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Objective Autoantibodies reactive with Ro52 (tripartite motif−containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjogren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease. Methods Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro−transcribed and −translated 35S-methionine−labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21. Results TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ≥3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128–238) and the B30.2/SPRY (amino acids 268–465) domains on TRIM38. Affinity-purified antibodies to TRIM38–CortBP-2 and TRIM38–B30.2/SPRY domains reacted with TRIM21. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

Background. Sjogren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease suggesting a dose effect on the X chromosome. Methods. We examined cohorts of Sjogren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects. Results. Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjogren's syndrome, one patient had 45,X/46,XX/47,XXX with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication were found among controls. In another Sjogren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer. Conclusions. Very rare X chromosome abnormalities are present among patients with either Sjogren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.

The objective of this study was to evaluate bone regeneration in 24 sockets grafted with a calcium phosphosilicate putty alloplastic bone substitute. A core was obtained from 17 sockets prior to implant placement for histomorphometry at 5 to 6 months postextraction. Radiographic analysis during the same postextraction healing period showed radiopaque tissue in all sockets. Histomorphometric analysis revealed a mean vital bone content of 31.76% (± 14.20%) and residual graft content of 11.47% (± 8.99%) after a mean healing period of 5.7 months. The high percentage of vital bone in the healed sites in combination with its timely absorption rate suggest that calcium phosphosilicate putty can be a reliable choice for osseous regeneration in extraction sockets.

Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.

Introduction Most radiolucent jaw lesions are benign and resolve with proper diagnosis and treatment. However, a small percentage of radiolucent jaw lesions are malignant and more difficult to manage. Methods A biopsy of the radiolucent jaw lesion associated with swelling after nonsurgical root canal therapy was submitted. Results The lesion had the combined diagnosis of diffuse large B-cell lymphoma with cystic involvement. The patient has since undergone radiation and chemotherapy treatments. Recall appointments indicate healing of the lesion, and no other areas of lymphoma have been found. Conclusions The existence of a nonhealing radiolucent jaw lesion emphasizes the importance of an early, definitive diagnosis with biopsy.

Objectives: The purpose of the present study was to demonstrate the biocompatibility and rigid osseointegration of a zirconia (Y-TZP) dental implant with acid-etched surface. Materials and methods: Eight zirconia (Y-TZP) implants (CeraRoot, Barcelona) were inserted in the hip of an adult sheep. The animal was sacrificed after 2 months. Four implants were used for histology and histomorphometric analysis, and the other four implants were used for removal torque test (RTQ). Results: The histological evaluation showed a direct bone to implant contact (BIC) with no signs of inflammatory or foreign body reaction. The histomorphometric analysis values ranged from 79.5 to 79.9% of BIC. The RTQ showed values ranging from 75 to 83 Ncm. Discussion: In this animal study, the biocompatibility of CeraRoot zirconia (Y-TZP) implants was demonstrated with the histologic observations of healthy bone tissue in direct contact with the zirconia (Y-TZP) implant surface. Moreover, the histomorphometric analysis and the RTQ confirmed a rigid fixation of the implant within the bone. Comparative studies with acid-etched titanium implants are needed to further evaluate the characteristics of CeraRoot zirconia dental implants.

Theoretical assumptions must correlate with clinical efficacy and good surgical outcomes to be of value to clinicians and patients. This article examines several common assumptions regarding the use of bone marrow aspirate to enhance bone grafting procedures. Contrary to these assumptions, evidence-based research suggests the following: (1) No more than 4 mL of bone marrow should be aspirated from a single donor site. Aspiration of more than that amount does not substantially increase the number of progenitor cells harvested but instead dilutes the concentration of progenitor cells with other nucleated cells from peripheral blood. (2) Bone marrow aspirate should not be concentrated using centrifuge technology. Rather than isolating desired cells, centrifuging concentrates all nucleated cells, increasing the overall metabolic activity to the detriment of the desired cells. (3) Increasing the volume of graft material brought to a graft site has the unwanted effect of increasing the diffusion distance for oxygen and nutrients and may lead to graft necrosis. (4) Histomorphometric analysis is the most effective method of evaluating bone graft outcomes because only such analysis allows for quantification of the percentage of bone and viable cells within a bone core biopsy.

Little is known regarding the histologic hard and soft tissue changes that occur in chronic periimplantitis situations in humans. It is critical to gain an understanding of all aspects of periimplantitis to develop appropriate therapeutic approaches.An 83-year-old African American man presented with a fractured implant affected by severe, chronic periimplantitis and surrounded by keratinized gingiva. A trephine biopsy of the implant and surrounding tissues was analyzed histologically.Histological analysis of the periimplantitis specimen revealed significant inflammatory infiltrate consisting predominantly of lymphocytes and plasma cells. In addition, epithelial migration and bone loss to the apical vent were noted.This case report documents a single case of periimplantitis that was left untreated for 7 years. The presence of significant keratinized tissue and a smooth surface implant failed to prevent fibrous encapsulation of the implant.

Monocytes are progenitor cells that lead the inflammatory cascade reaction responsible for guiding revascularization and regeneration of tissue at injury sites. They do this by secreting inductive cytokines responsible for endothelial cell migration. When released into the peripheral blood, monocytes enter tissues and become macrophages. Monocytes also trigger the body's defense mechanism against microbial invasion by lysing and removing cell debris and dead tissue. The aim of this article is to explain the role of monocytes in the processes of bone healing and regeneration and describe their interaction with stem cells and other entities. Results of a pilot histomorphometric study in which concentrated monocytes were combined with demineralized allograft material to augment implant-placement sites in 2 patients also are presented.

The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair.

