Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management.

The design and conduct of a 9-month multi-center clinical trial to evaluate the safety and efficacy of subgingivally delivered 5% sanguinarium chloride (SC) and 10% doxycycline hyclate (DH) from a biodegradable drug delivery system in the treatment of adult periodontitis is described. The 3-group randomized study of 180 adults with moderate to severe periodontitis was a modified double-blind parallel design. One group received DH, one group received SC, and the other group received the vehicle control (VC). Patients selected had two quadrants with a minimum of four periodontal pockets > or = 5 mm in depth with two sites > or = 7 mm. All qualifying sites exhibited bleeding on gentle probing. Qualifying sites were treated at baseline and again at 4 months. Clinical response was assessed by measuring attachment level, probing depth, and bleeding on probing at monthly examinations at qualifying sites and the entire dentition. The plaque index was measured monthly to verify oral hygiene status. The parallel design afforded the opportunity to distinguish between treatment effectiveness of SC, DH, and VC independent of possible crossover effects. Also the effectiveness of oral hygiene in untreated sites of the mouth could be evaluated. Finally, treatment effects in moderate (5 to 6 mm) and deep (> or = 7 mm) pockets in both treated and untreated sites could be compared. The design was capable of simulating a periodontal practice maintenance program and assessing the response according to maintenance and treatment history. Study management procedures that emphasized center examiner and therapist training and adherence to protocol and procedures to reduce variability are described.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results.

The clinical safety and effectiveness of a subgingivally delivered biodegradable drug delivery system containing either 10% doxycycline hyclate (DH), 5% sanguinarium chloride (SC) or no agent (VC) was evaluated in a 9-month multi-center trial. The study was a randomized parallel design with 180 patients who demonstrated moderate to severe periodontitis. All patients had at least two quadrants with a minimum of four qualifying pockets > or = 5 mm that bled on probing. Two of the qualifying pockets were required to be > or = 7 mm. At baseline and at 4 months all qualified sites were treated with the test article administered via syringe. Probing depth reduction (PDR), attachment level gain (ALG), bleeding on probing reduction (BOP), and plaque index were determined monthly. Analysis of efficacy data from the 173 efficacy-evaluable patients indicated that all treatments gave significant positive clinical changes from baseline at all subsequent timepoints. DH was superior to SC and VC in PDR at all timepoints (P < or = 0.01 to 0.001) with a maximum reduction of 2.0 mm at 5 months. For ALG, DH was superior to VC at months 2, 3, 4, 5, 6, 8, and 9 (P < or = 0.04 to 0.002) and superior to SC at months 5, 6, 7, 8, and 9 (P < or = 0.01 to 0.001) with a maximum ALG of 1.2 mm at 6 months. For BOP reduction, DH was superior to VC at all time points (P < or = 0.05) and to SC at months 3, 5, 6, 8, and 9 (P < or = 0.03). For DH, the maximum ALG in deep (> or = 7 mm) pockets was 1.7 mm and PDR 2.9 mm compared to 0.8 mm and 1.6 mm, respectively for moderate (5 to 6 mm) pockets. Test articles were applied without anesthesia and no serious adverse events occurred in the trial. The results of this study indicate that 10% doxycycline hyclate delivered in a biodegradable delivery system is an effective means of reducing the clinical signs of adult periodontitis and exhibits a benign safety profile.

2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system.

A biodegradable drug delivery system containing 5% sanguinarium (Sa) was compared to vehicle control (VC), scaling and root planing (SRP), and supragingival plaque control (SPC) in the treatment of adult periodontitis in 2 well-controlled clinical trials. Studies were 4-quadrant (split mouth) designs at 2 centers each, having 94 (Study A) and 107 (Study B) patients. All patients had at least 3 pockets between 5 and 9 mm that bled on probing, in each quadrant. Probing pocket depth (PD), clinical attachment level (AL), bleeding on probing (BOP), and plaque index were recorded at baseline, 14, 30, 60, and 90 days. All treatments gave statistically significant reductions from baseline for PD and BOP, and significant gains for AL. For PD reduction, SRP was superior to all test groups at all time points in both studies (p < 0.001). Sa was superior to VC in Study A at 14 and 30 days and to SPC at all time points. For AL gain at 90 days, in both studies, SRP gave gains of 0.42 and 0.78 mm respectively with superiority seen over the SPC group at 90 days (p < 0.001) in study A only, For BOP reduction, in Study A SRP was superior to Sa, VC, and SPC at 60 and 90 days (p < 0.005) and in Study B superiority to Sa and VC was at 90 days and to SPC at 60 days (p < 0.05). Sa was superior to VC for pocket depth in deep pockets only. Sa failed to demonstrate superiority over VC on a consistent basis. Analysis of residual Sa indicates that Sa potency was insufficient to show an advantage beyond clinical effects inherent in treatments with VC and SPC.

