Relationship between 1-, 3-, and 6-Month Gingival Bleeding Outcomes.

INTRODUCTION: Results from systematic reviews and meta-analyses show generally consistent antigingivitis effects between 3- and 6-mo observation time points with twice-daily use of stannous fluoride (SnF2) dentifrice. However, the relationship between 1-, 3-, and 6-mo gingivitis responses has not been investigated. METHODS: This pooled analysis was conducted to understand the relationship of 1-, 3-, and 6-mo gingival bleeding outcomes. Number of bleeding sites, derived from Löe-Silness Gingival Index (LSGI) or Gingival Bleeding Index, was identified as the primary end point of the analysis for the biological and clinical relevance. Randomized, double-blinded, controlled clinical studies meeting the following predefined selection criteria were identified: 1) published and unpublished gingivitis clinical trials conducted from 1995 to 2022 comparing efficacy of 0.454% SnF2 dentifrices to negative controls (sodium fluoride or sodium monofluorophosphate dentifrice) and 2) studies with a 3-mo assessment and at least a 1- or 6-mo assessment. RESULTS: The search resulted in ten 6-mo and fourteen 3-mo studies meeting selection criteria. A mixed-effects model was performed on the pooled data to assess gingival bleeding outcomes across time. The bleeding efficacy significantly increased between months 1 and 3 (P < 0.0001) and plateaued between months 3 and 6 (P = 0.007), supporting the fact that bleeding reduction relative to control established by 1 mo will increase and be maintained through 3 and 6 mo (R2 = 0.857). In addition, gingival bleeding and gingivitis efficacy, as measured by LSGI, were found to be highly correlated (R2 = 0.874). CONCLUSION: A clear relationship has been demonstrated between 1-, 3-, and 6-mo gingival bleeding outcomes in gingivitis clinical studies comparing SnF2 dentifrice to negative control dentifrice. These findings have important implications to the dental practice and scientific research as antigingivitis efficacy evaluations can be observed as early as 1 mo and are consistent with those seen at 3 or 6 mo. KNOWLEDGE TRANSFER STATEMENT: Outcomes from this investigation indicate that the clinical evaluation of antigingivitis efficacy at 1 mo is predictive of that at 3 and 6 mo, supporting studies of 1-mo duration as a viable method of knowledge acquisition. This more efficient, expedited research design has positive implications for patient care, clinical practice guidelines, protocols, and policies.

Stannous Fluoride Effects on Gene Expression of Streptococcus mutans and Actinomyces viscosus.

A genome-wide transcriptional analysis was performed to elucidate the bacterial cellular response of Streptococcus mutans and Actinomyces viscosus to NaF and SnF2. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of SnF2 were predetermined before microarray study. Gene expression profiling microarray experiments were carried out in the absence (control) and presence (experimental) of 10 ppm and 100 ppm Sn2+ (in the form of SnF2) and fluoride controls for 10-min exposures (4 biological replicates/treatment). These Sn2+ levels and treatment time were chosen because they have been shown to slow bacterial growth of S. mutans (10 ppm) and A. viscosus (100 ppm) without affecting cell viability. All data generated by microarray experiments were analyzed with bioinformatics tools by applying the following criteria: 1) a q value should be ≤0.05, and 2) an absolute fold change in transcript level should be ≥1.5. Microarray results showed SnF2 significantly inhibited several genes encoding enzymes of the galactose pathway upon a 10-min exposure versus a negative control: lacA and lacB (A and B subunits of the galactose-6-P isomerase), lacC (tagatose-6-P kinase), lacD (tagatose-1,6-bP adolase), galK (galactokinase), galT (galactose-1-phosphate uridylyltransferase), and galE (UDP-glucose 4-epimerase). A gene fruK encoding fructose-1-phosphate kinase in the fructose pathway was also significantly inhibited. Several genes encoding fructose/mannose-specific enzyme IIABC components in the phosphotransferase system (PTS) were also downregulated, as was ldh encoding lactate dehydrogenase, a key enzyme involved in lactic acid synthesis. SnF2 downregulated the transcription of most key enzyme genes involved in the galactose pathway and also suppressed several key genes involved in the PTS, which transports sugars into the cell in the first step of glycolysis.