The crestal approach to elevating the antral membrane by a resorbable StemVie Post is a modification of the sinus lift technique. This technique can add 4 to 10 mm bone height for severely atrophic ridges in areas that are difficult to access through a lateral window. The procedure is minimally invasive, simple, predictable, and has less postoperative morbidity because of smaller flap design and minimal osteotomy. If sufficient alveolar bone is present for stabilization, an implant can be placed simultaneous with antral elevation and graft. The StemVie Post completely resorbs and is replaced by the patient's own bone.

Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling.Twelve male adult Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load, six animals), or by immersion of the entire implant in a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation.Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P0.05).Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

Artz Z, Nemcovsky CE, Tal H Weinberg E, Weinreb M, Prasad H, Rohrer MD, Kozlovsky A. Simultaneous versus two-stage implant placement and guided bone regeneration in the canine: histomorphometry at 8 and 16 months. J Clin Periodontol 2010; 37: 1029–1038. doi: 10.1111/j.1600-051X.2010.01621.x. Abstract Aim: To compare the effect of timing of implant placement and guided bone regeneration (GBR) procedure on osseointegration and newly formed bone at 8 and 16 months. Material and Methods: In seven dogs, four different sites were bilaterally established: (1) an implant placed in a 6-month healed (6m-GBR) bovine bone mineral (BBM) grafted site; (2) a simultaneously placed implant with the grafted BBM (Si-GBR) followed by a membrane coverage; (3) an implant placed in a membrane-protected non-grafted defect; and (4) an implant placement in a naturally healed site (Cont). Histomorphometry was obtained at 8 and 16 months post-implant placement. Bone–implant contact (BIC), crestal bone resorption (CBR), vertical intra-bony (VIB) defect, bone (BAF) and particle (PAF) area fractions, and osteoconductivity (CON) levels were measured. Results: In all sites, BIC ranged between 62% and 79% with no significant differences. PAF ranged from 17% to 27%, with no effect of time. At 8 and 16 months, BAF was significantly smaller at the Si-GBR site when compared with all other sites, CON was significantly greater at the 6m-GBR site, and CBR and VIB were significantly smaller at the 6m-GBR when compared with the Si-GBR sites. Conclusions: The simultaneous and delayed techniques both showed a similar osseointegration level over time. However, the staged approach showed enhanced newly formed bone, higher osteoconduction around the grafted mineral, less CBR, and smaller vertical bone defect over time compared with the combined approach.

Purpose The purpose of this study was to evaluate the effectiveness of using titanium screws in combination with particulate human mineralized allograft, in a “tenting” fashion, to augment large vertical alveolar ridge defects for implant placement. Materials and Methods This prospective case study evaluated augmentation in consecutive patients with large (>7 mm) vertical alveolar ridge defects. Vertical ridge augmentation was performed using mineralized allograft placed around titanium screws to tent out the soft tissue matrix. The ridges were clinically evaluated 4 to 5 months after augmentation, and implants were placed at that time. Bone cores were harvested from all patients for histologic evaluations. Results Fifteen patients were treated in this prospective case study, and the mean vertical augmentation was 9.7 mm. Two patients had wound dehiscence resulting in loss of graft and requiring secondary grafting before implant placement. Five patients required 2-stage grafting procedures to achieve ideal ridge height before implant placement. Clinical evaluation of the grafted sites upon re-entry revealed uniform ridge anatomy. Histomorphometric analysis of 7 specimens revealed a mean bone content of 43%. A total of 32 implants were placed into grafted sites in 15 patients. All implants were integrated and successfully restored. Mean follow-up was 16.8 months after implant placement. Conclusions Tenting of the periosteum and soft tissue matrix with titanium screws maintains space and minimizes resorption of mineralized particulate allograft. This technique offers predictable functional and esthetic reconstruction of large vertical defects without the use of autogenous bone and is capable of osseointegration. More studies are needed to evaluate the stability of vertically grafted bone after long-term loading.

The uncoupling of osteoblastic and osteoclastic activity is central to disorders such as osteoporosis, osteolytic malignancies, and periodontitis. Numerous studies have shown explicit functions for bone morphogenetic proteins (BMPs) in skeletogenesis. Their signaling activity has been shown in various contexts to be regulated by extracellular proteins, including Twisted gastrulation (TWSG1). However, experimental paradigms determining the effects of BMP regulators on bone remodeling are limited. In this study, we assessed the role of TWSG1 in postnatal bone homeostasis. Twsg1-deficient (Twsg1(-/-)) mice developed osteopenia that could not be explained by defective osteoblast function, because mineral apposition rate and differentiation markers were not significantly different compared with wildtype (WT) mice. Instead, we discovered a striking enhancement of osteoclastogenesis in Twsg1(-/-) mice, leading to increased bone resorption with resultant osteopenia. Enhanced osteoclastogenesis in Twsg1(-/-) mice was caused by increased cell fusion, differentiation, and function of osteoclasts. Furthermore, RANKL-mediated osteoclastogenesis and phosphorylated Smad1/5/8 levels were enhanced when WT osteoclasts were treated with recombinant BMP2, suggesting direct regulation of osteoclast differentiation by BMPs. Increase in detectable levels of phosphorylated Smad 1/5/8 was noted in osteoclasts from Twsg1(-/-) mice compared with WT mice. Furthermore, the enhanced osteoclastogenesis in Twsg1(-/-) mice was reversed in vitro in a dose-dependent manner with exposure to Noggin, a BMP antagonist, strongly suggesting that the enhanced osteoclastogenesis in Twsg1 mutants is attributable to increased BMP signaling. Thus, we present a novel and previously uncharacterized role for TWSG1 in inhibiting osteoclastogenesis through regulation of BMP activity.

