Hakan Orbay

Nippon Medical School, Sendai, Kagoshima-ken, Japan

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Publications (49)76.56 Total impact

  • Article: Molecular Imaging Strategies for In Vivo Tracking of MicroRNAs: a Comprehensive Review.
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    ABSTRACT: MicroRNAs (miRNAs) are single-stranded non-coding RNAs of ~22 nucleotides, which can negatively regulate gene expression through induction of mRNA degradation and/or post-transcriptional gene silencing. MiRNAs are key factors in the regulation of many biological processes such as cell proliferation, differentiation, and death. Since miRNAs are known to be in close association with cancer development, non-invasive imaging of miRNA expression and/or activity is of critical importance, for which conventional molecular biology techniques are not suitable or applicable. Over the last several years, various molecular imaging techniques have been investigated for imaging of miRNAs. In this review article, we summarize the current state-of-the-art imaging of miRNAs, which are typically based on fluorescent proteins, bioluminescent enzymes, molecular beacons, and/or various nanoparticles. Non-invasive imaging of miRNA expression and/or biological activity is still at its infancy. Future research on more clinically relevant, non-toxic techniques is required to move the field of miRNA imaging into clinical applications. Non-invasive imaging of miRNA is an invaluable method that can not only significantly advance our understandings of a wide range of human diseases, but also lead to new and more effective treatment strategies for these diseases.
    Current Medicinal Chemistry 05/2013; · 4.86 Impact Factor
  • Article: Preclinical Efficacy of Slow-Release bFGF in Ischemia-Reperfusion Injury in a Dorsal Island Skin Flap Model.
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    ABSTRACT: The effect of slow-release basic fibroblast growth factor (bFGF) on ischemia-reperfusion injury was examined using an island skin flap model in rats. Paired rectangular island skin flaps were elevated on the dorsum of 30 Fischer rats. The flaps were subjected to 6 hours of ischemia. Before reperfusion the flaps were injected with acidic gelatin hydrogel microspheres + phosphate-buffered saline (PBS) (group I), 20 μg slow-release bFGF + PBS (group II), 50 μg slow-release bFGF + PBS (group III), and 150 μg slow-release bFGF + PBS (group IV). The mean percent flap survival area and the average number of vessels detected by microangiography were significantly higher in group IV (p < 0.05) than in groups I, II, and III. The immunohistochemical staining for vasculogenic growth factors was quantitatively higher in group IV (p < 0.01). In conclusion, slow-release bFGF prevents ischemia-reperfusion injury by upregulating the secretion of vasculogenic growth factors.
    Journal of Reconstructive Microsurgery 04/2013; · 1.43 Impact Factor
  • Article: Concentration of PDGF-AB, BB and TGF-β1 as Valuable Human Serum Parameters in Adipose-derived Stem Cell Proliferation.
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    ABSTRACT: Introduction: Human serum (HS) has attributes similar to fetal bovine serum (FBS) in the proliferation and differentiation of human adipose-derived stem cells (hASCs) when compared in vitro. The purpose of this study was to determine what types of HS, with respect to the concentrations of endogenous growth factors, could be made available for hASC proliferation. Methods: HS was collected from 2 groups of healthy donor (freshly isolated HS [n=9], and HS preserved for 4 years [n=7]). All sera were isolated with a Cellaid(®) HS isolation device (JMS Co., Ltd, Hiroshima, Japan) and then classified into 3 groups based on the concentrations (high, middle, and low) of platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor-beta 1 (TGF-β1) by means of enzyme-linked immunoassay screening. The hASCs were isolated from subcutaneous fat using a collagenase enzymatic digestion process and were cultured in control media, each supplemented with HS from a different group. Cell numbers were counted on days 2, 4, 7, and 14, and the relationship between cell proliferation and the level of each growth factor was investigated. Results: The proliferation of hASCs correlated with the concentration of each growth factor. The cut-off points for PDGF-AB, PDGF-BB, and TGF-β1 in HS [necessary for hASC proliferation when compared with FBS] were 10 ng/mL, 1.5 ng/mL, and 15 ng/mL, respectively. There was no correlation between the storage period of HS and the proliferation potential of hASCs. Conclusions: These results suggest that the effectiveness of HS on hASC proliferation depends on the concentrations of endogenous PDGFs. In addition, the Cellaid(®) device used in this study allows the simultaneous release of several growth factors from platelets, and our results have shown that it can be used to collect HS for future hASC-based therapies.
    Journal of Nippon Medical School 01/2013; 80(2):140-7.
