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1.
Int J Cancer ; 136(8): 1781-91, 2015 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25274141

RESUMEN

Soft tissue sarcomas (STS) are heterogeneous malignant tumors of mesenchymal origin. Due to low incidence and high number of different histological subtypes, their pathogenesis and thus potential targets for their therapy remain barely investigated. Several studies revealed significant higher EPHB4 expression in malignancies such as prostate and colorectal cancer showing survival advantages for these tumor cells. Therefore we studied the expression of EPHB4 in a total of 46 clinical human specimens of different STS and human fibroblasts. EPHB4 mRNA and protein expression were significantly increased in synovial sarcoma. After targeting EPHB4 in fibrosarcoma, synovial sarcoma, liposarcoma and MFH sarcoma cell lines by siRNA or by inhibition of autophosphorylation using the specific EPHB4 kinase inhibitor NVP-BHG712 a decreased proliferation rate/vitality of synovial- and fibrosarcoma cells was observed. Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells towards fibroblasts and endothelial cells. In addition, we assessed the anti-metastatic effect of EPHB4 inhibition in vivo by intraperitoneal administration of the EPHB4 inhibitor in an appropriate sarcoma lung metastasis xenograft model. As result 43% of NVP-BHG712 treated mice (n = 3/7) developed pulmonary metastases whereas all control mice (n = 5) revealed lung metastases. The residual 57% of mice (n = 4/7) showed only small local tumor cell spots. Size measurements of the Vimentin positive area explained significant decrease in lung metastasis formation (p < 0.05) after EPHB4 kinase inhibition. In summary, these data provide first evidence of the importance of EPHB4 in the tumorigenesis of synovial sarcoma and present EPHB4 as a potential target in the therapy of this malignancy.


Asunto(s)
Expresión Génica/genética , Receptor EphB4/genética , Receptor EphB4/metabolismo , Sarcoma/genética , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Sarcoma/metabolismo , Sarcoma/patología
2.
Zentralbl Chir ; 139 Suppl 2: e103-8, 2014 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-21294083

RESUMEN

OBJECTIVE: Extravasations account for most iatrogenic injuries. The aim of the study was to analyse the results of surgery in patients with extravasations and to draw conclusions for future treatment. MATERIALS AND METHODS: 24 patients with soft-tissue defects after extravasations were treated between 1999 and 2009 in our hospital. The cases were analysed retrospectively. We looked at the drugs causing tissue necrosis and the localisation in relation to the number of interventions and reconstruction complexity. RESULTS: In 83 % (n = 20) of cases tissue necrosis was caused by chemotherapeutic agents, in 8 % (n = 2) by contrast mediums and in 4 % (n = 1) by antibiotics and insulin. 70 % of the cases involved the upper extremity, in 30 % the thoracic wall was affected. 38 % of the extravasations occurred over venous access ports. In mean 2 ±â€Š1.5 interventions were necessary for defect coverage. Two patients died as a direct result of the extravasations, one due to sepsis originating from an infected necrosis area and one due to right-heart failure with prior pulmonary damage. CONCLUSION: Most extravasations can be treated without surgery. In cases of toxic extravasations or pressure-caused ischaemia rapid surgical intervention is necessary to prevent the necrosis progressing to deeper tissue layers.


Asunto(s)
Extravasación de Materiales Terapéuticos y Diagnósticos/cirugía , Enfermedad Iatrogénica , Adulto , Anciano , Anciano de 80 o más Años , Tejido Conectivo/patología , Tejido Conectivo/cirugía , Extravasación de Materiales Terapéuticos y Diagnósticos/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Reoperación , Estudios Retrospectivos , Piel/patología
3.
Antimicrob Agents Chemother ; 55(5): 2325-34, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21343458

RESUMEN

Wound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 10(5) CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.


