Tissue engineering and regenerative approaches to improving the healing of large bone defects.

Despite the high innate regenerative capacity of bone, large osseous defects fail to heal and remain a clinical challenge. Healing such defects requires the formation of large amounts of bone in an environment often rendered hostile to osteogenesis by damage to the surrounding soft tissues and vasculature. In recent years, there have been intensive research efforts directed towards tissue engineering and regenerative approaches designed to overcome this multifaceted challenge. In this paper, we describe and critically evaluate the state-of-the-art approaches to address the various components of this intricate problem. The discussion includes (i) the properties of synthetic and natural scaffolds, their use in conjunction with cell and growth factor delivery, (ii) their vascularisation, (iii) the potential of gene therapies and (iv) the role of the mechanical environment. In particular, we present a critical analysis of where the field stands, and how it can move forward in a coordinated fashion.

Validation of Histologic Bone Analysis Following Microfil Vessel Perfusion.

The ability to examine bone vascularity using Micro-Computed Tomography (µCT) following vessel perfusion with Microfil® and to subsequently perform histologic bone analysis in the same specimen would provide an efficient method by which the vascular and cellular environment of bone can be examined simultaneously. The purpose of this report is to determine if the administration of Microfil® precludes accurate histologic assessment of bone quality via osteocyte count and empty lacunae count. Sprague-Dawley rats (n=6) underwent perfusion with Microfil®. Left hemi-mandibles were harvested, decalcified and underwent vascular analysis via µCT prior to sectioning and staining with Gomori's Trichrome. Quantitative Histomorphometric evaluation was performed. Ninety-five percent confidence intervals were used to determine statistical differences from an established set of controls (n=12). Histologic analyses were successfully performed on specimens that had undergone previous perfusion. Quantitative measures of bone cellularity of perfused versus control specimens revealed no statistical difference in osteocyte count per high-power field (95.33 versus 94.66; 95 percent CI,-7.64 to 6.30) or empty lacunae per high-power field (2.73 versus 1.89, 95 percent CI, -1.81 to 0.13). Here we report a statistical validation allowing for histological analysis of cell counts in specimens in which Microfil® perfusion has previously been performed.

Association between habitual snoring, middle ear disease, and speech problems in young children with non-syndromic cleft palate anomalies.

The purpose of this study was to investigate the association between habitual snoring (HS), middle ear disease (MED), and speech problems in children with cleft palate. This cross-sectional study included children aged 2.0-7.9 years with non-syndromic cleft palate anomalies. Parents completed the Pediatric Sleep Questionnaire and a questionnaire about MED. Audiograms and speech assessment were also conducted. Ninety-five children were enrolled; 15.2% of families reported HS, 97.6% MED, and 17.1% speech problems. HS (37.5% vs 10.3%, P = 0.007) and early episodes of MED (92.3% vs 58.2%, P = 0.021) were more likely to be reported for children with isolated cleft palate when compared to those with cleft lip and palate. Children with cleft lip and palate had a higher frequency of MED with effusion compared to those with Robin sequence (86.4% vs 57.1%, P = 0.049). The odds ratio for HS in children with ≥1 episode of MED in the last year was 7.37 (95% confidence interval 1.55-35.15, P = 0.012). There was a trend for children with speech problems reported by parents to have HS (30.8% vs 11.5%, P= 0.076). Anatomical factors play a role in the frequency of upper airway symptoms in children with cleft palate. A recent history of at least one episode of MED was associated with an increased frequency of HS.

Prophylactic amifostine prevents a pathologic vascular response in a murine model of expander-based breast reconstruction.

BACKGROUND: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS: 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS: Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.

Failure of methylprednisolone, ibuprofen, or prostacyclin to reduce HCl-induced pulmonary albumin leak in dogs.