  • Article: Reconstruction of sternal defects with pectoralis major muscle flap
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    ABSTRACT: The earliest treatment of the median sternotomy defects was serial debridements and secondary healing. The muscle flaps that can be used in reconstruction of the presternal defects are pectoralis major muscle flap, rectus abdominis muscle flap, vertical rectus abdominis muscle flap, latissimus dorsi muscle flap with or without skin island, bipedicled pectoralis-rectus muscle flap, and external oblique muscle flap. Pectoralis major muscle flap can be used either as bilateral or unilateral rotation advancement flap, island flap, turnover flap, split turnover flap, and segmental muscle flap. Forty-eight patients with median sternotomy defects, who were treated with pectoralis major muscle flap, were included in this study. The complications were mortality, flap loss, flap dehiscence, persistent infection, and hematoma. The patients were evaluated in terms of functional loss after the operation by shoulder movement measurements. Various techniques of flap transfer can be used for the closure of a presternal defect; almost all presternal defects can be covered with the pectoralis major muscle in a single stage operation. In our opinion, the pectoralis major muscle flap should be the first choice of treatment for sternal defects.
    European Journal of Plastic Surgery 04/2012; 30(5):223-228.
  • Article: Effects of adipose-derived stem cells on improving the viability of diced cartilage grafts.
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    ABSTRACT: Diced cartilage grafts are useful for dorsal nasal augmentation; however, long-term resorption usually occurs. The aim of this study was to examine the effects of adipose-derived stem cells on the viability of diced cartilage grafts. Twenty Fischer rats were divided into four groups with diced cartilage grafts wrapped in the following components: abdominal fascia (group I), Surgicel (group II), abdominal fascia plus adipose-derived stem cells (group III), or Surgicel plus adipose-derived stem cells (group IV). Grafts were placed subcutaneously along the dorsal midline, and the weights were recorded both before implantation and after explantation. Histologic examination was performed after 8 weeks using hematoxylin and eosin, safranin O, van Gieson, glial fibrillary acid protein, and von Willebrand factor immunofluorescence staining. The percentage reduction in weight, indicating resorption, was significantly lower in group III (p < 0.01). Both the number of nucleated lacunae per unit area and the proteoglycan content were significantly higher in group III compared with the other groups (p < 0.05). Elastic fibers around the regenerating cartilage islands were seen by van Gieson staining in the fascia groups but not in the Surgicel groups. Glial fibrillary acid protein was also significantly higher in group III (p < 0.01). There was no statistically significant difference in vascular density among the treatment groups (p > 0.05). These findings suggest that adipose-derived stem cells can maintain the viability of diced cartilage, although the exact mechanism remains to be defined. Because adipose-derived stem cells are autologous and easy to harvest, they may be useful for improving the long-term outcomes of diced cartilage grafting.
    Plastic and reconstructive surgery 02/2012; 129(2):369-77. · 2.74 Impact Factor
  • Article: Nuclear magnetic resonance spectroscopy as a useful tool for ingredient analysis of synthetic materials.
    Plastic and reconstructive surgery 01/2012; 129(1):197e-198e. · 2.74 Impact Factor
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    Article: Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications.
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    ABSTRACT: Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.
    Stem cells international. 01/2012; 2012:461718.
  • Article: Altered expression of apoptosis-related genes in human dermal microvascular endothelial cells in high-glucose condition.
    Wound Repair and Regeneration 01/2012; 20(1):A7. · 2.91 Impact Factor
  • Article: Differentiated and undifferentiated adipose-derived stem cells improve function in rats with peripheral nerve gaps.
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    ABSTRACT: The effect of differentiated and undifferentiated adipose-derived stem cells on the repair of peripheral nerve gaps was studied. Adipose-derived stem cells were maintained in differentiation medium for 2 weeks. The expression of Schwann cell proteins S-100, nerve growth factor receptor (NGFR) p75 and integrin β4 was examined by immunofluorescence staining and real time-polymerase chain reaction (real time-PCR) at the end of the differentiation period. A 10-mm gap on the left sciatic nerves of 20 Fischer rats was created and bridged with silicone tube (group I), silicone tube filled with collagen gel (group II), nerve graft (group III), silicone tube filled with adipose-derived stem cells (group IV) and silicone tube filled with differentiated adipose-derived stem cells (group V). In vitro, the positivity of differentiated adipose-derived stem cells for S-100, NGFR p75 and integrin β4 by immunofluorescence staining was 31%, 27% and 12%, respectively. Fold changes by real time-PCR in comparison with undifferentiated cells were 48.4, 168.7 and 284.85, respectively. In vivo, a walking track analysis did not yield any statistically significant differences after 3 months postoperatively; however, after 6 months, group IV (sciatic function index (SFI) = -49.1 ± 13.1) and V (SFI = -52.6 ± 5.7) showed significant improvement compared to other groups (I: -73.3 ± 5.07, II: -79.6 ± 12.01, III: -74.8 ± 12.89) (p < 0.05). Nerve conduction velocity after 6 months was higher in groups IV (4.44 ± 0.3 mm ms(-1)), V (4.25 ± 0.3 mm ms(-1)) and III (4 ± 0.3 mm ms(-1)) than in groups I (2.5 ± 2.25 mm ms(-1)) and II (2.35 ± 1.58 mm ms(-1)) (p > 0.05). Myelin fibre density and myelinated fibre/unmyelinated fibre ratio were significantly higher in the midnerve and the distal nerve in groups IV and V (p < 0.05). These results reveal the therapeutic potential of adipose-derived stem cells in nerve reconstruction.