Comparison of the distribution of Actinomyces in dental plaque on inserted enamel and natural tooth surfaces in periodontal health and disease.

The distribution of Actinomyces naeslundii, Actinomyces viscosus and Actinomyces odontolyticus in healthy and diseased adult populations was studied in 3 different ways. First, supragingival plaque formation at 2 through 72 h was examined in 12 periodontally healthy adults using a removable pre-measured surface of enamel bonded to molars and premolars. Second, a cross-sectional examination of the composition of both supragingival and subgingival plaque of unknown age was conducted in 205 adults exhibiting periodontal health to moderate disease. Third, the effects of oral hygiene instruction and root planing on the subgingival microflora of a subset of 19 subjects with moderate periodontitis were examined. The evaluation of 12 adults revealed that the predominant species in early plaque formation (2, 4 and 8 h) was A. odontolyticus. A. viscosus and A. naeslundii were present in developing plaques in almost all subjects in 2-h plaque, but absent in half the subjects when 4-, 8- or 24-h plaque was examined. These two species significantly increased in numbers per mm2 enamel surface area in 48- and 72-h plaques. A. odontolyticus was not related to clinical signs of periodontal disease in 205 adults, and its subgingival proportions in plaque did not change following periodontal treatment of 19 individuals. A. naeslundii was found in significantly higher numbers in supragingival than subgingival plaques in the 205 adults examined. The mean proportion of A. naeslundii significantly decreased as the magnitude of probing depth and attachment loss increased. The proportions of A. naeslundii and A. viscosus were found to be significantly increased in subgingival plaques following periodontal treatment.

Comparison of plaque microflora between Chinese and Caucasian population groups.

This investigation was designed to compare the predominant plaque micro-organisms from a Chinese group of patients exhibiting periodontitis with an age-, sex- and periodontal disease-matched Caucasian group of patients. In addition to race, the 2 population groups differed with respect to diet and oral hygiene habits, or effectiveness at removing plaque. Clinical measurements were determined along with an evaluation for micro-organisms in supragingival and subgingival plaque. Although the Chinese and Caucasian population groups were similar with respect to composition of micro-organisms in subgingival plaque, notable differences were observed in supragingival plaque. The Chinese group had higher mean proportions of spirochetes, motile rods. Fusobacterium spp. and dark-pigmented Bacteroides species, while the Caucasian group had higher mean proportions of cocci, total Actinomyces spp., A. viscosus and total Streptococcus spp. in supragingival plaque. The microbial differences observed in supragingival plaque may be explained at least in part, if not totally, by the higher plaque index scores of the Chinese versus Caucasian population groups.

Effect of toothbrushing with 0.4% stannous fluoride and 0.22% sodium fluoride gel on gingivitis for 18 months.

This study determined the effect of brushing with 0.4% stannous fluoride (SnF2) or 0.22% sodium fluoride (NaF) on clinical and microbial parameters associated with gingivitis. The study included three groups of 281 subjects. Subjects in all three groups were instructed to brush twice daily with an ADA-accepted fluoride dentifrice, rinse their mouths with water, and subsequently brush with 0.4% SnF2, 0.22% NaF, or a fluoridefree placebo gel. More stain was detected in the SnF2 group than in the other two groups at all periods except at baseline. However, no differences were observed in gingivitis, bleeding, or mean proportions of microbial forms in the SnF2 or NaF groups when compared with the placebo group at 18 months. Results indicate that 0.4% SnF2, or 0.22% NaF is no more effective than a placebo in reducing gingivitis.

Porous hydroxyapatite grafts in chronic subcrestal periodontal defects in rhesus monkeys: a histological investigation.

