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1.
BMJ Open ; 11(9): e045239, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475143

RESUMO

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Mamilos/cirurgia
2.
Lasers Med Sci ; 36(4): 855-862, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32813259

RESUMO

The common limitation of surgical revascularization procedures for severe tissue ischemia due to cardiovascular diseases is the need to interrupt blood flow during the intervention. We aim to introduce a new technique that allows a sutureless, non-occlusive revascularization. A 3-step technique was developed using rabbit's aorta to simulate a side-to-side anastomosis model. It enables the creation of a bypass circuit for revascularization. The first step was the soldering of 2 vessels in a side-to-side fashion based on the laser-assisted vascular anastomosis (LAVA) principle using a diode laser emitting irradiation at 810 nm with an albumin-based solder patch between them, followed by the creation of a channel within the patch using either a holmium-doped yttrium aluminum garnet laser (Ho:YAG) at λ = 2100 nm or a xenon-chloride excimer laser (XeCl) at λ = 308 nm. Thereby, a bypass circuit was created, thus allowing a non-ischemic revascularization. The system was deemed functional when a flow was observed across the anastomosis. The highest average tensile strength recorded after side-to-side LAVA using a diode laser power of 3.2 W for 60 s was 2278.6 ± 800 mN (n = 20). The Ho:YAG laser created the channels with less tension on the anastomosis than the excimer laser. Histological analysis showed limited thermal damage and good patch-tissue adaptation. The preliminary results of this feasibility study outline the foundations for an entirely sutureless laser-assisted revascularization procedure. The next studies will evaluate the rheological parameters across the bypass circuit to optimize the post-anastomotic flow.


Assuntos
Anastomose Cirúrgica/métodos , Lasers Semicondutores , Animais , Aorta/cirurgia , Estudos de Viabilidade , Projetos Piloto , Coelhos , Resistência à Tração
3.
Ann Anat ; 234: 151624, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33129977

RESUMO

INTRODUCTION: In order to achieve a satisfactory functional and aesthetic result a thin skin flap is often required in surgical reconstruction of various body regions. Perforator flaps based on either the superficial or deep branch of the superficial circumflex iliac artery (SCIA) have been used for this purpose mainly in the Asian population. Recently the superficial plane has been established as a new way of elevating the flap. Anatomical studies and details of this new flap are lacking. MATERIAL AND METHODS: Wide areas were harvested subfascially from the groin of Thiel-fixated cadavers. Both deep and superficial branches of the superficial circumflex iliac artery were carefully dissected and individually injected with µAngiofil. After CT-imaging the flaps were raised on the superficial plane, perforators were marked and the flaps subsequently rescanned. High-resolution images of regions of interest were taken using micro-CT. RESULTS: A total of 21 flaps were harvested and analyzed. Both the deep and superficial branch provided more than three perforators per branch, however, the deep branch based flap was significantly larger (202 vs. 112 cm2, p < 0.01) and had a longer pedicle (9.1 vs. 6.6 cm, p < 0.01). Raising the flap in the superficial plane reliably reduces bulk and increases homogeneity. CONCLUSIONS: The SCIP flap appears to have a reliable vascular blood supply. The SCIA and its main branches and perforators have a consistent vascular pattern. The deep branch of the SCIA has the anatomic potential to be the preferred pedicle in case larger flaps with longer pedicles are necessary.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Aorta Abdominal , Artéria Ilíaca/cirurgia , Reprodutibilidade dos Testes
4.
Adv Sci (Weinh) ; 7(15): 2000912, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32775166

RESUMO

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X-ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle-based systems.

