bluuebunny/crossref_metadata_2025 huggingface dataset:
Connective Tissue Growth Factor in Drug‐Induced Gingival Overgrowth
Authors: Uzel M. Ilhan , Kantarci Alpdogan , Hong Hsiang‐Hsi , Uygur Cem , Sheff Michael C. , Firatli Erhan , Trackman Philip C.
Published: February 2005

Background: Drug‐induced gingival overgrowth is a known side effect of certain chemotherapeutic agents used for the treatment of systemic disorders. The pathogenesis and mechanisms responsible for this condition are not fully understood. This study assesses for the presence and localization of connective tissue growth factor (CTGF) in drug‐induced gingival overgrowth tissues. CTGF immunostaining was compared with sections stained with transforming growth factor (TGF)‐β1 and CD31 antibodies in order to investigate possible pathogenic mechanisms.

Methods: Gingival overgrowth samples were obtained from patients undergoing therapy with phenytoin (n = 9), nifedipine (n = 4), cyclosporin A (n = 5), and control tissues from systemically healthy donors (n = 9). Tissue sections were subjected to peroxidase immunohistochemistry and were stained with CTGF and TGF‐β1 polyclonal primary antibodies. Possible relationships between CTGF staining and angiogenesis were also studied using an anti‐CD31 antibody as a marker for endothelial cells. Staining was analyzed by computerassisted quantitative and semiquantitative methodology at 5 defined sites in all samples based on the location of specific landmarks including epithelium and underlying connective tissues.

Results: Cellular and extracellular CTGF content in phenytoin gingival overgrowth tissues was significantly (P <0.05) higher compared to the other gingival overgrowth tissues and the controls. Higher CTGF staining in phenytoin gingival overgrowth tissues was accompanied by an increased abundance of fibroblasts and connective tissue fibers. No strong association of CTGF staining with TGF‐β1 or CD31 staining was found.

Conclusions: The data from the present study show significantly higher CTGF staining in phenytoin‐induced gingival overgrowth tissues compared to controls, cyclosporin A‐, or nifedipine‐induced gingival overgrowth. Moreover, semiquantitative analyses of histologic samples support the concept that the phenytoin overgrowth tissues are fibrotic. These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin‐induced gingival overgrowth. J Periodontol 2001;72:921‐931.
Erythema Multiforme Secondary to Herpes Simplex Infection: A Case Report
Authors: Ayangco Lilibeth , Sheridan Phillip J. , Rogers Roy S.
Published: February 2005

Background: Erythema multiforme (EM) is a complex disease that may have cutaneous and/or mucosal involvement. The severity may range from mild to severe and potentially life threatening. The literature cites many factors including viruses, infections, and medications as causes. This report documents a patient who developed EM secondary to a herpes simplex viral (HSV) infection.

Methods: Two weeks following an eruption of herpes labialis, a 20‐year‐old white female patient developed acutely painful oral and labial ulcers accompanied by target skin lesions. A diagnosis of erythema multiforme (EM) was made. The patient was treated with antivirals, analgesics, and symptomatic therapy.

Results: Nine days after the onset of symptoms, the oral and cutaneous lesions had started to heal and the patient no longer required pain medication.

Conclusions: Although the etiology of EM is still often unknown, infections with herpes simplex virus have been implicated as a possible precipitating factor. This case illustrates the association of the occurrence of EM with an HSV infection. J Periodontol 2001;72:953‐;957.
Levels of Platelet‐Activating Factor in Gingival Crevicular Fluid and Gingival Tissue in Specific Periodontal Diseases
Authors: Emingil Gülnur , Çinarcik Serhat , Baylas Haluk , Hüseyinov Afig
Published: February 2005

Background: Platelet‐activating factor (PAF), a potent phospholipid mediator of inflammatory and immune reactions, is involved in a variety of biological responses seen in periodontal diseases. The aim of the present study was to examine the role of PAF in the pathogenesis of specific periodontal diseases.

Methods: PAF levels were investigated in gingival crevicular fluid (GCF) and gingival tissue (GT) samples of 12 patients with generalized aggressive periodontitis (GAgP), 6 patients with localized aggressive periodontitis (LAgP), 10 patients with chronic periodontitis (CP), 6 with gingivitis (G), and 6 periodontally healthy subjects (H). Periodontal status was evaluated by measuring probing depth, gingival index, papillary bleeding index, and plaque index. PAF was extracted from GCF samples passing through amberlit resin columns, purified by high performance liquid chromatographic method, and then analyzed by radioimmunoassay.

Results: GAgP, LAgP, and CP groups had significantly higher GCF PAF levels compared to the H group (P <0.005). Although statistically not significant, GCF PAF levels were also higher in the G group than those of the H group (P = 0.0784). GAgP, LAgP, and CP groups had similar GCF PAF levels (P >0.005). These groups had higher levels of GCF PAF than those of the G group, but the difference was significant only for the GAgP group (P <0.005). When the data were expressed as concentration, GAgP, LAgP, and CP groups were found to have higher concentrations of GCF PAF compared to the H group (P <0.005). GCF PAF concentration was similar in patient groups (P >0.005). All patient groups had significantly higher GT PAF levels compared to the H group (P <0.005). GAgP, LAgP, and CP groups had similar amounts of GCF and GT PAF (P >0.005). GAgP, LAgP, and CP groups had higher GT PAF levels than those of the G group, but the differences were only significant for LAgP and CP groups (P <0.005). No significant correlation was found between GCF and GT PAF levels and clinical parameters.

