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1.
J Invest Dermatol ; 141(6): 1482-1492.e4, 2021 06.
Article in English | MEDLINE | ID: mdl-33242499

ABSTRACT

Systemic sclerosis a chronic, fibrotic disorder associated with high disease-specific mortality and morbidity. Cutaneous manifestations include dermal thickening and obliteration of dermal adipose tissue. Accumulation of low-molecular-weight hyaluronan, which signals through the receptor for hyaluronan-mediated motility, RHAMM, leads to progressive fibrosis and is correlated with increased severity of systemic sclerosis. The purpose of this study is to test the efficacy of two function-blocking RHAMM peptides, NPI-110 and NPI-106, in reducing skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis. NPI-110 reduced visible measures of fibrosis (dermal thickness and collagen production, deposition, and organization) and profibrotic gene expression (Tgfb1, c-Myc, Col1a1, Col3a1). NPI-110 treatment also increased the expression of the antifibrotic adipokines perilipin and adiponectin. Both RHAMM peptides strongly reduced dermal RHAMM expression, predicting that dermal fibroblasts are peptide targets. Transcriptome and cell culture analyses using Rhamm-/- and Rhamm-rescued dermal fibroblasts reveal a TGFß1/RHAMM/MYC signaling axis that promotes fibrogenic gene expression and myofibroblast differentiation. RHAMM function‒blocking peptides suppress this signaling and prevent TGFß1-induced myofibroblast differentiation. These results suggest that inhibiting RHAMM signaling will offer a treatment method for cutaneous fibrosis in systemic sclerosis.


Subject(s)
Adipokines/metabolism , Extracellular Matrix Proteins/antagonists & inhibitors , Hyaluronan Receptors/antagonists & inhibitors , Peptides/pharmacology , Scleroderma, Systemic/drug therapy , Skin/pathology , Animals , Bleomycin/administration & dosage , Bleomycin/toxicity , Cell Differentiation/drug effects , Disease Models, Animal , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Female , Fibrosis , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Mice , Mice, Knockout , Peptides/therapeutic use , Proto-Oncogene Proteins c-myc/metabolism , Scleroderma, Systemic/chemically induced , Scleroderma, Systemic/pathology , Signal Transduction/drug effects , Skin/drug effects , Transforming Growth Factor beta1/metabolism
2.
Plast Reconstr Surg ; 145(1): 116-126, 2020 01.
Article in English | MEDLINE | ID: mdl-31881612

ABSTRACT

BACKGROUND: Radiofibrosis of breast tissue compromises breast reconstruction by interfering with tissue viability and healing. Autologous fat transfer may reduce radiotherapy-related tissue injury, but graft survival is compromised by the fibrotic microenvironment. Elevated expression of receptor for hyaluronan-mediated motility (RHAMM; also known as hyaluronan-mediated motility receptor, or HMMR) in wounds decreases adipogenesis and increases fibrosis. The authors therefore developed RHAMM peptide mimetics to block RHAMM profibrotic signaling following radiation. They propose that this blocking peptide will decrease radiofibrosis and establish a microenvironment favoring adipose-derived stem cell survival using a rat mammary fat pad model. METHODS: Rat mammary fat pads underwent a one-time radiation dose of 26 Gy. Irradiated (n = 10) and nonirradiated (n = 10) fat pads received a single intramammary injection of a sham injection or peptide NPI-110. Skin changes were examined clinically. Mammary fat pad tissue was processed for fibrotic and adipogenic markers using quantitative polymerase chain reaction and immunohistochemical analysis. RESULTS: Clinical assessments and molecular analysis confirmed radiation-induced acute skin changes and radiation-induced fibrosis in rat mammary fat pads. Peptide treatment reduced fibrosis, as detected by polarized microscopy of picrosirius red staining, increased collagen ratio of 3:1, reduced expression of collagen-1 crosslinking enzymes lysyl-oxidase, transglutaminase 2, and transforming growth factor ß1 protein, and increased adiponectin, an antifibrotic adipokine. RHAMM was expressed in stromal cell subsets and was downregulated by the RHAMM peptide mimetic. CONCLUSION: Results from this study predict that blocking RHAMM function in stromal cell subsets can provide a postradiotherapy microenvironment more suitable for fat grafting and breast reconstruction.