Plaque control evaluation of a stabilized stannous fluoride dentifrice compared to a triclosan dentifrice in a six-week trial.

OBJECTIVE: To compare the anti-plaque efficacy of a stabilized 0.454% stannous fluoride (referred to as SnF2) dentifrice versus a 0.3% triclosan dentifrice formulated with a copolymer and sodium fluoride (referred to as triclosan). METHODS: The study had a randomized, double-blind, two-treatment, parallel-group design, and compared plaque reduction from baseline after both three and six weeks of treatment with either the SnF2 or triclosan dentifrices using a manual toothbrush. Subjects brushed their teeth using their assigned treatment dentifrices according to the manufacturer's instructions. Following overnight plaque accumulation, levels of plaque were assessed by an experienced examiner using the Rustogi, et al. Modified Navy Plaque Index at the start of the study (baseline), and after three and six weeks of regular brushing. Groups were compared using analysis of covariance separately for Weeks 3 and 6, and by repeated measures for Weeks 3 and 6 combined. RESULTS: One-hundred and twenty subjects were randomized to treatment and 114 subjects completed the study. Both treatment groups showed a statistically significant reduction from baseline in mean plaque values for all three tooth areas (whole mouth, gingival margin, interproximal) at both Weeks 3 and 6 (p < 0.02 for all comparisons). Analysis of covariance showed a statistically significantly (p < 0.0001) lower adjusted mean plaque level for the SnF2 group compared to the triclosan group for all three tooth areas at both Weeks 3 and 6, and for Weeks 3 and 6 combined. Weeks 3 and 6 combined adjusted mean plaque was 36.5% lower for whole mouth for the SnF2 group versus the triclosan group. Weeks 3 and 6 combined adjusted mean plaque reduction from baseline was three times greater for the SnF2 group relative to the triclosan group. CONCLUSION: Both dentifrices showed statistically significant reductions from baseline in whole mouth, gumline, and interproximal accumulated overnight plaque after three and six weeks of brushing, but the SnF2 dentifrice showed statistically significantly greater plaque reductions versus the triclosan dentifrice.

A clinical evaluation of the plaque removal efficacy of five manual toothbrushes.

OBJECTIVE: To assess and compare the plaque removal efficacy of five different Oral-B manual toothbrushes: CrossAction Pro-Health (CAPH), CrossAction (CA), Exceed (EX), Advantage 123 (ADV 123), and Indicator (IND). METHODS: This was a single-use, five-treatment, examiner-blind, randomized, five-period (visit) crossover study, with 10 different treatment sequences (groups) that determined the order in which the five toothbrushes were assigned at study visits. Three toothbrushes had an advanced CrissCross bristle design (CAPH, CA, EX), while two had more standard designs with straight bristles (ADV 123 and IND). At the first visit, subjects disclosed their plaque with disclosing solution, and an examiner performed a baseline plaque examination using the Rustogi, et al. Modification of the Navy Plaque Index (RMNPI). Subjects brushed for one minute with their assigned toothbrush under supervision, after which they again disclosed their plaque and were given a second plaque examination. The same procedure was followed for each of the visits in turn. RESULTS: All five manual toothbrushes showed a statistically significant (p < 0.0001) reduction in plaque from baseline for the whole mouth (84% to 93%), gingival margin (74% to 88%), and approximal surfaces (95% to 99%). For pair-wise treatment comparisons for all three plaque measures, CAPH, CA, and EX demonstrated statistically significantly better plaque removal than ADV 123 and IND (all p < 0.018). No other treatment comparisons were statistically significant. CONCLUSION: All five manual toothbrushes showed highly effective plaque reduction for whole mouth, gingival margin, and approximal surfaces. Comparisons between brushes showed consistent advantages for CAPH, CA, and EX compared to ADV 123 and IND for all three plaque measures, indicating that advances in toothbrush design can further enhance plaque removal.

