Mark Bartold

Longitudinal displacement of the carotid wall and cardiovascular risk factors: associations with aging, adiposity, blood pressure and periodontal disease independent of cross-sectional distensibility and intima-media thickness

The recently discovered longitudinal displacement of the common carotid arterial wall (i.e., the motion along the same plane as the blood flow), may be associated with incident cardiovascular events and represents a novel and relevant clinical information. At present, there have only been a few studies that have been conducted to investigate this longitudinal movement. We propose here a method to assess noninvasively the wall bi-dimensional (two-dimensional [2-D], cross-sectional and longitudinal) motion and present an original approach that combines a robust speckle tracking scheme to guidance by minimal path contours segmentation. Our method is well suited to large clinical population studies as it does not necessitate strong imaging prerequisites. The aim of this study is to describe the association between the longitudinal displacement of the carotid arterial wall and cardiovascular risk factors, among which periodontal disease. Some 126 Indigenous Australians with periodontal disease, an emerging risk factor, and 27 healthy age- and sex-matched non-indigenous control subjects had high-resolution ultrasound scans of the common carotid artery. Carotid intima-media thickness and arterial wall 2-D motion were then assessed using our method in ultrasound B-mode sequences. Carotid longitudinal displacement was markedly lower in the periodontal disease group than the control group (geometric mean (IQR): 0.15 mm (0.13) vs. 0.42 mm (0.30), respectively; p < 0.0001), independent of cardiovascular risk factors, cross-sectional distensibility and carotid intima-media thickness (p < 0.0001). A multivariable model indicated that the strongest correlates of carotid longitudinal displacement in adults with periodontal disease were age (β-coefficient = -.235, p = .03), waist (β-coefficient = -.357, p = 0.001), and pulse pressure (β-coefficient = .175, p = 0.07), independent of other cardiovascular risk factors, cross-sectional distensibility and pulse wave velocity. Carotid longitudinal displacement, estimated with our approach, is impaired in the periodontal disease group, independent of established cardiovascular risk factors and other noninvasive measures of arterial stiffness, and may represent an important marker of cardiovascular risk.

The Nature and Frequency of Bisphosphonate-Associated Osteonecrosis of the Jaws in Dental Implant Patients: A South Australian Case Series

PURPOSE To determine the number of bisphosphonate-associated cases of dental implant failure in South Australia. MATERIALS AND METHODS All general and specialist dentists who place dental implants in South Australia were contacted and asked to provide information on the total number of implants placed over the decade to December 2007. Cases of bisphosphonate-associated implant failure were identified. RESULTS All 46 practitioners involved in implant placement and the management of bisphosphonate-associated osteonecrosis of the jaws in South Australia were identified. Approximately 28,000 implants had been placed in 16,000 patients. We identified 7 cases of oral bisphosphonate-associated implant failure, with 3 cases of failure of osseointegration and 4 cases of successful implants losing integration after being placed on oral bisphosphonates. There were 5 women and 2 men, and the mean age was 65.7 years (range, 49-75 years). Only 1 was medically compromised, with steroids and diabetes. No cases of implant failure in intravenous bisphosphonate cases were identified. On the basis of the assumption that 5% of the patients were taking an oral bisphosphonate, 1 in 114 (0.89%) had implant failure. CONCLUSION In patients taking oral bisphosphonates, a failure to integrate or subsequent loss of integration may occur when oral bisphosphonates are started after successful implant placement. The rate of failure is low, at less than 1%.

Porphyromonas gingivalis Peptidylarginine Deiminase, a Key Contributor in the Pathogenesis of Experimental Periodontal Disease and Experimental Arthritis

Objectives To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions. Methods A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA. Results The development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group. Conclusion This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.

The effect of a periodontal intervention on cardiovascular risk markers in Indigenous Australians with periodontal disease: the PerioCardio study

BackgroundIndigenous Australians experience an overwhelming burden of chronic disease, including cardiovascular diseases. Periodontal disease (inflammation of the tissues surrounding teeth) is also widespread, and may contribute to the risk of cardiovascular diseases via pathogenic inflammatory pathways. This study will assess measures of vascular health and inflammation in Indigenous Australian adults with periodontal disease, and determine if intensive periodontal therapy improves these measures over a 12 month follow-up. The aims of the study are: (i) to determine whether there is a dose response relationship between extent and severity of periodontal disease and measures of vascular health and inflammation among Indigenous Australian adults with moderate to severe periodontal disease; and (ii) to determine the effects of periodontal treatment on changes in measures of vascular health and inflammation in a cohort of Indigenous Australians.Methods/DesignThis study will be a randomised, controlled trial, with predominantly blinded assessment of outcome measures and blinded statistical analysis. All participants will receive the periodontal intervention benefits (with the intervention delayed 12 months in participants who are randomised to the control arm). Participants will be Indigenous adults aged ≥25 years from urban centres within the Top End of the Northern Territory, Australia. Participants assessed to have moderate or severe periodontal disease will be randomised to the studys intervention or control arm. The intervention involves intensive removal of subgingival and supragingival calculus and plaque biofilm by scaling and root-planing. Study visits at baseline, 3 and 12 months, will incorporate questionnaires, non-fasting blood and urine samples, body measurements, blood pressure, periodontal assessment and non-invasive measures of vascular health (pulse wave velocity and carotid intima-media thickness). Primary outcome measures are pulse wave velocity and carotid intima-media thickness.DiscussionThe study will assess the periodontal-cardiovascular disease relationship among Indigenous Australian adults with periodontal disease, and the effectiveness of an intervention aimed at improving periodontal and cardiovascular health. Efforts to understand and improve Indigenous oral health and cardiovascular risk may serve as an important means of reducing the gap between Indigenous and non-Indigenous health in Australia.Trial RegistrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000817044

