Expression of growth mediators in the gingival crevicular fluid of patients with aggressive periodontitis undergoing periodontal surgery.

OBJECTIVES: To describe changes in growth factor mediators in the gingival crevicular fluid (GCF) of patients with aggressive periodontitis (AgP) undergoing regenerative (GTR) and access flap (AF) surgery. MATERIALS AND METHODS: This was a 12-month, single-blind, split-mouth RCT involving 18 AgP patients with a bilateral intrabony defect which was treated with GTR or AF. GCF was collected prior to surgery and at subsequent follow-up visits from 3 days to 12 months post-operatively, and the levels of angiopoietin-1 (Ang-1), vascular-endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), bone morphogenetic protein-2 (BMP-2), osteoprotegerin (OPG), tissue inhibitor of metalloproteinase 1 (TIMP-1), keratinocyte growth factor (KGF) and platelet-derived growth factor-AB (PDGF-AB) were measured. At baseline, 6 and 12 months post-surgery, periodontal clinical parameters were evaluated. ANOVA was applied to test for differences in the amount of mediators (p < 0.05). RESULTS: Higher amounts of BMP-2 and OPG and a higher area under the curve (AUC) of KGF at the GTR versus AF sites were observed. The maximum change in the amount of KGF correlated significantly with periodontal clinical parameters at the GTR sites at 6 and 12 months. The AUC over 30 days of the amount of Ang-1, VEGF and KGF significantly correlated with periodontal clinical parameters at the AF sites at 6 months. CONCLUSIONS: AF and GTR differentially affected the profile of the growth mediators in GCF, and significant correlations between certain GCF mediators and periodontal clinical outcomes were identified. CLINICAL RELEVANCE: GCF components represent attractive prognostic markers for periodontal tissues undergoing repair or regeneration. However, the available evidence is not robust enough to suggest the use of a specific marker, and future adequately powered studies are warranted to identify the most relevant mediators that could be applied in clinical practice.

Manpower planning in periodontology--how many specialists do we need?

Given that one of the major focus points within this issue of the journal is 'practical periodontal medicine' and the relationship between periodontal disease and systemic chronic diseases, it is surprising that we have no indication of the manpower required to secure better oral and general health in this field. Despite many of the heralded improvements in dental health reported in the Adult Dental Health Survey 2009, as monitored by the falling rates of edentulous subjects and decayed, missing and filled teeth (DMF), the overall increase between 1998 and 2009 in the number of subjects with deep pockets from 6% to 8% has largely gone unnoticed! This is a major concern given that most other indicators of oral health have improved over this time period. Furthermore, the tissue damage associated with periodontitis is largely irreversible, and has consequences not only for oral function and quality of life, but also may adversely impact on aspects of general health. This article aims to highlight why we need specialists in periodontics, which patients should be referred to them, how big a problem periodontal disease is and how many specialists in periodontics would be required to meet this treatment need. Estimates are made using the information gained from the Adult Dental Health Survey 2009 and the Office for National Statistics 2011 census, along with estimates of the average patient pool managed within specialist periodontal practices. However, the paper emphasises that these are estimates based on incomplete information which would be necessary to allow more complete models of manpower planning to be used.

R-Ras interacts with filamin a to maintain endothelial barrier function.

The molecular mechanisms regulating vascular barrier integrity remain incompletely elucidated. We have previously reported an association between the GTPase R-Ras and repeat 3 of Filamin A (FLNa). Loss of FLNa has been linked to increased vascular permeability. We sought to determine whether FLNa's association with R-Ras affects endothelial barrier function. We report that in endothelial cells endogenous R-Ras interacts with endogenous FLNa as determined by co-immunoprecipitations and pulldowns with the FLNa-GST fusion protein repeats 1-10. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In these cells FLNa and R-Ras co-localize at the plasma membrane. Knockdown of R-Ras and/or FLNa by siRNA promotes vascular permeability, as determined by TransEndothelial Electrical Resistance and FITC-dextran transwell assays. Re-expression of FLNa restored endothelial barrier function in cells lacking FLNa whereas re-expression of FLNaΔ3 did not. Immunostaining for VE-Cadherin in cells with knocked down R-Ras and FLNa demonstrated a disorganization of VE-Cadherin at adherens junctions. Loss of R-Ras and FLNa or blocking R-Ras function via GGTI-2133, a selective R-Ras inhibitor, induced vascular permeability and increased phosphorylation of VE-Cadherin (Y731) and Src (Y416). Expression of dominant negative R-Ras promoted vascular permeability that was blocked by the Src inhibitor PP2. These findings demonstrate that maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa and that loss of this interaction promotes VE-Cadherin phosphorylation and changes in downstream effectors that lead to endothelial leakiness.