The purpose of this study was to examine the effects of methylprednisolone (MP), ibuprofen (I), and prostacyclin (PGI2) pretreatment on cardiopulmonary hemodynamics, arterial oxygenation, and pulmonary alveolar-capillary membrane permeability, measured with a gamma-scintigraphic technique, after acid instillation in the dog. All animals were placed on their right side and 2 ml/kg 0.1 N HCl was instilled into the endotracheal tube. Five untreated control dogs showed a significant (p less than 0.05) rise in slope index (SI), a scintigraphic measurement of pulmonary albumin flux, 30 minutes after acid injury. After 120 minutes there was a significant rise in mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) and a decrease (p less than 0.05) in cardiac output (CO) and PaO2. Two groups of five dogs each were pretreated with MP (30 mg/kg) and I (12.5 mg/kg), respectively. Thirty minutes after acid instillation both groups showed a significant rise in the SI, which was significantly greater than the values in the control animals in the case of MP. By 120 minutes after acid injury all changes in PAP, PVR, PaO2, and CO were not significantly different from those of control animals with the exception of the I group, which resisted any change in CO throughout the study. Another group of five dogs were pretreated with a constant infusion of PGI2 (3 micrograms/kg/min) starting 75 minutes before acid instillation. PGI2 produced a significant increase in CO that was also greater (p less than 0.05) than the CO in control animals before instillation of HCl. Pre-HCl SI in the dogs treated with PGI2 was slightly, but significantly, increased over control dogs. The SI and CO remained significantly higher than values in control animals 30 minutes after acid injury. The SI remained significantly higher than that of control animals at 120 minutes. After 2 hours changes in PAP, PVR, PaO2, and CO were without significant difference from those of control animals. These data support the conclusion that PGI2, I, or MP are not effective therapy for acid aspiration and that PGI2 and I may worsen the protein leak by increasing flow across the damaged capillary membrane.

Biomechanical study of sternal closure using rigid fixation techniques in human cadavers.

BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in sternal closure, as rigid fixation used in the craniofacial skeleton has shown greater stability, lower postoperative pain, and accelerated bone healing. We hypothesize that sterna fixed with titanium plates are more stable mechanically than sterna fixed with wires. METHODS: The sterna from human cadavers were used in this two-phased study. Phase I compared wires to four-hole titanium straight plates. Phase II compared wires to four-hole titanium custom H plates. The sterna were tested biomechanically using all fixation methods. RESULTS: Phase I showed no statistically significant difference in the stiffness or lateral displacement between the wired and straight plated sterna. Phase II showed a statistically significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05) in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results showed that custom titanium H plates were superior to wire fixation. Furthermore, our results established the importance of plate configuration in sternal fixation. Our study may have beneficial clinical implications, as decreased motion at the sternotomy site could mean less postoperative pain, a decreased incidence of infection, and accelerated bone healing.

Use of lumbar periosteal turnover flaps in myelomeningocele closure.

OBJECTIVE: We report our experience with a previously undescribed method of myelomeningocele closure, which is the use of bilateral lumbar periosteal flaps as an additional tissue layer in complex cases. These flaps reinforce the dural repair, act to protect the spinal cord, and may help to contain any potential cerebrospinal fluid leak from the primary repair of the cord, thereby preventing pseudomeningocele formation. METHODS: The repair involves the development of bilateral thoracolumbar fascial flaps in conjunction with periosteal flaps, which are elevated from adjacent lumbar pedicles and transverse processes, thus forming a composite tissue flap. These periosteally based flaps may be closed in a "pants over vest" fashion to completely cover the spinal defect, reinforcing the neurosurgical repair. The flap anatomy and dissection are detailed. RESULTS: Two representative cases in which the lumbar periosteal turnover flap procedure was used are reported. One patient was operated on during the early neonatal period for primary myelomeningocele repair; the other was operated on at age 5 years after a tethered cord release. Durable, stable soft tissue coverage of the spinal cord was obtained in both patients, with a postoperative follow-up period of at least 12 months. There was no recurrence of the pseudomeningocele noted preoperatively in the second patient. CONCLUSION: The lumbar periosteal turnover flap may be used to reinforce tenuous spinal cord and dural repairs in the myelomeningocele patient. This method provides a secure and watertight closure over the primary repair of the cord, may help to contain potential cerebrospinal fluid leaks, and adds an additional autologous tissue layer to standard skin or muscle flap repairs.

