A multicentre study comparing cervicography and cytology in the detection of cervical intraepithelial neoplasia

The efficacy of local delivery of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.     

Cholinergic mechanism and blood pressure regulation in the central nervous system

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control). 20 microg of rhTGF-beta1 in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-beta1. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histometric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-beta1, to control defects, statistically significant differences were found for area (1.8+/-0.4 and 1.3+/-0.6 mm2, respectively; p<0.05) and density (0.3+/-0.1 and 0.2+/-0.03, respectively; p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinical model. Within the limitations of study, it may be concluded that rhTGF-beta1 has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.     

Assessment of an experimental bone wax polymer plus TGF-beta 1 implanted into calvarial defects

The study reported describes an experimental biodegradable polymer ceramic composite with wax-like handling properties that was combined with 2.0 micrograms of recombinant human transforming growth factor beta (rhTGF-beta(1)). The polymer/rhTGF-beta(1) combination was introduced into standard-sized calvarial defects in rabbits to evaluate biodegradability, biocompatibility, hemostasis control, and bone promotion. The experimental wound model was a standard-size circular calvarial defect 8 mm in diameter. The experimental design included 24 skeletally mature New Zealand white rabbits divided evenly between two time periods (6 and 12 weeks) and among three experimental treatments (untreated defects and defects treated with polymer with or without rhTGF-beta(1)). Evaluations consisted of clinical examinations, standarized radiography, radiomorphometry, as well as histology and histomorphometry. Data were analyzed by an Analysis of Variance (ANOVA) and Fisher's Protected Least Significant Difference test at each time period (level of significance p < or = 0.05). Radiomorphometry data indicated that standard-sized defects treated with the wax-like polymer alone and the polymer plus 2.0 micrograms of TGF-beta(1) were significantly more radiopaque than control sites at both 6 and 12 weeks. Histomorphometric data revealed the amount of new bone was significantly greater at 6 weeks in the polymer plus 2.0 micrograms of TGF-beta(1) and in the control group than in the polymer alone. Moreover, at 12 weeks, there was significantly more new bone in the control than in either the polymer alone or the polymer plus 2.0 micrograms of TGF-beta(1). We speculate the incomplete biodegradation of the polymer ceramic composite contributed to the radiopacity and may have retarded osseous regeneration. It is important that the bone wax-like polymer material was biocompatible and acted as a hemostatic agent.     

Helicobacter pylori and socioeconomic factors in Russia

Transforming growth factor beta 1 (TGF-beta 1) is a polyfunctional regulatory cytokine that has been shown to have roles in extracellular matrix interactions, soft tissue healing, and osteogenesis. Twenty-five microL of recombinant human TGF-beta 1 was added to guanidine-extracted demineralized bone matrix carrier and the implants were used to fill a 14-mm osteoperiosteal critical calvarial defect in New Zealand white rabbit model. The defects were allowed to heal over 4 weeks and the degree of new bone formation was assess by radiodensitometry and undecalcified bone histomorphometry techniques. Implants with TGF-beta 1 showed complete bridging of the gap with new bone in all cases, while the controls showed fibrous tissue repair of the gap with little or no new bone formation. These results demonstrate the ability of TGF-beta 1 to induce new bone in a brief time period in an inactive carrier.     

Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model

The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.     

Effect of acetaldehyde generated from ethanol by ADH-transfected CHO cells on their membrane fatty acid profiles

Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 microgram rhTGF-beta 1 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 micrograms rhTGF-beta 1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTGF-beta 1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-beta 1 stimulated implants. RhTGF-beta 1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.     

Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels

The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.     

Misrepresentation of publications by applicants for radiology fellowships: is it a problem?

In light of the recently described experimental technique of in vivo bone reconstitution with biotechnologic methods (from bone marrow stromal cells) and the prefabrication flap procedures, the possibility to obtain autologous bone growth in a myocutaneous flap, thus creating a composite osteomyocutaneous preformed flap, is postulated. Human bone marrow stromal cells were delivered into the latissimus dorsi of athymic mice by a porous hydroxyapatite ceramic model. Eight weeks after the implantation, histologic examination revealed the presence of spongious bone tissue. A simple myocutaneous flap was thus transformed into a composite osteomyocutaneous flap. This flap is called the biotechnologic prefabricated flap, because it was the result of ex vivo expanded osteogenic precursor cells and in vivo bone tissue neoformation. The shape of the bone flap was exactly the same as the shape of the ceramic model used. A possible clinical application may be the correction of skeletal defects. The advantages of this procedure are simple surgical execution, the possibility of preshaping the graft to the exact characteristics of the defect, and the availability of autogenous donor tissue without donor site morbidity.     

