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1.
J Pers Med ; 13(11)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-38003885

RESUMO

This case report describes the surgical management of a patient with a complex hand trauma. This injury included tendon, vascular, and nerve injuries, a partial amputation of the index finger, fractures of the third proximal phalanx, and destruction of the metacarpophalangeal joint of the fifth finger. Firstly, the acute treatment of a complex hand injury is described. Secondly, the planning and execution of a joint reconstruction using a vascularized lateral femoral condylar flap, assisted by an individual 3D model, is illustrated. Precise reconstruction of the affected structures resulted in good revascularization as well as an anatomical bone consolidation. Intensive physical therapy, including autonomous proprioceptive range-of-motion exercises by the patient, resulted in significant functional improvement of the hand in daily life. Overall, we report on the successful reconstruction of a metacarpophalangeal joint by using a vascularized flap from the lateral femoral condyle. Furthermore, this case report highlights the efficacy of integrating individualized 3D printing technology to plan complex reconstructions, opening up promising opportunities for personalized and optimized interventions.

2.
Medicina (Kaunas) ; 59(7)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37512018

RESUMO

This case report focuses on a 17-year-old polytrauma patient who suffered a septic wound infection after an open reduction and internal fixation (ORIF) and soft tissue reconstruction with a pedicled flap, which led to a substantial bone and soft tissue defect of the lower leg. After thorough antibiotic treatment and after ensuring a non-septic wound, the defect was reconstructed using a contralateral free fibula flap designed as a flow through flap in a double loop manner to accommodate two fibular fragments and an ipsilateral ALT flap. Early weight bearing was initiated 11 days after the free flap transfer under external fixation, with full weight bearing achieved in 36 days with external fixation. After the removal of external fixation, full weight bearing was able to be reinitiated after 13 days, leading to the patient's return to normal activity 6 months after the bony reconstruction. This case presents an innovative approach to treating a complex defect, with the final decision on using two separate free flaps instead of a single osteofasciocutaneous free flap resulting in a good bony reconstruction and soft tissue coverage, and with the use of external fixation enabling early rehabilitation.


Assuntos
Retalhos de Tecido Biológico , Osteomielite , Procedimentos de Cirurgia Plástica , Humanos , Adolescente , Fíbula/lesões , Coxa da Perna , Retalhos de Tecido Biológico/cirurgia , Osteomielite/etiologia , Osteomielite/cirurgia , Resultado do Tratamento , Extremidade Inferior
3.
Int Wound J ; 19(5): 1133-1140, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34939308

RESUMO

Negative-pressure-wound-therapy is commonly used in clinical routine for wound management. Aim of the present study was to assess the feasibility and safety of using an additional container to collect wound fluid during ongoing negative-pressure-wound-therapy. In this present prospective observational study, patients with negative-pressure-wound-therapy were included. An additional container was inserted in the connecting tube between the wound and the vacuum generating device. The following 3 days, the container was changed daily and replaced by a new one. Further safety outcome parameters were assessed. A questionnaire was answered by the responsible surgeon. Twenty-two patients with negative-pressure-wound-therapy with a median (IQR) age of 58.5 (53.0-70.0) years were included in the present study. In median, the duration of negative-pressure-wound-therapy was 5.0 (4.6-5.5) days. In mean ± SD the collected volume of the wound fluid in millilitres (mL) was on day one 7 ± 4 on day two 8 ± 7 and 10 ± 11 on day three. In one patient, there was <0.1 mL of clear water in the additional container. No safety concerns due to the additional container were observed. This study demonstrates that collecting wound fluid during ongoing negative-pressure-wound-therapy over a time period of 3 days is feasible and safe. No safety concerns were observed.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Idoso , Estudos de Viabilidade , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Cicatrização
4.
J Plast Reconstr Aesthet Surg ; 75(1): 160-172, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34635456

