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Characteristics of UV-induced repair patches relative to the nuclear skeleton in human fibroblasts.

We have tried to characterize the nucleotide excision repair (NER) events associated with the nuclear skeleton in both repair-proficient and repair-deficient human cell lines following UV irradiation. The repair patches were labelled with biotin-16-dUTP and the repair sites were visualized by fluorescence microscopy using fluorescence-conjugated antibodies to biotin. The intensities of repair labelling measured for the three human cell lines of normal, xeroderma pigmentosum group C (XP-C) and Cockayne syndrome group B (CS-B) are in good agreement with their known repair capabilities. Digestion of nuclei with DNase I markedly solubilized the repair patches in normal (3-fold reduction after 1 h post-UV incubation) and transcription-coupled repair (TCR)-defective Cockayne syndrome cells (6-fold reduction after 1 h post-UV incubation). The intensity of repair labelling remained the same in TCR-proficient XP-C cells after DNase I digestion, indicating that the repair events mediated by the TCR pathway are tightly associated with the nuclear skeleton. Treatment with ammonium sulphate after DNase I digestion further reduced the intensity of repair patches in both normal and Cockayne syndrome cells, but not in XP-C cells. The tight association of repair patches generated by the TCR pathway with the nucleoskeleton in XP-C cells reinforces the concept of functional compartmentalization of the nucleus, where NER is highly heterogeneous.

Cell Nucleus↗

The thick tail mutation contains anomalies of the axial skeleton.

Analysis of the skeletal effects of thick tail (Tht), a radiation-induced mutation, has revealed numerous anomalies in the axial skeleton. The affected regions include the atlantal-occipital region as well as the lumbar (Lu) and caudal (Ca) vertebrae in which the ossified adult structures are either missing or reduced in size. Skeletons of juvenile Tht heterozygotes exhibit a malformed occipital bone, atlas, smaller Ca vertebrae, and delayed ossification of the affected adult structures. The diminished amount of cartilage and bone suggests that the Tht gene may be functioning during the formation of these tissues.

Animals↗

Mobilization of the entire midfacial skeleton: "wing"-shaped midfacial osteotomy.

Hypoplasia and retrusion of the midfacial skeleton may only involve the dentoalveolar area or central facial region (nasal and paranasal [Binder's syndrome]) or the whole midface (paranasal, maxillary, malar, and zygomatic areas). The principal clinical findings are flattened paranasal, cheek, and malar areas. Class III malocclusion or normal dental occlusion can also be present. Treatment of midface retrusion is difficult because the final result depends on a high degree of harmonic aesthetic appreciation, the use of adequate surgical technique (adequate facial osteotomy), and the final relation obtained between soft tissue and facial bones. Many surgical treatments have been proposed for correction of midfacial retrusion. A new osteotomy is proposed involving advancement of maxillary and malar bones and the lower half of both zygomatic arches, when the whole midfacial skeleton is retrused and hypoplastic (both maxillary and malar bones are involved). The orbital osseous structures are not included in the osteotomy; the infraorbitary nerve remains intact. Using this technique, all clinical features are corrected. The advancement and mobilization of the whole body of the maxillary and malar bones along the lower part of the zygomatic arch contribute to three-dimensional facial reconstruction because they produce an increase in anteroposterior projection of the middle third facial region. Rigid internal fixation by means of miniplates and screw of 1.5 or 2 mm on four principal maxillary buttresses is used. No onlay bone grafts are used for obturing the gaps of osteotomy.

Adult↗

Dismantling and reassembling of the facial skeleton in tumor surgery of the craniomaxillofacial area. History, surgical anatomy, and notes of surgical technique: Part 1.

In recent years, access osteotomies have been suggested to reach areas of the craniofacial skeleton that hitherto would not have been easily resectable. Some techniques of disassembling of the facial skeleton have been described in the past. In some cases, however, when the bony fragments were not pedicled to the soft tissue, reabsorption was noted. For this reason, new dismantling techniques with adequate blood supply to the bony fragments have been developed. Apart from the maxillo cheek flap, other composite flaps have been described. These flaps may be combined if necessary in selected cases. An overview of the surgical anatomy and surgical strategies will be presented. These reported techniques may be considered a major step forward in the treatment of deeply localized tumors in the craniomaxillofacial area.