Asunto(s)
Compuestos Aza/administración & dosificación , Compuestos Aza/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/patogenicidad , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Administración Tópica , Animales , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Ratas , Porcinos , Infección de Heridas/microbiología
4.
Eur Arch Otorhinolaryngol ; 268(11): 1541-7, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21792686

RESUMEN

Current data have now attributed a viral etiology and causality of Human papillomavirus (HPV). Epidemiological analysis of the last decade demonstrates a rapid increase of HPV-associated HNSCC. Genomic detection of HPV DNA in the nuclei of certain oro-pharyngeal cancer cells gives strong evidence of a viral etiology in HNSCC. Non-smokers, non-drinkers, and a sexual debut at a younger age and other sexual risk factors have an increased risk of HPV-positive oropharyngeal cancer. Sexual transmission is considered to play a causal role. In contrast to HPV-negative HNSCC most studies reveal a favorable prognosis for HPV-positive tumors. There is evidence of alterations in the p53 pathway through expression of E6 oncogene with subsequent induction of tumor cell proliferation. Synergies between viral oncogenes and other carcinogens are hypothesized. HPV alone appears to be insufficient as the sole cause of HNSCC; this may explain the long latency period between HPV infection and cancer development. There is now sufficient evidence for a causal role for HPV in HNSCC. As in cervical cancer, HPV requires oncogenes and co-factors for tumor development. Thus, inhibition or loss of such co-factors may lead to tumor regression. The vast amounts of epidemiological, molecular pathological and in vitro experimental data are consistent with the hypothesis that HPV does indeed have a causal role. We await final validation from animal experimentation in which regression of HPV-positive tumors will follow from loss or inhibition of E6 and E7.


Asunto(s)
ADN Viral/análisis , Neoplasias de Cabeza y Cuello , Papillomaviridae/genética , Infecciones por Papillomavirus , Salud Global , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/virología , Humanos , Incidencia , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Factores de Riesgo
5.
Unfallchirurg ; 114(7): 634-8, 2011 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-20859608

RESUMEN

Due to social and demographic changes as well as new leisure activities, the number of frostbite injuries in the general population is on the increase. Because the injuries are primarily located on the hands and feet the consequences for those concerned are devastating. We provide help in grading and introduce concrete therapeutic regimes for frostbite which are illustrated by three case reports from our clinical experience with varying risk profiles.


Asunto(s)
Traumatismos de los Pies/diagnóstico , Traumatismos de los Pies/terapia , Congelación de Extremidades/diagnóstico , Congelación de Extremidades/terapia , Traumatismos de la Pierna/diagnóstico , Traumatismos de la Pierna/terapia , Niño , Humanos , Masculino , Persona de Mediana Edad
6.
Br J Dermatol ; 163(1): 121-7, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20346023

RESUMEN

BACKGROUND: Increasing numbers of antibiotics have lost efficiency because of bacterial resistance. The consequences can be severe when surgical wounds become infected during postoperative care. Natural peptide antibiotics, the so-called host defence peptides (HDPs), have been investigated since the 1990s in a search for alternative treatment strategies. HDPs build up a protection shield against pathological microorganisms, especially in human epithelium. The use of HDPs is currently being discussed as a new antimicrobial therapeutic strategy. Accordingly, a profound knowledge of the quantitative relationships of the effectors is essential. OBJECTIVES: To evaluate differences in HDP expression between postoperatively inflamed and healthy epithelium. METHODS: Expression profiles of the genes encoding HDP human beta-defensin (hBD)-1 (DEFB1, previously known as HBD-1), hBD-2 (DEFB4A, previously known as HBD-2), hBD-3 (DEFB103A, previously known as HBD-3) and psoriasin (S100A7) were assessed in samples of surgical wound healing disorders (n = 27) and healthy epithelium (n = 16) by using real-time polymerase chain reaction. Immunohistochemical staining was performed in the same samples. RESULTS: A significant overexpression of DEFB4A (P < 0.001), DEFB103A (P = 0.001) and S100A7 (P < 0.001) was found in cutaneous surgical site infections. Immunohistochemistry revealed intensely elevated protein levels of psoriasin in infected wounds, and differences in distribution with respect to the epithelial layers. CONCLUSIONS: The study demonstrates upregulated mRNA expression and protein levels of HDPs in postoperatively inflamed epithelium. The results may be a starting point for novel pharmacological treatments.