5.
Transplant Direct ; 6(9): e592, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32851125

RESUMO

BACKGROUND: The lymphatic system may play an important role in local immunomodulation in vascularized composite allotransplantation (VCA). Currently, there is no standardized VCA model that includes the regional draining lymphatic tissue. The aim of this study was to develop a rapid and efficient orthotopic hindlimb transplantation model in rats that included the draining lymphatic basin to permit further evaluation of the lymphatic system's role in VCA. METHODS: Thirty transplantations from Brown Norway rats to Lewis rats were performed. To include the regional lymphatic tissue, the superficial epigastric vessels were preserved to allow retrieval of the corresponding inguinal lymph nodes, including the inguinal fat pad, with the hindlimb. A cuff technique was used for the vein, whereas the conventional microsurgical technique was used for the arterial anastomosis. Vascular patency was confirmed through laser Doppler analysis at postoperative day 1 and histological analysis after euthanasia. RESULTS: The presence and vascularization of the inguinal lymph nodes were verified with indocyanine green lymphoscintigraphy at the time of transplantation. Mean total ischemia time was 69 ± 24 minutes, and mean recipient operation time was 80 ± 19 minutes. Overall transplant survival rate was 93.3%. Laser Doppler analysis showed vascular (technical) success, indocyanine green lymphoscintigraphy confirmed the presence of lymph nodes and the histological analysis revealed patent anastomoses. CONCLUSIONS: We successfully developed an experimental orthotopic hindlimb transplantation model in rats that includes the draining inguinal lymphatic basin, which is an important asset in further research on lymphatic tissue and its role in VCA.

6.
J Bone Joint Surg Am ; 102(6): 510-518, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-31804239

RESUMO

BACKGROUND: Defects in the distal third of the leg are difficult to cover and often require free tissue transfer, even for defects of limited sizes. Propeller flaps have been designed specifically as an alternative to free tissue transfer but at times have been associated with unacceptably high complication rates. We therefore aimed to prospectively assess our own institutional experience with this technique and to define its role in lower-limb reconstruction. METHODS: All patients who had been managed with reconstruction of the distal part of the leg with a propeller flap between 2014 and 2017 were included in the study. Demographic, clinical, and follow-up data on the patients and surgical procedures were recorded with special focus on the complication profile. RESULTS: Twenty-six patients underwent propeller flap reconstruction of the distal part of the leg: 12 flaps were based on the posterior tibial artery, and 14 were based on the peroneal artery. Postoperative complications developed in association with 1 of the 12 flaps based on the posterior tibial artery, compared with 8 of the 14 flaps based on the peroneal artery (p = 0.015). Moreover, the presence of a higher Charlson comorbidity index (≥2) was strongly associated with the development of postoperative complications (p < 0.001). CONCLUSIONS: Propeller flaps are a reliable option for traumatic reconstruction in carefully selected patients with lower-limb defects. In our experience, the rate of complications was higher for propeller flaps based on the peroneal artery and for patients with a Charlson comorbidity index of ≥2, whereas posterior tibial artery-based propeller flap reconstruction was a reliable surgical option for patients with a small defect in the distal third of the lower limb. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Traumatismos da Perna/cirurgia , Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos/métodos , Lesões dos Tecidos Moles/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Clin Hemorheol Microcirc ; 71(3): 291-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29914012

RESUMO

BACKGROUND: Improvement of skin microcirculation would be beneficial in transplanted tissues and thus, there is a demand for effective, reliable and harmless angiogenic treatments. The aim of this study was to assess the effect of capsaicin application (CA), the remote effect of capsaicin application (REC), the impact of remote ischemic conditioning (RIC), and the impact of combined remote ischemic conditioning with capsaicin application (Comb) on human skin microcirculation. METHODS: Perfusion changes were assessed using a laser Doppler device (easyLDI, Aimago Lausanne). 30 healthy volunteers were enrolled and divided into two groups: 1) CA and REC: perfusion was assessed on both forearms after application of capsaicin cream on one forearm with an exposure time of 40 minutes. 2) RIC and Comb: perfusion of one forearm was assessed after four cycles of 5 min blood occlusion and 5 min reperfusion using a tourniquet on the contralateral upper arm and application of capsaicin on the ipsilateral forearm. Baseline skin perfusion measurements of both forearms were carried out initially and were used as intra-individual reference. RESULTS: 1) Skin perfusion significantly increased after capsaicin application (CA = +328.3% , p > 0.05). There was no remote skin perfusion change due to capsaicin (REC). 2) RIC significantly improves skin perfusion (RIC = +20.0% , p < 0.05). The combination of RIC and CA does not improve skin perfusion compared to CA alone (Comb). CONCLUSIONS: The conditioning techniques RIC and CA showed a significant increase in human skin perfusion, CA being superior to RIC. However, the combination of CA and RIC showed no additional improvement potential as compared to CA alone. Furthermore, a remote effect of capsaicin application could not be demonstrated. These results encourage to analyze if the conditioning treatments are also beneficial for transplanted tissue survival.


