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Blood Chemistry and its Relation to Periodontal Problems*
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when afflicted by an acute rhinitis, and, in th at event, needs but an occasional simple irrigation, which he should be taught to give himself. T h e advantage of an intra-nasal ventilation over all other methods of treatm ent lies in the fact that it connects a normally sterile but now disturbed sinus w ith the nor mally practically sterile chamber of the nose. L et me protest, therefore, w ith all the emphasis at my command against the
removal of any or all the lining of the sinus and let me brand such interference as a perniciously meddlesome procedure. M ay I close w ith the admonition to taboo the curet, to spare the lining of the maxil lary sinus or any part of it and to carry away the thought th at since this highly specialized membrane is never restored, if destroyed, our duty lies in its preserva tion rather than in its wanton destruc tion.
BLOOD CHEM ISTRY AN D ITS RELATION TO PERIO D O N TA L PROBLEMS* By SYDNEY R. MILLER, M.D., Baltimore, Md.
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A P P E A R before you w ith mingled feelings of pleasure, regret and fear. Pleasure, not merely because you have so graciously honored me, but particularly because it affords me the op portunity to acknowledge again the per sonal debt which every physician owes to the dental profession. M edicine and dentistry are not fundam entally separate professions, but rather branches of one art and science, which has the common aim of the prevention and alleviation of human illness and suffering. Internists, particularly, have been intrigued and stimulated in the recent years by the correlations which have been established between dental and gingival conditions, on the one hand, and diseased conditions elsewhere in the body. I t is a pleasure to note how eager your particular branch of dentistry is in the quest for inform ation *R ead before the A m erican A cadem y of Periodontology, W ashington, D. C., Oct. 3, 1929. Jo u r. A . D . A ., M a rch , 1930
as to how extra-oral conditions may influ ence the teeth and the tissues adjacent to them. Regrets intrude mainly perhaps be cause of selfish motives engendered by an admitted paucity of dental knowledge, which is a daily handicap. In my days at medical school, dentistry as related to medicine was an utterly untouched sub ject. Now, an internist is presumed to be one whose grasp on his own subject is fairly encyclopedic, particularly as far as he is equipped to appraise and utilize the significance of factors which primarily are not purely medical. I t is lamentable that physicians today know and use so little dental discernment. T h e Carnegie Foundation Report on D ental Education in this country and Canada has already done much to point the w a y ; yet in seven of the foremost medical schools in the U nited States, no systematic instruction is given the students of medicine in modern concepts of dentistry.
M iller— Blood Chemistry and Periodontal Problems T h e moral is obvious and the hope is expressed that early correction of such a state may come, sponsored in large meas ure by the insistence of such organizations as yours. People are much more con cerned regarding a dentist’s or physician’s ability to adapt facts which may be of value to them than in their academic propensities. Regret is inevitable when one sees so often the woful disregard of facts which physicians and dentists alike dis play— bad judgm ent, we call it. Good judgm ent, as defined by a patient of mine, consists of an accurate knowledge of the facts, combined w ith a proper considera tion of the value of things. M a rk this w e ll: T h e tremendous advances in know l edge have made it necessary for the den tist to know something of medicine and the physician, of dentistry, if, as advisers in m atters of health, we are to use good judgm ent. Since we cannot know all, it becomes a m atter of knowing the rela tively im portant and unim portant value of things in our practice. T h e last feeling— one of fear— is per haps not truly that, but rather timidity, for I strongly suspect I shall have little th at is new in the way of information to give, little w ith which you are not already familiar. As a m atter of fact, this paper w ill tu rn out to be quite com parable to the school boy’s definition of s a lt: “A substance which makes potatoes taste bad when you don’t put it on.” N egative facts will be much more appar ent than positive ones; w hat we do know, much more impressive than w hat we do. Paradoxical as it may sound, the inherent difficulties of our problem constitute a fortunate state of affairs. Difficulties do or should arouse the normal emotion of w onder and its associated instinct of curiosity. Together, they “stim ulate the impulse to examine more closely the object or difficulty which excites them .”
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T h e curious mind is ever alert. I t re mains sensitive to all th at is doubtful or unsettled. Demand for the solution of a perplexity is the steadying and guiding factor in the entire process of reflection. I t is w ith such a view th a t I shall attem pt to cover the subject allotted, in an effort to make obvious, accredited facts, as well as the gaps in our knowledge, w ith the hope that they may soon be bridged.
T H E SIGNIFICANCE OF CHEM ISTRY TO LIFE AND DISEASE Chemistry is so deeply involved in life phenomena as to become of necessity a partner w ith medicine and dentistry in their efforts to preserve life. Life itself is a chemical function. T h e body is made up of innumerable cells, each one a min iature chemical factory, carrying out its allotted task and making its own con tribution to the substance and function of the body as a whole. By reason of this physiologic division of labor, each cell contributes that special activity which is essential to the association of chemical processes that constitute the living indi vidual. T h e energy of the body is all derived from the chemical energy of the food; and the sum of the chemical changes involved, w hether they lead to molecular simplification, as in combustion, or to complexity, as in the m anufacture of tissue capable of carrying on vital func tion, is known as metabolism. T h e laws governing metabolism are predetermined and fixed, and operate in terminably. Individuals are but incidents in a chemical sense. Life persists and health obtains, provided metabolism pro ceeds along normal lines. Variations result in altered function and illness of varying degree; marked aberrations end in death. In health, N ature is consistent: normal chemical processes result in nor mal function. Even in disease, her ways
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are not haphazard ; uniform alteration in metabolism w ill probably result in a uni form type of perversion of function. T h is may find expression subjectively in symp toms or objectively in signs, and may be accompanied by correlated chemical changes which can be determined quali tatively or quantitatively in the labora tory. I t is this consistency which makes diagnosis possible. T h ree considerations enter into the process of establishing both a clinical diagnosis and appropriate therapy: (1 ) w hat the patient can tell of his illness— his history, as we call it; (2 ) the objec tive findings which the dentist or phy sician can discover through the utilization of his five senses; and (3 ) the laboratory findings as revealed through, studies of the blood of various types, the body juices and the execreta, and by the roentgen rays. I t is to blood chemistry findings in particular that attention is directed to day.
APPLIED CHEMISTRY IN CLINICAL M EDICINE T h e application of chemistry to medical diagnosis, prognosis and treatm ent is a field so large th at no one could adequately discuss it w ithin the scope of a single paper or volume. Inorganic, organic, col loidal, physical and biophysical chemistry has each added its share of the knowledge by which we know more today about life and its progression. In times past, in the study of the excretory organs especially, the main emphasis was placed on the changes in the character of the excretion, as for example, the urine, gastric con tents, feces, sputum, saliva, cerebrospinal fluid, bile and various types of transu dates and exudates. These studies have been in no sense supplanted, nor has their value been one bit minimized by the pres ent tendency to study the blood, in order
to ascertain w hat has accumulated there as the result of the failure of an excre tory organ to carry out its function, or the decrease of substances norm ally present, for any reason whatsoever. T h is change in point of view is the raison d'etre for modern clinical blood chemistry. I t seems quite unnecessary at this time to indulge in any discussion as to the technic of blood chemistry studies, the choice of methods, colorimeters, etc. Suf fice it to say, the procedure is not difficult, though quite beyond the daily practical utilization of the average dentist or physician. Fifteen to tw enty cubic centi meters of whole blood, secured, prefer ably, in. the m orning before the patient has eaten, and put in an oxalated bottle to prevent coagulation, w ill suffice to per m it all of the examinations ordinarily employed. These studies may be grouped as follow s: (1 ) Those to detect evidences of de ficient nitrogen elimination. (a ) U rea nitrogen (nonprotein nitrogen). (b ) Blood uric acid. (c) Blood creatinin. (2 ) Those to detect evidences of faulty carbohydrate metabolism. (a ) Blood sugar. (3 ) Those employed to detect dis turbances in the acid-base equilibrium, referred to usually as acidosis and the rarer condition of alkalosis. (4 ) Those used to detect faulty fat metabolism— cholesterin. (5 ) Those which detect alterations in inorganic constituents, including chlorids, magnesium, phosphates and calcium. Group I .— E v id e n c e s of d e f e c tiv e nitrogen elimination are of the greatest use in the clinical conditions of nephritis, acute or chronic, and especially those in which there in much glom erular degen eration or destruction. I t is particularly
M iller— Blood Chemistry and Periodontal Problems in such diseases that blood chemistry gives evidences of nitrogen retention as shown by the determination of the so-called non protein nitrogen, urea nitrogen (about one-half nonprotein nitrogen), uric acid or creatinin. T h e kidneys in health and disease have so-called thresholds for the elimination of these substances. T hus, creatinin is handled or eliminated w ith greatest ease, uric acid somewhat less so, and nonprotein nitrogen or urea, least of all. In general, therefore, nonprotein nitrogen values w ill show rises above norm al before the others. W h en creatinin becomes permanently high, it is generally regarded as a reflection of the very serious and advanced state of renal disease, w ith an outlook for shorter and shorter life as the values rise. Abnormal nonprotein nitrogen values are found in conditions other than ne phritis, as, for example, in anhydremja, protracted vomiting and diarrhea, gout and arthritis, obstructive lesions of the genito-urinary tract, various forms of poisoning, especially mercury, intestinal obstruction and cardiac decompensation. O n the other hand, the degree of nitrogen retention does not by any means parallel in all instances the severity of the under lying condition. As a m atter of fact, these determinations, in my experience, are more directional and confirmative than truly diagnostic. Properly used clinical judgm ent w ill more often predict w hat the blood findings w ill show than n o t; whereas, too implicit reliance on these tests w ill deceive and disillusion the casual clinician. In all of the conditions in which blood nitrogen studies may be of value, a clinical diagnosis is relatively simple and the blood findings become more of value in following the clinical course of the disease than in a truly diagnostic sense. Single estimations are but rarely of permanent, conclusive value,
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and, in the early stages of clinical nephritis, are quite as often normal as otherwise. U ric acid in the blood is almost always increased in the clinical condition of gout. W hen there is no true renal involvement, there is no constant increase in the more usual forms of arthritis, especially the infectious type. Group I I .— Blood sugar determina tions find their greatest value in both the diagnosis and the treatm ent of di abetes mellitus. O u r knowledge of blood sugar variations is perhaps more exact than any other constituent of the blood. By proper sugar tolerance tests, alimen tary glycosuria can readily be differ entiated from true diabetes, and so-called renal diabetes from the pancreatic form. Studies of blood sugar and sugar toler ance are of further aid in the recognition of some of the disorders of the glands of internal secretion other than the pancreas. T hus, the condition of acromegaly, or overactivity of the pituitary gland, is ac companied by a low carbohydrate toler ance, associated w ith overgrowth of the bony framework, hag teeth, e tc .; under functioning of this gland, w ith an in creased tolerance for sugars. I t is inter esting in passing to note th at insulin w ill control acromegalic diabetes, but not so successfully as in the pure pancreatic form. Group I I I .— For the normal life and functioning of each cell in the body, a constant environment is necessary; name ly, the blood, the composition and re action of which is regulated w ithin very narrow limits. In health, this so-called acid base equilibrium is perennially main tained, despite the constant introduction of acids and bases in our food, and their formation w ithin the body. W e shall soon cease to cherish or tolerate the daily
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phrase, “ acidity of the blood,” once we remember that blood as acid as distilled w ater, or as alkaline as ordinary tap water, is incompatible w ith life. W hen, for any reason, an impairment in this acid base mechanism occurs, and the transfer of carbon dioxid from the tissues to the breath is interfered with, acidosis, which may be acute or chronic, super venes. I t occurs almost always secondarily to some other disease, particularly dia betes, in some forms of nephritis char acterized by phosphorus retention, con ditions causing dehydration of the body (cholera, severe diarrhea), the excessive intake of certain salts and in many types of toxemia. T h e reverse condition, spoken of as alkalosis, ensues when there is an excessive loss of acid from the body or an abnormally large intake of alkali, and, once developed, may closely simulate the condition known as tetany. Both acidosis and alkalosis, suspected clinically, can be quantitatively rec ognized by the employment of a variety of blood chemical studies, the easiest of which is the determination of the hydrogen-ion concentration. Group I V .— Blood chemistry methods dealing w ith altered fat metabolism need but a w ord in passing. T h e ir develop ment is not w ell established, and though blood cholesterin studies are of sugges tive value in certain rare forms of ne phritis, jaundice and the primary ane mias, they have as yet no practical clin ical application.
