david kohavi - Academia.edu (original) (raw)

Papers by david kohavi

PubMed, Jun 1, 2000

Two approaches for obtaining bone augmentation around implants by guided tissue regeneration are ... more Two approaches for obtaining bone augmentation around implants by guided tissue regeneration are described. In the first, bone is regenerated simultaneously with implant placement, which is a time saving tactic. However, when initial stability of the implant cannot be obtained because of insufficient bone volume, a staged approach must be considered. In the staged approach, the bone is augmented and the implant is inserted later. The staged approach offers improved primary stability, allows the implant to be inserted in mature bone, and enables examination of the newly augmented bone before a decision is made whether or not to use it as an implant site. Two case reports are presented which illustrate the approaches.

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PubMed, Jul 1, 2003

Various statistics have shown that avulsion (total displacement of tooth out of its socket) follo... more Various statistics have shown that avulsion (total displacement of tooth out of its socket) following traumatic injuries is relatively infrequent, ranging from 0.5 to 16% of traumatic injuries in the permanent dentition. The maxillary central incisors are the most frequently avulsed teeth. Avulsion of teeth occurs most often in children from 7 to 9 years of age, when the permanent incisors are erupting. Most frequently, avulsion involves a single tooth; but multiple avulsion are occasionally encountered. Fractures of the alveolar socket wall are often associate with avulsion. After the tooth is lost, an almost certain sequelae is the rapid resorption of alveolar bone. In many cases, only a very thin crestal bony lamella remains after healing of the alveolus, with clinically obvious horizontal and vertical depressions. In a young patient missing an anterior tooth, the operator may find implant insertion, in the proper anatomical position, difficult or impossible, because of inadequate bone volume. This situation aggravates with time because of continuous resorption and relative growth of the adjacent alveolar bone around the teeth. New and predictable bone augmentation techniques allow compensation for bone reduction while waiting for completion of growth. In cases of localized ridge augmentation, the amount of initial bone volume and its shape dictate whether implant insertion and bone augmentation will be performed simultaneously. The indications for this approach are: sufficient bone volume to achieve initial implant stability and a predictably high success rate for the augmentation. When bone volume and shape do not allow for initial stability, there is indication for a staged approach, in which the bone is initially augmented, the results are evaluated and the implant is then inserted. The first stage, the bone regeneration phase, may last between 8-10 months. The second, the implant integration period, may take an additional 6-8 months. The effect of growth on the augmented bone is not quite clear and there is only a paucity of information concerning the use of bone regeneration procedures in growing patients. Clinical decision when to start implant treatment after avulsion is dependent not only on the timing of implant insertion, but also on bone regeneration procedures. When most of horizontal and vertical bony walls of the extraction site is lost, augmentation procedure as a measure to reduce the deficiency, may be considered even in preadolescents. Three cases describing different clinical situations following avulsion, tooth replacement, resorption, regeneration treatment and implant insertion are discussed.

Journal of Biomedical Materials Research, Aug 1, 1993

The effect of 40‐ to 60‐mesh hydroxyapatite (HA) granules (Calcitek, Inc., Carlsbad, CA) on the p... more The effect of 40‐ to 60‐mesh hydroxyapatite (HA) granules (Calcitek, Inc., Carlsbad, CA) on the process of primary mineralization during bone healing was examined following insertion of the HA granules into rat tibial bone after marrow ablation. Response to HA was assessed by monitoring morphometric and biochemical changes in matrix vesicles, which are extracellular organelles associated with initial calcification. Following insertion of HA, matrix vesicle‐enriched membranes (MVEMs) were isolated from the tissue adjacent to the implant and from the endosteum of the contralateral limb at 3,6,14, and 21 days and from a nonimplanted control group (t = 0). MVEM alkaline phosphatase‐ and phospholipase A2‐specific activities were increased on days 6 (peak) and 14; phosphatidylserine content was also elevated on days 6 and 14 (peak). Comparable changes were seen in the contralateral limb but at lesser magnitudes. Morphological changes were observed as well. The number of matrix vesicles/μm2 matrix increased on days 6 (peak) and 14. The mean diameter of the matrix vesicles was elevated on days 6 (peak), 14, and 21. Mean distance from the calcifying front increased on day 6 but was decreased on days 14 and 21. These results indicated that HA behaves like bone‐bonding implants in that there is a stimulation of matrix vesicle enzymes, increased phosphatidylserine content, and increase numbers of matrix vesicles. However, the increases occur only after 6 days postimplantation, indicating a delay in response when compared to normal healing. This delay is confirmed by the morphometric measurements. HA causes a reduction in the response associated with marrow ablation. In addition, the effects of HA are comparable locally and systemically but with different intensity. These observations suggest that osteogenic cells are able to compensate for the inhibitory effects of HA and primary calcification involves normal matrix vesicle production and maturation, if somewhat delayed and reduced in magnitude. The ability to support primary mineral formation may contribute to the successful bonding of HA with surrounding osseous tissue. © 1993 John Wiley & Sons, Inc.