Immunomodulatory properties of mesenchymal stem cell in experimental arthritis in rat and mouse models: A systematic review

BACKGROUND Despite recent advances in the treatment of arthritis with the development of disease-modifying antirheumatic drugs, 30% of patients still fail to respond to treatment. Given the potent anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) and their ability to repair damaged cartilage, bone, and tendons, it has been proposed that MSC could be ideal for cell-based treatment of arthritis. OBJECTIVE This systematic review investigates evidence from studies on the therapeutic efficacy of MSC in rodent models of arthritis. METHODS PubMed, Embase, MEDLINE, and Wed of Science were searched to June 2015 for quantitative studies examining the outcome of treating animal models of arthritis with MSC. Inclusion criteria were as follows: administration of mesenchymal stem as a treatment approach for arthritis; animal models only; and published in English. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS The literature search identified 30 studies which met the inclusion criteria. A range of MSC populations were assessed in various rodent models of arthritis. Of these, 19 demonstrated positive outcomes while 11 studies failed to demonstrate positive effects. Owing to the extensive variation in the experimental design, cells investigated and the outcome measures described in the manuscripts, no meta-analysis was possible. Furthermore, the numerical values for the primary outcome measure of clinical paw score were frequently not published in the manuscripts analyzed, as they were only illustrated in graphical form. CONCLUSIONS Numerous studies have investigated the utility of a range of MSC populations in the treatment of experimental arthritis. The results obtained from these studies have been highly inconsistent, with multiple studies identifying a statistically significant improvement in arthritis scores after treatment with MSC, while other studies identified a statistically significant deterioration in arthritis scores and thirdly some studies showed no effect. Further studies using standardized protocols and outcome measures are needed to determine fully the potential of MSC populations in the treatment of experimental arthritis.

Differentiation of iPSC to Mesenchymal Stem-Like Cells and Their Characterization

Mesenchymal stem cells (MSC) are a unique population of adult stem cells that have the capacity to differentiate into numerous cell types as well as the ability to modulate the immune system. As such, MSC represent a promising stem cell population for use in the clinical treatment of a range of disorders involving tissue regeneration as well as the immune system. The lack of accessibility to MSC is currently limiting the use of MSC in mainstream clinical treatment strategies. It is therefore imperative for the future success of stem cell-based treatment approaches that are more reliable, and accessible sources of MSC are identified. The present chapter describes a method for generating MSC-like cells from induced pluripotent stem cells (iPSC), with equivalent growth and functional properties to parental MSC populations.

Psychological distress and self-rated oral health among a convenience sample of Indigenous Australians

OBJECTIVES This study sought to: a) estimate the frequency of poor self-rated oral health as assessed by a summary measure; b) compare frequency according to sociodemographic, behavioral, and psychological distress factors; and (3) determine if psychological distress was associated with poor self-rated oral health after adjusting for confounding. METHODS Data were from a convenience sample of Indigenous Australian adults (n = 289) residing in Australias Northern Territory. Poor self-rated oral health was defined as reported experience of toothache, poor dental appearance or food avoidance in the last 12 months. A logistic regression model was used to evaluate socio-demographic, behavioral, and psychological distress associations with poor self-rated oral health (SROH). Effects were quantified as odds ratios (OR). RESULTS The frequency of poor SROH was 73.7 percent. High psychological distress, measured by a Kessler-6 score ≥8, was experienced by 33.9 percent of participants. Poor SROH was associated with high levels of psychological distress, being older, being female, and usually visiting a dentist because of a problem. In the multivariable model, factors that were significantly associated with poor SROH after adjustment for other covariates included having a high level of psychological distress (OR 2.74, 95% CI 1.25-6.00), being female (OR 2.22, 95% CI 1.03-4.78), and usually visiting a dentist because of a problem (OR 3.57, 95% CI 1.89-6.76). CONCLUSIONS Poor self-rated oral health and high levels of psychological distress were both highly frequent among this vulnerable population. Psychological distress was significantly associated with poor self-rated oral health after adjustment for confounding.

Factors Associated with Routine Dental Attendance among Aboriginal Australians

Objectives. To determine factors associated with routine dental attendance in Aboriginal Australians. Methods. Data of 271 Aboriginal adults residing in Australia’s Northern Territory were used. Routine dental attendance was defined as last visiting a dentist less than one year ago or visiting a dentist for a check-up. Both bivariate and multivariable analytical techniques were used. Results. While 27% visited a dentist in the past year, 29% of these visited for a check-up. In bivariate analysis, being female, low psychological distress, and low clinical attachment loss (CAL) were associated with visiting a dentist within last year. Being aged younger than 39 years, male, no oral health impairment, being caries-free, low CAL, and low apolipoprotein B were associated with visiting for a check-up. Clinical attachment loss remained associated with visiting a dentist less than one year ago while being younger than 39 years and having no oral health impairment remained associated with usually visiting for a check-up in multivariable analysis. Conclusions. Younger age, no oral health impairment, and low CAL were associated with routine dental attendance among Indigenous Australians.