This article highlights potential uses for harvested fat and describes the current state of the a... more This article highlights potential uses for harvested fat and describes the current state of the art regarding adipose stem cells.
Objective: The objective of this pilot, retrospective, radiographic study was to determine if chi... more Objective: The objective of this pilot, retrospective, radiographic study was to determine if children with unilateral cleft lip/palate (CL/P) have more maxillary sinus congestion than age and gender matched controls without CL/P. Methods: With IRB approval, three-dimensional cone beam computerized tomographs (3D CBCT) of children 8-14 yoa with unilateral CL/P and surgical lip repair (n=12) and controls (age and gender matched; n=12) were selected randomly from pre-existing orthodontic records. Following reliability studies, one investigator segmented the right and left sinuses from each CBCT using Dolphin 3D Imaging Software (v11.5). Each sequential coronal section (0.4 mm thickness) was manually measured by outlining the maxillary sinus bone boundaries and the airspace on each slice. The software calculated the total cross-sectional surface area of the bony maxillary sinus and air space of each slice. Total area was summed and multiplied by the slice thickness (voxel size - 0.4mm)...
Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remode... more Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, ...
Annals of transplantation : quarterly of the Polish Transplantation Society
Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their... more Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their significance in transplant recipients. A 64-year-old female liver transplant recipient developed Leuconostoc sepsis originating from a bile leak after extended exposure to vancomycin. The infection was readily controlled clindamycin, however, the patient died later on unrelated to the infection. Five articles on Leuconostoc infections in transplant patients were found in PubMed including two liver recipients with intraabdominal infection due to biliary complications and four stem cell recipients with sepsis. Leuconostoc spp. should be considered pathogens in transplant recipients who are exposed to vancomycin.
The authors report the cause of and risk factors for mortality in infants with Robin sequence and... more The authors report the cause of and risk factors for mortality in infants with Robin sequence and identify characteristics associated with quality-of-life outcomes. The authors performed an 11-year retrospective review of all infants with Robin sequence treated at a neonatal intensive care unit. Patient characteristics were correlated to mortality and quality-of-life measures. Emergency room visits and hospital admissions were used to assess quality-of-life outcomes. Significant variables were identified by means of univariate analysis. One hundred eighty-one consecutive infants were identified. Patient characteristics included the following: isolated, 32.6 percent; syndromic, 31.5 percent; gastrointestinal, 38.1 percent; pulmonary, 32.6 percent; cardiac, 30.9 percent; central nervous system, 25.4 percent; and two or more organ system anomalies, 69.6 percent. Mortality was 16.6 percent; two deaths were related to airway obstruction problems. There were no deaths in isolated Robin sequence (p = 0.002). Mortality was statistically associated with cardiac anomalies (p < 0.001), central nervous system anomalies (p = 0.001), and two or more organ system abnormalities (p = 0.001). Variables associated with an increased rate of emergency room visits were cardiac anomalies (p = 0.04) and two or more organ system abnormalities (p = 0.04). The presence of two or more organ system abnormalities (p = 0.04) was associated with an increased hospital admission rate. Mortality and negative quality-of-life measures in Robin sequence are not directly related to respiratory obstruction. Isolated Robin sequence confers no increased risk of mortality. There is a high incidence of cardiac and central nervous system anomalies, which are significantly associated with mortality. Cardiac and cranial imaging should be performed during the initial evaluation of infants with Robin sequence. Risk, III.
Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model ... more Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.