Journal of Breath Research, Jul 18, 2013

Two phase oil-water mouthwash has been previously shown to efficiently bind oral microorganisms, ... more Two phase oil-water mouthwash has been previously shown to efficiently bind oral microorganisms, relying on their cell surface hydrophobicity. The aim of the present in vitro study was to test the cetylpyridinium chloride (CPC) retention and volatile sulfide compounds (VSCs) adsorption abilities of the oil droplets created by mixing of a two phase oil-water solution. VSC adsorption was assayed using a salivary incubation assay and garlic powder solutions, and demonstrated using microscopic sulfide assay. CPC retention was assayed by kinetic and endpoint measurement of Streptococcus salivarius outgrowth using microplate (ELISA) reader. Results showed that the isopropyl myristate (IPM) oil droplets in the two phase solutions were able to adsorb 68-80% of VSCs. CPC at a concentration of 0.05% was most affectively retained by the oil droplets showing a significantly increase in residual antibacterial activity against Streptococcus salivarius. These results taken together, suggests that VSC adsorption and CPC retention by IPM oil droplets may be two additional mechanisms in the activity of the two phase mouthwash formulation.

Bone and Mineral, May 1, 1992

In vivo regulation of matrix vesicles (MV) during primary bone formation was examined using tibia... more In vivo regulation of matrix vesicles (MV) during primary bone formation was examined using tibia1 marrow ablation in rats as the experimental model. The effects of bone-bonding and nonbonding implants on the number of MVl/drn* of matrix and the alkaline phosphatase (ALPase) and phospholipase A, (PA,) activities of MV-enriched microsomes (MVEM) isolated from the healing bone were studied. MV concentration, ALPose, and PA, were increased by bone-bonding implants by day 3 post-surgery; a similar effect was seen in the contralateral limb, but at a lower magnitude. Nonbonding implants had no effect at day 3 and decreased MV concentration and PA, activity at later time points; the same behavior was observed in the contralateral limb. These results demonstrate that MVs are influenced in a differential manner by implant materials, both locally and systemically, and can be regulated during primary mineralization.

Journal of Dental Research, Feb 1, 1979

Enamel powder and slabs treated with 50% phosphoric acid containing 0.5% and 2% NaF for 1 minute ... more Enamel powder and slabs treated with 50% phosphoric acid containing 0.5% and 2% NaF for 1 minute were analysed for Fdeposition, residual-F, x-ray diffraction and bond strength to Epoxylite 9075. F-deposition increased with the level of NaF. Hydroxyand fluoridated hydroxy-apatite and DCPD were present in all samples. Calcium fluoride was detected mostly in samples treated with 2% NaF. CPMH was absent. Residual-F, after water rinsings, was significantly reduced in the enamel powder treated with 2% NaF only. Additional washing with 1M KOH for 24 hr did not release any more fluoride (Fig 1). Residual-F, of the enamel slabs treated with 2% NaF, was not significantly different from that of untreated enamel (Fig 2). Tensile bond strength between resin to etched enamel with pure acid or acid containing 0.5% NaF was not significantly different: both were significantly higher as compared to the system etched with acid containing 2% NaF (Table).

Clinical Oral Implants Research, 1995

Critical events in the adaptation of osseous tissues to implant materials involve initial calcifi... more Critical events in the adaptation of osseous tissues to implant materials involve initial calcification of the newly synthesized bone. Previous studies indicated that bone‐bonding but not nonbonding glass ceramics increase the matrix vesicle number, thereby compensating for delayed maturation of the extracellular organelles. The present study assessed whether this was also true for metal implants commonly used in orthopaedics and oral medicine. Bone‐bonding titanium (Ti) or nonbonding stainless steel (SS) implants were placed in the right tibias of Sabra rats following ablation of the marrow. At 3, 6, 14, and 21 days postinjury, newly formed endosteal bone in the treated and contralateral limbs was removed and matrix vesicle‐enriched membranes isolated. Alkaline phosphatase and phospholipase A2 specific activities and phosphatidylserine (PS) content were determined and compared with those of a nonsurgical control group. Results show that matrix vesicle alkaline phosphatase and phosp...

