Biomedical subjects

David W Paquette

Publications and source records attributed to David W Paquette.

7 recordsLinked to original sources

PubMed2006

Risk factors for endosseous dental implant failure.

Failures of endosseous dental implants are rare and tend to cluster in patients with common profiles or risk factors. Clinical trials indicate that factors related to implant devices, anatomy, occlusion,systemic health or exposures, microbial biofilm, host immuno-inflammatory responses, and genetics may increase the risk for im-plant complications or loss. In general, factors associated with the patient appear more critical in determining risk for implant failure than those associated with the implant itself. Several risk factors can be modified. For example, the patient can modify smoking and the clinician can modify implant selection, site preparation,and loading strategy. In identifying these factors and making appropriate interventions, clinicians can enhance success rates while improving oral function, esthetics, and patient well-being.

Dental Implantation, Endosseous↗

PubMed2006

Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines.

BACKGROUND: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs. METHODS: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3% MEG, 0.3% GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests. RESULTS: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing (%BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P<0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P<0.05). Although placebo-treated beagles demonstrated %BOP scores of 43% at week 8, GED- and MEG-treated beagles exhibited %BOP scores of 21% and 26%, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels. CONCLUSION: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.

Administration, Topical↗

PubMed2005

Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial.

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.

Adult↗

PubMed2005

Pocket depth reduction as an outcome measure of inflammation and soft tissue changes in periodontitis trials.

Randomized, controlled clinical trials are prospective studies involving human subjects that are designed to assess disease interventions by comparing end-points related to patient well-being. The purpose of this article is to examine the parameter probing (or pocket) depth as a meaningful end-point for evaluating novel periodontitis therapies. Probing depth provides an estimate of the inflamed, ulcerated lesion secondary to periodontitis disease. Probing depth measurements strongly correlate with the concentrations of host inflammatory mediators implicated in the pathogenesis of periodontitis; these mediators are generated locally secondary to the etiologic biofilm. Probing depth is a well-recognized and routine diagnostic parameter for periodontitis. It is easy to measure and interpret, sensitive to change with treatment, and correlates with other parameters of interest. Evidence from cohort studies indicates that increased probing depth is predictive of periodontitis events such as alveolar bone resorption and tooth loss. Clinical trials assessing probing depth as an efficacy outcome should feature standardization and calibration procedures to decrease measurement bias and variability. In addition, the analysis and presentation of probing-depth data should include the overall population, prognostic subcohorts, and consideration of clinical relevance. Probing depth is the most commonly reported outcome in periodontitis clinical trials and is a meaningful end-point for investigators and clinicians to judge the efficacy of periodontitis interventions.

Chronic Disease↗

PubMed2004

The periodontal-cardiovascular link.

Cardiovascular disease (CVD) and periodontitis are common chronic conditions, and the former remains a major contributor to human mortality. Recent attention has focused on a potential link between periodontal disease and CVD. Observational studies consistently indicate that people with destructive periodontitis may be 1.3 to 2 times more likely to have CVD. This association appears to be biologically plausible, and investigations in atherosclerosis animal models demonstrate larger atheroma sizes in animals infected with the periodontal pathogen, Porphyromonas gingivalis, compared with control animals. Although direct intervention data on the effects of periodontal therapy on CVD risk in patients are not currently available, indirect data suggest that mechanical periodontal therapy can decrease surrogate cardiovascular markers such as serum C-reactive protein. After a recent systematic review on the periodontal-cardiovascular link, a consensus panel concluded that patients and clinicians should be informed that periodontal therapy may prevent the onset or progression of CVD.

Animals↗

PubMed2002

The periodontal infection-systemic disease link: a review of the truth or myth.

Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.

Animals↗

PubMed2002

Minocycline microspheres: a complementary medical-mechanical model for the treatment of chronic periodontitis.

Locally delivered antimicrobials represent an expanding class of therapeutics that may complement conventional mechanical treatments for chronic periodontitis. Currently available locally delivered antimicrobials include a tetracycline fiber, chlorhexidine chip, doxycycline gel, and newly approved minocycline microspheres. This last therapeutic is formulated to contain 3 mg polyglycolide-co-dl lactide (PGLA) copolymer and 1 mg of minocycline per unit (pocket) dose. As the polymer microspheres resorb, minocycline is released locally within the periodontal pocket at effective concentrations for at least 14 days. Recently, three phase 3 human clinical trials were conducted to assess the efficacy and safety of minocycline microspheres in patients with moderate-to-advanced chronic periodontitis. Data from an open-label trial involving 173 subjects indicated that minocycline microspheres plus scaling and root planing (SRP) at baseline produced significant improvements in pocket depth (PD) (> or = 1.5 mm) at 1 and 3 months. Retreatment with minocycline microspheres at 3 and 6 months maintained these improvements for 12 months. Two concurrent, blinded studies cumulatively recruited 748 periodontitis subjects who were randomized to SRP plus minocycline microspheres, SRP plus vehicle (placebo), or SRP alone at baseline. Minocycline microspheres or the vehicle were readministered per the randomization at 3 and 6 months. Patients receiving minocycline microspheres plus SRP exhibited significantly greater PD reduction at 1, 3, 6, and 9 months compared to patients receiving SRP plus vehicle or SRP alone. Overall, mean PD reduction with adjunctive minocycline-microsphere treatment increased when patients with more advanced periodontitis (mean PD > or = 6 mm or 7 mm) were considered. Similarly, significant improvements in clinical attachment level and percent bleeding on probing were observed among advanced periodontitis patients treated with SRP plus minocycline microspheres relative to controls. Patients treated with minocycline microspheres plus SRP were 50% more likely to shift to an overall mean PD < 5 mm or to a more maintainable case definition. No increased incidence of adverse events or tetracycline resistance were observed with minocycline-microsphere treatment. The data from these clinical trials indicate that minocycline microspheres plus SRP are safe in patients and more effective than SRP alone in reducting the signs of chronic periodontitis.

Analysis of Variance↗