Conclusions: The results of the present study indicate that PAF is likely to be an important mediator in regulating inflammatory responses in the human periodontal tissues. To our knowledge, this is the first report investigating PAF levels in GCF and GT in specific periodontal diseases. We believe that this potent phospholipid mediator may need to be considered in the pathogenesis of periodontal diseases. J Periodontol 2001;72:1032‐1037.
Effect of Non‐Surgical Periodontal Therapy on C‐Telopeptide Pyridinoline Cross‐Links (ICTP) and Interleukin‐1 Levels
Authors: Al‐Shammari Khalaf F. , Giannobile William V. , Aldredge Wayne A. , Iacono Vincent J. , Eber Robert M. , Wang Hom‐La , Oringer Richard J.
Published: February 2005

Background: Biochemical markers harvested from gingival crevicular fluid (GCF) may be useful to identify and predict periodontal disease progression and to monitor the response to treatment. Ctelopeptide pyridinoline cross‐links (ICTP), a host‐derived breakdown product specific for bone, and interleukin‐1β (IL‐1), a potent boneresorptive cytokine, have been associated with periodontal tissue destruction. The aim of this study was to examine the effect of nonsurgical periodontal therapy on GCF levels of ICTP and IL‐1.

Methods: Twenty‐five chronic periodontitis subjects were monitored at 8 sites per subject at baseline prior to scaling and root planing and 1, 3, and 6 months after therapy. Four shallow (probing depths <4 mm) and 4 deep (probing depths ≥5 mm) sites were monitored for both marker levels and clinical parameters. GCF was collected for 30 seconds on paper strips, and levels of ICTP and IL‐1 were determined using radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques, respectively. Clinical measurements included probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP).

Results: Deep sites exhibited significantly (P <0.001) higher ICTP and IL‐1 levels compared to shallow sites at all time intervals. ICTP demonstrated a stronger association to clinical parameters than IL‐1 including a modest correlation (r = 0.40, P <0.001) between ICTP and attachment loss. Significant improvements in PD, CAL, and BOP were observed at 1, 3, and 6 months in all sites (P <0.01). However, non‐surgical mechanical therapy did not significantly reduce ICTP and IL‐1 levels over the 6‐month period. Further examination of subjects based on smoking status revealed that ICTP levels were significantly reduced at 3 and 6 months and IL‐1 levels reduced at 3 months among non‐smokers only.

Conclusions: A single episode of non‐surgical mechanical therapy did not significantly reduce biochemical markers associated with bone resorption in patients exhibiting chronic periodontitis. Future longitudinal studies are warranted to specifically evaluate the relationship between C‐telopeptide pyridinoline cross‐links and periodontal disease progression. J Periodontol 2001;72:1045‐1051.
Failure of Resin Ionomers in the Retention of Multi‐Rooted Teeth With Class III Furcation Involvement: A Rebuttal Case Report
Authors: Fowler Edward B. , Breault Lawrence G.
Published: February 2005

Background: Severe periodontal furcation invasion has long been a treatment dilemma for the clinician. Many techniques have been advocated in the treatment of multi‐rooted posterior teeth ranging from conventional scaling and root planing (SRP), apically positioned flaps, root amputations, root resections, tunnel procedures, guided tissue regeneration, and restorations. The keys to success depend on the clinician's ability to access the furcation to remove local factors and create an environment that enhances the patient's own hygiene efforts. Long‐term success in treating teeth with furcation invasion depends upon tooth retention and arresting the destructive processes within the furcation area.

Methods: A Class III furcation invasion in a mandibular molar was treated by surgical access for SRP along with obliterating the furcation utilizing a resin ionomer restoration.

Results: Initially, the patient was asymptomatic. Within 3 months of treatment, the patient presented with suppuration that was refractory to local efforts. Radiographs taken only 5 months postsurgery demonstrated advanced bone loss apical to the restoration. The tooth ultimately was extracted because mobility increased and the tooth became symptomatic.

Conclusions: The clinician must consider the multi‐factorial etiology of periodontal breakdown within a furcation. For this patient, the technique of sealing off the exposed furcation with restorative material appeared to have resulted in progressive bone loss and accelerate tooth loss. This single case report is presented as a rebuttal to recently published articles, which have demonstrated excellent results when treating furcations with ionomer restorations. J Periodontol 2001;72:1084‐1091.
A Comparison of the Success of Root Resected Molars and Molar Position Implants in Function in a Private Practice: Results of up to 15‐Plus Years
Authors: Fugazzotto Paul A.
Published: February 2005

Background: When faced with a furcated molar, today's clinician must decide between a number of treatment options, including root resection, tooth removal, and implant placement. This paper assesses the results in one private clinical practice of root resection and subsequent restoration or molar implant placement and subsequent restoration. Clinical considerations in treatment selection are discussed.

