Biomedical subjects

J G McCarthy

Publications and source records attributed to J G McCarthy.

At least 37 records · Page 2Linked to original sources

PubMed1999

Moebius syndrome: the new finding of hypertrophy of the coronoid process.

The first detailed description of congenital facial paralysis was reported by Moebius in 1888. It is characterized by either unilateral or bilateral paralysis of the facial muscles and an associated abducens palsy. The present report is of two patients with Moebius syndrome, who were also diagnosed with trismus at birth. Each patient also demonstrated bilateral hypertrophy of the coronoid process of the mandible. In effect, the zygoma obstructed the excursion of the mandible because of a "coronoid block." A three-dimensional computed tomography scan demonstrated normal temporomandibular joints but bilateral hypertrophy of the coronoid processes and micrognathia. Both patients demonstrated less than 10 mm of oral excursion. Bilateral coronoidectomies were performed through an intraoral approach. The oral excursions after surgery increased to at least 20 mm. In each of these patients, the coronoid process was enlarged relative to the zygoma, which was of normal size and configuration. The trismus was associated with blocking of the coronoid by the anterior zygoma, preventing open or full excursion of the hypoplastic mandibles. Moebius syndrome can have a variable presentation at birth. In two patients, the authors describe a new finding of hypertrophy of the coronoid process and trismus secondary to obstruction of the coronoid by the hypertrophic zygomas during oral excursions. Each patient is described, and a review of the literature is discussed.

Abnormalities, Multiple↗

PubMed1999

Increased IGF-I and IGF-II mRNA and IGF-I peptide in fusing rat cranial sutures suggest evidence for a paracrine role of insulin-like growth factors in suture fusion.

Premature cranial suture fusion, or craniosynostosis, can result in gross aberrations of craniofacial growth. The biology underlying cranial suture fusion remains poorly understood. Previous studies of the Sprague-Dawley rat posterior frontal suture, which fuses at between 12 and 20 days, have suggested that the regional dura mater beneath the cranial suture directs the overlying suture's fusion. To address the dura-suture paracrine signaling that results in osteogenic differentiation and suture fusion, the authors investigated the possible role of insulin-like growth factors (IGF) I and II. The authors studied the temporal and spatial patterns of the expression of IGF-I and IGF-II mRNA and IGF-I peptide and osteocalcin (bone morphogenetic protein-4) protein in fusing posterior frontal rat sutures, and they compared them with patent coronal (control) sutures. Ten Sprague-Dawley rats were studied at the following time points: 16, 18, and 20 days of gestation and 2, 5, 10, 15, 20, 30, 50, and 80 days after birth (n = 110). Posterior frontal and coronal (patent, control) sutures were analyzed for IGF-I and IGF-II mRNA expression by in situ hybridization by using 35S-labeled IGF-I and IGF-II antisense riboprobes. Levels of IGF-I and IGF-II mRNA were quantified by counting the number of autoradiograph signals per cell. IGF-I and osteocalcin immunoreactivity were identified by avidin-biotin peroxidase immunohistochemistry. IGF-I and IGF-II mRNA were expressed in dural cells beneath fusing sutures, and the relative mRNA abundance increased between 2 and 10 days before initiation of fusion. Subsequently, IGF-I and IGF-II mRNA were detected in the suture connective tissue cells at 15 and 20 days during the time of active fusion. In contrast, within large osteoblasts of the osteogenic front, the expression of IGF-I and IGF-II mRNA was minimal. However, IGF-I peptide and osteocalcin protein were intensely immunoreactive within these osteoblasts at 15 days (during the period of suture fusion). These data suggest that the dura-suture interaction may be signaled in a paracrine fashion by dura-derived growth factors, such as IGF-I and IGF-II. These peptides, in turn, stimulate nearby osteoblasts to produce bone-promoting growth factors, such as osteocalcin.

Animals↗

PubMed1998

In vitro prefabrication of human cartilage shapes using fibrin glue and human chondrocytes.

