bluuebunny/crossref_metadata_2025 huggingface dataset:
Antisense Oligonucleotide of Tissue Inhibitor of Metalloproteinase‐1 Induces the Plasminogen Activator Activity in Periodontal Ligament Cells
Authors: Shibata Yasuko , Takiguchi Hisashi , Abiko Yoshimitsu
Published: February 2005

Background: Matrix metalloproteinases (MMPs), produced by both infiltrating and resident cells of the periodontium, play a role in physiologic and pathologic events. It is recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. Although it is known that pro‐MMPs are activated by the plasminogen activator (PA)/plasmin system, and that the activated MMPs are inactivated by tissue inhibitor of metalloproteinases (TIMPs), participation of TIMPs in the PA/plasmin system has not been defined.

Methods: We investigated the effects of the antisense oligonucleotide, consisting of a 21‐base sequence from the human TIMP‐1 gene including the first ATG initiation codon, on PA/plasmin activities in the cultured medium of periodontal ligament (PDL) fibroblastic cells. Antisense or sense oligonucleotides were directly added into cell‐cultured medium, and enzyme activities from the PDL cells were measured.

Results: Antisense TIMP‐1 oligonucleotide specifically stimulated the PA activity dose‐dependently. Other oligonucleotides, sense TIMP‐1 or antisense TIMP‐2, did not affect PA activity in PDL cells. The PA activity increased by antisense TIMP‐1 oligonucleotide was due to an increase of urokinase‐type PA (uPA) protein, but not that of tissue‐type PA by means of immunoblotting. Furthermore, the stimulation of PA activity in the conditioned medium by adding antisense oligonucleotide for TIMP‐1 was not due to the decreasing levels of PA inhibitor‐1, an inhibitor of PA.

Conclusions: TIMP‐1 controls the synthesis of uPA in the PDL cells. Control of the TIMP‐uPA system is important in inflammatory periodontal ligament healing. J Periodontol 1999;70:1158‐1165.
Smoking Influences Decision Making in Periodontal Therapy: A Retrospective Clinical Study
Authors: Papantonopoulos George H.
Published: February 2005

Background: Mechanical periodontal therapy consists of a non‐surgical course, followed by surgical treatment to eliminate or reduce remaining pathological pockets. Only if diligent mechanical therapy fails are additional measures considered. It has been documented that smoking interferes with the host defense mechanisms. This study addresses the question is meticulous non‐surgical periodontal therapy equally successful in smokers and non‐smokers? If not, is a thorough and cumbersome non‐surgical approach in smokers worth undertaking?

Methods: Thirty‐five smokers and 35 non‐smokers were selected retrospectively from a pool of 306 patients treated in a private practice over a 17‐month period. All had at least 14 teeth present with 8 presenting with gingival pockets ≥6 mm. Non‐surgical treatment was performed in 6 to 10 appointments and results were evaluated 6 to 12 weeks after therapy. Bleeding on probing sites with probing depths ≥5 mm were then considered for surgical treatment.

Results: Before treatment smokers had statistically significantly higher mean percent of pockets 4 to 5 mm and ≥6 mm (40.36 ± 10.65 and 26.51 ± 11.95, respectively, compared to 30.38 ± 7.57 and 20.42 ± 10.03 for nonsmokers) and showed significantly lower proportional reduction of these parameters with treatment (50.80 ± 33.76 and 81.36 ± 19.82 for pocket 4 to 5 mm and 6 mm, compared to 68.43 ± 21.23 and 91.7 ± 8.92 for nonsmokers). A multivariate analysis gave smoking, plaque control, and initial percent of sites ≥6 mm to be significant predictors of the percent of teeth in need of further therapy. In non‐smokers, treatment was apparently successful in all tooth types with the exception of upper first and second molars (28.5% failure) and lower second molar (20% failure). In smokers, rates of further treatment needs were particularly high in the premolar‐molar area in both jaws, ranging from 31.4% to 48.5% for an individual tooth type; 42.8% of smokers and 11.5% of non‐smokers needed further treatment in 16% of their teeth (pretest probability). A decision analysis showed that for smokers with at least 1 of 5 sites ≥6 mm, one should initiate surgical treatment, rather than first treat non‐surgically. If the point of indifference that the decision is correctly set at 95%, the pretest probability should be >12%. There is a higher risk that non‐surgical therapy will fail, for instance if we lower the point of indifference to 60%, the pretest probability should be 7>31%.

Conclusions: It is concluded that smoking impairs healing after nonsurgical periodontal therapy. The decision analysis of this study questions the need for a thorough course of non‐surgical treatment in smokers with advanced periodontal disease. J Periodontol 1999;70:1166‐1173.
An 18‐Year Longitudinal Study of Untreated Mucogingival Defects
Authors: Freedman Arnold L. , Green Kevan , Salkin Leslie M. , Stein Marc D. , Mellado Jose R.
Published: February 2005

Background: A study was conducted to observe the changes in areas with untreated mucogingival defects over an 18‐year period. The results in this group after 4 and 10 years were previously published.

Methods: Upon entering dental school, a group of 39 freshman dental students were assessed for plaque index, gingival index, probing depth, and width of keratinized tissue. At that time, 112 sites of inadequate keratinized gingiva were found. Seventeen of the original 39 participants with a total of 61 sites were reassessed for the same parameters after 18 years.

