Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins.

There is increasing evidence that cells of the epithelial root sheath synthesize enamel matrix proteins and that these proteins play a fundamental role in the formation of acellular cementum, the key tissue in the development of a functional periodontium. The purpose of the present study was to explore the effect of locally applied enamel matrix and different protein fractions of the matrix on periodontal regeneration in a buccal dehiscence model in monkeys. Buccal, mucoperiosteal flaps were raised from the canine to the 1st molar on each side of the maxilla. The buccal alveolar bone plate, the exposed periodontal ligament and cementum were removed. Various preparations of porcine enamel matrix with or without vehicles were applied before the flaps were repositioned and sutured. After 8 weeks, the healing was evaluated in the light microscope, and morphometric comparisons were made. Application of homogenized enamel matrix or an acidic extract of the matrix containing the hydrophobic, low molecular weight proteins, amelogenins, resulted in an almost complete regeneration of acellular cementum, firmly attached to the dentin and with collagenous fibers extending over to newly formed alveolar bone. After application of fractions obtained by neutral EDTA extraction containing the acidic, high molecular weight proteins of the enamel matrix, very little new cementum was formed and hardly any new bone. The results of the controls in which no test substance was applied before the repositioning of the flap, were very similar to those obtained with the EDTA extracted material. Propylene glycol alginate (PGA), hydroxyethyl cellulose and dextran were tried as vehicles for the enamel matrix preparations. Only PGA in combination with the amelogenin fraction resulted in significant regeneration of the periodontal tissues.

Periodontal regeneration with enamel matrix derivative in one human experimental defect. A case report.

The purpose of the present study was to histologically assess the effect of enamel matrix derivative on periodontal regeneration in one human experimental defect. Experimental surgery was performed in a healthy male volunteer to create a buccal dehiscence defect in a mandibular incisor. Following bone removal and conditioning of the exposed root surface, enamel matrix derivative was applied onto the root surface. The flaps were then replaced and sutured. Clinical healing was uneventful. After 4 months, the experimental tooth together with the surrounding soft and hard tissues were removed surgically for histological evaluation. The microscopic examination revealed formation of a new acellular extrinsic fibre cementum, which was firmly attached to the underlying dentin. A new periodontal ligament with inserting and functionally-oriented collagen fibres and an associated alveolar bone was also present. The new cementum covered 73% of the original defect. Regain of bone was 65% of the presurgical bone height. It was concluded that adjunctive use of enamel matrix derivative could provide a regenerative technology with a potential for true periodontal regeneration.

Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects.

The aim of the present clinical trial was to compare the long-term effect of EMDOGAIN treatment as an adjunct to modified widman flap (MWF) surgery with the effect of MWF and placebo treatment. The investigation was a placebo-controlled, randomized multicenter trial involving 33 subjects with 34 paired test and control sites. The protocol required 2 interproximal sites, appropriately separated, in the same jaw with probing pocket depths > or = 6 mm and an associated intrabony defect with a depth of > or = 4 mm and a width of > or = 2 mm as measured on a radiograph. Only predominantly 1- and 2-wall defects were included. Clinical attachment gain and radiographic bone gain were used as primary outcome variables. Assessments were made at baseline, 8, 16 and 36 months. Mean values for clinical attachment level gain in test and control sites at 8 months were 2.1 mm and 1.5 mm, respectively; at 16 months, 2.3 mm and 1.7 mm, respectively; and at 36 months 2.2 mm and 1.7 mm, respectively; and the differences were statistically significantly different at each time point (p < 0.01). The radiographic bone level continued to increase over the 36 months at the EMDOGAIN-treated sites, while it remained close to the baseline level at the control sites. The statistically significant (p < 0.001) radiographic bone gain at 36 months of 2.6 mm at EMDOGAIN-treated sites corresponded to 36% gain of initial bone loss or 66% defect fill. The present trial has demonstrated that topical application of EMDOGAIN onto diseased root surfaces associated with intrabony defects during MWF periodontal surgery will promote an increased gain of radiographic bone and clinical attachment compared to control (placebo application) surgery in the same patient. There was no evidence to indicate any clinical adverse effects from application of EMDOGAIN conjunction with periodontal surgery.