We report the first generation of human cartilage from fibrin glue using a technique of molding chondrocytes in fibrin glue developed in our laboratory. Human costal chondrocytes were suspended in cryoprecipitate and polymerized into a human nasal shape with bovine thrombin. After culture in vitro for 4 weeks, this construct was implanted subcutaneously into a nude mouse. The final construct harvested after 4 weeks in vivo demonstrated some preservation of its original features. Histological analysis showed features of native cartilage, including matrix synthesis and viable chondrocytes by nuclear staining. Biochemical analysis demonstrated active matrix production. Biomechanical testing was performed. To our knowledge this is the first reported creation of human cartilage from fibrin glue, and the first creation of human cartilage in vitro. This technique may become a promising means of engineering precisely designed autogenous cartilage for human reconstruction.

Adolescent↗

PubMed1998

Hypertrophy and asymmetry of the facial muscles: a previously unrecognized association.

We present 6 patients who do not satisfy the criteria for inclusion into any known diagnostic group, although they share similar physical findings. All had facial findings suggestive of either mild deformational plagiocephaly or craniofacial microsomia; however, hypertrophic and occasionally hyperactive muscles of the face appear to be the unifying and distinctive feature of the group. Contraction of hypertrophic postauricular muscles on the affected side resulted in movement and contraction of the pinna. Hypertrophy of the mentalis and masseter muscles was also frequently observed. Additionally, anomalous neck musculature was seen in 4 of the 6 patients. In 2 patients, the hypertrophy of certain of these muscles produced enough deformity to warrant excision. This is the first report of such an association in the literature. Possible explanations are discussed.

Child↗

PubMed1998

Controlled multiplanar distraction of the mandible: device development and clinical application.

Distraction osteogenesis has been shown to be an effective method of lengthening and augmenting endochondral bone. It has also been applied effectively in the reconstruction of the membranous bones of the craniofacial skeleton. With the accumulation of clinical experience in mandibular distraction, the differences between endochondral and membranous bone distraction have become apparent, especially in the limitations of uniplanar distraction for the three-dimensional reconstruction of the deficient mandible. Distraction of the mandible in a single plane cannot satisfy fully the functional and structural requirements of the patient with malocclusion as well as deficiency of the skeletal and soft tissue. This study reports the development and clinical use of a multiplanar mandibular distraction device with the ability to achieve linear distraction (Z-plane or sagittal), angular distraction (Y-plane or vertical), and transverse distraction (X-plane or coronal). The device contains two independent gear arrangements attached to two arms that extend from the central unit. Therefore, the trajectory of the regenerated bone may be changed during the distraction process. The device also allows manipulation of the various planes of movement independent of each other. Furthermore, the rotational points for the multiplanar distraction devices are located at a single point; therefore only a single osteotomy and two pin sites are required. The multiplanar distraction device allows the surgeon to customize and contour the dimensions of the distraction process by controlling the trajectory of the translation of the regenerated bone.

Child, Preschool↗

PubMed1998

The combination of endoscopy and distraction osteogenesis in the development of a canine midface advancement model.

