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1.
Plast Reconstr Surg ; 138(5): 844e-855e, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27782996

RESUMO

BACKGROUND: The objective of this study was to evaluate the antimicrobial performance of a rifampin/minocycline-coated, non-cross-linked, acellular porcine dermal matrix (XenMatrix AB) compared to an uncoated, non-cross-linked, acellular porcine dermal matrix (Strattice) after implantation/inoculation with methicillin-resistant Staphylococcus aureus or Escherichia coli in a dorsal rabbit model. METHODS: Forty male New Zealand White rabbits were bilaterally implanted with XenMatrix AB or Strattice grafts and inoculated with clinically isolated methicillin-resistant S. aureus (5 × 10 colony-forming units/ml) or E. coli (1 × 10 colony-forming units/ml). At 2 and 8 weeks, sites were analyzed for viable methicillin-resistant S. aureus/E. coli colony-forming units, abscess formation, and histologic response (n = 5 rabbits per group per bacterium per time point). RESULTS: XenMatrix AB completely inhibited bacterial colonization of the graft, inhibited abscess formation, reduced inflammation and encapsulation, and improved neovascularization compared with Strattice. XenMatrix AB implants exhibited significantly fewer colony-forming units compared with Strattice implants at 2 weeks (methicillin-resistant S. aureus) (p < 0.01) and at 2 and 8 weeks (E. coli) (p < 0.05). In addition, XenMatrix AB implants demonstrated a significantly lower abscess score at 2 weeks (methicillin-resistant S. aureus) and 8 weeks (E. coli) (p < 0.01 in both cases). For both types of bacteria and both time points evaluated, XenMatrix AB implants exhibited minimal inflammation and encapsulation and a lack of neutrophils. In contrast, Strattice implants displayed marked inflammatory and neutrophilic responses and moderate encapsulation. CONCLUSIONS: This study demonstrated the antimicrobial performance of a rifampin/minocycline-coated bioprosthetic (XenMatrix AB) in a rabbit inoculation model. XenMatrix AB completely inhibited bacterial colonization of the graft, with minimal host inflammation and encapsulation, and improved neovascularization compared with Strattice.


Assuntos
Derme Acelular , Antibacterianos/administração & dosagem , Infecções por Escherichia coli/prevenção & controle , Minociclina/administração & dosagem , Rifampina/administração & dosagem , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Animais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Infecções por Escherichia coli/etiologia , Masculino , Staphylococcus aureus Resistente à Meticilina , Minociclina/uso terapêutico , Coelhos , Rifampina/uso terapêutico , Infecções Estafilocócicas/etiologia , Suínos , Resultado do Tratamento
2.
Surg Endosc ; 30(9): 3691-701, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27369286

RESUMO

BACKGROUND: The objective of this study was to evaluate the mechanical and histological properties of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh (Phasix™ ST) compared to partially absorbable (Ventralight™ ST), fully absorbable (Phasix™), and biologically derived (Strattice™) meshes in a porcine model of ventral hernia repair. METHODS: Bilateral abdominal surgical defects were created in twenty-four Yucatan pigs, repaired with intraperitoneal (Phasix™ ST, Ventralight™ ST) or retromuscular (Phasix™, Strattice™) mesh, and evaluated at 12 and 24 weeks (n = 6 mesh/group/time point). RESULTS: Prior to implantation, Strattice™ demonstrated significantly higher (p < 0.001) strength (636.6 ± 192.1 N) compared to Ventralight™ ST (324.3 ± 37.1 N), Phasix™ ST (206.9 ± 11.3 N), and Phasix™ (200.6 ± 25.2 N). At 12 and 24 weeks, mesh/repair strength was significantly greater than NAW (p < 0.01 in all cases), and no significant changes in strength were observed for any meshes between 12 and 24 weeks (p > 0.05). Phasix™ mesh/repair strength was significantly greater than Strattice™ (p < 0.001) at 12 and 24 weeks, and Ventralight™ ST mesh/repair strength was significantly greater than Phasix™ ST mesh (p < 0.05) at 24 weeks. At 12 and 24 weeks, Phasix™ ST and Ventralight™ ST were associated with mild inflammation and minimal-mild fibrosis/neovascularization, with no significant differences between groups. At both time points, Phasix™ was associated with minimal-mild inflammation/fibrosis and mild neovascularization. Strattice™ was associated with minimal inflammation/fibrosis, with minimal neovascularization at 12 weeks, which increased to mild by 24 weeks. Strattice™ exhibited significantly less neovascularization than Phasix™ at 12 weeks and significantly greater inflammation at 24 weeks due to remodeling. CONCLUSIONS: Phasix™ ST demonstrated mechanical and histological properties comparable to partially absorbable (Ventralight™ ST) and fully resorbable (Phasix™) meshes at 12 and 24 weeks in this model. Data also suggest that fully absorbable meshes with longer-term resorption profiles may provide improved mechanical and histological properties compared to biologically derived scaffolds.


Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Hérnia Ventral/cirurgia , Hidroxibutiratos , Telas Cirúrgicas , Animais , Feminino , Herniorrafia/métodos , Teste de Materiais , Modelos Animais , Suínos , Cicatrização
3.
Surg Innov ; 23(5): 442-55, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27354551

RESUMO

Background Despite meticulous aseptic technique and systemic antibiotics, bacterial colonization of mesh remains a critical issue in hernia repair. A novel minocycline/rifampin tyrosine-coated, noncrosslinked porcine acellular dermal matrix (XenMatrix AB) was developed to protect the device from microbial colonization for up to 7 days. The objective of this study was to evaluate the in vitro and in vivo antimicrobial efficacy of this device against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Methods XenMatrix AB was compared with 5 existing uncoated soft tissue repair devices using in vitro methods of zone of inhibition (ZOI) and scanning electron microscopy (SEM) at 24 hours following inoculation with MRSA or E coli These devices were also evaluated at 7 days following dorsal implantation and inoculation with MRSA or E coli (60 male New Zealand white rabbits, n = 10 per group) for viable colony-forming units (CFU), abscess formation and histopathologic response, respectively. Results In vitro studies demonstrated a median ZOI of 36 mm for MRSA and 16 mm for E coli for XenMatrix AB, while all uncoated devices showed no inhibition of bacterial growth (0 mm). SEM also demonstrated no visual evidence of MRSA or E coli colonization on the surface of XenMatrix AB compared with colonization of all other uncoated devices. In vivo XenMatrix AB demonstrated complete inhibition of bacterial colonization, no abscess formation, and a reduced inflammatory response compared with uncoated devices. Conclusion We demonstrated that XenMatrix AB possesses potent in vitro and in vivo antimicrobial efficacy against clinically isolated MRSA and E coli compared with uncoated devices.


Assuntos
Derme Acelular/efeitos dos fármacos , Minociclina/farmacologia , Rifampina/farmacologia , Transplante de Pele/métodos , Lesões dos Tecidos Moles/cirurgia , Animais , Materiais Revestidos Biocompatíveis , Quimioterapia Combinada , Sobrevivência de Enxerto , Imuno-Histoquímica , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Microscopia Eletrônica , Modelos Animais , Coelhos , Valores de Referência , Células-Tronco , Suínos
6.
Tissue Eng Part A ; 21(19-20): 2526-35, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26176992

RESUMO

The use of biologic scaffold materials adjacent to synthetic meshes is commonplace. A prevalent clinical example is two-staged breast reconstruction, where biologic scaffolds are used to provide support and coverage for the inferior aspect of the synthetic expander. However, limited data exist regarding either the kinetics of biologic scaffold integration or the host tissue response to the biologic scaffold materials used for this application or other applications in which such scaffold materials are used. The present study evaluated the temporal host response to a biological scaffold when placed adjacent to a synthetic material. Evaluation criteria included quantification of material contracture and characterization of the host cell response and tissue remodeling events. Results show a decreased thickness of the collagenous tissue layer at biologic scaffold/silicone interface compared to the abdominal wall/silicone interface during the 12-week experimental time course. All test materials were readily incorporated into surrounding host tissue.