A 4-quadrant comparative study of periodontal treatment using tetracycline-containing drug delivery fibers and scaling.

The present study describes results on selected clinical and microbiological parameters obtained by periodontal treatment with ethylene vinyl acetate fibers containing 25% by weight tetracycline hydrochloride placed into the periodontal pocket alone or in combination with scaling. Supragingival plaque control was maintained throughout the study by weekly professional cleaning and 0.2% chlorhexidine mouthrinses. Controls included untreated sites and sites treated by conventional scaling alone in a 4-quadrant split-mouth design. The experiment was conducted on 95 teeth from 10 subjects with periodontal pockets greater than or equal to 6 mm which initially bled on probing. All treatments resulted in changes indicative of effective therapy. Pocket depth was reduced, bleeding on probing decreased and gingival index scores decreased. Parallel to the clinical changes, all treatments reduced total bacterial numbers, % black-pigmented Bacteroides, motile bacteria, non-motile rods, and produced a proportionate increase in cocci. Fiber therapy with or without scaling reduced bacterial counts by approximately 2 orders of magnitude when evaluated at 62 days post-therapy. The combination of fiber therapy with scaling was particularly effective, suggesting a possible synergy between these forms of therapy. The combined therapy eliminated bleeding on probing, and black-pigmented Bacteroides, and produced the greatest mean reduction in pocket depth.

Nitrendipine-induced gingival overgrowth in dogs.

This study assessed the development of gingival overgrowth in dogs given nitrendipine, a new antihypertensive dihydropyridine. Nine male Beagle dogs with established plaque and gingivitis were used. Following a baseline examination, which involved assessment of plaque, gingivitis, and gingival enlargement, six dogs (test) received nitrendipine twice daily in a high dose, while 3 dogs (control) received placebo. Clinical scorings were repeated after 10 and 20 weeks. At termination of the study gingival biopsies were excised and examined morphometrically. Already at the 10-week examination definite changes in gingival size had occurred, and following 20 weeks of nitrendipine treatment the gingival enlargement had markedly increased. In none of the control dogs were there any signs of gingival size changes. The histopathological examination showed that the only principal changes in histopathological morphology were that areas of non-infiltrated connective tissue in test specimens showed an increase in vascularity and appeared more loose compared with the dense tissue in control specimens. The morphometric analysis demonstrated minor differences between test and control specimens in regard to all tissue fractions observed; however, such differences were numerically very small, and were not considered biologically significant. Thus, the results demonstrated that nitrendipine administered to Beagle dogs during a 20-week period causes marked overgrowth of gingival tissue of apparently normal composition. The fact that cases of gingival overgrowth have been reported among patients receiving other dihydropyridines suggest that the observed gingival overgrowth is an effect of this class of drugs.

Periodic subgingival antimicrobial irrigation of periodontal pockets. II. Microbiological and radiographical observations.

The purpose of this study was to evaluate the microbiological effects of repeated subgingival irrigation of deep periodontal pockets as a single measure of treatment as well as combined with mechanical debridement, and to study the concomitant radiographical changes of the alveolar bone. 2-3 interproximal sites per jaw quadrant in 10 patients showing a probing depth of greater than or equal to 6 mm and bleeding on pocket probing were selected for the study. The pockets in the various quadrants were randomly assigned to professionally performed subgingival irrigation with 0.2% chlorhexidine gluconate, 3% hydrogen peroxide or saline or to non-irrigation. During a first phase of treatment, the pockets were periodically irrigated (every 2nd-3rd day during weeks 1-2 and 5-6) and no subgingival mechanical debridement was performed. During a second phase, subgingival scaling and root planning were carried out with adjunctive subgingival irrigation of the pockets. During the entire trial, the patients' plaque control was carefully supervised. Sampling of the subgingival microflora was performed before and after the first and second treatment phases and 3 months after the termination of the active treatment. Dark-field assessment and cultivation of the bacterial samples were performed. The radiographical examination was carried out at the start of each treatment phase and 3 months after the termination of phase II and the radiographs were analysed by the use of a subtraction technique. The results demonstrated that periodic subgingival antimicrobial irrigation per se had only limited and transient effects on the subgingival microflora.(ABSTRACT TRUNCATED AT 250 WORDS)

