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1.
Sensors (Basel) ; 22(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502127

RESUMO

The abbreviated injury score (AIS) is commonly used as a grading system for inhalation injuries. While inhalation injury grades have inconsistently been shown to correlate positively with the time mechanical ventilation is needed, grading is subjective and relies heavily on the clinicians' experience and expertise. Additionally, no correlation has been shown between these patients' inhalation injury grades and outcomes. In this paper, we propose a novel inhalation injury grading method which uses deep learning algorithms in bronchoscopy images to determine the injury grade from the carbonaceous deposits, blistering, and fibrin casts in the bronchoscopy images. The proposed method adopts transfer learning and data augmentation concepts to enhance the accuracy performance to avoid overfitting. We tested our proposed model on the bronchoscopy images acquired from eighteen patients who had suffered inhalation injuries, with the degree of severity 1, 2, 3, 4, 5, or 6. As performance metrics, we consider accuracy, sensitivity, specificity, F-1 score, and precision. Experimental results show that our proposed method, with both transfer learning and data augmentation components, provides an overall 86.11% accuracy. Moreover, the experimental results also show that the performance of the proposed method outperforms the method without transfer learning or data augmentation.


Assuntos
Broncoscopia , Respiração Artificial , Humanos , Aprendizado de Máquina
2.
Plast Reconstr Surg Glob Open ; 10(3): e4197, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35317465

RESUMO

Necrotizing soft tissue infections (NSTIs) cause rapidly progressing destruction of skin and soft tissue, leaving large soft tissue defects and necessitating complex reconstruction. RECELL, an autologous cell harvesting device, provides a regenerative epidermal suspension (RES) from a small split-thickness skin biopsy for the substitution of (or in addition to) split-thickness skin grafting (STSG). We present a case of a 56-year-old man with extensive NSTI managed by serial debridement, leading to a degloving injury to the right upper extremity, axilla, flank and back, which was later reconstructed using RES application in conjunction with STSG and Integra placement. At his 2-week hospital follow-up, the patient was healing well with limited right upper extremity range of motion, but continued improvement seen with physical and occupational therapy. Due to the patient's significant soft tissue defect, a unique reconstructive plan was required using both Integra and RECELL in conjunction with STSG. RECELL, in conjunction with STSG, should be considered for the treatment of significant soft tissue defects such as those found in NSTI.

3.
Burns ; 48(5): 1246-1252, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34629187

RESUMO

INTRODUCTION: We examined the interactive effects of copper (Cu) and overweight (overweight) and obesity on outcomes of burn patients. We posited that higher baseline Cu among burn patients with overweight or obesity will be associated with poor clinical outcomes vs. patients with a normal weight. METHODS: A retrospective review was conducted on patients with ≥20% total burn surface area (TBSA) with an initial measurement of Cu. Patients were grouped by body mass index (BMI). The interactions between baseline Cu and BMI groups on multiple burn patient outcomes were examined in a series of multiple regression models. RESULTS: One-hundred-and-sixty patients met eligibility (age 43.9 ± 17.5, males 86.3%, normal weight:overweight:obesity = 53:38:69). BMI groups did not differ significantly on demographics, burn severity, or baseline biochemistry. Normal weight patients with higher baseline Cu had shorter ICU stay (ICUS), shorter length of stay (LOS), and had fewer operations (Ps < 0.05). In contrast, overweight and obese patients with higher baseline Cu had longer ICU stay (p = 0.001 and p = 0.034), LOS (p = 0.005 and p = 0.066), and increased operations (p = 0.001 and p = 0.067). CONCLUSIONS: Higher baseline Cu seems associated with adverse outcomes in overweight and obese burn patients. Further research is needed to confirm this association and explore the direction of causality.


Assuntos
Queimaduras , Sobrepeso , Adulto , Índice de Massa Corporal , Queimaduras/complicações , Cobre , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Retrospectivos
4.
J Burn Care Res ; 43(1): 141-148, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34329478

RESUMO

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior.