Asunto(s)
Infecciones Bacterianas/metabolismo , Proteínas S100/metabolismo , Enfermedades Cutáneas Infecciosas/metabolismo , Piel/metabolismo , Infección de la Herida Quirúrgica/metabolismo , beta-Defensinas/metabolismo , Adolescente , Adulto , Anciano , Infecciones Bacterianas/genética , Procedimientos Quirúrgicos Dermatologicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Proteína A7 de Unión a Calcio de la Familia S100 , Proteínas S100/genética , Enfermedades Cutáneas Infecciosas/genética , Infección de la Herida Quirúrgica/genética , Adulto Joven , beta-Defensinas/genética
7.
Eur Surg Res ; 44(1): 23-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19940483

RESUMEN

OBJECTIVE: Daily wound assessment, including dressing changes and the removal of old ointments causes discomfort for the patient. We therefore developed a new thermoreversible and transparent gel formulation that allows for filling wounds of different shapes and depths. The aim of the study was to investigate the effect of a wound covering gel on wound healing and the skin's microcirculation. MATERIALS AND METHODS: Investigations were carried out in a standardized and reproducible wound model (hairless mice SKH1/hr, n = 30). Three groups were studied by intravital fluorescence microscopy: treatment with polihexanide-preserved wound covering gel, a formulation containing 3% povidone (PVP)-iodine, and physiological saline for control. Microcirculatory standard parameters were analysed. RESULTS: The non-perfused area vanished within 14 days due to angiogenesis. The venular diameter, oedema formation and functional capillary density showed no significant differences between the three groups. CONCLUSION: The use of the newly developed wound covering gel has no toxic effects on microcirculation and angiogenesis and reveals no significant differences in the overall assessment of microcirculation compared to the control group and the well-established PVP-iodine. The transparent antibacterial wound covering gel allows for direct wound assessment. Due to its thermoreversible gel formulation it enables good wound contact and easy handling.


Asunto(s)
Antiinfecciosos Locales/efectos adversos , Hexanos/efectos adversos , Microcirculación/efectos de los fármacos , Polímeros/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Animales , Pabellón Auricular/lesiones , Masculino , Ratones , Ratones Pelados , Apósitos Oclusivos , Heridas Penetrantes/tratamiento farmacológico
8.
Langenbecks Arch Surg ; 394(2): 321-9, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18594854

RESUMEN

PURPOSE: The aim of this study was to examine the clinical course of patients with the rare finding of regional lymph node metastasis (RLNM) from soft tissue sarcoma. MATERIALS AND METHODS: Data from 28 out of 1,597 consecutive soft tissue sarcoma patients with RLNM were from the patients' charts and interviewing patients and general practitioners. Survival, including possible influencing factors, was statistically calculated. RESULTS: RLNM was seen in 21.4% for epithelioid sarcoma and 17.6% for clear cell sarcoma. All other entities presented RLNM rates below 10%. At follow-up after an average of 9.6 years, only three patients were alive with no evidence of disease. Survival was independent from surgical resection status of the primary tumor and the RLNM as well as from adjuvant radiation and chemotherapy. Tumor entity as well as the length of the time period from primary to RLNM affect survival. CONCLUSIONS: Surgical treatment as well as radiation and chemotherapy may improve survival in selected cases but probably have their value much more in terms of local disease control and improvement life quality of patients who probably already suffer from an aggressive systemic disease at time of nodal involvement.


Asunto(s)
Metástasis Linfática/patología , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Adolescente , Adulto , Quimioterapia Adyuvante , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Radioterapia Adyuvante , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/radioterapia , Adulto Joven
9.
Hautarzt ; 60(12): 984-91, 2009 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-19812986

RESUMEN

PURPOSE: Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS: Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS: Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION: This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.


Asunto(s)
Antiinfecciosos Locales/toxicidad , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Biguanidas/toxicidad , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Iminas , Técnicas In Vitro , Povidona Yodada/toxicidad , Piridinas/toxicidad
10.
Langenbecks Arch Surg ; 393(2): 207-12, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17242894