Cheek↗

CT-based size and shape determination of the craniofacial skeleton: a new scoring system to assess bony deformities in hemifacial microsomia.

The purpose of this study was to design a better craniofacial classification system for bony deformities in patients with hemifacial microsomia than the existing ones. It was meant to incorporate the deformity of the craniofacial skeleton other than that of the mandible. The "Mandibular Deformity Scoring" System (MDS), the "Cranial Deformity Scoring" System (CDS), the the "Craniofacial Deformity Scoring" System (CFDS) are three newly developed classification systems, which are based on three-dimensional computed tomography (3-D CT) reconstructions. The size and shape of the craniofacial structures of 34 children, 25 with hemifacial microsomia and 9 with minimal dysplasia or trauma, were determined from CT scans, using 3-D image segmentation and rendering. Contiguous 1.5-mm CT scans were made using a Philips Tomoscan 350 and were processed using a Cemax 1500X 3-D workstation. The precision of the 3-D imaging was assessed by repeated determinations carried out by two observers (intra- and interreliability). Accuracy of the bone determination technique was assessed by comparing the interpretations of the craniofacial skeleton by 3-D CT reconstructions of laser-stereolithographic 3-D models. Correlations of the Pruzansky/Kaban classification system and the newly developed classification systems were demonstrated by the use of the Pearson product moment correlation coefficients. The new CFDS (= CDS + MDS) provides an adequate basis for assessment of bony structures using three-dimensional imaging and demonstrates a high correlation with the known Pruzansky/Kaban classification system. This new scoring system can handle the wide variety of individual variation of the deformity seen in patients with hemifacial microsomia better than the existing scoring systems.

Case-Control Studies↗

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters.

We have investigated the role of the allylic 7-ketone in oxidized Delta5-steroids on antileukemic activity. We synthesized and studied a series of oxidized and non-oxidized steroidal esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto derivatives, on a molecular basis, regarding their ability to induce sister chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular basis, correlated well with their antileukemic potency against leukemia P388- and L1210-bearing mice, which proved to be significantly increased compared to that of the non-oxidized derivatives. Our results indicate that the role of the steroidal skeleton it is not only for the transportation of the alkylating agent into the cell, but also contributes directly to the mechanism of antileukemic action, by an as-yet unknown way. The main conclusion from this study is that the existence of the allylic 7-keto group in the skeleton of the Delta5-steroidal esters impressively enhances their antileukemic activity, while the toxicity remains at clinically acceptable levels, suggesting that this structural modification should be further investigated.

Androstenes↗

Cold defects in in-111 labeled leukocyte imaging of osteomyelitis in the axial skeleton.

Use of In-111 oxine labeled leukocytes in the detection of osteomyelitis of the peripheral skeleton usually presents few problems. However, the diagnosis of osteomyelitis is more difficult in marrow-bearing areas because uptake of indium is normal. Sixty-one In-111 labeled leukocyte scans, that had been performed to exclude osteomyelitis of the axial skeleton, pelvis, and proximal long bones, were reviewed. Eight cold defects were identified at sites of suspected osteomyelitis. Five of these were surgically proven osteomyelitis. Nineteen percent of all cases of osteomyelitis in these areas (5 of 26) presented as cold defects. This incidence of osteomyelitis presenting as cold defects is higher than previously reported. Therefore, the possibility of osteomyelitis should be strongly considered when a cold defect is identified in red marrow areas.

Humans↗

Marrow transplantation and targeted gene therapy to the skeleton.

Treatment of genetic or degenerative diseases severely affecting the entire skeleton may necessitate gene therapy involving transplantation of multipotential marrow cells. The ability of in vitro expanded adherent marrow cells enriched in pluripotent mesenchymal cell populations to remain competent to engraft, repopulate host tissues, and differentiate into bone and cartilage is advantageous for correction of skeletal-related diseases. However, to achieve phenotypic specificity and therapeutic or physiologic levels of proteins may require cell type specific expression of the gene. Tissue-specific promoter-controlled transgenes provide an efficacious approach to deliver therapeutic gene expression to repopulating chondrocytes and osteoblasts for treatment of cartilage and bone disorders or tumor metastasis to the skeleton. The bone-specific expression of a reporter gene controlled by the osteoblast-specific osteocalcin promoter after transplantation of a mixed population of marrow cells is shown. Tissue-restricted gene therapy potentially can be refined by use of a unique peptide targeting signal that directs the hematopoietic, chondrogenic, and osteogenic core binding factor/acute myelogenous leukemia transcription factors to subnuclear sites that support gene expression.