Video-assisted lateral intertransverse process arthrodesis. Validation of a new minimally invasive lumbar spinal fusion technique in the rabbit and nonhuman primate (rhesus) models

STUDY DESIGN: Cadaveric anatomic and in vivo survival animal studies were performed to develop a new arthrodesis technique for the lumbar spine. OBJECTIVES: To examine the feasibility, efficacy, and safety of a minimally invasive lumbar intertransverse process arthrodesis technique using an osteoinductive growth factor (rhBMP-2) delivered in a collagen sponge carrier. The technique was first developed using a rabbit model and modified for the nonhuman primate (rhesus monkey), a larger animal with the most similar bone biology to humans. SUMMARY OF BACKGROUND DATA: The morbidity of conventional posterolateral lumbar intertransverse process arthrodesis includes graft donor site morbidity; paraspinal muscle devascularization, denervation, and scarring and nonunion in up to 36% of patients. Minimally invasive anterior lumbar interbody arthrodesis techniques have been developed, but these often require a metal implant and carry risks to major vessels and development of retrograde ejaculation. A minimally invasive technique for posterolateral intertransverse process arthrodesis has not been described previously. METHODS: In Part 1, we examined seven New Zealand white rabbits and five rhesus monkeys at necropsy and during nonsurvival surgeries to determine the best access routes and to develop special instruments for video-assisted lateral intertransverse process arthrodesis. In Part 2, 38 New Zealand white rabbits underwent L4-L5 intertransverse process arthrodesis: the "OPEN" group (n = 16) underwent a standard open muscle-splitting approach using rhBMP-2 (bone morphogenetic protein) and collagen as a bone graft substitute; the "video-assisted control" group (n = 6) underwent video-assisted lateral intertransverse process arthrodesis with the collagen implant only (no growth factor); and the "video-assisted-BMP" group (n = 16) underwent video-assisted lateral intertransverse process arthrodesis with rhBMP-2 and collagen as the graft material. In Part 3, rhesus monkeys (n = 4) underwent video-assisted lateral intertransverse process arthrodesis using rhBMP-2 and collagen after laminectomy of L4-L5. RESULTS: In Part 1, we identified expedient, minimally invasive routes to the intertransverse process interval appropriate for each species: an intermuscular approach for the rabbit and a lateral, extramuscular approach for the rhesus monkey. In Part 2, all rabbits in the OPEN and video-assisted-BMP groups achieved solid intertransverse process lumbar fusions when assessed at 10 weeks. There were no neurologic impairments nor any difference between the two groups in the frequency of postoperative infection or other complications. None of the animals in the video-assisted control group showed evidence of fusion. In Part 3, exposure, decortication and grafting with rh-BMP-2 and collagen was accomplished successfully in all four monkeys through the video-assisted minimally invasive approach without complications. CONCLUSION: Video-assisted lateral intertransverse process arthrodesis is a feasible, effective, and safe method of lumbar spinal fusion in the rabbit and rhesus monkey. Use of this arthrodesis procedure will minimize the morbidity of paraspinal muscle denervation and devascularization seen with open intertransverse process fusion techniques, and the use of an osteoinductive growth factor will eliminate the problem of graft donor site morbidity and possibly increase the chances for successful fusion.     

Repair of craniofacial defects with hydroxyapatite cement

PURPOSE: The objective of this study was to evaluate the course of healing of craniofacial bone defects when filled with hydroxyapatite cement and to determine whether adding various percentages by weight of demineralized bone powder to the cement will result in enhanced bone formation. MATERIALS AND METHODS: The model for the study was the canine calvarium. The implants were placed into cranial defects and harvested at 3 or 6 months for qualitative evaluation by light microscopy, microradiography, and quantitative histomorphometry. RESULTS: The implantation of hydroxyapatite cement resulted in characteristic replacement of the material with new bone ingrowth. The addition of demineralized bone powder to the hydroxyapatite cement appeared to improve the handling characteristics of the cement; however, improvement in the replacement of the material by bone was not observed. The implantation of only allogeneic demineralized bone showed limited new bone formation within the defect site. CONCLUSIONS: Hydroxyapatite cement formed an effective osseoconductive scaffold for bone replacement. The addition of demineralized bone powder to the cement to serve as a carrier of osseoinductive factors did not result in additional bone being formed.     

