental infections or irritations, apical orgingival, condensing osteitis or very slight rarefyingosteitis. Since there is generally a familial phase, theyare grouped as inherited susceptibility. The blood ioniccalcium tends to have a low normal for the group, andwhen involved with some rheumatic group disturbances,to which such patients are easily subject, the blood cal-cium is often much reduced. The bactericidal efficiencyof blood is low in such patients, and, when involved,often relatively very low. Their affections are veryfrequently of the streptococcal or so-called rheumaticgroup degenerative diseases, as diseases of the heart,kidney, or digestive tract, proliferative arthritis, acuterheumatism, and tonsillitis. They very seldom developcancer or tuberculosis, and if they do develop the latter,prove to be the group in which is found the tendency torecover. In them, lung tubercles and glands tend tocalcify; and, so far as this disease is concerned, t!1isseems to suggest why so many persons who have tuber-culosis recover, as shown by the results of postmortems.I have visited several sanatoriums for tuberculosispatients, looking for ( among other data) cases of mul-tiple deforming proliferative arthritis and tuberculosisassociated, and have not yet found it. I will be gladto be informed of such cases. We might expect to findthe other type-namely, the degenerative-which has ahigher than normal ionic calcium, though it also isapparently a very rare association.

These new data have suggested the desirability ofstudying the effect of producing an arthritis or anassociated streptococcal lesion in rabbits, and then sub-mitting them to comparison with controls inoculatedwith tuberculosis only. These studies are in progress,and while deductions are not yet j~stifiable, the resultsare strongly suggestive, as indicated by the'lung pictureshown in Figure 3, in which zones of calcification areseen in tubercles of a rabbit that was inoculated withstreptococci some weeks before receiving the culture oftubercle bacilli, both intravenously. We have not foundsuch calcifications in lungs of rabbits receiving only thetubercle bacillus. There has also been an apparentlen!lthenin~ of life for these rabbits.~

26

Fig. 3.-Zol1es of calcificatiol1 il1 lul1g of treated tuberculous rabbit.

Fig. 4.-Fibrosis and calcifications in lungs of patient with quiescentpulmonary tuberculosis.

3~

27

By the application of these principles to clinicaiobservation, some interesting and instructive data havebeen accumulated, and there is evidence that a properapplication of this newly observed principle and its rela-tionship may have important prognostic value in thestudy of cases of tuberculosis, for it seems demonstratedthat those patients who produce a calcification processas a reaction about their zone of rarefaction at the apexof an infected root are the same individuals who experi-ence a remission and healing process in the course ofan active tuberculous infection, presumably because ofthe presence of calcification in the fibrosis about thezones of pulmonary tuberculous infection. This is alsoa condition reported by pathologists to be present in thelungs of those individuals who have apparently had nohistory of tuberculosis, but, from the presence of calci-fied tubercles, have apparently had the infection and haverecovered from it by maintaining a zone of calcification,or as a process that is incidentally accompanying thespontaneous recovery. The roentgenogram of the teeth,illustrating the type of local dental pathologic changepresented by the patient marked B in Figure 1, is of awoman, aged 32, who has had pulmonary tuberculosisfrom which she had an elevation of temperature forabout a year and recovered. Figure 4 shows the appear-ance of the lung, which the roentgenologic diagnosticianthus interpreted and diagnosed :

Trachea in midline. Heart and aorta normal. Right chestsmaller than left. Diaphragm adherent at costophrenic angle.Hilium normal. Intercostal spaces narrower than on leftside. Apex lagging. Definite infiltration with moderatefibrosis in the upper lobe and apex. Left chest: Diaphragmand costophrenic angle clear. Hilium contains several calci-fied glands and moderate infiltration in the upper lobe andapex. Diagnosis: Tuberculosis with fibrosis both upperchests.

