Possibilities for static and dynamic stabilization of the spine in lesions of the anterior and posterior ligament complex

Defects of the dorsal and ventral ligament complexes of the lumbar spine results to an instability of the functional spinal unit. For the prognosis of secondary instability due to disko-ligamentous injuries the functional insufficiency of the lasting scars is a larger problem than the primary loss of osseous stability with fast healing tendency. The main goal of the present biomechanical study in vitro was to demonstrate the different grades of instability in the correlation to progressive disko-ligamentous defects as well as stabilisation through dynamic and static procedures. With a transpedicular screw-ringband-system the segmental function was preserved and instability was abolished. After rigid instrumentation with a fixateur intern remained a residual range of motion due to which can result refuse to bending moments without spondylodesis in an implant failure.     

Transcutaneous reduction and external fixation for the treatment of noncomminuted zygoma fractures

PURPOSE: This study evaluated the effectiveness of the treatment of noncomminuted monofragment zygoma fractures with closed reduction using transcutaneous threaded pins and an external fixation device instead of open reduction and internal rigid fixation. PATIENTS AND METHODS: In 46 patients, transcutaneous pin was inserted into the center of the fractured zygoma, and the segment was reduced by moving the pin to counteract the initial vector force of injury. After reduction, the fractured segment was immobilized by the external fixation device for 9 to 14 days. RESULTS: All patients except one showed accurate fracture reduction without malunion or any complications. CONCLUSION: This method has advantages over the conventional closed methods in the management of uncomplicated noncomminuted fractures of the zygoma.     

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.     

Treatment of stable burst fracture of the atlas (Jefferson fracture) with rigid cervical collar

STUDY DESIGN: A retrospective review of a clinical series. OBJECTIVE: To evaluate the use of a rigid cervical collar alone as the treatment for stable Jefferson fracture, and to devise an algorithm for treatment of Jefferson fracture with or without an associated cervical injury. SUMMARY OF BACKGROUND DATA: The traditional treatment for Jefferson fracture, if there is no indication for surgery, is immobilization by halo vest. Because halo vest placement is associated with intracranial infection and a significant degree of patient discomfort, slightly less rigid forms of external immobilization may be useful for the treatment of stable Jefferson fractures. No standard protocol calling for the use of one form of stabilization device has been reported. MATERIALS: The medical records and radiographs of 16 consecutive patients with Jefferson fracture during a 2-year period were reviewed. Each patient underwent a complete cervical radiograph series and a computed tomographic scan. The mean C1 lateral mass displacement was 1.8 mm. Cervical spine radiographs, including lateral flexion-extension views were obtained 10 to 12 weeks after injury before the removal of an external immobilization device. RESULTS: Of these 16 patients, 1 sustained a complete injury, and 7 sustained an incomplete injury. Eight patients were neurologically intact. Twelve patients sustained a stable Jefferson fracture and were treated with a rigid cervical collar (Miami-J collar [Jerome Medical, Moorestown, NJ]) alone from 10 to 12 weeks. The patient sustaining the complete neurologic injury died of multisystem trauma. All 15 live patients showed no instability on their follow-up plain radiographs before the removal of an external stabilization device. Six patients underwent further plain radiographs approximately 1 year after the fracture and similarly demonstrated no instability. CONCLUSIONS: Isolated stable burst fracture of the atlas can be treated effectively with a rigid cervical collar alone for 10 to 12 weeks with good neurologic recovery and segmental stability. Unstable Jefferson fractures with concurrent unstable fracture of other cervical vertebrae, especially C2, requires surgical stabilization.     