To date, most clinicians and researchers have been using platelet concentrate within the range of 4x to 8x baseline. In this case report a new procedure involving strategic pooling and triple spin was developed and used to concentrate platelets to 23x baseline. The concentrate alone was infused into morselized resorbable collagen sponge, activated with calcium chloride and autologous thrombin, then placed as an autologous graft into the left sinus floor of a healthy 80-year-old woman. The floor of the sinus had approximately 2 mm of bony height. A computed tomography scan taken after 5 months showed that new bone was formed and it was as dense as native bone around the surgical site. From the computed tomography scan bone density analysis using Hounsfield Units revealed that the bone formed was D3 bone (518.3 +/- 224.9 Hounsfield Units) and it was as dense as native bone on the axial, coronal and sagittal slices. Histomorphometric analysis of 2 bone core biopsies taken after 6 months showed that 1 core had 34% bone of which 98% was vital new bone and the other core had 39% bone of which 100% was vital new bone. The height of the bone formed in the sinus floor was 12 mm. It was also characterized by good trabecular pattern and connectivity. The quality of the bone generated was such that 2 endosseous implants were placed and torqued to 30 N cm after the cores were removed.

Recent literature suggests that giant cell angiofibroma (GCAF) is a variant of solitary fibrous tumor (SFT) and not just a related lesion. Herein we present a case of apparent SFT with giant cells, including floret cells and focal pseudovascular areas, which are defining features of GCAF. The tumor occurred in the tongue of an 84-year-old female and depicted an encapsulated, patternless spindle cell proliferation in a fibromyxoid stroma with focal dense collagenous areas and scattered floret-type multinucleated giant cells seen primarily in the periphery, as well as pseudovascular spaces, numerous capillaries, and hemangiopericytomalike areas. Immunohistochemical investigation revealed positive staining for CD34 and positive immunoreaction for estrogen and progesterone receptors. We support the present notion that GCAF is a histologic subtype of SFT.

BACKGROUND Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. MATERIAL AND METHODS rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. RESULTS Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact ( approximately 75%; p

Purpose To evaluate the influence of bone marrow aspirate when added to bone block allograft to repair osseous defects. Background Bone-marrow aspirate has been combined with xenograft and allograft particulate material and has produced a significant quantity of new bone growth. However, the use of allograft bone blocks has advantages in some clinical situations. This article discusses cell-based therapies by means of in vivo transplantation of stem cells derived from bone-marrow aspirate and incorporated into allograft corticocancellous bone block for bone regeneration. Materials A technique for combining bone-marrow aspirate with block allografts was developed. To evaluate its influence in repairing osseous defects, a maximum of 3 to 4 mL of bone marrow was aspirated from the anterior iliac crest of 5 patients who had severely atrophic maxillary and mandibular ridges. Five sites were grafted with allograft bone blocks saturated with bone-marrow aspirate and secured with bone screws (ACE Surgical Supply Company, Inc. Brockton, MA). At one of the sites a core specimen was taken 4 months after implant placement and submitted for standard histologic and histomorphometric analysis. Results After 4 to 8 months of healing, all the grafts had integrated into the recipient bone. Implants were placed at all 5 sites and osseointegrated successfully. Examination of the bone core showed the graft to be well-integrated, with 54% of the core consisting of bone and 46% of marrow. Eighty-nine percent of the bone was vital. Conclusion Impregnation of bone-marrow aspirate into allograft bone block activates the body's ability to form new bone. The bone-marrow aspiration technique is less invasive than harvesting autogenous bone from a second surgical site, offers predictable results, and is cost effective.

Objective: To assess the impact of overloading on peri-implant bone level and the bone-to-implant contact (BIC) in the presence of healthy or inflamed peri-implant tissues. Materials and methods: Four screw-shaped machined implants were placed bilaterally in the mandible of four beagle dogs and left submerged for 3 months. Prosthetic abutments were connected either in supra-occlusal contact with the opposite teeth (overloaded) or in infra-occlusal position (unloaded). In each dog, cotton floss ligatures were placed unilaterally around abutments to promote plaque accumulation; the contralateral side was brushed three times a week. There were four experimental sites, two implants in each: loaded uninflamed (LU), loaded inflamed (LI), unloaded uninflamed (UU), and unloaded inflamed (UI). Clinical and radiographic parameters were recorded at baseline and every 3 months throughout the observation period. At 12 months, the dogs were sacrificed and histomorphometric analysis was performed. Results: Implants with ligature-induced peri-implantitis presented high inflammatory indices throughout the observation period. Clinical parameters did not change from baseline for both LU and UU. Loading significantly increased the percentage of BIC (BIC%) (P

Calcium sulfate (CS) is widely used as a bone graft binder and expander. Recent reports indicate that carboxymethylcellulose (CMC) can improve the clinical properties of CS when used as binder for particulate bone grafts; however, limited information is available on the effects of CMC on bone regeneration. The purpose of this study was to evaluate the histologic and morphometric characteristics of bone formation in calvarial defects grafted with a CS-based putty containing 10% CMC in combination with allogeneic demineralized bone matrix (DBM). Bone formation and graft/binder resorption were compared with a surgical grade CS and DBM in paired critical-sized calvarial defects in 25 Wistar rats (350-450 g). Six animals each provided paired defects at 7, 14, 21, and 28 days postsurgery for nondecalcified processing and microscopic analysis. Defects grafted with CS or CS-CMC putty as the DBM binder exhibited similar patterns and proportions of bone formation, fibrous tissue/marrow, and residual DBM particles. Comparable mean +/- SD proportions of new bone formation (31.7 +/- 9.5 and 33.7 +/- 12.9), fibrous tissue/marrow (54.2 +/- 8.3 and 53.0 +/- 10.8), residual DBM particles (8.3 +/- 6.8 and 10.1 +/- 6.3), and residual binder material (5.5 +/- 4.6 and 3.7 +/- 3.5) were found at 28 days for defects grafted with CS and CS-CMC putty, respectively. Thus, CMC was found to improve the handling characteristics of CS and, when used in conjunction with DBM, supported comparable levels bone formation and patterns of binder/scaffold resorption as CS and DBM in a calvarial defect model.