Volume maintenance of onlay bone grafts in the craniofacial skeleton: micro-architecture versus embryologic origin.

The superior volume maintenance of membranous over endochondral bone has been shown in several studies and provides the basis for its preferred clinical use as an onlay grafting material in the craniofacial skeleton. The scientific rationale for this seeming embryologic advantage, however, has never been proven. Our hypothesis is that the pattern of onlay bone graft resorption is primarily determined by a graft's micro-architecture (relative cortical and cancellous composition) rather than its embryologic origin (membranous versus endochondral). Twenty-five adult New Zealand, White rabbits were used for this study. Eight animals were killed at 3 weeks, eight animals at 8 weeks, and nine animals at 16 weeks. Three graft types were placed onto each rabbit cranium: cortical bone graft of membranous origin and cortical and cancellous bone graft of endochondral origin. Fluorochrome markers were injected into all living rabbits at 1, 6, and 14 weeks. Microcomputed tomography scanning was performed on all of the bone grafts to determine postsacrifice volumes and to obtain detailed information regarding the bone graft's trabecular architecture. In addition, specimens were examined histologically. Volume analysis showed a statistically greater resorption rate in the cancellous endochondral bone graft than in either the endochondral or membranous cortical bone grafts (p < 0.05) for all time points. In addition there was no significant difference in the resorption rates between the endochondral and membranous cortical bone grafts. A post-test power analysis (alpha = 5 percent) of the volume data comparing the two types of cortical bone grafts showed that a difference in resorption of 8.9 percent would be detected with a 90-percent probability. Previous studies, which have shown a seeming superiority of membranous over endochondral bone grafts, used composite grafts composed of both cortical and cancellous portions. By separating these components, we have shown that cortical bone grafts maintain their volumes significantly better than cancellous bone grafts. In addition, we found no statistical difference in the resorption rates between the two cortical onlay bone grafts of different embryologic origins, a finding that has never been previously published. From our results, we believe cortical bone to be a superior onlay grafting material, independent of its embryologic origin. We believe these results challenge the currently accepted theories of bone graft dynamics and may lead to a change in the way clinicians approach bone graft selections for craniofacial surgery.

A current 10-year retrospective survey of 199 surgically treated orbital floor fractures in a nonurban tertiary care center.

This study characterizes the surgically treated patient population suffering from orbital floor fractures by use of current data from a large series consisting of 199 cases taken from a nonurban setting. Data were gathered through a retrospective chart review of patients surgically treated for orbital floor fractures at the University of Michigan Health System, collected over a 10-year period. Data regarding patient demographics, signs and symptoms of presentation, cause of injury, nature of injury, associated facial fractures, ocular injury, and associated nonfacial skeleton trauma were collected. In total, there were 199 cases of orbital floor fractures among 189 patients. Male patients outnumbered female patients by a 2:1 ratio and were found to engage in a wider range of behaviors that resulted in orbital floor fractures. Motor vehicle accidents were the leading cause of orbital floor fractures, followed by physical assault and sports-related mechanisms. The ratio of impure to pure orbital floor fracture was 3:1. The most common signs and symptoms associated with orbital floor fractures, in descending order, were periorbital ecchymosis, diplopia, subconjunctival hemorrhage, and enophthalmos. Associated facial fractures were found in 77.2 percent of patients, the most prevalent of which was the zygoma-malar fracture. Serious ocular injury occurred in 19.6 percent of patients, with globe rupture being the most prevalent, accounting for 40.5 percent of those injuries. There was a 38.1 percent occurrence of associated nonfacial skeletal trauma; skull fracture and intracranial injury were the most prevalent manifestations. Associated cervical-spine fractures were rare (0.5 percent). Statistical examination, using odds ratios and chi-squared analysis, demonstrated significant associations that have not previously been reported. Impure and pure orbital floor fractures revealed striking differences in several demographic aspects, including mechanism of injury, signs and symptoms of presentation, spectrum of associated trauma, and the severity of concomitant trauma.

