Future priorities for a successful dental school.

Priorities for success for a dental school of the future are considered. University relations, demographic changes, digital information technology and functional genetic technology are emphasised as important environmental pressures that will influence the priorities. The goal advocated for university relations is creating a culture in which the dental school is viewed as integral and necessary to the University's mission. Financial stability, quality research and scholarship and provision of health care for employees may be important ingredients. Keeping an eye on demographic changes and taking the school's business where the customers are is another key to success in the future. Ethnic diversity, changing approaches with changing disease patterns, flexibility in schedule and collaborations in areas of need are strategies to be considered. The emerging field of functional genetics typifies a new biology with which currency will be needed in a health-sciences field. Necessity for faculty development, adoption of molecular diagnostic technologies, emphasis on risk assessment and preventive counselling, and a shift to a wellness model are likely consequences. Digital information technology will result in increased distance-learning opportunity. Dental schools will also need to make accommodating changes in curriculum structure available. Conversion to electronic imaging and totally electronic patient records are likely to become standard.

Investigation of the influences of puberty, genetics, and environment on the composition of subgingival periodontal floras.

The classical twin model was utilized in this study in an attempt to determine the importance of host genetics to the composition of the subgingival flora. Simultaneously, the effect of puberty on the flora composition was assessed. The compositions of the floras were significantly different at ages 11 and 14 in the same people, indicating that transition to an adult flora composition may be initiated during puberty. However, the numbers of subjects who had prepubertal and postpubertal testosterone levels in this study were too small to demonstrate significant differences based solely on testosterone level (P = 0.053 and 0.11 for tests of unrelated members, i.e., all twins "a," the first twin of each pair, and all twins "b," the second twin of each pair). Sixteen unrelated 11-year-old subjects had prepubertal levels of less than 30 ng of testosterone per dl of serum, and only six of these unrelated subjects had levels above 300 ng/dl by age 14. Of their twin siblings, who formed the second group of unrelated individuals, 15 had prepubertal levels and only 5 reached postpubertal levels. Unpaired t tests indicated that Veillonella atypica, Prevotella denticola, and Prevotella melaninogenica were among the species that contributed most to changes in flora composition during puberty. The compositions of subgingival floras of 11-year-old monozygous and dizygous male twins were significantly more similar than those of unrelated subjects in the study (P = 0.004 and 0.009, respectively). At 12.5 years of age, the floras of monozygous twins remained more similar than those of unrelated subjects (P = 0.001), but the dizygous-twin floras were not significantly more similar than those of unrelated people. This difference corresponded with moderate and varied testosterone levels within dizygous-twin pairs at age 12.5. By age 14 both monozygous and dizygous twins again had floras with compositions more similar than those of unrelated people (P = 0.008 and 0.002, respectively). Estimates of the genetic contributions to the increased similarity of the floras of twins as compared with floras of unrelated people indicated that the concentrations of several species in the flora may be influenced by host genetic factors. The prevalence of certain other species appeared to be controlled primarily by environment.

Differential diagnosis in clinical trials of therapy for periodontitis.

For purposes of clinical trials of therapies for periodontitis, it is recommended that population samples be identified as adult periodontitis (systemically modified or not systemically modified), early onset periodontitis (localized or juvenile, generalized or rapidly progressive, or associated with systemic disease), or necrotizing ulcerative periodontitis, avoiding overlapping criteria. Population samples of adult or early onset periodontitis modified by or associated with systemic conditions should be used in clinical trials only when the intent is to study effect on the specifically modified condition. Objective identification of the modifying systemic condition should be required for all subjects in such trials. Population samples should be homogeneous for the diagnosis, whether systemically modified or not. Refractory periodontitis, prepubertal periodontitis, and periodontitis associated with systemic disease are not recommended as useful descriptors of population samples without discrete identification of underlying systemic abnormality for all included subjects. Definition of population sample by a bacteriological or a host response feature is not recommended unless the trial is specifically aimed at that feature and the sample is homogeneous for it. All trials of efficacy should include physical or radiographic measurement of attachment level or bone height as a critical outcome variable. Results from trial in one form of periodontitis should not be applied directly to other forms.