RESUMO

BACKGROUND: With the experience-based hypothesis of low donor site morbidity (DSM) for free flaps from the distal femur, this cohort study aimed to evaluate the DSM according to objective and reproducible criteria. METHODS: One hundred and fifty-six patients who had a flap harvest from either the medial or lateral femoral condyle region between 2005 and 2017 were included. A retrospective chart review was performed for all patients. In total, 97 patients were available for a follow-up examination. Outcomes were assessed according to objective (Knee Society Score; Larson Knee Score; OAK Score; 0-100 points), patient-reported (IKDC Score; KOOS Score; 0-100 points), and radiologic criteria (Kellgren and Lawrence Score; MRI Osteoarthritis Knee Score). RESULTS: The median follow-up time was 1529 days (range: 248-4,810). The mean Knee Society Score (94.8 ± 10.1), Larson Knee Score (94.5 ± 10.1), and OAK Score (95.5 ± 6.6) showed nearly unimpaired knee function. The overall patient-reported DSM was low (IKDC Score: 86.7 ± 17.4; KOOS Score: 89.3 ± 17.1). Osteochondral (OC) flaps had a significantly higher DSM, regardless of the donor site. Bone flaps did not show any relevant radiologic morbidity in the Kellgren and Lawrence Score. Besides the procedure-associated cartilage lesions at the OC donor sites, MRI Osteoarthritis Knee Score did not show any significant presence of further knee pathologies in the bilateral MRI Scans. The obvious cartilage lesions did not have a relevant impact on the knee function of most patients. CONCLUSION: The DSM for bone and soft-tissue flaps from the femoral condyle region is negligible. OC flaps are associated with a significantly higher DSM, although a clinically relevant impact on knee function was not evident in the majority of patients.


Assuntos
Cartilagem Articular , Retalhos de Tecido Biológico , Fraturas Intra-Articulares , Osteoartrite , Cartilagem Articular/cirurgia , Estudos de Coortes , Fêmur , Retalhos de Tecido Biológico/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Morbidade , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos
5.
J Foot Ankle Surg ; 57(5): 1020-1023, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29804922

RESUMO

Despite various therapy options, the prophylactic and symptomatic treatment of recurrent ulcerations in the diabetic foot are still challenging. We report the application of a free vascularized medial femoral condyle flap to prevent the recurrence of pressure ulcer in a patient with diabetic foot syndrome. Our patient had type 2 diabetes and presented with pressure ulcers and osteomyelitis of metatarsal heads 2 and 3 after a great toe amputation. We chose to use a medial femoral condyle flap as a damper in the area of the metatarsal heads because of the relatively young age and good vascularity of our patient. We shaped the graft like a ski to distribute the pressure and prevent perforation of the plantar skin. Good results were achieved for wound healing, pain reduction, and improvement of gait. No pressure ulceration had recurred after a 3-year follow-up period. The versatility of the osteomyocutaneous graft from the medial femoral condyle is an important reconstructive tool for addressing major surgical problems. We present the first use of a medial femoral condyle flap in the treatment of a pressure ulcer in a diabetic foot. In selected patients, our method could prevent premature and extended amputations, thereby providing good improvement in patients' quality of life.


Assuntos
Amputação Cirúrgica/métodos , Pé Diabético/cirurgia , Fêmur/cirurgia , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica/métodos , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Plast Reconstr Aesthet Surg ; 71(7): 967-975, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29655665

RESUMO

BACKGROUND: The medial femoral condyle (MFC) flap is based on the descending genicular artery (DGA), which is a vessel with different variations in its course and branching patterns. Many studies have dealt with the vascular anatomy of the MFC. However, the results of the investigations differ markedly. METHODS: The authors performed a systematic literature search in MEDLINE for articles published until May 2017 on the vascular anatomy of the DGA. After the screening, 23 relevant studies with a similar topic were included into this comprehensive analysis. RESULTS: The systematic review examined the lengths and diameters of the individual arteries with regard to the vascularized bone flap of the MFC. The DGA is present in 94% of cases with an average length of 1.8 cm. In 63% of the investigated cases, the DGA divides into three terminal branches. The articular branch has an average length of 7.7 cm, the saphenous branch has a length of 10.7 cm, and the muscular branch has a length of 3.2 cm. CONCLUSION: To ensure a secured survival of this free flap, a detailed understanding of the convoluted vascular anatomy above the MFC is necessary. We recommend the Dubois classification for a systematic classification of the anatomical patterns of the DGA.We present a summary of all anatomical studies dealing with the vascular supply to the MFC and the DGA to date.