Assuntos
Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/efeitos adversos , Tecido Conjuntivo/efeitos dos fármacos , Feminino , Ratos , Ratos Sprague-Dawley , Alicerces Teciduais/efeitos adversos
7.
Pediatr Blood Cancer ; 62(9): 1518-22, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25631103

RESUMO

BACKGROUND: Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients. METHODS: The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg. RESULTS: No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98-100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2-100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8). CONCLUSIONS: The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Metotrexato/antagonistas & inibidores , gama-Glutamil Hidrolase/administração & dosagem , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/sangue , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Creatinina/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Custos de Medicamentos , Avaliação de Medicamentos , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Inativação Metabólica/efeitos dos fármacos , Infusões Intravenosas , Injeções Intravenosas , Leucovorina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Osteossarcoma/sangue , Osteossarcoma/complicações , Osteossarcoma/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Adulto Jovem , gama-Glutamil Hidrolase/economia , gama-Glutamil Hidrolase/uso terapêutico
8.
Tissue Eng Part A ; 21(1-2): 35-44, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24941900

RESUMO

BACKGROUND: Acellular dermal matrices (ADMs) have been commonly used in expander-based breast reconstruction to provide inferolateral prosthesis coverage. Although the clinical performance of these biologic scaffold materials varies depending on a number of factors, an in-depth systematic characterization of the host response is yet to be performed. The present study evaluates the biochemical composition and structure of two ADMs, AlloDerm(®) Regenerative Tissue Matrix and AlloMax™ Surgical Graft, and provides a comprehensive spatiotemporal characterization in a porcine model of tissue expander breast reconstruction. METHODS: Each ADM was characterized with regard to thickness, permeability, donor nucleic acid content, (residual double-stranded DNA [dsDNA]), and growth factors (basic fibroblast growth factor [bFGF], vascular endothelial growth factor [VEGF], and transforming growth factor-beta 1 [TGF-ß1]). Cytocompatibility was evaluated by in vitro cell culture on the ADMs. The host response was evaluated at 4 and 12 weeks at various locations within the ADMs using established metrics of the inflammatory and tissue remodeling response: cell infiltration, multinucleate giant cell formation, extent of ADM remodeling, and neovascularization. RESULTS: AlloMax incorporated more readily with surrounding host tissue as measured by earlier and greater cell infiltration, fewer foreign body giant cells, and faster remodeling of ADM. These findings correlated with the in vitro composition and cytocompatibility analysis, which showed AlloMax to more readily support in vitro cell growth. CONCLUSIONS: AlloMax and AlloDerm demonstrated distinct remodeling characteristics in a porcine model of tissue expander breast reconstruction.


Assuntos
Derme Acelular , Mamoplastia/métodos , Glândulas Mamárias Animais/cirurgia , Dispositivos para Expansão de Tecidos , Animais , Modelos Animais de Doenças , Feminino , Células Gigantes/patologia , Humanos , Teste de Materiais , Camundongos , Células NIH 3T3 , Neovascularização Fisiológica , Sus scrofa
9.
Pharmacogenomics ; 15(8): 1065-78, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25084200

RESUMO

AIM: Our objective was to describe the association between voriconazole concentrations and CYP2C19 diplotypes in pediatric cancer patients, including children homozygous for the CYP2C19*17 gain-of-function allele. MATERIALS & METHODS: A linear mixed effect model compared voriconazole dose-corrected trough concentrations (n = 142) among CYP2C19 diplotypes in 33 patients (aged 1-19 years). Voriconazole pharmacokinetics was described by a two-compartment model with Michaelis-Menten elimination. RESULTS: Age (p = 0.05) and CYP2C19 diplotype (p = 0.002) were associated with voriconazole concentrations. CYP2C19*17 homozygotes never attained therapeutic concentrations, and had lower dose-corrected voriconazole concentrations (median 0.01 µg/ml/mg/kg; p = 0.02) than CYP2C19*1 homozygotes (median 0.07 µg/ml/mg/kg). Modeling indicates that higher doses may produce therapeutic concentrations in younger children and in those with a CYP2C19*17/*17 diplotype. CONCLUSION: Younger age and the presence of CYP2C19 gain-of-function alleles were associated with subtherapeutic voriconazole concentrations. Starting doses based on age and CYP2C19 status could increase the number of patients achieving therapeutic voriconazole exposure.