Subject(s)
Adipose Tissue/metabolism , Extracellular Matrix Proteins/metabolism , Fibrosis/metabolism , Hyaluronan Receptors/metabolism , Radiation Injuries, Experimental/metabolism , Adipogenesis/drug effects , Adipogenesis/physiology , Animals , Biomarkers/metabolism , Disease Models, Animal , Fibrosis/drug therapy , Peptides/pharmacology , Protein Glutamine gamma Glutamyltransferase 2
3.
J Craniofac Surg ; 29(6): 1625-1628, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29742579

ABSTRACT

OBJECTIVES: The authors describe a case of congenital calvarial hemangioma successfully managed using propranolol therapy. Presenting symptoms, radiological and pathological features, differential diagnosis, and management of this rare congenital mass are described. CASE PRESENTATION: A 2-year-old boy presented with a 1-year history of a growing right parietal skull mass. No obvious etiology was apparent. No focal neurological deficits or associated craniofacial anomalies were identified. Plain film imaging demonstrated focal thickening of the right parietal bone with internal trabeculations in a sunburst appearance. Computed tomography (CT) scan showed bone thickening with coarsening of the bony trabeculae, minor irregularity of the outer table, unaffected inner table, and no evidence of aggressive features. A diagnostic biopsy of the lesion was performed in the operating room. Microscopic examination was consistent with hemangioma. Based on histological and radiological features of the lesion, it was identified as a cavernous hemangioma. Medical treatment utilizing propranolol was initiated for over 3 years with interval reduction in the lesion size. MRI head following treatment with propranolol demonstrated reduction of the mass compared to preoperative imaging. CONCLUSIONS: Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma's intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations.


Subject(s)
Hemangioma, Cavernous/diagnosis , Hemangioma, Cavernous/drug therapy , Propranolol/therapeutic use , Skull Neoplasms/diagnosis , Skull Neoplasms/drug therapy , Vasodilator Agents/therapeutic use , Child, Preschool , Hemangioma, Cavernous/congenital , Humans , Male , Parietal Bone , Skull Neoplasms/congenital
4.
J Pediatr Urol ; 14(2): 172.e1-172.e6, 2018 04.
Article in English | MEDLINE | ID: mdl-29482891

ABSTRACT

INTRODUCTION: Botulinum toxin A (BTX-A) is a neurotoxin that inhibits acetylcholine release by cleaving cytosolic synaptosome-associated protein 25 (SNAP-25) and results in bladder relaxation. A BTX-A intravesical injection has been established as an effective option for treating detrusor overactivity. STUDY DESIGN: Sixty female Sprague Dawley rats were equally divided into control and experimental groups. Control Groups 1 to 3 received: BTX-A 10 units + saline instillation; hyaluronan-phosphatidylethanolamine (HA-PE) 0.5 g + saline instillation; and BTX-A 5 Uintra-detrusor injections, respectively. Treatment Groups 4 to 6 received: Alexa®594-labeled BTX-A 10 U + HA-PE 0.5 g + saline instillation; BTX-A 5 U + HA-PE 0.2-0.5 g instilled for 60 min; and BTX-A 10 U + HA-PE 0.2-0.5 g instilled for 30 min, respectively. All procedures were performed under isoflurane general anesthesia. The primary outcome of this study was the degree of SNAP-25 staining in control and experimental groups compared to Group 3 (detrusor muscle injection). Urodynamic studies were performed at baseline and at day 14 after 1% acetic acid (AA) instillation, to evaluate the maximum pressure during filling (MP) and inter-contraction intervals (ICI). Group 4 rats were examined for Alexa®594 fluorescence to demonstrate physical translocation of BTX-A-HA-PE complex. Standard histology was performed to assess the effect of HA-PE on bladder mucosa and detrusor muscle. RESULTS: Group 3 showed the least SNAP-25 staining (7.3 ± 5.0%) compared with all groups except Group 5A (12.4 ± 12.27%, P = 1.0). Group 6A, which had high HA-PE dose but a shorter instillation time, showed fairly extensive SNAP-25 staining (22.9 ± 10%). Confocal microscopy of Group 4 confirmed the presence of Alexa®594 fluorescence across the urothelium. Urodynamic parameters were not significantly different at baseline (P = 1.0). After acetic acid instillation, Group 5A showed minimal change in ICI, which was comparable to ICI in Group 3 rats. DISCUSSION: SNAP-25 staining in Group 5A was comparable to Group 3, suggesting that adequate HA-PE and instillation time allows the efficacy of this carrier mechanism to be comparable to standard intra-detrusor injections. All other groups showed significantly higher SNAP-25 staining compared to Group 3. A dose response effect was demonstrated; higher dose of HA-PE (Group 5A vs Group 5B) and longer instillation time (Group 5 vs Group 6) led to lower SNAP-25 staining. CONCLUSION: This novel method of BTX-A delivery to the bladder using a carrier (HA-PE) is promising and requires further investigation. Using a larger animal model, identifying an optimal dose of HA-PE and instillation time, and reproducing the current results are further required to validate this carrier.