Association between periodontitis and common variants in the promoter of the interleukin-6 gene.

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n=454) there were moderate associations for -1363T allele (p=0.011) and for -174GG and -1363GG genotypes with diagnosis of periodontitis (respectively, p=0.044, OR=1.6, 95% CI=1.0-2.4, and p=0.017, OR=1.8, 95% CI=1.1-2.8, adjusted for age, gender and smoking). Haplotypes containing the -174G>C, -1363G>T and -1480C>G polymorphisms were associated with diagnosis of periodontitis (p=0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and -1480C>G and -6106A>T SNPs (p=0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 -1480 CC and -6106 TT increased the adjusted OR for LAgP (OR=3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.

A familial analysis of aggressive periodontitis - clinical and genetic findings.

BACKGROUND AND OBJECTIVE: Family history is a primary diagnostic criterion for current classification of aggressive periodontitis (AgP). However, results of previous studies have shed controversy over the degree of familiarity of AgP and its possible inheritance mechanisms. The aims of this study were to estimate the percentage of affected relatives of AgP individuals, to analyse the disease phenotypes in relatives and to explore the distributions of genetic polymorphisms of interleukin-6 (IL-6) in AgP patients and in diseased and healthy relatives. MATERIAL AND METHODS: Patients with AgP were clinically examined and asked to provide relatives for examination. First-degree relatives were clinically and radiographically diagnosed. Blood samples were collected, DNA was extracted and analysis of single nucleotide polymorphisms of IL-6 (at positions -174, -1363 and -1480) by polymerase chain reaction was performed in patients and relatives. RESULTS: Fifty-five AgP patients provided relatives for examination. A total of 100 first-degree relatives were assessed and 10 of them (10%) were found to have AgP. All relatives diagnosed with AgP had the same disease as the corresponding proband (localized AgP/localized AgP or generalized AgP/generalized AgP). The same IL-6 genotypes (-174 GG, -1480 CC) previously associated with AgP showed a tendency for association with AgP in relatives. CONCLUSION: This pilot study confirmed a relatively high risk for relatives of AgP patients to have AgP (10%). Genetic polymorphisms in the IL-6 gene may have an impact in aetiopathogenesis. This study provides a sample size calculation for a novel study design using healthy relatives as control subjects.

Gene polymorphisms and the prevalence of key periodontal pathogens.

Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. The aim of this project was to study whether gene polymorphisms of inflammatory markers are associated with the presence of viable periodontopathogenic bacteria. We extracted genomic DNA from 45 young adults diagnosed with generalized aggressive periodontitis to study Fc receptors, formyl peptide receptor, Interleukin-6, tumor necrosis factor-alpha, and vitamin D receptor polymorphisms. The presence and viable numbers of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis were determined by culture, and their identities confirmed by PCR. Multiple logistic regressions revealed that both Fcgamma receptor and IL-6 -174 polymorphisms were associated with increased odds of detecting A. actinomycetemcomitans, P. gingivalis, and T. forsythensis after adjustment for age, ethnicity, smoking, and periodontitis extent. These findings support the hypothesis that complex interactions between the microbiota and host genome may be at the basis of susceptibility to aggressive periodontitis.

NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study.

INTRODUCTION: Neutrophils (PMN) in aggressive periodontitis (AgP) patients have been reported to be hyperactive especially with regards to superoxide production. Polymorphisms in genes influencing PMN function have been proposed as candidate risk factors for AgP. The aim of this study was to test the association of specific gene polymorphisms affecting PMN functions with AgP. MATERIALS AND METHODS: Two hundred and twenty-four patients with confirmed diagnosis of AgP and 231 subjects with healthy periodontium took part in the study. A blood sample was collected from subjects and genotypes for p22phox (CYBA) NADPH oxidase, FP, Fcalpha and Fcgamma receptors were analysed in a blind fashion. RESULTS: The C242T p22phox NADPH oxidase T allele was significantly associated with AgP in a multiple logistic regression model adjusting for confounders, and this was observed for all subjects [p = 0.002, odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.27-2.83] and Caucasians (p = 0.009, OR=2.07, 95% CI = 1.20-3.59). Concomitant presence of C242T p22phox NADPH oxidase T allele and FcgammaRIIIb NA1 homozygosity was associated with the generalized AgP phenotype in Caucasians (p = 0.001, OR = 30.35, 95% CI = 3.81-241.97). CONCLUSIONS: C242T p22phox NADPH oxidase and FcgammaR polymorphisms may predispose to AgP through a modulation of neutrophil superoxide production.