Periodic subgingival antimicrobial irrigation of periodontal pockets (I). Clinical observations.

The present investigation was undertaken to study the clinical effect of professionally performed periodic subgingival irrigation per se and as an adjunct to scaling and root planing. 10 patients suffering from moderate-severe periodontal disease participated in the study. Following an initial 3-month period of supervised supragingival plaque control, a total of 102 periodontal sites with probing pocket depth greater than or equal to 6 mm and "bleeding on probing" were selected and subjected to a Baseline examination comprising assessments of oral hygiene and gingival conditions, probing depths and probing attachment levels. The pockets in the various jaw quadrants were randomly assigned to one of the following treatment groups: (1) periodic subgingival irrigation with hydrogen peroxide, (2) periodic subgingival irrigation with chlorhexidine, (3) periodic subgingival irrigation with saline and (4) no subgingival treatment. During the first part of the study (baseline-32 weeks), no mechanical debridement of the subgingival area was performed. The irrigation treatment was carried out by the operator 3 times per week during weeks 1 + 2 and 5 + 6 of the trial. In the 2nd part of the trial (32-52 weeks), the sites were subjected to scaling and root planing combined with professional irrigation during weeks 32-38. The previously non-irrigated control sites were not subjected to adjunctive irrigation when mechanically debrided. During the entire study, the patients were recalled for professional tooth cleaning once every 4 weeks. Re-examinations were carried out at 4, 6, 32, 40 and 52 weeks. The results revealed that repeated professional irrigation of unscaled periodontal pockets with chlorhexidine or hydrogen peroxide resulted in a temporarily reduced frequency of bleeding sites, but not in any clinically significant changes in probing assessments. A similar improvement of bleeding scores was observed in the saline-irrigated control group. Scaling and root planing, in combination with an optimal supragingival plaque control, resulted in a marked resolution of the clinical symptoms of periodontal disease. Adjunctive irrigation with chlorhexidine or hydrogen peroxide did not improve the healing result above and beyond that obtained after mechanical debridement alone or in combination with saline irrigation. Hence, the study failed to demonstrate that professionally performed periodic subgingival irrigation with chlorhexidine or hydrogen peroxide, used alone or in combination with thorough mechanical debridement, has a significant therapeutic effect.

Examiner agreement in estimating changes in periodontal bone from conventional and subtraction radiographs.

It has previously been shown that computer-assisted subtraction of serially-obtained radiographs yields a higher degree of accuracy in the detection of small changes in the marginal periodontal bone than conventional radiographs. This study concerns another important aspect of such diagnostic methods, namely the intra- and inter-examiner agreement rates. On 10 patients with moderate to severe periodontal bone loss involved in a clinical trial to evaluate the effectiveness of subgingival antimicrobial irrigation, conventional radiographs were taken at baseline and after 32 and 52 weeks. The changes in terms of gain or loss of bone occurring between the examination at baseline and that after 32 weeks, as well as those occurring between the examination performed after 32 weeks and that made after 52 weeks, were evaluated by means of conventional radiographs and by subtraction images. Both types of image were interpreted by each of 4 observers. The images were read a 2nd time after a period of at least 2 weeks. The inter-observer as well as the intra-observer agreement were assessed by calculating 3 different measures of agreement: the overall agreement, the specific agreement and the kappa value. Regardless of measure, higher inter-observer agreement rates were found for all observers when the subtraction technique was employed. A similar pattern was found with respect to the intra-observer agreement rates.

