RESUMO
OBJECTIVES: Atherosclerosis is a hallmark of cardiovascular disease. Shear stress on endothelial cells has been linked to atherogenesis and to fibrous cap thinning and rupture. Pericytes reside in the sub-endothelial space of vessels and have vasoprotective effects. They are subjected to shear stress when endothelial cell integrity is disrupted. The aim was to investigate the susceptibility and response of pericytes to shear stress. METHODS: Endothelial cells and pericytes were seeded in two dimensional monocultures and co-cultures, and in a novel three dimensional co-culture system and were subjected to no, low and high shear stress (0, 10, 30 dyne/cm2) for 48 h. The morphological response to flow was assessed by histology and the expression of extracellular matrix proteins was analysed using quantitative polymerase chain reaction, immunoblotting, and ELISA. RESULTS: While endothelial cells aligned into flow direction, pericytes aligned perpendicularly (p < .001), indicating that they must be capable of sensing flow. When pericytes were embedded into a 3D matrix they showed similar alignment and pericytes built long processes towards the lumen. Under shear stress endothelial cells upregulated "a disintegrin and metalloproteinase with thrombospondin motif 1" (ADAMTS-1) (p < .01) and pericytes upregulated "tissue inhibitor of matrix metalloproteinase" (TIMP) 3 (p < .05), an inhibitor of ADAMTS-1, meanwhile differential expression of extracellular matrix (ECM) proteins could be detected in co-cultures of both cells. For TIMP3 expression direct cell-cell contact between endothelial cells and pericytes was required. CONCLUSION: The experiments highlight that pericytes are able to sense direct flow thereby regulating ECM proteins known to be involved in vascular remodelling. Furthermore, pericytes counter-regulate endothelial ADAMTS-1 by protective TIMP3 expression to prevent matrix degradation and maintain vascular stability. For this protective effect direct cell contact was necessary. This observation might represent an adaptive, protective mechanism of pericytes to counteract endothelial damage in the onset of atherosclerosis.
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Proteína ADAMTS1/metabolismo , Células Endoteliais/fisiologia , Pericitos/fisiologia , Resistência ao Cisalhamento/fisiologia , Estresse Mecânico , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Técnicas de Cultura de Células , HumanosRESUMO
Background: Medial implants help a multitude of patients to gain more health, mobility and thus, quality of life. In collaboration with a still growing expectation of life especially, i.e., within Western industrial countries, this has led to an increasing use of implants over the last years. However, although biomechanical characteristics of modern implant materials have improved considerably, one big challenge still exists - the implant-associated infection. Early diagnostic and therapeutic interventions could clearly mitigate this issue, but are general practitioners sufficiently informed regarding this topic? Material and Methods: In March 2013 and in close cooperation with the Lower Saxony association of general practitioners, we initiated a survey to elucidate the information demands of general practitioners regarding the topic of medical implants. A total of 939 members of the association were contacted via fax and 101 (10.8â%) responded. Based on the obtained data, we then evaluated which topics are most interesting for this group of medical professionals. Results: The survey clearly indicates that general practitioners request more general implant-related data, e.g., type and specification of an implant as well as its location within the individual patient and contact addresses of the implanting hospital, but also want more specific information regarding diagnostic and therapeutic strategies in the case of implant-associated complications. Conclusion: The present article reports in detail on the conducted fax survey and shows some initial strategies as to how the identified challenges might be faced.
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Medicina Geral/educação , Capacitação em Serviço , Próteses e Implantes , Inquéritos e Questionários , Telefac-Símile , Currículo , Diagnóstico Precoce , Intervenção Médica Precoce , Alemanha , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/terapiaRESUMO
INTRODUCTION: Polytrauma is the leading cause of morbidity and mortality in young adults (aged 35-45 years). At 30-40%, traumatic hemorrhage is the most frequent preventable cause of death. Approximately every fourth patient with multiple injuries suffers from trauma-induced coagulopathy. METHODS: The current knowledge of prehospital resuscitation of patients with multiple injuries based on a selective literature research and experience in a level I trauma center are presented. RESULTS: Hemorrhagic shock is a clinical diagnosis and the recognition by the first responding emergency physician requires rapid evaluation of the accident situation, injury pattern and patient's hemodynamic status. In the future, tools will help to reliably estimate shock. Development of trauma-induced coagulopathy is multifactorial and is characterized by interaction of tissue damage, shock, hypothermia, acidosis and dilution. Preclinical therapy follows the concept of damage control resuscitation and involves bleeding hemostasis, permissive hypotension with a target systolic blood pressure between 80 and 90 mmHg (≥80 mmHg in presence of traumatic brain injury) by modest infusion of primarily crystalloid solutions, avoiding hypothermia and acidosis. CONCLUSION: The current knowledge and therapy recommendations are presented.