Subject(s)
Botulinum Toxins, Type A/administration & dosage , Drug Carriers/administration & dosage , Hyaluronic Acid/administration & dosage , Phosphatidylethanolamines/therapeutic use , Urinary Bladder, Neurogenic/drug therapy , Urinary Bladder/drug effects , Administration, Intravesical , Analysis of Variance , Animals , Disease Models, Animal , Female , Neuromuscular Agents/administration & dosage , Random Allocation , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Treatment Outcome , Urodynamics
5.
Pediatr Emerg Care ; 33(10): e103-e104, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28968312

ABSTRACT

A mallet finger is a flexion deformity of a finger at the distal interphalangeal joint due to an injury of the extensor mechanism at the base of the distal phalanx. Most common in middle-aged men, injuries in the pediatric population are less common and rare in toddlers. We describe a case of missed mallet finger and its subsequent treatment in a female toddler.


Subject(s)
Finger Injuries/complications , Hand Deformities, Acquired/diagnosis , Child, Preschool , Diagnostic Errors , Female , Finger Injuries/therapy , Hand Deformities, Acquired/etiology , Hand Deformities, Acquired/therapy , Humans , Splints
6.
J Craniofac Surg ; 27(2): 504-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26967083

ABSTRACT

Current approaches to facial reconstruction are based on the assumption of facial symmetry, though this has yet to be established in the literature. Through quantitative and qualitative analysis, symmetry of normal, male faces is examined here using the zygomatic complex as a bellwether for the rest of the facial skeleton. Three-dimensional models reconstructed from the computed tomography scans of 30 adult male patients displaying normal facial skeletal anatomy were analyzed. Seven zygomatic landmarks were identified on all craniofacial models, and asymmetry scores were calculated based on the average deviation distance upon reflection of 1 hemiface across the midfacial plane. Deviation maps were then generated for each zygomatic pair to enable visualization of the asymmetry. All landmarks displayed a slight (<3 mm) deviation from perfect symmetry, and analysis of zygomatic form asymmetry revealed an average of 0.4 mm of surface deviation between hemifaces. The presence of such slight asymmetries in the zygoma warrants further investigation as to the clinical relevance of such skeletal asymmetries from both an esthetic and biomechanical consideration to provide insight as to the proper approach to zygomatic restoration in cases of zygomatic fracture.


Subject(s)
Face/anatomy & histology , Facial Bones/anatomy & histology , Imaging, Three-Dimensional/methods , Zygoma/anatomy & histology , Adult , Anatomic Landmarks/anatomy & histology , Anatomic Landmarks/diagnostic imaging , Anatomic Variation , Esthetics , Face/diagnostic imaging , Facial Asymmetry/diagnostic imaging , Facial Asymmetry/pathology , Facial Bones/diagnostic imaging , Frontal Bone/anatomy & histology , Humans , Male , Models, Anatomic , Orbit/anatomy & histology , Tomography, X-Ray Computed/methods , Young Adult , Zygoma/diagnostic imaging
7.
J Craniofac Surg ; 26(6): 1997-2001, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26355983

ABSTRACT

The accurate assessment of symmetry in the craniofacial skeleton is important for cosmetic and reconstructive craniofacial surgery. Although there have been several published attempts to develop an accurate system for determining the correct plane of symmetry, all are inaccurate and time consuming. Here, the authors applied a novel semi-automatic method for the calculation of craniofacial symmetry, based on principal component analysis and iterative corrective point computation, to a large sample of normal adult male facial computerized tomography scans obtained clinically (n = 32). The authors hypothesized that this method would generate planes of symmetry that would result in less error when one side of the face was compared to the other than a symmetry plane generated using a plane defined by cephalometric landmarks. When a three-dimensional model of one side of the face was reflected across the semi-automatic plane of symmetry there was less error than when reflected across the cephalometric plane. The semi-automatic plane was also more accurate when the locations of bilateral cephalometric landmarks (eg, frontozygomatic sutures) were compared across the face. The authors conclude that this method allows for accurate and fast measurements of craniofacial symmetry. This has important implications for studying the development of the facial skeleton, and clinical application for reconstruction.