Assuntos
Capsaicina/uso terapêutico , Isquemia/etiologia , Pele/fisiopatologia , Adulto , Capsaicina/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Isquemia/patologia , Masculino , Microcirculação , Adulto Jovem
8.
PLoS One ; 13(11): e0207802, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30475867

RESUMO

BACKGROUND: Distal flap necrosis is a frequent complication of perforator flaps. Advances in nanotechnology offer exciting new therapeutic approaches. Anti-inflammatory and neo-angiogenic properties of certain metal oxides within the nanoparticles, including bioglass and ceria, may promote flap survival. Here, we explore the ability of various nanoparticle formulations to increase flap survival in a rat model. MATERIALS AND METHODS: A 9 x 3 cm dorsal flap based on the posterior thigh perforator was raised in 32 Lewis rats. They were divided in 4 groups and treated with different nanoparticle suspensions: I-saline (control), II-Bioglass, III-Bioglass/ceria and IV-Zinc-doped strontium-substituted bioglass/ceria. On post-operative day 7, planimetry and laser Doppler analysis were performed to assess flap survival and various samples were collected to investigate angiogenesis, inflammation and toxicity. RESULTS: All nanoparticle-treated groups showed a larger flap survival area as compared to the control group (69.9%), with groups IV (77,3%) and II (76%) achieving statistical significance. Blood flow measurements by laser Doppler analysis showed higher perfusion in the nanoparticle-treated flaps. Tissue analysis revealed higher number of blood vessels and increased VEGF expression in groups II and III. The cytokines CD31 and MCP-1 were decreased in groups II and IV. CONCLUSIONS: Bioglass-based nanoparticles exert local anti-inflammatory and neo-angiogenic effects on the distal part of a perforator flap, increasing therefore its survival. Substitutions in the bioglass matrix and trace metal doping allow for further tuning of regenerative activity. These results showcase the potential utility of these nanoparticles in the clinical setting.


Assuntos
Nanopartículas , Retalho Perfurante/fisiologia , Sobrevivência de Tecidos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cerâmica/química , Cerâmica/farmacologia , Ratos , Pele/citologia
9.
Xenotransplantation ; 25(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29057510

RESUMO

BACKGROUND: In pig-to-human xenotransplantation, interactions between human natural killer (NK) cells and porcine endothelial cells (pEC) are characterized by recruitment and cytotoxicity. Protection from xenogeneic NK cytotoxicity can be achieved in vitro by the expression of the non-classical human leukocyte antigen-E (HLA-E) on pEC. Thus, the aim of this study was to analyze NK cell responses to vascularized xenografts using an ex vivo perfusion system of pig limbs with human blood. METHODS: Six pig forelimbs per group, respectively, stemming from either wild-type (wt) or HLA-E/hCD46 double-transgenic (tg) animals, were perfused ex vivo with heparinized human blood for 12 hours. Blood samples were collected at defined time intervals, cell numbers counted, and peripheral blood mononuclear cells analyzed for phenotype by flow cytometry. Muscle biopsies were analyzed for NK cell infiltration. In vitro NK cytotoxicity assays were performed using pEC derived from wt and tg animals as target cells. RESULTS: Ex vivo, a strong reduction in circulating human CD45 leukocytes was observed after 60 minutes of xenoperfusion in both wt and tg limb groups. NK cell numbers dropped significantly. Within the first 10 minutes, the decrease in NK cells was more significant in the wt limb perfusions as compared to tg limbs. Immunohistology of biopsies taken after 12 hours showed less NK cell tissue infiltration in the tg limbs. In vitro, NK cytotoxicity against hCD46 single tg pEC and wt pEC was similar, while lysis of double tg HLA-E/hCD46 pEC was significantly reduced. Finally, circulating cells of pig origin were observed during the ex vivo xenoperfusions. These cells expressed phenotypes mainly of monocytes, B and T lymphocytes, NK cells, as well as some activated endothelial cells. CONCLUSIONS: Ex vivo perfusion of pig forelimbs using whole human blood represents a powerful tool to study humoral and early cell-mediated rejection mechanisms of vascularized pig-to-human xenotransplantation, although there are several limitations of the model. Here, we show that (i) transgenic expression of HLA-E/hCD46 in pig limbs provides partial protection from human NK cell-mediated xeno responses and (ii) the emergence of a pig cell population during xenoperfusions with implications for the immunogenicity of xenografts.