Assuntos
Unidades de Queimados/tendências , Queimaduras/terapia , Padrões de Prática Médica/estatística & dados numéricos , Benchmarking , Unidades de Queimados/economia , Recursos Comunitários , Humanos , Estados Unidos
5.
Metabolomics ; 16(3): 40, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170472

RESUMO

INTRODUCTION: Sepsis is a leading cause of mortality in burn patients. One of the major causes of sepsis in burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa. OBJECTIVES: To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa infection of burns. METHODS: Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B-I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. RESULTS: Serum levels of 19 metabolites were significantly increased in the B-I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism), malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans-4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B-I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. CONCLUSION: In all, 26 metabolites were identified, including a unique combination of five metabolites (trans-4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in burn patients.


Assuntos
Queimaduras/metabolismo , Pseudomonas aeruginosa/metabolismo , Sepse/metabolismo , Infecção dos Ferimentos/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Queimaduras/sangue , Queimaduras/microbiologia , Cromatografia Gasosa , Modelos Animais de Doenças , Feminino , Espectrometria de Massas , Metabolômica , Camundongos , Sepse/sangue , Sepse/microbiologia , Infecção dos Ferimentos/sangue , Infecção dos Ferimentos/microbiologia
6.
J Burn Care Res ; 40(6): 953-960, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31326982

RESUMO

Probiotics are often used in critically ill patients to prevent antibiotic-associated complications, including Clostridium difficile colitis. However, clinical evidence of their efficacy is lacking. The objective of this study is to assess the impact of prophylactic probiotic administration on bowel function, gut microbial diversity, and nutritional markers in adult burn patients. A retrospective cohort study was done on 108 burn patients aged 18 to 89. Patients were given >1 million colony-forming units per day of Lactobacillus acidophilus and Lactobacillus rhamnosus. Testing for C. difficile was used as a surrogate marker for the presence of diarrhea. Serum C-reactive protein and prealbumin values were measured. Additionally, the gut microbial diversity of eight patients was tracked via 16S quantitative PCR before and throughout the course of a standard probiotic regimen. Patients receiving oral probiotics had more reported diarrhea in the first and second weeks of treatment. In the second week, C-reactive protein levels were increased, while serum prealbumin levels were lower in patients receiving probiotics, suggesting potential malabsorption. Additionally, there was no difference in C. difficile infection, sepsis rates, emesis, or gastric residuals, indicating an absence of therapeutic benefit for probiotic administration in burn patients. Furthermore, it was determined that no discernible benefit to gut microbial diversity was conferred by probiotic therapy. Prophylactic probiotics in burn patients are not associated with improvements in patient outcomes and may in fact be associated with an increased incidence of diarrhea and malabsorption. Additional research is needed before routine use in burn patients.


Assuntos
Queimaduras/epidemiologia , Probióticos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Clostridioides difficile , Infecções por Clostridium/epidemiologia , Diarreia/epidemiologia , Feminino , Microbioma Gastrointestinal , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pré-Albumina/análise , Estudos Prospectivos , Estudos Retrospectivos , Sepse/epidemiologia , Texas/epidemiologia , Vômito/epidemiologia , Adulto Jovem
7.
mSystems ; 4(4)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31086830