Methods: A retrospective analysis of treated patients was carried out by examining active and inactive patient charts. When patients had discontinued therapy, every effort was made to determine the reason for leaving the private practice, so as to assess the impact of previously undocumented treatment failure on the statistics in question.

Results: A total 701 root resected molars and 1,472 molar implants were evaluated after ≥15 and 13 years in function, respectively. Resection of the distal root of a mandibular molar demonstrated the lowest success rate (75%). All other success rates for various root resected molars in function ranged from 95.2% to 100%. Lone standing implants in second molar positions demonstrated the lowest success rate (85%). All other implant use in molar positions demonstrated a success rate ranging from 97.0% to 98.6%. Root resected molars and molar implants demonstrated the highest degree of failure when they were lone standing terminal abutments. Seven out of 23 (30.4%) root resected molar failures, and 17 of 45 (37.8%) of the molar implant failures were associated with untreated parafunction. Cumulative success rates were 96.8% for root resected molars and 97.0% for molar implants. Success and failure are discussed by tooth and/or implant position, and resected root, where applicable. Possible ramifications of these findings upon treatment planning are also reviewed.

Conclusions: Both molar root resection and appropriate restoration and molar implant placement and restoration demonstrated a high degree of success in function. However, this success rate is markedly affected when either the root resected molar or molar implant is a lone standing terminal abutment. Care must be taken to choose the appropriate treatment modality for a given patient scenario. J Periodontol 2001;72:1113‐1123.
Osseointegrated Implants in Patients Treated for Generalized Chronic Periodontitis and Generalized Aggressive Periodontitis: 3‐ and 5‐Year Results of a Prospective Long‐Term Study
Authors: Mengel Reiner , Schröder Tim , Flores‐de‐Jacoby Lavin
Published: February 2005

Background: The successful use of osseointegrated implants in periodontally healthy patients has been documented in numerous longitudinal studies in recent years. However, the extent to which these positive results apply to periodontally diseased patients remains unclear. The aim of the present prospective longitudinal study of partially edentulous patients treated for generalized chronic periodontitis and generalized aggressive periodontitis was a clinical, microbiological, and radiographic comparison of teeth and implants and assessment of the implant success rate.

Methods: Five partially edentulous patients treated for generalized aggressive periodontitis (GAgP) and 5 treated for generalized chronic periodontitis (GCP) were enrolled in this study. The GAgP patients received 36 implants, and the GCP patients 12 implants. The teeth were examined 2 to 4 weeks before extraction of the non‐retainable teeth (baseline), and 3 weeks after insertion of the final abutments (second examination). All further examinations were performed during a 3‐month recall schedule over a 5‐year period for the GAgP patients and over a 3‐year period for the GCP patients. At each session clinical parameters were recorded at teeth and implants and the composition of the subgingival microflora was determined by dark‐field microscopy and DNA analysis. Intraoral radiographs of the teeth and implants were taken for control purposes at baseline; after insertion of the superstructure; and 1, 3, and 5 years later.

Results: The clinical findings indicated healthy periodontal and peri‐implant conditions in both patient groups throughout the study. However, an increased probing depth and an attachment loss were recorded in the GAgP patients after the third year (P <0.001). The distribution of the microorganisms revealed no significant differences between the patient groups or between implants and teeth. Moderate bone loss at teeth and implants was registered in both groups. The success rates recorded were 100% in the GCP patients and 88.8% (maxilla: 85.7%; mandible: 93.3%) in the GAgP patients.

Conclusions: The 3‐year and 5‐year follow‐ups show that osseointegrated implants may be successful in oral rehabilitation of partially edentulous patients treated for generalized aggressive periodontitis and generalized chronic periodontitis. However, as no significant differences were recorded between conditions at teeth and at implants, progression of the disease cannot be ruled out. J Periodontol 2001;72:977‐989.
Viral Etiology of Gingival Recession. A Case Report
Authors: Prato G. Pini , Rotundo R. , Magnani C. , Ficarra G.
Published: February 2005

Herpes simplex virus‐type 1 (HSV‐1) is responsible for both primary and recurrent infections of the oral mucosa. The aim of this case report is to show how HSV‐1 may cause periodontal damage such as gingival recession. A 26‐year‐old male patient presented in a private office for the treatment of gingival recessions. He reported that the recessions had appeared suddenly with marginal inflammation of the gingiva and vesicle formation; within a few hours, the gingival tissue had been completely destroyed. The lesions were accompanied by pain, fever, and regional lymphadenopathy. Two weeks later, the patient returned complaining of a recurrence accompanied by pain and lymphadenopathy. The following day, the patient's condition had worsened and the depth of the recession had increased. A biopsy was taken for histological examination. A free epithelial‐connective tissue graft was performed. Histological and direct immunofluorescence examinations confirmed the herpetic origin of the lesion. Eight months after surgery, a new herpetic lesion was detected in correspondence to the gingival margin of the first lower right premolar; therefore, acyclovir was prescribed. After 1 week, the antiviral therapy was completely successful; the gingival lesion disappeared, and no recession of the soft tissue margin was observed. Based on these clinical features, diagnosis of gingival recession induced by HSV‐1 must be carried out at an early stage to establish a successful therapy. J Periodontol 2002;73: 110‐114.
Thirty‐Six Month Follow‐up of 25 Patients Treated With Combination Anorganic Bovine‐Derived Hydroxyapatite Matrix (ABM)/Cell‐Binding Peptide (P‐15) Bone Replacement Grafts in Human Infrabony Defects. I. Clinical Findings
Authors: Yukna Raymond A. , Krauser Jack T. , Callan Donald P. , Evans Gerald H. , Cruz Renee , Martin Millicent
Published: February 2005

Background: Long‐term evaluation of periodontal therapy is important for clinical decision making.