BLOOD CALCIUM STUDIES OR CALCIUM METABOLISM Because of your chairm an’s emphasis on the subject as w ell as the fact that it adm ittedly is of extreme importance in the whole field of dentistry, I shall devote more time to the discussion of calcium metabolism than to all the others,
and shall pass over entirely any reference to magnesium and potassium in the blood, for, in a word, we know little of prac tical value about them, in a blood chem istry sense. As far as the phosphates go, retention is known to occur in inter stitial nephritis; whereas, a reduction is very commonly associated with active rickets, and is at least one factor in the improper calcification of bone in that disease. T h e importance of calcium has long been recognized, and as far back as 1647 Ambrose Paré, a famous surgeon, sug gested a relationship between absence or a deficiency of calcium and pronounced m alnutrition. I t was not until 1921 that K ram er and T isdall perfected a micro chemical method for quantitative blood calcium analysis, and, w ith but minor modifications, this is still the best method today. From an enormous literature, ably re viewed in 1928 by Stew art and Percival in Physiological Review s, one can cull briefly the following significant facts, and these in turn suggest certain practical applications : 1. Calcium salts, no m atter in w hat form, are absorbed w ith manifest diffi culty and by far most of the ingested calcium is lost in the feces. T h e absorp tion rate, or calcium availability, seems definitely related to protein intake, the sugar content of the diet and the solubil ity of calcium in hydrochloric acid ; whereas, any excess of phosphates lessens calcium availability to a high degree and invariably leads to defective bone forma tion. Finally, it seems conclusively set tled th at an unsatisfactory relation be tween three dietary factors — calcium, phosphorus and vitamin ,D — leads to pathologic bony changes, mainly, it is thought, because vitamin D seems both
M iller— Blood Chemistry and Periodontal Problems to increase calcium retention and at the same time either to stim ulate hydrochloric acid secretion in the stomach or inhibit the flow of alkaline intestinal juices. 2. T h e most obvious function of cal cium is related to the process of bone formation, but much inform ation is still lacking as to how the transference of calcium from the blood to the growing bone is effected. Calcium is requisite to the norm al functioning of all cells and is a factor necessary in preserving the cor rect balance of inorganic ions, spoken of as isotonicity. Calcium salts, when defi cient, seem to bear a relation to certain forms of diarrhea, and, conversely, when in excess, to obstinate constipation. Hence, the view that calcium exerts some regu lating influence on intestinal peristalsis. T here is much evidence that calcium plays no small role in m aintaining the proper hydrogen-ion concentration of the blood. T h e long recognized function of calcium w ith reference to the coagulation of the blood hardly requires more than a mere statement of the fact. Calcium is essen tial for muscular contractility and as well for the conductivity and irritability of nervous tissue. 3. As far as methods go, it appears that quantitative estimations of the serum calcium give the best results, and the ac cepted normal values range from 9 to 12 mg. per hundred cubic centimeters. T here is apparently little difference in the serum content of calcium in infants, adolescents and adults. T h e only definite physiologic fall in serum calcium occurs during preg nancy, and is followed by a rise to normal after delivery. 4. Finally, the factors which control the calcium content of the blood are not definitely and certainly known. By reason of the bony changes in acromegaly and eunuchism, the loss of calcium in hyper thyroidism and diabetes and other en
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docrine disturbances, one after another of the various glands of internal secretion has been assigned the controlling influ ence over calcium metabolism. A ll the evidence is inconclusive, except as the parathyroid glands are concerned. C lini cal and experimental studies w arrant the statement that whatever other functions they may possess, the parathyroid glands exercise a definite control over the con centration of calcium in the blood, and particularly in maintaining the internal calcium equilibrium. 5. T h e constancy of blood serum cal cium suggests that a delicate controlling mechanism must exist which balances ab sorption, deposition, utilization and elimi nation. T h ere is growing evidence, too, to suggest that the accepted figures for total serum calcium do not truthfully portray the amount of so-called available calcium, and until simple and accurate measures are, devised for estimating the available calcium in the blood, its ther apeutic uses cannot be placed upon a strictly satisfactory basis. Thus, in para thyroid tetany, primary or postoperative, the use of parathyroid extract seems more logical and is more effective than calcium administration ; and in rickets, the use of sunshine and vitamin D will do much more good than the use of calcium itself. Calcium is, and has been for years, given in many hemorrhagic conditions, in asthma, hayfever, urticaria and other con ditions in which a calcium deficiency, as sumed, is not borne out by consistent blood chemistry findings.
BLOOD CHEM ISTRY’S VALUE TO PERIODONTISTS Even in such an incomplete and cursory résumé of blood chemistry and its value to medicine, the query might aptly be made : In w hat possible way or ways can such knowledge be turned to the advan
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tage of the members of this special branch of the practice of dentistry? T h e answer, as I see it, is both easy and involved; but before attem pting an answer, let me di gress for the moment, and go into a field where the display of my dental ignorance may be pitiful. By derivation, your chosen profession is th at branch of dentistry concerned w ith the tissues around the teeth, and, in p ar ticular, those processes, of w hatever nature, which produce a breaking down of the periodontal structures. Such proc esses are broadly covered by the term periodontoclasia. Y our interests center not so much in the problems of dental caries, root canal fillings, periapical ab scesses and the like, though I suspect th at they enter much into your problems, as in those conditions which injure the gin givae, occlusive anomalies and their resul tan t mechanical effects, in the production of soft tissue injuries, food packs and their chemical influences, infections in their relation to soft parts and the teeth as well, and, finally, in the cementum surfaces and the various anomalies and deposits encountered in the practice of apoxesis. Perhaps this does not cover all your special interests, but to me it seems quite enough, and your pardon is craved if I have left you too small a field to in vade. Now, as nearly as I can see it, perio dontoclasia, in general, resolves itself into one of tw o main groups: G roup I, in which either intrinsic inherited or consti tutional factors, or acquired, extrinsic noninheritable factors exert their m align influences mainly through mechanical ir ritation, to which the secondary factors of infection may subsequently be added. These are prim ary and essentially local conditions. G roup II, the so-called sec ondary group, which in many instances overlaps the first, although more often
the local conditions are expressive of sys temic disorder or disease in quite the same sense th at D r. W ilm er regards the eye as an indicator of trouble elsewhere for which the eye itself is not the cause but of which it is the victim. G ra n t for the m oment the essential soundness of such a conception by a mere medical layman: it would seem, then, as far as blood chem istry is concerned, th at it has little if any value in the recognition and treatm ent of conditions in the first group, w ith perhaps one rather w ildly speculative exception. Recent and ever-increasing anthropo m etric studies serve to show more and more “type forms” or “habitus,” each manifesting certain apparent disease ten dencies. Already, we recognize clinically individuals of the asthenic, pyknotic, arthritic, neuropathic and digestive habitus, as well as those who show the thymicolymphatic constitution, and other endocrine imbalance, associated with which there are so m any dental anomalies, enamel hypoplasia and dentition defects. I t is conceivable th at biochemical studies applied in these groups, and particularly a t an early age in life, might shed some light on how constitutional heritage may be altered. T h e opportunity in this would come mostly through the teamwork and study of periodontists and pediatricians; for theirs, probably, would be the op portunity to see the earliest evidences of such abnormal states. W hen one comes to the second group of periodontoclasia cases, the situation is theoretically very different, yet practi cally, in my opinion, quite the same. T his is but another way of saying th at blood chemistry, as it is now understood, holds nothing of daily routine value to the periodontal specialist, except in an indi rect sense. L et me elaborate this by point ing out some of the dangers.