Objective More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67–86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18–123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients. Conclusion The estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.

Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p = 0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. © 2016.

Dental implants are widely accepted as the golden standard for the rehabilitation of an edentulous site following the extraction of a tooth. The ideal time for implant placement is dependent on the time required for partial or complete tissue healing and the adequacy of socket dimensions. The use of autologous growth factors is a promising new concept that aids clinicians in minimizing treatment time and increasing patient satisfaction. The purpose of this paper is to introduce a protocol for “accelerated-early” implant placement. In this protocol, platelet rich fibrin is employed to accelerate soft and hard tissue healing and to provide a better-healed recipient site for accelerated, early implant placement. Histological analysis revealed that at 6 weeks postextraction, the application of our approach resulted in delicate newly formed bone showing intense osteoblastic activity surrounded by connective tissue as well as areas of mineralized tissue. The present study is a proof-of-principle study of the acceleration of the physiologic postextraction healing sequelae with the use of autologous growth factors. The accelerated-early implant placement concept is a bioengineered protocol that may aid clinicians to achieve increased primary stability, by placing implants in ridges in an advanced stage of bone healing, while offering patients the benefits associated with early implant placement. Controlled studies are warranted to verify the reproducibility of this treatment concept and identify specific indications where the use of the presented technique can lead to significant clinical results.

Autoantibodies reactive with Ro52 (tripartite motif-containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease.Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro-transcribed and -translated (35) S-methionine-labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21.TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ≥3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128-238) and the B30.2/SPRY (amino acids 268-465) domains on TRIM38. Affinity-purified antibodies to TRIM38-CortBP-2 and TRIM38-B30.2/SPRY domains reacted with TRIM21.Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

Calcifying epithelial odontogenic tumor (CEOT) is a benign, locally aggressive odontogenic neoplasm characterized by sheets and nests of epithelial cells with deeply eosinophilic or occasionally clear cytoplasm, calcifications, and eosinophilic amorphous material that stains positive for amyloid. Although many cases of CEOT are associated with impacted teeth and occasionally appear radiographically as dentigerous cysts, a true cystic variant has not been previously reported. We report a 15-year-old white male with a large cystic maxillary lesion that filled most of the left maxillary sinus. It deformed the medial wall, the inferior orbital floor, and caused narrowing of the left inferior meatus. Histologically, the cystic lining showed characteristics of CEOT. An intraluminal component that featured histologic characteristics of CEOT was identified during surgery. The lesion was enucleated and the postsurgical course of the patient was uneventful. Because follow-up has been for less than 1 year, a meaningful long-term prognosis cannot be determined at present. However, the patient has not reported any symptoms or signs of recurrence during the follow-up period.

A synthetic peptide (P-15) analog of collagen added to anorganic bovine bone mineral (ABM) has recently been used as an enhanced bone graft material (ABM/P-15). The objective of this study was to test the contribution of ABM/P-15 in a new putty form (PEP) in two experimental membrane-protected defects: periodontal and intrabony. Its efficacy as filler biomaterial in guided tissue regeneration (GTR) and guided bone regeneration (GBR) procedures was evaluated histologically and morphometrically.In the maxillary canines, a facial mucoperiosteal flap was raised bilaterally in nine dogs. Two circular defects, 5 mm in diameter and 2 mm in depth, were made on each side: a fenestrated periodontal on the canine root and an intrabony in the alveolar diastema, anteriorly. PEP particles filled both defects on one side; the contralateral side was blood filled (control). All surgical sites were covered with a bioabsorbable membrane. Histologically, at 4 months, tissue blocks were made using the cutting/grinding non-decalcification method followed by morphometric analysis. In the periodontal fenestration root surface, the linear percentage of new cementum (%CEM), area percentage of new bone (%NB), and residual biomaterial particles (%PEP) were calculated. These same measurements were calculated at the intrabony sites, except cementum. The amount of direct NB to PEP contact was measured to assess the osteoconductivity level (OSC). The Pearson correlation test was used to evaluate any significant relationship between the different measured parameters.In the grafted and non-grafted fenestration root surface defects, %CEM averaged 59.5% and 73.9% (P0.02), respectively; %NB averaged 36.1% and 31.4%, respectively; and %PEP averaged 20.6%. The mean percentage of OSC was 52.4%. In the intrabony grafted and non-grafted sites, %NB averaged 50.7% and 60.1%, respectively (P0.02). Residual %PEP averaged 26.1%, and OSC averaged 35.6%. At the intrabony sites, higher %NB and lower %OSC were found compared to the fenestration sites (P0.001 and P0.03, respectively). Correlation analysis showed a negative correlation between %NB and %PEP at the fenestration defects. In between the two defect types, %OSC was significantly correlated (P0.05).ABM/P-15 putty showed osteoconductive and biocompatible qualities. However, at 4 months in this model, no enhanced regeneration was present compared to a higher CEM and NB growth detected at non-grafted membrane-protected sites.