Subject(s)
Cephalometry/statistics & numerical data , Facial Bones/anatomy & histology , Skull/anatomy & histology , Adult , Algorithms , Anatomic Landmarks/anatomy & histology , Cranial Sutures/anatomy & histology , Frontal Bone/anatomy & histology , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Imaging, Three-Dimensional/statistics & numerical data , Male , Principal Component Analysis , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray Computed/statistics & numerical data , Young Adult , Zygoma/anatomy & histology
8.
Plast Surg (Oakv) ; 23(1): 40-2, 2015.
Article in English | MEDLINE | ID: mdl-25821772

ABSTRACT

OBJECTIVE: To examine the effect of trauma velocity on the pattern of Le Fort I facial fractures. METHOD: A retrospective medical record review was conducted on a consecutive cohort of craniofacial traumas surgically treated by a single surgeon between 2007 and 2011 (n=150). Of these cases, 39 Le Fort fractures were identified. Patient demographic information, method of trauma and velocity of impact were reviewed for these cases. Velocity of impact was expressed categorically as either 'high' or 'low': high-velocity fractures were those caused by a fall from >1 story or a motor vehicle collision; low-velocity fractures were the result of assaults with a blunt weapon, closed fist or falls from standing height. The vertical position of each fracture was measured at its point of entry on the lateral buttress and its point of exit on the piriform aperture. To allow for comparison across individuals, values were expressed as ratios based on their location on the face relative to these landmarks. A Wilcoxon rank-sum test was used to compare the fracture heights caused by high- and low-velocity trauma. RESULTS: The results revealed that high-velocity traumas to the face create Le Fort I fractures at a higher point in the lateral buttress compared with low-velocity traumas. There was no difference between heights at the piriform aperture. CONCLUSION: High-velocity trauma resulted in higher Le Fort I fracture patterns compared with low-velocity trauma.


OBJECTIF: Examiner l'effet de la vélocité du traumatisme sur le profil des fractures faciales de Le Fort I. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse rétrospective des dossiers médicaux d'une cohorte consécutive de traumatisés craniofaciaux opérés par un même chirurgien entre 2007 et 2011 (n=150). De ce nombre, ils ont repéré 39 fractures de Le Fort. Ils ont extrait les caractéristiques démographiques des patients, le mode de traumatisme et la vélocité de l'impact, exprimée la vélocité deux catégories : « haute ¼ ou « faible ¼. Les fractures de haute vélocité étaient causées par des chutes de plus d'un étage ou un accident d'automobile. Les fractures de faible vélocité découlaient d'une agression à l'arme contondante ou au poing fermé ou de chutes à partir de la position debout. La position verticale de chaque fracture était mesurée à son point d'entrée sur la structure latérale et à son point de sortie dans l'orifice piriforme. Aux fins de comparaison, les valeurs étaient exprimées selon le ratio de l'endroit sur le visage par rapport à ces points de repère. Le test de Wilcoxon a été privilégié pour comparer la hauteur des fractures causées par des traumatismes à haute et à faible vélocité. RÉSULTATS: Les résultats ont démontré que les traumatismes faciaux à haute vélocité créaient des fractures de Le Fort I situées à un point plus élevé de la structure latérale que les traumatismes à faible vélocité. Il n'y avait pas de différences de hauteur à l'orifice piriforme. CONCLUSION: Les traumatismes à haute vélocité entraînaient des profils de fractures de Le Fort I situées à un point plus élevé que les traumatismes à faible vélocité.

9.
J Surg Educ ; 72(2): 228-34, 2015.
Article in English | MEDLINE | ID: mdl-25481801

ABSTRACT

PURPOSE: Competency-based medical education is becoming increasingly prevalent and is likely to be mandated by the Royal College in the near future. The objective of this study was to define the core technical competencies that should be possessed by plastic surgery residents as they transition into their senior (presently postgraduate year 3) years of training. METHODS: A list of potential core competencies was generated using a modified Delphi method that included the investigators and 6 experienced, academic plastic surgeons from across Canada and the United States. Generated items were divided into 7 domains: basic surgical skills, anesthesia, hand surgery, cutaneous surgery, esthetic surgery, breast surgery, and craniofacial surgery. Members of the Delphi group were asked to rank particular skills on a 4-point scale with anchored descriptors. Item reduction resulted in a survey consisting of 48 skills grouped into the aforementioned domains. This self-administered survey was distributed to all Canadian program directors (n = 11) via e-mail for validation and further item reduction. RESULTS: The response rate was 100% (11/11). Using the average rankings of program directors, 26 "core" skills were identified. There was agreement of core skills across all domains except for breast surgery and esthetic surgery. Of them, 7 skills were determined to be above the level of a trainee at this stage; a further 15 skills were agreed to be important, but not core, competencies. CONCLUSIONS: Overall, 26 competencies have been identified as "core" for plastic surgery residents to possess as they begin their senior, on-service years. The nature of these skills makes them suitable for teaching in a formal, simulated environment, which would ensure that all plastic surgery trainees are competent in these tasks as they transition to their senior years of residency.