Methods: A synthetic cell‐binding peptide (P‐15) combined with anorganic bovine‐derived hydroxyapatite bone matrix (ABM) was evaluated as a bone replacement graft in human periodontal osseous defects. Following initial preparation and reevaluation, flap surgery was performed. A variety of 1‐, 2‐, 3‐wall bony defects were curetted and root surfaces subjected to mechanical debridement only. The bone defects were grafted with ABM/P‐15, and the host flaps replaced or slightly coronally positioned. Weekly, then monthly deplaquing was performed until surgical reentry at 6 to 7 months. Patients were then followed on approximate 3‐month recalls for 3 years. Twenty‐five of the original 31 patients qualified for long‐term evaluation in that their ABM/P‐15 treated sites did not receive any additional therapy at the time of reentry.

Results: Significant clinical changes for the overall group of bony defects included improvement in mean clinical attachment level from 5.4 mm at surgery to 4.5 mm at the 6‐month reentry to 3.8 mm at 3 years. There was also a decrease in mean probing depth from 5.3 mm at surgery to 3.1 mm at the 6‐month reentry to 2.9 mm at 3 years. The mean gingival recession changed from +0.1 mm at surgery to 1.4 mm at the 6‐month reentry to 0.9 mm at 3 years. All of these differences were at least P <0.05 from surgery to the 6‐month reentry, and surgery to 3 years, but were not significant from reentry to 3 years via repeated measures analysis of variance.

Conclusions: These favorable 3‐year results with ABM/P‐15 suggest that it may have a beneficial effect in the long‐term clinical management of infrabony defects. Further long‐term randomized controlled studies are needed to better assess the role of ABM/P‐15 in long‐term healing of periodontal osseous defects. J Periodontol 2002;73:123‐128.
Periodontopathic Bacterial Infection in Childhood
Authors: Kimura Shigenobu , Ooshima Takashi , Takiguchi Miyako , Sasaki Yumi , Amano Atsuo , Morisaki Ichijiro , Hamada Shigeyuki
Published: February 2005

Background: Little information is available on periodontopathic bacterial infection in childhood. We assessed the prevalence by age of 10 putative periodontopathic microorganisms in periodontally healthy children using a polymerase chain reaction (PCR) assay.

Methods: Plaque samples were collected from the buccalmesial sulcus of the first molar or second primary molar in the right upper quadrant of 144 children (2 to 13 years old, 12 subjects from each year of age) who showed negligible periodontal inflammation. Using species‐specific primers of Porphyromonas gingivalis, Bacteroides forsythus, Prevotella intermedia, Prevotella nigrescens, Campylobacter rectus, Eikenella corrodens, Actinobacillus actinomycetemcomitans, Capnocytophaga ochracea, Capnocytophaga sputigena, and Treponema denticola, PCR amplification was performed with bacterial genomic DNA from plaque samples.

Results: The results indicated that C. rectus, E. corrodens, A. actinomycetemcomitans, C. ochracea, and C. sputigena were found in about 50% of the plaque samples from all age groups, while B. forsythus and P. intermedia were detected less frequently, and P. gingivalis and T. denticola were not found. In contrast, the percentage of P. nigrescens‐positive subjects increased with age in primary dentition, and reached about 50% at 7 years of age and older. Subject‐based analyses suggested that the number of bacterial species in the plaque samples increased gradually with age until 5 years old, and then reached a plateau after the mixed dentition period.

Conclusions: The colonization of many putative periodontopathic microorganisms can occur quite early in childhood without clinical signs of periodontal disease. However, colonization by P. gingivalis and T. denticola was not detected in periodontally healthy children. J Periodontol 2002;73:20‐26.
Enamel Matrix Proteins and Guided Tissue Regeneration With Titanium‐Reinforced Expanded PolytetrafluoroethyleneMembranes in the Treatment of Infrabony Defects: A Comparative Controlled Clinical Trial
Authors: Zucchelli G. , Bernardi F. , Montebugnoli L. , De Sanctis M.
Published: February 2005

Background: Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non‐resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects.

Methods: Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium‐reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year.

Results: The 1‐year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR‐treated compared to EMP‐treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures.

Conclusions: The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically‐sensitive sites and in reducing patient morbidity. J Periodontol 2002;73:3‐12.
Treatment of Gingival Recessions by Combined Periodontal Regenerative Technique, Guided Tissue Regeneration, and Subpedicle Connective Tissue Graft. A Comparative Clinical Study
Authors: Paolantonio Michele
Published: February 2005

Background: Many surgical techniques have been shown to be effective in correcting gingival recessions by covering the exposed root with soft tissue; however, the thickness of the gingival tissue over the root surface probably plays an important role in preventing the recurrence of tissue recession. The aim of the present study was to compare the results of a mucogingival bilaminar technique (BT), guided tissue regeneration (GTR), and a combined periodontal regenerative technique (CPRT) in achieving root coverage and increasing the gingival thickness 1 year after surgical treatment.