On studying the bone about the apexe~ of the tworoots of this molar in B, Figure 1, there wilI-be observedin the mesial root the distinct outlining of the zone ofcondensation about the zone of rarefaction. This toothis normally thin mesiodistally and broad buccolingually,which produces an egg-shaped chamber at the apex,and the roentgenogram is accordingly showing this ovalshell in its long diameter. The distal root being nor-mally more nearly round in shape, the buccolin.1{ual

28

diameter of the zone of rarefaction is less and therelation of the thickness of the zone of condensed boneto that of the diameter of the chamber of rarefaction inthis plane is relatively less, and accounts largely for thedifference in the appearance of the zone about the distalroot from that of the mesial root. The local structuralcondition-namely, the zone of condensation about thezone of rarefaction-I take it, indicates that during theperiod that this was taking place, this patient was in acondition in which calcifications occ~r in the presenceof all irritants such as that which obtains here.

When B of Figure 1 is compared with A of Figure 1,a distinct difference in these two types of reaction willbe seen. The patient shown in A has had a high capacityfor reaction, has never had systemic involvements, hasthe type of bone structure and type of reaction that wewould consider to be like that of the group in which thepatients, when they have tuberculosis, do not make asuccessful fight. A study of this girl's family historyshows that her father died at 34 of tuberculosis, andher brother at 15. If space permitted, I could presentother interesting and typical illustrations of thiscondition.

SUMMARY

I might briefly summarize here my interpretationof these local phenomena and their relation to the sys-temic defense. When a person has a normally highdefense, as expressed by absence of recurring rheumaticgroup lesions, he or she tends to make the warfareagainst the organisms and toxic materials coming fromthe openings at the apexes of the involved teeth as closeto the source of that infection as possible. This seemsto be a principal reason why these patients have thelarge zones of rarefaction. This large zone of radio-Iucence is generally occupied in these ind~viduals by ahighly vascularized, defensive tissue, whose functionappears to be chiefly that of a local quarantine station.When it is adequate and efficient, the bala1'lce of thebody is protected. The production of the local warfareexpresses itself as pus, which is eliminated usuallythrough a fistula and contains exceedingly few, andoften no, living organisms. It is apparently largelybecause these individuals can make a fight to a finishclose by the source that the balance of the body is safefrom injury from these disturbances. When, however ,

3'7

29

that patient with a normally high defense has an over-load, such as influenza, pregnancy.. grief, exposure orpoor nutrition, he is unable to continue the maintenanceof the adequate quarantine, the warfare is no longer afight to a finish immediately about the tooth, and theorganisms and their toxic products pass into the body,and that warfare, which should have been made inspecial tissues close to the source of the infection, mustnow be made in the various organs and tissues of thebody. The local dental involvement now ceases to beuncomfortable because of the absence of a local war-fare. The accumulating toxic and bacterial materialproduces general changes in the blood and in the defen-sive forces, and the final warfare may have to be madein various organs and tissues far from the source ofinvasion. Since the blood stream rapidly distributesthese materials to these various structures, the finalwarfare must be made there, and that organ or tissuetends to break which has been most weakened by someof the overloads mentioned above, or by that othernoncontrollable factor ( so far as the individual is con-cerned) , namely, his or her inherited susceptibility,which now proves to be a factor which relates to indi-vidual organs and tissues, and which apparently is thereason why heart disease, etc., runs in families.

In those persons with a high defensive mechanism,the long continued presence of the antigenic substancesof focal infections, such as chronically infected teeth,the evidence suggests, causes zones of irritation todevelop as sensitization reactions, which are completelyrelieved by the removal of the focal infection when itis the source of the antigen, as it frequently is. Thereis much more than a suspicion that these factors havemore than an association relation in the grouping ofcancer development cases in that group with the highstreptococcal defense.

Tuberculosis tends to be associated with'decalcifyingprocesses about dental infections and in patients with-out a previous tendency to dental caries. The prognosisin a cases of tuberculosis is suggested by the presenceof a zone of condensing osteitis about a zone (previouslydeveloped) of rarefaction.

May we not have here a new approach to the studyof both the streptococcal, rheumatic 2:roup, de2:enerative

30

diseases and the nonstreptococcal diseases, such astuberculosis and cancer ?

These new data furnish important suggestions, if nota preliminary basis, for diagnosis, prognosis and treat-ment, particularly for dental focal infections, andindicate the necessity for a greatly enlarged programof research on these fundamentals.

Calcium metabolism seems to playa most importantrol.e in both health and disease.

8926 Euclid Avenue.

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