Transient osteoporosis of the hip in pregnancy

STUDY DESIGN: Fresh calf lumbar spines were used to perform flexibility tests in multiple loading directions to compare the stabilizing effects of anterior and posterior rigid instrumentations. OBJECTIVE: To compare the biomechanical flexibility of anterior and posterior instrumentation constructs using an unstable calf spine model. SUMMARY OF BACKGROUND DATA: Unstable burst fractures of the thoracolumbar spine can be managed anteriorly or posteriorly. Controversy persists, however, on the merit of anterior fixation versus that of posterior fixation in terms of how much stability can be achieved. METHODS: Fifteen fresh calf spines (L2-L5) were loaded with pure unconstrained moments in flexion, extension, axial rotation, and lateral bending directions. After removal of L3-L4 disc and endplates to create an 1.5-cm anterior and middle column defect, testing was performed on five specimens after anterior Kaneda rod fixation, anterior University Plate fixation, or posterior ISOLA pedicle screw fixation (AcroMed, Cleveland, OH). Testing was repeated after inserting a polymethylmethacrylate block to stimulate an interbody anterior graft with instrumentation. RESULTS: All fixation devices provided a significant stabilizing effect in flexion and lateral bending. In extension, all constructs except ISOLA (AcroMed) without graft were stiffer than the intact specimen. In axial rotation with no graft, only the Kaneda device significantly reduced the flexibility from that of the intact specimen. The interbody graft provided additional rigidity to the ISOLA (AcroMed) instrumentation construct in flexion and extension and to the Kaneda construct in lateral bending. There was no significant effect of grafting in axial rotation. CONCLUSIONS: A short, transpedicular instrumentation, such as ISOLA (AcroMed), provided less rigid fixation in flexion and extension without the anterior structural graft. The Kaneda rod and University plate with grafting provided a significant stabilizing effect in all directions compared with the intact specimen. When no graft was inserted, the Kaneda device was more effective in preventing axial rotation than the other devices. In lateral bending, the University plate provided more rigid fixation than the Kaneda device without grafting.     

Fracture strengths of three core restorative materials supported with or without a prefabricated split-shank post

BACKGROUND: Conventional anterior cervical discectomy with fusion is thought to require postoperative neck immobilization for the promotion of bony fusion. Rigid internal fixation with anterior cervical plates may decrease graft-related complications and provide immediate stability. This stability may obviate postoperative external immobilization. METHODS: This report reviews one surgeon's experience with the use of rigid internal fixation for two-level anterior cervical discectomy and fusion for radiculopathy to promote early mobilization without external bracing. It compares outcomes and costs with a similar population of patients treated with anterior cervical discectomy and fusion who did not undergo rigid internal fixation. We compared patients who underwent two-level allograft anterior cervical discectomy and fusion with or without rigid internal fixation between 1989 and 1994 performed by a single surgeon (FJP) to evaluate the cost advantages and outcome of each procedure. All patients had clinical evidence of cervical radiculopathy unresponsive to medical therapy with magnetic resonance imaging confirmation of the appropriate nerve root impingement. Thirty-nine patients underwent two-level Cloward allograft fusion using Synthes anterior cervical locking plates, 25 underwent identical fusion without plating. Follow-up was 6 months to 4 years (mean, 31 months). RESULTS: Twenty-three of 25 patients in the nonplated group and 36 of 39 patients in the plated group achieved excellent or good outcomes using the Odom criteria. There were six complications (two major and four minor) in each group. Patients who underwent plating returned to light activities (mean, 17 vs. 29 days), driving (28 vs. 57 days), and unrestricted work (66 vs. 136 days) sooner than non-plated patients (p < 0.05, paired t test). No patient with plates was given external immobilization. CONCLUSIONS: Two-level anterior cervical discectomy and fusion with anterior plating for radiculopathy is safe, effective, and seems to provide shorter convalescence compared with conventional anterior cervical discectomy and fusion. Patients returned to unrestricted work sooner, thus reducing short-term disability. Rigid internal fixation may provide cost advantages to patients and insurance disability providers. The authors conclude that the increased cost of treatment for rigid internal fixation is more than offset by the benefits of earlier mobilization.     