Periodontal status among relatives of aggressive periodontitis patients and reliability of family history report.

OBJECTIVES: To assess the periodontal status of relatives of Aggressive Periodontitis (AgP) patients, and to evaluate the reliability of the family history report as provided by the proband. MATERIAL AND METHODS: Data from 54 AgP patients were gathered along with a family history report for each of their relatives. Only 27 patients (probands) had relatives willing to be examined. This yielded a total of 61 relatives from whom the periodontal status was obtained. The family history report for each examined relative was compared with the periodontal diagnosis made at examination to assess reliability. RESULTS: Eight percentage of the examined relatives, aged between 12-76, were diagnosed with AgP, while chronic periodontitis was present in 39%, gingivitis in 38% and 15% were healthy. If the report provided by the proband was positive, the likelihood of finding any type of periodontitis in that relative was 85.7%, whereas if the report was negative the likelihood of the absence of periodontitis was 70.6%. CONCLUSION: The percentage of examined relatives who were affected with AgP (8%), although lower than percentages reported in other AgP family studies, was still higher than the prevalence of the condition in random populations. Reliability of periodontal family history was considered good and more reliable when it was positive.

Functional gene polymorphisms in aggressive and chronic periodontitis.

There is strong evidence that genetic as well as environmental factors affect the development of periodontitis, and some suggestion that aggressive and chronic forms of the disease share the same genetic predisposition. This study addresses the hypothesis that there are both shared and unique genetic associations in these forms of periodontitis. A sample of 51 patients with aggressive disease, 57 patients with chronic disease, and 100 healthy controls was recruited for this study. Ten functional polymorphisms in 7 candidate genes were genotyped. The results show statistically significant (p

Changes in transforming growth factor-beta1 in gingival crevicular fluid following periodontal surgery.

OBJECTIVES: Growth factors play a major part in wound healing, including in the periodontium. However, the presence of growth factors in gingival crevicular fluid (GCF) in humans during periodontal wound healing has not yet been determined. Our hypothesis is that such factors are present in GCF and that changes in their levels might be of value as a prognostic marker of wound-healing activity and therapeutic progress following periodontal surgery. The aim of this study was therefore to measure transforming growth factor-beta1 (TGF-beta1) in GCF collected from sites that have undergone guided tissue regeneration (GTR) and conventional flap (CF) surgery and to compare these with GCF collected from unaffected healthy sites. MATERIALS AND METHODS: GCF samples were collected, using filter paper strips, at baseline (pre-surgical) and then at intervals up to 26 weeks from 16 patients undergoing GTR and from 11 patients undergoing CF surgery. After elution and acid treatment, TGF-beta1 levels were measured by ELISA. RESULTS: Treatment of periodontal defect sites significantly reduced the mean probing pocket depth (PPD) and improved the mean lifetime cumulative attachment loss (LCAL). Average GCF volumes also significantly increased at all sites at 2 weeks post-surgery and thereafter declined to baseline levels, except at the GTR test sites that were still elevated at 7 weeks. TGF-beta1 could be detected in almost all GCF samples, and 2 weeks after surgery, the average levels increased two-fold at the surgically treated but not at the control sites, which remained unchanged. CONCLUSION: TGF-beta1 is readily detectable in GCF and increases transiently following periodontal surgery. This suggests that changes in the levels of this growth factor in GCF might be useful for monitoring the progress of periodontal repair and regeneration.

Unification of the "burst" and "linear" theories of periodontal disease progression: a multilevel manifestation of the same phenomenon.

