ADVANCES IN DIAGNOSIS ANDDETECTION OF ORAL DISEASES

BJ. BAUM1, CJ. BURSTONE2, R. DUBNER1, P. GOLDHABER3, M.J. LEVINE4,WJ. LOESCHE5, and V. TERRANOVA4

"'National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland; 2Universityof Connecticut, School of Dental Medicine, Farmington, Connecticut; 3Harvard University School of

Dental Medicine, Boston, Massachusetts; 4SUNY at Buffalo, School of Dentistry, Buffalo, New York;and 5University of Michigan, School of Dentistry, Ann Arbor, Michigan

Adv Dent Res 3(1):7-13, May, 1989

ABSTRACT

Medicine, particularly with respect to diagnostic decision-making, has seen remarkable advances inthe last ten years. The art of diagnosis has become much more of a science. Basic science advanceshave moved from the laboratory into the hospital and radically changed the way a medical diagnosis is arrivedat or confirmed. Dentistry, especially oral diagnosis, as yet has not been a significant part of this general medicaladvance. However, several examples demonstrate that this situation is starting to change. Oral conditions arebeginning to be evaluated with greater precision and sophistication. This report reviews some recent advancesin oral diagnostic research and suggests where they will carry dentistry over the next 25 years.

INTRODUCTION

Medicine, particularly with respect to diagnosticdecision-making, has seen truly remarkable advancesin the last ten years. The art of diagnosis has becomemuch more of a science. Technological advances frombiochemistry, immunology, physics, etc., have movedfrom their laboratories into the hospital and com-bined to radically change the way a medical diagnosisis arrived at or confirmed.

Dentistry, especially oral diagnosis, as yet has notbeen a significant part of this general medical ad-vance. But there are many examples, some of whichare cited in the sections below, which demonstratethat this is beginning to change. Oral conditions arebeginning to be evaluated with considerably greatersophistication. It is the role of this paper to suggestwhere these advances in oral diagnostic research andapplication will carry the diagnostic side of theprofession over the next 25 years.

At the outset, it is worth stating that the authorsrecognize the precarious task of predicting the future,

A report of the AADR ad hoc Committee on New Frontiers in OralHealth Research

Please address all correspondence to Dr. Bruce J. Baum, ClinicalInvestigations and Patient Care Branch, National Institute of Den-tal Research, National Institutes of Health, Building 10, Room 1A-05, Bethesda, MD 20892.

particularly as it relates to biomedical science. Forexample, six years ago it would have been impossibleto predict the profound and pervasive impact thatAIDS would have on the biomedical research com-munity. Yet this "epidemic" has markedly influencedthe directions and nature of biologic research in 1988.Obviously, our level of confidence decreases with time,but we generally have accepted the notion that oraldiagnosis as a discipline will change dramatically overthe time frame considered. This change likely willreflect a much broader level of stomatological concernby future dentists than exists at present. In fact, asdiagnostic skills and methodologies become more so-phisticated, we believe that much professional oraldiagnosis will be performed outside of the traditionaldental office setting, occurring rather in a hospital-type environment, and indeed being performed byan expanded specialty of more intensively trained oraldiagnosticians. Just as dental research has contrib-uted, and will continue to contribute, toward shiftsin the nature of dental practice, research advances inoral diagnosis will contribute not only to changes inpatient evaluation and management, but also to shift-ing emphases in dental education. Future studentswill require greatly expanded training in many basicand clinical medical science disciplines in order toutilize the anticipated diagnostic advances. Indeed,for the transfer to the clinical profession of the "ad-vances" described in this paper, significant changes

BAUM et al. Adv Dent Res May 1989

in dental education and clinical practice behavior willhave to occur.

For purposes here, we have grouped anticipatedadvances into short-term (~5 years), intermediate (-10years), and long-term (-25 years) categories. We hopethese provide a convenient time-line for the reader,but we emphasize that the time course is most spec-ulative. Also, the number of predictions decreaseswith increasing time, reflecting what we feel is a greaterconfidence in our abilities to predict shorter-termtrends.

SHORT-TERM ADVANCES (-5 YEARS)

Research advances here focus on the transfer ofmethods and ideas, which are currently available inother biomedical areas, to oral diagnostic problems.In general, these examples were not hard to choose;in fact, there were many possibilities. However, alltopics selected have by now brought great benefit toseveral areas of clinical medical science and, impor-tantly, these topics have shown themselves to beclearly applicable to problems of the oral cavity. It isimportant to emphasize that these are diagnostic toolswhich are capable of being used now, the limitationbeing only problems in transfer to, or acceptance by,the profession.