Role of apolipoprotein CIII in triglyceride-rich lipoprotein metabolism

Fibroblast growth factor (FGF) has been reported to increase the volume of callus in a fracture model of rats. There are, however, no reports of successful repair of segmental bony defects by application of an FGF solution. In this study, the effects of basic FGF on the repair of segmental bony defects in the rabbit femur were examined. Minipellet, a new drug delivery system using atelocollagen, was employed to ensure effective delivery of FGF. Segmental bony defects (10 mm in length) were created in the right femurs of 19 rabbits. In pilot studies, no defects of this size healed spontaneously within 6 weeks. Bones were stabilized with miniexternal fixators. Minipellets containing basic FGF were implanted between fragments so as to bridge the two fragments. The healing processes were monitored radiographically and studied histologically. In rabbits in which FGF was added to the defect site at doses of 1.4 microgram or higher, approximately 90% of the defects were filled with new bone and cartilage within 6 weeks after minipellet implantation. In rabbits receiving placebo minipellets, however, approximately 15% of the defects were filled by callus within 6 weeks. Furthermore, this callus did not change into mature bone. An injection of 2 microgram of FGF solution to bony defects had no effect on the repair of segmental bony defects. These findings suggest that FGF plays a role in the production of adequate volumes of callus particularly in the initial stages of fracture healing and that sustained local release enables FGF to be effective at a low dose. In summary, large segmental bony defects healed after insertion of low-dose FGF minipellets. An adequate dose of FGF and an appropriate delivery system are required for successful healing of large bony defects. These findings imply the potential value of FGF minipellets in clinical practice.     

Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats

Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.     

The effect of transforming growth factor beta one (TGF-beta 1) on wound healing, with or without barrier membranes, in a Class II furcation defect in sheep

The purpose of this study was to analyse the effect of TFG-beta 1 on wound healing in standardized Class II furcation defects of 48 mandibular second premolar teeth in 24 sheep. The experimental design included a control group (carrier only, 25% pluronic F-127), and 2 experimental groups: group A (80 micrograms/ml TGF-beta 1 + carrier) and group B (80 micrograms/ml TGF-beta 1 + carrier covered with a barrier membrane). Sheep were killed either 2 wk or 6 wk after surgery. Mesiodistal sections of the decalcified specimens were quantified histologically using stereology. Percentage volumes of regenerated bone, fibrous connective tissue and cementum were calculated for each furcation defect. Mean values were analysed using multiple ANOVA; p values were calculated using paired and unpaired Student's t-tests. After 2 wk there was more bone in group B than either of the other 2 groups, but this was not statistically significant. By 6 wk more bone was present in group A than in the control group (p < 0.02) and also in group B when compared with both group A and the control group (p < 0.02 and p < 0.44), respectively. In the 4 wk between sampling significantly more bone had formed (group A < 0.05 and group B p < 0.003, respectively). A negative correlation existed between volumes of bone and fibrous connective tissue and no significant differences between the volumes of cementum were evident between any of the groups. This study demonstrated that TGF-beta 1 encouraged bone regeneration in Class II furcation defects in sheep, an effect enhanced by the presence of a barrier membrane. This is the first report on the use of TGF-beta 1 in conjunction with GTR in periodontal defects.     