Investigation of the influences of biomechanical force on the ultrastructure of human sagittal craniosynostosis.

This study presents comparisons of the ultrastructure of synostotic and open portions of synostotic sagittal sutures using histomorphometry, scanning electron microscopy, and microcomputed tomography. By using stereologic and histomorphometric analysis, this study proposes to demonstrate evidence of the influence of biomechanical force on the suture during the process of sagittal craniosynostosis. Finally, we propose to link the pathologic changes transforming normal suture fusion to craniosynostosis with concurrent changes in the polarity of suture fusion initiation. Seven infants (four boys and three girls) with sagittal craniosynostosis, ranging in age from 1.4 to 4.8 months (mean = 3.0 months), underwent sagittal synostectomies. The synostotic bone specimens were sectioned into three regions: an open suture, partial synostosis, and complete synostosis. Microcomputed tomographic and scanning electron microscopic scanning as well as histomorphometry was performed on all specimens to obtain detailed qualitative and quantitative information regarding the trabecular microarchitecture of the synostosed suture. Microcomputed tomographic analysis determined the bone volume fraction, trabecular thickness, trabecular separation, bone surface to bone volume ratio, and anisotropy for all specimens. Our results showed significant differences in all of these quantitative measurements when comparing the complete synostotic suture with the open portion of the synostotic sutures (p < 0.05). Microcomputed tomographic stereologic analysis showed evidence of the influence of biomechanical force on the synostotic and open portions of the synostotic sutures. Results of scanning electron microscopy show a definite qualitative difference in the trabecular pattern of the partial and complete synostotic suture when compared with the open portion of the synostotic sagittal suture. In this study, we performed both qualitative and quantitative comparisons of the ultrastructure of the complete synostotic and nonsynostotic sagittal sutures using stereologic and histomorphometric techniques. We also demonstrated evidence of the influence of biomechanical force on the synostotic sagittal suture. Finally, we established a link between the pathologic changes transforming normal suture fusion to craniosynostosis and concurrent changes in both the vector and direction of suture fusion initiation.

Pediatric facial fractures: analysis of differences in subspecialty care.

At the University of Michigan, the pediatric facial fracture call schedule rotates through the plastic surgery, otolaryngology, and oral surgery services. This situation provides an opportunity to evaluate differences in the management of pediatric facial fractures between subspecialty groups. At this hospital, a retrospective review of all pediatric facial fracture cases within a 5-year period was undertaken. Sixty patients with 82 facial fractures were studied along subspecialty lines. Differences in patient groups, practice patterns, and treatment strategies based on subspecialty assignment were found. Overall treatment followed traditional lines, with plastic surgeons involved in all types of pediatric facial fractures, whereas otolaryngology and oral surgeons were more limited in their operative scope, despite equal call responsibilities. It is believed that the managed care arena is a competitive environment in which it will be important to know the strengths and weaknesses of the plastic surgery specialty, as well as those of competing specialties, as patient contracts are negotiated. The overlap of plastic surgery, otolaryngology, and oral surgery in the care of facial trauma could result in plastic surgeons being left off of managed care participant lists. This study highlights plastic surgeons as efficient deliverers of quality care for pediatric facial fractures. Although the treatment of these fractures has fallen into the duties shared by all three subspecialties, data such as those presented here should strengthen our ability to succeed in the evolving environment of managed care.

A comparative analysis of the microarchitecture of cortical membranous and cortical endochondral onlay bone grafts in the craniofacial skeleton.