The requirements for reconstruction in patients with midface hypoplasia can be formidable: a bicoronal scalp incision, Le Fort III or monobloc skeletal advancement, harvesting and insertion of bone grafts, application of rigid (and occasionally intermaxillary) fixation, blood transfusions, and prolonged operative time and hospitalization. The introduction of the endoscope offers the possibility of minimally invasive surgery with improved visualization of the osteotomy sites. The development of distraction osteogenesis as a surgical technique allows controlled and gradual advancement of the osteotomized skeletal segment and associated soft tissue. The purpose of this study was to develop a canine model of an endoscopically assisted Le Fort III osteotomy with attendant midface distraction. Four mongrels (20 kg in weight) were study subjects. Three 2-cm skin incisions were made (two perpendicular to the zygomaticomaxillary suture and one perpendicular to the nasofrontal suture). The soft tissue and periosteum were evaluated bluntly. Retractors specially designed for the project created a space for endoscopic visualization. Bilateral zygomatic, nasofrontal, and medial orbital wall osteotomies, corticotomies, or both were performed under endoscopic visualization using a reciprocating saw; the medial orbital wall sectioning was specifically not completed (i.e., corticotomy) to avoid laceration of the mucosa and attendant bleeding. The pterygomaxillary osteotomy was completed with an osteotome and mallet. Finally, the nasal septum was only partially divided with an osteotome to avoid excessive blood loss. Four distraction devices were placed across the above-noted osteotomies (two across the nasofrontal osteotomy and one across each lateral osteotomy). The animals were distracted 1 mm per day for 16 to 40 days after surgery (16-40 mm of linear distraction). Cephalograms and computed tomography scans were obtained before and after distraction. The animals were killed after remaining in fixation for 4 to 6 weeks after distraction. All soft tissue was removed and the skull was examined. Photos were obtained throughout the experiment for documentation. The study demonstrated that Le Fort III osteotomies can be performed successfully via small incisions with endoscopic assistance in canine subjects with excellent visualization and minimal bleeding. The advancement of the midface segment can be achieved by activation of an external distraction device.

Animals↗

PubMed1998

Controlled multiplanar distraction of the mandible, Part II: Laboratory studies of sagittal (anteroposterior) and vertical (superoinferior) movements.

The application of distraction osteogenesis in craniofacial surgery has significantly altered the treatment of congenital mandibular deficiencies. However, evaluation of results in both animal studies and clinical cases has revealed deficiencies, particularly in two areas. First, distraction using a uniplanar device in an anteroposterior direction can result in a persistent anterior open bite. Second, the lateralization of the distracted hemimandible was often limited, with insufficient incremental gain in the bigonial distance. To overcome these shortcomings, a multiplanar distraction device was developed and tested in the canine model. This report details canine studies addressing the first problem: combined anteroposterior or sagittal (z-axis) and superoinferior or vertical (y-axis) movements. Six dogs underwent bilateral mandibular distraction with an external (extraoral), multiplanar device and completed sagittal plus vertical distraction. Evaluation included clinical examination (facial form, jaw position, and occlusion), photography, cephalograms (posteroanterior, basilar, and lateral), three-dimensional computed tomography reconstructions, and examination of dry skulls. The dogs averaged 18.5 mm (range, 15-20 mm) of sagittal distraction and 41.0 degrees (range, 21-50 degrees) of vertical distraction. Marked anterior open bites were produced after vertical distraction secondary to premature contact of the maxillary and mandibular molars. Distraction in the vertical direction also had the additive effect of increasing the sagittal gains by approximately 5% to 10%. In conclusion, a multiplanar distraction device (with the potential for distraction in three planes) was effective in increasing mandibular anteroposterior thrust (sagittal distraction) and also in creating an anterior open bite (vertical or superoinferior distraction). Vertical distraction probably requires bilateral osteotomies to obtain optimal results. The preliminary gains in sagittal length are modified (reduced or increased) after distraction in a second plane (vertical and horizontal). Specifically, vertical distraction in the inferior direction (creating an open bite) also leads to isolated increases in the anteroposterior plane. Conversely, vertical distraction in the superior direction (closing an open bite), as seen in a human malocclusion, may lead to isolated decreases in the anteroposterior plane, but this question remains to be investigated in the laboratory.

Animals↗

PubMed1998

Airway management in children with major craniofacial anomalies.