Although there are a number of bone replacement graft materials that are currently available for clinical use, there are few studies that directly compare efficacy among graft treatments before implant placement. The purpose of this report was to compare 3 bone replacement graft materials (PepGen P-15 228 FLOW [DENTSPLY Friadent CeraMed, Lakewood, CO], Puros [Zimmer Dental, Carlsbad, CA], and C-Graft 228 [Clinician's Preference, Golden, CO]) for bone formation by clinical, histologic, and histomorphometric evaluation.In this prospective, intraoral pilot study, 13 maxillary sockets in 2 patients (both smokers) were grafted immediately after tooth extraction with C-Graft 228, Puros, or PepGen P-15 228 FLOW (containing additional PepGen P-15 228 particles; FLOW PUTTY). After 4 months, bone cores were retrieved and analyzed histologically.PepGen P-15 228 FLOW PUTTY produced a significantly (P0.01) higher amount of vital bone than C-Graft 228 or Puros. The amount of vital bone for FLOW PUTTY was 12-fold higher than for C-Graft 228 and 4-fold higher than Puros. Of 7 FLOW PUTTY treated sites, 7 showed14% vital bone versus 0 of 3 C-Graft 228 and 0 of 3 Puros treated sites. FLOW PUTTY treated sites showed new vital bone between particles of residual graft. C-Graft 228 treated sites showed residual particles in a background of connective tissue with very little bone. Puros treated sites showed nonvital bone particles in a background of connective tissue, with some new vital bone forming around the nonvital bone.PepGen P-15 228 FLOW PUTTY produced significantly greater vital bone as compared to Puros and C-Graft 228 after 4 months. A larger clinical study is required to confirm these results.

BACKGROUND Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone-implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnite)-modified surface. MATERIAL AND METHODS Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. RESULTS There were no remarkable differences in bone formation and apparent bone-implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone-implant contact was 71% and 57% (P=0.027) for TO-modified and CP-coated implants, respectively. CONCLUSIONS We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important.

This prospective study assessed vital bone quality and quantity after grafting maxillary sinuses with anorganic bone mineral containing a cell binding peptide (ABM/P-15) in combination with DFDBA (Mix I), hydrogel/ABM/P-15 (Mix II), or PRP (Mix III). Fifteen maxillary sinuses in 12 patients were grafted with the ABM/P-15 mixtures and after 4 to 5 months, cores were taken and analyzed histologically and histomorphometrically. Fifty-nine screw-type implants were placed. Mixes containing a spacer material (Mix I and II) produced greater average vital bone, more mature bone, and more interconnected bone bridges from the cortical (oral) end to the most apical portion, compared to a mix that lacked a spacer material (Mix III). None of the 59 implants failed with any graft material up to 5 months following implant placement. The study demonstrates that new trabecular bone is formed after grafting ABM/P-15 in the sinus floor; that more vital bone is formed when ABM/P-15 is mixed with a spacer material than without; and that implants can be successfully placed.

Translations [German, Spanish, Portugese, Japanese] AUTOR(EN): Stuart Froum, D.D.S.*, Sang-Choon ("ho, D.D.S.**. Nicolas Elian, D.D.S.***,Edwin Rosenberg D.D.S.#, Michael Rotarer,I).D.S.##. und IX-nnis Tamow. D.D.S.###. * Kti-mscher Professor und Diri'kmr der Umischen Far-schung, Aslmuai AbteUimg fur implantalgestitizteZahnheUhmde, Umversisflt New York, Kriser Den-lidzcntnon. New York, NY. ** KIUUMher Assiswn-zprqfessor und Miif>lieil des wissenschaftUchenForschungsteams, Ashman Abteihmg fiir imptan-tatgestiitzSe ZahnhdHande, Uruversitat New York,Kriser Dentalzentrum. New York. NY. *"* U'ilerda intemattonalen Forschungsprogramms, Assis-tenzprqfessor, Ashman Abieihvig fur wiphuuat-gestiitzle ZahnheUkunde, Universitai New York.Kriser lienhilzeninwi. New York, NY- # Professorfur Orthodontic und impkmiatgesiuizie '/jihnhet-Ikunde, Universiidt von Pennsylvania, Philadel-phia, FA. M Professor uml Letter. Berekh furOral wui KieferpathoJogie, Umversiteil i on Min-iH'sota. zithimwdizjnisihe Fakidtat, Minneapolis,MN. MM Professor und Vorsitzendcr, AshmanAbteihmg fiir implantatgestiitzte Zafmheilkunde,Vniversitiii New York, Kriser Dentalzenrrum, NewYork. NY. SchnftrrrkehrSnum .1. Froum. DOS, 17West >4th Street, Suite I (711 New York, New Yorkimi9. Telefon: 212 • 586 - 4209, Fax: 212 - 246- 75W eMciil: drfirxim@verizpn.netExtraktwnshiihlen und die Implantation von Ilydruxylapalit mil Membranbarriere:eine histologische StudieZVSAMMENFASSVNG: Kinluhrung: Zielset/ung dieser Pilotstudie war es, die Aus-wirkungen auf den Heilungspro/X'ss bei ExtraktionshOhlen zu untersiichen, wenn einabsorbierbares Hydroxylapalil (AH) und cin nichl absorbierbares anorganisches Rinder-knoehenmineral (ARK) /ur Reaktion in dcr Mundhiihlc* belassen wcrden. Eine Bedeckunt;dieser Materialien mit entweder einem azelluliircn. hautsimkturicrlen Allnlransplanlal(AHSA) odcr einer erweiterten PolytetranuiiraLhylnicmbranhaiTierc (ePTFA) warvorgesehen. Materialien und Mflhoden: Bui Zahnexlraktionsbchandlungen an 15 Pati-enten mil mangelhaften Bukkalplalten von 5 mm cnlsiandcn insgesymi 16 ZahnhOhlcn.Nat'h deni Zutallsprin/ip erfolgte eine Aut'tcilung der I'alienten in vier Hehandlungsgrup-pen. I. AH bedeckl mil AHSA. 2. AH bedeckt mil einer ePTFA-Mc-mbran. 3. ARKbedeckt mil AHSA. und 4 ARK bedeckt mil einer elTFA-Membran. Bin Primariiber/ugwurde in keinum der Falle versucht b/.w. erreifht. Sechs bis achi Monait? naeh Zahnex-traktion war die Implantatsetzung vorgesehen. Zu diesem Zeitpunkt wurden histulogischeKerne der behandeken Bereiche entnommen. Diese Kemstucke wurden weiter verarbeitet,mi! Stevenel-Blau / van Giesonschem Picrol'uchsin eingelarbl und millels histomorphoki-gischen Messungen analysiert. I'ro/entuale Anteile von vilalem Knochen, Gewebe undMark sowic verbleibenden Transplantatartikeln in den Gesamtkernen wurden ermittell-Ergebnisse: Durchschnilllieh betrug der Anteil an vitalem Knochengewebe 34.5 It (AHmil AHSA). 41.7 % (ARK mil AHSA), 27,6 % (ePTFA und AH) und^l7.K % (ePTFA undARK). In den mit AHSA bedeeklen acht Extraktionshohlen Canden sich durchschnittlich38 % an vitalem Knochen, wahrend die weiLercn aeht, mit eFTFA-Membranbarrierenbedecklen Hohlen nur 22