(1) Radionuclides in the Diagnosisof Periodontal Disease

Nuclear medicine as a medical specialty has grownenormously in the last dozen or so years. Manyradionuclides are in common clinical diagnostic usage,with more sophisticated probes being developed atan increasingly more rapid pace. The general prin-ciple involved is quite simple: The diagnostician ad-ministers a radiolabeled compound which showsparticular affinity for a tissue and which reflectssomething about the metabolic or functional state ofthe tissue. Thereafter, some type of detector is usedto quantitate the relative uptake of tracer in the tissueof interest. An excellent and common example ofradionuclide diagnostic testing is the use of 131I or 125Iin evaluations of thyroid gland metabolic status.

Recently, workers at the Harvard School of DentalMedicine have suggested the utilization of a radio-nuclide, technetium 99m-tin-diphosphonate (99mTc-Sn-MDP), as an indicator of active alveolar bone lossin the diagnosis of periodontal disease activity (Jeff-coat et al., 1985). Commonly used methods of de-tecting periodontal diseases require repeatedmeasurements over considerable time to assess rateof attachment loss {i.e., periodontal probing). Simi-larly, radiographic analyses show only post hoc de-struction of alveolar bone. Presently, there isconsiderable effort focused on methods of diagnosingactive periodontal disease (Fine and Mandel, 1986).Jeffcoat and her colleagues recognized that 99mTc-Sn-MDP was in routine medical use to detect bony

metastases, stress fractures, infections, etc., prior tothe presence of radiographic evidence. Accordingly,they reasoned that uptake of this bone-seeking radio-nuclide might provide a diagnostic mechanism to as-sess periodontal status in a single examination. Theirresults, found in the report cited above, and sum-marized in Fig. 1, offer strong support for the utilityof 99mTc-Sn-MDP in the diagnosis of periodontal dis-ease.

The possibilities for application of nuclear medicaltechnology to oral problems seem to be limitless, re-quiring only imagination, a good knowledge of tissuephysiology, and a cooperative chemist who can de-sign a radiolabeled ligand with appropriate targetspecificities. There are several radionuclides alreadyin general medical use which should soon find theirway into oral diagnosis another good example being99mTcO4~ for evaluating salivary gland dysfunction.We expect there will be considerable investigative ef-fort in this area over the next 5-10 years, resulting ina vastly more sophisticated armamentarium for oraldiagnosticians.

(2) Direct Imaging MethodsAnother major tool in medical diagnosis which has

yet to find its way into common oral diagnosis is theutilization of advanced direct imaging methods. Theclinical specialty of radiology has been expandedwidely due to the rapid development and applicationof a new generation of imaging devices. It would beeasy to devote this entire short-term advances section

Fig. 1 Schematic representation of detection of active periodontaldisease with 99m-tin-diphosphonate. A. Normal alveolar bone ap-pearance observed with little bone-seeking radiopharmaceuticaluptake (black flecks) associated with the bone about the teeth. B.Representation of area with evidence of past periodontal disease.There is horizontal bone loss about the teeth but no radiophar-maceutical uptake, indicating no active disease. C. Area similar tothat shown in B, but note that the middle tooth shows an adjacentarea of bone which has taken up large amounts of the 99m-tin-diphosphonate tracer, indicating an area of active bone loss. Thisarea may be detected by means of a small gamma emission detectorplaced on the patient's gingiva.

Vol. 3 No. 1 ADVANCES IN ORAL DIAGNOSIS

to these technologies. Indeed, as further indicatedbelow, we expect later advances in diagnosis to beparticularly directed at more sophisticated physicalscience probes.

As with radionuclides, we are best able to showthe value of such advanced imaging methods to oraldiagnosis through an example of recent applications.Considerable investigative effort, with an oral prob-lem area, has come from the use of ultrasound todetect swallowing disorders (dysphagia) of oral etiol-ogy. In principle, ultrasonography functions similarlyto sonar on a submarine i.e., transmitting a soundwave and, by detecting reflections of sound off ob-jects in its path, "visualizing" structures. In this case,ultrasound waves are passed through tissues, andreflections of these waves are converted to an imageby appropriate hardware. Ultrasound is an excellentmeans of visualizing soft tissues in active function{e.g., echocardiography).