OBJECTIVES: Delineation of clinical characteristics affecting the airway in a cohort of craniofacially deformed children. What factors differ between patients requiring and those not requiring surgical airway intervention? What factors predispose to the need for tracheotomy? When can decannulation be expected if tracheotomy is required? What interventions aid decannulation? STUDY DESIGN: Five-year retrospective chart review at tertiary center. METHODS: Two hundred fifty-one patients met the following entry criteria: enrollment in the New York University Institute of Reconstructive and Plastic Surgery's Craniofacial Clinic and admission to Tisch Hospital in Manhattan for surgery from 1990 to 1994. Hospital, clinic, and departmental office records were reviewed. All patients had major craniofacial bony anomalies and underwent administration of general anesthesia at least once. RESULTS: Nearly 20% of all children required tracheotomy (47/251). Craniofacial synostosis patients (Crouzon, Pfeiffer, or Apert syndrome) had the highest rate of tracheotomy (48% [28/59]). Mandibulofacial dysostoses patients (Treacher Collins or Nager syndrome) had the next highest rate (41% [28/59]). Patients with oculo-auriculo-vertebral sequence were less likely to undergo tracheotomy (22% [9/41]). Children with craniosynostosis rarely required a surgical airway, unless there was marked associated facial dysmorphism (1% [1/72]). The duration of cannulation was related to the age at tracheotomy in a bimodal distribution. Generally, tracheotomies required before age 4 years remained for several years, whereas those placed after age 4 were removed after several weeks. The presence of a cleft palate correlated with reduced risk for tracheotomy, but the presence of a ventriculoperitoneal shunt correlated with an increased risk for tracheotomy. Procedures selectively used to improve the airway included midface advancement, mandibular expansion, tonsillectomy and adenoidectomy, uvulopalatopharyngoplasty, anterior tongue reduction, and endoscopic tracheal granuloma excision. CONCLUSIONS: The likelihood for surgical airway management is related to specific craniofacial diagnosis. The length of tracheal cannulation is greatest for infants and young children who manifest severe airway compromise, often because of nasal obstruction in combination with other anatomic factors. Early tracheotomy is advocated for these patients to promote optimal growth and development. Choanal atresia is often misdiagnosed in these infants; nasal obstruction is actually secondary to midface retrusion. Staged surgical interventions can allow eventual successful decannulation in nearly all cases of craniofacial syndromes.

Adolescent↗

PubMed1998

Studies in cranial suture biology: up-regulation of transforming growth factor-beta1 and basic fibroblast growth factor mRNA correlates with posterior frontal cranial suture fusion in the rat.

The mechanisms involved in normal cranial suture development and fusion as well as in the pathophysiology of craniosyostosis are not well understood. The purpose of this study was to investigate the expression of several cytokines--transforming growth factor-beta-1 (TGF-beta1), basic fibroblast growth factor (bFGF), and interleukin-6 (IL-6)--during cranial suture fusion. TGF-beta exists in three mammalian isoforms that are abundant in bone and stimulate calvarial bone formation when delivered locally. Other bone growth factors including basic fibroblast growth factor and the interleukins regulate bone growth and are mitogenic for bone marrow cells and osteoblasts. The involvement of growth factors in the pathophysiology of craniosynostosis is supported by recent genetics data linking fibroblast growth factor receptor mutations to syndromal craniosynostoses. In this experimental study, in situ hybridization was used to localize and quantify the gene expression of TGF-beta1, bFGF, and IL-6 during cranial suture fusion. In the Sprague-Dawley rat, the posterior frontal cranial suture normally undergoes fusion between 12 and 22 days of age, whereas all other cranial sutures remain patent. All in situ analyses of fusing posterior frontal sutures were compared with the patent, control, sagittal sutures. Posterior frontal and sagittal sutures, together with underlying dura, were harvested from rats at 8, 12, 16, and 35 days of postnatal life to analyze posterior frontal suture activity before, during, and after fusion. In situ hybridization was performed on frozen sections of these specimens using DNA probes specific for TGF-beta1, bFGF, and IL-6 mRNA. A negative control probe to IL-6 in the sense orientation was also used to validate the procedure. Cells expressing cytokine-specific mRNA were quantified (in cells positive per 10(-1) mm2) and analyzed using the unpaired Student's t test. Areas encompassing the fibrous suture and the surrounding bone plates were analyzed for cellular mRNA activity. IL-6 mRNA expression showed a minimal rise in the posterior frontal suture at days 12 and 16, with an average count of 10 and 6 cells per 10(-1) mm2, respectively. The sagittal suture remained negative for IL-6 mRNA at all time points. TGF-beta1 and bFGF analyses were most interesting, showing marked increases specifically in the posterior frontal suture during the time of active suture fusion. On postnatal day 8, a 1.5-fold increase in posterior frontal suture TGF-beta1 mRNA was found compared with sagittal sutures (p = 0.1890, unpaired Student's t test). This difference was increased 26-fold on day 12 in posterior frontal suture TGF-beta1 expression (p = 0.0005). By day 35, posterior frontal suture TGF-beta1 mRNA had nearly returned to prefusion levels, whereas TGF-beta1 mRNA levels in the sagittal suture remained low. A similar upregulation of bFGF mRNA, peaking at day 12, was observed in posterior frontal but not sagittal sutures (p = 0.0003). Furthermore, both TGF-beta1 and bFGF mRNA samples with intact dura showed an intense dural mRNA expression in the time preceding and during active posterior frontal suture fusion but not in sagittal tissues. Our data demonstrate that TGF-beta1 and bFGF mRNA are up-regulated in cranial suture fusion, possibly signaling in a paracrine fashion from dura to suture. TGF-beta1 and bFGF gene expression were dramatically increased both in and surrounding the actively fusing suture and followed the direction of fusion from endocranial to epicranial. These experimental data on bone growth factors support the recent human genetics data linking growth factor/fibroblast growth factor receptor deletions to syndromal craniosynostoses. The ultimate aim of these studies is to understand the underlying mechanisms regulating suture growth, development, and fusion so surgeons may one day manipulate the biology of premature cranial suture fusion.