RESUMO

Trauma patients (TPs) are highly susceptible to infections, which often lead to sepsis. Among the numerous causative agents, Pseudomonas aeruginosa is especially important, as P. aeruginosa sepsis is often fatal. Understanding the mechanism of its pathogenesis in bloodstream infections is imperative; however, this mechanism has not been previously described. To examine the effect of trauma-induced changes in blood on the expression of P. aeruginosa genes, we grew strain UCBPP-PA14 (PA14) in blood samples from eight TPs and seven healthy volunteers (HVs). Compared with its growth in blood from HVs, the growth of PA14 in blood from TPs significantly altered the expression of 285 genes. Genes whose expression was significantly increased were related to carbon metabolism, especially malonate utilization and mannitol uptake, and efflux of heavy metals. Genes whose expression was significantly reduced included genes of the type VI secretion system, genes related to uptake and metabolism of amino acids, and genes related to biosynthesis and transport of the siderophores pyoverdine and pyochelin. These results suggest that during systemic infection in trauma patients, and to adapt to the trauma-induced changes in blood, P. aeruginosa adjusts positively and negatively the expression of numerous genes related to carbon metabolism and virulence, respectively. IMPORTANCE While a considerable body of knowledge regarding sepsis in trauma patients is available, the potential influence of trauma-induced changes in the blood of these patients on the pathogenesis of Pseudomonas aeruginosa is basically an unexplored area. Rather than using standard laboratory media, we grew P. aeruginosa in whole blood from either healthy volunteers or trauma patients. The specific changes in the P. aeruginosa transcriptome in response to growth in blood from trauma patients reflect the adaptation of this organism to the bloodstream environment. This knowledge is vital for understanding the strategies this pathogen uses to adapt and survive within the host during systemic infection. Such information will help researchers and clinicians to develop new approaches for treatment of sepsis caused by P. aeruginosa in trauma patients, especially in terms of recognizing the effects of specific therapies (e.g., iron, zinc, or mannitol) on the organism. Further, this information can most likely be extrapolated to all patients with P. aeruginosa septicemia.

8.
J Burn Care Res ; 39(5): 694-702, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-29800234

RESUMO

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG.


Assuntos
Queimaduras/cirurgia , Transplante de Pele , Coleta de Tecidos e Órgãos/instrumentação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Telas Cirúrgicas , Transplante Autólogo , Resultado do Tratamento , Cicatrização , Adulto Jovem
9.
J Surg Case Rep ; 2018(4): rjy058, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29644039

RESUMO

Condyloma acuminata, or anogenital warts, caused by human papillomavirus are the most common sexually transmitted disease. In rare cases, the disease could progress to an extensive neoplasm called Buschke-Löwenstein tumor (BLT), also known as giant condyloma acuminatum. BLT differs from normal condyloma acuminata by presenting with locally invasive growth, lack of spontaneous resolution, tendency for recurrence after treatment and potential for malignant transformation. We examine a BLT case reaching large dimensions in the anorectal region treated with neoadjuvant chemoradiation therapy and surgical excision of residual lesions. Furthermore, continuous follow-up care can help identify and prevent recurrence or malignant transformation of the tumor.

10.
Infect Immun ; 86(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29061710

RESUMO

The opportunistic pathogen Pseudomonas aeruginosa is a major cause of sepsis in severely burned patients. If it is not eradicated from the wound, it translocates to the bloodstream, causing sepsis, multiorgan failure, and death. We recently described the P. aeruginosa heparinase-encoding gene, hepP, whose expression was significantly enhanced when P. aeruginosa strain UCBPP_PA14 (PA14) was grown in whole blood from severely burned patients. Further analysis demonstrated that hepP contributed to the in vivo virulence of PA14 in the Caenorhabditis elegans model. In this study, we utilized the murine model of thermal injury to examine the contribution of hepP to the pathogenesis of P. aeruginosa during burn wound infection. Mutation of hepP reduced the rate of mortality from 100% for mice infected with PA14 to 7% for mice infected with PA14::hepP While comparable numbers of PA14 and PA14::hepP bacteria were recovered from infected skin, only PA14 was recovered from the livers and spleens of infected mice. Despite its inability to spread systemically, PA14::hepP formed perivascular cuffs around the blood vessels within the skin of the thermally injured/infected mice. Intraperitoneal inoculation of the thermally injured mice, bypassing the need for translocation, produced similar results. The rate of mortality for mice infected with PA14::hepP was 0%, whereas it was 66% for mice infected with PA14. As before, only PA14 was recovered from the livers and spleens of infected mice. These results suggest that hepP plays a crucial role in the pathogenesis of PA14 during burn wound infection, most likely by contributing to PA14 survival in the bloodstream of the thermally injured mouse during sepsis.