Previously, burst and linear theories for periodontal disease progression were proposed based on different but limited statistical methods of analysis. Multilevel modeling provides a new approach, yielding a more comprehensive model. Random coefficient models were used to analyze longitudinal periodontal data consisting of repeated measures (level 1), sites (level 2), teeth (level 3), and subjects (level 4). Large negative and highly significant correlations between random linear and quadratic time coefficients indicated that subjects and teeth with greater-than-average linear change experienced decelerated variation. Conversely, subjects and teeth with less-than-average linear change experienced accelerated variation. Change therefore exhibited a dynamic regression to the mean at the tooth and subject levels. Since no equilibrium was attained throughout the study, changes were cyclical. When considered as a multilevel system, the "linear" and "burst" theories of periodontal disease progression are a manifestation of the same phenomenon: Some sites improve while others progress, in a cyclical manner.

Is reduction of pocket probing depth correlated with the baseline value or is it "mathematical coupling"?

Previous studies using correlation or regression analysis have showed that treatment effects measured by the change in clinical parameters are often associated with baseline values of the same parameters. These studies, however, have a methodological weakness. Correlation/regression between baseline measures and the derived change variable invalidates the statistical procedures of testing the null hypothesis: that the coefficient of correlation/regression is zero. This is due to the phenomenon of mathematical coupling. To investigate the impact that this has on the observed correlation/regression coefficient when in reality this is zero, we used random simulations of hypothetical data to model the treatment of periodontal pockets. Results showed a strong probability of obtaining statistically significant correlation/regression coefficients. To separate this artificial effect of mathematical coupling from the true underlying biological relationship, one must apply appropriate analytical strategies to re-evaluate previous evidence within the periodontal literature.

Prevalence and extent of lifetime cumulative attachment loss (LCAL) at different thresholds and associations with clinical variables: changes in a population of young male military recruits over 3 years.

AIM: The aims of this study were to monitor the prevalence and progression of lifetime cumulative attachment loss (LCAL) in a group of young British male military recruits over a 3-year period, and to determine the relationship between signs of LCAL and selected periodontal variables. METHODS: 100 subjects, aged 16-20 years (mean 17 years) at baseline, were examined at 0 (baseline), 12 and 30 months. LCAL, probing depth, plaque, bleeding on probing, gingival colour and supra- and subgingival calculus were assessed on the mesio-buccal, disto-buccal, mesio-lingual and disto-lingual surfaces of all teeth present, excluding third molars. Data were analysed cross-sectionally at each examination. RESULTS: Over the period of the study, the prevalence of LCAL > or =1 and 2 mm ranged from 95-100%, whereas LCAL > or =3 mm ranged from 40-47%. The extent of LCAL > or =1 mm ranged from 76-86%. However, the extent of LCAL > or =2 mm was dramatically lower (10.5-12.7%), and LCAL > or =3 mm was uncommon (0.5-0.9%). Examining the number of subjects according to the number of sites affected above a threshold, showed that a small number of subjects have a large number of sites above threshold. Using Pearson's rank correlation coefficient a significant correlation (p<0.05) was found between LCAL and the periodontal variables of gingival bleeding and supra- and subgingival calculus. CONCLUSIONS: These data suggest that the onset and progression of chronic periodontitis can be seen in young adults, and in this group gingival bleeding and supra- and subgingival calculus are the variables most strongly associated with early periodontitis.

Flow cytometry analysis of guided tissue regeneration-associated human periodontal cells.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) barrier membranes have been widely used for guided tissue regeneration (GTR) of the human periodontal ligament (PL). However, the precise cellular and molecular events involved in the re-growth of the new tissue are still unclear. METHODS: Retrieved membranes and the newly-regenerated soft tissue (RT) underlying the membranes were used to examine the cells associated with GTR compared with normal human PL and gingival cells. Flow cytometry (FCM) was used, for the first time, to analyze the spindle-shaped fibroblast-like cells which were adherent to these membranes and the cells which grew out of the RT. RESULTS: The results showed that the membrane-associated (M) cells had the lowest rate of proliferation and appeared to be larger and more granular than the other types of cell. Moreover, both the M- and RT-derived cells were found to express higher levels of the extracellular matrix (ECM) proteins collagen type 1, fibronectin, tenascin, and decorin. In addition, evidence based on FCM profiles identified distinct sub-populations of GTR cells in which fibronectin expression was markedly up-regulated compared with normal PL cells and which also differed in size and granularity. CONCLUSIONS: The results of this study show that cells associated with GTR barrier membranes and with the underlying tissue appear to have distinct phenotypic and functional activities consistent with the production of new periodontal connective tissue and periodontal regeneration.

An application of multilevel modelling to longitudinal periodontal research data.

