bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet‐Derived Growth Factor (PDGF) Gene Delivery for Application in Periodontal Tissue Engineering
Authors: Giannobile William V. , Lee Caroline S. , Tomala Matthew P. , Tejeda Kristina M. , Zhu Zhimin
Published: February 2005

Background: A challenge in the reconstruction of periodontal structures is the targeted delivery of growth‐promoting molecules to the tooth root surface. Polypeptide growth factors such as platelet‐derived growth factor (PDGF) stimulate both cementogenesis and osteogenesis. Recent advances in gene therapy offer the advantage of delivering recombinant proteins to tissues for extended periods of time in vivo.

Methods: Recombinant adenoviral vectors encoding for the PDGF‐A gene were constructed to allow delivery of PDGF transgenes to cells. The recombinant adenoviruses were assembled using the viral backbone of Ad2/CMV/EGFP and replacing GFP (reporter gene encoding green fluorescent protein driven by the cytomegalovirus promoter [CMV] within adenovirus type 2) with the PDGF‐A gene. Root lining cells (cloned cementoblasts) were transduced with Ad2/PDGF‐A and evaluated for gene expression, DNA synthesis, and cell proliferation. PDGF‐inducible genes, c‐myc and osteopontin, were also evaluated following gene delivery of Ad2/PDGF‐A.

Results: The results revealed high level transduction of cementoblasts by gene transfer for 7 days as evidenced by flow cytometry and Northern blotting. Cementoblast DNA synthesis and subsequent proliferation were stimulated by Ad2/PDGF‐A at levels equal to or greater than continuous rhPDGF‐AA application. Strong message for the PDGF‐A gene and protein as evidenced by Northern blotting and immunocytochemistry was noted. Furthermore, the potent induction of c‐myc and osteopontin mRNA was found after PDGF gene delivery to cementoblasts.

Conclusions: These findings demonstrate that gene delivery of platelet‐derived growth factor stimulates cementoblast activity that is sustained above that of rhPDGF‐AA application. The use of gene therapy as a mode of growth factor delivery offers a novel approach to periodontal tissue engineering. J Periodontol 2001;72:815‐823.
Position Paper; Tissue Banking of Bone Allografts Used in Periodontal Regeneration
Authors:   The Committee on Research, Science and Therapy of the American Academy of Periodontology
Published: February 2005

This paper was prepared by the Committee on Research, Science and Therapy of the American Academy of Periodontology for the information of the dental profession. However, it may also be of interest to the lay public. It represents the position of the American Academy of Periodontology regarding tissue banking and the use of bone allografts in periodontal therapy. J Periodontol 2001;72:834‐838.
Surgical Crown Lengthening: A 12‐Month Clinical Wound Healing Study
Authors: Pontoriero Roberto , Carnevale Gianfranco
Published: February 2005

Background: Surgical crown lengthening has been proposed as a means of facilitating restorative procedures and preventing periodontal injuries in teeth with structurally inadequate clinical crowns or exposing tooth structure in the presence of deep, subgingival pathologies which may hamper the access for proper restorative measures. The few clinical studies in the current literature on postsurgical soft tissue modifications after crown lengthening procedures report conflicting results. The present study was designed to assess the alterations of the marginal periodontal tissues as an immediate outcome of surgical crown lengthening and over a 12‐month healing period.

Methods: The patient sample included 30 patients (84 teeth) who presented with various conditions hampering proper restorative measures in one or more teeth and, therefore, requiring surgical exposure of tooth substance. After initial supportive therapy, the patients were recalled for a baseline examination, and the following parameters were evaluated at interproximal and buccal/lingual sites of each experimental tooth: plaque index, gingival index, position of the gingival margin, probing depth, and attachment level. After baseline examination, the patients underwent apically positioned flap surgery with osseous and connective tissue attachment resection. During surgery, the amount of resection and the achieved lengthening of the clinical crown were evaluated. The patients were enrolled in a maintenance program including professional tooth cleaning every 2 to 4 weeks. The patients were reexamined 1, 3, 6, 9, and 12 months postoperatively.

Results: 1) Immediately after surgery, a significantly (P <0.001) increased clinical crown length of 3.7 ± 0.8 mm (mean) at interproximal and 4.1 ± 0.9 mm (mean) at buccal/lingual sites was achieved; 2) healing resulted in a statistically significant coronal displacement of the gingival margin of 3.2 ± 0.8 mm at interproximal (P <0.001) and 2.9 ± 0.6 mm at buccal/lingual (P <0.002) sites; and 3) as a consequence of this postsurgical soft tissue regrowth, the amount of the available tooth structure immediately after surgery decreased to 0.5 ± 0.6 mm at interproximal sites (P <0.0015) and to 1.2 ± 0.7 mm at buccal/lingual sites (P <0.001) at the 12‐month examination.

Conclusions: The results of the present clinical investigation demonstrated that during a 1‐year period of healing following surgical crown lengthening, the marginal periodontal tissue showed a tendency to grow in a coronal direction from the level defined at surgery. This pattern of coronal displacement of the gingival margin was more pronounced (P <0.001) in patients with “thick” tissue biotype and also appeared to be influenced by individual variations in the healing response (P <0.001) not related to age or gender. J Periodontol 2001;72:841‐848.
Clinical Evaluation of 3 Techniques to Augment Keratinized Tissue Without Root Coverage
Authors: Harris Randall J.
Published: February 2005

Background: The importance of keratinized tissue is a controversial subject. However, in some situations most clinicians would agree that surgical procedures to increase the amount of keratinized tissue without root coverage are indicated. In this study, 3 surgical procedures were compared in their ability to increase the width of keratinized tissue. They are: the epithelized autogenous masticatory mucosa graft (free gingival graft), autogenous predominately connective tissue graft (connective tissue graft), and acellular dermal matrix.