In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusions

STUDY DESIGN: Posterior spinal fusion segments were evaluated in adult mongrel dogs at 6, 12, and 26 weeks post-implantation. Four sites on each animal received implants consisting of recombinant human osteogenic protein-1 on a bone collagen carrier, bone collagen carrier alone, autogenous iliac crest bone, or no implant material. OBJECTIVE: To determine the efficacy of recombinant human osteogenic protein-1 as a bone graft substitute in achieving posterior spinal fusion and compare the results to those obtained using autogenous bone graft. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion generally includes onlay grafting of autogenous or allogeneic bone after decortication of bony surfaces of the vertebral elements. The search for an acceptable bone graft substitute material has in recent years centered upon proteins capable of inducing bone in vivo. Recombinant human osteogenic protein-1 has demonstrated efficacy in healing large segmental osteoperiosteal defects in rabbits, dogs, and monkeys and appears ideally suited as a bone graft substitute for spinal fusions. METHODS: The quality of fusion and new bone formation was evaluated using plain films, computed tomography, and magnetic resonance imaging. RESULTS: Radiographic and histologic studies demonstrated that recombinant human osteogenic protein-1-treated fusion segments attained a stable fusion by 6 weeks post-implantation and were completely fused by 12 weeks. The autograft sites demonstrated fusion at 26 weeks post-implantation. CONCLUSIONS: The results indicated that recombinant human osteogenic protein-1 is an effective bone graft substitute for achieving stable posterior spinal fusions in a significantly more rapid fashion than can be achieved with autogenous bone graft.     

Effects of recombinant human transforming growth factor-beta 1 or/and interleukin-6 on growth inhibition and proto-oncogene c-myc expression in human leukemia cells

OBJECTIVE: To examine the effect of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) alone or recombinant human interleukin 6 (rhIL-6) alone or in combination on proliferation inhibition of the human leukaemia cell line. METHODS: In the present study, using the human monoblastic cell line (U937) and human promyelocytic cell line (HL60) as an in vitro model, we analyzed the effect of two cytokins on proliferation inhibition with rate of 3H-TdR incorporation, the cellular content of DNA, DNA indices, the cell cycle and the expression of c-myc mRNA. RESULTS: With administration of rhTGF-beta 1 and rhIL-6, U937 cell growth was inhibited and the rate of 3H-TdR incorporation inhibition was increased. There was a decrease in the cellular content of DNA and DNA indices. And no change in the cell cycle was observed after administration of rhTGF-beta 1 or rhIL-6. However, there was an increase in G0/G1 phase cells and a decrease in G2M + S phase cells after administration of combination of rhTGF-beta 1 and rhIL-6. It was also found that rhIL-6 could inhibit proliferative responses of HL60 cells, meanwhile the inhibition could be enhanced by rhTGF-beta 1. The rate of 3H-TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00 following induction by rhIL-6 plus rhTGF-beta 1. Furthermore, G0/G1 phase cells increased while G2M + S cells decreased. CONCLUSIONS: These results suggest that combination of rhTGF-beta 1 and rhIL-6 acted in synergy to inhibit proliferation of both U937 and HL60 cell lines. Molecular hybridization test show that rhTGF-beta 1 alone, rhIL-6 alone or rhTGF-beta 1 and rhIL-6 in combination can inhibit U937 and HL60 cells expression of c-myc mRNA in a time and dose dependent manner. rhTGF-beta 1 and rhIL-6 in combination synergistically inhibited c-myc expression, which may be one of the machanisms for the actions of the two cytokines.     

Regeneration of diaphyseal bone defects using resorbable poly(L/DL-lactide) and poly(D-lactide) membranes in the Yucatan pig model

OBJECTIVES: To determine the effects of tubular resorbable polymer membranes on the healing of a segmental diaphyseal bone defect. DESIGN: A randomized prospective study using the minipig model. Animals were evaluated with in vivo roentgenograms on a biweekly basis until explanted at twelve weeks. SETTING: After surgery, animals were allowed unrestricted activity and weight bearing between twenty-four and forty-eight hours. ANIMALS: Fifteen yearling Yucatan minipigs. INTERVENTION: A 2.5- to 3.0-centimeter mid-diaphyseal defect was created in the middle third of the radius. Animals were assigned in groups of three to receive the following implants: (a) poly(L/DL-lactide), (b) poly(L/DL-lactide)-CaCO3, (c) poly(D-lactide), (d) poly(D-lactide)-CaCO3, and (e) an untreated defect. No adjunctive internal or external fixation was used as the ulna was left intact. MAIN OUTCOME MEASURES: The limbs were studied with in vivo anterior-posterior and lateral radiographs at biweekly intervals for the presence and pattern of bone formation. All limbs were explanted at twelve weeks postimplantation for methyl-methacrylate embedding and histologic and microradiographic study. RESULTS: The bone defects covered with membranes were completely reconstituted by six to eight weeks. Untreated defects healed with less bone formation and in a more disorganized pattern. Histologic evaluation of the implants demonstrated that the entire lumen of the implant was filled with bone, with some periosteal bone formation occurring on the outer surface of the membrane. There was direct apposition of bone onto the membrane surface or minimal fibrous tissue interposition between membrane and new bone. There was no foreign body or adverse reaction to the membrane. Untreated defects showed woven bone formation with clefts and irregularly shaped margins occupied by fibrous tissues or surrounding muscle tissues. CONCLUSIONS: This study supports the concept that a membrane enhances bone defect healing by excluding nonosseous tissues from a defect and providing structural scaffolding for periosteal and endosteal bone regeneration.     