Methods: In 45 systemically healthy, non‐smoking patients aged 33.6 ± 4.3 years with no periodontal pockets >4 mm, a Miller's Class I or II gingival recession was treated for root coverage: 15 patients underwent BT (connective tissue with partial‐thickness double pedicle graft), 15 GTR by a bioabsorbable membrane, and 15 CPRT by a collagen membrane and collagen‐incorporated hydroxyapatite. Before and 1 year after surgical treatments, the following clinical parameters were recorded: gingival recession (GR), probing depth (PD), clinical attachment level (CAL), keratinized tissue width (KT), and gingival thickness (GT); the percentage of root coverage was also calculated and the data were statistically analyzed.

Results: All 3 techniques yielded significant improvements in terms of GR decrease, CAL and KT gain, and GT increase compared to baseline values. Mean root coverage was 90.0%, 81.01%, and 87.12% in BT, GTR, and CPRT groups, respectively. Complete root coverage was observed in 60%, 40%, and 53.3% of subjects from the BT, GTR, and CPRT groups, respectively. No significant differences were observed among the 3 techniques in GR or CAL improvements; however, BT produced a significantly (P <0.01) greater increase of KT, and BT and CPRT groups showed a significantly (P <0.01) greater increase of GT compared to the GTR group.

Conclusions: BT, GTR, and CPRT successfully treated gingival recession defects, obtaining comparable percentages of root coverage, but BT and CPRT created a thick gingival tissue significantly greater than that achieved with GTR. J Periodontol 2002;73:53‐62.
Effect of Recombinant Human Bone Morphogenetic Protein‐2/Absorbable Collagen Sponge (rhBMP‐2/ACS) on Healing in 3‐Wall Intrabony Defects in Dogs
Authors: Choi Seong‐Ho , Kim Chong‐Kwan , Cho Kyoo‐Sung , Huh Ji‐Sun , Sorensen Rachel G. , Wozney John M. , Wikesjö Ulf M.E.
Published: February 2005

Background: Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in an absorbable collagen sponge (ACS) carrier is being evaluated as a candidate therapy for periodontal regeneration. The objective of this study was to evaluate regeneration of alveolar bone and cementum, and associated root resorption and ankylosis following surgical implantation of rhBMP‐2/ACS in a canine clinical model.

Methods: Bilateral 3‐wall intrabony periodontal defects were surgically induced in the premolar region in the maxilla and mandible in 8 young adult Korean mongrel dogs. The defects in each animal received rhBMP‐2/ACS (rhBMP‐2 at 0.2 mg/ml, total implant volume/defect ~ 0.1 ml) or buffer/ACS, or served as sham‐operated controls. Surgeries were sequenced for each animal to provide postmortem observations following 8‐ and 24‐week healing intervals. Treatment outcomes were evaluated using clinical, radiographic, and histometric parameters.

Results: Surgical implantation of rhBMP‐2/ACS resulted in accelerated enhanced bone formation in the 3‐wall intrabony periodontal defects but in no apparent enhancement of cementum regeneration. rhBMP‐2/ACS did not appear to be associated with aberrant healing events such as root resorption and ankylosis under these simulated clinical conditions.

Conclusions: Surgical implantation of rhBMP‐2/ACS may be used safely to support regeneration of alveolar bone in intrabony periodontal defects in dogs without aberrant events such as root resorption or ankylosis complicating the regenerative procedure. rhBMP‐2/ACS does not appear to have a significant effect on cementum regeneration and formation of a functional periodontal ligament in this model. J Periodontol 2002;73:63‐72.
Systemic Release of Endotoxins Induced by Gentle Mastication: Association With Periodontitis Severity
Authors: Geerts Sabine O. , Nys Monique , De Mol Patrick , Charpentier Joseph , Albert Adelin , Legrand Victor , Rompen Eric H.
Published: February 2005

Background: Periodontitis has recently been identified as a potential risk factor for systemic pathologies such as cardiovascular disease, the hypothesis being that periodontal pockets could release pro‐inflammatory bacterial components, for instance endotoxins, into the bloodstream. It is known that the oral cavity can be a source of circulating bacteria, but this has never been shown for bacterial endotoxins, and no evidence exists so far that the risk of systemic injury is related to the severity of periodontitis. The aim of the present study was to test the influence of gentle mastication on the occurrence of endotoxemia in patients with or without periodontal disease.

Methods: A total of 67 subjects were periodontally examined and grouped according to their periodontal status. This classification was based on an original index of severity of periodontal disease (periodontal index for risk of infectiousness, PIRI) aimed at reflecting the individual risk of systemic injury from the periodontal niches. Thus, the patients were classified into 3 risk groups: low, PIRI = 0; n = 25; moderate, 1 ≤PIRI ≤5, n = 27; and high 6 ≤PIRI ≤10, n = 15. Blood samples were collected before and 5 to 10 minutes after a standardized session of gentle mastication for detection of circulating endotoxins. Blood samples were tested with a chromogenic limulus amoebocyte lysate assay.