Assuntos
Proteínas de Bactérias/genética , Queimaduras/microbiologia , Heparina Liase/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Virulência/genética , Infecção dos Ferimentos/microbiologia , Animais , Feminino , Camundongos , Mutação/genética , Sepse/microbiologia , Pele/microbiologia
11.
BMC Microbiol ; 17(1): 233, 2017 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-29246112

RESUMO

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections in immunocompromised hosts including severely burned patients. In burn patients, P. aeruginosa infection often leads to septic shock and death. Despite numerous studies, the influence of severe thermal injuries on the pathogenesis of P. aeruginosa during systemic infection is not known. Through RNA-seq analysis, we recently showed that the growth of P. aeruginosa strain UCBPP-PA14 (PA14) in whole blood obtained from severely burned patients significantly altered the expression of the PA14 transcriptome when compared with its growth in blood from healthy volunteers. The expression of PA14_23430 and the adjacent gene, PA14_23420, was enhanced by seven- to eightfold under these conditions. RESULTS: Quantitative real-time PCR analysis confirmed the enhancement of expression of both PA14_23420 and PA14_23430 by growth of PA14 in blood from severely burned patients. Computer analysis revealed that PA14_23430 (hepP) encodes a potential heparinase while PA14_23420 (zbdP) codes for a putative zinc-binding dehydrogenase. This analysis further suggested that the two genes form an operon with zbdP first. Presence of the operon was confirmed by RT-PCR experiments. We characterized hepP and its protein product HepP. hepP was cloned from PA14 by PCR and overexpressed in E. coli. The recombinant protein (rHepP) was purified using nickel column chromatography. Heparinase assays using commercially available heparinase as a positive control, revealed that rHepP exhibits heparinase activity. Mutation of hepP resulted in delay of pellicle formation at the air-liquid interface by PA14 under static growth conditions. Biofilm formation by PA14ΔhepP was also significantly reduced. In the Caenorhabditis elegans model of slow killing, mutation of hepP resulted in a significantly lower rate of killing than that of the parent strain PA14. CONCLUSIONS: Changes within the blood of severely burned patients significantly induced expression of hepP in PA14. The heparinase encoded by hepP is a potential virulence factor for PA14 as HepP influences pellicle formation as well as biofilm development by PA14 and the protein is required for full virulence in the C. elegans model of slow killing.


Assuntos
Proteínas de Bactérias/genética , Regulação Enzimológica da Expressão Gênica , Heparina Liase/genética , Heparina Liase/metabolismo , Infecções por Pseudomonas/enzimologia , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/patogenicidade , Animais , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Queimaduras/sangue , Queimaduras/imunologia , Queimaduras/microbiologia , Caenorhabditis elegans/microbiologia , Escherichia coli/genética , Perfilação da Expressão Gênica , Heparina Liase/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Mutação/genética , Óperon/genética , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
PLoS One ; 11(3): e0149229, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26933952

RESUMO

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised hosts including severely burned patients. After multiplying within the burn wound, P. aeruginosa translocate into the bloodstream causing bacterial sepsis frequently leading to organ dysfunction and septic shock. Although the pathogenesis of P. aeruginosa infection of thermally-injured wounds has been extensively analyzed, little is known regarding the ability of P. aeruginosa to adapt and survive within the blood of severely burned patients during systemic infection. To identify such adaptations, transcriptome analyses (RNA-seq) were conducted on P. aeruginosa strain PA14 that was grown in whole blood from a healthy volunteer or three severely burned patients. Compared with growth in blood from healthy volunteers, growth of PA14 in the blood from severely burned patients significantly altered the expression of 2596 genes, with expression of 1060 genes enhanced, while that of 1536 genes was reduced. Genes whose expression was significantly reduced included genes related to quorum sensing, quorum sensing-controlled virulence factors and transport of heme, phosphate, and phosphonate. Genes whose expression was significantly enhanced were related to the type III secretion system, the pyochelin iron-acquisition system, flagellum synthesis, and pyocyanin production. We confirmed changes in expression of many of these genes using qRT-PCR. Although severe burns altered the levels of different blood components in each patient, the growth of PA14 in their blood produced similar changes in the expression of each gene. These results suggest that, in response to changes in the blood of severely burned patients and as part of its survival strategy, P. aeruginosa enhances the expression of certain virulence genes and reduces the expression of others.