Diagnosis of periodontal diseases.

This paper reviews current (Fall, 1990) information related to the diagnosis of periodontal diseases. As background, principles of diagnostic decision-making and conceptual shifts during the 1970's and 1980's are reviewed in brief. "Diseases" that appeared in many classification schemes for periodontal diseases in the early 1970's--for example, "periodontosis" and "occlusal trauma"--do not appear in most current classifications. A recent (1989a) classification recommended by the American Academy of Periodontology holds that "periodontitis" includes several different diseases. There is, indeed, evidence for several different forms of periodontitis, but the AAP's classification does not conform to the principles of diagnostic decision-making because of the significant overlap between and heterogeneities within its suggested "diseases". An alternative classification is suggested, based on a concept that the periodontal diseases are mixed infections whose outcome is modified by relative effectiveness of host response. This view suggests that the most usual forms, gingivitis and adult periodontitis, normally occur in persons with essentially normal defense systems. Variation in extent or severity of disease can be understood as a function of the local infection in hosts with various degrees of compromised resistance to the infection. Early-onset periodontitis (EOP) cases could be accounted for by those where host response is abnormal to some significant degree. The greater the abnormality, the greater the extent and severity of disease might be. Localized EOP cases would be those where a relatively effective specific response intervenes to ameliorate progress of disease after the initially rapid progression. Other issues are detection of disease activity and assessment of risk for disease progression. Non-cultural bacteriological tests are available, but have not yet been shown to detect or predict activity or risk. One difficulty in reaching such proof for those or other tests has been the lack of an appropriate "gold standard" for disease activity or progression. This is being remedied by development of improved automated probes and imaging technologies. Considerable effort is being devoted to determining whether factors in gingival crevicular fluid may have diagnostic utility. More evidence is needed before clinical utility is known, but several enzymes and cytokines have potential for aiding diagnostic decisions.

The microflora of periodontal sites showing active destructive progression.

20 adult periodontitis (AP) subjects were examined every 2 to 4 months and microbiological samples were collected and cultured when 2 mm or more loss of attachment (active sites) was detected by 2 examiners. Similar sites in which no progressive destruction was observed (control sites) also were sampled in the same subjects. By lambda-analysis, there was no statistically significant difference in floras of active (42 sites from 12 subjects) and control (36 sites from 12 subjects) sites or between the floras of the active and control sites and of 63 samples from 22 AP subjects that were examined previously in a cross-sectional study. By paired t test, no microbial species had a significantly greater association with active than with control sites. The only species that were detected in one or more samples from all subjects with active sites were Wolinella recta, Fusobacterium nucleatum, and Peptostreptococcus micros. Porphyromonas gingivalis and 9 other taxa were isolated from one-half or more of the persons with active sites. The composition of microbiological floras of all periodontitis samples was statistically significantly different from that of subjects with healthy gingiva. The composition of microfloras of sites in subjects with naturally-occurring gingivitis was intermediate between that of subjects with healthy gingiva and that of active and control sites in AP subjects.

Immunologic mechanisms of pathogenesis in periodontal diseases: an assessment.

Principal lines of evidence that immune reactions are central to the pathogenesis of periodontitis are reviewed. Necessary components of immunologic reactions are present in gingiva in the periodontal diseases. Differences between healthy and periodontitis patients with respect to some measures of immune function further indicate that immune reactions do occur in the gingiva during periodontitis. They are probably responsible for at least some of the destruction of connective tissue and bone that occurs. Classical antibody-mediated hypersensitivity reactions probably do not provide the reasons. Mechanisms are more likely to be found in the pro-inflammatory and tissue-degrading effects of cytokines released in host-protective, antigen-specific and polyclonal responses to oral bacterial constituents or products. Some evidence suggests that limitation of clinical destruction in localized early onset periodontitis (JP) may in part be a function of a protective antibody response which develops after an initial rapidly progressive infection. A relatively deficient immune responsiveness may allow progression to more severe and generalized disease (RPP). Suggestions are made for studies needed to confirm suspected pathogenetic mechanisms, approach resultant targeted therapies, and test hypotheses for contrasting roles of immune reactions in different clinical expressions of periodontitis.