    Journal of Plastic Reconstructive & Aesthetic Surgery 12/2011; 65(5):657-64. · 1.49 Impact Factor
  • Article: The use of NMR spectroscopy for identifying unknown foreign materials after aesthetic procedures.
    Journal of Plastic Reconstructive & Aesthetic Surgery 10/2011; 65(5):692-4. · 1.49 Impact Factor
  • Article: A 5-year assessment of safety and aesthetic results after facial soft-tissue augmentation with polyacrylamide hydrogel (aquamid): a prospective multicenter study of 251 patients.
    Plastic and reconstructive surgery 07/2011; 128(1):325-6; author reply 326-7. · 2.74 Impact Factor
  • Article: An objective evaluation of an injured vessel wall using fluorescein sodium before microvascular anastomosis in an experimental rat model.
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    ABSTRACT: The aim of this study was to establish an objective evaluation method for intraoperative detection of damaged vascular endothelium in avulsion injuries. Twenty male Fischer rats were randomly assigned to control or experimental groups ( N = 10, each). Crush-avulsion injury was performed on right femoral arteries. Resection of damaged segments was performed according to operative microscopic findings in the control group; fluorescein sodium was applied to the artery lumen before resection in the experimental group to help visualize the damaged endothelium. Microvascular repair was performed in five rats in each group. In the other animals, the whole length of the femoral arteries was resected to assess the actual extent of injury histologically. At the end of the follow-up period, patency of microvascular anastomoses was examined and the lengths of the resected segments were compared with the actual length of the injured segment measured histologically. The difference between these two measurements was statistically significant in the control group ( P < 0.05) but not in the experimental group ( P > 0.05). Anastomosis patency was significantly higher in the experimental group ( P < 0.0001). In conclusion, fluorescein sodium may help to accurately determine the length of the injured vascular segment in avulsion injuries.
    Journal of Reconstructive Microsurgery 05/2011; 27(5):321-6. · 1.43 Impact Factor
  • Article: Distally based superficial sural artery flap excluding the sural nerve.
    Plastic and reconstructive surgery 04/2011; 127(4):1749-50; author reply 1750-1. · 2.74 Impact Factor
  • Article: Acellular dermal matrix seeded with adipose-derived stem cells as a subcutaneous implant.
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    ABSTRACT: Soft tissue augmentation using autologous materials usually is associated with high resorption rates. To obtain more durable soft tissue filler, acellular dermal matrix (ADM) was seeded with adipose-derived stem cells (ASCs) in this study. For ADM preparation, split-thickness skin was obtained from the dorsum of two Fischer rats. Harvested skin was acellularized to obtain ADM and subsequently seeded in vitro with ASCs isolated from the same rats. Subcutaneous soft tissue augmentation was carried out in the dorsal area of 20 Fischer rats. The implant materials were ADM (group 1), ADM with ASCs (group 2), collagen type 1 gel (group 3), and collagen type 1 gel with ASCs (group 4). Each specimen was harvested after 8 weeks for quantitative evaluation of thickness, vascular density, and collagen content. Histologic analysis showed that ASCs were successfully seeded onto ADM. The thickness of the implanted material and the vascular density were highest 8 weeks postoperatively in group 2. The subpanniculus layer became significantly thicker in group 3 than in group 4. The collagen content was significantly higher in group 2 than in the other groups. These findings suggest that ADM seeded with ASCs forms the best implant material in terms of volume maintenance, vascular density, and collagen content.
    Aesthetic Plastic Surgery 03/2011; 35(5):756-63. · 1.41 Impact Factor
  • Article: Adipose-derived stem cells: current findings and future perspectives.