Methods: Forty‐five patients referred for treatment of areas with inadequate keratinized tissue were randomly assigned into 1 of 3 groups of 15 each. Each group was treated with 1 of the 3 surgical procedures to increase the width of keratinized tissue. The width of keratinized tissue pre‐ and postsurgery was evaluated.

Results: All 3 groups started with a similar width of keratinized tissue. All of the surgical procedures resulted in a statistically significant increase in the width of keratinized tissue: free gingival graft, 4.1 mm; connective tissue graft, 3.6 mm; and acellular dermal matrix, 4.1 mm.

Conclusion: A statistically significant increase in the amount of keratinized tissue was obtained with all 3 surgical procedures evaluated. J Periodontol 2001;72:932‐938.
Excision and Repair of the Peripheral Ossifying Fibroma: A Report of 3 Cases
Authors: Walters John D. , Will Joseph K. , Hatfield Russell D. , Cacchillo David A. , Raabe Donald A.
Published: February 2005

Background: The peripheral ossifying fibroma (POF), one of the most common gingival lesions, has a recurrence rate of nearly 20%. To minimize the reappearance of this lesion, it must be completely excised. In the maxillary anterior region, total excision of a POF can result in an unsightly gingival defect.

Methods: Three cases are presented in which a POF was excised from the gingiva facial to a maxillary central incisor. One of these lesions had previously undergone 2 cycles of conservative excision and recurrence. In all cases, the lesions were excised down to bone. Each of the resulting gingival defects was repaired by a distinct plastic surgery procedure, including a laterally positioned flap, a subepithelial connective tissue graft, and a coronally positioned flap.

Results: The defects resulting from the biopsies were satisfactorily repaired. The patients were followed over postsurgical intervals of 10 to 30 months. None of the lesions recurred.

Conclusions: It is customary to manage POF by aggressive excisional biopsy. Several different surgical approaches may potentially be used to repair the resultant gingival defect and minimize patient esthetic concerns. J Periodontol 2001;72:939‐944.
Flow Cytometry Analysis of Guided Tissue Regeneration‐Associated Human Periodontal Cells
Authors: Kuru L. , Parkar M.H. , Griffiths G.S. , Olsen I.
Published: February 2005

Background: Expanded polytetrafluoroethylene (ePTFE) barrier membranes have been widely used for guided tissue regeneration (GTR) of the human periodontal ligament (PL). However, the precise cellular and molecular events involved in the re‐growth of the new tissue are still unclear.

Methods: Retrieved membranes and the newly‐regenerated soft tissue (RT) underlying the membranes were used to examine the cells associated with GTR compared with normal human PL and gingival cells. Flow cytometry (FCM) was used, for the first time, to analyze the spindle‐shaped fibroblast‐like cells which were adherent to these membranes and the cells which grew out of the RT.

Results: The results showed that the membrane‐associated (M) cells had the lowest rate of proliferation and appeared to be larger and more granular than the other types of cell. Moreover, both the M‐ and RT‐derived cells were found to express higher levels of the extracellular matrix (ECM) proteins collagen type I, fibronectin, tenascin, and decorin. In addition, evidence based on FCM profiles identified distinct sub‐populations of GTR cells in which fibronectin expression was markedly up‐regulated compared with normal PL cells and which also differed in size and granularity.

Conclusions: The results of this study show that cells associated with GTR barrier membranes and with the underlying tissue appear to have distinct phenotypic and functional activities consistent with the production of new periodontal connective tissue and periodontal regeneration. J Periodontol 2001;72:1016‐1024.
Levels of Leukotriene B4 in Gingival Crevicular Fluid and Gingival Tissue in Specific Periodontal Diseases
Authors: Emingil Gülnur , Çinarcik Serhat , Baylas Haluk , Çoker Işil , Hüseyinov Afig
Published: February 2005

Background: Leukotriene B4 (LTB4), a product of the lipoxygenase pathway of arachidonic acid metabolism, exhibits numerous activities that can account for most of the features of host responses seen in periodontal diseases. The aim of the present study was to examine the role of LTB4 in the pathogenesis of specific periodontal diseases.

Methods: LTB4 levels were investigated in gingival crevicular fluid (GCF) and gingival tissue (GT) samples of 10 patients with chronic periodontitis (CP), 12 patients with generalized aggressive periodontitis (GAgP), 6 patients with localized aggressive periodontitis (LAgP), 6 patients 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. LTB4 was extracted from the samples by solid‐phase method using C18 cartridge and was purified by high performance liquid chromatographic method and then analyzed by radioimmunoassay.

Results: All patient groups had significantly higher levels of GCF and GT LTB4 compared to the control group (P <0.005). The CP patients had the highest LTB4 levels compared to those in other patient groups (P <0.005). GAgP, LAgP, and G groups had similar amounts of GCF and GT LTB4 (P >0.005). When the data were expressed as concentration, the CP group was found to have higher concentration of LTB4, compared to that of control group (P <0.005). GAgP, LAgP, and G groups had similar LTB4 concentration compared to that of control group (P >0.005). No significant difference was found between GAgP, LAgP, and G groups (P >0.005). The CP group had higher LTB4 concentration compared to both GAgP and LAgP groups (P <0.005). Although the CP group had a higher GCF LTB4 concentration compared to G group, this difference did not reach significance (P >0.005). No significant correlation was found between GCF and GT LTB4 levels and clinical parameters.