Animals↗

PubMed1998

Studies in cranial suture biology: regional dura mater determines overlying suture biology.

The influence of dura mater on adjacent cranial sutures is significant. By better understanding the mechanisms of normal suture fusion and the role of the dura mater, it may be possible to delineate the events responsible for the premature suture fusion seen in craniosynostosis. In the Sprague-Dawley rat, the posterior frontal suture normally fuses between 12 and 20 days of postnatal life and has proved to be an excellent model to describe normal suture fusion. The purpose of this study was to document the critical role that the dura mater-suture complex may play on cranial suture biology. Forty Sprague-Dawley rats at 8 days of age were divided into two groups of 20 animals each. The control group (group A) had surgical disruption of the dura mater-calvarial interface. This was accomplished by elevating a strip of cranium inclusive of the posterior frontal and sagittal sutures and replacement of the cranial strip back to its anatomic position, all with the dura mater left intact. The experimental group (group B) had the same calvarial elevation (strip craniectomy), but the sutural anatomy/alignment was rotated 180 degrees. This rotation placed the posterior frontal suture into the sagittal suture's anatomic position and the sagittal suture into the posterior frontal suture's anatomic position. All of these procedures were accomplished by leaving the underlying dura mater intact. Animals were killed at 20, 30, 40, and 50 days (12, 22, 32, and 42 days postoperatively), and tissue sections were examined with hematoxylin and eosin staining. Group A (control) showed normal but delayed suture activity. The posterior frontal suture fused, and the sagittal suture remained patent. Fusion was delayed, not beginning before 20 days (12 days postoperative) and showing complete fusion between 30 and 40 days. Group B (180-degree calvarial rotation) demonstrated that the suture in the posterior frontal anatomic position (actual sagittal suture) fused between 20 and 40 days, whereas the suture in the sagittal anatomic position (actual posterior-frontal suture) remained patent throughout the study. This study demonstrates that the location of the dura mater-suture complex is important in determining either suture patency or closure in this model. Normal closure of the suture overlying the posterior frontal dura mater demonstrates that the dura mater itself, or forces derived in specific cranial locations, determines the overlying suture biology.

Animals↗

PubMed1998

Immunolocalization of basic fibroblast growth factor and fibroblast growth factor receptor-1 and receptor-2 in rat cranial sutures.