Results: The results revealed that 19 sites showed a slight increase in keratinized tissue, 35 were unchanged (for a total of 54 stable sites), and 7 sites showed a slight decrease in keratinized tissue. The mean width of keratinized tissue at the beginning of the study was 1.74 ± 0.545 mm and 2.02 ± 0.885 mm after 18 years. This represented a small, but statistically significant increase in the width. The plaque index (PI) and gingival index (GI) of this group at baseline (PI = 0.77 ± 0.439 and GI = 0.93 ± 0.447) and at 18 years (PI = 0.36 ± 0.344 and GI = 0.65 ± 0.303) indicated a high level of oral hygiene and gingival health.

Conclusions: It was concluded that in the absence of gingival inflammation, areas with small amounts of keratinized tissue may remain stable over long periods of time. J Periodontol 1999;70:1174‐1176.
Single Nucleotide Polymorphisms of the N‐Formyl Peptide Receptor in Localized Juvenile Periodontitis
Authors: Gwinn Maureen R. , Sharma Ashu , De Nardin Ernesto
Published: February 2005

Background: Neutrophils from patients with localized juvenile periodontitis (LJP) exhibit decreased binding and responsiveness to various chemotactic agents, including N‐formyl‐lmethionyl‐l‐leucyl‐l‐phenylalanine (FMLP). This altered reaction of neutrophils is thought to account in part for the increased susceptibility of LJP patients to infections by periodontal organisms. Receptors for FMLP are involved in the activation and the subsequent response to certain chemotactic stimuli.

Methods: In order to determine if this decreased response is due to a genetic variation in the receptor, we directly compared DNA encoding the FMLP receptor from controls matched for gender and race and LJP patients by single strand conformation polymorphism analysis (SSCP).

Results: Using this technique, we observed a characteristic SSCP pattern in 29 out of 30 patient samples in the FMLP receptor DNA. This pattern differed from those obtained from the 20 control subjects as well as 31 patients with adult periodontitis. DNA sequencing of 30 patients indicated single nucleotide polymorphisms (SNPs) in the FMLP receptor DNA from the LJP patients when compared to 20 controls (P = 0.0005). Two single nucleotide base alterations were consistently seen: either a thymine to cytosine substitution at base 329 in 17 LJP patients or a cytosine to guanine substitution at base 378 in 5 LJP patients. A combination of both alterations were seen in 7 LJP patients. Both alterations resulted in amino acid changes in the second intracellular loop of the receptor, specifically phenylalanine to serine at residue 110 and cysteine to tryptophan at residue 126. This region of the FMLP receptor has recently been shown to play a role in ligand binding and Gprotein activation.

Conclusions: This study suggests that a molecular alteration in the second intracellular loop of the FMLP receptor molecules in LJP patients may play a role in the decreased chemotactic activity reported for some LJP patients. J Periodontol 1999;70:1194‐1201.
Changes in Gingival Crevicular Fluid Levels of Immunoglobulin A Following Therapy: Association With Attachment Loss
Authors: Grbic John T. , Lamster Ira B. , Fine James B. , Lam Kei S. , Celenti Romanita S. , Herrera‐Abreu Miriam , Singer Robert E.
Published: February 2005

Background: In previous studies, we demonstrated that increased levels of immunoglobulin A (IgA) in gingival crevicular fluid (GCF) may be “protective,” while increased levels of the polymorphonuclear lysosomal enzyme, β‐glucuronidase, in GCF were associated with increased risk of disease activity. In this study, we examined the effect of scaling and root planing (SRP) on the levels of β‐glucuronidase, IgG, and IgA in GCF over a 24‐week period and compared these to clinical attachment loss (CAL).

Methods: Twenty‐nine patients with periodontal disease were examined for attachment level, probing depth, plaque, and bleeding on probing at 6 sites per tooth. GCF was collected from the mesial aspect of all teeth excluding third molars and analyzed for β‐glucuronidase, IgG, and IgA. After baseline data were collected, each patient received SRP, and GCF was collected again at 2, 4, 6, 8, 12, and 24 weeks post‐SRP while clinical data were obtained at 4, 8, 12, and 24 weeks. In addition, we analyzed whether the magnitude of the IgA response to SRP would affect the rate of periodontal disease progression by examining GCF IgA levels at 2 time intervals: 2 to 4 weeks post‐SRP and 6 to 12 weeks post‐SRP.

Results: Seventeen patients (58.6%) exhibited at least 1 site losing ≥2.5 mm of CAL during the 24‐week study. β‐glucuronidase in GCF was significantly decreased at 2 weeks following SRP and then demonstrated a gradual increase throughout the study period. Levels of IgA in GCF significantly increased following SRP, reaching a peak at 6 weeks and then gradually decreasing throughout the study. Furthermore, we found an inverse relationship between GCF IgA levels at 6 to 12 weeks post‐SRP and the occurrence of CAL.

Conclusions: These results support the hypothesis that maintenance of high levels of IgA in GCF may be “protective” against periodontal attachment loss. Furthermore, levels of β‐glucuronidase appear to be a more sensitive indicator of gingival inflammation than clinical measures. J Periodontol 1999;70:1221‐1227.
Gingival Hemorrhage, Myelodysplastic Syndromes, and Acute Myeloid Leukemia. A Case Report
Authors: Chapple Iain L.C. , Saxby Michael S. , Murray James A.
Published: February 2005