Assuntos
Artérias/anatomia & histologia , Extremidade Inferior/irrigação sanguínea , Humanos , Retalhos Cirúrgicos/irrigação sanguínea
7.
Burns ; 43(6): 1195-1202, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28641917

RESUMO

BACKGROUND: Tissue expansion is frequently used in reconstructive surgery. Although the surgical procedure is typically considered simple, reported complication rates of tissue expansions exceed 40%. There is little evidence concerning risk factors for complications in tissue expansion in body regions other than breast. The aim was to determine risk factors for complications in non-breast tissue expansion. METHODS: 34 patients treated with subcutaneous tissue expanders between 2005 and 2014 were analyzed. Demographic data, body-mass index (BMI), mean arterial blood pressure (MAP), treatment indications, expansion site, previous expansion therapies in the same body region, smoking history, as well as expander characteristics (shape, volume, and filling mechanism) were ascertained. Complications were assessed and ranked according to severity based on the Clavien-Dindo classification. Binary logistic regression analysis adjusted for clinical characteristics was used. A p<0.05 was considered as statistically significant. RESULTS: Complications were observed in 26 out of 71 expanders analyzed (36.6%), of whom 10 led to therapy failure. Expanders used in the limbs, female gender, and high expander volume turned out as significant risk factors. Patients with both a high MAP and low BMI developed tissue necrosis significantly more often (p=0.002). The use of tissue expansion after a burn was not associated with an increased risk for complications. CONCLUSIONS: This is the first study revealing female gender and low BMI as risk factors in tissue expander surgery. Thus, careful patient selection is mandatory to avoid complications in tissue expansion. Burn patients do not develop complications more often.


Assuntos
Queimaduras/complicações , Cicatriz/cirurgia , Necrose/epidemiologia , Obesidade/epidemiologia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/epidemiologia , Dispositivos para Expansão de Tecidos , Expansão de Tecido , Adolescente , Adulto , Pressão Arterial , Índice de Massa Corporal , Criança , Pré-Escolar , Cicatriz/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
8.
Plast Reconstr Surg ; 137(6): 1024e-1032e, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27219254

RESUMO

BACKGROUND: The perforators of the free lateral femoral condyle flap have yet to be adequately described in humans. Therefore, the authors investigated the perforator vessels of the lateral femoral condyle flap in an anatomical study and discussed potential clinical applications with a particular interest in its indication with vascularized bone and/or iliotibial band for tendon repair surgery. METHODS: The authors dissected thighs of 28 cadavers to evaluate the anatomical properties of perforator vessels that branch from the superior lateral genicular artery and supply bone, cartilage, subcutaneous tissue, and the iliotibial band of the lateral femoral condyle. RESULTS: In each dissected thigh, the superior lateral genicular artery was present and the average pedicle length was 38 ± 10 mm. The average diameter of the superior lateral genicular artery, proximal to its distribution into the deep articular and superficial patellar branches, was 2 ± 0.5 mm. A communication between deep articular and superficial patellar branches was seen in 96 percent of the dissected thighs. In 24 cases (86 percent), the authors were able to show the iliotibial band perforating vessel and harvest a free lateral femoral condyle flap as an osteochondral fasciocutaneous bone flap with vascularized tendon. CONCLUSIONS: Altogether, the authors' results indicate that the blood supply of the lateral femoral condyle flap is consistent and the lateral femoral condyle flap could serve as a free composite flap for complex indications in hand or limb reconstructive surgery. Clinical studies to compare the lateral femoral condyle to other well-established microsurgical free flaps are warranted.


