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Biomedical subjects

M S Tonetti

Publications and source records attributed to M S Tonetti.

At least 19 recordsLinked to original sources

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.

Adult↗

Periodontal therapy: a novel acute inflammatory model.

OBJECTIVE AND DESIGN: We designed a clinical trial at the Eastman Dental Hospital with the objective of developing a novel in vivo inflammatory model. SUBJECTS: We recruited 55 subjects suffering from severe periodontitis. TREATMENT: Participants received intensive periodontal therapy. METHODS: Blood samples were collected at baseline and 1 and 7 and 30 days after treatment and processed for a series of biomarkers (TNF-alpha, IL-6, CRP and Fibrinogen) by high-sensitivity assays and differential blood counts (standard laboratory procedures). RESULTS: TNF-alpha levels were significantly raised only after 1 day of therapy (P<0.01) whereas IL-6 (P<0.01), CRP (P<0.001) and Fibrinogen (P<0.001) concentrations peaked 24 hrs after and returned to baseline values within one month following therapy. Mild neutrophilia, monocytosis and lymphopenia were also observed. CONCLUSIONS: Intensive periodontal therapy induces a one week moderate inflammatory response and therefore it is proposed as a novel therapeutic and reliable non drug-induced in vivo model of acute inflammation.

Acute Disease↗

Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol.

Severe periodontitis has been associated with increased systemic inflammation. In a three-arm preliminary randomized trial, we investigated the impact of standard (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP), interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis. Two months after treatment, both SPT and IPT resulted in significant reductions in serum CRP compared with the untreated control (0.5 +/- 0.2 mg/L for SPT, P = 0.030 and 0.8 +/- 0.2 mg/L for IPT, P = 0.001). Similar results were observed for IL-6. Changes in inflammation were independent of age, gender, body mass index, and ethnicity, but a significant interaction between cigarette smoking and treatment regimen was found. The IPT group also showed a decrease in total and LDL cholesterol after 2 months. Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects.

Adult↗

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections.

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.

Base Sequence↗

Periodontal therapy: a novel non-drug-induced experimental model to study human inflammation.

BACKGROUND: Chronic periodontitis causes a low-grade systemic inflammatory response; its standard treatment, however, induces an acute inflammatory response. The aim of this study was to describe the systemic inflammatory reactions to an intensive periodontal treatment regimen. METHODS: Fourteen otherwise healthy subjects suffering from severe chronic periodontitis were enrolled in a 1 month pilot single-blind trial. Intensive periodontal treatment, consisting of full-mouth subgingival root debridement delivered within a 6-h period, was performed. Periodontal parameters were recorded before and 1 month after completion of treatment. Blood samples were taken at baseline and 1, 3, 5, 7 and 30 days after treatment. Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-6 (IL-6) and C-reactive protein (CRP) serum concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood counts were also performed. RESULTS: One day after treatment, mild neutrophilia and monocytosis (p < 0.05) and lymphopenia (p < 0.01) were accompanied by a sharp increase in inflammatory markers (IL-1Ra, IL-6, p < 0.01). A 10-fold increase in CRP (p < 0.001) was detected on day 1 and its kinetics followed a pattern of a classical acute phase response (significantly raised concentrations up to 1 week, p < 0.01). At 3-7 days after treatment, subjects presented also with a mild tendency towards a normocytic anaemic state (p < 0.01) and a degree of lympho-thrombocytosis (p < 0.05). The observed changes were similar to those expected following the well-characterized endotoxin-challenge model of inflammation. CONCLUSIONS: Intensive periodontal treatment produced an acute systemic inflammatory response of 1 week duration and might represent an alternative to classic endotoxin-challenge or drug-induced models to study acute inflammation in humans.

Acute-Phase Reaction↗

Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers.

Severe periodontitis is associated with elevated inflammatory markers in otherwise healthy populations. However, the nature of this association has not been determined. Our aim was to assess whether the degree of response to periodontal therapy was associated with changes in serological markers of systemic inflammation. Ninety-four systemically healthy subjects with severe generalized periodontitis participated in a prospective six-month blind intervention trial. Periodontal parameters and inflammatory markers [C-reactive Protein (CRP) and Interleukin-6 (IL-6)] were evaluated prior to and 2 and 6 mos after delivery of standard non-surgical periodontal therapy. Six months after treatment, significant reductions in serum IL-6 (p < 0.001, median decrease 0.2 ng/L, 95% CI 0.1-0.4 ng/L) and CRP (p < 0.0001, median decrease 0.5 mg/L, 95% CI 0.4-0.7) were observed. Decreases in inflammatory markers were significant in subjects with above average clinical response to periodontal therapy after correction for possible confounders. Periodontitis may add to the systemic inflammatory burden of affected individuals.