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Transtornos da Coagulação Sanguínea/terapia , Serviços Médicos de Emergência/métodos , Hidratação/métodos , Traumatismo Múltiplo/terapia , Ressuscitação/métodos , Choque Hemorrágico/terapia , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Humanos , Traumatismo Múltiplo/complicações , Traumatismo Múltiplo/diagnóstico , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/etiologiaRESUMO
OBJECTIVE: To compare the in vitro efficacy of graft impregnation with nebacetin versus rifampin versus daptomycin against vascular graft infections caused by Staphylococcus epidermidis and Staphylococcus aureus and nebacetin versus rifampin against Pseudomonas aeruginosa and Escherichia coli. MATERIALS: Twenty-three Dacron-grafts (1 cm2) for each micro-organism were microbiologically tested and eight grafts per antibiotic underwent viability tests against human umbilical vein endothelial cells (ECs). Fifteen grafts (5/antibiotic agent) underwent 15 min impregnation and contamination with 4 ml bacterial solution (optical density (OD (600 nm)): 0.20 ± 0.02). After 24-h-incubation, all grafts were washed with phosphate-buffered saline and underwent sonification to release viable adherent bacteria. OD (600 nm) of the solution was measured. Afterwards, six 1:10 dilution steps took place and colony-forming units (CFUs) were counted. RESULTS: Nebacetin showed comparable efficacy to daptomycin against Gram-positive bacteria. Both eradicated more efficiently S. epidermidis than rifampin (daptomycin:0, rifampin:5 ± 7.3, nebacetin:0 CFU ml(-1), P = 0.0003). All antibiotics showed comparable antibacterial activity against S. aureus. Nebacetin was more efficient than rifampin to eradicate Gram-negative organisms (P. aeruginosa: rifampin:1308 ± 252, nebacetin:8 ± 8 CFU ml(-1), P = 0.01, E. coli: rifampin:294 ± 159, nebacetin:0.2 ± 0.5 CFU ml(-1), P = 0.001), while only rifampin was toxic against ECs (daptomycin:30.88 ± 5.44, rifampin:5.13 ± 5.08, nebacetin:28.50 ± 3.82 ECs/field, P = 0.0003). CONCLUSIONS: Nebacetin showed excellent in vitro antibacterial activity against both Gram-positive and -negative pathogens representing an effective candidate for vascular graft impregnation.
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Antibacterianos/farmacologia , Prótese Vascular/efeitos adversos , Daptomicina/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Pseudomonas aeruginosa/efeitos dos fármacos , Rifampina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/uso terapêutico , Bacitracina/farmacologia , Bacitracina/uso terapêutico , Células Cultivadas , Daptomicina/uso terapêutico , Humanos , Microscopia Eletrônica de Varredura , Neomicina/farmacologia , Neomicina/uso terapêutico , Rifampina/uso terapêuticoRESUMO
Injuries of internal carotid arteries caused by high energy trauma are rare but often combined with poor outcome. Blunt trauma to the head and neck as well as the use of newer motorcycle helmets together with crash circumstances should promptly lead to a differentiated polytrauma management with expansion of radiologic diagnostics. This could lead to a reduction of overlooked dissections and an increase in promptly and correctly treated injuries.