Quintessence international (Berlin, Germany : 1985), 1997

A passive fit between osseointegrated implants and the prosthesis supported by them is crucial to... more A passive fit between osseointegrated implants and the prosthesis supported by them is crucial to the correct distribution of the stress exerted on the implants. The accuracy of the impression procedure in duplicating the exact position of the implant abutment is one of the main contributors to passive fit. An impression technique is presented whereby the dentate and edentulous parts are duplicated in elastomeric material, providing both the flexibility needed to remove the impression and the required accuracy. Subsequent duplication of the implant zone with plaster, without removal of the tray, affords a high degree of accuracy.

Refuʾat ha-peh ṿeha-shinayim (Tel Aviv, Israel : 1969), 1978

Ideally, all finish lines should be placed supragingivally. Due to esthetic and carious considera... more Ideally, all finish lines should be placed supragingivally. Due to esthetic and carious considerations, however, subgingival placement of the finish line is preferred. No one type of finish line can be used for all crown preparations. In lower anterior teeth or periodontically-treated teeth, the knife-edge finish line appears to be the treatment of choice. In short teeth and preparations for porcelain and porcelain-gold crowns, the full shoulder bevelled preparation is the treatment of choice. In full gold and acrylic veneered gold crowns, as in endodontically-treated teeth, the chamfer preparation is the treatment of choice.

Frontiers in Pharmacology, 2021

The common use of dental and orthopedic implants calls for special attention to the immune respon... more The common use of dental and orthopedic implants calls for special attention to the immune response leading to peri-prosthetic bone loss and implant failure. In addition to the well-established microbial etiology for oral implant failure, wear debris and in particular titanium (Ti) particles (TiP) in the implant vicinity are an important trigger of inflammation and activation of bone resorption around oral and orthopedic implants, presenting an unmet medical need. Here, we employed bacterial-derived lipopolysaccharides (LPS) to model infection and TiP to model aseptic inflammation and osteolysis. We assessed inflammation in vitro by measuring IL1β, IL6 and TNFα mRNA expression in primary macrophages, osteoclastogenesis in RANKL-induced bone marrow derived pre-osteoclasts and osteolysis in vivo in a mouse calvarial model. We also assessed the trans-epithelial penetrability and safety of the tested compound in rats. Our results show that a lipophilic super-active derivative of vasoact...

Frontiers in Immunology, 2018

The worldwide number of dental implants and orthopedic prostheses is steadily increasing. Orthope... more The worldwide number of dental implants and orthopedic prostheses is steadily increasing. Orthopedic implant loosening, in the absence of infection, is mostly attributable to the generation of wear debris. Dental peri-implantitis is characterized by a multifactorial etiology and is the main cause of implant failure. It consists of a peri-implant inflammatory lesion that often results in loss of supporting bone. Disease management includes cleaning the surrounding flora by hand instruments, ultrasonic tips, lasers, or chemical agents. We recently published a paper indicating that US scaling of titanium (Ti) implants releases particles that provoke an inflammatory response and osteolysis. Here we show that a strong inflammatory response occurs; however, very few of the titanium particles are phagocytosed by the macrophages. We then measured a dramatic Ti particle-induced stimulation of IL1β, IL6, and TNFα secretion by these macrophages using multiplex immunoassay. The particle-induced expression profile, examined by FACS, also indicated an M1 macrophage polarization. To assess how the secreted cytokines contributed to the paracrine exacerbation of the inflammatory response and to osteoclastogenesis, we treated macrophage/preosteoclast cultures with neutralizing antibodies against IL1β, IL6, or TNFα. We found that anti-TNFα antibodies attenuated the overall expression of both the inflammatory cytokines and osteoclastogenesis. On the other hand, anti-IL1β antibodies affected osteoclastogenesis but not the paracrine expression of inflammatory cytokines, whereas anti-IL6 antibodies did the opposite. We then tested these neutralizing antibodies in vivo using our mouse calvarial model of Ti particle-induced osteolysis and microCT analysis. Here, all neutralizing antibodies, administered by intraperitoneal injection, completely abrogated the particle-induced osteolysis. This suggests that blockage of paracrine inflammatory stimulation and osteoclastogenesis are similarly effective in preventing bone resorption induced by Ti particles. Blocking both the inflammation and osteoclastogenesis by anti-TNFα antibodies, incorporated locally into a slow-release membrane, also significantly prevented osteolysis. The osteolytic inflammatory response, fueled by ultrasonic scaling Eger et al. Preventing Titanium Particle-Induced Osteolysis of Ti implants, results from an inflammatory positive feedback loop and osteoclastogenic stimulation. Our findings suggest that blocking IL1β, IL6, and/or TNFα systemically or locally around titanium implants is a promising therapeutic approach for the clinical management of peri-implant bone loss.