Aggregatibacter actinomycetemcomitans↗

Evaluation of the effect of tooth vitality on regenerative outcomes in infrabony defects.

BACKGROUND, AIMS: This investigation was designed to evaluate the null hypothesis of no differences in GTR outcomes in intrabony defects at vital and successfully root-canal-treated teeth. METHOD: 208 consecutive patients with one intrabony defect each were enrolled. Based on tooth vitality, the treated population was divided at baseline into 2 groups: one with 41 non-vital teeth and the other with 167 vital teeth. The 2 groups were similar in terms of patient and defect characteristics. RESULTS: A slight unbalance in terms of depth of the intrabony component was observed in the non-vital group compared to the vital group (6.9+/-2.1 mm versus 6.2+/-2.3 mm, p=0.08). All defects were treated with GTR therapy. At 1 year, the non-vital and the vital groups showed a clinical attachment level (CAL) gain of 4.9+/-2.2 mm and of 4.2+/-2 mm, respectively. The difference was statistically significant (p=0.03). To correct for the baseline unbalance in defect depth, data were expressed as a % of clinical attachment level gains with respect to the original intrabony depth of the defect. % CAL gains were 72.8+/-42.2% and 73+/-26.4% for vital and non-vital teeth, respectively: the difference was not statistically significant (p=0.48). Average residual pocket depths were 2.8+/-1 mm in the vital and 2.8+/-0.9 mm in the non-vital group. Tooth vitality was assessed at baseline, at 1-year and at follow-up (5.4+/-2.8 years after surgery): all teeth vital at baseline were still vital at follow-up with the exception of 2 teeth that received endodontic treatment for reconstructive reasons and for caries. At follow-up visit, the difference in CAL with respect to 1-year measurements was -0.9+/-0.8 mm in the vital group and -0.7+/-0.8 mm in the non-vital group, indicating stability of the regenerated attachment at the majority of sites. CONCLUSIONS: Data from this study demonstrate that root canal treatment does not negatively affect the healing response of deep intrabony defects treated with GTR therapy; furthermore GTR therapy in deep intrabony defects does not negatively influence tooth vitality.

Adolescent↗

Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability.

A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre-clinically. Silver has potent antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) < or =0.5 microg/ml. This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuard) in a group of 9 volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets > or =5 mm. Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days. At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The maximum mean silver concentration in GCF was 1,493 +/- 709 microg/ml (range 589-2,245). It decayed exponentially with a half-life of 7.1 +/- 6.1 days (2.7-20.4). Average silver concentrations in excess of 10 microg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 microg/mL at day 21. Total anaerobic counts decreased an average of 1.7 +/- 1.9 x 10(6) CFU/ml (p= 0.0078) from baseline to day 7, indicating that the silver was biologically active. A mild increase in cervical root discoloration was observed at day 21:0.25 +/- 0.31 stain index units. Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing. No systemic effects were observed. It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days. A specific microbiologic effect was also observed.

Absorbable Implants↗

The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: clinical outcomes and postoperative morbidity.

BACKGROUND: The aims of the present multi-center, randomized, controlled clinical trial were: 1) to compare the efficacy of the simplified papilla preservation flap with and without a barrier membrane in deep intrabony defects; 2) to evaluate the postoperative morbidity and surgical complications; and 3) to preliminarily test the impact of baseline tooth mobility on clinical outcomes. METHODS: This parallel group, randomized, multi-center, controlled clinical trial involved 112 patients in 8 periodontal practices in 4 countries. A deep intrabony defect in each patient was accessed with the simplified papilla preservation flap. In the test defects, a bioabsorbable membrane was positioned. Patients' experiences with the surgical procedure and postoperative period were evaluated with a questionnaire. Clinical outcomes included clinical attachment level (CAL) and probing depth (PD) changes. RESULTS: Complete observations were available for 55 test and 54 control defects. CAL gains at 1 year were 3.5 +/- 2.1 mm in the guided tissue regeneration (GTR) group and 2.6 +/- 1.8 mm in the control group (P = 0.0117). CAL gains > or = 4 mm were observed in 50.9% of GTR sites and 33.3% of control sites. A significant center effect of 2.1 mm was observed (P= 0.01). Initial PD (P= 0.01) and baseline tooth mobility (P= 0.036) were significant covariates. During the procedure, 30.4% of test and 28.6% of controls reported feeling moderate pain, and subjects estimated the hardship of the procedure at 24 +/- 25 visual analog scale (VAS) units in the test group, and at 22 +/- 23 VAS in controls. In terms of the investigated outcomes, differences between test and control groups were not statistically significant. Among the postoperative complications, edema was most prevalent at week 1, and more frequently associated with the test treatment (P= 0.01). In the test group, 53.6% of membranes were exposed at week 3. CONCLUSIONS: The present study further supports the added benefits of guided tissue regeneration with respect to access flap alone in the treatment of deep intrabony defects, as well as the general efficacy of GTR in different clinical settings. Furthermore, our study indicates a possible influence of baseline tooth mobility on clinical outcomes.