Workers at the National Institutes of Health haveutilized this technology to evaluate and characterizeswallowing disorders in the oropharyngeal region(Shawker et al., 1983). The dorsum of the tongue:airinterface offers virtually perfect impedance to an ul-trasound wave, resulting in a sharp visualization ofthe tongue during function (Fig. 2). Swallows usingendogenous oral secretions ("dry" swallows) or thosewith a bolus of fluid present {e.g., water; "wet" swal-lows) can be followed in real time, recorded on video

A. B.

Fig. 2 Schematic diagram of midline sagittal views of the tongueand floor of the mouth as seen on ultrasound scan. The area en-compassed by the scan is indicated by the somewhat truncated"V-shape" (-80 sector). The ultrasound transducer is positionedunder the chin. Dashed lines indicate structures not seen in scanand are placed here only for reference. A. The tongue at rest. Thereis a small air space between the tongue and palate. B. A waterbolus (5 mL) has been placed in the mouth and is held anteriorly,anticipating a command to swallow. The air space above the pos-terior tongue is no longer visible. Abbreviations used are T, tonguetip; H, hyoid bone; E, epiglottis. Swallow analysis can be per-formed with only endogenous secretions present (i.e., saliva, asdepicted in A, termed "dry swallow") or with an exogenous fluidbolus (/.., water, depicted in B, termed "wet swallow"). Tonguemovement is recorded on videotape at a rate of 30 frames/sec andcan be analyzed by stop-frame analysis.

tape, and analyzed for time kinetics, pattern of mo-tion, irregular gestures, etc. This is a non-invasive,readily repeatable technique which allows for imag-ing of oral functions and tissues heretofore impossi-ble with conventional radiologic tools. In actuality,little study of oropharyngeal dysphagia has occurred,yet it appears to be a reasonably common entity(Hughes et al, 1987). For example, patients with hy-pofunctional salivary glands, regardless of etiology{e.g., radiation, autoimmune disease, pharmacologi-cal), routinely display, and complain of, swallowingdifficulty. Also, many patients, post-treatment for headand neck tumors, may suffer from a dysphagia oforopharyngeal etiology.

There are other imaging tools (computer-assistedtomographic analysis; magnetic resonance) which arein increasingly more common use in medical diag-nosis and which have also been applied to oral prob-lems, e.g., temporomandibular joint disorders (Skalericet al., 1987). They have potentially broad applicationsto oral tissues. We certainly expect this general fieldto contribute considerably to advances in oral diag-nosis over the next 5-10 years.

(3) Humoral Markers for Pain and Tissue InjuryRecent advances in the understanding of the bio-

chemistry and pharmacology of pain pathways haveled to the use of chemical intermediates as markersof both pain and tissue injury. Currently used meth-ods to analyze these markers in conjunction withmanagement decisions for pain patients are an ex-cellent example of how humoral analyses may be em-ployed or adapted to problems in oral diagnosis. Forinstance, pain produces physiological responses in-volving activation of the hypothalamic-pituitary-ad-renal axis and the consequent secretion ofneurohumoral agents from these tissues. Thus, cor-ticotropin-releasing factor is released from the hy-pothalamus; adrenocorticotrophic hormone, beta-endorphin, and beta-lipotropin are released from thepituitary; and the adrenal medulla releases mono-amines and opiate peptides. All of these humoralagents can be easily measured via standard immu-nochemical methods (radioimmunoassay) and cor-related with behavioral measures of pain and stress(Fig. 3). Recent studies have shown that opiate ago-nists given during surgery suppress beta-endorphinrelease and reduce pain, while opiate antagonistsstimulate the release of beta-endorphins and are as-sociated with increased pain (Hargreaves et al., 1986).Thus, the levels of opioid peptides in plasma seemto be useful diagnostic markers for quantitating theamount of pain and stress perceived by patients. Sim-ilar analyses can be performed for norepinephrineand serotonin.