Conclusions: The results of the present study indicate that LTB4 is likely to be an important mediator in regulating inflammatory responses in the human periodontal tissues. This lipid mediator may play an important role in the pathophysiology of periodontal disease. J Periodontol 2001;72:1025‐1031.
Nitric Oxide Synthase Activity in Neutrophils From Patients With Localized Aggressive Periodontitis
Authors: Shibata Kazuyuki , Warbington Martha L. , Gordon Barbara J. , Kurihara Hidemi , Van Dyke Thomas E.
Published: February 2005

Background: Localized aggressive periodontitis (LAgP) is associated with neutrophil dysfunction including defective chemotaxis and reduced calcium influx factor activity. Nitric oxide (NO) and its enzyme, nitric oxide synthase (NOS), have been suggested to be involved in chemotaxis. Some reports, however, were unable to detect either NO or NOS in human neutrophils. In this study, we focused on NOS activity in LAgP neutrophils and examined the involvement of NOS in chemotaxis of normal neutrophils and NOS activity in neutrophils from normal subjects and patients with LAgP.

Methods: Neutrophils from 10 normal subjects and 10 LAgP patients were isolated from peripheral venous blood. Membrane associated‐NOS (MA‐NOS) and soluble NOS (S‐NOS) were extracted from cells with or without FMLP stimulation. NOS activity was measured using the radiolabeled L‐arginine to L‐citrulline conversion assay.

Results: Nω‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of NOS, significantly inhibited FMLP‐induced chemotaxis (P <0.01) and dibutyryl cGMP, an activator of cGMP‐dependent protein kinase, significantly attenuated the inhibition by LNAME (P <0.01). Unstimulated and FMLP‐stimulated MA‐NOS activity in LAgP neutrophils was statistically significantly higher than that in normal neutrophils (P <0.05). S‐NOS activity in LAgP neutrophils was higher than that in normal neutrophils.

Conclusions: This study suggests that NOS is present in human neutrophils and may be involved in FMLP‐induced chemotaxis in normal neutrophils. NOS activity is increased in LAgP and is negatively correlated to chemotaxis response. J Periodontol 2001;72:1052‐1058.
The Osteoinductive Potential of Demineralized Freeze‐Dried Bone Allograft in Human Non‐Orthotopic Sites: A Pilot Study
Authors: Paul Brian F. , Horning Gregory M. , Hellstein John W. , Schafer Duane R.
Published: February 2005

Background: The use of demineralized freeze‐dried bone allograft (DFDBA) in periodontal therapy is widely accepted. In addition to histologic studies demonstrating its role in regenerating the attachment apparatus, its recognized ability to exhibit osteoinduction in small laboratory mammals has prompted many clinicians to regard it as osteoinductive when utilized in periodontal therapy. Despite such a theoretical deduction, evaluating and establishing the osteoinductive potential of DFDBA in humans has been problematic. The purpose of this study was to investigate, through the use of a novel implantation/recovery model, the potential of DFDBA to induce new bone formation at sites not normally considered capable of de novo osteogenic activity.

Methods: Seven patients scheduled to undergo periodontal therapy utilizing non‐absorbable membranes agreed to have sterile polypropylene mesh capsules placed adjacent to the primary surgical site for the purpose of this investigation. One capsule was left empty while the second capsule contained DFDBA. At the appropriate time interval for removal of the therapeutic membrane, the capsules were removed and submitted for histologic analysis. Five of the subjects had procedures directed at regenerating bone within molar furcations (guided tissue regeneration) and had the membranes and associated capsules removed between 6 and 8 weeks. The 2 remaining patients had procedures directed toward ridge augmentation (guided bone regeneration) and had the membranes removed either at 8 or 9 months, respectively. In addition, one of the 2 long‐term membrane patients had liberal cortical penetration performed directly beneath the implanted capsule.

Results: Histologic analysis of all recovered capsules by 2 independent oral and maxillofacial pathologists could not confirm the presence of either osteoblastic or osteoclastic activity associated with the DFDBA particles, although the 2 longer‐term specimens clearly exhibited trace amounts of vital bone non‐contiguous with the implanted material.

Conclusions: The results of this pilot study do not support the osteoinductive potential of DFDBA when utilized in quantities normally associated with periodontal bone grafting, although they do support the use of this implantation/recovery model to study other preparations and mechanisms of bone formation. J Periodontol 2001;72:1064‐1068.
Treatment of Gingival Overgrowth Induced by Manidipine Administration. A Case Report
Authors: Ikawa Kyoko , Ikawa Motohide , Shimauchi Hidetoshi , Iwakura Masaki , Sakamoto Seizaburo
Published: February 2005

Background: It is well known that severe gingival overgrowth (GO) is induced in patients taking certain calcium channel blockers (CCB) for the treatment of hypertension, angina pectoris, and other diseases. No case has been reported to date of severe GO induced by manidipine hydrochloride (manidipine), a second generation CCB. This case report describes severe GO induced by manidipine in a female patient (43 years old) with hypertension and Sjögren syndrome (SS). The patient was administered manidipine and carteolol hydrochloride (carteolol) as antihypertensive drugs, together with bromhexine hydrochloride for the treatment of SS.