Absorbable Implants↗

Microsurgical approach to periodontal regeneration. Initial evaluation in a case cohort.

BACKGROUND: Improvements in flap design and soft tissue manipulation are considered key elements in improving the outcomes of regenerative periodontal surgery. Improved visual acuity and better soft tissue handling resulting from the application of a microsurgical approach hold great promise to further improve predictability of periodontal regeneration. The aim of this study was to preliminarily evaluate the outcomes of a microsurgical approach in the regenerative therapy of deep intrabony defects. METHODS: This patient cohort study involved 26 patients with one deep interdental intrabony defect each. They were treated with periodontal regeneration using guided tissue regeneration membranes. Defects were accessed with previously described papilla preservation flaps performed with the aid of an operating microscope and microsurgical instruments. A stringent plaque control regimen was enforced in all the patients during the 1-year observation period. Outcomes included evaluation of the complete primary closure of the interdental space (closure), gains in clinical attachment (CAL), and reductions in probing depths (PD). RESULTS: Closure was achieved in all treated defects and was maintained in 92.3% of cases for the entire healing period. Associated gains in CAL were 5.4 +/- 1.2 mm on average, corresponding to a CAL gain of 82.8 +/- 14.7% of the initial intrabony component of the defect. Average PD reduction was 5.8 +/- 1.4 mm and was associated with minimal increase in gingival recession (0.4 +/- 0.7 mm). CONCLUSIONS: The use a microsurgical approach was associated with very high ability to obtain and maintain primary closure of the interdental tissues over the barrier membranes. The procedure resulted in clinically important amounts of CAL gains and minimal recessions.

Adult↗

Sustained release of silver from periodontal wafers for treatment of periodontitis.

Periodontal wafers intended to treat the underlying infections in patients with periodontitis have been developed. The wafers consist of poly(lactic-co-glycolic acid) as a primary bioerodible polymeric component, poly(ethylene glycol) as a plasticizer and encapsulation aid, and silver nitrate as the antimicrobial agent. The wafers are capable of sustained in vitro release of bioactive silver for at least 4 weeks. The wafers exhibit silver release that follows erosion kinetics, confirming a bulk erosion/release mechanism. In clinical evaluation, sustained release of silver at bactericidal levels for at least 21 days is observed. Staining of hard and soft tissues due to the released silver is minimal and reversible.

Administration, Buccal↗

Initial extractions and tooth loss during supportive care in a periodontal population seeking comprehensive care.

BACKGROUND/AIMS: This retrospective survey was aimed at determining the prevalence of tooth extractions and the dental pathologies associated with them during both the active and maintenance phase of periodontal therapy in a periodontal population seeking comprehensive dental care. METHODS: A total of 273 randomly selected subjects from the oral prophylaxis clinic of the University of Berne were included. All subjects had received comprehensive care consisting of periodontal and restorative treatment and participated in a supervised maintenance program for an average of 67+/-46 months (range 5 to 278 months). The population consisted of 39.6% current smokers and 27.8% previous smokers. 6.2% of the patients had gingivitis, 20.5% mild periodontitis, 48.4% moderate and 24.9% severe periodontitis. The average frequency of the recall visits was 4.4+/-1.5 appointments/year (range 1.7-12 appointments/year). RESULTS: Results indicated that 574 out of a total of 6503 teeth were extracted; 311 teeth were extracted during active therapy and 263 during the supportive periodontal care (SPC) phase of therapy. 46% of patients received tooth extractions as part of their active treatment and 41% during their participation in the secondary prevention program. In the subgroup whose treatment plan included extractions the average number was 2.5+/-1.6 teeth per patient. Likewise, the patients who received extractions during recall lost an average of 2.35+/-1.9 teeth per subject with an incidence of 0.4+/-0.37 teeth per patient per year. These data reinforce the concept that a minority of the population is responsible for the majority of tooth extractions, both during active therapy and SPC. Periodontal disease was the only pathology observed at 57% of the extracted teeth; while caries, endodontic pathology and technical problems in the absence of periodontitis were observed in 29% of cases. CONCLUSIONS: These observations indicate that the rendered treatment was effective in the long-term maintenance of the dentition of these subjects and suggest that advanced periodontal disease represented the major cause of tooth loss in this population.