Assuntos
Extremidades/irrigação sanguínea , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Proteína Cofatora de Membrana/imunologia , Animais , Animais Geneticamente Modificados/imunologia , Citotoxicidade Imunológica/imunologia , Células Endoteliais/imunologia , Antígenos HLA/genética , Xenoenxertos/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Leucócitos/metabolismo , Proteína Cofatora de Membrana/genética , Transplante Heterólogo/métodos
10.
Mol Immunol ; 88: 116-124, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28641140

RESUMO

Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation. We used C1-easterase inhibitor (C1-INH) in this study because of its known inhibitory effects on the activation of the complement, coagulation and kinin cascades. Forelimbs of 8 large white pigs were amputated, subjected to ischemia, and then reperfused with autologous whole blood. All limbs were exposed to 9h of cold ischemia at 4°C. After 2h of cold ischemia the limbs were either perfused with of C1-INH (1U/ml in hydroxyethyl starch, n=8) or hydroxyethyl starch alone (n=7). After completion of the 9-h ischemia period, all limbs were ex vivo perfused with heparinized autologous whole blood for 12h using a pediatric heart lung machine to simulate in vivo revascularization. Our results show that I/R injury in the control group led to a significant elevation of tissue deposition of IgG and IgM, complement C3b/c, C5b-9 and MBL. Also, activation of the kinin system was significantly increased, namely bradykinin in plasma, and expression of bradykinin receptors 1 and 2 in tissue. In addition, markers for endothelial integrity like expression of CD31, VE-cadherin and heparan sulfate proteoglycans were decreased in reperfused tissue. Limb I/R injury also led to activation of the coagulation cascade with a significant elevation of fibrin and thrombin deposition and increased fibrinogen-like protein-2 expression. C1-INH treated limbs showed much less activation of plasma cascades and better protection of endothelial integrity compared to the reperfused control limbs. In conclusion, the use of the cytoprotective drug C1-INH significantly reduced I/R injury by protecting the vascular endothelium as well as the muscle tissue from deposition of immunoglobulins, complement and fibrin.


Assuntos
Cotos de Amputação/irrigação sanguínea , Cotos de Amputação/patologia , Proteína Inibidora do Complemento C1/uso terapêutico , Neovascularização Fisiológica/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Amputação , Animais , Bradicinina/sangue , Complemento C3b/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Fibrina/metabolismo , Fibrinogênio/metabolismo , Derivados de Hidroxietil Amido/uso terapêutico , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Receptores da Bradicinina/sangue , Traumatismo por Reperfusão/patologia , Suínos , Trombina/metabolismo
11.
Lasers Med Sci ; 32(6): 1343-1348, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28608190