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Acidentes de Trânsito , Lesões das Artérias Carótidas/cirurgia , Dissecação da Artéria Carótida Interna/etiologia , Dissecação da Artéria Carótida Interna/cirurgia , Motocicletas , Ferimentos não Penetrantes/etiologia , Ferimentos não Penetrantes/cirurgia , Adulto , Humanos , Masculino , Resultado do TratamentoRESUMO
The adsorption properties of bovine serum albumin (BSA) on pure titanium (99.99%+) were studied by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). For this purpose, films consisting of BSA were prepared on cleaned titanium sheets in a phosphate buffered solution under different conditions and analysed by ToF-SIMS. The dependence of the surface coverage on the concentration of the protein solution could be determined from the secondary ion mass spectrometry signals. The results agree satisfactorily with the corresponding results obtained by XPS. The observed adsorption behaviour can be fitted by the well-known formula describing a Langmuir isotherm. The Langmuir constant for pH 7 was found to be K = 174 ± 99 lg(-)1.
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Soroalbumina Bovina/química , Titânio/química , Adsorção , Animais , Bovinos , Concentração de Íons de Hidrogênio , Espectroscopia Fotoeletrônica , Espectrometria de Massa de Íon Secundário , Propriedades de SuperfícieRESUMO
OBJECTIVES: To evaluate bioartificial haemodialysis access grafts in a sheep model with respect to patency and morphology. MATERIAL AND METHODS: Bovine internal thoracic arteries (n=28) were decellularised. Fourteen grafts (DC grafts) were directly implanted as cervical AV shunts, the remaining were re-seeded with endothelial cells (ECs) derived from blood samples of the later ovine recipient (EC grafts) first. Following simulated punctures and duplex ultrasound scans to determine patency, grafts were explanted for immunohistochemical characterisation after 3 and 6 months, respectively. DC grafts underwent biomechanical testing for compliance (C), suture retention strength (SRT), and burst pressure (BP) before (n=6) and after (n=6) implantation. RESULTS: Following 3 and 6 months, the majority of EC (n=6/6; n=6/7) and DC grafts (n=5/6; n=5/7) were patent and not relevantly stenosed (peak systolic velocity: EC grafts=76 cm s(-1)±4; DC grafts=77 cm s(-1)±5). Simulated haemodialysis punctures revealed significantly shorter bleeding times in all bioartificial grafts than in native jugular veins (P>0.001). Comparing native carotid arteries with DC grafts prior to and post-implantation, the latter differed significantly with respect to C (P>0.001; P=0.005), whereas only pre-implant DC grafts differed regarding BP (P=0.002); no differences were observed for SRT. Histology revealed complete endothelial surface coverage of EC, but not DC grafts. Furthermore, DC grafts exhibited areas of pronounced tissue calcification. CONCLUSION: The preclinical development of a bioartificial haemodialysis access graft with promising mechanical and morphological properties in a sheep model is feasible.
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Derivação Arteriovenosa Cirúrgica/instrumentação , Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Artéria Torácica Interna/transplante , Diálise Renal , Animais , Fenômenos Biomecânicos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Bovinos , Células Endoteliais/transplante , Estudos de Viabilidade , Hemodinâmica , Imuno-Histoquímica , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/cirurgia , Teste de Materiais , Modelos Animais , Desenho de Prótese , Ovinos , Fatores de Tempo , Alicerces Teciduais , Ultrassonografia Doppler em Cores , Grau de Desobstrução VascularRESUMO
Injuries of great vessels, such as the subclavian or vertebral arteries in childhood are rare. More frequent and therefore better described are dissections of the vertebral artery, which frequently occur following low energy trauma. The combination of dissection of the vertebral and subclavian arteries described in this case study led to sensory affections of the left arm. Therapeutic anticoagulation is the therapy of choice to avoid possible ischemic insults. The therapeutic approach of injuries to the subclavian artery remains unclear and is in the focus of discussions.