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    ABSTRACT: Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.
    Discovery medicine 02/2011; 11(57):160-70.
  • Article: Perforating arteries of the anteromedial aspect of the thigh: an anatomical study regarding anteromedial thigh flap.
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    ABSTRACT: Because the skin of anteromedial thigh region usually is thinner, pliable, hairless it can be preferred based on the requirements of the recipient site. In this way more information is necessary about the perforators of anteromedial thigh region. The aim of this cadaveric study was described to provide useful knowledge about localizations and number of anteromedial thigh perforators. Study was carried out on 16 lower extremities of 9 cadavers. The area in anteromedial aspect of the thigh searched for perforators was defined between the anterolateral border of sartorius and the posterior border of gracilis. The diameters of the dissected perforators were measured and the locations were documented. A total of 204 perforators were dissected in 16 lower extremities. The majority of musculocutaneous perforators were from gracilis (24 of 37) and there were at most 3 musculocutaneous perforators arising from gracilis muscle. 167 septocutaneous perforators were identified. Origin of all perforators was determined as 52 from deep femoral artery, 25 from proximal part of femoral artery and 127 from distal part of femoral artery and their branches. Perforators with the largest diameter were the ones arising from the intermuscular septa between the adductor (longus and magnus) and sartorius muscles. The mean diameter of the perforators was 0.75 ± 0.11 mm and ranged between 0.61 and 0.96 mm. The septocutaneous perforators of the anteromedial aspect of the thigh are as much important as the musculocutaneous perforators and all they are with adequate to perform anteromedial thigh flap. This study provides numerical overview, useful perception about the localization of the perforators of the anteromedial aspect of the thigh and detailed anatomical basis for anteromedial thigh flap to be an important alternative.
    Anatomia Clinica 10/2010; 33(3):241-7. · 0.93 Impact Factor
  • Article: The utilization of teres major muscle in facial paralysis reanimation: an anatomic study.
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    ABSTRACT: This study explores vascular and morphologic anatomy of the teres major muscle, which can be an alternative to donor muscles used in functional muscle transfer in long-standing facial paralysis reanimation. A total of 14 teres major muscles from 7 embalmed cadavers were dissected and examined. Diameters and lengths of major and minor arteries supplying the muscle, venous pedicle diameter, neural pedicle diameter and length, their entrances into the muscle, the extendibility of neurovascular pedicles, when necessary, and the morphology of muscle were evaluated. Mean results obtained for teres major muscle in the study were as follows: the longest distance between the starting point and the area where the tendon started was 17.1 +/- 0.34 cm (range, 14.5-18.8 cm), the distance between the widest points was 5.8 +/- 0.5 cm (range, 5.1-6.2 cm), the thickest area was 3.4 +/- 0.9 cm (range, 2.8-3.9 cm), and surface area was 58.2 +/- 1.02 cm2 (range, 48.1-62.7 cm2). The major pedicle of the muscle, which is type 2 according to Mahtnes-Nahai classification, has a length of 3.0 +/- 0.6 cm (range, 2.4-3.6 cm) and a diameter of 2.7 +/- 0.21 mm (range, 1.85-3.4 mm). The nerve that provides motor innervation to the muscle is 5.9 cm (range, 4.1-9.9 cm) in length and 1.7 mm (range, 1.2-2.5 mm) in diameter. As a result of this preliminary study, we think that morphologic and neurovascular structures of this muscle is suitable for use in long-standing facial paralysis reanimation.
    The Journal of craniofacial surgery 06/2009; 20(3):926-9. · 0.81 Impact Factor
  • Article: Vascular anatomy of the metatarsal bones and the interosseous muscles of the foot.
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    ABSTRACT: Utilization of the metatarsal bones and interosseous muscles in foot reconstruction should be based on the vascular anatomy of the metatarsal bones and interosseous muscles. We studied the vascular anatomy of the metatarsal bones and the interosseous muscles to design a split metacarpal musculoosseous flap and dorsal interosseous muscle flap. Twenty-two feet from eleven cadavers that had been embalmed in formalin were studied. Dissection was done using a dissection microscope (x3.5), delineating meticulously the arcuate artery, dorsal metatarsal arteries and the small branches arising from the metatarsal arteries. The dorsal metatarsal arteries do not course at the midline of the interosseous muscles. The first dorsal metatarsal artery proceeds close to the first metatarsal bone in the first metatarsal space. While proceeding to the distal, it shoots out a branch that individually feeds the lateral head of the first dorsal metatarsal muscle and medial face of the second metatarsus, thereby feeding muscle and bone. Except for this branch, the first dorsal metatarsal gives off segmental and periosteal branches that individually feed the medial heads of the first dorsal metatarsal muscle and first metatarsal bone. The second, third and fourth metatarsal arteries proceed close to the third, fourth and fifth metatarsal bones in the metatarsal spaces. In these courses, the arteries give out segmental branches to both faces of the interosseous muscles and periosteal branches to the medial face of metatarsal bones. For defects or disease of the ankle bones, the metatarsal bones can be split at the medial border distally, and a split metatarsal musculoosseous flap, based proximally on the dorsal metatarsal artery, can be done. Distal intermetatarsal anastomoses between the dorsal and plantar vascular networks enables a split metatarsal musculoosseous flap based distally, including the dorsal metatarsal artery for bony defects of the proximal phalanx.