RESUMO

Microvascular surgery is time consuming and requires high expertise. Laser-assisted vascular anastomosis (LAVA) is a promising sutureless technique that has the potential to facilitate this procedure. In this study, we evaluate the handling of our soldering material and the 1-week patency rate in a porcine model. Six pigs were subjected to LAVA. For each pig, the saphenous artery on one side was transected while the contralateral side was used as control. A porous polycaprolactone scaffold soaked in 40% (w/w) bovine serum albumin solution in combination with 0.1% (w/w) indocyanine green was wrapped at the anastomosis site and at the control site. Both sides were then soldered with a diode laser coupled into a light diffuser fiber emitting radiation with a wavelength of 808 nm and a power of 2-2.2 W. Vessels were successfully soldered with a 100% immediate patency rate. The 1-week patency rate was 83% for the anastomoses versus 67% for the control side. Vessels irradiated for 80 to 90 s tended to maintain the highest patency rate. Macroscopically, there was no difference between the two sides. The patch was easy to handle provided that the environment could be kept dry. This study shows the potential and the limitations of endoluminal LAVA as a one-step procedure without the use of stay sutures. Further studies are needed to improve the soldering material, the long-term patency rate, and standardized irradiation parameters. The long-term effects of laser soldering on the vessel wall remain to be determined.


Assuntos
Angioplastia , Terapia a Laser/métodos , Microvasos/cirurgia , Anastomose Cirúrgica , Animais , Circulação Sanguínea , Lasers Semicondutores/uso terapêutico , Microvasos/patologia , Modelos Animais , Sus scrofa , Suínos , Temperatura
12.
GMS J Med Educ ; 33(4): Doc57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27579357

RESUMO

INTRODUCTION: Various different learning methods are available for planning tuition regarding the introduction to surgical hand disinfection. These learning methods should help to organise and deal with this topic. The use of a video film is an alternative to conventional tuition due to the real presentation possibilities of practical demonstration. OBJECTIVE: This study examines by way of comparison which form of communication is more effective for learning and applying surgical hand disinfection for medical students in their first year of studies: video-based instruction or conventional tuition. METHODOLOGY: A total of 50 first-year medical students were randomly allocated either to the "Conventional Instruction" (CI) study group or to the "Video-based Instruction" (VI) study group. The conventional instruction was carried out by an experienced nurse preceptor/nurse educator for the operating theatre who taught the preparatory measures and the actual procedure in a two-minute lesson. The second group watched a two-minute video sequence with identical content. Afterwards, both groups demonstrated practically the knowledge they had acquired at an individual practical test station. The quality (a) of the preparation and (b) of the procedure as well as (c) the quality of the results was assessed by 6 blind experts using a check list. The acceptability of the respective teaching method was also asked about using a questionnaire. RESULTS: The group performance did not differ either in the preparation (t=-78, p<0.44) or in the quality (t=-99, p<0.34). With respect to performance, it was possible to demonstrate a strong treatment effect. In the practical (t=-3.33, p<0.002, d=0.943) and in the total score (t=-2.65, p<0.011, d=0.751), the group with video-based instruction achieved a significantly better result. In response to the question as to which of the two learning methods they would prefer, the significant majority (60.4%) of students stated video instruction. CONCLUSION: In this study, the use of the video-based instruction emerged as the more effective teaching method for learning surgical hand disinfection for medical students and is preferable to conventional instruction. The video instruction is associated with a higher learning effectiveness, efficiency and acceptability.


Assuntos
Desinfecção das Mãos , Estudantes de Medicina , Gravação em Vídeo , Adulto , Avaliação Educacional , Feminino , Humanos , Aprendizagem , Masculino , Inquéritos e Questionários
13.
Wounds ; 28(7): E26-30, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27428721

RESUMO

Skin reactions are known adverse effects of radiation therapy. Despite advances in skin care products, there is still a demand for optimal skin care products to improve the therapy of these lesions. The authors report the use of a polylactide-based copolymer (Suprathel, PolyMedics Innovations GmbH, Denkendorf, Germany) as a temporary skin substitute for covering the skin defects of a patient with moist desquamation due to radiation.