Results: Overall, blood levels of endotoxin after mastication were found to be significantly higher than before mastication (0.89 ± 3.3 pg/ml versus 3.0 ± 5.8 pg/ml; P = 0.0002). Likewise, the incidence of positive endotoxemia rose from 6% before mastication to 24% after mastication (P = 0.001). When accounting for the PIRI index, endotoxin levels and positive endotoxemia proved to be significantly higher in patients with severe periodontal disease than in the subjects with low or moderate periodontitis.

Conclusions: Gentle mastication is able to induce the release of bacterial endotoxins from oral origin into the bloodstream, especially when patients have severe periodontal disease. This finding suggests that a diseased periodontium can be a major and underestimated source of chronic, or even permanent, release of bacterial pro‐inflammatory components into the bloodstream. J Periodontol 2002;73:73‐78.
An Organotypic In Vitro Model That Mimics the Dento‐Epithelial Junction
Authors: Oksanen Jaana , Hormia Marketta
Published: February 2005

Background: The dento‐epithelial junction forms the primary periodontal defense structure against oral microbes. The cells of the junctional epithelium (JE) attach both to a basement membrane (BM) facing the connective tissue and to a hard dental tissue by structurally similar but molecularly distinct mechanisms. Here we describe a new organotypic cell culture model for the dento‐epithelial junction comprising not only epithelial and mesenchymally derived components, but also a tooth surface equivalent.

Methods: Rat palatal keratinocytes were seeded on fibroblast‐collagen gels. A tooth slice was placed on top of the epithelial cells and the multilayer cultures were grown at the air‐liquid interface. Formation of the epithelial structures, BM components, and the epithelial attachment to the tooth surface were studied by immunofluorescence and light and electron microscopy. The findings were compared to the structure of the dento‐epithelial junction in vivo.

Results: A well‐differentiated stratified epithelium was formed. Under the tooth slice the epithelium remained thin and non‐differentiated. Attachment of the epithelial cells to the tooth surface was mediated by hemidesmosomes (HDs) as in vivo. Laminin‐5 (Ln‐5) was present in the extracellular matrix (ECM) between the tooth and the epithelium as well as in the BM structure between the epithelium and the fibroblast‐collagen matrix. Instead, Ln‐10/11 was present only at the mesenchymal tissue side as is known to be the case in vivo.

Conclusions: The organotypic model presented expresses the characteristic structural and molecular features of the dentoepithelial junction and may be applied for studying physiological and pathological processes in the epithelial attachment. J Periodontol 2002;73:86‐93.
Histological Comparison of Healing Extraction Sockets Implanted With Bioactive Glass or Demineralized Freeze‐Dried Bone Allograft: A Pilot Study
Authors: Froum Stuart , Cho Sang‐Choon , Rosenberg Edwin , Rohrer Michael , Tarnow Dennis
Published: February 2005

Background: Various materials have been used immediately following tooth extraction to fill and/or cover the socket in an attempt to limit or prevent ridge resorption. The purpose of the present pilot study was to establish a reliable model to investigate the effect of various bone graft and bone replacement materials on extraction socket healing. This study also compared healing extraction sockets 6 to 8 months postimplantation of a bioactive glass (BG) or demineralized freeze‐dried bone allograft (DFDBA) to an unfilled socket control (C).

Methods: Following tooth extraction, a total of 30 sockets in 19 patients were randomly divided into 3 treatment groups: 10 sockets received BG, 10 sockets DFDBA, and 10 sockets served as unfilled controls. Primary coverage was achieved by flap advancement over each socket. Six to 8 months postextraction at time of implant placement, histological cores of the treatment sites were obtained. These cores were processed, undecalcified sections prepared and stained with Stevenel blue/van Gieson's picric fuchsin, and histomorphometrically analyzed. Vital bone, connective tissue and marrow, and residual graft particles were reported as a percentage of the total core.

Results: A model system was described in humans and used to evaluate the healing response in the 3 treatment groups. Results concluded that mean vital bone present was 59.5% for BG‐, 34.7% for DFDBA‐, and 32.4% for C‐treated sites. These differences were not statistically significant. However, the residual implant material was significantly higher in DFDBA‐treated (13.5%) versus BG‐treated sockets (5.5%).

Conclusions: Although the differences in percent vital bone were not statistically significant among the 3 treatment groups in this pilot study, BG material was observed to act as an osteoconductive material which had a positive effect on socket healing at 6 to 8 months postextraction. Further research following implant placement in treated and control sockets is warranted to determine if bone implant contact is improved in BG‐filled versus unfilled sockets. J Periodontol 2002;73:94‐102.
Specific Fibronectin Fragments as Markers of Periodontal Disease Status
Authors: Huynh Quang Ngoc , Wang Shaohui , Tafolla Elizabeth , Gansky Stuart A. , Kapila Sunil , Armitage Gary C. , Kapila Yvonne L.
Published: February 2005

Background: The diagnosis of progressing periodontal disease typically relies on retrospective methods that detect changes in the amount of periodontal breakdown. Fibronectin (FN) fragments are found in vivo in association with periodontal disease, and specific FN fragments compromise periodontal ligament cell functions in vitro. The overall goal of this crosssectional study was to determine whether specific FN fragments are present in gingival crevicular fluid (GCF) and can be used as markers for periodontal disease status. The eventual goal is to test these FN fragments in a longitudinal study as potential markers of disease activity.