M iller— Blood Chemistry and Periodontal Problems You have all witnessed the destructive effects th at the so-called focal infection theory has left in its wake. Fortunately, the problem, though still not solved, is bein^ viewed and dealt w ith in a more rational way. In an article in the D ental Cosmos in 1921, I called attention to some of the utterly absurd tests and ridiculous interpretations thereof which overzealous dentists were employing as the final criteria of the need, or other wise, of extractions. T h e same menace confronts the medical profession today, in a period when tests, form ulas and ma chines of precision, valuable as they are, are lessening the power to observe and provoking atrophy of logical deductive thinking. T o interpret at all blood chem ical findings is not possible w ithout close clinical correlation: wide variations occur unless the factors of diet, fluid balance, etc., are carefully considered; and last, but by no means least, obvious pathologic deviations are by no means always sig nificant in the w ay that one is taught to believe. U seful as they are, I am con vinced that they have, as yet, value only when properly employed in selected cases. T h is opinion is a result of analyzing thou sands of blood chemistry studies routinely applied in both w ard and private practice. Applying this certain personal convic tion to your profession, I should feel that your knowledge of blood chemistry would better be translated into the early recog nition of periodontal diseases not appar ently falling into G roup I, and hence probably due to some systemic disorder which needs ferreting out by medical aid. I t would be interesting teamplay for the periodontist and internist to note, for example, any relation between local oral disease, in terms of advance or re gression, in a chronic nephritic, for in stance, and the rise or fall of retained nitrogenous substances; or a series of dia
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betics in relation to their freedom from glycosuria or consistently elevated blood sugar concentrations; a group of asthenic neuropaths in relation to their pro nounced pyorrheal tendencies and subnor mal blood chemical findings, and the alterations in .each during periods of in duced normal nutrition, w ith saner ways of thinking. M any other fascinating problems might be mentioned, but these w ill serve the point that I wish to stress once ag ain: leave blood chemistry alone for the present, but recognize more quickly as dentists your need for help from an internist, just as we are growing ever more alert to the hostility of perio dontal disease to health alone, and its sinister effects on established systemic disease. In w hat way periodontal disease affects blood chemical findings, I do not know ; nor have I been able to find any literature dealing w ith this phase of the question. If a large percentage of cases of perio dontoclasia are local secondary manifesta tions of such diseases as nephritis, dia betes, abnormal blood conditions and dis orders of endocrine and autonomic nervous system origin, abnormalities found in a blood chemical sense cannot logically be ascribed to the oral conditions at all. Further, to believe that many such systemic conditions have their etiology in the mouth, is, I take it, bad judgm ent; for an accurate knowledge of the facts w arrants no such valuation of the find ings to date. As far as I can see, periodon tal disease, especially the suppuratiye form, for which, as yet no specific vege table or protozoan organisms have been proved directly responsible, can influence blood chemical findings only by exerting a further malign influence on the primary systemic affection. Painstaking periodon tal-medical correlation alone w ill affirm or refute this conception.
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CONCLUSIONS studies w ith the clinical manifestations of T h e principles of preventive periodon disease. M any purely laboratory re tia are, in a large measure, educational in searches have failed for w ant of clinical character, demanding th at the details of direction. I t is helpful not to forget that correct oral hygiene, proper and sufficient some of the most notable achievements in gingival stim ulation and the adequate medicine, and in dentistry, too, I suspect, application of w ell established dietetic have been accomplished by men whose laws be taught to young and old, w ith an lives were spent far from laboratories or inspired insistency. T h e elimination of seats of learning. L et me mention four: all irritating oral conditions is the me Harvey was an obscure physician, strug chanical and technical side of your prob gling to make a living, when he first lem. A n ever broadening conception of began to think of the circulation of the the reciprocal relations between systemic blood. Jenner, among the worries of a diseases and periodontal lesions is the country practice, discovered vaccination inspirational side, which everyone needs against smallpox. Koch was a local phy in his daily work. sician when he began his work on tuber culosis. M ackenzie was a busy general I t is hoped that the meager glimpse practitioner in England, when he laid the into the realm of chemistry and its reve lations in a medical sense w ill serve as a foundations for his epoch-making work genuine stimulus for the w ork which lies on the heart. H istory and experience w arrant the ahead. I do not mean in any sense to .leave the impression that the advances in assertion th at most progress is assured blood chemistry have not been valuable when clinician and laboratory worker or practical: they have. Y et their value, pull together, each recognizing the diffi in the last analysis, is more directional culties faced by the other, and equally than definite, more confirmative than determined that those difficulties shall be conclusive, and more suggestive than solved as a result of their m utual efforts. final. T h a t deviations from the normal, In clinical medicine, the true value of in a chemical sense, concern you as well laboratory methods has been enhanced as internists, there can be no d o u b t; but rather than lessened by the frank recog refinements, both in methods and inter nition of their limitations, and this has pretation, need to be made before the been particularly true of many of the finer variations can be given their proper blood chemistry tests. and practical valuation. I t is not too Progress in any altruistic profession is, much to hope or believe that, in the not by the very nature of things, inevitable. distant future, such advances w ill be ac I t is most consistent when plasticity of complished. thought regularly surpasses the bigotry M uch of the w ork done, and to be of narrowmindedness. I t is stimulated in done, is so technical and, in many in an atmosphere of appreciation and by stances, so remote in its relation to frank, constructive criticism. I t is fostered practical medicine, th a t the busy practi when the ideas or whims of the individual tioner and dentist cannot keep pace w ith are kept constantly subservient to the it all, if, indeed, he could grasp w hat it weight of judiciously proven opinion. is all about. B ut bear in mind th at the W ith such a point of view, dentistry can true aim of medical and dental research confidently expect increasing aid from is , to reconcile the results of laboratory medicine, and medicine from dentistry,
M ille r— Blood Chemistry and Periodontal Problems as we eventually learn more exactly just w hat the chemistry of health and disease really means.
DISCUSSION
Justin D. Towner, M emphis, Tenit.:
The presen t theory re g a rd in g the etiology of p erio dontoclasia is to w a rd the alkalosis index, and I should like to ask D r. M ille r w h at blood research could be m ade to establish the tru th of this a p p are n t tendency. W e know th a t the pocket-form ing type of p erio dontoclasia is directly opposed to the condi tions in w hich w e find caries. In the f o r m er, reactions a re a lk a lin e ; in the latter, acid, and the one w hich assum es the ascend ency m ore or less com pletely controls the other. T h is is suggestive only of fu rth e r research, w hich has ju st begun to open up an avenue w hich we all m ay enter, and to w hich som ething of definite value m ay be contributed. Rudolph Kronfeld, Chicago, III.: W e often found th a t teeth w hich w ere lost by early loosening show ed v ery h a rd and w ell-calci fied crow ns and yellow ish enam el and w ere highly re sistan t to caries. P oorly calcified teeth w ith a bluish w hite enam el and a -g re a t susceptibility to caries seldom are lost by periodontoclasia, and show a fa v o ra b le rate of eruption. So it seems th a t there is a cer ta in antagonism betw een periodontoclasia a n d caries.
A rthur II. M erritt, N ew York City: D r. M ille r has answ ered m any questions th a t h a v e a g ita te d the m inds of m any of us fo r se v e ra l y e ars. A ll of us know th a t there a re cases arisin g in daily practice w hich seem to have a systemic background. In a case w hich recently cam e u n d e r m y observation, in a w om an, aged 25, the thirtytw o teeth w ere so seriously involved in bone destruction and periodontal d isturbance th a t one of the best o ral surgeons in N ew Y ork ad vocated th e ir complete rem oval. She ap p e are d to be in excellent h e alth except th a t she, in an effort to m ain tain h e r boyish fig ure, w as p erh ap s u ndernourished. I de cided th a t th ere m ust be some explanation of this case outside the mouth. I asked the fam ily physician to m ake a carefu l physical exam ination. H e reported on the blood ex am in atio n and urinalysis as w ell as m aking the re g u la r physical exam ination. H e w as unable to find any explanation fo r the condi
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tion in the m outh. W ith the a p p ro v al of the patient, a nother physician w as chosen who w as know n to be exceedingly careful in m ak ing, and p a rticu la rly w ell qualified to m ake, such exam inations. H e reported th a t he could find nothing abnorm al, and yet her m outh w as so seriously involved th a t one of the best o ral consultants recom m ended the com plete extraction of h e r teeth to the fam ily physician w ho had taken him into consulta tion. I rem em ber a fe w y ears ago a n article (w ritte n by a m an in E n g la n d ) w hich w as com m ented on by the editor of Dental Cosmos, saying th a t dental caries w as the result of calcium deficiency and periodontoclasia w ith calcium sa tu ratio n . I should like to h ear from D r. M iller in re g a rd to this. M y own clinical observation has not confirm ed th a t statem ent.