Craniosynostosis is a common disorder with an unknown etiology. Recent genetic mapping studies have demonstrated a strong linkage between several familial craniosynostotic syndromes and mutations in fibroblast growth factor receptor 1 (FGF-R1) and 2 (FGF-R2). The purpose of this experiment was to investigate by immunohistochemistry the protein production of these receptors as well as of their most prevalent ligand, basic fibroblast growth factor (bFGF), before, during, and after sutural fusion in rat cranial sutures. The posterior frontal (normally fuses between postnatal days 12 and 22) and sagittal (remains patent) sutures of embryonic day 20 and neonatal days 6, 12, 17, 22, and 62 (n = 3 per group) were harvested, fixed, and decalcified. Five-micrometer sections were stained with polyclonal antibodies against bFGF, FGF-R1, and FGF-R2, and patterns of immunohistochemical staining were assessed by independent reviewers. Our results indicate that increased bFGF production correlates temporally with suture fusion, with increased staining of the dura underneath the fusing suture prior to fusion followed by increased staining within osteoblasts and sutural cells during fusion. FGF-R1 and, to a lesser extent FGF-R2 immunostaining revealed a different pattern of localization with increased immunostaining within the patent sagittal suture at these time points. These results implicate bFGF in the regulation of sutural fusion and may imply autoregulatory mechanisms in fibroblast growth factor receptor expression.

Animals↗

PubMed1998

Rat mandibular distraction osteogenesis: Part I. Histologic and radiographic analysis.

The application of distraction osteogenesis to craniofacial surgery has altered the approach and treatment of congenital and acquired craniofacial defects. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been described extensively, relatively little is known about the molecular regulation of this process. The elucidation of the molecular mechanisms of distraction osteogenesis has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Molecular analysis of distraction osteogenesis has been hindered by the use of large animal models in which only limited genetic information is available. In this study, a rat model of mandibular distraction osteogenesis is described. This report includes a pilot study (n = 50) to develop an appropriate distraction device and to determine the optimal placement of the osteotomy. The study subsequently included 80 animals, 35 of which were distracted at a rate of 0.25 mm per day for 6 days (1.5 mm total) and 35 that were distracted at a rate of 0.25 mm twice per day (3.0 mm total). These animals were killed at various time points (after latency and during the distraction and consolidation periods) and displayed histologic and radiographic findings of membranous bone distraction osteogenesis that were consistent with those in large ,animal and clinical models. In addition, five animals each were acutely lengthened 1.5 mm and 3.0 mm and demonstrated a fibrous nonunion. Furthermore, the utility of this model is demonstrated in the analysis of the molecular mechanisms of distraction osteogenesis by applying the polymerase chain reaction to total cellular RNA isolated from normal and distracted rat mandibles. In conclusion, it is believed that the rat model of distraction osteogenesis has significant advantages over traditional models, including decreased costs and facilitation of molecular analysis.

Animals↗

PubMed1998

A virtual reality system for bone fragment positioning in multisegment craniofacial surgical procedures.

This article reports our clinical experience since 1994 with rigid-motion tracking of bone fragments during craniofacial surgical procedures, using a virtual reality approach. Three noncollinear infrared diodes are fixed to the skull base. A pointer is used to register anatomic features on the patient to those on the computerized tomography-based model of the patient within a computer work station. Three diodes are then attached to each fragment just before the osteotomy is completed. Rigid motions of the fragment are thus tracked and reported to the surgeon by using virtual reality techniques. Errors in fragment positioning are reported both graphically and numerically with respect to a precomputed optimum fragment position. This guidance system allows multisegment midface osteotomies to be performed more precisely. The main problems encountered so far have been devascularization-infection and difficulties in maintaining correct position during application of rigid fixation. Devascularization-infection problems have been addressed by minimizing surgical exposure of the bone. Soft-fixation plates and temporary Kirschner wire fixation have helped with intermediate positioning, but an intraoperative mechanical positioning device would be useful in the future.

Adolescent↗

PubMed1997

Bone morphogenetic protein promotes vascularization and osteoinduction in preformed hydroxyapatite in the rabbit.