Reference values for extremity muscle strength obtained by hand-held dynamometry from adults aged 20 to 79 years

We present an 8-year experience with the Würzburg noncompression titanium miniplate system for the rigid fixation of the mandible during elective head and neck cancer surgery in a consecutive series of 100 patients. One half of the miniplates were used to fix mandibulotomies undertaken for surgical access. The remaining half were in patients undergoing reconstruction of segmental mandibular defects, the vast majority (92%) with vascularised bone grafts. One to four variously shaped miniplates were used per patient (mean = 1.5), plate size ranging from 4 to 40 holes. Fifteen patients (15%) developed complications which included 3 mandibular osteoradionecrosis, 8 broken, 5 infected, and 4 exposed plates. Three of the eight fractured plates were associated with nonunion. In this study, the main advantages of titanium miniplate fixation, namely case of application, decreased fixation time and malleability, were accompanied by a level of morbidity which, while comparing well with alternatives, may necessitate a reappraisal of this technique of fixation.     

Genetic analysis of the cap5 locus of Staphylococcus aureus

BACKGROUND: Fifteen patients with femoral shaft fractures complicated by infected nonunions were treated with a two-stage protocol. METHODS: In the first stage, radical debridement was performed along with antibiotic bead chains local therapy and external skeletal fixation. In the second stage, the debrided nonunion site was repaired with bone grafting and the external skeletal fixator was used until bony union was achieved. The time between the first and second stages of treatment was 2 to 6 weeks. The debrided bone defects ranged from 0.5 to 15 cm. Autogenous iliac cancellous bone grafting was performed in 11 patients, and microvascularized osteoseptocutaneous fibular transfer was performed in 4 patients. RESULTS: Wound healing and bone union were achieved in all 15 cases. The duration of external fixation of these patients ranged from 7 to 15 months, with an average of 9 months. Minor pin-track infection was seen in seven patients. Postoperative infection after the second-stage bone grafting occurred in three patients. These three infections were arrested by limited debridement along with 2 to 4 weeks of parenteral antibiotic therapy. In one case, stress fracture occurred at 11 months after microvascularized fibular transfer; this was managed with another 5 months of external skeletal fixation. With an aggressive physical therapy program, 10 patients achieved nearly full range of knee motion and 5 patients had relevant knee flexion deficits. The follow-up averaged 58 months (range, 40-76 months); no recurrence of osteomyelitis was observed even at 76 months. CONCLUSION: We have found that our two-stage treatment with antibiotic beads local therapy, definitive external skeletal fixation, and staged bone grafting is an acceptable treatment protocol for the management of femoral diaphyseal infected nonunion. It results in rapid recovery from osteomyelitis and a predictable recovery from nonunion.     

Orthognathic surgery: a hierarchy of stability

The stability and predictability of orthognathic surgical procedures varies by the direction of surgical movement, the type of fixation, and the surgical technique employed, largely in that order of importance. The most stable orthognathic procedure is superior repositioning of the maxilla, closely followed by mandibular advancement in patients in whom anterior facial height is maintained or increased. (If facial height is decreased by upward rotation of the chin, stability is compromised). The combination of moving the maxilla upward and the mandible forward is significantly more stable when rigid internal fixation is used in the mandible. Forward movement of the maxilla is reasonably stable, with or without rigid internal fixation, but mandibular setback often is not stable, and downward movement of the maxilla that creates downward rotation of the mandible is unstable. For mandibular setback, the inclination of the ramus at surgery appears to be an important influence on stability. It has been suggested that both interpositional synthetic hydroxyapatite grafting and simultaneous ramus osteotomy improve the stability of downward movement of the maxilla, but this has not been well documented. In two-jaw Class III surgery, the stability of each jaw appears to be quite similar to that of isolated maxillary advancement or mandibular setback. The least stable orthognathic procedure is transverse expansion of the maxilla. Although surgically assisted rapid palatal expansion has been suggested as a more stable alternative to segmental Le Fort I osteotomy, the patterns of movement resulting from the two procedures are different, and differences in stability have not been established.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.     

Treatment concept in infected bone and soft-tissue defects

The first priority when treating infected bone and soft-tissue defects is the maintenance or reconstruction of vitality, vascularity and stability. This means that when signs of infection are apparent, this is an immediate indication for operative revision with protective preparations on the tissue and radical debridement. Treatment of the soft-tissue damage is carried out with local or microsurgically connected muscle flaps. As for stability, in early infection the retention of well-bonded implants is often possible. If not, it is often necessary to change over to external fixation. Reconstruction of bone damage is carried out after the infection recedes, and complete healing is finally achieved by further treatment changes to conservative means or further stabilizing treatment.     

Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial clinical results

Bone quality, initial fracture displacement, severity of fracture comminution, accuracy of fracture reduction, and the placement of the internal fixation device are important factors that affect fixation stability. New high strength cements that are susceptible to remodeling and replacement for fracture fixation may lead to improved clinical outcome in the treatment of hip fractures. Norian SRS is an injectable, fast setting cement that cures in vivo to form an osteoconductive carbonated apatite of high compressive strength (55 MPa) with chemical and physical characteristics similar to the mineral phase of bone. It can be used as a space filling internal fixation device to facilitate the geometric reconstruction, load transfer, and healing of bone with defects and/or fractures in regions of cancellous bone. Furthermore, this cement can improve the mechanical holding strength of conventional fixation devices. Use of this material potentially could improve fracture stability, retain anatomy during fracture healing and improve hip function, thus achieving better clinical outcomes. In vivo animal studies have shown the material's biocompatibility, and cadaveric studies have shown the biomechanical advantage of its use in hip fractures. Initial clinical experience (in 52 femoral neck fractures and 39 intertrochanteric fractures) showed the potential clinical use of this innovative cement in the treatment of hip fractures.     

Load transmission through the callus site with external fixation systems: theoretical and experimental analysis

The fracture callus contribution to the total rigidity of external fixator-fractured bone element was analysed. This study was achieved from both theoretical and experimental perspectives. The theoretical study was done using the finite element method with a three-dimensional model. In this model, both the callus and the development of its elastic characteristics were considered. A series of 38 New Zealand-California white rabbits with tibial fractures treated with some external fixation system was used in this study. Such devices could reproduce either rigid or elastic features. The frame dynamization can be obtained at different fracture healing stages. Animals were classified into four series: (1) rigid fixators, (2) dynamized fixators two weeks after surgery, (3) three weeks after surgery and (4) four weeks after surgery. Tension tests were performed to evaluate callus strength. Theoretical results showed significant levels of callus load transmission (85.5%) when the callus elastic modulus is 1/100 of the elastic modulus of intact bone in an external fixator with rigid features. Experimental analysis of the callus obtained with different external fixator systems did not show differences among them. This fact implies that the immature callus theoretically modelled (E = 100 N mm-2) appears early in the rabbit fracture model (before two weeks, when first dynamization was made), for this reason no differences were found between the two types of treatment (rigid and dynamized systems). This fact questions the reliability of the dynamization process in external fixation of fractures and it implies accurate investigations in the clinical field.     

Bacterial walls, peptidoglycan hydrolases, autolysins, and autolysis

The use of a spacer has been recommended in interstitial brachytherapy for tongue cancer to reduce the radiation dose to the mandible. This article describes the development of two types of acrylic resin spacers, a mouth guard-type spacer for dentate patients, and a replica denture-type spacer for edentulous patients. These spacers can be used without suture retention and are comfortable for patients.     

Repair of defects in spondylolysis by segmental pedicular screw hook fixation. A preliminary report

STUDY DESIGN: Clinical testing of segmental pedicular screw hook fixation repairing defects in lumbar spondylolysis. OBJECTIVES: The authors tested segmental pedicular screw hook fixation using ISOLA implants (AcroMed Corp., Cleveland, OH) to maintain direct repair of the defect in pars interarticularis while fusion occurs. The device should not break while fusion takes place with out a postoperative body cast. SUMMARY OF BACKGROUND DATA: Previous techniques of direct repair of defects in lumbar spondylolysis have not been successful universally, and wire breakage has occurred despite the use of a postoperative body cast. METHODS: This technique stabilizes bone grafted to the detect by a pedicular screw, a hook, and a rod used in combination. Six patients with lumbar spondylolysis were treated by means of this technique. RESULTS: Postoperatively, all patients with low back pain or radicular pain experienced significant relief. Radiographs, including lateral flexion-extension radiographs and tomograms, showed five patients to have a bilateral union and one a unilateral union, and none of the instrumentation failed. CONCLUSION: This technique is considered useful for direct repair of the defects found in lumbar spondylolysis.     

Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices

STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids.     

Treatment of tibial defects and nonunions using ipsilateral vascularized fibular transposition

Eight patients had nine ipsilateral vascularized fibular transpositions (IVFTs) in the period 1978-1987. The procedure, which involves no microvascular anastomosis, was done for difficult problems of the tibia including two long-standing posttraumatic nonunions, three allograft nonunions after tumor surgery, and four segmental tibial defects also after tumor surgery. The average duration of problems before surgery was 3.5 years, and the patients averaged 3.1 procedures before IVFT. The patients were followed for an average of 52.4 months. The average time to union was 4.2 months, and in all patients the grafts healed within six months. Late fracture of the graft developed in two patients after fixation removal; one required an additional procedure, and both eventually healed. Ipsilateral vascularized fibular grafting is a useful alternative to conventional, nonvascularized grafts for difficult tibial nonunions and segmental defects. It offers the advantages of a vascularized graft (early healing and hypertrophy), yet avoids the time-consuming microvascular anastomosis and distant donor site morbidity of free fibular grafts.     

Stability of posterior spinal instrumentation and its effects on adjacent motion segments in the lumbosacral spine

STUDY DESIGN: An in vitro biomechanical analysis of three anterior instability patterns was performed using calf lumbosacral spines. Stiffness of the constructs was compared, and segmental motion analyses were performed. OBJECTIVES: To clarify the factors that alter the stability of the spinal instrumentation and to evaluate the influence of instrumentation on the residual intact motion segments. SUMMARY OF BACKGROUND DATA: Recently, many adverse effects have been reported in fusion augmented with rigid instrumentation. Only few reports are available regarding biomechanical effects of stability provided by spinal instrumentation and its effects on residual adjacent motion segments in the lumbar-lumbosacral spine. METHODS: Eighteen calf lumbosacral spine specimens were divided into three groups according to instability patterns--one-level, two-level, and three-level disc dissections. Six constructs were cyclically tested in rotation, flexion-extension, and lateral bending of intact spines, of destabilized spine, and of spines with four segmental posterior instrumentation systems used to extend the levels of instability (Cotrel-Dubousset compression hook and three transpedicular screw fixation systems). During each test, stiffness values and segmental displacements were measured. RESULTS: The rigidity of the instrumented construct increased as the fixation range became more extensive. Although application of the instrumentation effectively reduced the segmental motion of the destabilized vertebral level, the motion at the destabilized level tended to increase as the number of unstable vertebral levels increased, and the fixation range of the instrumentation became more extensive. Instrumented constructs produced higher segmental displacement values at the upper residual intact motion segment when compared with those of the intact spine. In contrast, the instrumented constructs decreased their segmental displacement values at the lower residual intact motion segment with higher magnitude of the translational (shear) motion taking place compared with the intact spine in flexion-extension and lateral bending. These changes in the motion pattern became more distinct as the fixation range became more extensive. CONCLUSIONS: As segmental spinal instrumentation progresses from one level to three levels, the overall torsional and flexural rigidity of the system increases. However, segmental displacement at the site of simulated instability becomes more obvious. Application of segmental instrumentation changes the motion pattern of the residual intact motion segments, and the changes in the motion pattern become more distinct as the fixation range becomes more extensive and as the rigidity of the construct increases.     

Bony healing of large cranial and mandibular defects protected from soft-tissue interposition: A comparative study of spontaneous bone regeneration, osteoconduction, and cancellous autografting in dogs