Subject(s)
Clinical Competence , Competency-Based Education/standards , Education, Medical, Graduate/methods , Internship and Residency/methods , Surgery, Plastic/education , Canada , Cross-Sectional Studies , Delphi Technique , Educational Measurement , Female , Humans , Male , Quality Improvement , Reference Standards , Task Performance and Analysis , Young Adult
10.
Plast Surg (Oakv) ; 22(4): 233-6, 2014.
Article in English | MEDLINE | ID: mdl-25535459

ABSTRACT

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular abnormality clinic at the authors' institution between October 2007 and February 2012 was performed. Anthropometric measures (height and BMI) and blood pressure were analyzed. RESULTS: A total of 290 visits (119 patients) to the pediatric vascular abnormality clinic were reviewed. Of these, 18 patients received medical treatment and their anthropometry was analyzed. BMI percentile increased significantly in patients treated with corticosteroids (P=0.0039). Corticosteroid treatment also resulted in a significant decrease in height percentile (P=0.0078). Anthropometric measures did not cross percentiles in children treated with propranolol. A significant decrease in systolic blood pressure was noted in the propranolol group (P=0.03), but no hypotensive values were recorded. Median treatment duration was significantly longer when patients received propranolol (372 versus 133 days; P=0.0033). CONCLUSION: Propranolol for the treatment of infantile vascular abnormalities does not share the unfavourable effects on patient anthropometry that corticosteroids exhibit; however, a longer duration of therapy is required.


HISTORIQUE: L'hémangiome infantile est la principale tumeur bénigne autolimitative de l'enfance. Le traitement est réservé aux hémangiomes qui obstruent des structures vitales ou provoquent une importante défiguration. La corticothérapie était privilégiée, mais à compter de 2008, le propranolol a rapidement été adopté en raison de son efficacité. Il n'y a pas de données publiées sur les effets à long terme du propranolol. OBJECTIF: Décrire les effets à long terme du propranolol et des corticoïdes sur les mesures anthropométriques (taille, indice de masse corporelle [IMC]) et la tension artérielle chez les enfants. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse prospective des bases de données de toutes les visites de patients à la clinique pédiatrique d'anomalies vasculaires de l'établissement des auteurs en raison d'un hémangiome infantile entre octobre 2007 et février 2012. Ils ont analysé les mesures anthropométriques (taille et IMC) et la tension artérielle. RÉSULTATS: Les chercheurs ont examiné 290 visites (119 patients) à la clinique pédiatrique d'anomalies vasculaires. De ce nombre, 18 patients ont reçu un traitement médical. Les chercheurs ont évalué leurs mesures anthropométriques. Le percentile d'IMC a augmenté de manière significative chez les patients sous corticothérapie (P=0,0039). La corticothérapie s'associait également à une diminution importante du percentile de taille (P=0,0078). Par contre, les mesures anthropométriques ne traversaient pas les percentiles chez les enfants traités au propranolol. Leur tension artérielle systolique était beaucoup plus faible (P=0,03), mais aucune valeur hypotensive n'a été enregistrée. Par ailleurs, la durée médiane du traitement était considérablement plus longue chez les patients qui prenaient du propranolol (372 jours au lieu de 133; P=0,0033). CONCLUSION: Pour soigner les anomalies vasculaires des enfants, le propranolol n'a pas les mêmes effets défavorables sur l'anthropométrie que les corticoïdes. Cependant, le traitement est plus long.

11.
Biomed Res Int ; 2014: 727459, 2014.
Article in English | MEDLINE | ID: mdl-25276814

ABSTRACT

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa(647)-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa(647)-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa(647)-HA-PE penetrated into and was retained within the epidermis than Alexa(647)-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis.


Subject(s)
Hyaluronic Acid/pharmacology , Keratinocytes/cytology , Keratinocytes/drug effects , Phosphatidylethanolamines/pharmacology , Polymers/pharmacology , Administration, Topical , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Epidermal Cells , Epidermis/drug effects , Epidermis/metabolism , Extracellular Matrix Proteins/deficiency , Extracellular Matrix Proteins/metabolism , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Hyaluronan Receptors/metabolism , Inflammation/pathology , Keratinocytes/metabolism , Mice, Inbred C57BL
12.
Biomed Res Int ; 2014: 103923, 2014.
Article in English | MEDLINE | ID: mdl-25157350

ABSTRACT

Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM) remodeling (Ballard et al., 2006) increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA) and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to "cancerization" of the tumor microenvironment.