Clinical evaluation of brushing time and plaque removal potential of two manual toothbrushes.

AIM: To compare plaque removal efficacy of Oral-B CrossAction (CA) used for 1 min with an American Dental Association (ADA) manual toothbrush used for 2 or 5 min in an examiner-blind, three-treatment, six-period crossover study. MATERIALS AND METHODS: After refraining from all oral hygiene procedures for 23-25 h, subjects were randomly assigned to one of nine possible six-period (visit) treatment sequences. Plaque was assessed at baseline (Rustogi Modified Navy Plaque Index). Post-brushing scores were recorded after brushing with a marketed dentifrice and the assigned toothbrush for the specified duration. The same procedure was followed at each of six subsequent visits. Clinical measurements were carried out by the same examiner. RESULTS: Forty subjects completed the study. All three treatments effectively removed plaque from the whole mouth, along the gingival margin and from approximal surfaces. Whole mouth and gingival margin plaque removal scores with CA for 1 min did not differ significantly from scores with the ADA toothbrush used for 2 min. The ADA brush used for 5 min showed significantly greater whole mouth (P < 0.001) and gingival margin (P < 0.001) plaque reduction than the two other treatments. Approximal plaque removal scores did not differ between the three treatments. CONCLUSIONS: Efficient plaque removal can be achieved after 1 min of brushing with CA. The amount of plaque removed did not differ significantly from that achieved with the ADA brush after 2 min of brushing. Greater whole mouth and gingival margin plaque removal scores were seen with the ADA brush after 5 min.

The relative anticaries effectiveness of three fluoride-containing dentifrices in Puerto Rico.

The objective of this research was to evaluate the anticaries effectiveness of a low-dose (500 ppm F, low-NaF) sodium fluoride dentifrice, a high-dose (2,800 ppm F, high-NaF) sodium fluoride dentifrice and an experimental 0.454% stabilized stannous fluoride (1,100 ppm F) with sodium hexametaphosphate (SnF2-HMP) dentifrice, each relative to a standard 1,100 ppm F sodium fluoride positive control dentifrice. Subjects (n = 955, with approximately 239 per group) with a mean age of 10.6 (approximately 9-12 years) were randomly assigned to one of four dentifrice treatments. Two calibrated examiners independently measured visual-tactile caries as DMFS that was supplemented with a radiographic examination at baseline, 12 months and 24 months for each subject. Generally similar results were independently observed by both examiners at the conclusion of the 2-year study period. Considering all subjects that attended at least 60% of the supervised brushing sessions, statistically significantly less caries was observed in the high-NaF group compared to the control group. Similarly, statistically significantly less caries was observed in the SnF2-HMP group as compared to the control group. Differences in caries increments between the low-NaF and control groups were not statistically significant. One of the examiners observed these same statistically significant differences after 1 year. In conclusion, the results of this clinical trial indicated that while no difference in caries increments was observed between the low-NaF and control groups, both the high-NaF and the SnF2-HMP groups experienced significantly fewer lesions than the control group.

The challenges of validating diagnostic methods relative to a conventional two-year caries clinical trial.

This paper is directed to the question, "What are the appropriate validation criteria for the use of a new clinical trial methodology as a replacement for a conventional two- to three-year caries study?" It is important to recognize that the objective of a two- to three-year randomized, controlled caries trial is to test a precisely framed hypothesis, regarding an experimental product's efficacy relative to a control product. The external validity of conventional two- to three-year caries clinical studies in determining the efficacy and safety of anti-caries products is well-accepted. However, caries clinical trials are not without limitations and have increasingly been viewed as inefficient with respect to measuring the disease process in a holistic manner. The endpoint of a caries lesion with loss of enamel integrity (cavitation) focuses on one end of the caries progression continuum at the expense of early caries initiation and progression. Several early caries detection methods have been developed that correlate with mineral loss of the tooth surface. These diagnostics differ from conventional visual-tactile and radiographic methods in that they are capable of detecting early non-cavitated lesions, and this can generate continuous data. As diagnostic methods become accepted, they will lead to study designs that diverge from the conventional two- to three-year caries studies. Modification of the existing two- to three-year conventional caries design for assessment of product effectiveness, whether by the introduction of a new diagnostic method or by modification of the overall clinical design, must result in a clinical design that is able to differentiate known treatments on the basis of caries prevention efficacy. Given that the fluoride dose response has been characterized in the literature, this should form the basis of any validation package for new methodologies. In conclusion, a minimum expectation for acceptance as a replacement to conventional testing should be that the method or design can differentiate products of known efficacy from one another and that the efficacy relationship observed in a two- to three-year conventional study can be observed with the new method or design.

