Mechanisms of initiation and progression of periodontal disease.
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Biomedical subjects
Publications and source records attributed to W B Clark.
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Longitudinal data of attachment level (AL) or the alveolar bone level are often used to assess the progression of periodontal disease. This paper tries to identify the most efficient method to detect the changes of AL in a general periodontal research environment; that is, a sequential decision based on multiple sites. Several existing methods suggested in the periodontal research literature such as the tolerance, running median, cusum, and regression methods as well as change-point detection methods in the statistical literature are examined. It is found that the regression method is most convenient among the several methods that are equally effective in change detection. Formulae, tables and their usage are discussed in detail.
Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Actinomyces strains to heat, trypsin, or proteinase K abolished most coaggregations. All pairs were disaggregated by the addition of sodium dodecyl sulfate, but only those coaggregations involving P. intermedia 113 were reversed by the addition of 2.0 M urea. P. intermedia 27 was sensitive to periodate oxidation, whereas the partner strains were stable to this treatment. Most coaggregations occurred in the presence of saliva; however, reactions involving P. intermedia 27 were not as strong as those of buffer-suspended cells. Treatment of both P. intermedia 113 coaggregations pairs with proteinase K and the results obtained from suspensions of these pairs in saliva suggest that different surface molecules of this P. intermedia strain may mediate each of these coaggregations. These data suggest that all of these coaggregations involve either a protein or glycoprotein on the Prevotella strain, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces strain.
Attachment level has been used as the "gold standard" for assessment of the progression of periodontal disease. However, the measurement of attachment level by periodontal probing can be subject to a large number of error sources. Recently, we have designed experiments by using an electronic probe to identify the magnitude of error components due to the instrument, gingival tissue condition, position or probing angle, and time interval between replicate probings. Even with a very careful clinical setting, a few percent of uncontrollable large errors or outliers could not be avoided. A previously used 'option-3' probing scheme to reduce the unexpected large error is justified from the mathematical viewpoint.
Refractory periodontitis is considered by many investigators to be a separate disease entity that is descriptive of a particular patient who has multiple sites, rather than a few individual sites, that do not respond to conventional periodontal treatment modalities. Such patients continue to demonstrate loss of attachment and alveolar bone despite frequent periodontal treatment which includes surgical intervention, scaling and root planing, and often systemically-administered tetracycline. Controlled clinical studies have demonstrated that both clindamycin-hydrochloride and amoxicillin/clavulanate potassium (Au) are beneficial when used in conjunction with periodontal scaling. Gordon et al. found improvements in attachment levels, inflammation, suppuration, and a decrease in pocket depths for up to 2 years following a 7-day course of clindamycin given in conjunction with a full-mouth scaling. The incidence of disease activity decreased from an annual rate of 8% of all sites prior to antibiotic treatment to 0.5% after treatment. Magnusson, reporting on a similar group treated with a 14-day course of Au, found an average loss of attachment of 2.2 mm and an increase in pocket depth of 1.5 mm in sites demonstrating disease progression prior to antibiotic treatment. At 3 months post-antibiotic therapy, these sites had regained an average of 2 mm of attachment and pocket depths had decreased an equivalent amount. Both attachment levels and pocket depths remained relatively stable for up to 12 months post-therapy. In an ongoing study, 30 subjects with refractory periodontitis were treated with either clindamycin or Au in conjunction with scaling or scaling plus a placebo. Prior to antibiotic treatment, but while being scaled at 3-month intervals, sites with disease activity lost an average 2.4 mm of attachment. At 3 months post-treatment, the clindamycin-treated group showed an average gain of 2.1 mm, the Au-treated group gained 1.9 mm, and the scaling group gained 1.4 mm in attachment. The clindamycin group remained relatively stable for up to 21 months and the Au group remained stable for about 15 months without additional treatment. Five of the 6 subjects treated with scaling alone required additional treatment within 9 months. Preliminary analyses have indicated that at least two patterns or rates of attachment loss may be associated with refractory periodontitis and that each pattern may be indicative of a different microflora. The pattern associated with a relatively rapid loss of attachment was characterized by a Gram-negative flora which contained spirochetes, P. intermedia, and Fusobacterium species.(ABSTRACT TRUNCATED AT 400 WORDS)