Animals↗

Bone mineral measurements of the central skeleton by in vivo neutron activation analysis for routine investigation os osteopenia.

In vivo neutron activation analysis has been used to measure bone mineral content in the central skeleton where osteoporotic fractures occur. To be of diagnostic value, the results must be normalized for body size. From data obtained from 74 healthy children and adults up to 55 years of age, we have found that the calcium in the central skeleton is approximately proportional to the cube of the subject's height. The correlation for the adults alone has an r value of 0.81. When data from both adults and children are used, r = 0.95. The validity of this cubic height relationship to the Ca concentration measurements has been further substantiated by studies on rats. The total femur calcium content of 110 rats from weanling to 25 weeks of age was proportional to the overall femur (length) 3.6 (or (length)2.6 per unit length) with r = 0.99. When the level of Ca content is related to data on normal subjects of the same body size (giving the Calcium Bone Index or CaBI) a good separation is obtained between normal volunteers and osteoporotic subjects. Volunteers who were 20 to 55 years of age had CABI 1.0 "/- .12 (SD) while osteoporotics had CaBI 0.69 +/- .10 (SD). When the calcium content as determined by in vivo activation analysis is expressed as a CaBI, it provides a powerful tool for the diagnosis of osteopenia. We suggest that all bone measurements, including peripheral ones, be normalized for body size in order to increase their diagnostic value.

Activation Analysis↗

Cranial nerve VII region of the traumatized facial skeleton: optimizing fracture repair with the endoscope.

OBJECTIVE: Cranial nerve VII (CN VII) is anatomically positioned adjacent to the condylar neck of the mandible and arch of the midface. Fracture treatment of this region of the facial skeleton remains controversial because of difficult surgical access. Conservative management rarely achieves anatomic fracture repair and can result in irreversible structural deformity and dysfunction. Traditional operative methods require access through very visible facial incisions and risk injury to the facial nerve. We report endoscopic methods of facial fracture repair in the region of CN VII that achieve excellent fracture reduction and stabilization, with minimal risk of facial nerve injury by using hidden incisions. METHODS: A consecutive series of 65 endoscopically assisted facial fracture repairs were analyzed. Endoscopic repairs of the condylar neck (n = 40) of the mandible were performed through an intraoral incision. Endoscopic arch repairs (n = 25) of the midface were performed through a preauricular incision. Outcomes were evaluated by postoperative fracture reduction on radiographs, occlusion, interincisal jaw opening, and facial nerve function. RESULTS: Thirty-seven of 40 condylar neck mandible fractures went on to anatomic bone union, whereas 3 of 40 had either incomplete fracture reduction or re-fracture through the plate. There was one temporary palsy of CN VII that completely resolved spontaneously. Jaw opening exceeded 40 mm by the 8th postoperative week. Computed tomographic images demonstrated anatomic arch repair in all 25 endoscopically repaired cases. Six of seven endoscopically repaired Le Fort III facial fractures went on to restoration of their premorbid occlusion. One of seven had an excellent restoration of the occlusal interface but a cant to the occlusal plane. Two of seven had improved but incomplete restoration of the malar prominence and enopthalmos ipsilateral to the side of endoscopic arch repair. Eight of 25 endoscopic arch repairs developed temporary paralysis of the frontal branch of CN VII that recovered completely by the 10th postoperative week. CONCLUSION: We have developed novel endoscopically assisted techniques to facilitate repair of facial fractures in the region of CN VII. These techniques have been successfully applied to accurately restore the facial skeleton to its preinjury anatomic position in the region of CN VII with minimal risk of facial paralysis by using limited and well-hidden incisions.

Adolescent↗

Blood supply of the upper craniofacial skeleton: the search for composite calvarial bone flaps.