Methods: At the initial periodontal examination, probing depth (PD, average 4.83 mm), plaque control record (PCR, 84.3%), bleeding on probing (BOP, 100%), and gingival overgrowth index (GOI, 2.42) were assessed. The patient received periodontal treatment without cessation or replacement of the causative drug. Initial treatment included oral hygiene and scaling and root planing (SRP) under local anesthesia. As corrective therapy, remaining pockets were surgically removed and fixed bridges placed to establish proper occlusion.

Results: Obvious reductions in PCR (10.0%), PD (1.93 mm), GOI (0.02), and BOP (4.7%), together with a disappearance of GO, were obtained. Salivary secretion was increased after the periodontal and prosthetic treatments. Histological features were similar to those of nifedipine‐induced GO.

Conclusions: This case indicated that manidipine may act as a potent inducer of severe GO, and that conventional periodontal treatments without a major change of the causative drugs can yield satisfactory clinical responses. J Periodontol 2002;73:115‐122.
Smoking and Polymorphisms of the Interleukin‐1 Gene Cluster (IL‐1β, IL‐1α, and IL‐1RN) in Patients with Periodontal Disease
Authors: Meisel P , Siegemund Annett , Dombrowa Sylke , Sawaf H , Fanghaenel Jutta , Kocher Th
Published: February 2005

Background: Polymorphisms within the interleukin‐1 cluster are known to be associated with adult periodontal disease. However, interactions of genetic with other risk factors, especially smoking, remain questionable. The aim of this cross‐sectional study was to evaluate the genetic influence on periodontal variables in relation to environmental factors.

Methods: One‐hundred fifty‐four (154) Caucasian subjects were clinically and radiographically assessed for their periodontal status, their smoking history recorded, and their allelic pattern of IL‐1α, IL‐1β, and IL‐1RN polymorphisms determined by genotyping.

Results: In assessing periodontitis with mean probing depth, mean attachment loss, or mean bone loss, no differences were found in allele frequencies or combined allotypes between subjects with mild or moderate versus those with severe signs of periodontitis. However, the extent of attachment loss defined as percentage of sites >4 mm was signifi‐cantly associated with the composite genotype of IL‐1α/1β in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI] 1.03 to 16.70; P = 0.02). No differences were found in genotype negative subjects irrespective of their smoking status. They had nearly identical attachment loss as genotype positive non‐smokers. Similar non‐significant results were found with respect to extent of bone loss. An increased risk of more extended attachment loss was observed also in individuals carrying mutations of the combined genotype IL‐1α/IL‐1RN, again showing enhanced risk only in genotype‐positive and smoking subjects.

Conclusions: The results provide evidence that the composite genotypes studied show interaction with smoking, the main exposition‐related risk factor of periodontal disease. Non‐smoking subjects are not at increased risk, even if they are genotype‐positive. J Periodontol 2002;73:27‐32.
Clinical Response to 2 Different Therapeutic Regimens to Treat Peri‐Implant Mucositis
Authors: Porras Roberto , Anderson Gissela B. , Caffesse Raul , Narendran Sena , Trejo Pedro M.
Published: February 2005

Background: Maintenance of implants is imperative, since implants, like teeth, are susceptible to bacterial plaque accumulation and calculus formation, and thus at risk of developing peri‐implant mucositis or peri‐implantitis.

Methods: This study determined the clinical effects of chlorhexidine treatment on peri‐implant mucositis at 1 and 3 months as determined by the modified plaque index, the modified sulcus bleeding index, clinical attachment level, and probing depth. Through DNA probes, the effect of chlorhexidine on the microbial flora of mucositic lesions was also evaluated. The population consisted of 16 adult male and female subjects (ages 34 to 76). After the baseline examination, the subjects received a dental prophylaxis and were randomly assigned to the test or control group. Subjects in the test group received antiseptic therapy (Treatment 1), which included mechanical cleansing and oral hygiene instructions supplemented by the local irrigation with chlorhexidine 0.12%, using a plastic syringe, and the topical application of a 0.12% chlorhexidine gel. The subjects in the control group received only mechanical cleansing and oral hygiene instructions (Treatment 2).

Results: Both modalities of treatment were effective in reducing peri‐implant mucositis and probing depths, and improving attachment levels. The trends suggested that mechanical cleansing alone may be sufficient to treat and reduce peri‐implant mucositis at 1 and 3 months after treatment. The addition of chlorhexidine to mechanical debridement did not enhance the results as compared to mechanical debridement alone.

Conclusions: Mechanical debridement as well as mechanical debridement supplemented with chlorhexidine can be beneficial to patients with peri‐implant mucositis. Both treatments resulted in a reduction of plaque, inflammation, and probing depth, as well as a gain in clinical attachment level, and are effective in suppressing or eradicating the pathogenic bacteria often associated with peri‐implant inflammation. J Periodontol 2002;73:1118‐1125.
Effects of Simvastatin Gels on Murine Calvarial Bone
Authors: Thylin Michael R. , McConnell Jay C. , Schmid Marian J. , Reckling Ryon R. , Ojha Junu , Bhattacharyya Indraneel , Marx David B. , Reinhardt Richard A.
Published: February 2005

Background: The cholesterol‐lowering drug simvastatin has been shown to stimulate murine calvarial bone growth after multiple injections. The purpose of this study was to test if similar bone stimulation could be induced by 2 single‐dose drug delivery systems appropriate to periodontal therapy.