Myelodysplasia syndrome (MDS) presenting as spontaneous gingival hemorrhage is described. Gingival hemorrhage is recognized as a symptom of MDS, a rare group of potentially fatal hematological disorders, but it has not previously been documented as a presenting sign. The diagnostic pitfalls are discussed with the case, and the need for careful interpretation of laboratory findings in conjunction with clinical signs is emphasized. Finally, the MDSs are defined, classified and discussed with respect to their relevance to the clinical periodontist, from a diagnostic, therapeutic, and management standpoint. J Periodontol 1999;70:1247‐1253.
Morphological Study of Root Surfaces in Teeth With Adult Periodontitis
Authors: Abelleira Antonio Crespo , Cobos María Ángeles Rodríguez , Boquete Isaac Manuel Fuentes , Oreja María Teresa Castaño , Barreiro Francisco Javier Jorge , Pato Raquel Beatríz Rodríguez
Published: February 2005

Background: Our study correlates the histological alterations in the cementum (especially resorption areas) of teeth with the different stages of adult periodontitis. Methods: Sixty‐seven teeth affected by adult periodontitis and 7 healthy teeth extracted from patients over 40 years old were used. The teeth were divided into 3 groups according to radiographic data: group 1: five teeth with bone loss less than one‐third of the normal alveolar height; group 2: thirty‐one teeth with bone loss between one and two thirds; and group 3: thirty‐one teeth with bone loss greater than two thirds. The samples were prepared for light and scanning electron microscopy, considering the gingival, middle, and apical thirds in each root.

Results: Two control teeth, 4 teeth in group 1, and all teeth in groups 2 and 3 showed resorption areas. Regarding the gingival third, the control teeth did not show any resorption, while 25% of affected teeth in group 1, 38.7% of teeth in group 2, and 35.5% of teeth in group 3 exhibited resorption. Regarding the middle third, 50% of affected teeth belonging to the control group and group 1; 67.7% of teeth in group 2; and 87.1% of teeth in group 3 showed resorption. Regarding the apical third, all teeth belonging to the control group and group 1 showed resorption, while 93.5% and 87.1% of teeth in groups 2 and 3, respectively, exhibited resorption. Most of the resorptions did not extend beyond the cementum. However, in 29.0% of teeth in group 2 and 38.7% of teeth in group 3, resorption had spread as far as the dentin. All the lesions in the control group and group 1 were practically repaired, while only 71.0% of teeth in group 2 and 61.3% of teeth in group 3 showed some sign of reparation. However, in groups 2 and 3, practically all lesions affecting dentin were repaired.

Conclusions: These data suggest that the spread of root resorption is associated with inflammation. This study also suggests that the capacity for repair of root resorption is diminished with greater severity of periodontitis. J Periodontol 1999;70:1283‐1291.
In Situ Localization and Characterization of Active Proteases in Chronically Inflamed and Healthy Human Gingival Tissues
Authors: Sarment David P. , Korostoff Jonathan , D'Angelo Marina , Polson Alan M. , Feldman Roy S. , Billings Paul C.
Published: February 2005

Background: Studies have indicated an important role for host‐derived proteases in the pathogenesis of periodontal disease. The objectives of this study were: 1) to develop an assay measuring protease activity in situ and 2) to localize and characterize the enzymatic activity in intact inflamed and healthy gingiva.

Methods: Gingival specimens were prepared and overlaid with a quenched fluorescent substrate. Protease activity was visualized by fluorescence microscopy and correlated with histologic features.

Results: In inflamed tissues, enzymatic activity was detected mainly in the connective tissue (predominantly matrix metalloproteases) and, to some extent, in the epithelium (predominantly serine proteases). In contrast, clinically healthy tissues failed to exhibit significant amounts of protease activity. Quantitative and qualitative characteristics of protease activity in intact tissues were found to be pH dependent.

Conclusions: The method described here enabled assessment of active proteases in intact tissues where cell‐cell and cell‐matrix interactions had been maintained. Our results indicate that there are substantial differences in the distribution of specific proteases between clinically healthy and inflamed periodontal tissues. J Periodontol 1999;70:1303‐1312.
Longitudinal Study of Dental Implants in a Periodontally Compromised Population
Authors: Sbordone Ludovico , Barone Antonio , Ciaglia Renato Nicodemo , Ramaglia Luca , Iacono Vincent J.
Published: February 2005

Background: The purpose of this longitudinal study was to determine the clinical status and the composition of the subgingival microbiota of dental implants and natural teeth in patients with a history of periodontitis. Methods: Twenty‐five partially edentulous patients treated for moderate to advanced adult periodontitis and having a total of 42 implants participated in this 3‐year study. The assessment of clinical status was done 1, 2, and 3 years after prosthetic loading (T1, T2, and T3, respectively). Clinical parameters evaluated included probing depth (PD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). The subgingival microbiota at peri‐implant and periodontal sites were analyzed at T1 and T2.

Results: No significant difference in clinical parameters between implants and teeth and within the 2 groups between different time points was observed through the study. PD and CAL measurements of sampled periodontal and peri‐implant sites did not show any statistically significant difference through the study and between the 2 groups. PI of sampled periodontal sites showed a statistically significant improvement during the study. From the morphological observation of the subgingival microbiota, a significant difference in the composition of motile rods between implants and teeth was found at T1. There were no differences detected in the subgingival microbiota, culturally identified at peri‐implant and periodontal sites for the duration of the study.