Periodontal diseases are thought to result from inflammatory responses to bacterial challenges in the gingival crevicular area. Antibodies are a major host-protective mechanism in many bacterial infections. Consequently, the antibody responses to suspected periodontal pathogenic bacteria have been extensively measured as to their relationship to diseases and specificity for suspected pathogens associated with progressing disease sites. Recently, studies on the bacterial immunogen characterization, antibody-subclass identification, and antibody biological capabilities have been reported. Although increased antibody levels to certain suspected periodontal pathogens were associated with periodontal diseases in humans, little evidence exists as to the role of these antibodies in the infectious process. In vivo experiments in animals indicated that specific antibodies against certain suspected periodontal pathogens were associated with suppression of bacterial colonization, limiting the spread of infection, and a decrease in alveolar bone loss. However, in vitro as well as in vivo experiments suggested that phagocytic cells are required for efficient bactericidal activity of antibodies and that the presence of other sensitized immune cells may either have inhibited or enhanced the infectivity of certain periodontal pathogens. Possible explanations for the observed inconsistencies are presented and the potential for utilization of specific anti-periodontal pathogen responses in the understanding and prevention of diseases is discussed.
We have recently isolated from the gingival pockets, periapical lesions and saliva some anaerobic gram-negative, black-pigmented rods. Many of these isolates exhibited phenotypic characteristics similar to Prevotella intermedia (Bacteroides intermedius). However, several of these isolates, although resembling P. intermedia in most of the phenotypic expressions, were capable of fermenting lactose, a biochemical characteristic atypical of P. intermedia. These atypical clinical isolates (strains capable of fermenting lactose) and isolates exhibiting more typical phenotypic characteristics (i.e., lactose nonfermenting) were definitively identified as P. intermedia by DNA-DNA hybridization using a photoprobe biotin method. Quantitative hybridization of clinical isolates with labeled DNA of P. intermedia-type strains (ATCC 25611 and ATCC 33563) showed that almost all the clinical strains isolated from disease sites of adults belonged to the ATCC 25611 group, whereas strains isolated from the saliva of children belonged to the ATCC 33563 group. These data, together with the phenotypic characterization of the isolates, suggested that P. intermedia is a heterogeneous species both phenotypically and genetically.
Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naïve mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.
4 probing designs have been employed to investigate the reproducibility of the Florida Probe. 3 groups (each composed of 10 subjects) were selected for the study: healthy adults, gingivitis subjects, and periodontitis subjects. The 4 probing designs were as follows: (a) the probe tip was left in the sulcus between successive probings; (b) the probe tip was removed from the gingival margin between probings but the next probing followed immediately; (c) successive whole-mouth probings were interrupted by a 5-min interval and a mouthrinse; (d) there was a 4-week interval between each probing. 3 measurements were taken for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation was found to be around 0.3 mm, which is considerably smaller than that found in most previous studies. The errors associated with the periodontal condition and probing effect were also estimated. The variance components obtained here can be used for determining the sample size in controlled clinical studies.
The aim of this study was to evaluate the effect of 3 mouthrinses, Listerine Antiseptic (thymol), Peridex (chlorhexidine), Perimed (povidone iodine and hydrogen peroxide), and a placebo (water) on the development of dental plaque and gingivitis, when used as the only oral hygiene procedure for 14 days. 71 subjects were entered into a randomized, double-blind study. At the baseline examination, papillary bleeding score (PBS), and plaque index (PI) were registered, after which subjects received supragingival prophylaxis and were assigned to 1 of 4 study cells. Subjects were asked to refrain from all oral hygiene procedures except for the supervised 14-day 2 x daily rinsing with the assigned preparation. At day 14, the same clinical parameters were again registered. Statistical analysis was performed by a one-way analysis of variance (ANOVA) to compare the 4 groups, followed by Duncan's multiple range test to determine specific group differences. At baseline, average PBS and PI scores were similar for all 4 groups. After 14 days, the average PBS for Peridex and Perimed was significantly lower than for Listerine Antiseptic and water. The frequency of interdental units with a PBS greater than 2 was significantly lower for Peridex and Perimed than for Listerine Antiseptic and water. We concluded that both Peridex and Perimed were effective in reducing plaque and gingivitis when used as a 2 x daily mouthrinse by subjects refraining from other oral hygiene procedures. In vitro, a synergistic effect was assumed when inhibition was achieved with Perimed at the same or greater dilution than was achieved with povidone-iodine alone.