Assuntos
Traumatismos em Atletas/cirurgia , Ciclismo/lesões , Artéria Subclávia/lesões , Artéria Subclávia/cirurgia , Traumatismos Torácicos/cirurgia , Dissecação da Artéria Vertebral/cirurgia , Artéria Vertebral/lesões , Artéria Vertebral/cirurgia , Ferimentos não Penetrantes/cirurgia , Adolescente , Angiografia , Anticoagulantes/administração & dosagem , Braço/irrigação sanguínea , Braço/inervação , Traumatismos em Atletas/diagnóstico por imagem , Criança , Terapia Combinada , Hemotórax/cirurgia , Heparina/administração & dosagem , Humanos , Masculino , Artéria Subclávia/diagnóstico por imagem , Síndrome do Roubo Subclávio/diagnóstico por imagem , Síndrome do Roubo Subclávio/cirurgia , Traumatismos Torácicos/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Ferimentos não Penetrantes/diagnóstico por imagemRESUMO
Boron (B) toxicity has become important in areas close to the Mediterranean Sea where intensive agriculture has been developed. The objective of this research was to study the effects of B toxicity (0.5 mM and 2.0 mM B) on nitrogen (N) assimilation of two tomato cultivars that are often used in these areas. Leaf biomass, relative leaf growth rate (RGR(L)), concentration of B, nitrate (NO(3) (-)), ammonium (NH(4) (+)), organic N, amino acids and soluble proteins, as well as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthase (GS), glutamate synthetase (GOGAT) and glutamate dehydrogenase (GDH) activities were analysed in leaves. Boron toxicity significantly decreased leaf biomass, RGR(L), organic N, soluble proteins, and NR and NiR activities. The lowest NO(3) (-) and NH(4) (+) concentration in leaves was recorded when plants were supplied with 2.0 mM B in the root medium. Total B, amino acids, activities of GS, GOGAT and GDH increased under B toxicity. Data from the present study prove that B toxicity causes inhibition of NO(3) (-) reduction and increases NH(4) (+) assimilation in tomato plants.
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Boro/toxicidade , Nitratos/metabolismo , Nitrogênio/metabolismo , Compostos de Amônio Quaternário/metabolismo , Compostos de Amônio Quaternário/farmacologia , Solanum lycopersicum/metabolismo , Glutamato Desidrogenase/metabolismo , Glutamato Sintase (NADH)/metabolismo , Glutamato-Amônia Ligase/metabolismo , Região do MediterrâneoRESUMO
To gain an insight into the role of lignification and membrane permeability in the root response to boron (B) toxicity, lignification-related enzymes and a number of physiological and oxidative stress parameters were analyzed in two tomato (Solanum lycopersicum L.) cultivars (Kosaco and Josefina) subjected to 0.05 (control), 0.5 and 2mM B during 16 days. 2mM B supply inhibited root growth and increased the root B concentration in both tomato cultivars. Although excess B increased the hydrogen peroxide (H2O2) concentration in Kosaco, no major changes were observed in other oxidative-stress-related parameters. High levels of B supply also induced higher lignin deposition in Kosaco roots but did not in Josefina ones. The latter result was associated with an increase of the polyphenol oxidase (PPO), guaiacol peroxidase (GPOX) and soluble syringaldazine peroxidase (SPOX) activity in Kosaco roots. Boron toxicity did not induce lipid peroxidation but increased the leakage of K(+) and the passive efflux of B in tomato roots. We conclude that high concentrations of B do not cause major oxidative or membrane damage in tomato roots. The data also indicate that high levels of B supply induce a higher lignin deposition in Kosaco roots but not in Josefina ones. This phenomenon suggests that lignification is not an essential factor reducing root growth in tomato plants, however, it proves that exist a high genotypic variation in response to excess B at root level.