Assuntos
Transplante Ósseo/métodos , Aloenxertos Compostos/irrigação sanguínea , Aloenxertos Compostos/cirurgia , Fêmur/irrigação sanguínea , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/cirurgia , Artérias/anatomia & histologia , Cartilagem/irrigação sanguínea , Feminino , Humanos , Masculino , Tela Subcutânea/irrigação sanguínea , Tendões/irrigação sanguínea
9.
Burns ; 41(4): 714-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25678085

RESUMO

INTRODUCTION: The aim of this study was to characterize the epidemiology of pediatric and adolescent burns admitted to the Children's Burns Unit at the Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria, between January 1st 1988 and December 31st 2012. METHODS: This is a retrospective review over the past 25-years and describes admission rate by gender and age groups, causes of burns, anatomical sites of burns, extent and depth of injury, length of hospital stay, child abuse and in-hospital mortality. RESULTS: In the studied 25 year-period, 1586 pediatric burn patients were admitted. 1451 patients were "acute" admissions, 64 "secondary" admissions and 71 patients did not fulfill the inclusion criteria. Of the 1451 patients, 930 (64%) were male and 521 (36%) female. The majority of patients - 880 or 60.6% - were children from 1 to 5 years of age. Domestic burns occurring at home resulted in 1164 (80.2%) of injuries and scalds were the most common type of thermal trauma with 945 (65.1%) patients. According to the extent of injury 1106 (76.2%) patients suffered burns of <10% with an median length of hospital stay of 3 days. 14 children (0.98%) - 8 girls and 6 boys - were confirmed victims of abuse and 4 patients (0.3%) died. CONCLUSION: The study provides a good opportunity to review changes in burn care over a long time period, at a single center, including children and adolescents, with stable surgical and rehabilitation staff. The data is also important for the design of prevention programs and establishment of burn care capacities, since the analysis showed no change in the incidence of burn related admissions over the time period studied.


Assuntos
Unidades de Queimados , Queimaduras/epidemiologia , Maus-Tratos Infantis/estatística & dados numéricos , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Adolescente , Distribuição por Idade , Áustria/epidemiologia , Superfície Corporal , Queimaduras/etiologia , Queimaduras/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Distribuição por Sexo , Índices de Gravidade do Trauma
10.
Breast J ; 20(5): 461-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25041092

RESUMO

UNLABELLED: Acellular dermal matrices (ADM) have been used frequently in therapeutic and prophylactic breast procedures. To date there have been no reports on vascularisation of ADMs and formation of tissue around them as seen with modern non-invasive imaging techniques such as contrast-enhanced ultrasound (CEUS). In this case series, we used CEUS to investigate the features of ADM in relation to vascular ingrowth and scaffold for "new" tissue formation. This is a retrospective evaluation of patients who underwent successful skin- and nipple-sparing mastectomy (SSM, NSM) with immediate IBBR using ADM from May 31, 2010, through December 28, 2012. Over a 24-month period, 16 patients, with an average age of 44 years (range 27-70 years), were evaluated with CEUS. No contrast agent allergies or side effects were reported for the ultrasound examination. After contrast agent injection (1-18 months postoperatively), homogeneous normal enhancement in the ADM and peripheral region with physiological tissue formation was seen in all patients. In this small study, the most obvious contribution of CEUS is the in vivo evaluation of vascular ingrowth and tissue formation after IBBR with ADM after follow-up of 1-18 months postoperatively. LEVEL OF EVIDENCE III: Retrospective cohort or comparative study; case-control study; or systematic review of these studies.


Assuntos
Derme Acelular , Implante Mamário , Mama/irrigação sanguínea , Mastectomia , Adulto , Idoso , Implantes de Mama , Meios de Contraste , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia Mamária , Cicatrização
11.
Burns ; 40(6): 1116-20, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24438740

RESUMO

BACKGROUND AND AIM: Deep dermal and full-thickness burn wounds are excised and grafted with split-thickness skin grafts. Especially in less compliant patients such as young children, conventional fixing methods can often be ineffective due to high mobility rates in this age group. The aim of this retrospective single-centre study was to give an overview of our experience in the fixation of autologous split-thickness skin grafts (ASTSGs) on burn wounds by negative pressure wound therapy (NPWT) in paediatric patients. METHODS: A retrospective analysis describing 53 paediatric patients with burns or burn-related injuries who were treated as 60 individual cases were conducted. All patients received ASTSGs secured by NPWT. RESULTS: Of the individual cases, 60 cases with a mean age of 8±6 years (the youngest was 3 months, the eldest was 24 years old) were treated in a single procedure with ASTSG and NPWT. Total burn surface area (TBSA) was, median (med) 4.5% (3.0-12.0%). The TBSA of deep dermal thickness to full-thickness (IIb-III°) burns was med 4.0% (2.0-6.0%). The TBSA treated with ASTSG and NPWT was med 3.5% (2.0-6.0%). Take rate was, med 96% (90-99%) with a total range of 70-100%. The only significant correlation that could be found was between the grafted TBSA and the take rate. The smaller the grafted TBSA the better the take rate resulted, as expected. In three cases, major complications were noted. CONCLUSION: To sum up our experience, the NPWT system has developed itself to be a constant, well-implemented and useful tool in securing ASTSGs to the wound bed. The main advantage of the technique is a much higher mobility of the patient compared to conventional fixation methods. The high compliance rate of an often challenging group of patients such as children recompenses possible higher costs compared to conventional fixation methods.