Assuntos
Citocromo P-450 CYP2C19/genética , Voriconazol/farmacocinética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Citocromo P-450 CYP2C19/sangue , Feminino , Genótipo , Haplótipos , Homozigoto , Humanos , Lactente , Masculino , Farmacogenética , Voriconazol/sangue , Voriconazol/uso terapêutico
10.
J Pediatr ; 165(3): 447-52.e4, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24768254

RESUMO

OBJECTIVE: To investigate the use of a trigger tool for the detection of adverse drug events (ADE) in a pediatric hospital specializing in oncology, hematology, and other catastrophic diseases. STUDY DESIGN: A medication-based trigger tool package analyzed electronic health records from February 2009 to February 2013. Chart review determined whether an ADE precipitated the trigger. Severity was assigned to ADEs, and preventability was assessed. Preventable ADEs were compared with the hospital's electronic voluntary event reporting system to identify whether these ADEs had been previously identified. The positive predictive values (PPVs) of the entire trigger tool and individual triggers were calculated to assess their accuracy to detect ADEs. RESULTS: Trigger occurrences (n = 706) were detected in 390 patients from 6 medication triggers, 33 of which were ADEs (overall PPV = 16%). Hyaluronidase had the greatest PPV (60%). Most ADEs were category E harm (temporary harm) per the National Coordinating Council for Medication Error Reporting and Prevention index. One event was category H harm (intervention to sustain life). Naloxone was associated with the most grade 4 ADEs per the Common Terminology Criteria for Adverse Events v4.03. Twenty-one (64%) ADEs were preventable, 3 of which were submitted via the voluntary reporting system. CONCLUSION: Most of the medication-based triggers yielded low PPVs. Refining the triggers based on patients' characteristics and medication usage patterns could increase the PPVs and make them more useful for quality improvement. To efficiently detect ADEs, triggers must be revised to reflect specialized pediatric patient populations such as hematology and oncology patients.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Doenças Hematológicas/tratamento farmacológico , Hospitais Pediátricos , Neoplasias/tratamento farmacológico , Dano ao Paciente/prevenção & controle , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino
11.
Pediatr Blood Cancer ; 61(2): 373-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23955991

RESUMO

Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted.


Assuntos
Anafilaxia/induzido quimicamente , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/prevenção & controle , Metotrexato/uso terapêutico , Osteossarcoma/tratamento farmacológico , Anafilaxia/tratamento farmacológico , Neoplasias Ósseas/complicações , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Osteossarcoma/complicações , Prognóstico
12.
ISRN Surg ; 2013: 862549, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23762628

RESUMO

Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and (2) Ventralight ST Mesh + transfascial sutures (TSs). Procedure time and mesh centering accuracy overtop of a simulated surgical defect were evaluated. Results. Echo PS demonstrated a 38.9% reduction in the overall procedure time, as compared to TS. During mesh preparation and positioning, Echo PS demonstrated a 60.5% reduction in procedure time (P < 0.0001). Although a trend toward improved centering accuracy was observed for Echo PS (16.2%), this was not significantly different than TS. Conclusions. Echo PS demonstrated a significant reduction in overall simulated LVHR procedure time, particularly during mesh preparation/positioning. These operative time savings may translate into reduced operating room costs and improved surgeon/operating room efficiency.