Potential modern alternative designs for caries clinical trials (CCTs) and how these can be validated against the conventional model.

The main reasons that industry runs caries clinical trials (CCTs) are to provide proof of efficacy and to collect in vivo safety data on new products. In recent years, predominantly due to declining caries levels and the use of positive controls, the cost of performing these CCTs has escalated. It is now reaching the stage where it is becoming commercially prohibitive to conduct new studies. This is likely to stifle innovation of new anticaries products, and we now need new, more discriminatory, faster, and less expensive study designs. There are many ways in which the design of CCTs may be changed, such as improving diagnostic efficiency, improving data handling/statistical modeling, and using high-risk populations. However, it is paramount that the overriding principle behind CCT design validation must be that the results/conclusions from any new design are in line with those shown previously by 'conventional' CCTs, to ensure the maintenance of standards for both efficacy and safety. It is suggested that the validation of any new trial design must involve comparisons with regimens previously shown in conventional CCTs to have different anticaries efficacies. For example, since several clinical trials have shown convincing evidence for a monotonic dose response for fluoride at least up to levels of 2500 ppm F, one could choose two products, differing solely in their fluoride level. One aim for this workshop is to identify and agree on validation principles for new clinical trial designs. This will facilitate general international acceptance of novel smaller/faster CCTs designs both now and in the future. We recognize that any new design must not compromise the standard of proof of either efficacy or safety. In addition, any principles will need to take account of current understanding of the caries process, while recognizing the need for change to match future developments in cariology. Finally, the mechanism of action of the test product must be considered, in assessments of the acceptability of novel designs, if this differs markedly from the regimens used to validate the design.

In situ evaluation of sodium hexametaphosphate-containing dentifrices.

The purpose of this investigator-blinded, five-treatment, crossover human intraoral study was to evaluate the effects of two experimental dentifrice formulations containing either stannous fluoride (SnF(2)) or sodium fluoride (NaF) packaged with sodium hexametaphosphate in a dual-phase delivery system on demineralization-remineralization using an in situ model system. The experimental dentifrice formulations' ability to alter demineralization-remineralization was compared to a series of three controls: SnF(2)-positive control, NaF-positive control and no-fluoride placebo-negative control. The single-section crown model, developed at the University of Iowa, was used to assess the fluoride efficacy of two experimental products versus the placebo containing no fluoride and positive controls. The results of the current in situ study suggest a clinical level of anticaries activity for the experimental SnF(2) and NaF dentifrice formulations that was as good as either of the positive controls, when evaluated using polarized light microscopy. This supports the conclusion that the use of the sodium hexametaphosphate ingredient does not interfere with the normal fluoride activity of these toothpastes. In addition, the experimental SnF(2) product was numerically better than both the NaF and placebo controls at preventing demineralization of sound root surfaces.

Plaque removal efficacy of a battery-operated toothbrush compared to a manual toothbrush.