Conclusions: In conclusion, implants were colonized by the indigenous periodontal microbiota and were well maintained in patients with a history of periodontitis. No significant association between progressing or non‐progressing periodontal or peri‐implant sampled sites in terms of loss of attachment and infection with at least one of the searched periodontal pathogens was found, suggesting that the presence of putative periodontopathogens at peri‐implant and periodontal sites may not be associated with future attachment loss or implant failure. J Periodontol 1999;70:1322‐1329
Microvascular Changes After Placement of Titanium Implants: Scanning Electron Microscopy Observations of Machined and Titanium Plasma‐Sprayed Implants in Dogs
Authors: Matsuo Masato , Nakamura Takatsuna , Kishi Yoshiaki , Takahashi Kazuto
Published: February 2005

Background: The purpose of this study was to clarify the osseointegration process of titanium implants through study of the vascular architecture and bone apposition. The smooth machined‐surface implant is tightly fixed to the bone by its threads. The rough titanium plasma‐sprayed (TPS) coated implants give a scaffold for new bone. Methods: Twelve beagle dogs were used, and 2 surface types of implants were inserted in the mandible. Vascular injection was given 14, 30, and 120 days after surgery. The soft tissue was digested by proteinase solution, and specimens were examined by scanning electron microscope (SEM).

Results: Fourteen days after placement of machined implants, new vessels could be seen branching out from the vascular network of the bone marrow. In TPS implants, a vascular network was seen between the bone‐implant interface. At 30 days, the vessels were arranged in a groove corresponding to the machined fixture. With TPS implants, new bone was visible along the surface of the fixture, and the vascular network was buried in the bone. At 120 days after placement of machined implants, bone had formed a smooth surface. A few blood vessels were arranged along the bone surface. With TPS implants, a rough bone surface and flat vessels were observed on its surface.

Conclusions: Implants become osseointegrated in different ways, depending on their structures and the characteristics of their surfaces. From the microcirculation point of view, the vessels are an important factor for the remodeling of bone. J Periodontol 1999;70:1330‐1338.
Effect of Periodontitis and Smoking on Blood Leukocytes and Acute‐Phase Proteins
Authors: Fredriksson Margareta I. , Figueredo Carlos M.S. , Gustafsson Anders , Bergström Kurt G. , Åsman Björn E.
Published: February 2005

Background: We have previously found hyperreactive neutrophils, intrinsic or induced, in periodontitis patients by in vitro quantitation of free oxygen radicals. The effects of periodontitis and cigarette smoking on blood parameters have generally been described separately. Our aim was to compare these systemic effects of periodontitis and cigarette smoking, separately and in combination, in order to study the hyperreactivity in peripheral neutrophils.

Methods: Blood cells and acute‐phase proteins were studied in 40 periodontitis patients and 43 healthy controls. The generation of free oxygen radicals from neutrophils was measured as luminolenhanced chemiluminescence (CL) after activation of their Fcγ receptors with opsonized Staphylococcus aureus.

Results: An increase in CL in peripheral neutrophils from periodontitis patients was confirmed. Smoking had no significant effect on CL. The periodontitis patients had higher concentrations of C‐reactive protein (CRP) than the controls. ANOVA analysis showed that the increase in neutrophil count, haptoglobin, and α‐1 antitrypsin levels was significantly influenced by cigarette smoking. IgG2 was lower in patients than in controls (P <0.017, ANOVA), and there was an interaction between periodontitis and smoking (P <0.047, ANOVA). The lower concentration of IgG2 in patients who smoke may impair neutrophil function and be a mechanism by which smoking aggravates periodontitis.

Conclusions: In general, the combination of periodontitis and cigarette smoking alters the parameters studied. The effects of periodontitis on CRP and IgG2 means that periodontal lesions may also leak agents, priming the peripheral neutrophils to increased CL. J Periodontol 1999;70:1355‐1360.
Chlorhexidine‐Induced Changes to Human Gingival Fibroblast Collagen and Non‐Collagen Protein Production
Authors: Mariotti Angelo J. , Rumpf Deborah A.H.
Published: February 2005

Background: Chlorhexidine (CHX) has been used extensively as an adjunctive therapy in the treatment of periodontal disease. It is well known that chlorhexidine is toxic to bacteria, but recent evidence has suggested that chlorhexidine may also have deleterious effects on gingival fibroblast proliferation as well as collagen and non‐collagen protein production in cell culture. The purpose of this study was to examine the effects of chlorhexidine on gingival fibroblast proliferation as well as collagen and non‐collagen protein production in cell culture.

Methods: Human gingival fibroblasts were incubated in MEM containing chlorhexidine concentrations ranging from 1 µM to 1300 µM at 37°C for 1, 5, or 15 minutes. Control cells received an equal volume of MEM without chlorhexidine for similar times at 37°C. Following incubation, the media were removed, cells washed twice with MEM supplemented with 10% FBS, and fibroblasts in treatment and control groups were allowed to recover in the same media for 24 hours.

Results: In all strains, cellular proliferation was dependent on the concentration of solubilized chlorhexidine in cell culture but independent of the duration of chlorhexidine exposure. The average inhibitory concentration necessary to reduce cellular proliferation by 50% (ID50) was 222.1 µM. In regard to collagen and non‐collagen protein production, fibroblasts exposed to chlorhexidine concentrations (1 µM) well below the ID50 had a 65% reduction in collagen production and a 57% reduction in noncollagen protein production.