Methodologic aspects of body water kinetic dynamic studies

Tissue status at the site of experimental bone defects filled by two compositions based on polyacrylamide gel and hydroxyapatite with (experimental group) and without (controls) lysozyme was studied in rats by the histomorphological method. "Negative" symptoms, such as inflammation, formation of osteocyte-free bone at the interface of the defect, and reduction of red bone marrow were more manifest in the controls than in animals treated with lysozyme. In the test group substitution of composite material for connective tissue structures and bone reparation were much more active and rapid than in the controls. Inflammation and dystrophic changes at the interface of defects were less pronounced and gradually resolved.     

Basic fibroblast growth factor promotes bone ingrowth in porous hydroxyapatite

The effect of basic fibroblast growth factor on tissue ingrowth and differentiation in porous hydroxyapatite of coralline origin was studied in a bone chamber model. The hydroxyapatite with or without basic fibroblast growth factor was placed in 22 mm3 titanium bone conduction chambers implanted bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of the chamber only at 1 end. It then penetrated the porous hydroxyapatite inside the chamber. The distance that the ingrown tissue had reached into the material then was measured on histologic slides. Because fibrous tissue always reached further into the material than did bone, both total tissue ingrowth and bone ingrowth distances were measured. In implants supplemented with 0.04 microg basic fibroblast growth factor in a hyaluronate gel carrier, the bone ingrowth distance was increased by 70% at 6 weeks, as compared with paired controls in the contralateral leg. The total tissue ingrowth distance also was increased by 58%. When the dose of basic fibroblast growth factor was increased to 1.0 microg, still using the hyaluronate carrier, there was no difference in bone ingrowth compared with controls, but this dose still increased the total tissue ingrowth. In hydroxyapatite with 1.5 microg basic fibroblast growth factor without hyaluronate gel at 4 weeks, no increase in bone ingrowth was shown, but total tissue ingrowth was increased. At 6 weeks, bone ingrowth and total tissue ingrowth were increased by 41% and 33%, respectively. With a lower dose of 0.15 microg without carrier, only the total ingrowth distance was increased. The results suggest that basic fibroblast growth factor may promote tissue ingrowth into porous hydroxyapatite and that bone ingrowth may be increased by appropriate doses. The hyaluronate gel carrier reduced the optimal dose.     

The clinical, angiographic and procedural predictors of thrombosis and restenosis in Micro stent II (AVE) coronary stents]

In the present study, the potential of a diphenylphosphorylazide-crosslinked type I bovine collagen membrane was evaluated in the healing of mandibular bone defects applying the biological concept of guided bone regeneration. The experiment was carried out on 25 Wistar rats. After exposing the mandibular ramus bilaterally, 5 mm diameter full-thickness circular bone defects were surgically created. While the defect on one side was covered by the membrane (experimental), the defect on the other side was left uncovered (control) before closure of the overlying soft tissues. The rats were sacrificed in groups of 5 after 7, 15, 30, 90, and 180 days of healing. Although at early stages of healing similar amounts of bone formation were observed in the experimental and control defects, after 1 month of healing, most of the experimental defects were completely closed with new bone, while in the control defects, only limited amounts of new bone were observed at the rims and in the lingual aspect of the lesions. In the 90- and 180-day animals, all experimental defects were completely closed, while in the control defects, no statistically significant increase in bone regeneration was observed. The increase in percentage of bone regeneration in the experimental defects was statistically significant between the 15-day specimens as compared with the 7-day specimens (P < 0.01) and likewise between 30-day and 15-day specimens (P < 0.001). It can be concluded that a DPPA-crosslinked collagen membrane yields biocompatibility, ad hoc mechanical hindrance, and handling characteristics suitable for guided bone regeneration applications in this experimental model.