Assuntos
Queimaduras/terapia , Tratamento de Ferimentos com Pressão Negativa , Transplante de Pele/métodos , Adolescente , Adulto , Bandagens , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Estudos Retrospectivos , Transplante Autólogo , Cicatrização , Adulto Jovem
12.
Wound Repair Regen ; 21(3): 482-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23627267

RESUMO

A gelatinase-based device for fast detection of wound infection was developed. Collective gelatinolytic activity in infected wounds was 23 times higher (p ≤ 0.001) than in noninfected wounds and blisters according to the clinical and microbiological description of the wounds. Enzyme activities of critical wounds showed 12-fold elevated enzyme activities compared with noninfected wounds and blisters. Upon incubation of gelatin-based devices with infected wound fluids, an incubation time of 30 minutes led to a clearly visible dye release. A 32-fold color increase was measured after 60 minutes. Both matrix metalloproteinases and elastases contributed to collective gelatinolytic enzyme activity as shown by zymography and inhibition experiments. The metalloproteinase inhibitor 1,10-phenanthroline (targeting matrix metalloproteinases) and the serine protease inhibitor phenylmethlysulfonyl fluoride (targeting human neutrophil elastase) inhibited gelatinolytic activity in infected wound fluid samples by 11-37% and 60-95%, respectively. Staphylococcus aureus and Pseudomonas aeruginosa, both known for gelatinase production, were isolated in infected wound samples.


Assuntos
Bactérias/enzimologia , Técnicas Microbiológicas/instrumentação , Peptídeo Hidrolases/biossíntese , Infecção dos Ferimentos/diagnóstico , Desenho de Equipamento , Humanos , Reprodutibilidade dos Testes , Infecção dos Ferimentos/enzimologia , Infecção dos Ferimentos/microbiologia
14.
Exp Dermatol ; 20(6): 508-13, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21488974

RESUMO

Human neutrophil elastase (HNE) and cathepsin G (CatG) are involved in the pathogenesis of a number of inflammatory disorders. These serine proteinases are released by neutrophils and monocytes in case of infection. Wound infection is a severe complication regarding wound healing causing diagnostic and therapeutic problems. In this study we have shown the potential of HNE and CatG to be used as markers for early detection of infection. Significant differences in HNE and CatG levels in infected and non-infected wound fluids were observed. Peptide substrates for these two enzymes were successfully immobilised on different surfaces, including collagen, modified collagen, polyamide polyesters and silica gel. HNE and CatG activities were monitored directly in wound fluid via hydrolysis of the chromogenic substrates. Infected wound fluids led to significant higher substrate hydrolysis compared with non-infected ones. These different approaches could be used for the development of devices which are able to detect elevated enzyme activities before manifestation of infection directly on bandages. This would allow a timely intervention by medical doctors thus preventing severe infections.


Assuntos
Catepsina G/metabolismo , Elastase de Leucócito/metabolismo , Infecção dos Ferimentos/diagnóstico , Infecção dos Ferimentos/enzimologia , Ferimentos e Lesões/enzimologia , Bandagens , Biomarcadores/análise , Biomarcadores/metabolismo , Catepsina G/análise , Compostos Cromogênicos , Exsudatos e Transudatos/enzimologia , Humanos , Úlcera da Perna/diagnóstico , Úlcera da Perna/enzimologia , Elastase de Leucócito/análise , Úlcera por Pressão/diagnóstico , Úlcera por Pressão/enzimologia , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/enzimologia , Cicatrização/fisiologia
15.
Diagn Microbiol Infect Dis ; 71(1): 12-23, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21388768