Methods: GCF was collected from 94 subjects with untreated periodontitis from clinically healthy, mild/moderate periodontitis, and severe periodontitis sites. Sites were defined on the basis of clinical criteria, including gingival bleeding index, probing depth, and clinical attachment level. Western immunoblotting was used to detect FN fragments in GCF using antibodies to specific FN domains, including the collagen/gelatin‐, central cell‐, and carboxyl terminal heparin‐binding domains, plus the CS‐1 site on the alternatively spliced V region and the EIIIA region. FN fragments identified by immunoblotting and analyzed by NIH image software were scored based on pixel intensity and an ordinal grade scale.

Results: We identified several fragments highly associated with severe periodontitis sites, including 40‐kDa, 120‐kDa, and 68‐kDa fragments.

Conclusions: This study demonstrates that specific FN fragments are markers for periodontal disease status and supports the role of FN fragments as potential components in the pathogenesis of periodontal disease. J Periodontol 2002;73:1101‐1110.
Influence of the Size of the Microgap on Crestal Bone Levels in Non‐Submerged Dental Implants: A Radiographic Study in the Canine Mandible
Authors: King Gaston N. , Hermann Joachim S. , Schoolfield John D. , Buser Daniel , Cochran David L.
Published: February 2005

Background: Accumulating evidence suggests that alveolar crestal bone resorption occurs as a result of the microgap that is present between the implant–abutment interface in dental implants. The objective of this longitudinal radiographic study was to determine whether the size of the interface or the microgap between the implant and abutment influences the amount of crestal bone loss in unloaded non‐submerged implants.

Methods: Sixty titanium implants having sandblasted with large grit, acid‐etched (SLA) endosseous surfaces were placed in edentulous mandibular areas of 5 American fox hounds. Implant groups A, B, and C had a microgap between the implant–abutment connection of <10 µm, 50 µm, or 100 µm, respectively, as did groups D, E, and F, respectively. Abutments were either welded (1‐piece) in groups A, B, and C or nonwelded (2‐piece screwed) in D, E, and F. All abutment interfaces were placed 1 mm above the alveolar crest. Radiographic assessment was undertaken to evaluate peri‐implant crestal bone levels at baseline and at 1, 2, and 3 months after implant placement whereupon all animals were sacrificed.

Results: The size of the microgap at the abutment/implant interface had no significant effect upon crestal bone loss. At 1 month, most implants developed crestal bone loss compared with baseline levels. However, during this early healing period, the non‐welded group (D, E, and F) showed significantly greater crestal bone loss from baseline to one month (P <0.04) and 2 months (P <0.02) compared with the welded group (A, B, and C). No significant differences were observed between these 2 groups at 3 months (P >0.70).

Conclusions: Crestal bone loss was an early manifestation of wound healing occurring after 1 month of implant placement. However, the size of the microgap at the implant‐abutment interface had no significant effect upon crestal bone resorption. Thus, 2‐piece non‐welded implants showed significantly greater crestal bone loss compared with 1‐piece welded implants after 1 and 2 months suggesting that the stability of the implant/abutment interface may have an important early role to play in determining crestal bone levels. At 3 months, this influence followed a similar trend but was not observed to be statistically significant. This finding implies that implant configurations incorporating interfaces will be associated with biological changes regardless of interface size and that mobility between components may have an early influence on wound healing around the implant. J Periodontol 2002;73:1111‐1117.
The Role of CD4+ Cells In Vivo on the Induction of the Immune Response to Porphyromonas gingivalis in Mice
Authors: Sosroseno Wihaskoro , Bird Philip S. , Gemmell Erica , Seymour Gregory J.
Published: February 2005

Background: It has previously been suggested that CD4+ T cells play a pivotal role in regulating the immune response to periodontal pathogens. The aim of the present study therefore was to determine delayed type hypersensitivity (DTH), spleen cell proliferation, serum and splenic anti‐Porphyromonas gingivalis antibody levels, and lesion sizes following challenge with viable P. gingivalis in CD4‐depleted BALB/c mice immunized with P. gingivalis outer membrane proteins (OMP).

Methods: Four groups of BALB/c mice were used. Groups 1 and 2 were injected intraperitoneally (ip) with saline for 3 consecutive days and then weekly throughout the experiment. Groups 3 and 4 were injected ip with rat immunoglobulin and a monoclonal rat anti‐mouse CD4 antibody, respectively. Two days later, group 1 mice were injected ip with saline only, while all the other groups were immunized ip with P. gingivalis OMP weekly for 3 weeks. One week later following the last immunization of OMP, 3 separate experiments were conducted to determine: 1) the DTH response to P. gingivalis OMP by measuring footpad swelling; 2) the levels of antibodies to P. gingivalis in serum samples and spleen cell cultures using an enzymelinked immunosorbent assay, as well as spleen cell proliferation after stimulation with OMP; and 3) the lesion sizes after a subcutaneous challenge with viable P. gingivalis cells.