The process of cutaneous wound healing and contraction is a complex orchestra of temporally and s... more The process of cutaneous wound healing and contraction is a complex orchestra of temporally and spatially controlled signaling moieties and pathways. Rho-kinase (ROCK) has been implicated as a key downstream effector of transforming growth factor β1 (TGF-β1) signal transduction, which ultimately coordinates α-smooth muscle actin (α-SMA)-mediated wound contraction. Previous in vitro studies of ROCK inhibition have demonstrated decreased fibroblast contraction and epithelial advancement after wounding. In vivo systemic ROCK inhibition revealed modest late wound healing attenuation in contrast to α-SMA knock-out rodents. The goal of this investigation was to explore the effect of local delivery of a ROCK inhibitor on an in vivo murine model of wound healing. Full-thickness cutaneous wounds were created in 24 white mice and were treated daily with local topical delivery of 100 μL of 10(-4) M ROCK inhibitor (Y27632) or saline control. Percent wound surface area over time and compensatory epithelial advancement was quantified. After 12 days, tissue was harvested for assessment of inflammatory cellular density, immunohistochemistry for α-SMA, and TGF-β protein expression. Wounds subjected to local ROCK inhibition were significantly larger than controls at early time points, and this effect of delayed wound contraction in ROCK-inhibited wounds persisted for 7 days after wounding (P < 0.05). The effect of ROCK inhibition on delay of wound contraction was normalized at day 12. There was no significant difference between control and ROCK-inhibited groups in the area of the nascent epithelium beyond the wound margin, wound inflammatory cellular density, and TGF-β1 expression. However, ROCK inhibition led to as statistically significant decrease in α-SMA stress fiber formation compared to controls [32.5% (3.5%) vs 17.4% (2.6%); P < 0.05]. Local delivery of a ROCK inhibitor delayed the time course of murine wound contraction in a manner similar to that previously reported in α-SMA knock-out rodents, thus demonstrating an effective method for in vivo ROCK inhibition. Accordingly, α-SMA stress fiber formation was inhibited in treated wound beds without altering local inflammation, TGF-β1 expression, or epithelial wound edge advancement.
Background Surgical experience and anecdotal data on the most effective method of harvesting, pre... more Background Surgical experience and anecdotal data on the most effective method of harvesting, preparing, and injecting autologous fat grafts are inconsistent and conflicting. Because the limitation of fat grafting is its resorption, understanding how various handling techniques affect adipocyte survival is crucial to optimizing its long-term survival.
The aim of this study is to evaluate the efficacy, safety profile and the complications associate... more The aim of this study is to evaluate the efficacy, safety profile and the complications associated with mandibular distraction osteogenesis (MDO) performed in infants < 4kg with Robin sequence (RS). A 11-year retrospective review of all infants (< 6 months) with MDO treated RS was performed. Patients < 4 kg (experimental) and ≥ 4 kg (control) who underwent MDO were compared. Demographics, medical comorbidities, improvement in apnea/hypopnea index (AHI), need for tracheostomy, repeat distraction, and complications were evaluated. One hundred twenty-one patients underwent MDO. 81 patients were < 4 kg while 40 were ≥ 4 kg. The mean follow up was 2.8 years in patients < 4 kg and 3.0 years in the control group. Mean age and weight at time of distraction were 23 days old / 3.1 kg and 2.7 years / 11 kg; respectively. There was no significant difference in success of MDO to treat airway obstruction in the < 4 kg group versus the control group (92.6% vs. 88.9%; p = 0.49). T...
Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, Jan 8, 2015
Robin sequence (RS) is defined as the triad of micrognathia, glossoptosis and airway obstruction.... more Robin sequence (RS) is defined as the triad of micrognathia, glossoptosis and airway obstruction. A popular surgical treatment is mandibular distraction osteogenesis (MDO). In this study, it is demonstrated that the associated variables change, dependent on the manner in which failure is defined. These multiple failure outcomes are used to construct a scoring system to predict MDO failure. A retrospective database of neonatal MDO patients was constructed. Failure outcomes studied included tracheostomy; a decrease in the apnea-hypopnea index (AHI) but an AHI >20; and death. A combination of bivariate and regression analysis was used to produce significantly associated variables and a scoring system. Statistical analysis demonstrated the association of gastroesophageal reflux; age >30 days; neurologic anomaly; airway anomalies, other than laryngomalacia; an intact palate; and pre-operative intubation on the outcome variables studied. Multiple scoring systems were produced with r...