Methods: ICR Swiss mice were treated with the following protocols: 1) injection of methylcellulose gel alone, subcutaneously over the calvarium (INJ‐GEL; n = 8); 2) injection of gel with simvastatin (INJ‐SIM; 2.2 mg, n = 16); 3) polylactide membrane (PLA) containing gel alone implanted over calvarium (MEM‐GEL; n = 10); 4) implanted PLA membrane containing gel and simvastatin (MEM‐SIM; n = 10); and 5) untreated mice (n = 12). Animals were sacrificed after 22 or 44 days, calvaria decalcified and stained with hematoxylin and eosin, and images digitized and measured for bone thickness and area. Data were compared using analysis of variance.

Results: INJ‐SIM stimulated a 53% (P = 0.02) increase at the thickest point of calvarial bone, while MEM‐SIM caused a highly significant (P ≤0.0005) increase in bone thickness (159% to 172%) and bone area (144% to 180%) compared to gel controls. Simvastatin gels caused soft tissue inflammation, which appeared to be related to bone increases. If INJ‐SIM animals showing leakage of gel and/or no inflammation were excluded from analysis, INJ‐SIM resulted in more bone (58% to 83%) than gel controls. An insignificant amount of SIM‐stimulated bone was lost over the long term (44 days).

Conclusions: A single, high dose of simvastatin gel can stimulate murine cranial bone apposition, particularly when delivered under an occlusive membrane. Both approaches should be investigated further for possible development for periodontal therapy. J Periodontol 2002;73:1141‐1148.
Subpedicle Acellular Dermal Matrix Graft and Autogenous Connective Tissue Graft in the Treatment of Gingival Recessions: A Comparative 1‐Year Clinical Study
Authors: Paolantonio Michele , Dolci Marco , Esposito Paola , D'Archivio Domenico , Lisanti Luca , Di Luccio Alfonso , Perinetti Giuseppe
Published: February 2005

Background: Many surgical techniques have been proposed for the correction of dental root exposition. Among these, bilaminar techniques (BTs) have been reported as offering the best results in terms of root coverage (RC). However, BTs require a second surgical site to harvest the graft, with discomfort for the patient. The use of an acellular dermal matrix (ADM) avoids the need for a donor site. The aim of this study was to compare the clinical results of 2 BTs by autogenous connective tissue (CT) or ADM.

Methods: In 30 systemically healthy, non‐smoking patients aged 34.5 ± 5.2 years, who showed no periodontal pockets >4 mm after a hygienic phase, a Miller's class I or II gingival recession was treated for root coverage. All patients underwent a BT: in 15 patients, an autogenous connective tissue graft was employed (CT group); in the other 15 subjects, ADM was used as a subepithelial graft (ADM group). Prior to and 1 year after surgical treatment, the following clinical parameters were recorded: gingival recession (GR), probing depth (PD), clinical attachment level (CAL), width of keratinized tissue (KT), and gingival thickness (GT); the percentage of RC (%RC) was also calculated, and the data were statistically analyzed. The number of weeks needed to obtain complete healing with mature tissue appearance was also recorded.

Results: Both groups yielded significant improvements in terms of GR decrease, CAL and KT gain, and GT increase as compared to baseline values. The mean %RCs were 88.80 ± 11.65% and 83.33 ± 11.40% in the CT and ADM groups, respectively. Complete RC was observed in 46.6% of patients from the CT group, and 26.6% of the ADM group patients. No significant differences were observed between the two techniques for GR, CAL, and GT improvements; however, the CT group produced a significantly (P <0.01) greater increase in KT as compared to the ADM group. Complete healing of the surgical procedure was observed 6.20 ± 1.01 and 8.93 ± 1.33 weeks after suture removal in the CT and ADM groups, respectively (P <0.001).

Conclusions: The CT and ADM subepithelial grafts were similarly able to successfully treat gingival recession defects; however, the CT group obtained a significantly greater increase in KT, and showed a quicker complete healing. J Periodontol 2002;73:1299‐1307.
Expression and Activity of Hyaluronidase in Human Periodontal Ligament Fibroblasts
Authors: Ohno Shigeru , Ijuin Chise , Doi Takeyoshi , Yoneno Kiyoshi , Tanne Kazuo
Published: February 2005

Background: Hyaluronan is a major component of the extracellular matrix of periodontal ligament (PDL) contributing to the structural and functional integrity. Hyaluronans contribute to the buffering effect of the PDL during chewing, and they are also important in inflammation and wound healing. Hyaluronan is known to be synthesized and turned over by the resident PDL cells, although the mechanisms of hyaluronan metabolism still remain unclear. Hyaluronidase (HAase), an endoglycosidase, degrades hyaluronan into small fragments. Currently, 3 human HAases, HYAL1, HYAL2, and PH‐20, have been identified and well characterized.

Methods: This study was conducted to investigate the expression and activity of these HAases in cultured human PDL fibroblasts and to elucidate the mechanisms involved in hyaluronan metabolism under normal and inflammatory conditions. Human PDL fibroblasts derived from the periodontium of 3 premolars were cultured with or without interleukin (IL)‐1β (0.1 to 10 ng/ml) and tumor necrosis factor (TNF)‐α (1 to 100 ng/ml) for 0 to 48 hours. The expression of HAase mRNA was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) and quantitative real‐time PCR, and the enzymatic activity was examined using hyaluronan zymography.

Results: PDL fibroblasts expressed HYAL1 and HYAL2 mRNAs, but not PH‐20 mRNA. The expression of HYAL1 mRNA was enhanced by about 3.5‐ and 3.7‐fold at maximum after 1‐hour stimulation with 1 ng/ml IL‐1β and after 3‐hour stimulation with 10 ng/ml TNF‐α, respectively. The expression of HYAL2 and PH‐20 mRNAs was not affected by stimulation with cytokines. HAase activity was detected in conditioned medium from PDL fibroblast cultures, and the activity was enhanced by treatment with 10 ng/ml TNF‐α.