Journal of long-term effects of medical implants, 1999

Several implant materials used in dental and orthopedic surgery were placed in rat tibial bones t... more Several implant materials used in dental and orthopedic surgery were placed in rat tibial bones to study their effects on mineralization. The implants consisted of bone bonding and non-bonding materials. Changes in mineralization were defined by morphometric analysis of matrix vesicle distribution at the implant interface and in normal bone healing following marrow injury. Bone-bonding materials induced an increase in matrix vesicle activity. This finding was supported by study of the biochemical changes in the same model that manifested high correlations to the morphometrical observations with regard to enhancement or delay of primary mineralization. In addition, the study of healing using nuclear methods indicated that implants alter bone healing as shown by the different uptakes of 99mTc and 32P in the different bone compartments. Decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggested that cleavage of 99mTc-MD32P into its technetium and methy...

American Journal of Orthodontics, 1983

Twenty-three patients who had completed treatment to resolve the unilateral palatal impaction of ... more Twenty-three patients who had completed treatment to resolve the unilateral palatal impaction of a maxillary canine by orthodontic means were examined 2.3 years (mean) after all appliances had been discarded. Scores were noted for the plaque index, gingival index, attached gingiva, pocket depth, and bone support on each of the affected teeth and also on the contralateral canine which had been unaffected and thus acted as a control. In addition, the teeth immediately adjacent to both canines were similarly scored. The results indicated no significant difference in the plaque index and the amount of attached gingiva, while the gingival index, pocket depth, and particularly the bone support all showed statistically valid differences. It is suggested that in these cases a postorthodontic assessment of the state of the supporting tissues be performed and periodontal treatment instituted in those requiring it.

The objective of this study was to investigate whether intermittent administration of parathyroid... more The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 μg PTH[1-34]/kg subcutaneously were given to the PTH group rats (n = 10) for four weeks, and the controls (n = 10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1-34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1-34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1-34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1-34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction.

The Journal of Prosthetic Dentistry, 1995

In vivo adsorption of salivary proteins onto prosthetic titanium components was analyzed after ex... more In vivo adsorption of salivary proteins onto prosthetic titanium components was analyzed after exposure of titanium abutments to the oral environment for a period of 2 to 6 weeks. Gel electrophoresis and Western immunoblotting were used to separate and identify the proteins, which were mainly a-amylase and serum albumin. Selective adsorption of proteins enables attachment of specific oral bacteria and thus may alter the composition of the dental plaque formed on titanium surfaces. (J PROSTHET DENT 1995;74:531-4.) Plaque development on exposed surfaces of teeth and restoration materials begins with an acquired pellicle (AP). The AP consists primarily of glycoproteins, mucins, and enzymes present in saliva.l4 Ellingsen 5 demonstrated that serum proteins such as albumin and IgG are adsorbed by titanium surfaces. 5 In an in vitro study, Wolinsky et al. 6 found that larger amounts of salivary proteins adsorbed to enamel than to titanium. Electrostatic-type interaction between charged ions is one of the main routes in the formation of AP on teeth and other materials. 7 Thus, the greater quantities of salivary proteins adsorbing to enamel may be explained by the greater distribution of phosphate groups and calcium ions on enamel surfaces in relation to the titanium oxide layer. This can result in a reduced affinity between titanium and charged salivary proteins, s, 9 After the adsorption of the proteins, bacteria begin to adhere to the AP. 1~ A number of studies suggest that microorganisms selectively adhere to certain proteins. 10-15 In the oral cavity, different adsorbed salivary proteins may dictate which oral bacteria first adhere and how the plaque will develop. Because titanium and enamel differ in their engagement of salivary components, the plaque developing on a titanium surface and its potential pathogenicity may also differ. After stage II surgery, in which osseointegrated implants are exposed to the oral environment, a titanium healing abutment is connected to the implant.