OBJECTIVE: To introduce the concepts of random coefficient multilevel models through an application to periodontal research data. BASIC RESEARCH DESIGN: Multilevel models with random coefficients are illustrated using periodontal data that comprise four levels: repeated measurements at level-1, sites at level-2, teeth at level-3, and subjects at level-4. The study explores random coefficient models--where random variation occurs about explanatory variable coefficients. Outcomes considered are lifetime cumulative attachment loss and pocket probing depth. PARTICIPANTS: The study data were taken from a survey of periodontal disease involving 100 white male trainee engineers aged between 16 and 20 entering the apprentice training school at the Royal Air Force-Halton, UK. RESULTS: The application of multilevel modelling to longitudinal data provides a new way of exploring old problems. The multilevel random coefficient models provide an opportunity to examine the 'linear' and 'burst' theories of periodontal disease progression, leading to the postulation that both can be unified within the multilevel framework. CONCLUSIONS: The multilevel methodology illustrates how advances in the understanding of oral health can be achieved with the advent of new statistical methods

Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches.

AIM: In the present 6-month multicentre trial, the outcome of 2 different approaches to non-surgical treatment of chronic periodontitis, both involving the use of a locally delivered controlled-release doxycycline, was evaluated. MATERIAL AND METHODS: 105 adult patients with moderately advanced chronic periodontitis from 3 centres participated in the trial. Each patient had to present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth (PPD) of > or =5 mm and bleeding following pocket probing (BoP), out of which at least 2 sites had to be > or =7 mm and a further 2 sites > or =6 mm. Following a baseline examination, including assessments of plaque, PPD, clinical attachment level (CAL) and BoP, careful instruction in oral hygiene was given. The patients were then randomly assigned to one of two treatment groups: scaling/root planing (SRP) with local analgesia or debridement (supra- and subgingival ultrasonic instrumentation without analgesia). The "SRP" group received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia. In addition, at a 3-month recall visit, a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided. This was followed by subgingival application of an 8.5% w/w doxycycline polymer at sites with a remaining PPD of > or =5 mm. The patients of the "debridement" group were initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia, and followed by application of doxycycline in sites with a PPD of > or =5 mm. At month 3, sites with a remaining PPD of > or =5 mm were subjected to scaling and root planing. Clinical re-examinations were performed at 3 and 6 months. RESULTS: At 3 months, the proportion of sites showing PPD of < or =4 mm was significantly higher in the "debridement" group than in the "SRP" group (58% versus 50%; p<0.05). The CAL gain at 3 months amounted to 0.8 mm in the "debridement" group and 0.5 mm in the "SRP" group (p=0.064). The proportion of sites demonstrating a clinically significant CAL gain (> or =2 mm) was higher in the "debridement" group than in the "SRP" group (38% versus 30%; p<0.05). At the 6-month examination, no statistically significant differences in PPD or CAL were found between the two treatment groups. BoP was significantly lower for the "debridement" group than for the "SRP" group (p<0.001) both at 3- and 6 months. The mean total treatment time (baseline and 3-month) for the "SRP" patients was 3:11 h, compared to 2:00 h for the patients in the "debridement" group (p<0.001). CONCLUSION: The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis.

The influence of partial and full-mouth recordings on estimates of prevalence and extent of lifetime cumulative attachment loss: a study in a population of young male military recruits.

BACKGROUND: Previous studies have shown that the use of index teeth may underestimate the prevalence of chronic periodontitis in adults. However, there is little information on the effect of using index teeth to estimate the prevalence of early periodontitis in younger adults and the effect this may have on planning treatment needs and health care resources. The aim of this study was to compare full mouth examination with partial examination using index teeth in a group of young British males. METHODS: One hundred subjects aged between 16 and 20 years (mean 17 years) on entry to the study were examined at baseline, 12 months later, and 30 months later. Lifetime cumulative attachment loss (LCAL) > or =1 mm was measured on the mesio-buccal, disto-buccal, mesio-lingual, and disto-lingual surfaces of all teeth, excluding third molars. All data were entered into a database. The indices used to express LCAL were prevalence, defined as the percentage of subjects with LCAL > or =1 mm, 2 mm, or 3 mm, and extent, defined as the percentage of sites with LCAL > or =1 mm, 2 mm, or 3 mm. Two sets of index teeth were chosen to compare with full mouth recordings, Ramfjord index teeth and the Periodontal Index for Treatment (PIT) teeth. RESULTS: The prevalence of LCAL > or =1 mm was similar (approaching 100%) for the full mouth and both partial mouth recordings. However, as LCAL increased from a minimum of 1 to 3 mm, partial mouth recording resulted in an underestimation of the prevalence of disease. LCAL > or =2 mm was underestimated by up to 22% and LCAL > or =3 mm by up to 36%. The extent of LCAL was less affected by partial mouth recording, in that the percentage of sites with no sign of early attachment loss was underestimated by up to 11%. However, the percentage of sites with LCAL > or =1 mm and 2 mm were overestimated by 11% and, 7% respectively. CONCLUSIONS: These data indicate that the use of index teeth in epidemiological studies which include young adults may result in an underestimation of the prevalence of early periodontitis and an overestimation of the extent.