A comparable monitoring of another area of oraldiagnostic concern, tissue injury (trauma, post-sur-gery), can be achieved by following plasma levels ofsubstances such as prostaglandins, leukotrienes, bra-dykinin, and substance P. All of these analyses also

10 BAUM et at. Adv Dent Res May 1989

Fig. 3 - Schematic representation of the role olf humoral mediatorsin pain relief. An injury to the tooth sends a nerve impulse to thebrain causing release of CRF (corticotropin-releasing factor) fromthe hypothalamus. CRF next signals the pituitary to secrete B-endorphins (p-End) in response to this pain stress. (3-Endorphinscirculate through the blood stream and may act to relieve paineither at the site of injury (the tooth), or in the brain. (3-Endorphinscan be easily measured in blood samples taken from patients by aradioimmunoassay procedure and can then be used as a "physio-logical" measure to compare with behavioral measures of painmade in parallel.

utilize radioimmunoassays with specific antibodies.These diagnostic tests allow for accurate staging ofclinical problems and therefore for accurate, and morespecific, therapeutic intervention.

Development of other humoral analyses which cor-relate with oral health status will likely be the subjectof considerable investigative effort over the next fewyears. The cited, currently available examples clearlyattest to the increased accuracy, specificity, and sen-sitivity of such procedures as well as to their appli-cability and usefulness with respect to problems facedby the oral diagnostician.

INTERMEDIATE ADVANCES (-10 YEARS)

Research advances here focus on the developmentof new diagnostic tools/methodologies, which are notuniversally available to clinical medicine and den-tistry, but which at present exist conceptually, andpractically, in the laboratory setting. These predic-tions are derived from advances at the "current edge"of modern biology.

(1) Molecular Probes for Identifying Tumor Cellsand Identifying Specific Therapies

There has been a veritable explosion of knowledgein the last few years about how cell growth is con-

trolled. The focus of this development can arguablybe assigned to cellular oncogenes, eukaryotic cellulargenes which have considerable homology to onco-genes from transforming viruses. Several categoriesof cellular oncogenes, and their phenotypic proteinproducts, have been identified, and nucleotide probesare available to detect their presence in cells. At pres-ent, many laboratory studies are directed towardidentifying oncogene expression or amplification fol-lowing developmental or mitogenic stimuli. How-ever, a few studies have identified the presence ofamplified oncogenes in human malignancies. For ex-ample, Aaronson and his colleagues at the NationalCancer Institute have demonstrated amplification ofthe mac oncogene in -15% of human mammary car-cinomas (King et al, 1985). Similarly, a research groupin Japan has identified oncogene amplification in asalivary gland carcinoma (Semba et al., 1985). Thesemalignant cells may be thought to display their un-controlled growth due to this amplification process.The specific derepression event(s) allowing for geneamplification is at present not known, but we cananticipate progress toward its identification within fiveor so years. Thus, we can predict that in 10 years, forsome malignant tumors, we will know the gene de-rangement which results in uncontrolled cell growth,including the actual perturbed, permissive geneticswitch. Similarly, we will know, and be able to iden-tify (immunologically), the protein products of theseoncogenes.

Accordingly, we expect that oral diagnostic re-search related to cancer will in part be directed atidentifying these genetic signals. This will allow fu-ture diagnosticians to use these types of probes rou-tinely to identify the specific etiology of a malignanttumor, both by molecular hybridization studies withbiopsy samples and by analyses of tissue or serumfor protein products of malignant transformation. Inprinciple, these techniques are quite simple (Fig. 4).For example, nucleotide probes can interact specifi-cally (hybridize) with complementary nucleic acid se-quences in cells in situ or in extracted DNA. If theoligonucleotide probe is labeled (e.g., isotopically), itcan be detected readily, thereby indicating the pres-ence of the gene sequence of interest. The proteinproducts of these genes can be easily identified byimmunoassays, as noted earlier. With such precisediagnostic knowledge, it will also be possible to de-sign exact therapeutic reagents for specific types oftumors. These can be targeted only to cells expressingthe malignant aberration a considerable advanceover current non-specific forms of chemotherapy whichaffect normal as well as tumor cells. These advances,for general medicine, are now not far from achievingroutine practicality. Indeed, the techniques describedin Fig. 4 have been applied to identify viruses in var-ious tissues and have been useful in suggesting theviral etiology of a specific oral AIDS-associated lesion(e.g., Greenspan et al., 1985).

Vol. 3 No. 1 ADVANCES IN ORAL DIAGNOSIS U

A.