The purpose of this investigation was to evaluate the histologic response to replamineform (porous) hydroxyapatite grafts in chronically inflamed, surgically created, periodontal pockets in Rhesus monkeys. Forty-eight subcrestal defects were surgically created in 8 Rhesus monkeys. Orthodontic wires were adapted to the base of the defects and left in place for 8 weeks. The defects were randomly assigned a treatment modality so that 8 granular porous and 8 block porous hydroxyapatite grafts were done. Eight sites were left as unoperated controls. Twenty-four contralateral sham-operated sites were treated by open curettage. Histometric measurements of the length of regenerated connective tissue attachment were recorded. Block hydroxyapatite, granular hydroxyapatite, and sham-operated sites exhibited similar amounts of regenerated connective tissue attachment, which was significantly greater than that which occurred in unoperated controls. Newly formed bone was observed within the porous channels of the hydroxyapatite grafts as well as in direct apposition on the surface of implant particles. New bone, cementum, and periodontal ligament was observed in grafted sites and in defects treated by open curettage. In some instances healing occurred by means of a long junctional epithelium. Histology confirmed that unoperated defects remained as unhealed, inflamed periodontal pockets. The results of this study suggest that porous hydroxyapatite grafts have the potential to regenerate the attachment apparatus in primates.

The effect of professional and home subgingival irrigation with antimicrobial agents on gingivitis and early periodontitis.

The purpose of this investigation was to study the effect of a professionally applied subgingival antimicrobial agent (stannous fluoride) delivered at periodontal prophylaxis, combined with home personal subgingival delivery of an antimicrobial agent (iodine) on patients with gingivitis and early periodontitis. A control group of 32 individuals was instructed to use dental floss and a sulcular toothbrushing method as a regular oral hygiene regimen. The test group of 42 subjects received professional subgingival irrigation with a 1.64% stannous fluoride solution delivered after scaling. These subjects were also instructed in the home subgingival delivery of an iodine solution along with the use of dental floss and sulcular toothbrushing. Subjects were clinically evaluated at baseline and again after eight weeks. Individuals in the test group, when compared to the control group, had a significantly lower gingival index score at eight weeks. In addition, the test group had significantly lower bleeding and gingival index scores at eight weeks when compared to baseline. Professional subgingival irrigation with stannous fluoride, when combined with home subgingival delivery of an iodine solution, was effective in improving gingival health for patients with gingivitis and early periodontitis.

Four-year investigation of salt and peroxide regimen compared with conventional oral hygiene.

This study of 171 subjects compared the effectiveness of a patient-applied salt and peroxide oral hygiene regimen with the use of conventional oral hygiene methods on clinical measures of periodontal disease, and determined patient compliance with and acceptance of using these two oral hygiene regimens. Results indicated that both regimens, when combined with professional care, were effective in changing clinical measures of periodontal disease to a state favoring periodontal health.

Relationship between lactate dehydrogenase and myeloperoxidase levels in human gingival crevicular fluid and clinical and microbial measurements.

The present study was designed to determine, in a cross-sectional study, whether there was any relationship between levels of lactate dehydrogenase (LDH) and myeloperoxidase (MPO) in gingival crevicular fluid (GCF) and clinical periodontal status or microbial parameters. Another objective was to determine, in a longitudinal study, the effect of a single session of root planning on GCF levels of LDH and MPO and the relation to changes in clinical and microbial measurements. 15 and 12 test subjects with moderate to severe periodontal disease were seen in the cross-sectional and longitudinal study, respectively. 1 healthy and 2 diseased sites were evaluated in each subject. Higher LDH and MPO levels in GCF were closely associated with higher clinical and microbial signs of periodontal disease. Root planing was effective in reducing these enzymes in GCF, with an accompanying decrease in clinical and microbial signs associated with disease. The return of LDH to baseline levels at 3 months after instrumentation, without a corresponding return of clinical signs of disease, may serve as a marker for subclinical periodontal pathology.

Salt and peroxide compared with conventional oral hygiene. I. Clinical results.