The purpose of this study was to compare spontaneous bone regeneration, osteoconduction, and bone autografting in critical size calvarial and mandibular defects (defects which do not heal spontaneously during the lifetime of the animal) that were protected from soft-tissue interposition. Eighteen adult mongrel dogs underwent osteotomies to create a unilateral 30-mm segmental defect in the midbody of the edentulated right mandible and bilateral 15-mm x 20-mm full-thickness window defects in the parietal bones. The defects were either left empty, implanted with coralline hydroxyapatite (HA) blocks, or autografted with iliac cancellous bone. All defects were protected with a macroporous titanium mesh and the segmental mandibular defects were additionally stabilized by internal plate fixation. Specimens were retrieved after 2 and 4 months and three undecalcified longitudinal central sections including the osteotomy interfaces were prepared from each specimen for histometry and histology. Sections were analyzed for volume fractions of bone, soft tissue, and implant using scanning electron microscopy, backscatter electron imaging and histometric computer software. In the mandibular model, the empty defects exhibited the greatest amount of bone formation after 4 months (47.3 percent), which was greater than the amount of bone in the autografted group (34.8 percent) and significantly greater than the amount of bone within the hydroxyapatite implants (19.0 percent, p < 0.05). In the cranial defects, the autografted specimens demonstrated the greatest volume fraction of bone after 4 months (27.3 percent), which was significantly greater than within both the empty defects (18.2 percent, p < 0.05) and the hydroxyapatite implants (18.2 percent, p < 0.05). New bone formation in the mandibular defects united the cut ends at 4 months regardless of treatment and originated predominantly from the periosteum which remained present only along the alveolar border after surgical closure. In the calvarial defects, periosteum was not preserved and bone regenerated centripetally, originating from the diplo? without any evidence of dural osteogenesis. Bone bridging was incomplete in the empty cranial defects at 4 months. In both the mandibular and cranial specimens, new bone at 2 months was a mixture of woven and parallel fibered bone. At 4 months, the new bone had remodeled almost entirely into mature Haversian bone. This study demonstrated a remarkable ability of defect protection with a macroporous protective sheet to facilitate bone regeneration in critical size mandibular and cranial bone defects. When active osteogenic periosteum was present, as in our mandibular model, we concluded that defect protection alone was sufficient to allow for healing even of critical size defects. When periosteum was absent as in our cranial defects, the limited spontaneous bone formation benefited from the added contributions of cancellous grafting and osteoconductive implants, both of which promoted bone bridging across the defects. We suggest that in the future a resorbable macroporous protective sheet would be advantageous in comparison to a titanium mesh to facilitate bone regeneration by preventing soft-tissue prolapse and allowing the migration of mesenchymal cells and the proliferation of blood vessels from the adjacent soft tissues into the bone defect. Finally, this study identified the need to differentiate critical size defects into those with and without defect protection and periosteum.     

Inhibition of UDP-glucuronosyltransferase by 5'-O-amino acid and oligopeptide derivatives of uridine: structure-activity relationships

The inhibitory effect of a series of 5'-O-amino acid and oligopeptide derivatives of uridine on rat liver UDP-glucuronosyltransferase (UGT) activities was investigated using two assay systems. A quantitative structure-activity relationship (QSAR) study was performed. The compounds include a lipophilic residue linked to the nucleoside by a variable spacer. Moreover, half of the derivatives have two spacers linked to the uridine moiety. Compound 1, a serine derivative of isopropylideneuridine, was found to be the most potent inhibitor of both 4-nitrophenol (4-NP) and phenolphthalein (PPh) glucuronidation, with an I50 of 0.45 mM and 0.22 mM, respectively. Kinetic studies with this substance revealed a mixed type of inhibition towards 4-NP and UDP-glucuronic acid, with apparent Ki values of 150 microM and 120 microM, respectively. The dipeptide derivatives 11-14 exhibited a low activity against 4-NP conjugation. However, a marked suppression of PPh glucuronidation was found with compounds 11 and 13. Generally, compounds with two spacers are more inhibitory against the UGT activities studied. The QSAR analysis outlined the significance of the spacers with a minimum length of 5 atoms and lipophilic residues linked to them for the inhibitory effect of the compounds. The most significant contribution to this effect is given by the six-atom spacer for both 4-NP and PPh substrates. 4-NP converting UGT isoforms seem to respond more specifically to the inhibitors: a five-atom for the first and six-atom for the second spacer enhance binding to both 4-NP and PPh conjugating isoenzymes, while a long second spacer contributes to inhibitor binding to UGT isoforms only converting PPH.