Actinobacillus actinomycetemcomitans in families afflicted with periodontitis.

The purpose of this study was to determine the prevalence of Actinobacillus actinomycetemcomitans (Aa) in individuals from families where at least one individual has an early onset form of periodontitis. Twenty-three families with 73 subjects were evaluated in this study. Forty-seven early onset periodontitis subjects outside the 23 families were also studied. Prevalence of detection of Aa in family members ranged from 49% to 66% among groups constituted by clinical findings indicative of no loss of attachment, adult periodontitis, generalized severe juvenile periodontitis, or localized juvenile periodontitis. Whether the data were analyzed by subject or by site, no statistical differences could be found in prevalence (proportion of positive samples) among those clinical groups. The only significant difference was that localized juvenile periodontitis subjects had higher concentrations of Aa in their Aa-positive sites than did the other clinical groups. The prevalence of Aa-positive sites in subjects without attachment loss, but who are members of families in which early onset periodontitis is represented, was much higher than in other reports where periodontally healthy subjects were not related to early onset periodontitis cases. This suggests that Aa may be transmitted among members of families in which one or more members has an early onset form of periodontitis.

Thermal regulation of FMLP receptors on human neutrophils.

Polymorphonuclear leukocytes (PMNs) from subjects diagnosed as having juvenile periodontitis (JP) have been categorized on the basis of their chemotactic (CTX) response to f-met-leu-phe (FMLP) when assayed concurrently with PMNs from periodontally healthy subjects (HP). When PMNs from JP groups demonstrating depressed CTX were assayed for lysosomal enzyme secretion (LES) in response to FMLP, there were no significant differences with respect to rate or amount. Significant differences were observed between HP and chemotactically depressed JP cells when assessed for FMLP receptor ligand binding at 23 degrees C, but not at 4 degrees C. Receptor differences observed at 23 degrees C in HP cells included an increase in amount of total binding, number of receptors, and available displaceable binding sites, compared with the chemotactically depressed JP PMNs, whereas the receptor affinities were similar. These data suggest that differences in FMLP receptor density in JP PMN that are chemotactically depressed may be related to processes that modulate receptor mobility and/or expression.

Antibody synthesis specific for nonoral antigens in inflamed gingiva.

In vitro experimentation indicates that periodontitis-associated bacteria contain potent polyclonal B-cell activators (PBA). We reasoned that if PBA were operative in vivo, plasma cells specific for nonoral antigens should be present in the inflamed gingival tissues, which are characterized by a plasma cell infiltrate. To test this, rabbits with experimental periodontitis were immunized in the hind legs with the histochemically detectable antigen horseradish peroxidase (HRP) or glucose oxidase (GO). At various times after secondary immunization, inflamed gingival tissue was removed, sectioned, and treated histochemically to reveal plasma cells that specifically bound HRP or GO. Remarkably, by 9 days after secondary immunization, hundreds of HRP- or GO-binding plasma cells were found in the inflamed gingival tissue of immunized rabbits. The presence of these plasma cells, observed 7 to 10 days after booster immunization, was further substantiated by the presence of large amounts of locally produced HRP- or GO-specific antibody in gingival crevicular fluid. By 1 month after secondary immunization, the number of antigen-binding plasma cells had decreased dramatically, but a small number of antigen-specific plasma cells were detected for as long as 9 months after secondary immunization. The large number of HRP- or GO-specific plasma cells observed 9 days after immunization led us to see whether recently stimulated cells were more susceptible to PBA. Peripheral blood lymphocytes (PBL) were obtained at different times after booster immunization and cultured in the presence or absence of a PBA from Fusobacterium nucleatum. At 7 days after immunization, PBL spontaneously differentiated into antibody-forming cells in culture, and this process was enhanced by PBA. In contrast, PBL taken months after immunization produced little antibody in culture, and enhancement by PBA was difficult to detect. Compared with resting B cells, the recently stimulated B cells clearly differentiated more readily into antibody-forming cells. In conclusion, antibody synthesis specific for nonoral antigens did occur in inflamed gingival tissue, and a number of mechanisms, including PBA, probably contributed to this phenomenon.