13.
Plast Reconstr Surg ; 131(5): 741e-751e, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23629113

RESUMO

BACKGROUND: Postmastectomy breast reconstruction remains one of the most frequently performed plastic surgery procedures in the United States. Acellular dermal matrix has been used extensively in expander-implant breast reconstruction and therefore is an appropriate material to be used to develop a clinically relevant animal model of breast reconstruction. METHODS: The study population consisted of 18 female Yorkshire pigs, which were assigned randomly to bilateral expander breast reconstruction with either AlloMax Surgical Graft or AlloDerm Regenerative Tissue Matrix (n = 9 per group). Each group was further randomized to 4-, 8-, or 12-week time points (n = 3), to evaluate integration and neovascularization by means of microcirculatory and histologic techniques. RESULTS: Microcirculatory analysis revealed early acellular dermal matrix angiogenesis at 4 weeks on the skin flap surfaces only, and well-formed vasculature on both acellular dermal matrix surfaces at 8 weeks. Both surfaces were vascularized and exhibited detectable flow at 12 weeks after implantation. Progressive acellular dermal matrix angiogenesis was also histologically observed over time by means of hematoxylin and eosin-stained slides, as indicated by direct vascular identification/scoring at 4, 8, and 12 weeks. CONCLUSIONS: The authors have developed a clinically relevant large-animal model of breast reconstruction using acellular dermal matrix. The acellular dermal matrix inflammatory, neovascularization, and tissue integration response should be evaluated in an in vivo setting that accurately simulates the anatomy, biomaterials, surgical techniques, and timeframes encountered in human postmastectomy breast reconstruction to appropriately predict clinical performance. Neovascularization of the acellular dermal matrix with detectable blood flow took place after postimplantation week 8, a much slower process than previously reported in models not clinically relevant to acellular dermal matrix-assisted tissue expander breast reconstruction.


Assuntos
Derme Acelular , Mamoplastia/métodos , Modelos Animais , Neovascularização Fisiológica/fisiologia , Sus scrofa , Dispositivos para Expansão de Tecidos , Animais , Implante Mamário/métodos , Feminino , Humanos , Glândulas Mamárias Animais/cirurgia , Mastectomia/métodos , Microcirculação/fisiologia , Complicações Pós-Operatórias , Alicerces Teciduais
14.
Ther Drug Monit ; 35(3): 332-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23666574

RESUMO

PURPOSE: The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex. METHODS: Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses. RESULTS: Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively). CONCLUSIONS: Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.


Assuntos
Monitoramento de Medicamentos/métodos , Imunossupressores/farmacocinética , Neurofibromatose 1/tratamento farmacológico , Sirolimo/farmacocinética , Adolescente , Fatores Etários , Teorema de Bayes , Superfície Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Modelos Biológicos , Dinâmica não Linear , Estudos Retrospectivos , Sirolimo/administração & dosagem , Fatores de Tempo
15.
J Surg Res ; 184(2): 766-73, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23582230

RESUMO

BACKGROUND: Phasix mesh is a fully resorbable implant for soft tissue reconstruction made from knitted poly-4-hydroxybutyrate monofilament fibers. The objectives of this study were to characterize the in vitro and in vivo mechanical and resorption properties of Phasix mesh over time, and to assess the functional performance in a porcine model of abdominal hernia repair. MATERIALS AND METHODS: We evaluated accelerated in vitro degradation of Phasix mesh in 3 mol/L HCl through 120 h incubation. We also evaluated functional performance after repair of a surgically created abdominal hernia defect in a porcine model through 72 wk. Mechanical and molecular weight (MW) properties were fully characterized in both studies over time. RESULTS: Phasix mesh demonstrated a significant reduction in mechanical strength and MW over 120 h in the accelerated degradation in vitro test. In vivo, the Phasix mesh repair demonstrated 80%, 65%, 58%, 37%, and 18% greater strength, compared with native abdominal wall at 8, 16, 32, and 48 wk post-implantation, respectively, and comparable repair strength at 72 wk post-implantation despite a significant reduction in mesh MW over time. CONCLUSIONS: Both in vitro and in vivo data suggest that Phasix mesh provides a durable scaffold for mechanical reinforcement of soft tissue. Furthermore, a Phasix mesh surgical defect repair in a large animal model demonstrated successful transfer of load bearing from the mesh to the repaired abdominal wall, thereby successfully returning the mechanical properties of repaired host tissue to its native state over an extended time period.


Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/instrumentação , Hidroxibutiratos , Telas Cirúrgicas/normas , Animais , Modelos Animais de Doenças , Herniorrafia/métodos , Técnicas In Vitro , Masculino , Teste de Materiais , Peso Molecular , Estresse Mecânico , Suínos
16.
J Clin Oncol ; 29(33): 4351-7, 2011 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-22010014

RESUMO

PURPOSE: To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB). PATIENTS AND METHODS: Enrolled patients received two cycles of topotecan (approximately 1.2 mg/m(2)/d) and cyclophosphamide (400 mg/m(2)/d) for 5 days followed by four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing (target systemic exposure with area under the curve of 50 to 70 ng/mL/hr) was performed. Peripheral-blood stem cell (PBSC) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5, respectively. Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume. Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles. RESULTS: Thirty-one patients were enrolled onto the study. No deaths related to toxicity or dose-limiting toxicities occurred during induction. Mucositis rarely occurred after topotecan cycles (9.7%) in contrast to 30% after MSKCC cycles. Thirty patients underwent PBSC collection with median 31.1 × 10(6) CD34+ cells/kg (range, 1.8 to 541.8 × 10(6) CD34+ cells/kg), all negative for tumor contamination by immunocytochemical analysis. Targeted topotecan systemic exposure was achieved in 26 (84%) of 31 patients. At the end of induction, 26 patients (84%) had tumor response and one patient had progressive disease. In the overall cohort, 3-year event-free and overall survival were 37.8% ± 9.4% and 57.1% ± 9.4%, respectively. CONCLUSION: This pilot induction regimen was well tolerated with expected and reversible toxicities. These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Quimioterapia de Indução , Neuroblastoma/tratamento farmacológico , Inibidores da Topoisomerase I/administração & dosagem , Topotecan/administração & dosagem , Adulto , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neuroblastoma/mortalidade , Projetos Piloto , Topotecan/efeitos adversos , Topotecan/farmacocinética
18.
Plast Reconstr Surg ; 125(2): 446-453, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20124830

RESUMO

BACKGROUND: To plan abdominal perforator-based microsurgical breast reconstruction, duplex ultrasound is often employed to preoperatively identify the location of abdominal wall perforating vessels. Recently, several groups have published the use of computed tomography angiography for preoperative planning in perforator flap breast reconstruction. The purpose of this study was to compare the accuracy of computed tomography angiography in locating clinically useful abdominal wall perforators with that of duplex ultrasound. METHODS: A prospective study was conducted of 22 consecutive patients undergoing 30 abdomen-based microsurgical breast reconstructions using both preoperative computed tomography angiography and duplex ultrasound. Perforator data were obtained with both computed tomography angiography and ultrasound. The two largest perforators were chosen per abdominal side for comparison between studies. In addition, the locations of perforators were confirmed at surgery. RESULTS: Computed tomography angiography preoperatively identified 83 of the largest perforators, while only 55 of these large perforators (66.3 percent) were preoperatively identified on ultrasound. No superficial inferior epigastric arteries were identified by ultrasound. However, in all eight breast reconstructions performed with the superficial inferior epigastric system, the superficial inferior epigastric arteries were identified preoperatively as adequate size for microsurgical transfers, with an average diameter of 1.6 mm. CONCLUSIONS: There are many advantages to preoperative computed tomography angiography for planning abdominal perforator-based microsurgical breast reconstruction, including accurate identification of perforating vessels, the underlying branching pattern of the deep inferior epigastric artery, and the presence of the superficial inferior epigastric vessels. This study demonstrates the superiority of computed tomography angiography over duplex ultrasound as a tool for preoperative planning of perforator-based breast reconstruction.