Comparison of clinical outcomes following treatment of chronic adult periodontitis with subgingival scaling or subgingival scaling plus metronidazole gel.

BACKGROUND, AIMS: Conventional treatment of chronic periodontitis involves mechanical debridement of periodontal pockets. Recently, subgingival antimicrobials have been used adjunctively following such debridement. This 2-centre study compared the clinical effects of subgingival scaling (SRP) with SRP plus subgingival application of 25% metronidazole gel, Elyzol (SRP+gel), in patients with chronic adult periodontitis. METHOD: Voluntary informed written consent was obtained from 45 subjects at the Eastman (mean age 46, range 34-63) and 43 subjects at RAF Halton (mean age 47, range 34-71) who participated in this blind, randomised split-mouth design study. All had at least 2 sites in each quadrant with probing pocket depth (PPD) > or = 5 mm. PPD, bleeding on probing (BOP), and clinical probing attachment levels (CAL) measured using a stent, were recorded at baseline and at 1, 3, 6 and 9 months post-therapy. After subgingival scaling of all quadrants, 2 quadrants were randomly selected to be treated with metronidazole gel. RESULTS: A paired t-test on baseline values showed no bias between groups. Both treatments effectively reduced the signs of periodontitis. At each follow-up visit, reduction in PPD, CAL and BOP after the combined treatment was greater than for SRP alone. Paired t-tests showed that the improvement in the SRP+gel group was statistically significantly better (p<0.001) than for SRP alone (mean 0.5 +/- 0.6 mm. 95% CI 0.4-0.6 mm.) Similarly, the % of sites which improved to a final pocket depth of < or = 3 mm and the % of sites which improved over the 9 months of the study by as much as > or = 2 mm were greater for SRP+gel than for SRP alone. CONCLUSIONS: At the end of the study, the mean reductions for PPD were 1.0 mm (SRP) compared to 1.5 mm (SRP+gel), and for CAL they were 0.4 mm (SRP) compared to 0.8 mm (SRP+gel), with mean difference for CAL between treatments of 0.4 +/- 0.6 mm (95% confidence intervals of 0.3-0.6 mm). The combination therapy of SRP+gel was superior to the conventional treatment of SRP alone, and these differences were maintained for 9 months.

The application of multilevel modelling to periodontal research data.

OBJECTIVE: To explain the theory of multilevel modelling and demonstrate its application in the analysis of dental research data. BASIC RESEARCH DESIGN: Multilevel modelling was introduced using dental data comprising four levels: repeated measurements at level-1, sites at level-2, teeth at level-3, and subjects at level-4. Variance components models (which have no explanatory variables) were evaluated for all outcome measures. Explanatory variables were added to the models with outcomes for both lifetime cumulative attachment loss and pocket probing depth. Salient features of the multilevel models were discussed. PARTICIPANTS: Research data were obtained from a longitudinal survey of periodontal disease conducted on 100 white male trainee engineers aged between 16 and 20 years entering the apprentice training school at Royal Air Force Halton, England. RESULTS: The statistical methods revealed that periodontal measures demonstrate considerable variation at all levels of the multilevel structure. Models for lifetime cumulative attachment loss and pocket probing depth illustrated that risk factors operated at more than one level. Supragingival calculus was a risk factor at the subject-level (subjects experiencing more sites with the condition had greater attachment loss and greater pocketing) whilst there was apparently a protective effect occurring at the site (sites with the condition had less attachment loss and less pocketing). CONCLUSIONS: This study demonstrates that multilevel modelling is a more powerful research tool than single-level techniques for the analysis of hierarchical dental data. Researchers using these techniques are well equipped to analyse complex hierarchical data structures, such as those often found within dentistry.