Early reconstruction of large osseous defects in children is often delayed due to limited availability of autogenous bone graft donor sites. With the advent of growth factors, osteoinductive proteins, and delivery matrices, it is possible to fabricate new bone at extraskeletal sites. Due to their own blood supply, adequate bony volume, and decreased resorption, vascularized bone flaps have demonstrated greater success in restoring large bony defects compared with nonvascularized bone grafts. The purpose of this study is to prefabricate a vascularized bone flap in the immature-age rabbit using the auricularis anterior muscle as a muscle pedicle. Sixteen female New Zealand White rabbits, 2.0 to 2.5 kg, were divided into two groups. Group 1 contained 8 animals that had T-shaped, 10 x 6 x 4-mm hydroxyapatite (HA) implants combined with 100-microgram bovine-derived bone morphogenetic protein (BMP) placed supraperiosteally and fixed deep to the auricularis anterior muscle. Implants with HA alone were placed in the same animal and secured to the contralateral auricularis anterior muscle. Group 2 contained 8 animals that had HA/BMP placed subperiosteally and fixed deep to the auricularis anterior muscle, while implants with HA alone were secured in the same animal to the contralateral auricularis anterior muscle. In each group, 4 animals were sacrificed at 4 and 8 weeks. The animals underwent randomized bilateral carotid artery injection with micropaque barium suspension just prior to sacrifice to help maintain vascularity. At harvest the implants and surrounding muscle and cranium were removed en bloc. New bone formation in the HA implants was examined by using routine histology and scanning electron microscopic backscattering image (quantitative) analysis. Microradiographs were performed on representative specimens. At 4 weeks postimplantation, backscattering analysis in the subperiosteal HA/BMP showed a mean 17.1% bone ingrowth vs. 11.3% of HA alone (p < 0.05). Supraperiosteal HA/BMP showed a mean 12.9% bone ingrowth vs. 0% of HA alone (p < 0.05). At 8 weeks, backscatter analysis of supraperiosteal HA/BMP showed a mean 19.33% bone ingrowth vs. 0% of HA alone (p < 0.05). Subperiosteal HA/BMP showed a mean 22% bone ingrowth vs. 20.85% of HA alone. This was the only group that did not have statistically significant results. Implant histology demonstrated woven bone within the interstices of HA/BMP placed either supra- or subperiosteally. In the HA-alone implants placed supraperiosteally, fibrovascular ingrowth was seen without any evidence of bone formation. In the HA-alone implant placed subperiosteally, woven bone was seen at the calvarium-implant junction. Microradiographs also demonstrated vascularization and bone formation similar to that seen on scanning electron microscopy. BMP-treated specimens appeared to have slightly greater vascularity than the nontreated specimens. The greatest bone formation occurred with the HA/BMP implant placed subperiosteally in the immature rabbit. Furthermore, these results demonstrate the potential prefabrication of vascularized bone flaps as early as 4 to 8 weeks. The clinical advantage of HA permits the surgeon to design osseous flaps that are customized in shape, fill all contour defects, and have little resorptive properties. Such prefabricated bone with an axial blood supply may allow for ultimate transfer as a pedicle or free flap to reconstruct osseous defects in children.

Angiography↗

PubMed1997

Intracranial hypertension in a patient with craniofacial synostosis and patent sutures.

Craniosynostosis is often associated with restrictive cranial vault deformities, diminished intracranial volume, and intracranial hypertension. Advances in imaging techniques have provided a method of intracranial volume analysis that has demonstrated a more complicated relationship between craniofacial abnormalities and elevated intracranial pressures. Studies have confirmed a decrease in intracranial volume in the presence of craniosynostosis, but this association is not found in every patient. We report an unusual case of elevated intracranial pressure in a patient with the clinical stigmata of Crouzon's syndrome but with patent cranial vault sutures.

Cranial Sutures↗

PubMed1997

Vector of device placement and trajectory of mandibular distraction.