Assuntos
Queimaduras/complicações , Queimaduras/microbiologia , Regulação Bacteriana da Expressão Gênica , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/genética , Adulto , Queimaduras/sangue , Humanos , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/sangue , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum , Transcriptoma , Sistemas de Secreção Tipo III/genética
13.
Burns Trauma ; 2(4): 201-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27602383

RESUMO

The early determination of healing potential in indeterminate thickness burns may be difficult to establish by visual inspection alone, even for experienced burn practitioners. This case series explores the use of indocyanine green (ICG) fluorescence using portable bedside assessment as a potential tool for early determination of burn depth. Three subjects with indeterminate thickness burns had daily perfusion assessment using ICG fluorescence assessment using the SPY machine (SPY®, Lifecell Corp., NJ, USA) in addition to standard burn care. The fluorescence was quantified as a percentage of the perfusion of intact skin, and areas of hypo- and hyper-perfusion were indicated. The study was concluded when the burn surgeon, blinded to the ICG results, made a clinical determination of the need for skin grafting or discharge. The perfusion in areas of differing depth of burn were compared over the entire study period to determine both the magnitude of difference, and the point in the time course of healing when these changes became evident. Significant differences in perfusion were noted between burned areas of varying depth. These differences were evident as early as the first post-burn day, and persisted till the completion of the study. ICG fluorescence represents a potential adjunct in burn assessment in this first longitudinal study of its use; however much more systematic research will be required to judge the feasibility of clinical implementation.

14.
Med Microbiol Immunol ; 202(2): 131-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23007678

RESUMO

Diabetic patients are more susceptible to the development of chronic wounds than non-diabetics. The impaired healing properties of these wounds, which often develop debilitating bacterial infections, significantly increase the rate of lower extremity amputation in diabetic patients. We hypothesize that bacterial biofilms, or sessile communities of bacteria that reside in a complex matrix of exopolymeric material, contribute to the severity of diabetic wounds. To test this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to cause biofilm-associated infections. Utilizing this model, we observed that diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired bacterial clearing and wound closure in comparison with their non-diabetic littermates. While treating diabetic mice with insulin improved their overall health, it did not restore their ability to resolve P. aeruginosa wound infections or speed healing. In fact, the prevalence of biofilms and the tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice were treated with insulin. Insulin treatment was observed to directly affect the ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that the chronically wounded diabetic mouse appears to be a useful model to study wound healing and biofilm infection dynamics, and suggest that the diabetic wound environment may promote the formation of biofilms. Further, this model provides for the elucidation of mechanistic factors, such as the ability of insulin to influence antimicrobial effectiveness, which may be relevant to the formation of biofilms in diabetic wounds.


Assuntos
Antibacterianos/farmacologia , Biofilmes , Diabetes Mellitus Experimental/complicações , Farmacorresistência Bacteriana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/uso terapêutico , Aderência Bacteriana , Doença Crônica , Diabetes Mellitus Experimental/tratamento farmacológico , Feminino , Perfilação da Expressão Gênica , Insulina/administração & dosagem , Insulina/farmacologia , Camundongos , Prevalência , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/epidemiologia
15.
Artif Organs ; 36(2): 139-50, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22339724