Background: Previous studies have shown a limited potential for bone augmentation following guided bone regeneration (GBR) in horizontal alveolar defects. Surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) significantly enhances bone regeneration in such defects; however, sufficient quantities of bone for implant dentistry are not routinely obtained. The objective of this study was to evaluate the potential of rhBMP-2/ACS to enhance GBR using a space-providing, macro-porous expanded polytetrafluoroethylene (ePTFE) device. Methods: Bilateral, critical size, supra-alveolar, peri-implant defects were surgically created in four Hound Labrador mongrel dogs. Two turned and one surface-etched 10-mm titanium dental implant were placed 5 mm into the surgically reduced alveolar ridge creating 5-mm supra-alveolar defects. rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml) or buffer/ACS was randomly assigned to left and right jaw quadrants in subsequent animals. The space-providing, macro-porous ePTFE device was placed to cover rhBMP-2/ACS and control constructs and dental implants. Gingival flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks postsurgery for histologic and histometric analysis. Results: Bone formation was significantly enhanced in defects receiving rhBMP-2/ACS compared to control. Vertical bone gain averaged (±SD) 4.7±0.3 and 4.8±0.1 mm, and new bone area 10.3±2.0 and 8.0±2.5 mm2 at turned and surface-etched dental implants, respectively. Corresponding values for the control were 1.8±2.0 and 1.3±1.3 mm, and 1.8±1.3 and 1.2±0.6 mm2. Bone–implant contact in rhBMP-2-induced bone averaged 6.4±1.4% and 9.6±7.5% for turned and surface-etched dental implants, respectively (P=0.399). Corresponding values for the control were 14.6±19.4% and 23.7±9.7% (P=0.473). Bone–implant contact in resident bone ranged between 43% and 58% without significant differences between dental implant surfaces. Conclusions: rhBMP-2/ACS significantly enhances GBR at turned and surface-etched dental implants. The dental implant surface technology does not appear to substantially influence bone formation.

The purpose of this study was to evaluate histologically the contribution of inorganic bovine bone biomaterial in a new experimental bone defect in dogs at different healing periods and to examine newly formed bone around the grafted mineral particles and their relationship in membrane-protected (test) and non-protected intrabony (control) defects.Four round intrabony defects, 5 x 4 mm were made bilaterally (at different times) on the lateral bony mandibular angle in eight dogs. Two defects were filled with bovine bone mineral (BBM) particles and two remained non-grafted but were blood clotted. A collagen membrane covered each defect type (n = 4). This procedure was repeated on the contralateral side at a different given time to obtain two different healing periods in each dog. Thus, four specimens were obtained at 3, 6, 12, and 24 months postoperatively for each healing period. The non-decalcification method (Donath technique) with Stevenel's blue and van Gieson's picro fuchsin staining was used for histological examination.Newly formed bone was observed at all examined defect types. The BBM particles were clearly evident regardless of the healing period. At 3 and 6 months, newly formed bone, woven in nature, was incorporated with the grafted particles. High cellular bone with occasional osteoclasts was noted towards the surface of the mineral particles. No substantial difference was observed between the protected and the non-protected defects except for higher ossified centers around the membrane-protected defects. At the non-grafted sites, the membrane-protected defect showed newly formed bone near the bony walls, and particularly under the membrane, establishing a bony bridge over the defect at the healing periods. The non-grafted unprotected defect (control) showed bone formation only at the base and close to the bony walls leaving a healed concave configuration. At 1 and 2 years, the grafted sites showed full bone healing configuration. However, the grafted particles still dominated the previous defect area and were completely surrounded by the newly formed bone. Osteons and lamellar bone arrangement were established but the bone was still highly cellular and osteoclasts could still be identified. The non-grafted membrane-protected sites showed excellent bone healing although areas of non-mineralized soft tissue were often seen. The control sites healed but still presented with a concave surface configuration.BBM biomaterial is a highly osteoconductive material. In a 4-wall bony defect, newly formed bone was well evident in establishing excellent bone healing configuration with or without a regenerative biological barrier. The grafted material dominated the experimental sites with no substantial resorption at any healing period up to 2 years observation.

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.