Journal of Bone and Mineral Research, 2010

Low bone mass is highly prevalent among patients receiving endosseous implants. In turn, the impl... more Low bone mass is highly prevalent among patients receiving endosseous implants. In turn, the implantation prognosis in low-density skeletal sites is poor. However, little is known about the mechanostructural determinants of implant anchorage. Using metabolic manipulations that lead to low bone density and to its rescue, we show here that anchorage is critically dependent on the peri-implant bone (PIB). Titanium implants were inserted horizontally into the proximal tibial metaphysis of adult rats 6 weeks after orchiectomy (ORX) or sham ORX. Systemic intermittent administration of human parathyroid hormone (1-34) [iahPTH(1-34)] or vehicle commenced immediately thereafter for 6 weeks. The bone-implant apparatus was then subjected to image-guided failure assessment, which assesses biomechanical properties and microstructural deformation concomitantly. Anchorage failure occurred mainly in PIB trabeculae, 0.5 to 1.0 mm away from the implant. Mechanically, the anchorage performed poorly in ORX-induced low-density bone, attributable mainly to decreased trabecular number. iahPTH(1-34) rescued the PIB density and implant mechanical function by augmenting trabecular thickness (Tb.Th). However, implant biomechanical properties in low-density bone were relatively insensitive to implant surface treatment that affected only the osseointegration (%bone-implant contact). These results support a model wherein anchorage failure involves buckling of the weakest trabecular struts followed by sequential failure of the stronger trabeculae. Treatment with iahPTH(1-34) induced thicker struts, which were able to delay and even prevent failure of individual elements, thus implicating trabecular thickness as a prime target for enhancing implant anchorage by systemic bone anabolic therapy.

Journal of Bone and Mineral Research, 2007

The distribution of trabecular structures in mammalian long bone metaphyses has been insufficient... more The distribution of trabecular structures in mammalian long bone metaphyses has been insufficiently explored. We show in rats that the trabecular bone structural parameters display a decreasing gradient, toward the diaphysis, that can be defined mathematically. This gradient is applicable for optimizing the reference volume in metabolic studies and for retrospective correction of implant positioning. Introduction: The mammalian metaphyseal trabecular bone is unevenly distributed. Hence, defining a standard reference volume is critical for morphometric analyses in metaphyseal sites. Materials and Methods: The distal femoral and proximal tibial metaphyses of adult orchietomized (ORX) or sham-ORX rats were scanned by CT 6 wk postoperatively. Morphometric analysis based on 3D image data was performed in 450-m-thick transversal segments defined consecutively from the primary spongiosa toward the diaphysis. The results were subjected to curve-fit analysis. A similar approach was used for proximal tibial metaphyseal sites carrying titanium implants inserted horizontally 6 wk post-ORX and examined 2-12 wk after implantation. Results: The respective curve-fit analysis in both femur and tibia revealed decreasing linear/quadratic and logarithmic gradients for all morphometric parameters in the sham-ORX animals. The ORX animals showed similar gradients with roughly similar slopes but lower values. For the bone volume (BV/TV) and connectivity (Conn.D) densities, the magnitude of the ORX effect vastly increased toward the diaphysis. The trabecular number was unaffected in ORX femora and tibias. The trabecular thickness showed a constant decrease in the femur and was unchanged in the tibia. These findings are useful for the determination and reporting of reference volumes in morphometric studies. Implementing the curve-fit analysis for retrospective correction of implant positioning revealed differences in BV/TV, Tb.N, Conn.D, and percent implant surface in contact with bone (%OI) between the sham-ORX and ORX rats. These differences were otherwise undisclosed. In addition, a temporal increase in %OI was shown only for the corrected measurements. Conclusions: We show the feasibility of modeling trabecular bone structures using mathematical tools. Such modeling may be used as an experimental tool. Moreover, if proven applicable to human skeletal structures, it may be further developed for the diagnosis of metabolic bone diseases and evaluation of therapeutic measures.

Clinical Oral Implants Research, 1991