Assuntos
Angiografia , Mamoplastia/métodos , Cuidados Pré-Operatórios/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler Dupla , Abdome/diagnóstico por imagem , Abdome/cirurgia , Adulto , Artérias Epigástricas/diagnóstico por imagem , Feminino , Humanos , Imageamento Tridimensional , Microcirurgia/métodos , Estudos Prospectivos , Radiografia Abdominal , Ultrassonografia Doppler em Cores
19.
Ann Plast Surg ; 64(3): 311-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20179480

RESUMO

There are multiple techniques used to reconstruct the vagina after oncologic extirpation. However, the long-term functional results of vaginal reconstruction are not well appreciated.A review was conducted of all 27 consecutive patients undergoing vaginal reconstruction from 1990 to 2007. A modified Sexual Adjustment Questionnaire was mailed to patients. Also, a review of all published studies of myocutaneous vaginal reconstructions with postoperative sexual function was performed.Patients underwent vertical rectus abdominis myocutaneous flap (18), gracilis (4), pudendal artery fasciocutaneous flaps (3), or rectus and peritoneum flaps (2). Of 27 patients, 14 (52%) had postoperative complications. Of 12 patients, 6 (50%) reported sexual function. This compares with an overall 52.3% return to sexual function reported in 8 studies of myocutaneous vaginal reconstruction.Vaginal reconstruction yielding sexual function remains a challenge to the reconstructive surgeon. Preoperative education of the patient about sexual function is of paramount importance.


Assuntos
Coito/fisiologia , Satisfação do Paciente , Procedimentos de Cirurgia Plástica/métodos , Vagina/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
20.
Plast Reconstr Surg ; 124(6): 2173-2178, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19952677

RESUMO

BACKGROUND: Trainees in plastic surgery graduating in the midst of the current economic recession face unique financial challenges. These issues have the potential to affect future training and practice plans. METHODS: A 13-item questionnaire regarding issues influencing career plans was administered to senior plastic and reconstructive surgery trainees attending the 2009 American Society of Plastic Surgery Senior Residents Conference, in Austin, Texas. RESULTS: Of 97 conference attendees, 57 (58.7 percent) completed the survey representing all regions of the United States (33.3 percent of trainees nationwide). Trainees in the traditional training model (i.e., plastic surgery fellowship after surgery residency) were significantly less likely to pursue additional subspecialty training (29.6 percent) compared with trainees in integrated (76.9 percent) or combined programs (58.8 percent) (p = 0.012). Trainees who have dependents were significantly more likely to go into practice without fellowship (69 versus 38.2 percent, p = 0.031). Outstanding educational debt (>$50,000 or >$100,000) did not influence future practice plans. Trainees who are concerned about the national economic recession trended toward entering practice without fellowship training (70.0 versus 40.5 percent, p = 0.052). Of the factors surveyed, only anticipated fellowship training was significantly associated with plans to pursue academic practice (p = 0.002). CONCLUSIONS: The majority of graduating trainees enter private practice without additional subspecialty fellowship training. Neither exceptional debt nor concern about the current economic recession was the primary determinant of future career plans, whereas trainees in a traditional model of plastic surgery and trainees with dependents were more likely to enter practice without further fellowship training.


Assuntos
Escolha da Profissão , Economia , Internato e Residência/estatística & dados numéricos , Padrões de Prática Médica/tendências , Prática Privada/estatística & dados numéricos , Cirurgia Plástica/tendências , Adulto , Distribuição de Qui-Quadrado , Tomada de Decisões , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Emprego/estatística & dados numéricos , Bolsas de Estudo/estatística & dados numéricos , Feminino , Humanos , Masculino , Probabilidade , Estatísticas não Paramétricas , Cirurgia Plástica/economia , Cirurgia Plástica/educação , Inquéritos e Questionários , Incerteza , Estados Unidos , Adulto Jovem
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