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OBJECTIVES: To compare the efficacy, safety, and side effects of hydromorphone and morphine administered as patient-controlled analgesia (PCA) for postoperative pain therapy after cardiac surgery with median sternotomy. DESIGN: A retrospective analysis of data from 2 prospective, single-blinded, randomized trials. SETTING: A single-center intensive care unit at a university hospital. PARTICIPANTS: Forty-one adult patients undergoing cardiac surgery with median sternotomy. INTERVENTIONS: Postoperative pain therapy at the intensive care unit was performed by PCA with intravenously administered bolus doses of 0.2 mg of hydromorphone (n = 21) or 2 mg of morphine (n = 20). MEASUREMENTS AND MAIN RESULTS: Pain at rest and under deep inspiration regularly was assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, cardiac output, oxygen saturation, and respiratory rate were monitored, and adverse events were registered. The median (range) NRS rating at rest was 1.5 (0-5) after hydromorphone and 0.5 (0-5) after morphine, respectively (p = 0.41). The median NRS rating under deep inspiration was 3 (0-6) after hydromorphone and 4 (0-7) after morphine, respectively (p = 0.074). The dose ratio of morphine to hydromorphone during PCA was 5.7 (95% confidence interval: 2.9-7.6). Hemodynamics and respiration were stable and did not differ significantly. Postoperative nausea and vomiting were the most frequent adverse events, which were observed in 29% of the patients after hydromorphone and in 35% after morphine, respectively (p = 0.74). CONCLUSIONS: There were no significant differences in analgesic efficacy and safety between hydromorphone and morphine when used for postoperative pain therapy with PCA after cardiac surgery with median sternotomy.
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Procedimientos Quirúrgicos Cardíacos , Hidromorfona , Adulto , Analgesia Controlada por el Paciente , Analgésicos Opioides , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Método Doble Ciego , Humanos , Hidromorfona/efectos adversos , Morfina , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Prospectivos , Estudios Retrospectivos , Esternotomía/efectos adversosRESUMEN
Airway management in children can be challenging. A hybrid technique using a video laryngoscope-assisted flexible bronchoscopic nasotracheal intubation allowed a successful airway management in a two-year-old child with a large tongue tumor.
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Fetal calf serum (FCS) is frequently used as a growth factor and protein source in bone-marrow-derived mesenchymal stromal cell (BMSC) culture media, although it is a xenogenic product presenting multiple disadvantages including but not limited to ethical concerns. A promising alternative for FCS is human platelet lysate (hPL), which is produced out of human platelet concentrates and happens to be a stable and reliable protein source. In this study, we investigated the influence of hPL in an expansion medium (ESM) and an osteogenic differentiation medium (ODM) on the proliferation and osteogenic differentiation capacity of human BMSC. Therefore, we assessed population doublings during cell expansion, performed alizarin red staining to evaluate the calcium content in the extracellular matrix and determined the activity of alkaline phosphatase (ALP) as osteogenic differentiation correlates. The proliferation rate of BMSC cultured in ESM supplemented with hPL exceeded the proliferation rate of BMSC cultured in the presence of FCS. Furthermore, the calcium content and ALP activity was significantly higher in samples incubated in hPL-supplemented ODM, especially in the early phases of differentiation. Our results show that hPL can replace FCS as a protein supplier in cell culture media and does not negatively affect the osteogenic differentiation capacity of BMSC.
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Plaquetas/metabolismo , Células de la Médula Ósea/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Albúmina Sérica Bovina/metabolismo , Animales , Bovinos , Proliferación Celular , Células Cultivadas , HumanosRESUMEN
Recent studies have demonstrated that surface characteristics, porosity, and mechanical strength of three-dimensional 45S5-type bioactive glass (BG)-based scaffolds are directly correlated with osteogenic properties. Three-dimensional BG-based scaffolds obtained from maritime natural sponges (MNSs) as sacrificial templates exhibit the required morphological properties; however, no in vivo data about the osteogenic features are available. In this study, uncoated (Group A) and gelatin-coated (Group B) crystalline MNS-obtained BG-based scaffolds were evaluated mechanically and seeded with human mesenchymal stem cells prior to subcutaneous implantation in immunodeficient mice. Before implantation and after explantation, micro-computed tomography scans were conducted, and scaffolds were finally subjected to histomorphometry. Scaffolds of both groups showed bone formation. However, Group B scaffolds performed distinctly better as indicated by a significant increase in scaffold volume (8.95%, p = 0.039) over the implantation period compared with a nonsignificant increase of 5.26% in Group A scaffolds in micro-computed tomography analysis. Furthermore, percentage bone area was 10.33% (±1.18%) in the Group B scaffolds, which was significantly (p = 0.007) higher compared with the 8.53% (±0.77%) in the Group A scaffolds in histomorphometry. Compressive strength was enhanced significantly by gelatin coating (9 ± 2 vs. 4 ± 1 MPa; p = 0.029). The presence of gelatin on the remnant parts was verified by scanning electron microscopy and X-ray spectroscopy, demonstrating the coatings' resilience. MNS-obtained BG-based scaffolds were thus confirmed to exhibit osteogenic properties in vivo that can significantly be enhanced by gelatin coating.