Subject(s)
Carcinogenesis/metabolism , Carcinogenesis/pathology , Extracellular Matrix Proteins/metabolism , Hyaluronan Receptors/metabolism , Hyaluronic Acid/metabolism , Wound Healing , Animals , Humans , Signal Transduction , Stromal Cells/metabolism , Stromal Cells/pathology
13.
J Craniofac Surg ; 24(6): 2023-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24220396

ABSTRACT

INTRODUCTION: This study aimed to use video analysis techniques to determine the velocity, impact force, angle of impact, and impulse to fracture involved in a video-recorded bicycle accident resulting in facial fractures. Computed tomographic images of the resulting facial injury are presented for correlation with data and calculations. To our knowledge, such an analysis of an actual recorded trauma has not been reported in the literature. MATERIALS AND METHODS: A video recording of the accident was split into frames and analyzed using an image editing program. Measurements of velocity and angle of impact were obtained from this analysis, and the force of impact and impulse were calculated using the inverse dynamic method with connected rigid body segments. These results were then correlated with the actual fracture pattern found on computed tomographic imaging of the subject's face. RESULTS: There was an impact velocity of 6.25 m/s, impact angles of 14 and 6.3 degrees of neck extension and axial rotation, respectively, an impact force of 1910.4 N, and an impulse to fracture of 47.8 Ns. These physical parameters resulted in clinically significant bilateral mid-facial Le Fort II and III pattern fractures. DISCUSSION: These data confer further understanding of the biomechanics of bicycle-related accidents by correlating an actual clinical outcome with the kinematic and dynamic parameters involved in the accident itself and yielding a concrete evidence of the velocity, force, and impulse necessary to cause clinically significant facial trauma. These findings can aid in the design of protective equipment for bicycle riders to help avoid this type of injury.


Subject(s)
Athletic Injuries/physiopathology , Bicycling/injuries , Biomechanical Phenomena , Facial Bones/injuries , Skull Fractures/physiopathology , Video Recording , Acceleration , Athletic Injuries/surgery , Facial Bones/physiopathology , Facial Bones/surgery , Humans , Imaging, Three-Dimensional , Skull Fractures/classification , Skull Fractures/surgery , Tomography, X-Ray Computed
14.
Med Eng Phys ; 35(12): 1843-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23891670

ABSTRACT

During reconstructive surgery of the face, one side may be used as a template for the other, exploiting assumed bilateral facial symmetry. The best method to calculate this plane, however, is debated. A new semi-automatic technique for calculating the symmetry plane of the facial skeleton is presented here that uses surface models reconstructed from computed tomography image data in conjunction with principal component analysis and an iterative closest point alignment method. This new technique was found to provide more accurate symmetry planes than traditional methods when applied to a set of 7 human craniofacial skeleton specimens, and showed little vulnerability to missing model data, usually deviating less than 1.5° and 2 mm from the intact model symmetry plane when 30 mm radius voids were present. This new technique will be used for subsequent studies measuring symmetry of the facial skeleton for different patient populations.


Subject(s)
Facial Bones/anatomy & histology , Facial Bones/diagnostic imaging , Image Processing, Computer-Assisted/methods , Tomography, X-Ray Computed , Automation , Computer Simulation , Facial Bones/surgery , Humans , Plastic Surgery Procedures , Time Factors
15.
Can J Plast Surg ; 21(3): 173-7, 2013.
Article in English | MEDLINE | ID: mdl-24421649

ABSTRACT

BACKGROUND: Ideal eyebrow aesthetics give a framework for brow rejuvenation and surgical procedures do not always provide satisfying results. Previous studies have shown elevation of the medial brow with aging; however, they failed to characterize overall shape changes. OBJECTIVE: To characterize changes in eyebrow slope with increasing age to better direct brow rejuvenation. METHODS: From standardized anteroposterior facial photographs of 100 women 20 to 80 years of age, eyebrow height was measured at the medial limbus and arch apex from a mid-pupillary horizontal. The slope of the eyebrow was calculated. Using group analysis, mean height and slope were compared using the Mann-Whitney U test. Regression analysis was used to determine the relationship between slope and age. RESULTS: Mean slope significantly decreased from 20 to 29 years of age to 40 to 49 years of age (0.22 versus 0.12; P=0.03), and then increased between 40 and 49 years of age and ≥60 years of age (0.12 versus 0.21; P=0.05). Medial height did not change significantly, and arch apex significantly decreased between 20 and 29 years of age and 40 and 49 years of age. Regression analysis showed a quadratic relationship between age and slope, with the decrease in slope until the fifth decade of life being directly related to increasing age. After this, age was not a significant contributor to slope changes. CONCLUSIONS: With increasing age, the slope of the eyebrow decreases until the fifth decade dependent on age. After the fifth decade, age no longer plays a significant role. Therefore, choice of brow lift technique should be carefully selected.