This article highlights potential uses for harvested fat and describes the current state of the a... more This article highlights potential uses for harvested fat and describes the current state of the art regarding adipose stem cells.
Objective: The objective of this pilot, retrospective, radiographic study was to determine if chi... more Objective: The objective of this pilot, retrospective, radiographic study was to determine if children with unilateral cleft lip/palate (CL/P) have more maxillary sinus congestion than age and gender matched controls without CL/P. Methods: With IRB approval, three-dimensional cone beam computerized tomographs (3D CBCT) of children 8-14 yoa with unilateral CL/P and surgical lip repair (n=12) and controls (age and gender matched; n=12) were selected randomly from pre-existing orthodontic records. Following reliability studies, one investigator segmented the right and left sinuses from each CBCT using Dolphin 3D Imaging Software (v11.5). Each sequential coronal section (0.4 mm thickness) was manually measured by outlining the maxillary sinus bone boundaries and the airspace on each slice. The software calculated the total cross-sectional surface area of the bony maxillary sinus and air space of each slice. Total area was summed and multiplied by the slice thickness (voxel size - 0.4mm)...
Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remode... more Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, ...
Annals of transplantation : quarterly of the Polish Transplantation Society
Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their... more Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their significance in transplant recipients. A 64-year-old female liver transplant recipient developed Leuconostoc sepsis originating from a bile leak after extended exposure to vancomycin. The infection was readily controlled clindamycin, however, the patient died later on unrelated to the infection. Five articles on Leuconostoc infections in transplant patients were found in PubMed including two liver recipients with intraabdominal infection due to biliary complications and four stem cell recipients with sepsis. Leuconostoc spp. should be considered pathogens in transplant recipients who are exposed to vancomycin.
The authors report the cause of and risk factors for mortality in infants with Robin sequence and... more The authors report the cause of and risk factors for mortality in infants with Robin sequence and identify characteristics associated with quality-of-life outcomes. The authors performed an 11-year retrospective review of all infants with Robin sequence treated at a neonatal intensive care unit. Patient characteristics were correlated to mortality and quality-of-life measures. Emergency room visits and hospital admissions were used to assess quality-of-life outcomes. Significant variables were identified by means of univariate analysis. One hundred eighty-one consecutive infants were identified. Patient characteristics included the following: isolated, 32.6 percent; syndromic, 31.5 percent; gastrointestinal, 38.1 percent; pulmonary, 32.6 percent; cardiac, 30.9 percent; central nervous system, 25.4 percent; and two or more organ system anomalies, 69.6 percent. Mortality was 16.6 percent; two deaths were related to airway obstruction problems. There were no deaths in isolated Robin sequence (p = 0.002). Mortality was statistically associated with cardiac anomalies (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), central nervous system anomalies (p = 0.001), and two or more organ system abnormalities (p = 0.001). Variables associated with an increased rate of emergency room visits were cardiac anomalies (p = 0.04) and two or more organ system abnormalities (p = 0.04). The presence of two or more organ system abnormalities (p = 0.04) was associated with an increased hospital admission rate. Mortality and negative quality-of-life measures in Robin sequence are not directly related to respiratory obstruction. Isolated Robin sequence confers no increased risk of mortality. There is a high incidence of cardiac and central nervous system anomalies, which are significantly associated with mortality. Cardiac and cranial imaging should be performed during the initial evaluation of infants with Robin sequence. Risk, III.
Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model ... more Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.