PURPOSE: Recently, a new power toothbrush has been marketed with a design that fundamentally differs from other marketed power toothbrushes, in that it incorporates a round oscillating head, in conjunction with fixed bristles. The objective of this study was to compare the plaque removal efficacy of a control manual toothbrush (Colgate Navigator) to this experimental power toothbrush (Crest SpinBrush) following a single use. MATERIALS AND METHODS: This study was a randomized, controlled, examiner-blind, 4-period crossover design which examined plaque removal with the two toothbrushes following a single use in 40 completed subjects. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. RESULTS: Baseline plaque scores were 1.77 for both the experimental toothbrush and control toothbrush treatment groups. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.48 while the control toothbrush delivered an adjusted mean difference of 0.35. The experimental toothbrush removed, on average, 37.6% more plaque than the control toothbrush. These results were statistically significant (P< 0.001). With respect to buccal surfaces, the experimental toothbrush delivered an adjusted mean difference between baseline and post-brushing plaque scores of 0.54 while the control toothbrush delivered an adjusted mean difference of 0.42. This represents 27.8% more plaque removal with the experimental toothbrush compared to the control toothbrush. These results were also statistically significant (P= 0.001). Results on lingual surfaces also demonstrated statistically significantly (P< 0.001) greater plaque removal for the experimental toothbrush with an average of 53.4% more plaque removal.

Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.

There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.

Reduction in dental caries with four concentrations of sodium fluoride in a dentifrice: a meta-analysis evaluation.

Information on the effects of fluoride concentrations above 1,100 ppm in dentifrices is not extensive in the literature. The objective of this meta-analysis was to examine and compare the anticaries effectiveness (in terms of DMFS scores) of 1,700 ppm, 2,200 ppm and 2,800 ppm F- ion (as sodium fluoride) dentifrices vs. an 1,100 ppm F- ion (as sodium fluoride) control dentifrice based on results from six double-blind, randomized clinical studies, each conducted over a two- to three-year period. The studies each enrolled approximately 1,200-2,000 male and female school children per treatment group in grades I through 8, and were conducted in areas with low fluoride content water supplies in the states of Indiana, Pennsylvania, Ohio and Oregon. Separate meta-analyses were performed on the study results (DMFS increment scores determined by visual-tactile examinations supplemented with radiographs) for the one-year, two-year and three-year examinations. Comparisons of the 1,700 ppm F-, 2,200 ppm F-, and 2,800 ppm F- groups vs. the 1,100 ppm F- group were based on pooling the effect sizes for these comparisons from the individual studies. The effect sizes were calculated in two different ways, reflecting the analyses that were performed in the original studies: 1) effects based on the sample means and variances; and 2) effects based on the adjusted sample means and mean squared error from an analysis of covariance. The results obtained from this meta-analysis provide evidence that the use of a 2,800 ppm F- ion, as sodium fluoride, dentifrice results in statistically significantly lower caries increment than the use of an 1,100 ppm F- ion, as sodium fluoride, dentifrice. This result was noted after one, two, and three years of dentifrice use. The 1,700 ppm F- and 2,200 ppm F- dentifrice groups showed some directional advantages over the 1,100 ppm F- dentifrice group, however the analysis did not establish these groups as statistically significantly better than 1,100 ppm F-. The meta-analysis based on analysis of covariance results was somewhat more sensitive to treatment group differences than the analysis based on sample means and variances, as was expected.

Identification and consequences of distinct Löe-Silness gingival index examiner styles for the clinical assessment of gingivitis.