Conclusions: These results suggest that chlorhexidine will induce a dose dependent reduction in cellular proliferation and that concentrations of chlorhexidine that have little effect on cellular proliferation can significantly reduce both collagen and noncollagen protein production of human gingival fibroblasts in vitro. Hence, the introduction of commercially available concentrations (0.12%) or diluted commercial concentrations (as low as 0.00009%) of chlorhexidine to surgical sites for short periods of time prior to wound closure can conceivably have serious toxic effects on gingival fibroblasts and may negatively affect wound healing. J Periodontol 1999;70:1443‐1448.
Regulation of Gingival Fibroblast Interleukin‐6 Secretion by Cyclosporine A
Authors: Morton Rakhi Sinha , Dongari‐Bagtzoglou Anna I.
Published: February 2005

Background: Cyclosporine A (CsA) is a widely used immunosuppressant, with clinical applications ranging from organ transplants to chronic inflammatory diseases. One of the side effects associated with CsA treatment is the development of gingival overgrowth. Exuberant growth of connective tissue within the periodontium can result from hyperactivity of resident fibroblasts. Fibroblasts are capable of secreting interleukin‐6 (IL‐6), which has been shown to enhance proliferation as well as collagen and glycosaminoglycan synthesis by these cells. We tested the hypothesis that one of the pathogenetic mechanisms underlying CsA‐induced fibrosis is an enhanced IL‐6 secretion by gingival fibroblasts (GF) in response to this drug.

Methods: The ability of CsA to upregulate GF IL‐6 secretion alone or in combination with bacterial challenge or other inflammatory cytokines was tested in an in vitro system. Fibroblast cultures were established from systemically healthy gingival tissue donors and were challenged with CsA in the absence or presence of bacteria, IL‐1β, or tumor necrosis factor (TNF) α as co‐stimulants. Nifedipine and phenytoin were also tested to further support findings with CsA. After 72 hours of incubation, culture supernatants were collected and analyzed for IL‐6 content by ELISA.

Results: We have shown that GF respond to CsA with an increase in IL‐6 secretion. The magnitude of this response varies among cultures derived from different tissue donors. We have also demonstrated that GF IL‐6 responses to bacterial challenge or TNFα are downregulated by CsA. However, CsA synergizes with IL‐1β to further upregulate IL‐6 secretion, and this effect is shared by phenytoin and nifedipine.

Conclusions: We conclude that one of the pathogenetic mechanisms underlying drug‐induced gingival overgrowth may be enhanced secretion of IL‐6 by GF in response to these medications. This is the first report on direct and indirect effects of gingival overgrowth‐related medications on GF IL‐6 metabolism. This work will lay the foundation for future studies directed towards the development of prevention or treatment modalities for gingival overgrowth based on blocking the fibrogenic activities of IL‐6 at the cellular level. J Periodontol 1999;70:1464‐1471.
Successful Treatment of Pulpal‐Periodontal Combined Lesion in a Birooted Maxillary Lateral Incisor With Concomitant Palato‐Radicular Groove. A Case Report
Authors: Wei Pein‐Chi , Geivelis Milton , Chan Chiu‐Po , Ju Yuh‐Ren
Published: February 2005

Palato‐radicular groove (PRG) is a common developmental anomaly of maxillary incisors, whereas PRG associated with a birooted maxillary incisor is relatively infrequent. The clinical significance of PRG is related to the incidence of localized periodontitis with or without pulpal pathosis, depending on the depth, extent, and complexity of the groove. Successful treatments of PRG in singlerooted incisors have been reported in the literature. However, treatment of PRG in birooted incisors has often been ineffective. This case report describes a pulpal‐periodontal combined lesion occurring on a birooted maxillary left lateral incisor with concomitant PRG in a 13‐year‐old boy which was successfully treated by conventional endodontic therapy in combination with periodontal treatment including accessory root resection, radiculoplasty and bone grafting. Seven‐year follow‐up is included in this report. The basis of a successful result is accurate diagnosis and elimination of inflammatory irritants and contributory factors. Awareness of the existence of this abnormality by the clinician is important. J Periodontol 1999;70:1540‐1546.
Long‐Term Results of a Minimally Invasive Surgical Approach for Bone Grafting
Authors: Harrel Stephen K. , Nunn Martha E. , Belling Claire M.
Published: February 2005

A retrospective analysis of the results obtained from regenerative surgery performed utilizing a minimally invasive surgical approach was performed. Bone grafting procedures were performed at 194 sites in 87 patients using small incisions and minimal flap reflection. There were 44 females with a mean age of 52.7 years and 43 males with a mean age of 54.9 years. The mean healing time at which data were collected was 21.7 months. Postsurgical data were collected at the time of routinely scheduled supportive periodontal therapy (SPT) appointments by 2 evaluators. Mean changes in probing depth and attachment levels were evaluated utilizing a Wilcoxon sign rank test. Mean improvement in probing depth was 4.58 mm (P <0.0001) and attachment level was 4.87 mm (P <0.0001). These improvements were seen for all levels of initial prognosis (good to poor) and appeared to be stable over time. The postsurgical gingival margin was at or within 1 mm of the cemento‐enamel junction (CEJ) for 58% of the sites treated. This was interpreted to indicate good retention of soft tissue height postsurgically. It was concluded that the minimally invasive approach for bone grafting yielded results that were equivalent to more traditional surgical approaches utilizing longer incisions and greater reflection. J Periodontol 1999;70:1558‐1563.
Comparative Clinical Study of a Bioabsorbable Membrane and Subepithelial Connective Tissue Graft in the Treatment of Human Gingival Recession
Authors: Borghetti Alain , Glise Jean‐Marc , Monnet‐Corti Virginie , Dejou Jacques
Published: February 2005

Background: Connective tissue grafts and guided tissue regeneration (GTR) are the most current procedures in the treatment of gingival recession, but very few clinical comparative studies have been conducted.