The process of cutaneous wound healing and contraction is a complex orchestra of temporally and s... more The process of cutaneous wound healing and contraction is a complex orchestra of temporally and spatially controlled signaling moieties and pathways. Rho-kinase (ROCK) has been implicated as a key downstream effector of transforming growth factor β1 (TGF-β1) signal transduction, which ultimately coordinates α-smooth muscle actin (α-SMA)-mediated wound contraction. Previous in vitro studies of ROCK inhibition have demonstrated decreased fibroblast contraction and epithelial advancement after wounding. In vivo systemic ROCK inhibition revealed modest late wound healing attenuation in contrast to α-SMA knock-out rodents. The goal of this investigation was to explore the effect of local delivery of a ROCK inhibitor on an in vivo murine model of wound healing. Full-thickness cutaneous wounds were created in 24 white mice and were treated daily with local topical delivery of 100 μL of 10(-4) M ROCK inhibitor (Y27632) or saline control. Percent wound surface area over time and compensatory epithelial advancement was quantified. After 12 days, tissue was harvested for assessment of inflammatory cellular density, immunohistochemistry for α-SMA, and TGF-β protein expression. Wounds subjected to local ROCK inhibition were significantly larger than controls at early time points, and this effect of delayed wound contraction in ROCK-inhibited wounds persisted for 7 days after wounding (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The effect of ROCK inhibition on delay of wound contraction was normalized at day 12. There was no significant difference between control and ROCK-inhibited groups in the area of the nascent epithelium beyond the wound margin, wound inflammatory cellular density, and TGF-β1 expression. However, ROCK inhibition led to as statistically significant decrease in α-SMA stress fiber formation compared to controls [32.5% (3.5%) vs 17.4% (2.6%); P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05]. Local delivery of a ROCK inhibitor delayed the time course of murine wound contraction in a manner similar to that previously reported in α-SMA knock-out rodents, thus demonstrating an effective method for in vivo ROCK inhibition. Accordingly, α-SMA stress fiber formation was inhibited in treated wound beds without altering local inflammation, TGF-β1 expression, or epithelial wound edge advancement.
Background Surgical experience and anecdotal data on the most effective method of harvesting, pre... more Background Surgical experience and anecdotal data on the most effective method of harvesting, preparing, and injecting autologous fat grafts are inconsistent and conflicting. Because the limitation of fat grafting is its resorption, understanding how various handling techniques affect adipocyte survival is crucial to optimizing its long-term survival.
The aim of this study is to evaluate the efficacy, safety profile and the complications associate... more The aim of this study is to evaluate the efficacy, safety profile and the complications associated with mandibular distraction osteogenesis (MDO) performed in infants < 4kg with Robin sequence (RS). A 11-year retrospective review of all infants (< 6 months) with MDO treated RS was performed. Patients < 4 kg (experimental) and ≥ 4 kg (control) who underwent MDO were compared. Demographics, medical comorbidities, improvement in apnea/hypopnea index (AHI), need for tracheostomy, repeat distraction, and complications were evaluated. One hundred twenty-one patients underwent MDO. 81 patients were < 4 kg while 40 were ≥ 4 kg. The mean follow up was 2.8 years in patients < 4 kg and 3.0 years in the control group. Mean age and weight at time of distraction were 23 days old / 3.1 kg and 2.7 years / 11 kg; respectively. There was no significant difference in success of MDO to treat airway obstruction in the < 4 kg group versus the control group (92.6% vs. 88.9%; p = 0.49). T...
Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, Jan 8, 2015
Robin sequence (RS) is defined as the triad of micrognathia, glossoptosis and airway obstruction.... more Robin sequence (RS) is defined as the triad of micrognathia, glossoptosis and airway obstruction. A popular surgical treatment is mandibular distraction osteogenesis (MDO). In this study, it is demonstrated that the associated variables change, dependent on the manner in which failure is defined. These multiple failure outcomes are used to construct a scoring system to predict MDO failure. A retrospective database of neonatal MDO patients was constructed. Failure outcomes studied included tracheostomy; a decrease in the apnea-hypopnea index (AHI) but an AHI >20; and death. A combination of bivariate and regression analysis was used to produce significantly associated variables and a scoring system. Statistical analysis demonstrated the association of gastroesophageal reflux; age >30 days; neurologic anomaly; airway anomalies, other than laryngomalacia; an intact palate; and pre-operative intubation on the outcome variables studied. Multiple scoring systems were produced with r...
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