Bacteriology of human gingivitis.

The subgingival bacterial floras of naturally occurring gingivitis in adults and children were characterized and compared with the floras of other periodontal conditions previously studied. The composition of the gingivitis floras was found to be distinct from that of floras associated with health or with moderate, severe, or juvenile periodontitis. There were no major differences between the floras of naturally-occurring gingivitis and the floras of the human experimental gingivitis model. Data indicated that the flora of healthy sites within a mouth is influenced by the number of inflamed sites, which argues against independence of sites bacteriologically. Proportions of ten bacterial species increased in both gingivitis and periodontitis, as compared with health, in both adults and children. These species were found in both affected and unaffected sites of people with gingivitis. The numbers of five other cultivable species and the "large treponeme", which was not cultivated, increased in gingivitis and periodontitis of adults only. Significant differences in non-spirochetal floras between children and adults were not found, although they were in the experimental gingivitis model studied previously. Cultivable spirochetes did differ between children and adults. Children had fewer samples positive for spirochetes, and children's positive samples contained greater proportions of T. socranskii subsp. paredis. Some species that predominate in periodontitis, but which are absent from healthy gingivae, were found as a small percentage of the flora in gingivitis. This suggests that increased serum and blood in the gingival crevice encourage species that relate to periodontitis.

Relationship of serum antibody to attachment level patterns in young adults with juvenile periodontitis or generalized severe periodontitis.

The goal of this study was to relate attachment loss patterns in early onset periodontitis subjects (juvenile periodontitis n = 47 and severe (generalized) periodontitis n = 52) with antibody reactivities to 25 bacterial strains which were suspected periodontal pathogens. The 25 antibody reactivities were screened by correlation analysis. Eleven strains were found to be significantly related to attachment loss. Using these 11 reactivities, stepwise multiple linear regression with plaque and age as covariates was used to further relate the reactivities within each subject group. Plaque was significantly related to the number of teeth with slight, moderate, or severe attachment loss. A significant inverse relationship was found between antibody reactivity with Haemophilus actinomycetemcomitans Y4 and the number of teeth having slight or moderate attachment loss. Similarly a significant inverse relationship between antibody reactivity with Bacteroides gingivalis and the number of teeth having moderate or severe attachment loss was found. The inverse relationship between the two antibody reactivities and attachment loss patterns were independent of the positive relationship of plaque. These relationships suggest that the failure to mount a substantial antibody response to these organisms leads to greater and more widespread periodontal disease in early onset periodontitis subjects.

Early onset periodontitis: a comparison and evaluation of two proposed modes of inheritance.

Two rare types of familial periodontitis, a localized form usually diagnosed in late adolescence, and a more generalized form with a latter mean age of diagnosis, have been analyzed with respect to genetic models currently favored in the dental literature. These include autosomal recessive and X-linked dominant (partial penetrance) inheritance. Since there is variation in severity, extent, age of onset, altered sex ratio of affected individuals, and a low population prevalence, it is not surprising that genetic mechanisms heretofore have not been revealed. We have compared the likelihoods of 33 kindreds ascertained through affected probands under the above genetic models. Our findings include (1) several families in which both forms of early onset periodontitis co-occur, making it unlikely that the clinical varieties of the disease have unrelated genetic causes; (2) the autosomal recessive model is far more likely than the X-linked dominant model. The superiority of the recessive hypothesis arises from the fact that there are only a few instances of affected individuals having affected parents and because the skewed sex ratio is shown to be incompatible with X-linked inheritance. These conclusions are largely insensitive to the assumptions of the analysis. We conclude that the X-linked dominant hypothesis is inadequate, and while the autosomal recessive model is by no means proven, it is clearly favored.