RESUMO

An effective hemoglobin (Hb)-based blood substitute that acts as a physiological oxygen carrier and volume expander ought to stimulate erythropoiesis. A speedy replacement of blood loss with endogenous red blood cells should be an essential feature of any blood substitute product because of its relatively short circulatory retention time and high autoxidation rate. Erythropoiesis is a complex process controlled by oxygen and redox-regulated transcription factors and their target genes that can be affected by Hb physicochemical properties. Using an in vitro cellular model, we investigated the molecular mechanisms of erythropoietic action of unmodified tetrameric Hb (UHb) and Hb cross-linked with adenosine-5'-triphosphate (ATP), adenosine, and reduced glutathione (GSH). These effects were studied under normoxic and hypoxic conditions. Results indicate that these Hb solutions have different effects on stabilization and nuclear translocation of hypoxia-inducible factor (HIF)-1 alpha, induction of the erythropoietin (EPO) gene, activation of nuclear factor (NF)-kappa B, and expression of the anti-erythropoietic agents-tumor necrosis factor-alpha and transforming growth factor-beta 1. UHb suppresses erythropoiesis by increasing the cytoplasmic degradation of HIF-1 alpha and decreasing binding to the EPO gene while inducing NF-kappa B-dependent anti-erythropoietic genes. Cross-linked Hb accelerates erythropoiesis by downregulating NF-kappa B, stabilizing and facilitating HIF-1 alpha binding to the EPO gene, under both oxygen conditions. ATP and adenosine contribute to normoxic stabilization of HIF-1 and, with GSH, inhibit the NF-kappa B pathway that is involved in the suppression of erythroid-specific genes. Proper chemical/pharmacological modification is required to consider acellular Hb as an erythropoiesis-stimulating agent.


Assuntos
Substitutos Sanguíneos/química , Substitutos Sanguíneos/farmacologia , Glutationa/química , Glutationa/farmacologia , Hematínicos/química , Hematínicos/farmacologia , Trifosfato de Adenosina/química , Trifosfato de Adenosina/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Hipóxia Celular , Linhagem Celular , Reagentes de Ligações Cruzadas/química , Eritropoetina/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
PLoS One ; 6(11): e27317, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22076151

RESUMO

Chronic wound infections are typically polymicrobial; however, most in vivo studies have focused on monospecies infections. This project was designed to develop an in vivo, polymicrobial, biofilm-related, infected wound model in order to study multispecies biofilm dynamics and in relation to wound chronicity. Multispecies biofilms consisting of both Gram negative and Gram positive strains, as well as aerobes and anaerobes, were grown in vitro and then transplanted onto the wounds of mice. These in vitro-to-in vivo multi-species biofilm transplants generated polymicrobial wound infections, which remained heterogeneous with four bacterial species throughout the experiment. We observed that wounded mice given multispecies biofilm infections displayed a wound healing impairment over mice infected with a single-species of bacteria. In addition, the bacteria in the polymicrobial wound infections displayed increased antimicrobial tolerance in comparison to those in single species infections. These data suggest that synergistic interactions between different bacterial species in wounds may contribute to healing delays and/or antibiotic tolerance.


Assuntos
Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/microbiologia , Biofilmes/crescimento & desenvolvimento , Interações Microbianas , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/farmacologia , Bactérias/patogenicidade , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/genética , Biodiversidade , Doença Crônica , DNA Bacteriano/genética , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Especificidade da Espécie , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico
18.
J Exp Psychol Appl ; 17(3): 210-32, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21942312