    Journal of Plastic Reconstructive & Aesthetic Surgery 07/2008; 62(9):1227-32. · 1.49 Impact Factor
  • Article: Innervation of three weight-bearing areas of the foot: an anatomic study and clinical implications.
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    ABSTRACT: The aim of this cadaver study is to improve our knowledge on the anatomy of the sensory fibres of the three weight-bearing areas of the plantar region. Previous studies mainly focused on the innervation of the heel but the innervation of the other two weight-bearing areas over the most medial and lateral metatarses have been neglected and are not well known. The study was carried out on 10 feet of five male cadavers. The tibial nerve was dissected down to the fat pads over the heel and the first and fifth metatarsal heads under the microscope. The distances of the branching point of the tibial nerve and origins of the medial and inferior calcaneal nerves to a line drawn from the centre of the medial malleolus to the centre of the calcaneous were all measured. The tibial nerve was divided into two branches called the lateral and medial plantar nerves 23.45 mm proximal to the predefined axis. The medial plantar nerve passed underneath the abductor hallucis muscle and gave two sensory branches to the fat pad over the first metatarsal head. The lateral plantar nerve coursed beneath the abductor hallucis and flexor digitorum brevis muscles and supplied innervation of the fat pad over the fifth metatarsal head. The sensory innervation of the heel was provided by medial calcaneal and inferior calcaneal nerves. The medial calcaneal nerve originated from the tibial nerve 41.89 mm proximal to the axis. It divided into two or three branches innervating the fat pad over the heel. The inferior calcaneal nerve originated from the lateral plantar nerve (70%) or the medial calcaneal nerve (30%) 10.66 mm proximal to the axis. This study describes the sensory fibres to the heel and the previously neglected weight-bearing areas over the first and fifth metatarses. Reconstruction of defects in these areas is very difficult so every attempt should be made to protect the sensory fibres during any surgical procedure.
    Journal of Plastic Reconstructive & Aesthetic Surgery 02/2008; 61(5):557-61. · 1.49 Impact Factor
  • Article: Maxillary artery: anatomical landmarks and relationship with the mandibular subcondyle.
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    ABSTRACT: The maxillary artery can be injured during procedures in the subcondylar portion of the mandible. Thorough knowledge of this region is mandatory to avoid accidental puncture of the maxillary artery, which can lead to profuse bleeding that is hard to control. In 16 halves of eight embalmed cadaver heads, the maxillary artery was dissected from the branching point to the entrance point to the maxillary sinus. Its anatomical relationships with certain landmarks were recorded numerically. The mean distance of the branching point of the maxillary artery to the tragal pointer was 16.2 mm (range, 14.97 to 16.80 mm) in the horizontal plane and 21.4 mm (range, 19.14 to 23.53 mm) in the vertical plane. The mean vertical distance of the branching point to the Frankfort horizontal plane was 25.7 mm (range, 24.86 to 27.47 mm). The mean distance of the branching point of the maxillary artery to the tip of the condyle was 22.4 mm (range, 21.66 to 23.99 mm). The mean distance of the artery to the medial border of the subcondylar portion of the mandible was 6.8 mm (range, 4.06 to 8.47 mm). The mean distance between the deepest point of the sigmoid notch and the junction of the maxillary artery and sigmoid notch was 5.1 mm (range, 4.97 to 5.95 mm). The mean distance of the maxillary artery-sigmoid notch junction to the tragal pointer was 22.9 mm (range, 20.95 to 25.05 mm). The maxillary artery can be injured during surgical procedures performed in the temporomandibular region. Its relationship with the subcondylar portion of the mandible varies.
    Plastic and reconstructive surgery 01/2008; 120(7):1865-70. · 2.74 Impact Factor