Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction.

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

Periodontal disease is associated with carotid plaque area: the Malmö Offspring Dental Study (MODS).

BACKGROUND: Periodontal disease is associated with cardiovascular disease (CVD) but it is unknown if periodontal disease severity is associated with asymptomatic carotid plaque. The aim of the current population-based, observational study was to investigate if signs of periodontal disease are associated with the occurrence of carotid plaque and total plaque area (TPA). METHODS: The Malmö Offspring Study (MOS) is a population-based study. MOS participants underwent a thorough cardiovascular phenotyping, including carotid ultrasonography. The Malmö Offspring Dental Study (MODS) invited participants of MOS for dental examination, including periodontal charting. Multivariable regression models were used to analyse the presence of carotid plaque and TPA in relation to periodontal parameters. RESULTS: In all, 831 MODS participants were recruited, out of which 495 belonged to the children generation with mean age of 53 years, 63% had carotid plaque and 38% had moderate or severe periodontal disease. In models adjusted for CVD risk factors, the OR for having carotid plaque in subjects with vs without periodontal disease was 1.75 (95% CI: 1.11-2.78). In a linear model with TPA as dependent and number of periodontal pockets ≥ 4 mm as independent variable, the adjusted beta-coefficient was 0.34 mm2 (95% CI 0.16-0.52). CONCLUSION: Individuals within the highest quartile of periodontal pockets are expected to have 9 mm2 larger TPA compared to those without pockets. Our results suggest that intervention studies addressing periodontal disease could be useful for prevention of CVD.

Statins in nonsurgical and surgical periodontal therapy. A systematic review and meta-analysis of preclinical in vivo trials.

The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial and pro-osteogenic properties, and thus have been tested as an adjunct to periodontal treatment. The present systematic review aimed to answer the following focused research question: What is the effect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studies of experimentally induced periodontitis (EIP) and/or acute/chronified periodontal defect (ACP) models? A literature search (of Medline/PubMed, Embase/Ovid, CENTRAL/Ovid) using the following main eligibility criteria was performed: (i) English or German language; (ii) controlled preclinical in vivo trials; (iii) local and/or systemic statin use in EIP and/or ACP models; and (iv) quantitative evaluation of periodontal tissues (i.e., alveolar bone level/amount, attachment level, cementum formation, periodontal ligament formation). Sixteen studies in EIP models and 7 studies in ACP models evaluated simvastatin, atorvastatin or rosuvastatin. Thirteen of the EIP (81%) and 2 of the ACP (29%) studies presented significantly better results in terms of alveolar bone level/amount in favor of statins. Meta-analysis based on 14 EIP trials confirmed a significant benefit of local and systemic statin use (P < .001) in terms of alveolar bone level/amount; meta-regression revealed that statin type exhibited a significant effect (P = .014) in favor of atorvastatin. Three studies reported a significantly higher periodontal attachment level in favor of statin use (P < .001). Complete periodontal regeneration was never observed; furthermore, statins did not exert any apparent effect on cementum formation. Neither local nor systemic use of statins resulted in severe adverse effects. Statin use in periodontal indications has a positive effect on periodontal tissue parameters, supporting the positive results already observed in clinical trials. Nevertheless, not all statins available have been tested so far, and further research is needed to identify the maximum effective concentration/dose and optimal carrier.

Periodontal treatment and HbA1c levels in subjects with diabetes mellitus.

It has earlier been reported that individuals with poorly controlled diabetes have severe periodontal disease (PD) compared to well-controlled diabetes. This longitudinal interventional study compared periodontal treatment outcomes with HbA1c level changes in four groups of diabetic and non-diabetic patients with or without PD, respectively. HbA1c, bleeding on probing (BOP), plaque index and periodontal pocket depth (PPD) 4 < 6 mm and ≥6 mm were recorded at baseline to 3 months after non-surgical treatment and 3-6 months for surgical treatment in subjects with or without T2D, and with or without PD. A total of 129 patients were followed from baseline to 6 months. Diabetics with PD and without PD showed reductions in HbA1c levels with a mean value of 0·3% after 3 months and mean values of 1% and 0·8%, respectively, after 6 months. Diabetics with PD showed higher levels of BOP versus non-diabetics without PD (P < 0·01) and versus diabetics without PD (P < 0·05) at baseline. After 6 months, diabetics with PD showed higher number of PPD 4 < 6 mm versus diabetics without PD (P < 0·01) and non-diabetics with PD (P < 0·01). Diabetics without PD showed higher levels of PPD 4 < 6 mm versus non-diabetics without PD (P < 0·01). Surgical and non-surgical periodontal treatment in all groups improved periodontal inflammatory conditions with a decrease in HbA1c levels in a period of three and 6 months. No change was seen in the number of pockets PPD 4 < 6 mm in diabetic subjects with PD after non-surgical and surgical treatment.