RESUMO

Minimally invasive surgery (MIS) is performed for a growing number of treatments. Whereas open surgery requires large incisions, MIS relies on small incisions through which instruments are inserted and tissues are visualized with a camera. MIS results in benefits for patients compared with open surgery, but degrades the surgeon's perceptual-motor performance. We used a laparoscopic simulator to measure effects of type (top, front, side) and number (1, 3) of camera views on manual manipulation and manual aiming tasks. These experimental manipulations had implications for perceptual and cognitive processing including frame of reference, movement compatibility, compression, task-information specificity, information integration, attentional demands, and information extraction. Camera views generally degraded performance compared with direct viewing, but learning occurred. Generally, a top view resulted in the best performance, followed by front and side views. Benefits of multiple views depended on practice and the direction of grasper movement. Mappings between movement direction and camera view, the consistency of those mappings, and task difficulty affected performance. The benefits and costs for perceptual and cognitive processing that were introduced by a given camera view were not necessarily weighted equally. Costs and benefits must be considered specifically for each task and for each combination of camera view and movement direction. Surgeons may consider using a top view, using side views only when necessary, and using a consistent view when performing repetitive movements.


Assuntos
Competência Clínica , Laparoscópios , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Desempenho Psicomotor , Adulto , Percepção de Profundidade , Feminino , Humanos , Laparoscopia/métodos , Masculino
19.
Burns ; 37(2): 312-21, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21130579

RESUMO

PURPOSE: Topical treatment of burn wounds is essential as reduced blood supply in the burned tissues restricts the effect of systemic antibiotics. On the burn surface, microorganisms exist within a complex structure termed a biofilm, which enhances bacterial resistance to antimicrobial agents significantly. Since bacteria differ in their ability to develop biofilms, the susceptibility of these biofilms to topically applied antibiotics varies, making it essential to identify which topical antibiotics efficiently disrupt or prevent biofilms produced by these pathogens. Yet, a simple in vitro assay to compare the susceptibility of biofilms produced by burn wound isolates to different topical antibiotics has not been reported. METHODS: Biofilms were developed by inoculating cellulose disks on agar plates with burn wound isolates and incubating for 24h. The biofilms were then covered for 24h with untreated gauze or gauze coated with antibiotic ointment and remaining microorganisms were quantified and visualized microscopically. RESULTS: Mupirocin and triple antibiotic ointments significantly reduced biofilms produced by the Staphylococcus aureus and Pseudomonas aeruginosa burn wound isolates tested, as did gentamicin ointment, with the exception of one P. aeruginosa clinical isolate. CONCLUSIONS: The described assay is a practical and reproducible approach to identify topical antibiotics most effective in eliminating biofilms produced by burn wound isolates.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Queimaduras/microbiologia , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologia , Análise de Variância , Bacitracina/uso terapêutico , Biofilmes/crescimento & desenvolvimento , Quimioterapia Combinada , Gentamicinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Mupirocina/farmacologia , Neomicina/uso terapêutico , Pomadas/farmacologia , Polimixina B/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
20.
J Surg Res ; 163(2): 250-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20538291

RESUMO

BACKGROUND: Studies with limited sample sizes have found colorectal signet ring carcinoma (SRC), to be prognostically similar to high grade adenocarcinoma (HGA); the relationship of these tumors to undifferentiated adenocarcinoma (UND) has not yet been fully elucidated. This study of Surveillance, Epidemiology, and End Results (SEER) program data compared the histotypes. METHODS: Registered as having been diagnosed between 1988 and 2003 were 2,246 SRC, 32,999 HGA, and 920 UND. Analyses were performed to determine the presence or absence of differences in survival and extent at presentation. RESULTS: SRC, compared with HGA, was more likely to (1) be confined to an in situ stage or within a polyp, (2) have invaded visceral peritoneum, (3) have spread to contiguous organs, and (4) have metastasized. No differences between SRC and UND were seen, although this may have been due to small UND sample size. SRC was associated with a worse prognosis than HGA for patients with (1) T3 tumors, (2) contiguous organ spread, and (3) visceral peritoneal invasion. UND was associated with a worse prognosis than SRC among patients with metastases. CONCLUSIONS: These three histotypes of aggressive colorectal cancer are separate entities that should be regarded as such. Future study with respect to SRC should include further evaluation of T1 and T2 patients with appropriate sample size populations and the potential utility of peritoneal sampling and frozen section evaluation of non-mucosal margins.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
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