Assuntos
Melanoma/radioterapia , Poliésteres , Polímeros , Radiodermatite/patologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias Cutâneas/radioterapia , Pele Artificial , Idoso , Feminino , Humanos , Melanoma/patologia , Polímeros/farmacologia , Radiodermatite/terapia , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Cicatrização
14.
J Craniomaxillofac Surg ; 44(8): 958-63, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27325543

RESUMO

BACKGROUND: A huge number of procedures for forehead and brow rejuvenation have been described. Nevertheless, the surgical approach of brow aesthetics in terms of correction of brow fullness and symmetry has not been systematically evaluated in the literature. We recently proposed a 20-degree beveled brow incision technique for direct brow lifting. The aim of the present study is to evaluate the 20-degree beveled brow incision technique for brow reduction, reshaping and correction of brow symmetry. MATERIALS AND METHODS: Eighteen patients underwent brow reshaping by using the 20-degree beveled brow incision technique combined or not with other lifting procedure (brow lift, blepharoplasty, face lift). The surgical outcome was evaluated by photographic documentation and a questionnaire on patient satisfaction. Follow-up was at least 6 months. RESULTS: The surgical outcome in terms of brow symmetry, fullness and scaring was very good in 14 of 18 patients, good in 2 patients and poor in 2 patients. The last two patients were smokers. Motor or sensibility disorders were not observed. CONCLUSION: The 20-degree beveled brow incision technique seems to be saved and effective as surgical procedure to improve brow aesthetics in terms of symmetry and fullness while a supplement lifting maneuver is easily to perform.


Assuntos
Sobrancelhas , Testa/cirurgia , Cirurgia Plástica/métodos , Adulto , Idoso , Blefaroplastia/métodos , Estética , Sobrancelhas/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Ritidoplastia/métodos
15.
Transplantation ; 99(10): 2061-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25965410

RESUMO

BACKGROUND: Dysregulation of the coagulation system due to inflammatory responses and cross-species molecular incompatibilities represents a major obstacle to successful xenotransplantation. We hypothesized that complement inhibition mediated by transgenic expression of human CD46 in pigs might also regulate the coagulation and fibrinolysis cascades and tested this in ex vivo human-to-pig xenoperfusions. METHODS: Forelimbs of wild-type and hCD46/HLA-E double transgenic pigs were ex vivo xenoperfused for 12 hours with whole heparinized human blood. Muscle biopsies were stained for galactose-α1,3-galactose, immunoglobulin M, immunoglobulin G, complement, fibrin, tissue factor, fibrinogen-like protein 2, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI)-1. The PAI-1/tPA complexes, D-dimers, and prothrombin fragment F1 + 2 were measured in plasma samples after ex vivo xenoperfusion. RESULTS: No differences of galactose expression or deposition of immunoglobulin M and immunoglobulin G were found in xenoperfused tissues of wild type and transgenic limbs. In contrast, significantly lower deposition of C5b-9 (P < 0.0001), fibrin (P = 0.009), and diminished expression of tissue factor (P = 0.005) and fibrinogen-like protein 2 (P = 0.028) were found in xenoperfused tissues of transgenic limbs. Levels of prothrombin fragment F1 + 2 (P = 0.031) and D-dimers (P = 0.044) were significantly lower in plasma samples obtained from transgenic as compared to wild-type pig limb perfusions. The expression of the fibrinolytic marker tPA was significantly higher (P = 0.009), whereas PAI-1 expression (P = 0.022) and PAI-1/tPA complexes in plasma (P = 0.015) were lower after transgenic xenoperfusion as compared to wild-type xenoperfusions. CONCLUSIONS: In this human-to-pig xenoperfusion model, complement inhibition by transgenic hCD46 expression led to a significant inhibition of procoagulant and antifibrinolytic pathways.