John Oppie McCall, N ew York City: A t the D ental Clinic of N ew Y ork U niversity, College of D entistry, about fo u r y ears ago, a child of 11 y ears w as bro u g h t to my attention in the periodontoclasia clinic w ho h a d lost several of her perm an en t teeth, one or tw o incisors and also the first p erm anent m olars in the low er ja w . She h a d quite high re sistance to dental caries, and the condition of the m outh m ade it e vident w hy she had lost the teeth th a t w ere gone. She h a d as ex trem e a condition of periodontal destruction as I am sure w as to be found in D r. M e rritt’s case. W h ile it w as not believed th a t anything could be done fo r her, w e did try to help her, and finally I took her to m y ow n office, though she w as a clinic patient, to see if I could help h e r better there th an in the college clinic; but it w as all to no a v ail. In less th an tw o years, she h a d lost all her perm anent teeth and she is w e arin g fu ll upper and low er dentures today. T h a t w as before the age of 13, and the condition w a s entirely typical, as f a r as any clinical exam ination could ex plain, of perio d o n tal disease of the su p p u ra tive type w ith w hich w e are all fa m ilia r. H e r history w a s not conclusive in any re spect. H e r p a ren ts w ere ig n o ran t people w ho h a d difficulty in speaking and u n d e r sta n d in g E nglish a n d so the tak in g of the history w as v e ry unsatisfactory, but I am quite sure th a t she h a d no systemic d iso rd e r th a t w as a n ything out of the o rdinary. It w as quite probable th a t she suffered fro m rickets in a m ild degree in early childhood, but so h a v e m any o ther children w hom w e see w ho do not h ave such a disturbance in
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the m outh. T h is is the m ost serious case of its kind th a t I have seen, but I recall a boy of 16 who w as b ro u g h t to the clinic la te r w ith essentially the sam e condition. T h e re is no question th a t we h ave a systemic factor, but, as in the case of D r. M e rritt’s patient, exam ination (including a blood exam ination, but I think not blood calcium determ in atio n ) by physicians w ho w ere, I believe, com petent, failed to show anything w hich w ould give us any help eith er in a diagnostic w ay o r in the w a y of pointing to w a rd possible th e ra p e u tic aid. T h e subject of blood chem istry, of course, is n a tu ra lly associated in our m inds w ith disturbances of this kind because not only do w e see cases such as the ones th a t D r. M e rritt and I have cited, but w e also see cases w hich show exactly opposite conditions. It is quite a common th in g fo r us to see patients w ho have neglected th e ir mouths, who h ave perhaps suffered from serious dis eases, including diabetes, fo r instance, and w ho show little, if any, d isturbance of the periodontal tissues. T ra u m a tic occlusion does not in v ariab ly m ean a b reak in g dow n of the periodontal tissues in the o rd in a ry way, and it seems th a t there m ust be som e thing, not m erely a systemic condition, but som ething w hich could be determ ined in the blood by w ay of explaining these anom alous things. D r. M ille r has been g iv in g us a d vanced inform ation along this line. I realize th at the problem is a difficult one, and I hope th a t he has become sufficiently interested in the subject th a t he w ill continue to study the subject of blood chem istry from the dental, and p a rtic u la rly from the periodontal standpoint, and come into closer relationship w ith d e n tists who m ay be able to help him clinically. I hope th a t he m ay soon give us the in fo rm a tion w hich we a re all looking fo r so eagerly.
Isador H irschfeld, N ew York City: A propos D r. M ille r’s question and suggestions, it seems th a t observations m ay help us in checking up these cases of periodontoclasia w ith systemic factors. I have in m ind a num ber of instances in w hich I have positive proof th a t gum recession w as, in certain cases, gen eralized and th a t the recession had ceased a t least a num ber of y ears p rio r to the tim e w hen I saw the patient, w ithout any local trea tm e n t or any special attention locally. W e have ano ther point to consider, and th a t is, these cases of periodontoclasia, called lately in E urope “the h orizontal type of p y o rrh ea ,” seem to be essentially not a
type of distrib u ted pyorrheal infection, but ra th e r a secondary infection, you m ight say, in addition to the uniform ly h o rizo n tal reces sion of the periodontal tissues. It is tru e we h ave tw o fa cto rs to contend w ith : the loss of the periodontal tissues w ith o u t local in fection and the b re ak in g dow n of tissues as a result of p eriodontal infection. I f we alread y h ave a pyorrheal condition superim posed on this g en eralized destruction of the periodon tium , w e a re not in a position to know through d eterm inations by m edical men at th a t tim e w h eth er the original systemic cause of this g en eralized recession is still present. In other w ords, if it is tru e th a t the original system ic etiologic factors h a v e a lre ad y been rem oved fo r some reason or other, p erhaps through the endocrine system, and w e have an infection present, are we in a position to know w h eth er the condition w e find at the present tim e is caused by system ic o r local causes ? H. J. Leonard, N ew York City: W e hope to in au g u ra te in Colum bia U niversity a series of chem ical studies along th is line, and it w ill be helpful to us if D r. M ille r w ill give us his idea as to w h a t p a rtic u la r factors in the blood one m ight analyze first in a t tem pting to determ ine the pro b ab le changes th a t have gone on, and th a t have delayed recovery from periodontoclasia. If we take as our hypothesis th a t there is some blood chem ical change w hich is the cause of p erio dontoclasia, w hat, in his opinion, w ould be the first th in g to look for alo n g th a t line? Celia Rich, Nashville, Tenn.: Could there be a serious endocrine d isturbance and the blood still be n orm al?
Dr. M iller (closing): D r. L eonard asked me previously as to how one w ould sta rt blood studies on the theory th a t there must be som ething w rong in the blood th a t in some w ay low ers local resistance and perm its condi tions to d e v elo p ; i. e., caries a n d periodonto clasia. T h a t im m ediately b rin g s up the whole subject of im m unity. W h a t is im m unity? Is it a chem ical process? It is so thought of by many, yes, but in w h a t phase of chem istry does it fa ll? Is it colloidal chem istry or is it lipoidal chem istry, or w h a tn o t? I t has not been settled. T h e re has been in recent years a g re a t deal w hich has suggested th a t im m unity is bound up v ery closely w ith the p ro p er blood ionization of inorganic sub stances m ore th an organic. T h a t a g ain is a hypothesis. I t is certain ly established th a t
M ille r— Blood Chemistry and Periodontal Problems the am ount of ionized calcium in*the blood, w hich is essentially w h a t one determ ines w h en he m akes a blood calcium study, is sus ceptible of not v e ry w ide v a ria tio n s from the accepted norm al w ithout reciprocal d is tu rb an c es in the acid-base equilibrium . W h a t relation th a t m ay b e ar to the question asked about the alkalosis index, I do not know offhand, but it probably w ould be slight, a n d the basis th a t it is so w ell established th a t the hydrogen-ion concentration of the blood can sw ing e v er so slightly, as determ ined by the m ost accurate electrical m ethods of precision, before w e get into the acidosis or alkalosis complex, th a t one w ould h a rd ly expect to find v ery conclusive evidence in term s of m outh conditions w hen the sw ing is in such extrem ely n a rro w m arg in s. As f a r as h ealth is concerned, we feel th a t th a t is so, re g ard less of dental conditions. P e rh a p s there should be refinem ent along the lines of hydrogen-ion studies and p a rtic u la rly m ore studies w ith reference to the proven relation, and w h a t the relationships th a t exist betw een a v ailab le calcium , a v ailab le phosphorus, and vitam in D re ally m ean. T h ere p e rh ap s w ould lie a m ore fru itfu l field fo r chem ical re search ra th e r th a n in correlated studies of clinical findings and blood chem istry m ethods. A s f a r as the definite show ing in the la b o ra tory goes, th a t in caries th ere is a calcium defi ciency and in periodontal disease an excess is not borne out by any studies th a t I know of w hich are satisfacto rily controlled w ith re f erence to dietetic factors, etc. T h e re ag ain is a fru itfu l field fo r accurate research, but you see th a t th ere m ust be c o rre latio n as re g a rd s not only w h a t you find in the m outh and w h a t you find in the lab o rato ry , but also w h a t the patien t takes into his m outh, in term s of food content, org an ic content, w a te r content, etc. As they are all involved in the thoroughly interm ingled process, you w ill nev er get resu lts except by team w ork of th at sort. T h e present m ethods em ployed in blood
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chem istry, as elaborated in the p ast eight or ten years, have reached such a stage th a t dis crepancies betw een the findings of tw o ob serv ers on the sam e blood should be m inim um unless one observer is color-blind. If he is color-blind, he is p a rtic u la rly u n fo rtu n ate in this w ork, because p ractically all the d e te r m inations are colorom etric. T h e results should check and do check, as a m atter of fact, betw een different lab o rato ries w ithin such sm all fractio n s of m illigram s th a t the d if ference m eans nothing. T h e last question asked is, “C an there be m ark ed endocrine d is turbances w ithout gross blood chem istry a lte r atio n ? Probably, yes. F or exam ple, the d e v i ations from norm al in a la rg e group of cases of pronounced hyperthyroidism are not p a r ticularly significant or strictly diagnostic, nor are they a lte re d by subsequent rem oval of the hy p erp lastic thyroid. One certain ly sees finer shades of endocrine disturbances as revealed by constitutional defects or stigm as w hich do not show enough in the w a y of deviation from the norm al to m ake those findings cap a ble as yet of accurate in terp retatio n . T h e re is an o th er fru itfu l field fo r someone to w ork in, to determ ine w h a t endocrines a re. T hey a re ju st as vague as the vitam ins, though w e know they are im portant. W e now know m uch about epinephrin a n d about insulin, and w e are beginning to le a rn th a t there is a p p a ren tly a close relationship betw een d ieta ry deficiencies and abnorm al chem ical findings in pernicious anem ia. W e do not know how to determ ine in the blood w h eth er a person has too m uch of the a n te rio r lobe or too little of the posterior lobe in the p itu itary g la n d ; and if the lobe is too larg e or too sm all, w h a t we can do about it. W h e th e r blood chem istry is capable of detecting finer shades of a lteratio n s in norm al o r abnorm al constituents of g la n d u la r origin m ight throw fu rth e r light either on dental problem s p rim a rily or on th e ir relation to alterations in in o rg an ic chem istry. I t is w o rth thinking about.