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Recent studies have provided evidence for human salivary proline-rich proteins (PRPs) serving as potential receptors in the acquired pellicle for Actinomyces viscosus type 1 fimbriae. We report here the isolation of mutants derived from A. viscosus T14V-J1 which are defective in binding to PRPs partially purified from parotid gland saliva. Mutagenesis with ethyl methanesulfonate preceded enrichment for cells nonreactive with PRPs by successive adsorptions with PRP-treated latex beads. Screening was accomplished by random selection of 250 isolated colonies from each of four enrichment cycles and reaction with PRP-treated latex beads in microtiter plates. Two mutants of independent origin were examined for adherence to hydroxyapatite treated with either PRPs, proline-rich glycoproteins, deglycosylated proline-rich glycoproteins, or whole saliva. Additional surface properties that were examined included agglutination with polyclonal antisera to type 1 and type 2 fimbriae, agglutination by a monoclonal antibody to type 1 fimbriae that inhibits adherence of the parent strain to saliva-treated hydroxyapatite, the ability to bind monoclonal antibody to the type 1 fimbrial subunit, and lactose-reversible coaggregation with Streptococcus sanguis 34. Both mutants exhibited reduced binding to hydroxyapatite treated with whole saliva or salivary protein preparations but were still capable of reaction with antiserum to type 1 and type 2 fimbriae. In addition, these mutants possessed the ability to bind monoclonal antibody to the type 1 fimbrial subunit in amounts comparable to the amount bound by the parent strain but were not agglutinated by the adherence-inhibiting monoclonal antibody. When considered with previously published data, these results suggest that an adhesive molecule is probably associated with type 1 fimbriae and allows for the interaction of A. viscosus with constituents in the salivary pellicle.
During the past few years, improvements in detecting longitudinal changes in clinical attachment or alveolar bone density have been introduced. For example, constant-force electronic probes and computer-assisted subtraction analysis of longitudinal radiographs have been reported to be more sensitive and reproducible in detecting changes in clinical attachment or alveolar bone density, respectively. Use of these new technologies requires that sources of measurement error be identified and their contribution quantified. This study investigated the reproducibility of a constant-force electronic probe in a careful clinical setting. Measurements were performed from individually fabricated acrylic stents. Three groups of subjects were selected for the study: 10 adults without oral disease, 10 adults with gingivitis, and 10 adults with moderate periodontitis. Four probing designs were employed to investigate the reproducibility of the probe. In design A, the probe tip was left in the sulcus between successive probings. In design B, the probe tip was removed from the gingival margin between probings but the next probing followed immediately. In design C, successive whole-mouth probings were interrupted by a 5-minute interval and a mouth rinse. In design D there was a 4-week interval between each successive probing. Three measurements were taken at each site for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation ranged from 0.2 to 0.3 mm depending on the periodontal health of the subject. This level of variation is considerably smaller than that found in most previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Three methods for detecting the progression of periodontal disease based on the change in attachment level on teeth are compared from a statistical point of view. Regardless of gradual or burst disease progression theories, the regression method is found to be the most efficient way to detect changes. The exact false alarm rate is computed when the decision is based on the maximum regression coefficient at all sites during several visits.
A 58-year-old man had a left jugulodigastric mass, which was found to be cystic by computed tomography, and no evidence of other lesions. Grossly and histologically, the surgical specimen consisted of a thin-walled, fluid-filled cyst lined by squamous epithelium that varied in appearance from benign to invasive squamous cell carcinoma. The findings supported a differential diagnosis of branchial cleft carcinoma (BCCA) versus cystic growth of a lymph node metastasis from an occult malignancy. On this basis, guided biopsies of the upper aerodigestive tract were performed, with strong suspicion of a tonsillar bed lesion. Microscopic examination revealed the primary tumor within tissue excised from the left tonsillar fossa. Comparison of the current case with cases of BCCA and cystic tonsillar metastases from the literature illustrated the potential pitfalls in rendering a diagnosis of BCCA. Recognition of this lesion as a distinctive clinical variant of oropharyngeal carcinoma is warranted.