Previous work in this laboratory established that an onlay bone graft's survival is determined primarily by its relative cortical and cancellous composition rather than its embryologic origin. A volumetric analysis of external bone graft resorption, however, does not explain the internal microarchitectural changes that may be occurring as these grafts become incorporated. To expand the knowledge of bone graft dynamics beyond volumetric parameters, a better understanding of the internal processes of bone graft remodeling is needed. In this comparative study of cortical onlay bone graft microarchitecture, the authors propose to show that cortical onlay bone grafts undergo measurable internal microarchitectural changes as they become incorporated into the surrounding craniofacial skeleton. In addition, the authors propose to further demonstrate similarities between the internal microarchitecture of cortical onlay bone grafts of different embryologic origin over time. Twenty-five adult New Zealand White rabbits were used for this study. They were divided into two groups of eight animals and one group of nine. The groups were killed at 3, 8, and 16 weeks. Cortical membranous and endochondral bone grafts were placed subperiosteally onto each rabbit's cranium. In addition, five ungrafted cortical endochondral and membranous bone specimens were used as controls. Microcomputed tomography (MCT) scanning and histomorphometric analysis were performed on all of the specimens to obtain detailed information regarding the microarchitecture of the cortical bone grafts. The parameters of bone volume fraction, bone surface area to volume, mean trabecular number, and anisotropy were used to give quantitative information about a bone's micro-organization. The results showed that there is no statistically significant difference between the cortical endochondral and the cortical membranous bone grafts for bone volume fraction, bone surface to volume, mean trabecular number, and anisotropy measurements for all time points. There were, however, statistically significant differences when comparing the control and 3-week groups to the 16-week group for all parameters. The advanced MCT technology and histomorphometric techniques proved to be effective in providing a qualitative and quantitative ultrastructural comparison of cortical endochondral and membranous onlay bone grafts over time. In this study, a statistically significant change in the internal microarchitecture of cortical onlay bone grafts of different embryologic origins was seen as they were remodeled and resorbed at all time points. Specifically, the onlay cortical bone grafts developed a less dense, more trabecular, and less organized internal ultrastructure. In addition, no difference in the three-dimensional ultrastructure of cortical endochondral and membranous bone was found. These results challenge some of the currently accepted theories of bone-graft dynamics and may eventually lead to a change in the way clinicians approach bone-graft selection for craniofacial surgery.

Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate.

Maternal cigarette smoking during pregnancy as a risk factor for having a child with cleft lip/palate has been suggested by several epidemiologic studies. However, most of these studies contained small sample sizes, and a clear association between these two factors could not be established. The U.S. Natality database from 1996 and a case-control study design were used to investigate the association between maternal smoking during pregnancy and having a child with cleft lip/palate. The records of 3,891,494 live births from the 1996 U.S. Natality database were extracted to obtain cleft lip/palate cases and random controls. The National Center for Health Statistics collects maternal and newborn demographic and medical data from the birth certificates of all 50 states. New York (excluding New York City), California, Indiana, and South Dakota did not collect smoking data, and the data from these states were excluded from the analysis. A total of 2207 live births with cleft lip/palate cases were identified, and 4414 controls (1:2 ratio) were randomly selected (using the SAS program) from live births with no congenital defects. Odds ratios and 95 percent confidence intervals were determined from logistic regression models, adjusting for confounding variables, including maternal demographic and medical risk factors. A significant association was found between any amount of maternal cigarette use during pregnancy and having a child with cleft lip/palate [unadjusted odds ratio 1.55 (1.36, 1.76), p < 0.001]. Univariate analysis showed that maternal education level, age, race, and maternal medical conditions (diabetes and pregnancy-associated hypertension) were potential confounders. After adjusting for these confounders, the odds ratio remained significant [Mantel-Haenszel odds ratio 1.34 (1.16, 1.54), p < 0.001]. To determine the dose response of cigarette smoking during pregnancy, the cigarette consumption per day was divided into four groups: none, 1 to 10, 11 to 20, and 21 or more. A dose-response relationship was found when comparing each smoking category with the no smoking reference group: 1.50 (1.28, 1.76), 1.55 (1.23, 1.95), and 1.78 (1.22, 2.59), respectively. This means that increased cigarette smoking during pregnancy resulted in increased odds of having a child with cleft lip/palate. This is the largest study to date to test the association between maternal cigarette smoking during pregnancy and having a newborn with cleft lip/palate. The significant trend in the dose-response relationship strongly suggests the association of smoking tobacco and this common congenital deformity. These results emphasize the public health risks associated with smoking during pregnancy. To prevent this devastating craniofacial anomaly, educational initiatives should be considered that will alert expectant mothers to the association between smoking during pregnancy and the occurrence of cleft lip/palate.