RESUMO

Detection of wound infection is based on evaluation of the well-known signs of inflammation like rubor (redness), calor (heat), tumor (swelling), and dolor (pain) by medical doctors and/or time-consuming procedures requiring special machinery. There is currently no rapid diagnostic device available for the indication of wound infection, which would especially be helpful in home care of chronic ulcer patients. In this study, a new concept for a fast diagnostic tool for wound infection based on lysozyme and elastase triggered release of dye from a peptidoglycan matrix was investigated. The matrix consisted of alginate/agarose and peptidoglycan covalently labeled with Remazol brilliant blue. Lysozyme activity in postoperative wounds and decubitus wound fluids was significantly elevated upon infection (4830 ± 1848 U mL(-1)) compared to noninfected wounds (376 ± 240 U mL(-1)). Consequently, incubation of 8% (w/v) labeled agarose/peptidoglycan blend layers with infected wound fluid samples for 2 h at 37 °C resulted in a 4-fold higher amount of dye released than measured for noninfected wounds. For alginate/peptidoglycan beads, a 7-fold higher amount of dye was released in case of infected wound fluid samples compared to noninfected ones. Apart from lysozyme, proteases [i.e., gelatinase matrix metalloproteinase MMP-2 and MMP-9 and elastase] were detected in wound fluids (e.g., using Western blotting). When dosed in ratios typical for wounds, a slight synergistic effect was measured for peptidoglycan hydrolysis (i.e., dye release) between lysozyme and these proteases. Incubation of a double-layer system consisting of stained and nonstained peptidoglycan with infected wound fluids resulted in a color change from yellow to blue, thus allowing simple visual detection of wound infection.


Assuntos
Ensaios Enzimáticos Clínicos/métodos , Peptidoglicano/metabolismo , Infecção dos Ferimentos/diagnóstico , Líquidos Corporais/enzimologia , Ensaios Enzimáticos Clínicos/instrumentação , Corantes/metabolismo , Gelatinases/metabolismo , Humanos , Muramidase/metabolismo , Peptídeo Hidrolases/metabolismo
16.
Traffic ; 12(7): 902-11, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21438969

RESUMO

Cytotoxic T lymphocytes (CTL) are potent killers of virally infected and tumorigenic cells. Upon recognition of target cells, CTL undergo polarized secretion of secretory lysosomes at the immunological synapse (IS) that forms between CTL and target. However, the molecular machinery involved in the polarization of secretory lysosomes is still largely uncharacterized. In this paper, we investigated the role of Rab7 in the polarization of secretory lysosomes. We show that silencing of Rab7 by RNA interference reduces the ability of CTL to kill targets. GTP-bound Rab7 and Rab interacting lysosomal protein, RILP, interact and both localize to secretory lysosomes in CTL. Over-expression of RILP recruits dynein to the membranes of secretory lysosomes and triggers their movement toward the centrosome. Together, these results suggest that Rab7 may play a role in secretory lysosome movement toward the centrosome by interacting with RILP to recruit the minus-end motor, dynein.


Assuntos
Vesículas Secretórias/metabolismo , Linfócitos T Citotóxicos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Dineínas/metabolismo , Guanosina Trifosfato/metabolismo , Células HeLa , Humanos , Lisossomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos , Mutação , Interferência de RNA , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas rab de Ligação ao GTP/genética , proteínas de unión al GTP Rab7
17.
Int J Antimicrob Agents ; 36(1): 84-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20456925

RESUMO

The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600 mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0-8h post dose in three representative patients. Mean peak concentrations of free linezolid in plasma, healthy subcutis, inflamed subcutis and cancellous bone were 16.6+/-3.0, 15.5+/-2.5, 15.8+/-2.8 and 15.1+/-4.1mg/L, respectively. The degree of tissue penetration as expressed by the ratio of the area under the concentration-time curve of free linezolid from 0-12h (fAUC(0-12)) in tissue to the fAUC(0-12) in plasma was 1.32+/-0.09, 1.12+/-0.22 and 1.09+/-0.11 for healthy subcutis, inflamed subcutis and bone, respectively. Based on currently available pharmacokinetic/pharmacodynamic targets, we conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infection complicated by osteomyelitis.