Each of five monoclonal antibodies (mAbs) prepared against the type 1 fimbriae of Actinomyces viscosus T14V reacted with a 54 kDa cloned protein previously identified as a fimbrial subunit. This purified protein completely inhibited the reaction of a specific anti-type-1-fimbria rabbit antibody with A. viscosus whole cells. Maximum values for the number of antibody molecules bound per bacterial cell ranged from 7 x 10(3) to 1.2 x 10(4) for the different 125I-labelled mAbs and was approximately 7 x 10(4) for 125I-labelled rabbit IgG or Fab against either type 1 fimbriae or the 54 kDa cloned protein. Although the different mAbs, either individually or as a mixture, failed to inhibit the type-1-fimbria-mediated adherence of A. viscosus T14V to saliva-treated hydroxyapatite, each rabbit antibody gave 50% inhibition of adherence when approximately 5 x 10(4) molecules of IgG were bound per cell. However, binding of each corresponding rabbit Fab had no significant effect on bacterial attachment unless much higher concentrations were used. These findings suggest that antibodies directed solely against the 54 kDa fimbrial subunit do not react with the putative receptor binding sites of A. viscosus T14V type 1 fimbriae. Instead, inhibition of attachment by the polyclonal antibodies may depend on an indirect effect of antibody binding that prevents the fimbria-receptor interaction.
Clinical assessment of the progression of periodontitis is based on the measurement of periodontal probing attachment levels over time. In calculating these changes, duplicate measurements from fixed reference points, including cemento-enamel junctions and acrylic stents, have been used to assist in detecting progressive disease. The Florida Probe has been previously shown to improve the reproducibility of these measurements when used with an acrylic stent. The objective of the present study was to evaluate the reproducibility of 2 models of the Florida Probe, the original stent model and the modified disk model, in measuring attachment level. The disk probe differs from the stent probe in that it uses the occlusal surface of the tooth as a static reference point in calculating changes in attachment level measurements. In 10 subjects, sites were probed 2 x by 2 examiners using both types of probe. Standard deviations and intra- and inter-examiner correlations were calculated. These results demonstrate that the new disk probe yields reproducible measurements similar to the stent probe and is therefore suitable for use in longitudinal clinical studies.
The aim of the present study was to analyze the relationship between attachment loss and clinical, microbiological, and immunological parameters in a group of 21 human subjects exhibiting poor response to previous periodontal therapy. All had been treated with periodontal surgery, tetracycline, and subsequent maintenance recalls to periodontists who, upon detection of disease progression, referred the subjects to our clinic. In our clinic, each subject received oral hygiene instruction and a thorough subgingival scaling and root planing utilizing as many appointments as necessary. Clinical indices, including gingival index, bleeding on probing, suppuration, plaque index, pocket depth, and duplicate measurements of attachment level from an acrylic stent, were collected at monthly intervals. Probing measurements were performed using the Florida Probe. When significant attachment loss (0.8-1.2 mm) was detected in at least 1 site, a bacterial sample was taken from that site and from a comparably deep, but non-progressing, control site. Microbial samples were enumerated by darkfield microscopy, on selective and non-selective media, and by predominant cultivable technique. Blood samples were also collected to determine antibody levels against potential pathogens. There was no difference in the amount of plaque present in sites gaining or losing attachment, but losing sites exhibited more bleeding and suppuration. 20 of the 21 subjects were tested; of these, 17 exhibited elevated serum antibody against one or more of the following microorganisms: Actinobacillus actinomycetemcomitans, Bacteroides, gingivalis, and Eikenella corrodens. However, few, if any, of the "classical" pathogens were detected in the plaque samples obtained at the time progressive disease was diagnosed. The only exception was Streptococcus intermedius, which occurred in slightly higher numbers in active sites.