Facial bone grafts: Contemporary science and thought.

BACKGROUND AND OBJECTIVES: The use of bone grafts is a vital component of a surgeon's armamentarium in the reconstruction of congenital and acquired deformities of the craniofacial region. A thorough understanding of bone graft physiology and the factors thought to affect graft behavior is essential in order to develop a more intelligent use of the grafts in clinical applications. METHODS AND MATERIALS: This article presents a brief review of the basic physiology of bone grafts along with a survey of pertinent concepts and research currently available. Mechanical stress, rigid fixation, graft orientation, and the recipient sites are reviewed. RESULTS AND/OR CONCLUSION: In an attempt to bring together various issues that exist in current bone graft science, the authors propose new concepts. They suggest that the mechanical environment in which a bone graft is placed, revascularization of the graft, and the interaction between those two factors are the major predictors of clinical results.

The ultrastructure and resorptive pattern of cancellous onlay bone grafts in the craniofacial skeleton.

The authors' laboratory has shown cancellous onlay bone grafts to resorb faster than cortical grafts. To understand the nature of cancellous bone grafts beyond volumetric measurements, a temporal analysis of the internal microarchitecture of these grafts was performed. Their hypothesis is that the forces of remodeling and resorption cause cancellous onlay bone grafts to develop a denser, more interconnected, and a more mechanically stable microarchitecture. Twenty-five adult New Zealand White rabbits were used in this study and were divided into three groups. Microcomputed tomography (MCT) was performed on all cancellous bone grafts to obtain detailed information regarding the microarchitecture of the cancellous bone. Bone graft specimens were examined histologically, and histomorphometric analysis was also performed. Their results show that cancellous onlay bone grafts develop a higher bone volume fraction, mean trabecular thickness, connectivity, and degree of anisotropy. Furthermore, cancellous onlay bone grafts developed a lower bone surface area-to-volume ratio and mean trabecular separation. The unique combination of MCT technology and histomorphometric techniques proved to be effective in providing a qualitative and quantitative ultrastructural analysis of cancellous onlay bone grafts over time. The authors were able to show changes in the internal microarchitecture of cancellous onlay bone grafts as they were remodeled and resorbed. Specifically, they found the cancellous onlay bone grafts to develop a more dense, less trabecular, more organized, and more interconnected internal ultrastructure over time. Their findings have helped to provide a reproducible description of the temporal sequence of changes in bone microarchitecture, revascularization, and internal remodeling.

Use of scanning electron microscopy in the evaluation of craniosynostosis.

The cause of craniosynostosis continues to elude researchers. Although several studies have looked at the ultrastructure of normal suture closure, no previous studies have examined the microarchitecture of the synostotic suture. Our goal was to assess the scanning electron microscope (SEM) as a viable and useful tool in examining craniosynostosis. Our hypothesis is that the SEM is a powerful analytical tool that can evaluate nonsynostotic, partial synostotic, and complete synostotic cranial sutures. We analyzed the cranial suture of 3 human infants with nonsyndromic sagittal craniosynostosis. The specimens were separated into three groups, which included regions of partial and complete synostosis and a region of open suture. Histological examination provided cellular and tissue data about craniosynostosis, whereas the SEM provided detailed information regarding the trabecular microarchitecture of the synostosed suture. The SEM produced quality images of complete and partially synostotic sutures and open sutures. At low magnification, the SEM characterized the general bony microarchitecture of cranial sutures in a manner different from, but complementary to, standard histological sections. At higher magnification, the SEM allowed us a look at the cellular population of craniosynostotic sutures in a way that surpasses standard light microscopy. The SEM is an excellent tool for the study of craniosynostosis and has proved invaluable in our ability to evaluate the microarchitecture and cellular population of the fusing suture. We believe we have proven our hypothesis by demonstrating the SEM to be a powerful analytical tool that can evaluate nonsynostotic, partial synostotic, and complete synostotic cranial sutures.