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BACKGROUND: To evaluate homograft implantation for the urgent treatment of vascular infections on the basis of the course of infection using microbiological findings in perioperatively obtained specimens and during homograft processing. PATIENTS AND METHODS: 85 patients were treated with cryopreserved homografts from 2004-2007. The microbiological findings of the decontamination process of homografts in the tissue bank were evaluated. The perioperative infection profile (microorganisms, CRP, leukocytes, body temperature) of the patients was analysed. RESULTS: Complete microbiological and clinical follow-up for the postoperative course was available for 35 patients, who were treated with homografts from the same tissue bank and finally included into this study. 55 cryopreserved homografts were implanted. 35/55 (64%) homografts were positive for microorganisms before decontamination. 3/35 (9%) homografts remained positive after the decontamination. 33 patients were operated for prosthetic graft infection and 2 for an infiltration of a large vessel from neighbouring malignant disease. The most common infection agent was Staphylococcus aureus. Thirty-day mortality was 20% (7/35). Only in 4/35 (11%) patients were the microorganisms of the intraoperative swabs also detected during the postoperative course. The microorganisms were ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. The patient with ORSA infection died on POD 11 from multiple organ failure and all other patients recovered. None of the postoperative swabs showed the homograft predecontamination microorganisms. Interestingly, a significant association (P = 0.003) between C-reactive protein increase two weeks after surgery and donor-recipient ABO mismatch was found. CONCLUSIONS: The implantation of homografts following the established decontamination is an alternative urgent therapeutic option in vascular infections with encouraging outcomes. The absence of the predecontamination focus in the postoperative specimens of patients, suggests that the postoperative course and outcomes show no strong relation to potential homograft contamination prior to the decontamination process.
Assuntos
Aneurisma Infectado/cirurgia , Aneurisma Roto/cirurgia , Artérias/transplante , Prótese Vascular/efeitos adversos , Criopreservação , Descontaminação , Próteses Valvulares Cardíacas/efeitos adversos , Infecções Relacionadas à Prótese/cirurgia , Coleta de Tecidos e Órgãos , Idoso , Aneurisma Infectado/microbiologia , Aneurisma Infectado/mortalidade , Aneurisma Roto/microbiologia , Aneurisma Roto/mortalidade , Artérias/microbiologia , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Sobrevivência de Enxerto , Mortalidade Hospitalar , Humanos , Artéria Ilíaca/microbiologia , Artéria Ilíaca/patologia , Artéria Ilíaca/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Artéria Pulmonar/microbiologia , Artéria Pulmonar/patologia , Artéria Pulmonar/cirurgia , Reoperação , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
OBJECTIVE: Detecting spinal cord ischemia early during replacement of the thoracoabdominal aorta remains a challenge. In a high risk population, we have re-evaluated the potential impact of ischaemia/damage markers (S100, lactate) in the peripheral blood and CSF for perioperative patient management. PATIENTS AND METHODS: Thirteen patients undergoing replacement of the thoracoabdominal aorta (6 female, age 63 (27-71)) with continuous CSF pressure monitoring and drainage were entered into the study. A total of 485 CSF (C) and serum (S) samples were collected and analysed for S100, lactate and glucose. RESULTS: Two patients suffered from spinal cord injury (SCI) (15%). During and early after surgery, there was a strong correlation between C-S100 levels (r=0.79) and C-lactate levels (r=0.77) with time in patients with SCI. In patients with SCI C-lactate levels increased soon after aortic cross-clamping, whereas C-S100 levels did not become significantly elevated until 6 hours after cross-clamping. CONCLUSION: An increase of C-lactate occurs much earlier than the increase in C-S100 in patients with SCI. Both parameters may be used to adjust protective and therapeutic measures intra- and postoperatively.
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Aorta Abdominal/cirurgia , Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Ácido Láctico/líquido cefalorraquidiano , Monitorização Intraoperatória/métodos , Proteínas S100/líquido cefalorraquidiano , Isquemia do Cordão Espinal/diagnóstico , Adulto , Idoso , Doenças da Aorta/sangue , Doenças da Aorta/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Projetos de Pesquisa , Proteínas S100/sangue , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/prevenção & controle , Isquemia do Cordão Espinal/sangue , Isquemia do Cordão Espinal/líquido cefalorraquidiano , Isquemia do Cordão Espinal/etiologia , Fatores de Tempo , Regulação para CimaRESUMO
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that cleave and degrade a wide spectrum of extracellular matrix components. By enhancing turnover of extracellular matrix, MMP activity is also known to play a key role in tumor cell invasion. Because extracellular protease activity requires efficient release of these proteases to the cellular surface, we investigated storage, transport, and exocytosis of MMP-2 and MMP-9 in human melanoma cells using immunofluorescence, electrical, and biochemical techniques. Immunolabeling of melanoma cells with antibodies specific for MMP-2 and MMP-9 led to the identification of two distinct populations of small cytoplasmatic vesicles containing MMP-2 or MMP-9, respectively. In combination with alpha-tubulin-specific antibodies, both vesicle populations were found to be aligned along the microtubular network. Moreover, the molecular motor protein kinesin is shown to be localized on most of these vesicles, providing evidence that the identified vesicles are actively propelled along microtubules toward the plasma membrane. The functional relevance of these findings is demonstrated using low dosage (5.9 nmol/L) of paclitaxel to affect the microtubular function of melanoma cells. Although cell proliferation is not altered, paclitaxel treatment impairs secretion of MMP-2/MMP-9 and significantly reduces invasive activity in our new cell invasion assay. In conclusion, we demonstrate in melanoma cells that microtubule-dependent traffic of MMP-containing vesicles and exocytosis are critical steps for invasive behavior and therefore are potential targets for specific antitumor drugs.