Methods: The purpose of this study was to compare 2 types of treatment of gingival recession in the same patients. Fourteen pairs of Miller Class I defects were selected in 14 patients. In each pair, one recession was randomly assigned for treatment by GTR using a bioabsorbable membrane, and the other treated by subepithelial connective tissue graft (CTG). Height of recession (HR), clinical attachment level (CAL), probing sulcus depth (PSD), height of keratinized tissue (HKT), and distance from the cemento‐enamel junction to the mucogingival junction (CEJ‐MGJ) were recorded before surgery and 6 months postoperatively.

Results: The initial width and height of recession were, respectively, 3.73 mm (SD 0.56) and 3.85 mm (SD 1.15) for the CTG group, and 4.04 mm (SD 0.92) and 4.28 mm (SD 1.20) for the GTR group. The differences were not significant. CAL changes were not different. Both in the CTG group and in the GTR group, mean HR reduction was 2.89 mm (SD 1.18), representing a mean root coverage of 76% and 70.2%, respectively. The difference was not significant. HKT mean gain was significantly greater (P = 0.0001) with CTG (2.03 mm, SD 0.92) than with GTR (0.42 mm, SD 0.91). The GTR technique displaced the mucogingival junction significantly (P = 0.007) more coronally (2.35 mm, SD 1.44) than the CTG technique (0.78 mm, SD 1.23).

Conclusions: Within the limits of this study, no difference could be found between subepithelial connective tissue graft and GTR with a bioabsorbable membrane with regard to root coverage, but the GTR technique did not increase the height of keratinized tissue and displaced the mucogingival junction more coronally at 6 months. J Periodontol 1999; 70: 123‐130.
Recombinant Human Bone Morphogenetic Protein‐2 Stimulation of Bone Formation Around Endosseous Dental Implants
Authors: Cochran David L. , Schenk Robert , Buser Daniel , Wozney John M. , Jones Archie A.
Published: February 2005

Background: Successful endosseous implant placement requires that the implant be stable in alveolar bone. In certain cases, the implant can be stabilized in native bone but some part of the implant is not covered by bone tissue. This often occurs during placement of implants into extraction sites or in areas where bone resorption has occurred and the ridge width is not sufficient to completely surround the implant. In those cases, the clinician usually employs a procedure to encourage bone formation. These procedures typically include a bone graft and/or membrane therapy. Recent advances have led to the isolation, cloning, and production of recombinant human proteins that stimulate bone formation. One of these bone morphogenetic proteins (rhBMP‐2) has been extensively studied in animal models and is currently being tested in human clinical trials.

Methods: In this study, rhBMP‐2 was tested using a collagen sponge carrier to stimulate bone formation in defects in the canine mandible around endosseous dental implants. Six animals had a total of 48 implants placed. rhBMP‐2 with the collagen carrier was implanted around 24 of these, the remainder having only the collagen carrier placed. Half the sites were covered with a nonresorbable expanded polytetrafluoroethylene membrane. Histologic analysis was performed after 4 and 12 weeks. The area of new bone formed, percentage of bone‐to‐implant contact in the defect area, and percentage fill of the defect was calculated.

Results: The addition of rhBMP‐2 resulted in significantly greater amounts of new bone area and percentage of bone‐to‐implant contact and with more percentage fill after 4 and 12 weeks of healing. The area of new bone formed was reduced after 4 weeks when a membrane was present but after 12 weeks, there was no significant difference between membrane and non‐membrane treated sites. In some specimens, new bone was found coronal to the membranes, with rhBMP‐2 – treated sites having greater amounts than non‐rhBMP‐2 – treated sites.

Conclusions: These data demonstrate that a bone differentiation factor significantly stimulates bone formation in peri‐implant bone defects in the canine mandible. In addition, bone‐to‐implant contact was significantly enhanced along the rough implant surface. Membrane‐treated sites had less new bone formation after 4 weeks of healing but were similar to non‐membrane sites after 12 weeks. These results demonstrate that rhBMP‐2 can be used to stimulate bone growth both around and onto the surface of endosseous dental implants placed in sites with extended peri‐implant osseous defects. J Periodontol 1999; 70: 139–150.
Use of Alendronate in Peri‐Implant Defect Regeneration
Authors: Meraw Stephen J. , Reeve Charles M. , Wollan Peter C.
Published: February 2005

Background: Previous studies have demonstrated an increase in bone mass and density with use of systemic alendronate sodium. This agent acts as an inhibitor of osteoclast activity, and is thought to result in more net osteoblastic activity. The objective of this study was to determine the effects of locally applied alendronate sodium on guided bone regeneration around dental implants.

Methods: Six adult mongrel dogs were divided into 2 groups: one group received alendronate‐coated dental implants, and the other group served as control. Two types of dental implants were used in each dog: hydroxyapatite (HA)‐coated and titanium machine‐polished (TMP), for a total of 4 groups. Dental implants were placed immediately after extraction of the right and left second, third, and fourth mandibular premolars; a resorbable collagen membrane was secured over the implants and defects; and the flaps were closed primarily. Fluorescent labels were administered intravenously on days 0, 6, 12, and 22 to measure bone formation rate. Dogs were sacrificed on day 28. The specimens were sectioned and mounted, and bone formation rate was recorded with a computerized microscopic digitizer. Specimens were stained with Stevenel's blue and van Gieson's picric fuchsin. Bone‐to‐implant contact was recorded with a computerized microscopic digitizer.

Results: The results indicated a significant effect of locally applied alendronate (P < 0.0001) with both types of implants (HA and TMP), as well as the HA coating (P < 0.02) on increased bone formation rate. Additionally, alendronate had a significant effect on bone‐to‐implant contact, with an increase in the TMP model (P < 0.0001) and a decrease in the HA model (P < 0.0001). HA coating also had a significant effect on increasing bone‐to‐implant contact (P < 0.04).