This study investigated the blood supply of the upper craniofacial skeleton by injection studies. The major supply to the calvaria is provided by the middle meningeal artery and its branches. This vessel is difficult for the plastic surgeon to exploit in composite bone-flap design. The majority of the outer surface of the craniofacial skeleton is supplied by tiny perforators from the overlying periosteum. The vascular interconnections within the periosteum are poorly developed. For this reason, the galea and the overlying vascular network (derived from the superficial temporal, occipital, supraorbital, and supratrochlear vessels) should be left broadly attached to the bone when transferring a vascularized calvarial bone flap. Dissection of the scalp away from this vascular network should be carried out just below the hair follicles. By observing these principles, vascularized calvarial bone can be transferred on the superficial temporal, deep temporal, supraorbital, supratrochlear, or occipital vessels. Details of the use of each are discussed.

Adult↗

An experimental study on the effect of rigid fixation on the developing craniofacial skeleton.

Rigid fixation of the craniofacial skeleton has proven of great value in adult orthognathic and traumatic reconstructive surgical procedures. This technique has gained increased acceptance in the surgical treatment of infants and young children with congenital malformations, despite the fact that its effects on subsequent craniofacial growth are unknown. To examine this question, an experimental model using 25 young kittens was developed to compare rigid fixation with conventional wire fixation, with and without osteotomy. Our findings demonstrate a regional restriction of growth in the developing craniofacial skeleton when both wire and plate and screw fixation are utilized in concert with osteotomy. Further, a compensatory growth was observed in individual animals when plate fixation was utilized that was not seen in the wire-treated group. This suggests that there is a dynamic growth interaction between restriction and compensation in this setting.

Animals↗

Age-related changes of the craniofacial skeleton: an anthropometric and histologic analysis.

With the development of increasingly sophisticated methods for the alteration of bony facial form consequent to age, it is imperative that the surgeon have a fundamental knowledge of the age-related changes the skeleton may undergo. To understand these changes better, a detailed anthropometric and histomorphic analysis of the craniofacial skeleton as a function of age was undertaken. The study consisted of a detailed craniometric analysis of 160 skulls selected randomly from a Caucasian population of skeletal remains totaling 1500 specimens. Additionally, a histologic analysis of the supraorbital ridge in a separate preserved cadaver population was performed. Although the results showed individual variation as expected, definite changes in craniofacial morphology were observed. These included (1) appreciable reduction of facial height, most marked in the maxilla and mandible, and strongly correlated with loss of teeth, (2) modest increase in facial width, (3) modest increase in facial depth, except in those regions associated with tooth loss, and (4) general coarsening of bony prominences. Histomorphic analysis demonstrated increasing porosity with age, more marked in the female population. Although these changes represent population trends, in any given patient, any or all of them may be present to varying degrees. Surgeons should be aware of these possibilities and consider selective alterations of the skeletal foundation, either separately or in concert with the overlying soft-tissue envelope, in order to optimize the results of surgery for the aging face.

Adult↗

Cyanoacrylate fixation of the craniofacial skeleton: an experimental study.

This study examined the feasibility of achieving bone fixation of the upper facial skeleton using n-butyl-2-cyanoacrylate. We compared the fixation obtained with this adhesive to that obtained with plates and screws in an animal model. The stability of fixation of both osteotomies and onlay grafts was studied in six minipigs. Three osteotomies were performed on each side of the skull. Additionally, a parietal split-thickness autograft was fixated to the nasal bone as an onlay. Plates and screws were used on the right and adhesive on the left. The animals were killed at 6 weeks, and both sides were compared biomechanically and histologically. Clinical assessment showed stability of all fragments. No statistical difference was found in the comparison of the maximum torque to failure between analogous plated and glued sides. Radiographic cephalometry revealed no significant displacement of the fragments. Histologic analysis demonstrated bony union. In this study, n-butyl-2-cyanoacrylate was as effective as plates and screws in the fixation of surgically created osteotomies of the upper facial skeleton.

Animals↗

SMAS fixation to the facial skeleton: rationale and results.

The trend in modern facial rejuvenation surgery is to reposition the ptosis of the superficial soft-tissue mass relative to the facial skeleton. The logical method of supporting the superficial tissue is to reattach it to the underlying skeleton, thereby replicating the function of the retaining ligaments. Five hundred consecutive face lifts involving deep fixation of the submucosal aponeurotic system flap to the periosteum of the zygoma were reviewed for complications and side effects. Expected complications, such as irregularities, dimpling, and palpable sutures, occurred in fewer than 1 percent of cases, confirming the safety of this method. The conclusion from this experience is relevant to all methods of deep-layer facial rejuvenation surgery, including the endoscopic approach.