Adolescent↗

Effect of interleukin-1 gene polymorphisms on gingival inflammation assessed by bleeding on probing in a periodontal maintenance population.

Bleeding on probing (BOP) is the most significant clinical parameter for the assessment of periodontal inflammation. The aim of this prospective longitudinal trial was to study the association between allelic variants of the IL-1 gene complex and gingival inflammation. Three hundred and twenty-three randomly selected periodontal maintenance patients (64.4% females) received a periodontal examination that included probing depth measurements and BOP at each of 4 supportive periodontal therapy (SPT) appointments. A blood sample taken from each subject was analysed for the presence of specific allotypes of the IL-1 gene complex. Two polymorphisms located at +4845 bp in the IL-1 alpha region and at +3954 bp in the IL-1 beta region were evaluated by a polymerase chain reaction method; 35.3% of the examined subjects were positive for specific combinations of allotypes of the IL-1 gene complex previously associated with an increased risk for severe periodontitis. The population consisted of 90 current smokers and 94 former smokers. An analysis of the association between the IL-1 genotype and BOP in the whole population (including smokers) did not reach statistical significance because of the overriding effect of smoking. A subset analysis of the 139 never smokers indicated that genotype positive patients had a significantly elevated chance of presenting an increase in the BOP% over a 4-appointment recall period (p = 0.03) after correcting for oral hygiene. In fact, patients who were genotype-negative had a 50% smaller chance of showing increases in BOP% during SPT. A further analysis explored the relationship between the genotype and the level of BOP% at the most recent recall visit. A generalized linear model showed a statistically significant effect of the genotype status after correcting for plaque accumulation and prevalence of residual pockets (> or = 5 mm). Genotype-negative subjects had significantly lower BOP% (p = 0.0097). It is concluded that the increased BOP prevalence and incidence observed in IL-1 genotype-positive subjects indicates that some individuals have a genetically determined hyper-inflammatory response that is expressed in the clinical response of the periodontal tissues.

Adult↗

Advances in periodontology.

Advances in periodontal science and practice over the last decade have radically changed the understanding of periodontal diseases and have opened new, exciting prospects for both medical and surgical therapy of periodontal diseases. Establishment of the aetiology and pathogenesis of periodontitis, understanding of the unique genetic and environmental susceptibility profile of affected subjects, and recognition of the systemic implications of periodontal infections are the key research findings. The use of randomised, controlled, clinical trials has allowed the development of evidence-based periodontology. Adjunctive antimicrobial therapy, regenerative periodontal surgery, periodontal plastic surgery, bone regeneration surgery in the light of implant treatment, and advanced soft tissue management at implant sites have radically changed practice.

Anti-Infective Agents, Local↗

Long-term clinical outcomes of abutments treated with guided tissue regeneration.

STATEMENT OF PROBLEM: Guided tissue regeneration (GTR) is an efficacious and predictable treatment modality for deep intrabony defects around natural teeth and abutments. However, long-term prognosis of abutments treated with regeneration has to be proven. PURPOSE: This study investigated the long-term stability of clinical outcomes obtained with regeneration in strategically important abutments. MATERIAL AND METHODS: Sixteen deep intrabony defects around strategically important abutments in 16 patients were treated according to the principles of GTR. After completion of initial periodontal therapy and placement of long-term provisional fixed partial dentures, nonresorbable membranes were applied. Membranes were removed after 6 weeks. All patients remained in a supervised recall program. Final fixed partial dentures were placed 1 year after surgery. Clinical outcomes were evaluated at 1 year and then 4 to 8 years after surgery. RESULTS: Clinical attachment level gains of 5.3 +/- 1.8 mm, reductions in pocket depth (6.1 +/- 2 mm), and increases in the percentage of radiographic bone support (31% +/- 18%) were observed at 1 year. At long-term follow-up visits, clinical attachment levels remained stable with respect to 1 year (-0.1 +/- 0.6 mm; P =.4). The percentage of radiographic bone support slightly increased as compared with 1 year (1% +/- 3%, P =. 04), and pocket depths (0.8 +/- 0.8 mm, P =.004). CONCLUSIONS: This study indicated that tooth support can be gained with GTR and maintained over time in patients recalled regularly.

Adult↗