Conclusions: The results indicate that alendronate increases early bone formation rate around dental implants. Additionally, the local application as described resulted in greater bone‐to‐implant contact with TMP implants. J Periodontol 1999; 70: 151‐158.
Option‐4 Algorithm for Third Generation Disc Probe: Agreement of Selected Site‐Specific Relative Attachment Level Measurements and Detection of Longitudinal Site‐Specific Attachment Level Change
Authors: Breen Harry J. , Rogers Pauline A. , Slaney Roger E. , Gillett Ian R. , Johnson Newell W.
Published: February 2005

Background: Longitudinal site‐specific attachment level change (SSAC), identified from serial relative attachment level measurements (RAL), is the principal indicator of progression/regression of periodontal diseases. Many variables confound RAL reproducibility and affect measurement error. The Option‐4 algorithm was designed to reduce measurement error and improve accuracy and sensitivity of SSAC detection. The study aimed to evaluate the performance of the Option‐4 algorithm.

Methods: A precalibrated clinician recorded full mouth RAL with a third generation disc probe on 4 occasions over 6 months in 16 subjects (mean age 48.1 years) with moderately advanced chronic adult periodontitis (2,312 sites). Option‐4 allowed up to 4 RAL recordings per site per visit until 2 values had differences ≤ 1.0 mm and their mean was ≤1.0 mm from the previous visit mean: the clinician made the selection if these criteria were unfulfilled.

Results: Within‐visit agreement ≤1.0 mm was ≥ 99.6%: all withinvisit correlation coefficients = 0.98 (P < 0.001). At each visit, mean difference in Option‐4 values was < 0.05 mm, mean absolute difference (ignoring direction) was ≤ 0.34 mm. Mean site‐specific variances ranged from 0.092 mm2 to 0.097 mm2 across all visits. Subject thresholds for site‐specific attachment level change (from estimated 95% confidence limits of visit 1 data) ranged from 0.52 mm to 0.67 mm. Linear SSAC (by linear regression) and betweenvisit patterns of SSAC were investigated. SSAC was detected in 100% subjects and at 51.0% measured sites. Linear SSAC (R2 ≥ 0.90: P ≤ 0.05) occurred at 105 sites (4.5%): 32 sites (1.4%) deteriorated, 73 sites (3.1%) improved. Between‐visit SSAC occurred at 1,074 sites (46.5%): 391 sites (16.9%) deteriorated, 295 sites (12.8%) improved, and 388 sites (16.8%) showed exacerbation/remission patterns.

Conclusions: The Option‐4 algorithm produced high RAL agreement. Site‐specific attachment level change was detected in both directions in 100% subjects and at 51.0% measured sites. J Periodontol 1999; 70:159‐170.
Periodontitis and Anti‐Neutrophil Cytoplasmic Antibodies in Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Comparative Study
Authors: Novo Ernesto , Garcia‐MacGregor Ernesto , Viera Ninoska , Chaparro Neira , Crozzoli Yolanda
Published: February 2005

Background: This investigation was designed to determine and compare the distribution pattern of anti‐neutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in the presence or absence of periodontal disease.

Methods: Sera of 30 patients with SLE and 30 with RA were tested for ANCA utilizing an indirect enzyme immunosorbent assay (ELISA) directed to a neutrophil granular extract and 6 neutrophil granule proteins. A control group of 20 healthy individuals showing neither evidence of periodontal disease nor systemic compromise was also included in this study.

Results: For RA, the number of ANCA‐positive sera was very low but was evenly distributed among patients with and without periodontitis. Conversely, a high number of ANCA‐positive sera in SLE was found mostly in individuals presenting periodontal compromise. A statistically significant association between ANCA and periodontitis in SLE patients was found (P <0.005, chi square test).

Conclusions: A marked difference in the number and distribution of ANCA with respect to periodontitis between RA and SLE was found. Hyperresponsiveness of B cells and polyclonal B activation to periodontopathic bacteria in SLE might be accountable for the high numbers of ANCA and the close association observed between those autoantibodies and periodontitis in SLE. J Periodontol 1999;70:185‐188.
Periodontitis in the House Musk Shrew (Suncus murinus): A Potential Animal Model for Human Periodontal Disease
Authors: Takata Takashi , Matsuura Masahiro , Murashima Miwako , Miyauchi Mutsumi , Nikai Hiromasa
Published: February 2005

Background: Our understanding of periodontal diseases has been facilitated greatly by the use of animal models. However, no animal model has been identified that truly reflects the disease seen in humans. Suncus murinus, a rat‐sized laboratory house musk shrew, has received attention as a valuable animal model due to ease of handling. In the studies described here, periodontal conditions in Suncus murinus were evaluated to determine the usefulness of the shrew as an experimental model for understanding various aspects of periodontal diseases.

Methods: Periodontal tissues of 34 Suncus murinus (18 to 430 days old) were examined macroscopically, morphometrically, histologically, and ultrastructurally.

Results: Dentition pattern is I3/1, C1/1, P2/1, M3/3. Spontaneous gingival swelling with accumulation of plaque was observed in more than twothirds of animals older than 200 days. Morphometric analysis of alveolar bone demonstrated a pattern of bone loss that correlated closely with animal age. Histologically, periodontal lesions varying from gingivitis to periodontitis, similar to those observed in humans, were noted. Marked infiltration of lymphocytes and plasma cells in the connective tissue was noted, usually not seen in periodontal lesions of rodents. Although osteoclastic alveolar bone resorption was noted, active bone resorption was not a frequent feature in specimens obtained from chronic inflammatory lesions. Ultrastructurally, degradation of collagen fibers in the inflamed area and ingestion of collagen fibrils by fibroblasts in the deeper connective tissue were often seen.