Effect of selective antimicrobial therapy on plaque and gingivitis in the dog.

The present investigation was performed to assess the effect of selective antibiotic therapy on developing plaque and gingivitis in dogs, which at the start of the study had normal gingiva. Fifteen beagle dogs were used. Throughout the entire observation period the animals were fed a diet which favored plaque accumulation. A baseline examination involved assessments of plaque, gingivitis and gingival exudate. The subgingival bacterial flora was assessed by dark-field microscopy. Subsequently the teeth of the right jaws were allowed to accumulate plaque. A careful tooth-cleaning program was maintained in the left jaws. Plaque and gingivitis assessments were repeated and subgingival plaque sampled in the right jaws after 14 and 28 days. On experimental day 28 the second part of the study was initiated. The dogs were randomly distributed into three groups of five animals each. A new baseline examination was performed in the left jaws, after which all tooth cleanings were terminated. During the subsequent 28 days each group of dogs was treated with one of three antimicrobial compounds (vancomycin, metronidazole or clindamycin). Examinations were repeated after 14 and 28 days. The results demonstrated that systemic administration of antimicrobial substances can reduce the rate of plaque formation, change the composition of the developing subgingival microbiota and prevent (or retard) the onset of gingivitis. A comparison of the ability of the three compounds to prevent the formation of a "gingivitis-inducing" plaque revealed that metronidazole and clindamycin were markedly more effective than vancomycin. In fact, in dogs receiving metronidazole and clindamycin treatment, the initiation of gingivitis was almost entirely prevented during the 28 days of treatment.

The occurrence of mononuclear cells at sites of osteoclastic bone resorption in experimental periodontitis.

The placement of silk ligatures around the necks of teeth and into the gingival sulcus causes a rapid, acute inflammatory response leading to vigorous osteoclastic resorption of alveolar crestal bone. Associated with the large numbers of osteoclasts are mononuclear cells, predominantly fibroblast-like cells and macrophages. Some fibroblast-like cells contain intracellular collagen fibrils. It is suggested that in periodontal disease these mononuclear cells may compliment the action of osteoclasts by ingesting and degrading matrix molecules mobilized from bone but not ingested or degraded by osteoclasts.

The effect of metronidazole on the development of plaque and gingivitis in the beagle dog.

The present investigation was performed in order to assess if the administration of metronidazole changed the composition of developing plaque in dogs, which at the start of the study were free from signs of gingivitis. Five beagle dogs were used. Throughout the observation period the animals were fed a diet which favored plaque accumulation. A baseline examination involved assessments of plaque, gingivitis and gingival exudate. Gingival biopsies were sampled and the tissue examined by a point counting procedure. The composition of the subgingival bacterial flora was assessed by dark-field microscopy. The bacteria were characterized into the following types: coccoid cells, straight rods, filaments, fusiforms, motile and curved rods and spirochetes. Following the baseline examination the teeth of the right jaws were allowed to accumulate plaque. A careful tooth cleaning program was maintained in the left jaw quadrants. Plaque and gingivitis assessments were repeated and biopsies sampled in the right jaws after 7, 14 and 28 days of no tooth cleaning. On experimental day 28 the second part of the study was initiated. A baseline examination was performed in the left jaws, after which the tooth cleaning program also in this part of the dentition was terminated. During the subsequent 28-day period each animal was given a dosage of 20 mg metronidazole/kilogram bodyweight/day. Clinical examinations and biopsies were repeated after 7, 14 and 28 days. The results demonstrated that metronidazole administered via the systemic route during a 28-day period can effectively decrease plaque and gingivitis development in dogs. The bacterial flora from subgingival sites of healthy gingiva was dominated by coccoid cells and straight rods. During the phase of developing gingivitis the percentage of coccoid cells and rods tended to decrease, while motile rods and spirochetes increased. During the 28 days of metronidazole treatment the subgingival plaque flora maintained its "healthy" composition, i.e. a gradual influx of motile rods and spirochetes was prevented.