Conclusion: These results suggest that PDL fibroblasts express HAases and generate HAase activity essential for extracellular hyaluronan metabolism under physiological and inflammatory conditions. J Periodontol 2002;73:1331‐1337.
Mediators of Periodontal Osseous Destruction and Remodeling: Principles and Implications for Diagnosis and Therapy
Authors: McCauley Laurie K. , Nohutcu Rahime M.
Published: February 2005

Osteoclastic bone resorption is a prominent feature of periodontal disease. Bone resorption via osteoclasts and bone formation via osteoblasts are coupled, and their dysregulation is associated with numerous diseases of the skeletal system. Recent developments in the area of mediators of osteoclastic differentiation have expanded our knowledge of the process of resorption and set the stage for new diagnostic and therapeutic modalities to treat situations of localized bone loss as in periodontal disease. This review describes the current state of knowledge of osteoclast differentiation and activity, mediators, and biochemical markers of bone resorption and their use and potential use in clinical periodontics. Finally, therapeutic strategies based on knowledge gained in the treatment of metabolic bone diseases and in periodontal clinical trials are discussed, and the potential for future strategies is proposed relative to their biologic basis. The intent is to update the field of periodontics on the current state of pathophysiology of the osteoclastic lesion and outline diagnostic and therapeutic strategies with a rational basis in the underlying biology. J Periodontol 2002;73:1377‐1391.
A 3‐Year Longitudinal Evaluation of Subpedicle Free Connective Tissue Graft for Gingival Recession Coverage
Authors: Lee Yong‐Moo , Kim Jin Y. , Seol Yang‐Jo , Lee Young‐Kyu , Ku Young , Rhyu In‐Chul , Han Soo‐Boo , Choi Sang‐Mook , Chung Chong‐Pyoung
Published: February 2005

Background: The purpose of this study was to longitudinally evaluate, over a 3‐year period, the reduction of gingival recession through use of a subepithelial free connective tissue graft placed under a coronally advanced partial‐thickness pedicle flap.

Methods: Twenty‐one buccal recession defects (mean 3.67 mm; range 3 to 4.5 mm; Miller Class I, II, and III) in 15 patients were treated using this technique. Amount of gingival recession (GR), clinical attachment loss (CAL), and width of keratinized gingiva (WKG) were followed for 3 years after surgery. The measurements were performed at presurgery, and 1, 3, 6, 12, 18, 24, and 36 months postsurgery.

Results: GR decreased from 3.67 ± 0.58 mm at baseline to 0.33 ± 0.43 mm at 36 months, representing a reduction of 3.33 mm, corresponding to 91.28% mean root coverage. CAL was significantly decreased at 36 months from 5.26 ± 0.77 mm to 2.14 ± 0.57 mm. At 36 months, 3.12 mm of attachment gain was obtained. WKG significantly increased after 36 months (1.95 mm). GR, CAL, and WKG had the most positive outcomes at 12 months and were maintained at stable levels throughout the 36‐month observation period.

Conclusions: These results indicate that the connective tissue graft with a partial thickness coronal advancement pedicle is a predictable method for root coverage and, provided that optimal maintenance care is provided, the clinical outcomes gained by this technique can be well maintained. J Periodontol 2002;73:1412‐1418.
Pyostomatitis Vegetans as an Early Sign of Reactivation of Crohn's Disease: A Case Report
Authors: Ayangco Lilibeth , Rogers Roy S. , Sheridan Phillip J.
Published: February 2005

Background: The structures and lining of the oral cavity are an accessible mirror reflecting the health of an individual. They may play an important role in detecting and monitoring systemic diseases. Certain conditions that primarily affect other regions of the body may cause signs and symptoms in the mouth, either as the initial presenting symptom or in conjunction with other systemic manifestations.

Methods: Pyostomatitis vegetans, which occurred in a patient with a history of Crohn's disease, was diagnosed as an early sign of disease reactivation.

Results: The patient was treated with a topical fluorinated corticosteroid gel, which led to the improvement of the oral lesions. However, the oral lesions continued to recur over a period of several months until the underlying inflammatory bowel disease came under control.

Conclusions: This report emphasizes the relationship of pyostomatitis vegetans to inflammatory bowel disease and the importance of the oral lesions as initial presenting signs of systemic disease or activity. J Periodontol 2002;73:1512‐1516.
Histological Evaluation of 4 Cases of Root Coverage Following a Connective Tissue Graft Combined With an Enamel Matrix Derivative Preparation
Authors: Carnio João , Camargo Paulo M. , Kenney E. Barrie , Schenk Robert K.
Published: February 2005

Background: The purpose of this report was to evaluate the histological characteristics of 4 clinically successful root coverage procedures performed with a combination of a connective tissue (CT) graft and an enamel matrix derivative (EMD) preparation.

Methods: Four maxillary teeth (3 canines and 1 first premolar) that presented with mucogingival problems and Miller's Class II and III gingival recession were evaluated in the study. Surgical therapy for root coverage consisted of autogenous CT grafts combined with the topical application of EMD. Following healing, treated teeth were extracted with a portion of their buccal attachment apparatus. Two teeth were extracted at 6 months and 2 teeth at 1 year postoperatively. Specimens were prepared for histology and analyzed by light microscopy.