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when afflicted by an acute rhinitis, and, in th at event, needs but an occasional simple irrigation, which he should be taught to give himself. T h e advantage of an intra-nasal ventilation over all other methods of treatm ent lies in the fact that it connects a normally sterile but now disturbed sinus w ith the nor mally practically sterile chamber of the nose. L et me protest, therefore, w ith all the emphasis at my command against the
removal of any or all the lining of the sinus and let me brand such interference as a perniciously meddlesome procedure. M ay I close w ith the admonition to taboo the curet, to spare the lining of the maxil lary sinus or any part of it and to carry away the thought th at since this highly specialized membrane is never restored, if destroyed, our duty lies in its preserva tion rather than in its wanton destruc tion.
BLOOD CHEM ISTRY AN D ITS RELATION TO PERIO D O N TA L PROBLEMS* By SYDNEY R. MILLER, M.D., Baltimore, Md.
I
A P P E A R before you w ith mingled feelings of pleasure, regret and fear. Pleasure, not merely because you have so graciously honored me, but particularly because it affords me the op portunity to acknowledge again the per sonal debt which every physician owes to the dental profession. M edicine and dentistry are not fundam entally separate professions, but rather branches of one art and science, which has the common aim of the prevention and alleviation of human illness and suffering. Internists, particularly, have been intrigued and stimulated in the recent years by the correlations which have been established between dental and gingival conditions, on the one hand, and diseased conditions elsewhere in the body. I t is a pleasure to note how eager your particular branch of dentistry is in the quest for inform ation *R ead before the A m erican A cadem y of Periodontology, W ashington, D. C., Oct. 3, 1929. Jo u r. A . D . A ., M a rch , 1930
as to how extra-oral conditions may influ ence the teeth and the tissues adjacent to them. Regrets intrude mainly perhaps be cause of selfish motives engendered by an admitted paucity of dental knowledge, which is a daily handicap. In my days at medical school, dentistry as related to medicine was an utterly untouched sub ject. Now, an internist is presumed to be one whose grasp on his own subject is fairly encyclopedic, particularly as far as he is equipped to appraise and utilize the significance of factors which primarily are not purely medical. I t is lamentable that physicians today know and use so little dental discernment. T h e Carnegie Foundation Report on D ental Education in this country and Canada has already done much to point the w a y ; yet in seven of the foremost medical schools in the U nited States, no systematic instruction is given the students of medicine in modern concepts of dentistry.
M iller— Blood Chemistry and Periodontal Problems T h e moral is obvious and the hope is expressed that early correction of such a state may come, sponsored in large meas ure by the insistence of such organizations as yours. People are much more con cerned regarding a dentist’s or physician’s ability to adapt facts which may be of value to them than in their academic propensities. Regret is inevitable when one sees so often the woful disregard of facts which physicians and dentists alike dis play— bad judgm ent, we call it. Good judgm ent, as defined by a patient of mine, consists of an accurate knowledge of the facts, combined w ith a proper considera tion of the value of things. M a rk this w e ll: T h e tremendous advances in know l edge have made it necessary for the den tist to know something of medicine and the physician, of dentistry, if, as advisers in m atters of health, we are to use good judgm ent. Since we cannot know all, it becomes a m atter of knowing the rela tively im portant and unim portant value of things in our practice. T h e last feeling— one of fear— is per haps not truly that, but rather timidity, for I strongly suspect I shall have little th at is new in the way of information to give, little w ith which you are not already familiar. As a m atter of fact, this paper w ill tu rn out to be quite com parable to the school boy’s definition of s a lt: “A substance which makes potatoes taste bad when you don’t put it on.” N egative facts will be much more appar ent than positive ones; w hat we do know, much more impressive than w hat we do. Paradoxical as it may sound, the inherent difficulties of our problem constitute a fortunate state of affairs. Difficulties do or should arouse the normal emotion of w onder and its associated instinct of curiosity. Together, they “stim ulate the impulse to examine more closely the object or difficulty which excites them .”
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T h e curious mind is ever alert. I t re mains sensitive to all th at is doubtful or unsettled. Demand for the solution of a perplexity is the steadying and guiding factor in the entire process of reflection. I t is w ith such a view th a t I shall attem pt to cover the subject allotted, in an effort to make obvious, accredited facts, as well as the gaps in our knowledge, w ith the hope that they may soon be bridged.
T H E SIGNIFICANCE OF CHEM ISTRY TO LIFE AND DISEASE Chemistry is so deeply involved in life phenomena as to become of necessity a partner w ith medicine and dentistry in their efforts to preserve life. Life itself is a chemical function. T h e body is made up of innumerable cells, each one a min iature chemical factory, carrying out its allotted task and making its own con tribution to the substance and function of the body as a whole. By reason of this physiologic division of labor, each cell contributes that special activity which is essential to the association of chemical processes that constitute the living indi vidual. T h e energy of the body is all derived from the chemical energy of the food; and the sum of the chemical changes involved, w hether they lead to molecular simplification, as in combustion, or to complexity, as in the m anufacture of tissue capable of carrying on vital func tion, is known as metabolism. T h e laws governing metabolism are predetermined and fixed, and operate in terminably. Individuals are but incidents in a chemical sense. Life persists and health obtains, provided metabolism pro ceeds along normal lines. Variations result in altered function and illness of varying degree; marked aberrations end in death. In health, N ature is consistent: normal chemical processes result in nor mal function. Even in disease, her ways
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are not haphazard ; uniform alteration in metabolism w ill probably result in a uni form type of perversion of function. T h is may find expression subjectively in symp toms or objectively in signs, and may be accompanied by correlated chemical changes which can be determined quali tatively or quantitatively in the labora tory. I t is this consistency which makes diagnosis possible. T h ree considerations enter into the process of establishing both a clinical diagnosis and appropriate therapy: (1 ) w hat the patient can tell of his illness— his history, as we call it; (2 ) the objec tive findings which the dentist or phy sician can discover through the utilization of his five senses; and (3 ) the laboratory findings as revealed through, studies of the blood of various types, the body juices and the execreta, and by the roentgen rays. I t is to blood chemistry findings in particular that attention is directed to day.
APPLIED CHEMISTRY IN CLINICAL M EDICINE T h e application of chemistry to medical diagnosis, prognosis and treatm ent is a field so large th at no one could adequately discuss it w ithin the scope of a single paper or volume. Inorganic, organic, col loidal, physical and biophysical chemistry has each added its share of the knowledge by which we know more today about life and its progression. In times past, in the study of the excretory organs especially, the main emphasis was placed on the changes in the character of the excretion, as for example, the urine, gastric con tents, feces, sputum, saliva, cerebrospinal fluid, bile and various types of transu dates and exudates. These studies have been in no sense supplanted, nor has their value been one bit minimized by the pres ent tendency to study the blood, in order
to ascertain w hat has accumulated there as the result of the failure of an excre tory organ to carry out its function, or the decrease of substances norm ally present, for any reason whatsoever. T h is change in point of view is the raison d'etre for modern clinical blood chemistry. I t seems quite unnecessary at this time to indulge in any discussion as to the technic of blood chemistry studies, the choice of methods, colorimeters, etc. Suf fice it to say, the procedure is not difficult, though quite beyond the daily practical utilization of the average dentist or physician. Fifteen to tw enty cubic centi meters of whole blood, secured, prefer ably, in. the m orning before the patient has eaten, and put in an oxalated bottle to prevent coagulation, w ill suffice to per m it all of the examinations ordinarily employed. These studies may be grouped as follow s: (1 ) Those to detect evidences of de ficient nitrogen elimination. (a ) U rea nitrogen (nonprotein nitrogen). (b ) Blood uric acid. (c) Blood creatinin. (2 ) Those to detect evidences of faulty carbohydrate metabolism. (a ) Blood sugar. (3 ) Those employed to detect dis turbances in the acid-base equilibrium, referred to usually as acidosis and the rarer condition of alkalosis. (4 ) Those used to detect faulty fat metabolism— cholesterin. (5 ) Those which detect alterations in inorganic constituents, including chlorids, magnesium, phosphates and calcium. Group I .— E v id e n c e s of d e f e c tiv e nitrogen elimination are of the greatest use in the clinical conditions of nephritis, acute or chronic, and especially those in which there in much glom erular degen eration or destruction. I t is particularly
M iller— Blood Chemistry and Periodontal Problems in such diseases that blood chemistry gives evidences of nitrogen retention as shown by the determination of the so-called non protein nitrogen, urea nitrogen (about one-half nonprotein nitrogen), uric acid or creatinin. T h e kidneys in health and disease have so-called thresholds for the elimination of these substances. T hus, creatinin is handled or eliminated w ith greatest ease, uric acid somewhat less so, and nonprotein nitrogen or urea, least of all. In general, therefore, nonprotein nitrogen values w ill show rises above norm al before the others. W h en creatinin becomes permanently high, it is generally regarded as a reflection of the very serious and advanced state of renal disease, w ith an outlook for shorter and shorter life as the values rise. Abnormal nonprotein nitrogen values are found in conditions other than ne phritis, as, for example, in anhydremja, protracted vomiting and diarrhea, gout and arthritis, obstructive lesions of the genito-urinary tract, various forms of poisoning, especially mercury, intestinal obstruction and cardiac decompensation. O n the other hand, the degree of nitrogen retention does not by any means parallel in all instances the severity of the under lying condition. As a m atter of fact, these determinations, in my experience, are more directional and confirmative than truly diagnostic. Properly used clinical judgm ent w ill more often predict w hat the blood findings w ill show than n o t; whereas, too implicit reliance on these tests w ill deceive and disillusion the casual clinician. In all of the conditions in which blood nitrogen studies may be of value, a clinical diagnosis is relatively simple and the blood findings become more of value in following the clinical course of the disease than in a truly diagnostic sense. Single estimations are but rarely of permanent, conclusive value,
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and, in the early stages of clinical nephritis, are quite as often normal as otherwise. U ric acid in the blood is almost always increased in the clinical condition of gout. W hen there is no true renal involvement, there is no constant increase in the more usual forms of arthritis, especially the infectious type. Group I I .— Blood sugar determina tions find their greatest value in both the diagnosis and the treatm ent of di abetes mellitus. O u r knowledge of blood sugar variations is perhaps more exact than any other constituent of the blood. By proper sugar tolerance tests, alimen tary glycosuria can readily be differ entiated from true diabetes, and so-called renal diabetes from the pancreatic form. Studies of blood sugar and sugar toler ance are of further aid in the recognition of some of the disorders of the glands of internal secretion other than the pancreas. T hus, the condition of acromegaly, or overactivity of the pituitary gland, is ac companied by a low carbohydrate toler ance, associated w ith overgrowth of the bony framework, hag teeth, e tc .; under functioning of this gland, w ith an in creased tolerance for sugars. I t is inter esting in passing to note th at insulin w ill control acromegalic diabetes, but not so successfully as in the pure pancreatic form. Group I I I .— For the normal life and functioning of each cell in the body, a constant environment is necessary; name ly, the blood, the composition and re action of which is regulated w ithin very narrow limits. In health, this so-called acid base equilibrium is perennially main tained, despite the constant introduction of acids and bases in our food, and their formation w ithin the body. W e shall soon cease to cherish or tolerate the daily
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phrase, “ acidity of the blood,” once we remember that blood as acid as distilled w ater, or as alkaline as ordinary tap water, is incompatible w ith life. W hen, for any reason, an impairment in this acid base mechanism occurs, and the transfer of carbon dioxid from the tissues to the breath is interfered with, acidosis, which may be acute or chronic, super venes. I t occurs almost always secondarily to some other disease, particularly dia betes, in some forms of nephritis char acterized by phosphorus retention, con ditions causing dehydration of the body (cholera, severe diarrhea), the excessive intake of certain salts and in many types of toxemia. T h e reverse condition, spoken of as alkalosis, ensues when there is an excessive loss of acid from the body or an abnormally large intake of alkali, and, once developed, may closely simulate the condition known as tetany. Both acidosis and alkalosis, suspected clinically, can be quantitatively rec ognized by the employment of a variety of blood chemical studies, the easiest of which is the determination of the hydrogen-ion concentration. Group I V .— Blood chemistry methods dealing w ith altered fat metabolism need but a w ord in passing. T h e ir develop ment is not w ell established, and though blood cholesterin studies are of sugges tive value in certain rare forms of ne phritis, jaundice and the primary ane mias, they have as yet no practical clin ical application.