Assuntos
Acetamidas/farmacocinética , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Osso e Ossos/química , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/complicações , Oxazolidinonas/farmacocinética , Pele/química , Acetamidas/administração & dosagem , Idoso , Antibacterianos/administração & dosagem , Humanos , Linezolida , Masculino , Pessoa de Meia-Idade , Osteomielite/tratamento farmacológico , Oxazolidinonas/administração & dosagem , Plasma/química , Infecções dos Tecidos Moles/tratamento farmacológico
18.
J Antimicrob Chemother ; 65(6): 1252-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20375031

RESUMO

OBJECTIVES: In the attempt to overcome increasing glycopeptide- and methicillin-resistant soft tissue infections, daptomycin is presently considered as an attractive alternative to the class of glycopeptides. However, daptomycin dosing and its ability to penetrate into inflamed target tissues are still a matter of controversy. Thus, in the present investigation, we set out to evaluate daptomycin's ability to penetrate into inflamed subcutaneous adipose tissue and bone in diabetic patients presenting with severe bacterial foot infection. PATIENTS AND METHODS: The microdialysis technique was utilized to collect interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone. Plasma and unaffected subcutaneous adipose tissue served as reference compartments. Serial sampling of specimens at steady-state was performed from 0 to 8 h post-dose in five patients (Group A) and from 8 to 16 h after study drug administration in another group of four patients (Group B). In all subjects, daptomycin was administered intravenously once daily at a dosage of 6 mg/kg body weight for 4 consecutive days at minimum. RESULTS: Equilibrium between free tissue and plasma concentrations was achieved approximately 2 h post-infusion. Under steady-state conditions, the degree of tissue penetration was assessed by the calculation of the ratio of free (f) AUC of daptomycin in plasma to the fAUC in tissues. The mean ratios of the fAUC0-16 tissue to the fAUC0-16 plasma were 1.44, 0.98 and 1.08 for healthy tissue, inflamed subcutaneous adipose tissue and bone, respectively. The corresponding ratios of the fAUCs from 0 to 24 h were 1.54, 1.06 and 1.17, respectively. CONCLUSIONS: With the reservation that pharmacokinetic-pharmacodynamic targets for daptomycin in tissues are currently not established, we conclude that daptomycin given at intravenous doses of 6 mg/kg body weight once daily may be considered an effective treatment regimen in diabetic patients suffering from bacterial foot infection and osteomyelitis.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Osso e Ossos/química , Daptomicina/administração & dosagem , Daptomicina/farmacocinética , Pé Diabético/tratamento farmacológico , Tela Subcutânea/química , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade
20.
J Plast Reconstr Aesthet Surg ; 63(7): e564-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20153277

RESUMO

If diagnosed late, post-surgical pyoderma gangrenosum (PSPG) is a rare, tricky and potentially life-threatening complication. Once diagnosed, immunosuppressive agents may provoke further complications. Well-intentioned extensive serial debridement may cause deep skin and soft-tissue defects, requiring skin grafting and possible flap surgery. The combination of necessary immunosuppressive treatment, protracted hospital stay and broad-spectrum systemic antimicrobial therapy may encourage serious acquired multidrug resistance (MDR). We report an unfortunate triad following breast reconstruction of PSPG, full-thickness chest wall defect and MDR with Acinetobacter baumannii infection. Interdisciplinary treatment using free flap surgery and negative-pressure wound therapy with instillation therapy (V.A.C.Instill(R) Wound Therapy) enabled survival and complete wound closure.


Assuntos
Infecções por Acinetobacter/etiologia , Acinetobacter baumannii , Farmacorresistência Bacteriana Múltipla , Mamoplastia/efeitos adversos , Pioderma Gangrenoso/etiologia , Parede Torácica , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/terapia , Acinetobacter baumannii/efeitos dos fármacos , Infecção Hospitalar/etiologia , Infecção Hospitalar/terapia , Desbridamento/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Pioderma Gangrenoso/patologia , Pioderma Gangrenoso/terapia , Retalhos Cirúrgicos/efeitos adversos
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