Developing implant dentistry education in Europe: the continuum from undergraduate to postgraduate education and continuing professional development.

INTRODUCTION: Implant dentistry is a treatment modality which has mainstream clinical practice of comprehensive care, which however is not adequately represented in the undergraduate dental curricula. A consensus workshop organised by ADEE in 2008, set the benchmarks for the knowledge and competences a modern dental practitioner must possess with regard to implant dentistry, as well as defined undergraduate and postgraduate pathways for the acquisition of these competences. Today, 5 years later, there exist several challenges for the implementation of these benchmarks in both undergraduate curricula but also post-graduation educational pathways. METHODS: A consensus workshop was organised by ADEE, bringing together 48 opinion leaders, including academic teachers of all disciplines related to implant dentistry, specialists, representatives of relevant scientific and professional associations, as well as industry delegates. The objectives of the workshop were to evaluate the existing scientific literature, reported experience and best practices in order to identify potential and limitations for the implementation of implant dentistry in the undergraduate curriculum, as well produce recommendations for the optimal educational structures for postgraduate programmes and continuing professional development. RESULTS: The scientific committee conducted two European-wide questionnaire surveys to better document the current state of education in implant dentistry. Upon completion of the surveys, reviewers were appointed to produce three scientific review papers, identifying current achievements and future challenges. Finally, during the 3 days of the workshop, all the evidence was reviewed and the main conclusions and recommendations that were adopted by all participants are reported in the present Consensus Paper. CONCLUSIONS: Implementation of implant dentistry in the undergraduate curriculum has improved significantly, but still lags behind the benchmarks set in 2008 and the diversity between institutions remains big. At the post-graduation level, there is currently a wide diversity of courses and pathways towards competences related to implant dentistry and there is at present a great need for quality assurance, as well as standardisation and transparency of the learning outcomes.

Global oral health inequalities: task group--periodontal disease.

Periodontal diseases constitute one of the major global oral health burdens, and periodontitis remains a major cause of tooth loss in adults worldwide. The World Health Organization recently reported that severe periodontitis exists in 5-20% of adult populations, and most children and adolescents exhibit signs of gingivitis. Likely reasons to account for these prevalent diseases include genetic, epigenetic, and environmental risk factors, as well as individual and socio-economic determinants. Currently, there are fundamental gaps in knowledge of such fundamental issues as the mechanisms of initiation and progression of periodontal diseases, which are undefined; inability to identify high-risk forms of gingivitis that progress to periodontitis; lack of evidence on how to prevent the diseases effectively; inability to detect disease activity and predict treatment efficacy; and limited information on the effects of integration of periodontal health as a part of the health care program designed to promote general health and prevent chronic diseases. In the present report, 12 basic, translational, and applied research areas have been proposed to address the issue of global periodontal health inequality. We believe that the oral health burden caused by periodontal diseases could be relieved significantly in the near future through an effective global collaboration.

Tissue augmentation and esthetics (Working Group 3).

INTRODUCTION: The remit of this working group was to update the existing knowledge base regarding bone augmentation for implant site development and soft-tissue grafting for esthetic outcomes. Four reviews from the working group formed the basis of this update. Moreover, clinical applications as well as suggestions for further research have been formulated. MATERIALS AND METHODS: The papers in the working group critically reviewed the literature. Four manuscripts were produced assessing (a) the outcomes of correcting dehiscence and fenestration defects at implant sites using various graft materials, (b) the outcomes of sinus floor augmentation at maxillary posterior sites with 6 mm or less residual bone height using various graft materials, (c) the association of the horizontal dimensions of buccal and interproximal bone with esthetic outcomes of implant-supported restorations, and (d) the outcomes of soft-tissue augmentations. RESULTS: The results and conclusions of the review process are presented in the following papers. The group's consensus statements, clinical implications, and directions for future research are presented in this article.