BLOOD CALCIUM STUDIES OR CALCIUM METABOLISM Because of your chairm an’s emphasis on the subject as w ell as the fact that it adm ittedly is of extreme importance in the whole field of dentistry, I shall devote more time to the discussion of calcium metabolism than to all the others,
and shall pass over entirely any reference to magnesium and potassium in the blood, for, in a word, we know little of prac tical value about them, in a blood chem istry sense. As far as the phosphates go, retention is known to occur in inter stitial nephritis; whereas, a reduction is very commonly associated with active rickets, and is at least one factor in the improper calcification of bone in that disease. T h e importance of calcium has long been recognized, and as far back as 1647 Ambrose Paré, a famous surgeon, sug gested a relationship between absence or a deficiency of calcium and pronounced m alnutrition. I t was not until 1921 that K ram er and T isdall perfected a micro chemical method for quantitative blood calcium analysis, and, w ith but minor modifications, this is still the best method today. From an enormous literature, ably re viewed in 1928 by Stew art and Percival in Physiological Review s, one can cull briefly the following significant facts, and these in turn suggest certain practical applications : 1. Calcium salts, no m atter in w hat form, are absorbed w ith manifest diffi culty and by far most of the ingested calcium is lost in the feces. T h e absorp tion rate, or calcium availability, seems definitely related to protein intake, the sugar content of the diet and the solubil ity of calcium in hydrochloric acid ; whereas, any excess of phosphates lessens calcium availability to a high degree and invariably leads to defective bone forma tion. Finally, it seems conclusively set tled th at an unsatisfactory relation be tween three dietary factors — calcium, phosphorus and vitamin ,D — leads to pathologic bony changes, mainly, it is thought, because vitamin D seems both
M iller— Blood Chemistry and Periodontal Problems to increase calcium retention and at the same time either to stim ulate hydrochloric acid secretion in the stomach or inhibit the flow of alkaline intestinal juices. 2. T h e most obvious function of cal cium is related to the process of bone formation, but much inform ation is still lacking as to how the transference of calcium from the blood to the growing bone is effected. Calcium is requisite to the norm al functioning of all cells and is a factor necessary in preserving the cor rect balance of inorganic ions, spoken of as isotonicity. Calcium salts, when defi cient, seem to bear a relation to certain forms of diarrhea, and, conversely, when in excess, to obstinate constipation. Hence, the view that calcium exerts some regu lating influence on intestinal peristalsis. T here is much evidence that calcium plays no small role in m aintaining the proper hydrogen-ion concentration of the blood. T h e long recognized function of calcium w ith reference to the coagulation of the blood hardly requires more than a mere statement of the fact. Calcium is essen tial for muscular contractility and as well for the conductivity and irritability of nervous tissue. 3. As far as methods go, it appears that quantitative estimations of the serum calcium give the best results, and the ac cepted normal values range from 9 to 12 mg. per hundred cubic centimeters. T here is apparently little difference in the serum content of calcium in infants, adolescents and adults. T h e only definite physiologic fall in serum calcium occurs during preg nancy, and is followed by a rise to normal after delivery. 4. Finally, the factors which control the calcium content of the blood are not definitely and certainly known. By reason of the bony changes in acromegaly and eunuchism, the loss of calcium in hyper thyroidism and diabetes and other en
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docrine disturbances, one after another of the various glands of internal secretion has been assigned the controlling influ ence over calcium metabolism. A ll the evidence is inconclusive, except as the parathyroid glands are concerned. C lini cal and experimental studies w arrant the statement that whatever other functions they may possess, the parathyroid glands exercise a definite control over the con centration of calcium in the blood, and particularly in maintaining the internal calcium equilibrium. 5. T h e constancy of blood serum cal cium suggests that a delicate controlling mechanism must exist which balances ab sorption, deposition, utilization and elimi nation. T h ere is growing evidence, too, to suggest that the accepted figures for total serum calcium do not truthfully portray the amount of so-called available calcium, and until simple and accurate measures are, devised for estimating the available calcium in the blood, its ther apeutic uses cannot be placed upon a strictly satisfactory basis. Thus, in para thyroid tetany, primary or postoperative, the use of parathyroid extract seems more logical and is more effective than calcium administration ; and in rickets, the use of sunshine and vitamin D will do much more good than the use of calcium itself. Calcium is, and has been for years, given in many hemorrhagic conditions, in asthma, hayfever, urticaria and other con ditions in which a calcium deficiency, as sumed, is not borne out by consistent blood chemistry findings.
BLOOD CHEM ISTRY’S VALUE TO PERIODONTISTS Even in such an incomplete and cursory résumé of blood chemistry and its value to medicine, the query might aptly be made : In w hat possible way or ways can such knowledge be turned to the advan
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tage of the members of this special branch of the practice of dentistry? T h e answer, as I see it, is both easy and involved; but before attem pting an answer, let me di gress for the moment, and go into a field where the display of my dental ignorance may be pitiful. By derivation, your chosen profession is th at branch of dentistry concerned w ith the tissues around the teeth, and, in p ar ticular, those processes, of w hatever nature, which produce a breaking down of the periodontal structures. Such proc esses are broadly covered by the term periodontoclasia. Y our interests center not so much in the problems of dental caries, root canal fillings, periapical ab scesses and the like, though I suspect th at they enter much into your problems, as in those conditions which injure the gin givae, occlusive anomalies and their resul tan t mechanical effects, in the production of soft tissue injuries, food packs and their chemical influences, infections in their relation to soft parts and the teeth as well, and, finally, in the cementum surfaces and the various anomalies and deposits encountered in the practice of apoxesis. Perhaps this does not cover all your special interests, but to me it seems quite enough, and your pardon is craved if I have left you too small a field to in vade. Now, as nearly as I can see it, perio dontoclasia, in general, resolves itself into one of tw o main groups: G roup I, in which either intrinsic inherited or consti tutional factors, or acquired, extrinsic noninheritable factors exert their m align influences mainly through mechanical ir ritation, to which the secondary factors of infection may subsequently be added. These are prim ary and essentially local conditions. G roup II, the so-called sec ondary group, which in many instances overlaps the first, although more often
the local conditions are expressive of sys temic disorder or disease in quite the same sense th at D r. W ilm er regards the eye as an indicator of trouble elsewhere for which the eye itself is not the cause but of which it is the victim. G ra n t for the m oment the essential soundness of such a conception by a mere medical layman: it would seem, then, as far as blood chem istry is concerned, th at it has little if any value in the recognition and treatm ent of conditions in the first group, w ith perhaps one rather w ildly speculative exception. Recent and ever-increasing anthropo m etric studies serve to show more and more “type forms” or “habitus,” each manifesting certain apparent disease ten dencies. Already, we recognize clinically individuals of the asthenic, pyknotic, arthritic, neuropathic and digestive habitus, as well as those who show the thymicolymphatic constitution, and other endocrine imbalance, associated with which there are so m any dental anomalies, enamel hypoplasia and dentition defects. I t is conceivable th at biochemical studies applied in these groups, and particularly a t an early age in life, might shed some light on how constitutional heritage may be altered. T h e opportunity in this would come mostly through the teamwork and study of periodontists and pediatricians; for theirs, probably, would be the op portunity to see the earliest evidences of such abnormal states. W hen one comes to the second group of periodontoclasia cases, the situation is theoretically very different, yet practi cally, in my opinion, quite the same. T his is but another way of saying th at blood chemistry, as it is now understood, holds nothing of daily routine value to the periodontal specialist, except in an indi rect sense. L et me elaborate this by point ing out some of the dangers.