Conclusions: These results indicate the potential utility of Suncus murinus as a model to study periodontal disease; e.g., chronic nature of the inflammatory periodontal lesions, similar to those in humans, as well as other advantages including size and ease of handling and housing of these animals. J Periodontol 1999;70:195‐200.
Gingival Fibromatosis Combined With Cherubism and Psychomotor Retardation: A Rare Syndrome
Authors: Yalçin Serhat , Yalçin Funda , Soydinç Mahtaban , Palandüz Sükrü , Günhan Ömer
Published: February 2005

Gingival fibromatosis is frequently an isolated condition, but rarely associated with some uncommon syndromes. This paper describes an 11‐year‐old patient with pronounced gingival enlargement, cherubic facial appearance, and psychomotor retardation and discusses the major aspects of the case. The most striking finding orally was the presence of grossly hyperplastic gingiva, which completely covered all teeth except the occlusal surfaces of some teeth. The swelling in the lower part of the face and the appearance of sclera beneath the iris suggest cherubism. The diagnosis was confirmed by the detection of giant cell regenerative granuloma and perivascular eosinophilic particles and osteoclasts after biopsy of the mandible. In this case, surgery was the only effective way to treat the patient. A full‐mouth gingivectomy procedure was performed under general anesthesia in 2 stages. The case was followed for 12 months and no recurrence was seen. An appropriate oral hygiene regimen was established. J Periodontol 1999;70: 201‐204.
Spontaneous Early Exposure of Submerged Implants: I. Classification and Clinical Observations
Authors: Tal Haim
Published: February 2005

Background: It is believed that during the osseointegration phase of submerged dental implants, complete mucosal coverage and isolation of the implant from the oral cavity avoids trauma and infection and establishes favorable conditions for osseointegration. Spontaneous early exposure is one of the complications that could adversely affect osseointegration of implants.

Methods: This study clinically classifies spontaneous early exposure and describes and analyzes this complication in a group of 148 patients treated with 372 submerged implants: 216 (58%) in the mandible and 156 (42%) in the maxilla. Edentulous sites were exposed by mid‐crestal incisions and full thickness gingival flaps. Incisions were closed in an attempt to achieve complete closure and healing by primary intention. Measurements were taken to avoid mechanical trauma to the mucosa over the implants. Patients were followed up weekly and examined to identify early exposures. Perforations were classified according to the degree of exposure from 0 (no perforations) to 4 (complete exposure).

Results: Of the implants 51 (13.7%) presented spontaneous early exposure,28 (13%) in the mandible and 23 (14.7%) in the maxilla. Class 2 perforation was the most frequent, followed by Class 3, Class 1 and Class 4. Inflammation at the mucosal orifices of the perforations was minimal, but no objective index (bleeding, probing) was taken in order to avoid morphological changes of the lesions that were biopsied for histological examination.

Conclusions: Early perforation and partial exposure of the implant's covering device are a focus for plaque accumulation which, if left untreated, may result in inflammation, damage to the peri‐implant mucosa, and possible periimplant loss. J Periodontol 1999;70:213‐219.
Topical and Systemic Antimicrobial Therapy in Guided Tissue Regeneration
Authors: Zucchelli G. , Sforza N.M. , Clauser C. , Cesari C. , De Sanctis M.
Published: February 2005

Background:Bacterial contamination of membrane material negatively affects healing after guided tissue regeneration (GTR) procedures; conversely, flap connective tissue integration on barrier material improves the clinical outcomes. The objective of this study was to evaluate the effect of topical application of antibiotics on: 1) clinical outcomes of GTR surgical procedures using titanium reinforced expanded polytetrafluoroethylene (ePTFE) periodontal membrane; 2) bacterial colonization of membrane material; and 3) flap connective tissue‐membrane integration.

Methods: Fifty‐six deep interproximal bony defects were treated with GTR surgical procedures using titanium reinforced ePTFE periodontal membranes. Patients were randomly assigned to 1 of the 2 antimicrobial treatment groups: the test group received weekly topical application of 25% metronidazole gel and the control group received systemic antibiotics (amoxicillin plus clavulanic acid 1g/day for 14 days). Clinical outcomes were assessed at 1 year; the amount of bacterial contamination and connective tissue integration on membrane material was evaluated at time of membrane removal by means of a morphological (SEM) method.

Results: No statistically significant difference was found between test and control groups in terms of clinical attachment (CAL) gain (baseline CAL — 12 months CAL; P = 0.2) and probing depth (PD) reduction (baseline PD — 12 months PD; P = 0.6). A greater increase in gingival recession (REC) (12 months REC — baseline REC) was found in the test group compared to the control group (P= 0.003). The SEM analysis revealed no statistically significant (t test) difference between test and control groups in the number of fields positive to integrated connective tissue (P = 0.82), while the number of fields positive to bacteria was statistically higher (P < 0.001) in the control group.

Conclusions: Local antibiotic administration is more effective than systemic use in preventing membrane contamination, but it does not improve clinical outcomes due to an interference of the vehicle (gel) with gingival tissues which may reduce the potential benefits derived from better control of the bacterial load. J Periodontol 1999; 70:239‐247.