Self-perceived oral health and salivary proteins in children with type 1 diabetes.

The aim was to validate self-perceived oral health with salivary IgG as an inflammatory parameter in children with type 1 diabetes. Unstimulated whole saliva samples were collected from 36 children with well controlled and 12 with poorly controlled type 1 diabetes and 40 non-diabetic children (Controls). Salivary flow rate, random blood glucose level, salivary protein concentration and immunoglobulin A and G levels were recorded using standard techniques. Data concerning oral health and diabetes status were collected. Self-perceived gingival bleeding (bleeding gums), bad breath and dry mouth were higher in diabetic children when compared with those in controls (P < 0.05). Gingival bleeding was frequently perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.001). Bad breath was common perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.0001). Salivary flow rate was lower in the diabetic children compared to controls (P < 0.01) with no difference between children with poorly controlled and well-controlled type 1 diabetes. Salivary IgG per mg protein concentration was higher in the diabetics when compared with the control group (P < 0.0001). IgG per mg protein levels were also higher in children with poorly controlled when compared with well-controlled type 1 diabetes (P < 0.05). There was no difference in IgA per mg protein and total protein concentrations between children with poorly controlled and well-controlled type 1 diabetes. Self-perceived gingival bleeding and salivary IgG per mg protein concentration were increased in children with type 1 diabetes compared with controls. These variables were also increased in children with poorly controlled compared with well-controlled type 1 diabetes.

Periodontitis and premature death: a 16-year longitudinal study in a Swedish urban population.

BACKGROUND AND OBJECTIVE: Growing experimental evidence implicates chronic inflammation/infection due to periodontal diseases as a risk factor for death. The objective was to evaluate the role of periodontitis in premature death in a prospective study. METHODS: The causes of death in 3273 randomly-selected subjects, aged 30-40 years, from 1985 to 2001 were registered. At baseline, 1676 individuals underwent a clinical oral examination (Group A) and 1597 did not (Group B). Mortality and causes of death from 1985 to 2001 were recorded according to ICD-9-10. RESULTS: In Groups A (clinically examined group) and B, a total of 110 subjects had died: 40 subjects in Group A, and 70 in Group B. In Group A significant differences were present at baseline between survivors and persons who later died, with respect to dental plaque, calculus, gingival inflammation and number of missing molars in subjects with periodontitis (p < 0.001). The multiple logistic regression analysis results of the relationship between being dead (dependent variable) and several independent variables identified periodontitis with any missing molars as a principal independent predictor of death. CONCLUSIONS: Young individuals with periodontitis and missing molars seem to be at increased risk for premature death by life-threatening diseases, such as neoplasms, and diseases of the circulatory and digestive systems.

Quantitative assessment of apoptotic and proliferative gingival keratinocytes in oral and sulcular epithelium in patients with gingivitis and periodontitis.

BACKGROUND: Periodontal disease is caused by a chronic infection inducing an inflammatory reaction that leads to a breakdown of tooth-supporting tissue. The maintenance of an equilibrium between the host defence and microorganisms in the sulcus is essential to preserve health. All multicellular organisms have mechanisms for killing their own cells, and use physiological cell death for defence, development, homeostasis and ageing. Apoptosis and proliferation are very important phenomena in regulating this and a disturbance is often associated with disease e.g. cancer, AIDS, Alzheimer's disease, rheumatoid arthritis. OBJECTIVE: The aim of this study was to determine whether the number of apoptotic and proliferative gingival keratinocytes differed between patients with gingivitis and those with periodontitis. MATERIAL AND METHODS: The distribution of neutrophil elastase, PCNA/cyclin, DNA fragmentation (apoptosis) and p53 was determined with immunocytochemical techniques. We used paraffin-embedded sections from gingival biopsies and did quantitative analyses. RESULTS AND CONCLUSION: These showed that 5-12% of the keratinocytes in the basal layers of the epithelium proliferated in the two groups. Fewer apoptotic cells were seen in the oral epithelium than in the sulcus in all subjects in both groups. Only in the most apical part of the sulcus, close to the junctional epithelium, did the number of apoptotic keratinocytes exceed the proliferative ones in patients with periodontitis.

Oral health and cardiovascular disease in Sweden.