M iller— Blood Chemistry and Periodontal Problems You have all witnessed the destructive effects th at the so-called focal infection theory has left in its wake. Fortunately, the problem, though still not solved, is bein^ viewed and dealt w ith in a more rational way. In an article in the D ental Cosmos in 1921, I called attention to some of the utterly absurd tests and ridiculous interpretations thereof which overzealous dentists were employing as the final criteria of the need, or other wise, of extractions. T h e same menace confronts the medical profession today, in a period when tests, form ulas and ma chines of precision, valuable as they are, are lessening the power to observe and provoking atrophy of logical deductive thinking. T o interpret at all blood chem ical findings is not possible w ithout close clinical correlation: wide variations occur unless the factors of diet, fluid balance, etc., are carefully considered; and last, but by no means least, obvious pathologic deviations are by no means always sig nificant in the w ay that one is taught to believe. U seful as they are, I am con vinced that they have, as yet, value only when properly employed in selected cases. T h is opinion is a result of analyzing thou sands of blood chemistry studies routinely applied in both w ard and private practice. Applying this certain personal convic tion to your profession, I should feel that your knowledge of blood chemistry would better be translated into the early recog nition of periodontal diseases not appar ently falling into G roup I, and hence probably due to some systemic disorder which needs ferreting out by medical aid. I t would be interesting teamplay for the periodontist and internist to note, for example, any relation between local oral disease, in terms of advance or re gression, in a chronic nephritic, for in stance, and the rise or fall of retained nitrogenous substances; or a series of dia
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betics in relation to their freedom from glycosuria or consistently elevated blood sugar concentrations; a group of asthenic neuropaths in relation to their pro nounced pyorrheal tendencies and subnor mal blood chemical findings, and the alterations in .each during periods of in duced normal nutrition, w ith saner ways of thinking. M any other fascinating problems might be mentioned, but these w ill serve the point that I wish to stress once ag ain: leave blood chemistry alone for the present, but recognize more quickly as dentists your need for help from an internist, just as we are growing ever more alert to the hostility of perio dontal disease to health alone, and its sinister effects on established systemic disease. In w hat way periodontal disease affects blood chemical findings, I do not know ; nor have I been able to find any literature dealing w ith this phase of the question. If a large percentage of cases of perio dontoclasia are local secondary manifesta tions of such diseases as nephritis, dia betes, abnormal blood conditions and dis orders of endocrine and autonomic nervous system origin, abnormalities found in a blood chemical sense cannot logically be ascribed to the oral conditions at all. Further, to believe that many such systemic conditions have their etiology in the mouth, is, I take it, bad judgm ent; for an accurate knowledge of the facts w arrants no such valuation of the find ings to date. As far as I can see, periodon tal disease, especially the suppuratiye form, for which, as yet no specific vege table or protozoan organisms have been proved directly responsible, can influence blood chemical findings only by exerting a further malign influence on the primary systemic affection. Painstaking periodon tal-medical correlation alone w ill affirm or refute this conception.
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CONCLUSIONS studies w ith the clinical manifestations of T h e principles of preventive periodon disease. M any purely laboratory re tia are, in a large measure, educational in searches have failed for w ant of clinical character, demanding th at the details of direction. I t is helpful not to forget that correct oral hygiene, proper and sufficient some of the most notable achievements in gingival stim ulation and the adequate medicine, and in dentistry, too, I suspect, application of w ell established dietetic have been accomplished by men whose laws be taught to young and old, w ith an lives were spent far from laboratories or inspired insistency. T h e elimination of seats of learning. L et me mention four: all irritating oral conditions is the me Harvey was an obscure physician, strug chanical and technical side of your prob gling to make a living, when he first lem. A n ever broadening conception of began to think of the circulation of the the reciprocal relations between systemic blood. Jenner, among the worries of a diseases and periodontal lesions is the country practice, discovered vaccination inspirational side, which everyone needs against smallpox. Koch was a local phy in his daily work. sician when he began his work on tuber culosis. M ackenzie was a busy general I t is hoped that the meager glimpse practitioner in England, when he laid the into the realm of chemistry and its reve lations in a medical sense w ill serve as a foundations for his epoch-making work genuine stimulus for the w ork which lies on the heart. H istory and experience w arrant the ahead. I do not mean in any sense to .leave the impression that the advances in assertion th at most progress is assured blood chemistry have not been valuable when clinician and laboratory worker or practical: they have. Y et their value, pull together, each recognizing the diffi in the last analysis, is more directional culties faced by the other, and equally than definite, more confirmative than determined that those difficulties shall be conclusive, and more suggestive than solved as a result of their m utual efforts. final. T h a t deviations from the normal, In clinical medicine, the true value of in a chemical sense, concern you as well laboratory methods has been enhanced as internists, there can be no d o u b t; but rather than lessened by the frank recog refinements, both in methods and inter nition of their limitations, and this has pretation, need to be made before the been particularly true of many of the finer variations can be given their proper blood chemistry tests. and practical valuation. I t is not too Progress in any altruistic profession is, much to hope or believe that, in the not by the very nature of things, inevitable. distant future, such advances w ill be ac I t is most consistent when plasticity of complished. thought regularly surpasses the bigotry M uch of the w ork done, and to be of narrowmindedness. I t is stimulated in done, is so technical and, in many in an atmosphere of appreciation and by stances, so remote in its relation to frank, constructive criticism. I t is fostered practical medicine, th a t the busy practi when the ideas or whims of the individual tioner and dentist cannot keep pace w ith are kept constantly subservient to the it all, if, indeed, he could grasp w hat it weight of judiciously proven opinion. is all about. B ut bear in mind th at the W ith such a point of view, dentistry can true aim of medical and dental research confidently expect increasing aid from is , to reconcile the results of laboratory medicine, and medicine from dentistry,
M ille r— Blood Chemistry and Periodontal Problems as we eventually learn more exactly just w hat the chemistry of health and disease really means.
DISCUSSION
Justin D. Towner, M emphis, Tenit.:
The presen t theory re g a rd in g the etiology of p erio dontoclasia is to w a rd the alkalosis index, and I should like to ask D r. M ille r w h at blood research could be m ade to establish the tru th of this a p p are n t tendency. W e know th a t the pocket-form ing type of p erio dontoclasia is directly opposed to the condi tions in w hich w e find caries. In the f o r m er, reactions a re a lk a lin e ; in the latter, acid, and the one w hich assum es the ascend ency m ore or less com pletely controls the other. T h is is suggestive only of fu rth e r research, w hich has ju st begun to open up an avenue w hich we all m ay enter, and to w hich som ething of definite value m ay be contributed. Rudolph Kronfeld, Chicago, III.: W e often found th a t teeth w hich w ere lost by early loosening show ed v ery h a rd and w ell-calci fied crow ns and yellow ish enam el and w ere highly re sistan t to caries. P oorly calcified teeth w ith a bluish w hite enam el and a -g re a t susceptibility to caries seldom are lost by periodontoclasia, and show a fa v o ra b le rate of eruption. So it seems th a t there is a cer ta in antagonism betw een periodontoclasia a n d caries.
A rthur II. M erritt, N ew York City: D r. M ille r has answ ered m any questions th a t h a v e a g ita te d the m inds of m any of us fo r se v e ra l y e ars. A ll of us know th a t there a re cases arisin g in daily practice w hich seem to have a systemic background. In a case w hich recently cam e u n d e r m y observation, in a w om an, aged 25, the thirtytw o teeth w ere so seriously involved in bone destruction and periodontal d isturbance th a t one of the best o ral surgeons in N ew Y ork ad vocated th e ir complete rem oval. She ap p e are d to be in excellent h e alth except th a t she, in an effort to m ain tain h e r boyish fig ure, w as p erh ap s u ndernourished. I de cided th a t th ere m ust be some explanation of this case outside the mouth. I asked the fam ily physician to m ake a carefu l physical exam ination. H e reported on the blood ex am in atio n and urinalysis as w ell as m aking the re g u la r physical exam ination. H e w as unable to find any explanation fo r the condi
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tion in the m outh. W ith the a p p ro v al of the patient, a nother physician w as chosen who w as know n to be exceedingly careful in m ak ing, and p a rticu la rly w ell qualified to m ake, such exam inations. H e reported th a t he could find nothing abnorm al, and yet her m outh w as so seriously involved th a t one of the best o ral consultants recom m ended the com plete extraction of h e r teeth to the fam ily physician w ho had taken him into consulta tion. I rem em ber a fe w y ears ago a n article (w ritte n by a m an in E n g la n d ) w hich w as com m ented on by the editor of Dental Cosmos, saying th a t dental caries w as the result of calcium deficiency and periodontoclasia w ith calcium sa tu ratio n . I should like to h ear from D r. M iller in re g a rd to this. M y own clinical observation has not confirm ed th a t statem ent.