Humans↗

Distraction osteogenesis of the craniofacial skeleton.

In summary, distraction osteogenesis is a safe and effective means of achieving bone lengthening. These techniques were originally applied to the long bones of the extremities; over the past 10 years they have been effectively applied to the bones of the craniofacial skeleton. The new bone regenerate that is observed after distraction osteogenesis is stable, and relapse rates after skeletal advancement are believed to be lower than with conventional osteotomy and bone graft techniques. There is considerable variability in distraction protocols employed in clinical practice, including differences in the types of devices used and in the rate, rhythm, latency, and period of consolidation for distraction osteogenesis. The greatest application for distraction osteogenesis in the craniofacial skeleton has been with mandible lengthening, for which there is presently a 10-year clinical experience. Midfacial advancement is a newer application of distraction osteogenesis, for which clinical experience has been accrued over the past 5 years. This latter experience indicates that distraction osteogenesis is a viable treatment option for lengthening of the hypoplastic mandible and midface. These techniques have advantages over conventional means of bone graft and rigid fixation because of the quality of the bone regenerate, the decrease in the long-term relapse rate of the advanced bone segments in both the mandible and the midface, and the simultaneous soft-tissue elongation that accompanies the distraction process. Distraction osteogenesis is particularly applicable to the correction of severe deformities of the mandible and midface in children with developmental hypoplasia and syndromic craniosynostosis. However, growth is an added variable in this patient population. The amount of overcorrection in lengthening of the hypoplastic bone required to compensate for continued growth discrepancy of the adjacent facial bones is difficult to predict. Therefore, the families of these patients should be informed that many children will require repeated operations at a later age as they reach skeletal maturity.

Child↗

The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats.

BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no significant effect on cancellous or cortical bone measurements. CONCLUSIONS: Chronic alcohol consumption significantly reduced bone formation. Exercise had no effect on the bone and did not attenuate any of the negative effects of alcohol. The results suggest that alcohol consumption weakens the skeleton and increases the incidence of endurance-exercise-related bone injuries. Thus, individuals who are participating in endurance exercise and consuming alcohol may be at greater risk for exercise-related skeletal injuries. Further investigation of the potential for alcohol to induce detrimental effects on the hearts of individuals participating in endurance exercise is indicated.

Alcohol Drinking↗

Assessment of the effects on growth of porous hydroxyapatite granule cranioplasty in the immature guinea pig craniofacial skeleton.

The immature guinea pig was used to study the effects on growth of porous granular hydroxyapatite used as an onlay cranioplasty and inlay cranioplasty to reconstruct full-thickness cranial defects in a growing craniofacial skeleton. Forty Hartley guinea pigs, 20 immature animals and 20 mature animals, were divided into four groups each containing five mature and five immature animals. The mature animals served as controls. Group I underwent elevation and replacement of the parietal periosteum. Group II underwent placement of hydroxyapatite between periosteum and parietal bone. Group III underwent elevation and replacement of autogenous bone flap after the formation of a 1 x 1-cm craniectomy defect in the parietal skull. Group IV underwent elevation of a 1 x 1-cm parietal craniectomy and reconstruction of the defect with hydroxyapatite granules placed between the dura and periosteum. Immature animals were killed at maturity at 3.5 months and mature animals were killed 2.5 months postoperatively. Macroscopic examination of the operative field, transverse and longitudinal cephalometric measurements, and histological sections encompassing the operative sites were compared. Macroscopically, all reconstructed operative sites were fully incorporated into the cranium. Histological staining of the sectioned operative site revealed no hydroxyapatite migration through the cranial bone or dura. No inflammatory or foreign body reaction was evident in the subcutaneous tissue, periosteum, or dura. No statistically significant cephalometric intergroup or intragroup differences were found at the conclusion of the study. The results of this study indicate that a granular porous form of hydroxyapatite may be used as an onlay or inlay cranioplasty in the immature guinea pig craniofacial skeleton without evidence of dural inflammation, granule migration, or growth restriction or retardation.

Age Factors↗