BACKGROUND: In clinical studies, gingivitis is most frequently assessed by the Löe-Silness gingival index (GI). The objective of this work was to develop an understanding of how clinicians experienced with GI differ with respect to how they apply GI and to assess the impact of different examination styles on statistical outcomes and magnitude of treatment differences. METHODS: A method was developed to mathematically relate the average GI score and degree of bleeding observed for a subject. Graphical analyses were used to profile examiner styles with respect to using the GI index. A prospective single-center, examiner-blind study comparing the effects of a staggered prophylaxis on gingivitis was then conducted, where a difference in gingivitis was created between two balanced groups by providing subjects a prophylaxis at two staggered time points. Subjects were assigned to one of two cohorts; within each cohort, group 1 subjects received a dental prophylaxis following the baseline examination and group 2 subjects received a dental prophylaxis 8 weeks later. Five to 7 days after the group 2 prophylaxis, all subjects were examined for GI. Twelve experienced clinicians participated. RESULTS: Retrospective analyses indicated the presence of distinct examiner styles which are based on the frequency that a given GI score (0, 1, 2, or 3) is measured by a clinician. In the prospective study, all 12 examiners observed statistically significant differences between the prophylaxis treatment groups at the final visit for both mean number of bleeding sites and mean GI; the magnitude ranged from 21.5% to 84.6% for mean number of bleeding sites and 9.4% to 39.2% for mean GI. There were 4 distinct styles employed by these experienced clinicians. CONCLUSIONS: Varying examiner styles impact the structure of resulting data. Importantly, the implementation of arbitrary thresholds (e.g., 20%) regarding percent treatment differences between groups as a guideline for judging the clinical significance is scientifically unsupported. A more scientific criterion in the field of gingivitis clinical testing would be the independent demonstration of statistical superiority compared to a negative control and/or a demonstration of similar or superior efficacy to clinically proven positive controls. In addition, interexaminer calibration is a mechanism that can be utilized to minimize the impact of different examiner styles in clinical settings involving more than one examiner.

A comparison of increment and incidence density analyses in evaluating the anticaries effects of two dentifrices.

This study aimed to determine whether incidence density (ID) calculations of caries incidence rates would provide a more sensitive means of detecting caries-preventive effects than would traditional techniques. A secondary analysis was conducted using data from a 1981 study in which three dentifrices were compared in a double-blind randomized clinical trial. Subjects were examined at baseline and 1, 2 and 3 years after baseline. Three-year DMFS increments were calculated for 1,754 subjects attending the baseline and 3-year examinations. Caries ID rates then were calculated for 2, 661 subjects who had at least two examinations, using each surface's net increment (-1, 0 or +1) as the numerator and the surface's time at risk as the denominator. Despite theoretical advantages, the ID method did not alter the conclusions drawn using DMFS increments, apparently because (a) subjects lost to follow-up were similar to those completing the study, and (b) loss to follow-up was similar among treatment groups.

Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.

Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were "at risk" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.

Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis.

OBJECTIVES: The purposes of this study were to evaluate the use of 0.12% chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar osteitis and to further examine subject-based risk factors associated with alveolar osteitis. STUDY DESIGN: The trial was a randomized, double-blind, placebo-controlled, parallel-group study conducted among 279 subjects, each of whom required oral surgery for the removal of a minimum of one impacted mandibular third molar. Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1 week after the surgical extractions. This regimen included a supervised presurgical rinse. Alveolar osteitis diagnosis was based on the subjective finding of increasing postoperative pain at the surgical site that was not relieved with mild analgesics, supported by clinical evidence of one or more of the following: loss of blood clot, necrosis of blood clot, and exposed alveolar bone. RESULTS: In comparison with use of the placebo mouthrinse, prophylactic use of the chlorhexidine mouthrinse resulted in statistically significant (p < 0.05) reductions in the incidence of alveolar osteitis. With chlorhexidine therapy, the subject- and extraction-based incidences of alveolar osteitis in the evaluable subset (271 subjects) were reduced, relative to placebo, by 38% and 44%, respectively. The corresponding odds ratios that describe the increased odds of experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for subject- and extraction-based analyses, respectively. In comparison with nonuse of oral contraceptives, the use of oral contraceptives in female subjects was related to a statistically significant increase in the incidence of alveolar osteitis (odds ratio = 1.92, p = 0.035). Relative to male subjects, the observed incidence of alveolar osteitis for female subjects not using oral contraceptives was not statistically significant (odds ratio = 1.18, p = 0.64). Smoking did not increase the incidence of alveolar osteitis relative to not smoking (odds ratio = 1.20, p = 0.33). CONCLUSIONS: These data confirm that the prophylactic use of 0.12% chlorhexidine gluconate mouthrinse results in a significant reduction in the incidence of alveolar osteitis after the extraction of impacted mandibular third molars. In addition, oral contraceptive use in females was confirmed to be a risk factor for the development of alveolar osteitis.