OBJECTIVE: The purpose of the present study was to assess the relation between dental health and cardiovascular disease in an adult Swedish population. MATERIAL AND METHOD: A questionnaire was sent to 4811 randomly selected Swedes. It contained 52 questions about dental care habits, oral health, cardiovascular disease and their socio-economic situation. Odd ratios for all cardiovascular diseases (CVD) and the subgroup myocardial infarction, stroke and high blood pressure were calculated with a logistic regression model adjusted for age, gender, smoking, income, civil status and education. These ratios were calculated for subjects > or =41 years since few people suffer from CVD before this. RESULTS: The national questionnaire was answered by 2839 (59%) people between 20-84 years of age and, of them, 1577 were 41 years of age or more. We found a significant association between self-reported bleeding gums (odds ratio 1.60, p=0.0017), presence of dentures (odds ratio 1.57, p=0.0076) and known CVD, which has also been reported in international studies. However, no association between loose teeth, deep pockets and known CVD was detected. CONCLUSION: The results indicate that oral health and, especially gingival inflammation is associated with CVD.

Long-term evaluation of osseointegrated dental implants in the treatment of partly edentulous patients.

AIM: The aim of this study was to evaluate the clinical, radiographic and microbiological status of implants after 10 years of functional load in patients treated for partial edentulism. METHOD: 15 patients, each successfully treated with 2-6 implants ad modum Brånemark placed in free-standing fixed prostheses, were included in the study. RESULTS: Clinical evaluation revealed similar degrees of inflammation around teeth and implants. The probing pocket depth (PPD) was significantly greater around implants than around teeth. The mean marginal bone loss during 10 years of functional load was comparable to that found at the time of the 5-year follow-up. 74% of the implants remained free of marginal bone loss exceeding 1 mm. Marginal bone loss exceeding 2 mm, was found at only 5 sites. No marked differences in bacteria were present between teeth and implants. T. denticola, S. intermedia and P. micros were the commonest organisms detected around teeth and implants. The periodontal pathogens A. actinomycetemcomitans, P. gingivalis, P. intermedia, B. forsythus, and T. denticola, were found at implants with a marginal bone loss of more than 2 mm. CONCLUSION: Our study shows that the long-term results with implants in partially dentate patients are similar to those seen in edentulous patients and that no significant change occurred after 5-year follow-up over an additional period of 5 years.

Immunolocalization of interleukin-8 and proliferating cell nuclear antigen in gingival keratinocytes in patients with periodontitis.

The aim of this study was to investigate the relation between local expression of IL-8 and the localization of neutrophilic granulocytes, using CD16 as a marker of neutrophils. We also investigated the correlation between IL-8 and epithelial proliferation using proliferating cell nuclear antigen (PCNA) as a marker of proliferation. The distribution of IL-8, CD16 and PCNA/cyclin was determined by immunocytochemical techniques. We used cryostat-cut sections from gingival biopsies harvested from 5 subjects with and 5 subjects without periodontitis. Our histological examination demonstrated that the localization of neutrophilic granulocytes in gingival tissue from patients with periodontitis did not correlate with the expression of IL-8. In all tissue sections from patients and controls, the inflammatory cells accumulated near the pocket epithelium and only a few leukocytes deviated from this pattern. In the patient group, keratinocytes not belonging to the pocket or junctional epithelium expressed IL-8 without any evidence of a chemoattractant effect on neutrophils. The marker of proliferation, PCNA/cyclin, was expressed in keratinocytes in the basal cell layer. The expression was less pronounced in the control group. Our finding that IL-8 was expressed in proliferating cells suggests that IL-8 may have a role in keratinocyte proliferation.

Factors affecting late fixture loss and marginal bone loss around teeth and dental implants.

BACKGROUND: The predictability and high success rate of implant treatment have averted attention from factors affecting fixture loss and bone loss around implants. PURPOSE: The goal of this study was to retrospectively evaluate late fixture loss and marginal bone loss around implants that have been in function for 5 years and to relate these findings to bone loss in the natural dentition. MATERIALS AND METHODS: One hundred and forty-three consecutively treated patients who had received an implant-anchored fixed prosthesis and completed a 5-year follow-up were selected. Intraoral and panoramic radiographs were used to assess bone loss. RESULTS: The bone loss was greater around remaining implants in patients who had lost implants after loading. No correlation was found between bone loss around implants and that around teeth. Only 2% of the fixtures were lost during 5 years of functional load. Most fixtures losses occurred in the edentulous maxilla. Seven of the nine patients who lost fixtures were smokers. CONCLUSION: These findings show that patients who lost implants also lost more bone around the remaining implants. There was no correlation between bone loss around implants and that around teeth, indicating that different interacting mechanisms are involved.