The purpose of this study was to evaluate morphometrically the rate of resorbability of an inorganic bovine bone material in a standardized intrabony defect in dogs whether protected or unprotected by a bioabsorbable membrane at different healing periods, and to assess histomorphometrically the amount of osteoconductivity of this material and final healing site configuration.In eight mongrel dogs, four round intrabony defects (5 x 4 mm) were made on the lateral mandibular angle, bilaterally at a different given time. Bovine bone mineral randomly filled two sites, while the other two were left with blood clot. A bioabsorbable collagen membrane covered each type of defect. The blood clotted uncovered sites served as controls. Section blocks for histology were made at 3, 6, 12, and 24 months. Following the non-decalcification method and staining with Stevenel's blue and van Gieson's picro fuchsin, morphometric analysis was performed on each specimen lesion type.Average bone area fraction at the bovine bone mineral uncovered sites (BBM) was 23.1%, 44%, 63.4%, and 58.8% at 3, 6, 12, and 24 months, respectively. Differences were statistically significant between 3 to 6 and 6 to 12 months (P0.001). Average particle area fraction was 35.6%, 29%, 27.6%, and 26.8% at the respective periods. Differences were statistically significant between 3 to 6 months (P0.05). In the bovine bone mineral membrane-protected (BBMM) sites, average bone area fraction was 26.4%, 51.7%, 61.2%, and 52.4% at 3, 6, 12, and 24 months, respectively. Differences were statistically significant between 3 to 6 months (P0.05). Average particle area fraction was 37.9%, 29.8%, 26.8%, and 33.7%, respectively. Differences between the two sites with regard to the newly formed bone and particle presence were insignificant. In both, the increasing pattern of osteoconduction as expressed by the osteoconductivity test along the different healing periods was similar, as well as the decreasing pattern of the remaining concavity of the healing site configuration. Multiple comparison analysis of bone area fraction disclosed statistically significant superiority (P0.05) of the membrane-ungrafted sites over BBM sites at 3 and 6 months and over BBMM sites at 6 months. Bone area fraction of the BBMM sites (51.7%) was statistically higher than the control sites (37.5%) (P0.05). At 12 months, all test sites were statistically superior over the controls with regard to the regenerated bone and its healing configuration; i.e., remaining concavity of the defect. The healing site configuration of the test sites was persistently different from the control sites at 24 months.Newly formed bone and complete healing were evident in the BBM and BBMM sites. The membrane contributed no substantial benefits. Bovine bone particle resorptive phase was observed up to 6 months. Thereafter, there was no continued resorption up to 24 months observation.

Liquid nitrogen cryotherapy has been advocated as an adjunct in the enucleation and curettage of locally aggressive lesions of the jaws. Simultaneous autogenous bone grafting has also been advocated to accelerate bone formation and reduce morbidity. There is, however, relatively little scientific basis for either of these hypotheses. In this study, nine Yucatan minipigs had artificial defects created in the mandible, which were treated with liquid nitrogen spray. Half of the defects were grafted with autogenous bone from the chin and half were closed primarily. Two animals were sacrificed 3 days postoperatively to measure the width of necrosis and the rest were sacrificed at 3 months to assess healing and new bone formation. It was found that drilling the artificial defects alone caused bone necrosis for a mean depth of 0.09 mm. Liquid nitrogen cryospray caused a mean depth of bone necrosis of 0.82 mm (range 0.51-1.52 mm). The defects that were bone grafted healed well clinically. Defects not bone grafted showed a 50% rate of wound breakdown and sequestrum formation with delayed healing. Vital staining showed a non-significantly greater rate of bone formation in the grafted defects. Digitally superimposed radiography showed a non-significantly greater bone density in the non-grafted defects at 3 months postoperatively. It appears that liquid nitrogen cryospray does devitalize an area of bone around defects in the mandible. The width of necrosis is usually less than 1 mm and subsequent healing is enhanced by autogenous bone grafting. This has clinical implications.

Because of the limited observations of published studies, the condition of hydroxyapatite after a long period of intraoral function remains a concern. This clinical report describes the histologic evaluation of a 9 year-old hydroxyapatite specimen retrieved from a human subject. The residual hydroxyapatite particles showed no sign of resorption, and tight contact with the surrounding bone was observed.

The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) dose on alveolar ridge augmentation and dental implant osseointegration. Bilateral, 5 mm supraalveolar, peri-implant defects were surgically created in 6 beagle dogs. rhBMP-2 (0.05, 0.1 or 0.2 mg/ml) in an absorbable collagen sponge (ACS) carrier was molded around the fixtures and wounds were closed. Treatment variations were alternated between animals (incomplete block design). Animals were sacrificed at week 8 postsurgery. Nine of twelve jaw quadrants healed uneventfully. Two jaw quadrants exhibited wound failure by week 4 and one by week 8 postsurgery. Radiographic bone regeneration was observed in defects without wound failure from week 4 postsurgery. Radiolucent voids of variable size and shape were observed and regressed over time. In weeks 6 through 8, there was an apparent increase in bone density and trabecular structure, while bone height and volume decreased. Histometric analysis revealed limited differences in bone regeneration between experimental conditions. Bone regeneration area averaged (+/- SD) 1.0 +/- 0.5, 3.5 +/- 1.4 and 2.3 +/- 0.4 mm2 for the 0.05, 0.1 and 0.2 mg/ml dose, respectively. There were no significant differences in osseointegration. Osseointegration in newly formed bone averaged 19 +/- 4%, 18 +/- 10% and 21 +/- 6% for the 0.05, 0.1 and 0.2 mg/ml rhBMP-2 sites, respectively. Collectively, the data suggest that there are no dramatic differences in bone induction and osseointegration within the selected dose and observation interval.

In the 100-year history of bone replacement in the human body for different purposes, a wide variety of surgical approaches and materials have been used. The techniques and materials selected significantly affect the outcome of bone replacement procedures in terms of bone formation volume and the quality and amount of vital bone. The choices facing the dental surgeon at the time of extraction, ridge augmentation, or sinus graft are wide-ranging. When choosing a bone graft material the surgeon should consider its ultimate effect on healing patterns in and around the alveolar bone at the endpoint of the procedure. As this article concludes, a better understanding of the materials and the results that can be predictably achieved with them can be valuable to the appropriately trained surgeon when preparing for these procedures.