Pediatric facial fractures: a demographic analysis outside an urban environment.

This study reviews all pediatric facial fractures treated operatively at the C.S. Mott Children's Hospital of the University of Michigan over a 5-year period. Previous series of pediatric facial fractures have been collected at large urban centers and may not be representative of all practice environments. Our institution is a level 1 trauma center that serves a patient population primarily from suburban and rural regions throughout the state. Referral and practice patterns at our institution gave us an important opportunity to analyze differences in patient care and management secondary to venue, and challenge the assumptions made by studies collected at large urban centers. We reviewed 80 fractures in 62 patients. Patient age ranged from 2 to 18 years old with the majority of patients (58%) between 15 and 18 years old. Most fractures resulted from motor vehicle accidents (43%) and there were no firearm injuries. Fracture sites included the mandible (38%), the frontonasoethmoid region (35%), the midface (17%), and the orbit (10%). Only two operative complications were reported. There were no cervical spine injuries. Median patient age was higher and mechanism of injury differed in our study compared with urban studies. Rapid changes in the health care delivery system and the emergence of managed care demand accurate demographic updates for the efficient allocation of valuable resources. Our results showed important differences with previous studies and imply that assumptions and analysis of the care of pediatric facial fractures based solely on data collected at large urban centers may be too parochial, and therefore subsequent health care decisions of resource allocation arrived at without respect to practice environment could be erroneous.

O2 binding properties of the product of the central exon of beta-globin gene.

The hypothesis that the exons of eukaryotic structural genes code for functional domains and that the partitioned arrangement of coding information may thus serve to mediate the rapid evolution of new and unique proteins from pre-existing exons is also supported by our recent studies which demonstrate that the product of the central exon of the human beta-globin gene is a complete functional domain capable of binding haem tightly and specifically. Moreover, an analysis of the structure/function changes induced by mutations in different parts of the haemoglobin molecule suggests that each of the three exon-encoded segments is primarily associated with different functions of haemoglobin (for example, haem-binding, haem-haem interaction). We have now extended our studies to determine whether the central fragment is sufficient for maintenance of a stable complex of ferrous haem with molecular oxygen and, if not, what are the minimal requirements for the expression of this activity. The results of our reconstitution experiments indicate that the isolated central exon peptide is unable to maintain a ferrous haem-dioxygen complex unless the side exon products and the complementary haem-containing subunit are present. A conformational change which accompanies the noncovalent association of fragments may account for the restoration of reversible oxygen binding.

Reasons for removal of rigid internal fixation devices in craniofacial surgery.

Despite the widespread use of rigid fixation techniques in craniofacial surgery, there is a paucity of studies in the literature that serve to better define the reasons for the subsequent removal of plates and screws. The current study appears to be the first to attempt to assess these issues among a broad range of craniofacial surgery patients. Fifty-five patients who underwent hardware removal following craniofacial surgery at the University of Michigan Medical Center between 1989 and 1995 were retrospectively studied via an in-depth chart review. Common reasons for hardware removal included palpable/prominent hardware in 19 patients (34.5%), loosening of plates and screws in 14 patients (25.5%), pain in 14 patients (25.5%), infection in 13 patients (23.6%), wound dehiscence/exposure of hardware in 11 patients (20%), and removal at the time of secondary procedures in 5 patients (9.1%). It is hoped that this study will serve as a tool to define more completely the risk of needing subsequent hardware removal among craniofacial surgery patients treated with rigid internal fixation.