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Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Melanoma Amelanótico/enzimologia , Melanoma Amelanótico/patologia , Microtúbulos/metabolismo , Animais , Vesículas Citoplasmáticas/enzimologia , Cães , Exocitose , Humanos , Melanoma Amelanótico/metabolismo , Invasividade Neoplásica , Paclitaxel/farmacologia , Frações Subcelulares/enzimologia , Células Tumorais CultivadasRESUMO
PURPOSE: Percutaneous dilatational tracheostomy (PDT) is a standard procedure routinely performed on intensive care units. While complication rates and long-term outcomes have been studied in different patient populations, there are few studies known to these authors involving PDT in trauma patients and the complications which may result. METHODS: Between March 2007 and August 2013, all instances and peri-procedural complications during PDT occurring on the trauma intensive care unit, a unit specialized in the care of injured patients and especially polytrauma patients, were documented. PDTs were performed by a surgeon with the assistance and supervision of another, using bronchoscopic guidance performed by the respiratory medicine department. RESULTS: 289 patients were included in the study, 225 men and 64 women with a mean age of 49 ± 21 years. Complications occurred in 37.4 % of cases. The most common complication, bleeding, occurred in 26.3 % of patients ranging from little to severe bleeding. Fracture of tracheal cartilage occurred in 6 % of PDT cases. Additional complications such as dislocation of the guidewire, hypotension, and oxygen desaturation were observed. Most complications did not require treatment. The second tracheal intercartilaginous space was successfully intubated in 82 % of cases. CONCLUSIONS: PDT is a safe procedure in trauma patients. When considering the severity of complications such as major blood loss, pneumothorax, or death, this evidence suggests that PDT is safer in trauma patients compared to other patient cohorts.
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Broncoscopia/métodos , Estado Terminal , Unidades de Terapia Intensiva , Traqueia/lesões , Traqueostomia , Estado Terminal/terapia , Dilatação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Guias de Prática Clínica como Assunto , Traqueostomia/instrumentação , Traqueostomia/métodos , Desmame do RespiradorRESUMO
Current prosthetic substitutes for heart valves and blood vessels have numerous limitations such as limited durability (biological valves), susceptibility to infection, the necessity of lifelong anticoagulation therapy (prosthetic valves), and reduced patency in small-caliber grafts, for example. Tissue engineering using either polymers or decellularized native allogeneic or xenogenic heart valve/vascular matrices may provide the techniques to develop the ideal heart valve or vascular graft. The matrix scaffold serves as a basis on which seeded cells can organise and develop into the valve or vascular tissue prior to or following implantation. The scaffold is either degraded or metabolised during the formation and organisation of the newly generated matrix, leading to vital living tissue. This paper summarises current research and first clinical developments in the tissue engineering of heart valves and vascular grafts.