Results: All treated teeth presented with clinical signs of successful root coverage. Histological observations of the 4 specimens revealed similar findings. The junctional epithelium was≤2 mm long. Apical to the junctional epithelium, dense CT fibers were found in close proximity to the root surface, but in general, no insertion of these fibers into the root was observed. In one 6‐month specimen, formation of new cementum and new bone was observed in the most apical end of the grafted area.

Conclusions: The results of this study suggest that a combination of CT grafts and EMD results mainly in an adhesion between the CT and root surface. Some periodontal regeneration may occur in some regions. The development of a long junctional epithelium was not observed with this combined therapy for the treatment of gingival recession. J Periodontol 2002;73:1534‐1543.
Cytokine Regulation of Gingival Fibroblast Lysyl Oxidase, Collagen, and Elastin
Authors: Hong Hsiang‐Hsi , Trackman Philip C.
Published: February 2005

Background: Systemic therapy with cyclosporin A, phenytoin, and nifedipine modulates cytokine levels in human gingival tissues. Functional relationships between altered cytokine levels and gingival extracellular matrix production are partially characterized. The present study investigates in cultured human gingival fibroblasts the regulation of lysyl oxidase, α‐1 type I collagen, and elastin by selected cytokines that are elevated in drug‐induced gingival overgrowth tissues.

Methods: Normal human gingival fibroblasts were cultured and then treated with selected cytokines: interleukin (IL)‐1β, IL‐6, platelet‐derived growth factor (PDGF)‐BB, and basic fibroblast growth factor (bFGF or FGF‐2). Cells were harvested at intervals, and changes in lysyl oxidase enzyme activity, and in mRNA levels of lysyl oxidase, α‐1 type I collagen, and elastin were determined.

Results: bFGF reproducibly and significantly decreased human gingival fibroblast lysyl oxidase and α‐1 type I collagen mRNA levels in a dose‐ and time‐dependent manner; 1 nM bFGF reduced lysyl oxidase and collagen mRNA levels to 53% and to less than 10% of control after 48 hours of treatment. Interestingly, bFGF downregulated lysyl oxidase enzyme activity by 10% to 20%. IL‐1, IL‐6, and PDGF‐BB did not significantly regulate lysyl oxidase enzyme activity, or α‐1 type I collagen, elastin, and lysyl oxidase mRNA levels under the conditions tested.

Conclusions: Previous studies have shown that modulated levels of bFGF occur in gingiva as a result of certain pharmacologic therapies. The present study suggests that modulated levels of bFGF likely influence gingival connective tissue metabolism. J Periodontol 2002;73:145‐152.
Evaluation of Pluronic Polyols as Carriers for Grafting Materials: Study in Rat Calvaria Defects
Authors: Fowler Edward B. , Cuenin Michael F. , Hokett Steven D. , Peacock Mark E. , McPherson James C. , Dirksen Thomas R. , Sharawy Mohamed , Billman Michael A.
Published: February 2005

Background: Pluronic polyols are a family of non‐ionic surfactants currently used as drug carriers for antibiotic, anti‐inflammatory, and anti‐neoplastic agents. Therapeutic administration of non‐ionic surface‐active agents is known to facilitate early collagen synthesis and microcirculation, thus promoting wound healing. The purpose of this study was to determine the in vivo effects of pluronic polyols combined with either an allograft or an alloplast on the healing of critical‐sized calvarial defects.

Methods: One hundred fifty (150) adult (95 to 105 days old) male Sprague‐Dawley rats weighing between 375 and 425 g were randomly and evenly assigned to each of 15 separate treatment groups and anesthetized, and 8 mm calvarial critical‐sized defects were created. Pluronic F‐68 (F‐68) or pluronic F‐127 (F‐127) was administered either topically or systemically and in conjuction with demineralized bone powder (DBP), tricalcium phosphate (TCP), or non‐grafted controls. Pluronic polyols are easily mixed with either DBP or TCP to improve handling ease. Calvaria were harvested at 12 weeks postsurgery and evaluated histomorphometrically, by contact radiography with subsequent densitometric analysis, through energy spectrometry utilizing a scanning electron microscope, and by fluorescent microscopy.

Results: There was a significant difference in the percentage of bone fill among the control, TCP, and DBP only groups, P <0.05. The only significant difference within any of these groups was between the TCP control and TCP plus systemic F‐127, P <0.05.

Conclusions: Although there were isolated differences, the overall trend was that the pluronic polyol and the mode of administration did not result in a significant change in bone wound healing as measured by the percentage of bone fill. Pluronic polyols may be considered as carriers for osseous graft materials. J Periodontol 2002;73:191‐197.
Distraction Osteogenesis and Histogenesis in Beagle Dogs: The Effect Gradual Mandibular Osteodistraction on Bone and Gingiva
Authors: Cope Jason B. , Samchukov Mikhail L. , Muirhead David E.
Published: February 2005

Background: No study has systematically evaluated the effect of distraction osteogenesis on the gingival tissues. Therefore, this study was designed to analyze the newly formed bone and gingiva during the consolidation period of mandibular osteodistraction using standard histologic techniques.

Methods: Seventeen skeletally mature male beagle dogs underwent 10 mm of bilateral interdental mandibular lengthening. After distraction, the regenerates were allowed to consolidate for 0, 2, 4, 6, or 8 weeks, then the animals were sacrificed and tissues harvested for analysis.