John Oppie McCall, N ew York City: A t the D ental Clinic of N ew Y ork U niversity, College of D entistry, about fo u r y ears ago, a child of 11 y ears w as bro u g h t to my attention in the periodontoclasia clinic w ho h a d lost several of her perm an en t teeth, one or tw o incisors and also the first p erm anent m olars in the low er ja w . She h a d quite high re sistance to dental caries, and the condition of the m outh m ade it e vident w hy she had lost the teeth th a t w ere gone. She h a d as ex trem e a condition of periodontal destruction as I am sure w as to be found in D r. M e rritt’s case. W h ile it w as not believed th a t anything could be done fo r her, w e did try to help her, and finally I took her to m y ow n office, though she w as a clinic patient, to see if I could help h e r better there th an in the college clinic; but it w as all to no a v ail. In less th an tw o years, she h a d lost all her perm anent teeth and she is w e arin g fu ll upper and low er dentures today. T h a t w as before the age of 13, and the condition w a s entirely typical, as f a r as any clinical exam ination could ex plain, of perio d o n tal disease of the su p p u ra tive type w ith w hich w e are all fa m ilia r. H e r history w a s not conclusive in any re spect. H e r p a ren ts w ere ig n o ran t people w ho h a d difficulty in speaking and u n d e r sta n d in g E nglish a n d so the tak in g of the history w as v e ry unsatisfactory, but I am quite sure th a t she h a d no systemic d iso rd e r th a t w as a n ything out of the o rdinary. It w as quite probable th a t she suffered fro m rickets in a m ild degree in early childhood, but so h a v e m any o ther children w hom w e see w ho do not h ave such a disturbance in
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the m outh. T h is is the m ost serious case of its kind th a t I have seen, but I recall a boy of 16 who w as b ro u g h t to the clinic la te r w ith essentially the sam e condition. T h e re is no question th a t we h ave a systemic factor, but, as in the case of D r. M e rritt’s patient, exam ination (including a blood exam ination, but I think not blood calcium determ in atio n ) by physicians w ho w ere, I believe, com petent, failed to show anything w hich w ould give us any help eith er in a diagnostic w ay o r in the w a y of pointing to w a rd possible th e ra p e u tic aid. T h e subject of blood chem istry, of course, is n a tu ra lly associated in our m inds w ith disturbances of this kind because not only do w e see cases such as the ones th a t D r. M e rritt and I have cited, but w e also see cases w hich show exactly opposite conditions. It is quite a common th in g fo r us to see patients w ho have neglected th e ir mouths, who h ave perhaps suffered from serious dis eases, including diabetes, fo r instance, and w ho show little, if any, d isturbance of the periodontal tissues. T ra u m a tic occlusion does not in v ariab ly m ean a b reak in g dow n of the periodontal tissues in the o rd in a ry way, and it seems th a t there m ust be som e thing, not m erely a systemic condition, but som ething w hich could be determ ined in the blood by w ay of explaining these anom alous things. D r. M ille r has been g iv in g us a d vanced inform ation along this line. I realize th at the problem is a difficult one, and I hope th a t he has become sufficiently interested in the subject th a t he w ill continue to study the subject of blood chem istry from the dental, and p a rtic u la rly from the periodontal standpoint, and come into closer relationship w ith d e n tists who m ay be able to help him clinically. I hope th a t he m ay soon give us the in fo rm a tion w hich we a re all looking fo r so eagerly.
Isador H irschfeld, N ew York City: A propos D r. M ille r’s question and suggestions, it seems th a t observations m ay help us in checking up these cases of periodontoclasia w ith systemic factors. I have in m ind a num ber of instances in w hich I have positive proof th a t gum recession w as, in certain cases, gen eralized and th a t the recession had ceased a t least a num ber of y ears p rio r to the tim e w hen I saw the patient, w ithout any local trea tm e n t or any special attention locally. W e have ano ther point to consider, and th a t is, these cases of periodontoclasia, called lately in E urope “the h orizontal type of p y o rrh ea ,” seem to be essentially not a
type of distrib u ted pyorrheal infection, but ra th e r a secondary infection, you m ight say, in addition to the uniform ly h o rizo n tal reces sion of the periodontal tissues. It is tru e we h ave tw o fa cto rs to contend w ith : the loss of the periodontal tissues w ith o u t local in fection and the b re ak in g dow n of tissues as a result of p eriodontal infection. I f we alread y h ave a pyorrheal condition superim posed on this g en eralized destruction of the periodon tium , w e a re not in a position to know through d eterm inations by m edical men at th a t tim e w h eth er the original systemic cause of this g en eralized recession is still present. In other w ords, if it is tru e th a t the original system ic etiologic factors h a v e a lre ad y been rem oved fo r some reason or other, p erhaps through the endocrine system, and w e have an infection present, are we in a position to know w h eth er the condition w e find at the present tim e is caused by system ic o r local causes ? H. J. Leonard, N ew York City: W e hope to in au g u ra te in Colum bia U niversity a series of chem ical studies along th is line, and it w ill be helpful to us if D r. M ille r w ill give us his idea as to w h a t p a rtic u la r factors in the blood one m ight analyze first in a t tem pting to determ ine the pro b ab le changes th a t have gone on, and th a t have delayed recovery from periodontoclasia. If we take as our hypothesis th a t there is some blood chem ical change w hich is the cause of p erio dontoclasia, w hat, in his opinion, w ould be the first th in g to look for alo n g th a t line? Celia Rich, Nashville, Tenn.: Could there be a serious endocrine d isturbance and the blood still be n orm al?
Dr. M iller (closing): D r. L eonard asked me previously as to how one w ould sta rt blood studies on the theory th a t there must be som ething w rong in the blood th a t in some w ay low ers local resistance and perm its condi tions to d e v elo p ; i. e., caries a n d periodonto clasia. T h a t im m ediately b rin g s up the whole subject of im m unity. W h a t is im m unity? Is it a chem ical process? It is so thought of by many, yes, but in w h a t phase of chem istry does it fa ll? Is it colloidal chem istry or is it lipoidal chem istry, or w h a tn o t? I t has not been settled. T h e re has been in recent years a g re a t deal w hich has suggested th a t im m unity is bound up v ery closely w ith the p ro p er blood ionization of inorganic sub stances m ore th an organic. T h a t a g ain is a hypothesis. I t is certain ly established th a t
M ille r— Blood Chemistry and Periodontal Problems the am ount of ionized calcium in*the blood, w hich is essentially w h a t one determ ines w h en he m akes a blood calcium study, is sus ceptible of not v e ry w ide v a ria tio n s from the accepted norm al w ithout reciprocal d is tu rb an c es in the acid-base equilibrium . W h a t relation th a t m ay b e ar to the question asked about the alkalosis index, I do not know offhand, but it probably w ould be slight, a n d the basis th a t it is so w ell established th a t the hydrogen-ion concentration of the blood can sw ing e v er so slightly, as determ ined by the m ost accurate electrical m ethods of precision, before w e get into the acidosis or alkalosis complex, th a t one w ould h a rd ly expect to find v ery conclusive evidence in term s of m outh conditions w hen the sw ing is in such extrem ely n a rro w m arg in s. As f a r as h ealth is concerned, we feel th a t th a t is so, re g ard less of dental conditions. P e rh a p s there should be refinem ent along the lines of hydrogen-ion studies and p a rtic u la rly m ore studies w ith reference to the proven relation, and w h a t the relationships th a t exist betw een a v ailab le calcium , a v ailab le phosphorus, and vitam in D re ally m ean. T h ere p e rh ap s w ould lie a m ore fru itfu l field fo r chem ical re search ra th e r th a n in correlated studies of clinical findings and blood chem istry m ethods. A s f a r as the definite show ing in the la b o ra tory goes, th a t in caries th ere is a calcium defi ciency and in periodontal disease an excess is not borne out by any studies th a t I know of w hich are satisfacto rily controlled w ith re f erence to dietetic factors, etc. T h e re ag ain is a fru itfu l field fo r accurate research, but you see th a t th ere m ust be c o rre latio n as re g a rd s not only w h a t you find in the m outh and w h a t you find in the lab o rato ry , but also w h a t the patien t takes into his m outh, in term s of food content, org an ic content, w a te r content, etc. As they are all involved in the thoroughly interm ingled process, you w ill nev er get resu lts except by team w ork of th at sort. T h e present m ethods em ployed in blood
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chem istry, as elaborated in the p ast eight or ten years, have reached such a stage th a t dis crepancies betw een the findings of tw o ob serv ers on the sam e blood should be m inim um unless one observer is color-blind. If he is color-blind, he is p a rtic u la rly u n fo rtu n ate in this w ork, because p ractically all the d e te r m inations are colorom etric. T h e results should check and do check, as a m atter of fact, betw een different lab o rato ries w ithin such sm all fractio n s of m illigram s th a t the d if ference m eans nothing. T h e last question asked is, “C an there be m ark ed endocrine d is turbances w ithout gross blood chem istry a lte r atio n ? Probably, yes. F or exam ple, the d e v i ations from norm al in a la rg e group of cases of pronounced hyperthyroidism are not p a r ticularly significant or strictly diagnostic, nor are they a lte re d by subsequent rem oval of the hy p erp lastic thyroid. One certain ly sees finer shades of endocrine disturbances as revealed by constitutional defects or stigm as w hich do not show enough in the w a y of deviation from the norm al to m ake those findings cap a ble as yet of accurate in terp retatio n . T h e re is an o th er fru itfu l field fo r someone to w ork in, to determ ine w h a t endocrines a re. T hey a re ju st as vague as the vitam ins, though w e know they are im portant. W e now know m uch about epinephrin a n d about insulin, and w e are beginning to le a rn th a t there is a p p a ren tly a close relationship betw een d ieta ry deficiencies and abnorm al chem ical findings in pernicious anem ia. W e do not know how to determ ine in the blood w h eth er a person has too m uch of the a n te rio r lobe or too little of the posterior lobe in the p itu itary g la n d ; and if the lobe is too larg e or too sm all, w h a t we can do about it. W h e th e r blood chem istry is capable of detecting finer shades of a lteratio n s in norm al o r abnorm al constituents of g la n d u la r origin m ight throw fu rth e r light either on dental problem s p rim a rily or on th e ir relation to alterations in in o rg an ic chem istry. I t is w o rth thinking about.