The 6093 line of transgenic mice exhibits altered bone development as a result of an insertional mutation by the transgene. Female transgenic mice show a marked kyphosis as early as 2 weeks of age. Vertebrae from female mice have lower total bone area and mineral content than age-matched, gender-matched controls, although the bone mineral density is not changed. The femur and tibia exhibit the opposite effect-increased bone area and mineral content. Fluorescent bone label experiments indicated an increased rate of bone mineral deposition in the femur during the early postnatal growth period, and bone marrow from femurs of 6093 females had increased numbers of fibroblast colony-forming units. Transgenic females also are obese and have altered thymocyte development, suggesting that the insertional mutation affects multiple cell populations. We hypothesize that these phenotypes arise as a result of an alteration in the function or developmental potential of a stromal cell or mesenchymal stem cell.

The use of the anorganic bovine bone mineral OsteoGraf/N combined with demineralized freeze-dried bone allograft has received widespread use in sinus elevations. This composite graft material has proven to be suitable, predictable, and successful for the placement and integration of endosseous implants in the edentulous, atrophic maxilla.In this case study, the current materials and accepted methodology were compared with the latest tissueengineered bone replacement graft material, PepGen P-15. PepGen P-15 is a combination of OsteoGraf/N and a synthetic peptide (P-15) that mimics the cell-binding domain of Type-I collagen responsible for cell migration, differentiation, and proliferation.The radiographic, histologic, and histomorphometric evaluations of the sinus grafted with PepGen P-15 showed enhanced bone formation within a shorter time interval compared with the composite graft material of OsteoGraf/N and demineralized freeze-dried bone allograft. (Implant Dent 2000;9:298-302)

The anatomy of the sagittal bands was studied in 56 cadaver digits. The sagittal band is part of an extensor retinacular system which is integrated with the extrinsic and intrinsic musculotendinous structures. The extensor retinacular system is a single unit with radial and ulnar components and has transverse, sagittal and oblique fibres. The transverse-sagittal fibres, along with the palmar plate, form a closed cylindrical tube which surrounds the metacarpal head. The oblique fibres form the triangular lamina distal to the sagittal band. The radial component of the sagittal band is often thinner and longer than the ulnar component. The sagittal band envelops the extensor digitorum tendon and the superficial fibres are thinner than deep fibres, especially in the central digits. The central digits have palmar soft tissue confluence on each side consisting of the sagittal band, palmar plate, annular pulley and deep transverse metacarpal ligament. The sagittal band also appears to envelop the superficial interosseous tendons on both sides. Our findings explain the propensity for radial sagittal band injuries and suggest that the sagittal band is the primary stabilizer of the extensor digitorum at the metacarpophalangeal joint.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in supra-alveolar peri-implant defects in 5 beagle dogs. Alveolar bone was reduced 5 mm in height in mandibular premolar areas and the premolars were extracted. Three 10 mm titanium fixtures were placed 5 mm into each reduced alveolar crest, leaving 5 mm in a supraalveolar position. Alternate quadrants in consecutive animals received a surgical implant consisting of 2 ml rhBMP-2 (0.43 mg/ml) in a type I bovine collagen carrier, or the carrier alone (control). Fixtures and surgical implants were submerged under the gingival flaps. The healing interval was 16 weeks. Histometric and radiographic evaluations were made. Defect height averaged (*SD) 5.3±O.2 and 5.1±0.2 mm for rhBMP-2 and control defects, respectively (P>0.05, n=5, paired, f-test) Bone regeneration (height) averaged 4.2+1.0 and 0.5±0.3 mm for rhBMP-2 and control defects, respectively (P>0.05). Bone regeneration (area) averaged 6.1±6.3 and 0.2±0.2 mm² for rhBMP-2 and control defects, respectively (P±0.05). Osseointegration within the confines of the defect averaged 19.1±10.1% and 8.2±4.6% for rhBMP-2 and control defects, respectively (P 0.05). The results suggest that there is a potential for rhBMP-2 induced bone regeneration and osseointegration in surgical peri-implant defects.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Histologic examination of the tissues surrounding a titanium alloy basket implant and a hydroxyapatite-coated titanium cylinder implant from the mandible of a cadaver were examined. The 67-year-old man died 37 months after first-stage surgery from cardiovascular failure. Clinical and radiographic examinations indicated that the implants were functional, immobile, and integrated. Light microscopy revealed that the gingival tissues adjacent to the implants were healthy and, in general, free of inflammatory cells. The transmucosal area demonstrated a tight connective tissue apposition to the implants. The sulcular epithelial appearance was similar to that of a natural tooth. Histomorphometric analysis revealed that 72.2 percent of the basket implant and 75.3 percent of the hydroxyapatite-coated implant were in direct contact with bone. Generally, the bone along the surface of the basket implant was thicker than the bone along the surface of the hydroxyapatite-coated cylinder. Bone grew through the vent hole areas of both implants.

The aim of this prospective, randomized, controlled, multicenter study was to evaluate and compare the histologic and histomorphometric aspects of extraction sockets grafted with two commercially available bovine bone xenografts: Endobon (test group) and Bio-Oss (control group). The study was designed to ensure that baseline variables between groups were as similar as possible to allow for a direct comparison of graft healing characteristics. Thirty-eight patients contributed 62 augmented extraction sites to the study. All sites were grafted with one type of bovine bone mineral and covered with a resorbable collagen membrane for 6 months of healing prior to implant placement surgery. The histologic outcomes between the two treatment groups are similar, with de novo bone (mean ± SD) for the test group at 28.5% ± 20% and for the control group, 31.4% ± 18%. Histologic specimens also include membrane remnants. All but two implants integrated successfully after 1 year of follow-up. This investigation provides support for the efficacy of bovine bone xenograft for socket preservation when subsequent implant placement is planned.

Objective To compare the performance of the American–European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjogren9s Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. Methods In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. Results Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG−/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. Conclusions The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.