Biopsy D N A

From ExtractedSuspectedOralTumor

+~ DNA FragmentsTreatWithRestrictionEndonuclease

Electro-phoresisin Agarose

Gel. CanStain withEthidiumBromide for DNA VisualizationorTransferby CapillaryAction toNitrocellulose Filter("Southern Blot")

DNALengthinBasePairs

Identifym

Oncogene

Presence with32p-Oligonucleotide Probe andAutoradiography. Probes forSeveral Oncogenes, Which areSuspected to be Involved, Can beTested

B.

ImmunocytochemicalStaining ofAcinar Cells

From a SalivaryTumor withAntibody toOncogene "ProteinProduct"

Fig. 4 Diagnostic methods to identify oncogenes in a biopsy froma patient's tumor. A. Using molecular biological/biochemical pro-cedures. B. Using immunocytochemical procedures. In Fig. 4B, thebiopsy is fixed and incubated with buffer containing antibody tothe oncogene "protein product". Next, the tissue is washed, anda second antibody, coupled to peroxidase, is added. After anotherwash, substrates for peroxidase are added. Deposited reactionproduct is seen (black dots) where the oncogene "protein product"is localized (here, in nucleus).

(2) Diagnostic Probes for Assessing FunctionalCapacity of Salivary Epithelial Cells

In the last two to four years, our knowledge abouthow saliva formation takes place has expanded enor-mously. We have recognized several of the ion chan-nels and carrier-mediated transporters which arenecessary for transepithelial cell water movement.These include Ca2' -activated K' channels, Ca2 ' -ac-tivated Cl channels, and the Na'/K'/Cl co-trans-porter. We also know most of the neurotransmitterreceptor control mechanisms involved in these fluid-generating events. Current laboratory developmentsin identifying receptors by experimental imagingmethods and the advent of isotopic probes for someion transport proteins (particularly the Na' /K' /Clco-transporter) suggest that research efforts in -10years hence will be directed at devising methods toallow oral diagnosticians to ask discrete questionsabout the status of an ion channel, a transport pro-tein, or a receptor coupling mechanism.

Salivary gland dysfunction is a reasonably commonoccurrence. Autoimmune exocrinopathies affect fromtwo to four million Americans, and iatrogenic causesof gland dysfunction (radiation, pharmaceuticals) are

frequently seen. In the extreme case (e.g., destructiondue to autoimmune disease or to radiation damage),gland dysfunction may be, at present, reasonablystraightforward to diagnose. However, there are manydisorders of salivary glands for which a definitive di-agnosis is difficult to reach. Obviously, managementof these diagnostically elusive situations is also in-adequate. There are now several examples in medi-cine of diseases which result from subtle disturbancesin receptors or transduction molecules. The best-characterized of such deficits is pseudohypoparathy-roidism (Van Dop and Bourne, 1983). It is highly likelythat there are salivary (and other oral tissue) disor-ders which result from such discrete molecular dis-turbances. Future research will take the currentgeneration of available molecular and immunologicprobes to more practical levels (e.g., radionuclidescoupled to probes; Drayer et al., 1982), making rou-tine assessments of the status of key acinar cell plasmamembrane proteins possible both in situ, during ac-tual function (Fig. 5), as well as with biopsied mate-rial in vitro.

Such diagnostic progress, coupled with the presentprogress with in vitro eukaryotic cell gene transfectionprocedures and the anticipated success of gene trans-fection techniques in humans, will pave the way forlong-term future research advances in managing sal-ivary disorders. For example, we can speculate thatsuch research will eventually lead to the following,or a similar, clinical management scenario. After de-termining that a patient is unable to secrete salivabecause acinar cells possess an apical membrane Clchannel which is defective and unresponsive to stim-uli, future clinicians will be able to target the insertionof the gene coding for a functional Cl channel, or amodifier molecule, via cell-directed vectors and thusrestore gland function (Wang and Huang, 1987).

The intermediate period covered here will be onethat will make commonplace the transfer of today'slaboratory molecular biological advances into the rou-tine clinical setting. Technically, it is becoming in-creasingly easier to produce nucleotide, peptide, orimmunologic probes of exquisite specificity. The oraldiagnostician of the not-too-distant future will indeedmake molecular diagnoses. We feel very confidentthat at the period around the turn of this century,oral diagnostic research will see such tools in con-ventional use for a variety of oral problems such asneoplasia and non-neoplastic oral mucosal diseases,viral infections, autoimmune disorders, and gusta-tory and other sensory dysfunctions.