Assuntos
Coagulação Sanguínea , Endotélio Vascular/metabolismo , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/metabolismo , Animais , Animais Geneticamente Modificados , Biópsia , Feminino , Fibrinólise , Membro Anterior , Galactose/química , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Microscopia de Fluorescência , Músculos/patologia , Perfusão , Plasminogênio/química , Suínos , Ativador de Plasminogênio Tecidual/química , Transgenes , Transplante Heterólogo
16.
Transplantation ; 99(4): 693-701, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25675194

RESUMO

BACKGROUND: Asialoglycoprotein receptor-1 (ASGR1) mediates capture and phagocytosis of platelets in pig-to-primate liver xenotransplantation. However, thrombocytopenia is also observed in xenotransplantation or xenoperfusion of other porcine organs than liver. We therefore assessed ASGR1 expression as well as ASGR1-mediated xenogeneic platelet phagocytosis in vitro and ex vivo on porcine aortic, femoral arterial, and liver sinusoidal endothelial cells (PAEC/PFAEC/PLSEC). METHODS: Porcine forelimbs were perfused with whole, heparinized human or autologous pig blood. Platelets were counted at regular intervals. Pig limb muscle and liver, as well as PAEC/PFAEC/PLSEC, were characterized for ASGR1 expression. In vitro, PAEC cultured on microcarrier beads and incubated with non-anticoagulated human blood were used to study binding of human platelets and platelet-white blood cell aggregation. Carboxyfluorescein diacetate succinimidyl ester-labeled human platelets were exposed to PAEC/PFAEC/PLSEC and analyzed for ASGR1-mediated phagocytosis. RESULTS: Human platelet numbers decreased from 102 ± 33 at beginning to 13 ± 6 × 10/µL (P < 0.0001) after 10 minutes of perfusion, whereas no significant decrease of platelets was seen during autologous perfusions (171 ± 26 to 122 ± 95 × 10/µL). The PAEC, PFAEC, and PLSEC all showed similar ASGR1 expression. In vitro, no correlation was found between reduction in platelet count and platelet-white blood cell aggregation. Phagocytosis of human carboxyfluorescein diacetate succinimidyl ester-labeled platelets by PAEC/PFAEC/PLSEC peaked at 15 minutes and was inhibited (P < 0.05 to P < 0.0001) by rabbit anti-ASGR1 antibody and asialofetuin. CONCLUSIONS: The ASGR1 expressed on aortic and limb arterial pig vascular endothelium plays a role in binding and phagocytosis of human platelets. Therefore, ASGR1 may represent a novel therapeutic target to overcome thrombocytopenia associated with vascularized pig-to-primate xenotransplantation.


Assuntos
Receptor de Asialoglicoproteína/metabolismo , Plaquetas/metabolismo , Transfusão de Sangue/métodos , Células Endoteliais/metabolismo , Membro Anterior/irrigação sanguínea , Fagocitose , Amputação , Animais , Receptor de Asialoglicoproteína/imunologia , Plaquetas/imunologia , Células Cultivadas , Células Endoteliais/imunologia , Feminino , Membro Anterior/cirurgia , Humanos , Masculino , Modelos Animais , Adesividade Plaquetária , Transdução de Sinais , Especificidade da Espécie , Suínos , Trombocitopenia/sangue , Trombocitopenia/imunologia , Fatores de Tempo , Transplante Heterólogo
17.
Ther Umsch ; 71(12): 759-64, 2014 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-25447091

RESUMO

The prophylactic (risk-reducing) mastectomy is a world-wide recognized method for specifically treating the increased breast cancer risk in patients showing a BRCA1 and/or BRCA2 mutation as well as other patient groups at increased breast cancer risk. This option should be offered to all patients having the pertinent risk profile. Breast reconstruction is an integral part of the risk-reducing mastectomy procedure and all possible methods of breast reconstruction, especially autologous tissue reconstruction should be offered to all patients having a medical indication and desiring this surgical treatment. These patients are best managed in certified Breast Care Centres where the different medical and surgical specialists can address interdisciplinary all aspects of genetic counselling, preoperative counselling, mastectomy and reconstructive techniques as well as the necessary postoperative surveillance.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Seleção de Pacientes , Prevenção Primária/métodos , Procedimentos Cirúrgicos Profiláticos/métodos , Procedimentos Desnecessários , Medicina Baseada em Evidências , Feminino , Humanos , Mastectomia/estatística & dados numéricos , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Medição de Risco , Resultado do Tratamento
18.
Sci Transl Med ; 6(249): 249ra110, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25122638

RESUMO

Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA.