HISTORIQUE: Une esthétique idéale du sourcil fournit un cadre pour rajeunir le front, mais les interventions chirurgicales ne donnent pas toujours des résultats satisfaisants. Des études antérieures ont démontré une élévation de la partie médiale du front avec le vieillissement, mais n'ont pas caractérisé les changements de forme globaux. OBJECTIF: Caractériser les changements de la courbe des sourcils avec l'âge, afin de mieux orienter le rajeunissement du front. MÉTHODOLOGIE: À partir de photographies faciales antéroposté-rieures normalisées de 100 femmes de 20 à 80 ans, les chercheurs ont mesuré la hauteur des sourcils par rapport au limbe médial et à l'apex de l'arche à partir du milieu de la pupille horizontale. Ils ont calculé la courbe des sourcils. Au moyen de l'analyse de groupe, ils ont comparé la hauteur et la courbe moyennes en se servant du test de Mann-Whitney. Ils ont utilisé l'analyse de régression pour déterminer le lien entre la courbe et l'âge. RÉSULTATS: La courbe moyenne diminuait considérablement entre 20 à 29 ans et 40 à 49 ans (0,22 par rapport à 0,12; P=0,03), puis augmentait entre 40 et 49 ans et 60 ans et plus (0,12 par rapport à 0,21;P=0,05). La hauteur médiane ne changeait pas de manière significative, tandis que l'apex de l'arche diminuait de manière significative entre 20 à 29 ans et 40 à 49 ans. L'analyse de régression a révélé un lien quadratique entre l'âge et la courbe, la diminution de la courbe jusqu'à la cinquième décennie étant directement proportionnelle à l'avancement en âge. Par la suite, l'âge n'était plus un élément significatif des changements de courbe. CONCLUSIONS: Avec l'âge, la courbe du sourcil diminue jusqu'à la cinquième décennie. L'âge ne joue plus un rôle important par la suite. Il faut donc choisir attentivement la technique de redrapage du front.

16.
J Craniofac Surg ; 23(5): 1324-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22948626

ABSTRACT

BACKGROUND: Facial fractures can be associated with brain and cervical spine injuries because impact forces are transmitted through the head and neck. Although major brain injury is commonly recognized in these patients, incidence of minor brain injury is not well-known, despite potential morbidity and mortality. OBJECTIVES: This prospective study aimed to determine the incidence of both major and minor brain injuries in 100 patients presenting to a craniofacial surgery service with facial fractures and to identify characteristics associated with brain injury. METHODS: Data were collected for a 9-month period by a craniofacial surgeon at a level I trauma center. A questionnaire and checklist were designed to capture information about major and minor brain injury in patients with facial fractures. Assessments were completed in the outpatient clinic, emergency department, hospital ward, or intensive care unit during the first patient encounters. RESULTS: The average age of patients was 34 years; 79% were male. Time between injury and assessment ranged from less than a few hours to 4 months. Incidence of brain injury was 67% overall: 29% with major brain injury and 38% with minor injury. Major brain injury was commonly diagnosed early in the emergency department or intensive care unit. Conversely, minor brain injury tended to be diagnosed late in the clinic. Patient age, mechanism of injury, and type of facial fracture predicted brain injuries overall, but mechanism of injury was the sole predictor of minor brain injury. CONCLUSIONS: Facial fractures are often associated with brain injury. A high level of suspicion is warranted for minor traumatic brain injuries.


Subject(s)
Brain Injuries/etiology , Maxillofacial Injuries/complications , Skull Fractures/complications , Adult , Analysis of Variance , Brain Injuries/epidemiology , Chi-Square Distribution , Female , Humans , Incidence , Logistic Models , Male , Prospective Studies , Risk Factors , Surveys and Questionnaires
17.
J Craniofac Surg ; 22(6): 2288-91, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22134259

ABSTRACT

Slit-ventricle syndrome (SVS) is characterized by headaches associated with subnormal ventricular size in patients with shunt-treated hydrocephalus. It commonly occurs in children who have had shunts placed at an early age and is diagnosed when computed tomography scans are carried out to investigate suspected shunt obstruction with an accompanying rise in intracranial pressure (ICP). Overdrainage of cerebrospinal fluid may additionally result in craniocephalic disproportion, potentially by dampening the normal expansile pulsations of the dura against the skull, which leads to craniostenosis. Management is controversial because many strategies have only short-term benefit, and surgical intervention is understandably often seen as a last resort.We present a case of a child with SVS and craniocephalic disproportion who was treated with urgent cranial expansion due to rising ICP. Intraoperative ICP monitoring demonstrates a rapid and sustained drop in ICP, and the patient made an uneventful return to his premorbid condition. We conclude that cranial vault expansion should be considered as an effective treatment for postshunt craniocephalic disproportion in patients with SVS.