Results: In CD4+ T‐cell–depleted mice (group 4), the DTH response and antigen‐stimulated cell proliferation were signifi‐cantly suppressed when compared to groups 2 and 3. Similarly, the levels of serum and splenic IgM, IgG, and all IgG subclass antibodies to P. gingivalis OMP were depressed. Delayed healing of P. gingivalis‐induced lesions was also observed in the CD4+ T‐cell–depleted group.

Conclusions: This study has shown that depletion of CD4+ T cells prior to immunization with P. gingivalis OMP led to the suppression of both the humoral and cell‐mediated immune response to this microorganism and that this was associated with delayed healing. These results suggest that the induction of the immune response to P. gingivalis is a CD4+ T‐cell–dependent mechanism and that CD4+ T cells are important in the healing process. J Periodontol 2002;73:1133‐1140.
The Effect of Duration and Force of Mechanical Toothbrushing Stimulation on Proliferative Activity of the Junctional Epithelium
Authors: Tomofuji Takaaki , Morita Manabu , Horiuchi Masazumi , Sakamoto Tomonori , Ekuni Daisuke , Yamamoto Tatsuo , Watanabe Tatsuo
Published: February 2005

Background: Gingival bleeding is frequently accompanied by an ulcerated epithelium, with repair depending on the proliferative activity of the epithelial cells. The present study examined the proliferative activity of the junctional epithelium (JE) under several different methods of toothbrushing stimulation.

Methods: Twelve dogs were used in this 3‐week experiment. Prior to the experiment, all teeth underwent daily removal of plaque and calculus using a scaler. Teeth were then divided into quadrants: 9 teeth in 3 quadrants (test, 3 per quadrant) were mechanically stimulated by toothbrushing for various time intervals (10, 20, or 40 seconds) and at various forces (100, 200, or 250 gf). The 3 teeth in the fourth quadrant served as controls. The proliferative activity of the basal cells of the junctional epithelium was evaluated for expression of proliferating cell nuclear antigen (PCNA). The numbers of PCNA‐positive basal cells and total basal cells were counted, and the width of the junctional epithelium was measured.

Results: Toothbrushing force significantly affected the PCNApositive basal cell ratio (P <0.05). The 200 g toothbrushing force produced the highest PCNA‐positive basal cell ratio, which was significantly higher than that using the 100 g force (P <0.05).

Conclusion: In junctional epithelium stimulated with a toothbrush, the PCNA‐positive basal cell ratio is more sensitive to toothbrushing force than to duration. J Periodontol 2002;73:1149‐1152.
Investigation of the Association Between Angiographically Defined Coronary Artery Disease and Periodontal Disease
Authors: Malthaner Scott C. , Moore Scott , Mills Michael , Saad Robert , Sabatini Robert , Takacs Vincent , McMahan C. Alex , Oates Thomas W.
Published: February 2005

Background: The association between periodontal disease and coronary artery disease (CAD) has been investigated in numerous studies with inconsistent results. Resolving these differences is complicated by the use of varying definitions of CAD. The aim of this study was to investigate the association between angiographically‐defined CAD and periodontal disease.

Methods: Non‐smoking, non‐diabetic patients, over 40 years of age, with no history of a myocardial infarction in the previous 6 months and who had undergone cardiac catheterization within the previous 12 months were enrolled in this study. Subjects were classified as having CAD (CAD+) if they had 50% stenosis in at least one major epicardial artery and classified as CAD negative (CAD–) if they had <50% stenosis in all identified arteries. Periodontal disease severity was measured through bleeding on probing, probing depth, clinical attachment level (CAL), gingival recession, number of missing teeth, and radiographic bone loss.

Results: One hundred (53 = CAD+; 47 = CAD–) patients were examined. CAD+ patients were more likely to be male (CAD+ 83.0% male; CAD– 40.4% male; P = 0.001), and were older (CAD+ 65.3 years; CAD– 60.8 years; P = 0.0138). Although all patients reported they were currently non‐smokers and had not smoked for at least 5 years, the fraction who were former smokers was greater for CAD+ patients (66% versus 24.4%; P = 0.0001) and mean pack/year history of smoking was higher for CAD+ patients (15.8 versus 4.5; P = 0.0003). Mean CAL (3.13 mm versus 2.78 mm; P = 0.0227), number of sites with CAL ≥6 mm (6.85 versus 3.32; P = 0.0242), radiographic bone loss (3.60 mm versus 3.18 mm; P = 0.0142) were greater for CAD+ patients than for CAD– patients. However, after adjustment for age and previous smoking history, factors common to both diseases, the associations of CAD and periodontal disease were reduced and were not statistically significant (odds ratio [OR]: mean CAL OR = 1.06; number of sites with CAL ≥6 mm OR = 1.03; mean radiographic bone loss OR = 1.31; P ≥0.2055).

Conclusions: After accounting for factors common to both periodontal disease and CAD, there was no significant association between periodontal disease and chronic CAD as assessed angiographically. Further investigations into the relationship between periodontal disease and CAD should clearly separate chronic CAD and acute coronary events. J Periodontol 2002;73:1169‐1176.