The role of preoperative planning, the geometric changes, and the long-term effects of mandibular distraction have not been previously reported. This study included 10 patients who underwent unilateral (5 patients) or bilateral (5 patients) mandibular distraction. Preoperative, postdistraction, and yearly radiographs (panoramic, posteroanterior, and lateral cephalograms) were reviewed. Postdistraction follow-up ranged from 12 to 70 months. Postdistraction, the mandibles showed evidence of anticipated growth without relapse. This growth rate was variable and dependent on the genetic program of the native bone. Previously reported improvement in temporomandibular joint morphology was maintained in the long term. The resulting shape of the neomandible was most influenced by the vector of placement of the distraction device. When placed vertically, ramal elongation was observed. When placed horizontally, anterior projection of the mandibular body occurred. When placed obliquely, ramal and body elongation occurred with preservation of the gonial angle. After 2 to 5 years of follow-up, continued growth of the neomandible was observed.

Cephalometry↗

PubMed1997

Immunolocalization of transforming growth factor beta 1, beta 2, and beta 3 and insulin-like growth factor I in premature cranial suture fusion.

The etiology of craniosynostosis remains unknown. The beta group of transforming growth factors (TGF-beta) and insulin-like growth factors (IGF-I and IGF-II) are known to induce new bone formation and, when added exogenously, cause accelerated closure of calvarial defects. The possible roles of these bone growth factors in premature cranial suture fusion in humans have not been explored. We analyzed a total of 20 cranial suture biopsy samples (10 synostotic and 10 normal) from 10 infants with single-suture craniosynostosis undergoing cranial vault remodeling. Using isoform-specific antibodies for TGF-beta 1, -beta 2, and -beta 3 and IGF-I, we demonstrated immunoreactivity of these growth factors were present in human cranial sutures; the TGF-beta 2 isoform was the most intensely immunoreactive. Most importantly, the TGF-beta isoforms and IGF-I showed more intense immunoreactivity in the actively fusing craniosynostotic sutures compared with the control patent sutures. Specifically, the TGF-beta isoforms and IGF-I were intensely localized in the osteoblasts synthesizing new bone at the suture margin. It is noteworthy that although the patent sutures were less immunoreactive for TGF-beta isoforms than fused sutures, there was a distinct pattern of the TGF-beta 3 isoform that was immunolocalized to the margin of the normal patent sutures. This suggests a possible role for TGF-beta 3 in maintaining cranial suture patency. The increased immunoreactivity of both TGF-beta 2 and IGF-I in the actively fusing sutures compared with the patent control sutures indicates that these growth factors may play a role in the biology underlying premature suture closure. To our knowledge, this is the first study showing the presence of TGF-beta 1, -beta 2, and -beta 3 and IGF-I in prematurely fusing human cranial sutures. In the future, manipulating the local expression of these growth factors at the suture site may enable plastic surgeons to modulate premature suture fusion.

Child, Preschool↗

PubMed1997

Histopathologic and biochemical changes in the muscles affected by distraction osteogenesis of the mandible.

Lengthening of the canine mandible using an intraoral distraction device was performed in order to study the effects of distraction on the associated muscles of mastication. Biopsies of the masseter and digastric muscles were taken after lengthening at four different time intervals to assess the temporal changes in the masticatory muscles of 10 dogs. Biopsies of the muscles on the contralateral side also were taken from 6 of these dogs before lengthening to establish a control group. Each biopsy was analyzed histologically and spectophotomerically for RNA, DNA and protein content. The digastric muscle underwent transient atrophy with initiation of distraction but regenerated completely after 48 days of fixation. The masseter muscle was unchanged initially but showed evidence of atrophy only after 20 mm of distraction it continued to exhibit evidence of atrophy during fixation. Protein synthesis was decreased significantly during periods of atrophy in the masseter; no such change was noted in the digastric. Unlike the masseter, the digastric fibers lie in a plane parallel to the vector of distraction. These findings suggest that any muscle affected by skeletal distraction in the same plane or vector (e.g., digastric) adapts with compensatory regeneration and hypertrophy. Moreover, those muscles lying in a different plane (e.g., masseter) show persistent evidence of atrophy with decreased protein synthesis.

Animals↗