The purposes of this 2-year longitudinal study were to: compare the clinical effectiveness of patient applied sodium bicarbonate, hydrogen peroxide, and sodium chloride (S/P) to the use of conventional oral hygiene methods and to investigate the motivational effect of using phase-contrast microscopy in teaching effective oral hygiene. Initially, 972 subjects were screened for signs of periodontitis. From these, 347 with early to moderate periodontitis were selected and each was randomly assigned to one of four home treatment regimens after scaling and root planing. The four treatment regimens included: conventional oral hygiene procedures, conventional oral hygiene procedures plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation, S/P oral hygiene, and S/P oral hygiene plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation. Plaque, bleeding, gingival inflammation, probing depth, and clinical attachment level were recorded at baseline, 8, 16, and 24 months. Subjects were recalled for reinforcement of oral hygiene and periodontal prophylaxis at various intervals. Data were analyzed based on disease severity, location of index sites and compliance. The results indicated that both conventional oral hygiene procedures and the S/P regimen were effective in reducing clinical signs of disease when combined with professional care. There were no differences between the two regimens in clinical effectiveness and trends favoring microscopic viewing of subgingival plaque for motivational purposes were not statistically significant.

Salt and peroxide compared with conventional oral hygiene. II. Microbial results.

This study was designed to investigate the effect of conventional oral hygiene (n = 116 subjects) versus a salt and peroxide oral hygiene regimen (n = 115 subjects) on subgingival microorganisms. Subgingival plaque for microscopic evaluation was obtained from eight index tooth sites in each of 231 adult subjects. Microbial forms were microscopically identified at baseline, 8, 16, and 24 months. For both oral hygiene groups, cocci were increased (P less than 0.05) and motile rods were decreased (P less than 0.05) at 8 months and returned to baseline by 16 months. Spirochetes were decreased (P less than 0.05) and remained low through 24 months in both oral hygiene groups. The frequency of agreement between clinical (bleeding) and microbial (greater than or equal to 15% spirochetes or motile rods or greater than or equal to 20% spirochetes + motile rods) criteria for instrumentation was 59.8%. It was also found that fewer total instrumentations for test subjects were observed when microbiological criteria were used as compared with clinical criteria. The greater number of instrumentations based on clinical criteria was highly significant (P less than or equal to 0.001). A significant change in microbial signs associated with peridontal disease may be obtained with either a conventional oral hygiene or a salt and peroxide oral hygiene home care regimen.

Salt and peroxide compared with conventional oral hygiene. III. Patient compliance and acceptance.

This study was undertaken to evaluate patient compliance with, and acceptance of, a salt and peroxide oral hygiene regimen compared with conventional oral hygiene regimens without or with the use of phase-contrast microscope viewing of subgingival plaque over a period of 2 years. A total of 231 subjects with early to moderate periodontitis were randomly divided into four groups. All groups were repeatedly instructed and motivated in their respective regimens. Subjects also received scaling and root planing using clinical and microbial criteria. Compliance with, and acceptance of, the two oral hygiene regimens were determined at the end of the study using a structured self-administered questionnaire. Results indicated that 74% and 58% (P less than or equal to 0.01) of subjects in the conventional and salt/peroxide groups, respectively, used their assigned regimen 4 to 7 days a week during the entire study. More than half of the subjects (54%) using each of the oral hygiene regimens indicated that they flossed once daily. Inconvenience was cited by 23% of the conventional and 43% of the salt/peroxide groups (P less than or equal to 0.01) as the main reason for not using their regimens. Twenty-three per cent of conventional group and 14% of salt/peroxide group indicated that shared their oral hygiene supplies with others. Eighty per cent and 57% (P less than or equal to 0.01) of the conventional and salt/peroxide groups, respectively, stated that they liked their regimens. Ninety-six per cent of all subjects felt that their regimen helped their periodontal status.(ABSTRACT TRUNCATED AT 250 WORDS)

Repair of alveolar cleft defects with autogenous bone grafting: periodontal evaluation.

Twenty-six patients with cleft lip and palate (18 with unilateral and eight with bilateral clefts) with 34 canines that had erupted through grafted alveolar cleft defects were studied to evaluate their periodontal status. The results were compared with 58 canines erupted through a normal alveolus in 29 noncleft control patients. The overall periodontal status revealed a higher plaque index in the patients with cleft compared to the orthodontic control patients, but parameters of gingival index, probing depth, and attachment loss had no significant differences between these groups. The cleft-associated canines had more than 90 percent of their possible clinical attachment levels intact at the examination. This indicated that grafting of these alveolar cleft defects resulted in a clinically satisfactory periodontium to support these canines as they erupted through the osseous grafts for periods of at least 2 to 8 years following surgery.