MUC7 gene expression and genetic polymorphism.

This study examined differential expression of several mucin genes in the human submandibular gland and trachea, MUC7 tissue and species specificity, and MUC7 genetic polymorphism. Mucin gene expression examined by RT-PCR indicated that MUC1, MUC4 and MUC7 are expressed in the human submandibular gland, while MUC1, MUC2, MUC4, MUC5 and MUC7 are expressed in the human trachea. Northern blot analysis confirmed the expression of MUC7 in the human trachea and MUC4 in the human submandibular gland. Northern blot analysis also demonstrated that MUC7 is not expressed in the submandibular/sublingual gland complexes of hamster, mouse and rat. Southern blot analysis suggested the presence of a MUC7 homologue in monkey genomic DNA. Genetic polymorphism studies of MUC7 by PCR and Southern blot analysis revealed the presence of a limited variable number of tandem repeats (VNTR) polymorphism.

Evaluation of the clinical predictability of hydroxyapatite-coated endosseous dental implants: a review of the literature.

Although the use of hydroxyapatite-coated (HA-coated) endosseous implants in the treatment of dental patients has been established, their clinical predictability remains controversial. This study is an analysis of the clinical predictability and indications for use of HA-coated endosseous implants. This study also discusses the biochemical composition of commercial HA coatings in relation to in vivo predictability, potential concerns, and potential advantages of HA coatings. Clinical studies suggest that HA-coated implants have short-term survival rates (ranging from 6 months to 6 years) that are comparable to short-term survival rates of titanium implants. In addition, clinical data suggest that HA-coated implants may be valuable treatment modalities when placing implants (1) in type IV bone, (2) in fresh extraction sites, (3) in grafted maxillary and/or nasal sinuses, or (4) when using shorter implants (less than or equal to 10 mm). However, long-term controlled studies are required to validate these observations.

Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7).

Previous biochemical studies have determined that human saliva contains high and low molecular weight mucin glycoproteins (MG1 and MG2, respectively) that are structurally distinct. In this study, we describe the isolation and characterization of overlapping cDNA clones which code for the MG2 protein core. DNA sequencing revealed a translated region of 1131 nucleotides encoding a protein of 377 amino acid residues with a molecular mass of 39 kDa. The first 20 N-terminal residues were very hydrophobic and probably comprise the MG2 leader peptide. The region encoding the secreted protein can be divided into three distinct domains; unique 5'- and 3'-translated regions containing 4 and 1 potential N-glycosylation sites, respectively, and a central region of six almost perfect tandem repeats of 23 amino acid residues with a high number of Thr and Ser. No sequence homology with any other human or animal mucins, and no significant homology to any other proteins was found. MG2 mRNA is about 2.5 kilobases long, and its expression appears to be species-, tissue-, and cell-specific. We propose to name this gene MUC7 in accordance with the mucin genes cloned to date named MUC1-MUC6.

Structural features of the low-molecular-mass human salivary mucin.

The low-molecular-mass human salivary mucin has at least two isoforms, MG2a and MG2b, that differ primarily in their sialic acid and fucose content. In this study, we characterize further these isoforms, particularly their peptide moieties. Trypsin digests of MG2a and MG2b yielded high- and low-molecular-mass glycopeptides following gel filtration on Sephacryl S-300. The larger glycopeptides from MG2a and MG2b had similar amino acid compositions and identical N-terminal sequences, suggesting common structural features between their peptides. An oligonucleotide probe generated from the amino acid sequence of the smaller glycopeptide from MG2a was employed in Northern-blot analysis. This probe specifically hybridized to two mRNA species from human submandibular and sublingual glands. A cDNA clone selected from a human submandibular gland cDNA expression library with antibody generated against deglycosylated MG2a also hybridized to these two mRNA species. In both cases, the larger mRNA was polydisperse, and the hybridization signal was more intense in the sublingual gland. In addition, the N-terminal amino acid sequence of the larger glycopeptide was found to be part of one of the selected MG2 cDNA clones.