Subject(s)
Ciliary Motility Disorders/complications , Ciliary Motility Disorders/surgery , Encephalocele/complications , Encephalocele/surgery , Hydrocephalus/etiology , Hydrocephalus/surgery , Polycystic Kidney Diseases/complications , Polycystic Kidney Diseases/surgery , Slit Ventricle Syndrome/complications , Slit Ventricle Syndrome/surgery , Child , Ciliary Motility Disorders/diagnostic imaging , Decompression, Surgical , Encephalocele/diagnostic imaging , Humans , Hydrocephalus/diagnostic imaging , Intracranial Pressure , Male , Polycystic Kidney Diseases/diagnostic imaging , Retinitis Pigmentosa , Slit Ventricle Syndrome/diagnostic imaging , Tomography, X-Ray Computed
18.
Can J Plast Surg ; 18(4): e50-2, 2010.
Article in English | MEDLINE | ID: mdl-22131848

ABSTRACT

Pulmonary emboli are rare, yet serious, complications of body contouring surgery. When they occur, they more often follow as complications of long, invasive procedures in adults. The present report details a case of bilateral pulmonary emboli in an obese 15-year-old boy with hypogonadism undergoing bilateral mastectomy for gynecomastia. The diagnosis of bilateral pulmonary emboli was made on the basis of clinical presentation and positive ventilation/perfusion scan. The patient responded well to heparin anticoagulation treatment. The relevance of pediatric obesity, pediatric body contouring surgery and the risk of thromboembolic events in pediatric patients are discussed.

19.
Plast Reconstr Surg ; 120(5): 1348-1356, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17898611

ABSTRACT

The majority of patients with a unilateral cleft nasal deformity still benefit from additional nasal surgery in their teenage years, despite having undergone a primary nasal repair. However, the secondary nasal deformity of these patients stands in sharp contrast to those of children who have not benefited from primary repair. The authors' algorithm for the definitive correction of these secondary deformities considers the differences in these two patient groups and defines their indications for rib cartilage grafts and their method of using septal and ear cartilage in the repair. Balancing the muscle forces on the septum and alar cartilage is emphasized in both the primary and secondary repair. Both cartilage malposition and hypoplasia of the lower lateral cartilage complex have been identified as factors contributing to the deformity.


Subject(s)
Algorithms , Cleft Lip/surgery , Nose/surgery , Rhinoplasty , Cartilage/transplantation , Humans , Maxilla/surgery , Rhinoplasty/methods , Ribs/transplantation
20.
J Surg Res ; 139(2): 243-52, 2007 May 15.
Article in English | MEDLINE | ID: mdl-17433895

ABSTRACT

BACKGROUND: Understanding the effects of muscle function on facial bone growth may help us treat children with facial anomalies. Facial bone growth is known to be a result of both genetic and epigenetic influences. One of the main epigenetic factors controlling growth is thought to be muscle action. The purpose of this study was to establish a model of single facial muscle paralysis and to identify the effects masseter muscle paralysis has on mandible and zygoma growth. METHODS: Twenty New Zealand white rabbits were divided into control, paralysis, and sham groups. Masseter muscle paralysis was achieved with botulinum toxin A (BTX). Computed tomographic and single-photon emission computed tomography (SPECT) scans and cephalometric measurements were performed. Masseter weights and mandible and zygoma volumes, shapes, and metabolism were measured. RESULTS: Eighteen animals completed the study. Significant decreases in zygoma and mandible volumes with minimal changes in shape were seen on the paralyzed sides. SPECT showed a decrease in bone production in both zygomas and mandibles on the paralyzed sides. CONCLUSIONS: An animal model has been created in which the effects of single muscle paralysis on bone growth can be studied. Masseter muscle function may be responsible in maintaining mandible and zygoma volume by controlling bone production. Masseter function alone has less influence on mandible and zygoma shape.


Subject(s)
Mandible/growth & development , Masseter Muscle , Paralysis/physiopathology , Zygoma/growth & development , Animals , Body Weight , Botulinum Toxins, Type A , Cephalometry , Female , Mandible/diagnostic imaging , Mandible/pathology , Masseter Muscle/physiopathology , Neuromuscular Agents , Organ Size , Paralysis/chemically induced , Paralysis/diagnosis , Rabbits , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Zygoma/diagnostic imaging , Zygoma/pathology
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