LONG-TERM ADVANCES (-25 YEARS)

It would not be surprising that by this time, in theeconomically advanced countries of the world, tra-ditional oral diseases (caries, periodontal diseases) willnot be significant clinical problems. Simple kits, touse at home, will be available for general monitoring

22 BAUM et al. Adv Dent Res May 1989

HealthyControl

Patient with UnknownSalivaryDysfunction

Inject a hypotheticalprobe of interest, in thiscase an iodinated ligandwhich binds to a Ca 2 + -activated CI" channel in acinarcells. Visualize planes ofsalivary glands by a computerizedtomographic analysis.

No liganddetected indicatinga lack of Ca2+-activatedCI" channels in salivaryglands or the presence ofa defective channel incapableof interacting with the ligand.

S M / S L

Detectionof ligandpresumablyinteractingwith "normal"Ca2+-activatedCI" channelsP = area of parotid glandsSM / SL = area of submandibular /sublingual glands.

Fig. 5 Use of a radionuclide-coupled probe, in conjunction withphoton emission computed tomography, to assess the functionalstatus of salivary acinar cell Cl~ channels.

of dental disease, salivary gland function, oral infec-tions, etc. In addition, it is possible that most formsof cancer will be easily diagnosed and readily treated.There will still be a place for biologically oriented di-agnoses within dentistry, although we speculate thatmany "oral" diagnostic decisions will be in the handsof a relatively small group of highly trained individ-uals (-5000) who will practice in sophisticated diag-nostic centers and concentrate on what now mightbe thought of as subtle glandular, neural, muscular,and skeletal disorders of the head, neck, and face.Research emphasis in diagnosis will be substantiallydifferent from that seen today; physical science willdominate over biological science. Phenomenal gen-eral technological advances will be made in the aero-space, communications, and defense industries overthe next 20-30 years, with spin-offs to all facets ofdaily life. This will lead to revolutionary applicationsin physiology and health sciences. In many ways, tous now, these belong in the realm of science fiction.

We expect to see many patients (and patient sam-ples) interacting with diagnostic instrumentation andcomputers, using imaging techniques far more ad-vanced than found in today's biophysics labs {i.e.,electron spin resonance, nuclear magnetic resonance,x-ray diffraction). There will be little or none of pres-ent-day physical diagnosis practiced. Clinicians willless frequently lay hands on patients to assess pa-thology. Diagnosis will not be done at the first signor symptom of a problem but on a very routine (be-cause instrumentation will make it easy) and veryfrequent basis. Patients who at such screening visitsshow indications of developing pathology will be moreintensively examined, and disordered molecules thencorrected or excised. Diagnosis research at this timewill be directed at both submolecular and supramo-lecular levels. Individuals involved will have biolog-ical backgrounds but will be heavily trained in physicsand engineering and will direct their efforts towardproducing sophisticated molecular clinical-imagingtools.

CONCLUSION

All of medicine will change dramatically over thenext 25 years, perhaps diagnosis more than most areas.The changes will be fueled by advances in other, non-related, fields, but also by the elimination of manymodern diseases. For comparison, take the case ofthe medical diagnostician who graduated in 1940 be-fore World War II and only retired last year frompractice. He (she) has witnessed a dramatic shift inthe diseases he was called upon to detect, the meanswith which he could detect them, and the tools withwhich he could treat them. Similarly, the oral diag-nostician will be shifted in focus dramatically in thenext 10-25 years. By the turn of this century, ad-vances in oral diagnosis will be a full partner of main-stream medical advances.

It is, as noted earlier, hard for us to predict withany reasonable level of accuracy advances beyond a~ 10-year time-point. We all, however, recognize thatadvances are occurring at exponential rates. Most im-portantly, we believe that the next 10 years or so area time of almost unrestricted opportunity in oral di-agnosis research. It is a time of new directions, whichcan be taken readily from guidelines offered throughcurrent advances in biology and medicine. We be-lieve that this should give considerable encourage-ment both to young oral health investigators concernedabout future clinical research opportunities and to thedental profession at large, because new practice vis-tas will be charted. Since many of these advances arein areas which are non-traditional with respect todental practice, we believe that substantial attentionmust be paid to transferring advances to the clinicalarm of the profession. This portends significantchanges in dental education directed both at the ac-

Vol. 3 No. I ADVANCES IN ORAL DIAGNOSIS 13

quisition of the necessary scientific background andthe alteration of existing "practice behaviors".

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