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Células Inmovilizadas , Cerámica , Materiales Biocompatibles Revestidos , Gelatina , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Osteogénesis , Andamios del Tejido/química , Animales , Células Inmovilizadas/citología , Células Inmovilizadas/metabolismo , Células Inmovilizadas/trasplante , Cerámica/química , Cerámica/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Femenino , Gelatina/química , Gelatina/farmacología , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Ratones , Ratones SCID , Persona de Mediana EdadRESUMEN
Since the amount of autologous bone for the treatment of bone defects is limited and harvesting might cause complications, synthetic bone substitutes such as the popular ß-tricalcium phosphate (ß-TCP) based Vitoss have been developed as an alternative grafting material. ß-TCPs exhibit osteoconductive properties, however material-initiated stimulation of osteogenic differentiation is limited. These limitations might be overcome by addition of 45S5 bioactive glass (BG) particles. This study aims to analyze the influence of BG particles in Vitoss BA (20 wt% BG particles with a size of 90-150 µm) on osteogenic properties, cell vitality and cell proliferation in direct comparison to Vitoss by evaluation of the underlying cellular mechanisms. For that purpose, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stem cells (MSC) and underwent osteogenic differentiation in-vitro for up to 42 days. Cell vitality, proliferation, and osteogenic differentiation were monitored by quantitative gene expression analysis, determination of alkaline phosphatase activity, PrestoBlue cell viability assay, dsDNA quantification, and a fluorescence-microscopy-based live/dead-assay. It was demonstrated that BG particles decrease cell proliferation but do not have a negative impact on cell vitality. Especially the early stages of osteogenic differentiation were significantly improved in the presence of BG particles, resulting in earlier maturation of the MSC towards osteoblasts. Since most of the stimulatory effects induced by BG particles took place initially, particles exhibiting another surface-area-to-volume ratio should be considered in order to provide long-lasting stimulation.
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Sustitutos de Huesos/farmacología , Diferenciación Celular/efectos de los fármacos , Cerámica/farmacología , Osteogénesis/efectos de los fármacos , Andamios del Tejido/química , Adulto , Sustitutos de Huesos/química , Fosfatos de Calcio/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cerámica/química , Femenino , Vidrio/química , Humanos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Persona de Mediana Edad , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Cultivo Primario de Células , Silicatos/farmacología , Propiedades de SuperficieRESUMEN
Research concerning bone substitutes is one of the most challenging fields in orthopedic research and has a high clinical relevance, especially since the currently available bone substitutes are limited in their osteostimulative capabilities. In vitro models for the evaluation of the properties of bone substitutes allow the use of human mesenchymal stem cells (hMSCs) seeded onto scaffolds, but suffer from the lack of a physiological environment for those cells. Most in vivo models include the use of non-hMSC and are therefore lacking in clinical relevance. To overcome these issues, in vivo models were created that allow the evaluation of hMSC-seeded bone substitutes, combining the advantages of the use of human cells with the physiological conditions of an organism in vivo. In brief, models usually aim for bone formation in immunocompromised rodents. The subcutaneous implantation of scaffolds is most widely performed, showing low complication rates along with good results, but suffering from inferior vascularization of the implants and the absence of the realistic structural and mechanical conditions of bone. Orthotopic implantation, for example in calvarian or long bone defects, provides the most appropriate surrounding for hMSC-seeded scaffolds. However, parallel host-induced bone formation is a major limitation. This review summarizes in vivo models for the evaluation of the osteogenic potency of bone substitutes seeded with mesenchymal stem cells of human origin.
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Sustitutos de Huesos/farmacología , Células Madre Mesenquimatosas/citología , Modelos Biológicos , Osteogénesis/efectos de los fármacos , Humanos , Células Madre Mesenquimatosas/efectos de los fármacosRESUMEN
Three-dimensional 45S5 bioactive glass (BG)-based scaffolds are being investigated for bone regeneration. Besides structural properties, controlled time-dependent alteration of scaffold morphology is crucial to achieve optimal scaffold characteristics for successful bone repair. There is no in vitro evidence concerning the dependence between structural characteristics and dissolution behavior of 45S5 BG-based scaffolds of different morphology. In this study, the dissolution behavior of scaffolds fabricated by the foam replica method using polyurethane foam (Group A) and maritime sponge Spongia Agaricina (Group B) as sacrificial templates was analyzed by micro-computed-tomography (µCT). The scaffolds were immersed in Dulbecco's Modified Eagle Medium for 56 days under static cell culture conditions and underwent µCT-analysis initially, and after 7, 14, and 56 days. Group A showed high porosity (91%) and trabecular structure formed by macro-pores (average diameter 692 µm ± 72 µm). Group-B-scaffolds were less porous (51%), revealing an optimal pore size distribution within the window of 110-500 µm pore size diameter, combined with superior mechanical stability. Both groups showed similar structural alteration upon immersion. Surface area and scaffold volume increased whilst density decreased, reflecting initial dissolution followed by hydroxycarbonate-apatite-layer-formation on the scaffold surfaces. In vitro- and/or in vivo-testing of cell-seeded BG-scaffolds used in this study should be performed to evaluate the BG-scaffolds' time-dependent osteogenic properties in relation to the measured in vitro structural changes.