Assuntos
Aloenxertos Compostos/efeitos dos fármacos , Enzimas/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Animais , Especificidade de Anticorpos/efeitos dos fármacos , Especificidade de Anticorpos/imunologia , Biomarcadores/sangue , Linhagem Celular , Ativação do Complemento/efeitos dos fármacos , Proteínas do Sistema Complemento/metabolismo , Citocinas/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Imunidade Humoral/efeitos dos fármacos , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Ratos , Pele/efeitos dos fármacos , Pele/metabolismo , Tacrolimo/sangue , Tacrolimo/farmacologia , Fatores de Tempo , Triglicerídeos/química
20.
Xenotransplantation ; 21(3): 230-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24635052

RESUMO

BACKGROUND: Besides α1,3-galactosyltransferase gene (GGTA1) knockout, several transgene combinations to prevent pig-to-human xenograft rejection are currently being investigated. In this study, the potential of combined overexpression of human CD46 and HLA-E to prevent complement- and NK-cell-mediated xenograft rejection was tested in an ex vivo pig-to-human xenoperfusion model. METHODS: α1,3-Galactosyltransferase knockout heterozygous, hCD46/HLA-E double transgenic (transgenic) as well as wild-type pig forelimbs were ex vivo perfused with whole, heparinized human and autologous pig blood, respectively. Blood samples were analyzed for the production of porcine and/or human inflammatory cytokines as well as complement activation products. Biopsy samples were examined for deposition of human and porcine C3b/c, C4b/c, and C6 as well as CD62E (E-selectin) and CD106 (VCAM-1) expression. Apoptosis was measured in the porcine muscle tissue using TUNEL assays. Finally, the formation of thrombin-antithrombin (TAT) complexes was measured in EDTA plasma samples. RESULTS: No hyperacute rejection was seen in this model. Extremity perfusions lasted for up to 12 h without increase in vascular resistance and were terminated due to continuous small blood losses. Plasma levels of porcine cytokines IL1ß, IL-6, IL-8, IL-10, TNF-α, and MCP-1 as well as human complement activation markers C3a (P = 0.0002), C5a (P = 0.004), and soluble C5b-9 (P = 0.03) were lower in blood perfused through transgenic as compared to wild-type limbs. Human C3b/c, C4b/c, and C6 as well as CD62E and CD106 were deposited in tissue of wild-type limbs, but significantly lower levels (P < 0.0001) of C3b/c, C4b/c, and C6 deposition as well as CD62E and CD106 expression were detected in transgenic limbs perfused with human blood. Transgenic porcine tissue was protected from xenoperfusion-induced apoptosis (P < 0.0001). Finally, TAT levels were significantly lower (P < 0.0001) in transgenic limb as compared to wild-type limb xenoperfusions. CONCLUSION: Transgenic hCD46/HLA-E expression clearly reduced humoral xenoresponses since all, the terminal pathway of complement activation, endothelial cell activation, muscle cell apoptosis, inflammatory cytokine production, as well as coagulation activation, were all downregulated. Overall, this model represents a useful tool to study early immunological responses during pig-to-human vascularized xenotransplantation in the absence of hyperacute rejection.


Assuntos
Animais Geneticamente Modificados , Transfusão de Sangue/métodos , Rejeição de Enxerto/prevenção & controle , Antígenos de Histocompatibilidade Classe I/genética , Proteína Cofatora de Membrana/genética , Suínos/genética , Transplante Heterólogo , Animais , Apoptose , Biomarcadores , Proteínas do Sistema Complemento/metabolismo , Citocinas/metabolismo , Técnicas de Inativação de Genes , Marcadores Genéticos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Técnicas In Vitro , Proteína Cofatora de Membrana/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
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