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Vasos Sanguíneos/citologia , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Valvas Cardíacas/citologia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Animais , Bioprótese/efeitos adversos , Reatores Biológicos , Prótese Vascular/efeitos adversos , Adesão Celular/fisiologia , Materiais Revestidos Biocompatíveis , Endotélio Vascular/citologia , Fibroblastos/citologia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Mioblastos/citologia , Desenho de PróteseRESUMO
OBJECTIVE: For reasons that are still unclear, biologic heart valve prostheses undergo degeneration after implantation. We studied the possible role of the immune system in this process. METHODS: We examined the expression of immunologically relevant molecules by human cardiac valve endothelium in situ and in vitro and studied re-endothelialization of implanted allogeneic and xenogeneic valvular surfaces using explanted bioprostheses and valves obtained from donor hearts at cardiac retransplantation. RESULTS: We demonstrate that human cardiac valve endothelial cells express molecules capable of initiating immune responses and might therefore play a role in the degeneration of viable cardiac valve prostheses. Also, we show evidence of re-endothelialization on the surfaces of xenografts and allografts but not on valves obtained from previously transplanted hearts. CONCLUSION: Inasmuch as valves from previously transplanted hearts seem to be free from degeneration, we conclude that reduction of the immunogenicity of allograft valve prostheses by HLA matching or immunosuppressive treatment might further improve long-term results after allograft valve replacement.
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Bioprótese , Endotélio Vascular/imunologia , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/imunologia , Antígenos CD/análise , Insuficiência da Valva Aórtica/imunologia , Insuficiência da Valva Aórtica/cirurgia , Células Cultivadas , Endocárdio/imunologia , Análise de Falha de Equipamento , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/cirurgia , Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Teste de Histocompatibilidade , Humanos , Técnicas Imunoenzimáticas , Reoperação , Fator de von Willebrand/análiseRESUMO
OBJECTIVE: Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. METHODS: Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. RESULTS: Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. CONCLUSION: Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.
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Bioprótese , Retrovirus Endógenos , Próteses Valvulares Cardíacas , Infecções por Retroviridae/transmissão , Engenharia Tecidual/métodos , Animais , DNA Viral/análise , Retrovirus Endógenos/isolamento & purificação , Monócitos/virologia , Valva Pulmonar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ovinos , Suínos/virologiaRESUMO
AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones. METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates. RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 +/- 0.60 mPa.s, mean +/- SEM, r= 28) and mixed stones (3.50 +/- 0.68 mPa.s; r= 8) compared to hepatic bile (0.92 +/- 0.06 mPa.s, r= 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0.65; P < 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P < 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles. CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.
Assuntos
Bile/metabolismo , Colelitíase/metabolismo , Mucinas/metabolismo , Fosfolipídeos/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , ViscosidadeRESUMO
OBJECTIVE: Fresh frozen plasma (FFP) substitution is currently standard practise in cardiac surgery. In this study we investigate whether elective coronary artery bypass grafting (CABG) surgery is feasible without the administration of blood products compared to the substitution of fresh frozen plasma. PATIENTS AND METHODS: From September 1997 to April 1998, 120 consecutive patients underwent CABG surgery at our institution. In the FFP group patients (n=60; men, n=43; women, n=17; mean age: 64+/-8.5 years) received 4 units of fresh frozen plasma (FFP) intraoperatively. In comparison, patients in the control group (n=60; men, n=44; women, n=16; mean age: 65+/-7.5 years) did not receive FFP. Main endpoints included perioperative hematologic parameters, blood loss, and the amount of blood products that were administered. RESULTS: Intraoperatively, the substitution of packed red blood cells (pRBC) in the FFP group was significantly higher compared with the control group (0.63+/-0.94 units/patient vs. 0.12+/-0.38 units/patient, P=0.001). Postoperatively, patients in the FFP group required significantly more pRBC products than patients in the control group (0.78+/-1.09 vs. 0.42+/-0.77, P=0.024). There were no significant differences in hemoglobin (FFP group: 99+/-11.1 g/dl; control group: 105+/-13.5 g/dl) and hematocrit levels (FFP group: 30+/-3.39%; control group: 32+/-4%). Also, no significant differences regarding the postoperative blood loss was observed between groups (FFP group: 588+/-224 vs. control group: 576+/-272 ml/24 h). CONCLUSIONS: This study clearly demonstrates that the avoidance of routine intraoperative FFP administration does not lead to an increase in blood loss postoperatively compared to patients that received FFPs. Furthermore, we did not observe increased requirements for postoperative FFP infusion in patients that did not receive FFPs intraoperatively.