Augmented levels of macrophage and Th1 cell-related cytokine mRNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis.

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of the salivary and lachrymal glands resembling Sjögren's syndrome (SS), representing an animal model to study this disease. We used in situ hybridization with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4 and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland infiltrates was evaluated by immunohistochemistry. Cells expressing tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-12 mRNA were strongly up-regulated at about the time of onset of sialoadenitis, suggesting a role of these cytokines in development of the disease. Interferon-gamma (IFN-gamma) and cytolysin mRNA-expressing cells were gradually up-regulated over the disease course up to 5 months of age, the time when sialoadenitis is at its height, favouring a role of these cytokines in progression of the disease as well. Low levels of IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing cells were observed at 2, 3 and 4 months of age, and were almost undetectable at 5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as well as of MHC class II and MHC class I expression were seen at 3 months, with CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months of age. These data argue for a major role of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, IL- 12, IFN-gamma and cytolysin in initiation and perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction with an insufficiency of the anti-inflammatory cytokines TGF-beta and IL-10.

Coordinate up-regulation of the beta-chemokine subfamily in autoimmune sialoadenitis of MRL/lpr mice.

Mononuclear cell (MNC) infiltration of the salivary and lacrimal glands is a major feature in Sjogren's syndrome (SS) and its animal model, murine autoimmune sialoadenitis (MAS). To investigate factors that influence selective infiltration by MNC of submandibular glands in young and adult MRL/lpr mice with MAS, expression of mRNA encoding the beta-chemokines monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation, normal T-cell expressed and secreted (RANTES) was investigated by in situ hybridization. MCP-1 protein production was also evaluated by immunohistochemistry. Young mice with MAS showed an early up-regulation of mRNA expression for MCP-1, MIP-1beta and RANTES, while MIP-1alpha mRNA expression was not affected. Adult mice with MAS showed a further up-regulation of mRNA expression for MCP-1, MIP-1beta and RANTES, and a remarkably strong up-regulation for MIP-1alpha. Immunohistochemistry revealed that MCP-1 protein production paralleled MCP-1 mRNA expression in both young and adult mice. These observations implicate MCP-1, MIP-1beta and RANTES as potential chemokines in induction of MAS, and MCP-1, MIP-1beta, RANTES and prominently MIP-1alpha in progression and perturbation of MAS.

The IBP genes of maize are expressed in non-meristematic, elongating cells of the seedling and in abortive floral organs.

The transcription start site of the maize Shrunken-1 (Sh-1) gene is sufficient for transcriptional initiation in the absence of other promoter elements and is recognized in vitro by the Initiator Binding Protein (IBP). We describe here in situ hybridization experiments performed on various maize tissues to quantify IBP transcription at the cellular level. IBP transcripts are found in the endosperm and in differentiating, enlarging cells of the shoot and the root of the maize seedling. This expression pattern overlaps with that of the Sh-1 gene and is therefore compatible with the hypothesis that the Sh-1 transcription start site is a target for IBP. In the developing spikelets of male and female inflorescences IBP transcript levels are very high in those organs that are later aborted when flowers become unisexual. Overexpression of the maize IBP1 gene product in transgenic tobacco causes a reduction in internodal elongation and effects gibberellin hormonal balance. The cellular expression pattern described here establishes IBP transcripts as an interesting molecular marker for enlarging, and presumably differentiating, cells released from the root or shoot apex.

Trabecular bone volume and bone mineral density in the mandible.

OBJECTIVES: To explore the possible correlation between trabecular bone volume and bone mineral density in the mandible. METHODS: Bone mineral density of the trabecular bone was obtained by quantitative computed tomography of 22 edentulous anterior and posterior sections of nine mandibles obtained at autopsy. A computer-based image analysis system was used for morphometric measurements to derive trabecular bone volume from contact radiographs. RESULTS: A significant correlation was found between trabecular bone volume and bone mineral density. The trabecular bone volume varied significantly between and within mandibles. CONCLUSION: The high correlation between trabecular bone volume and bone mineral density means that the use of quantitative computed tomography prior to implant treatment is a valid procedure.