Results: Mineralization began at the host bone margins at the end of the distraction period, followed by a progressive increase in bone surface area, with a concomitant decrease in fibrous tissue. The gingiva initially underwent mild inflammatory and reactive changes during distraction and during the first few weeks of consolidation. The rate of bone formation gradually increased from the end of distraction to the fourth week of consolidation, at which time it remained constant until sometime before the eighth week, when it tapered off slightly as remodeling began. From the second through the eighth week of consolidation, regenerative changes and neohistogenesis were seen in the gingival tissues.

Conclusions: Osteodistraction has the potential to drastically decrease the total treatment time for alveolar bone augmentation prior to dentoalveolar implant placement since the regenerate bone rapidly mineralizes within approximately 8 to 10 weeks after the distraction period and the gingiva responds favorably to increased length by regeneration rather than by degeneration. Although the results appear favorable, similar data should be evaluated in human clinical trials. J Periodontol 2002:73:271‐282.
The Causes of Early Implant Bone Loss: Myth or Science?
Authors: Oh Tae‐Ju , Yoon Joongkyo , Misch Carl E. , Wang Hom‐Lay
Published: February 2005

The success of dental implants is highly dependent on integration between the implant and intraoral hard/soft tissue. Initial breakdown of the implant‐tissue interface generally begins at the crestal region in successfully osseointegrated endosteal implants, regardless of surgical approaches (submerged or nonsubmerged). Early crestal bone loss is often observed after the first year of function, followed by minimal bone loss (≤0.2 mm) annually thereafter. Six plausible etiologic factors are hypothesized, including surgical trauma, occlusal overload, peri‐implantitis, microgap, biologic width, and implant crest module. It is the purpose of this article to review and discuss each factor. Based upon currently available literature, the reformation of biologic width around dental implants, microgap if placed at or below the bone crest, occlusal overload, and implant crest module may be the most likely causes of early implant bone loss. Furthermore, it is important to note that other contributing factors, such as surgical trauma and periimplantitis, may also play a role in the process of early implant bone loss. Future randomized, well‐controlled clinical trials comparing the effect of each plausible factor are needed to clarify the causes of early implant bone loss. J Peridontol 2002;73:322‐333.
Endoscopic Visualization of the Submarginal Gingiva Dental Sulcus and Tooth Root Surfaces
Authors: Stambaugh Roger V. , Myers Gayle , Ebling Wendell , Beckman Bruce , Stambaugh Kathleen
Published: February 2005

Background: Direct, real‐time visualization of the hard and soft tissues within the gingival sulcus may aid the clinician in diagnosis and therapy of periodontal disease. This report describes an endoscope specifically designed for this purpose and the interpretation of dental endoscopic images.

Methods: Medical endoscope technology was modified for application in the dental environment. A fixed, fused fiber optic bundle, less than 1 millimeter in diameter, was coupled to an active matrix LCD‐TFT flat panel video monitor for viewing by the clinician. A bilumen sheath was designed to provide irrigation of the sulcus and a sterile barrier between the patient and the fiber bundle. Standard dental curets and ultrasonic scalers were adapted for instrumentation aided by the endoscope.

Results: Endoscope technology has been successfully adapted for use in periodontal diagnosis and therapy. Techniques for identification and interpretation of the hard and soft tissue images, as well as the location of root deposits and caries, have been developed.

Conclusions: The dental endoscope gives the clinician direct, real‐time visualization and magnification of the subgingival tooth root surface, aiding in the location of deposits on the tooth root. The subgingival soft tissue, including the gingival attachment, sulcus wall, and sulcus contents, can be assessed. Identification and location of subgingival caries, root fractures, tooth root deposits, post perforations, and open restoration margins may aid the clinician in diagnosis and therapy. J Periodontol 2002;73:374‐382.
Human Gingival Fibroblasts Produce Nitric Oxide in Response to Proinflammatory Cytokines
Authors: Daghigh Farzaneh , Borghaei Ruth C. , Thornton Ruth D. , Bee Joseph H.
Published: February 2005

Background: Although nitric oxide (NO) synthesis is increased in periodontal disease (PD), little is known about the possible sources of production by gingival tissues. In fact, gingival tissues from patients with periodontitis demonstrate greater levels of inducible nitric oxide (iNOS) expression than healthy tissue. Macrophages are the source of the iNOS expression, with endothelial cells also contributing. In the present study, our hypothesis has been that human gingival fibroblasts (HGF) also have the ability to produce NO. We have established for the first time that HGF express increased levels of iNOS and modulate NO synthesis in response to proinflammatory cytokines that act synergistically.

Methods: NO production under basal conditions or following incubation with tumor necrosis factor (TNF‐α), interleukin (IL)‐1β, and inferferon (IFN)‐γ was assessed by measurement of stable NO metabolites, nitrite, and nitrate, in a microplate adaptation of the Griess assay. Total RNA was isolated from HGF for determination of iNOS mRNA levels.

Results: We have shown that NO production is elevated in HGF that are stimulated simultaneously by TNF‐α, IL‐1β, and IFN‐γ. Northern blot analysis confirmed that the production of iNOS mRNA by HGF is upregulated in the presence of these cytokines. Addition of mercaptoethyl guanidine (MEG), a specific inhibitor of iNOS, profoundly reduced the production of NO in HGF. Non specific inhibitors of iNOS, L‐NG‐monomethyl arginine (L‐NMMA), and L‐arginine‐methyl ester (L‐NAME) had little or no effect on NO produced in HGF.

Conclusions: These results suggest that elevated NO production could be important in the pathogenesis of PD, and also suggest the ability of an iNOS inhibitor to modulate the disease. Treatments with drugs to block the production of nitric oxide or block its effects might be therapeutically valuable. J Periodontol 2002;73:392‐400.