RESUMEN

BACKGROUND AND AIMS: Synchronous and heterochronous multiple soft tissue sarcoma of the extremities is very rare. Out of 1,201 of our patients, 4 patients presented with symmetrical bilateral soft tissue sarcoma of the extremities. The aim of this study was to identify possible reasons for this unusual manifestation of sarcomas. MATERIALS AND METHODS: The patients' data was acquired by review of the patients' charts and follow-up information was gathered by phone calls to the patients or their relatives and their general practitioners. RESULTS: All tumours were located at the extremities and were diagnosed as leiomyosarcoma in two patients, malignant fibrous histiocytoma and clear cell sarcoma in one patient each. No other individual or family history of cumulation of neoplasms was known in the patients. The median interval between the diagnoses was 3 1/2 years (range: 4 months to 9 1/2 years). In two patients a second primary sarcoma of the same entity was considered the most likely diagnosis, whereas in one patient a contralateral lymph node metastasis and in one other patient an atypical soft tissue metastasis had to be taken into account. A positive family history with a father with malignant fibrous histiocytoma may indicate a hereditary predisposition in one patient. Aside from irradiation effects, exposition to other carcinogenic agents or genetic predisposition, the reasons for the clustering of soft tissue sarcoma in one same patient remain still unclear. Only one patient, although suffering from disseminated metastatic disease was living at follow-up time, the other three patients had already died. CONCLUSION: The interpretation of the bilateral manifestation of soft tissue sarcoma remains open, but predicts an unfavourable outcome.


Asunto(s)
Extremidades/cirugía , Neoplasias Primarias Secundarias/cirugía , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/análisis , Femenino , Estudios de Seguimiento , Histiocitoma Fibroso Maligno/patología , Histiocitoma Fibroso Maligno/cirugía , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Índice Mitótico , Necrosis , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Secundarias/patología , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Sarcoma de Células Claras/patología , Sarcoma de Células Claras/cirugía , Neoplasias de los Tejidos Blandos/patología , Adulto Joven
11.
Eur J Med Res ; 13(11): 505-10, 2008 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-19073386

RESUMEN

OBJECTIVE: Wound healing in burn wounds presents a challenge in healthcare, and there is still a lack of alternatives in topical burn wound treatments. - The purpose of this study was to evaluate the efficacy of a new therapeutic ointment (MEBO) in the treatment of partial thickness burns. METHODS: 40 patients received either topical treatment with Moist Exposed Burn Ointment (MEBO) or standard Flammazine treatment. All patients suffered from partial-thickness burn injuries (< 20% TBSA). Wounds were evaluated for 60 up to days regarding wound healing, water loss, inflammation, and pain alleviation. RESULTS: For transepidermal water loss, there was a difference of 2.3 gr/m2/h between MEBO, and Flammazine, favoring MEBO. However, this difference was not statistically significant (p=0.78). For all secondary efficacy parameter results were similar. - CONCLUSIONS: This study showed that MEBO ointment for topical treatment of burn injuries presents an attractive alternative for the topical treatment of limited partial thickness thermal burns.


Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Quemaduras/tratamiento farmacológico , Pomadas/administración & dosificación , Sulfadiazina de Plata/administración & dosificación , Administración Tópica , Adolescente , Adulto , Anciano , Vendajes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Umbral del Dolor/efectos de los fármacos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Agua/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Adulto Joven
12.
Eur J Med Res ; 11(11): 471-8, 2006 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-17182359

RESUMEN

PEGT/PBT-block-copolymer dermis substitutes were inserted into dorsal skinfold chambers of balb/c mice (n=36). Scaffolding matrices with 3 different pore diameters (pore diameter: <75 micro m, 75-212 micro m and 250-300 micro m) were analyzed on days 7, 14, and 21 post implantation by scanning electron and light microscopy. The quantification of matrix fragmentation was performed using image-analytical software analySIS(R). The fragmentation rate in scaffolding matrices with a pore size of < 75 micro m was observed to be higher than in matrices of larger pore sizes. Image-analytical evaluation over 21 days revealed a reduction of the copolymer matrix by approximately 32% for the <75 micro m matrices, 23% for the 75-212 micro m matrices and 18% for the matrices, where pore size ranged between 250 micro m and 300 micro m. Twenty-one days after implantation, the matrix pores of 75-212 micro m and 250-300 micro m scaffolds were totally filled by vascularized fibrous tissue. Contrarily, an increased formation of foreign-body giant cells was observed in matrices with pore size <75 micro m. The pore size of the scaffolding PEGT/PBT dermis substitutes affects their degradative behaviour in vivo.


Asunto(s)
Poliésteres/uso terapéutico , Polietilenglicoles/uso terapéutico , Piel Artificial , Ingeniería de Tejidos , Animales , Femenino , Ratones , Ratones Endogámicos BALB C , Resultado del Tratamiento
13.
Chirurg ; 77(11): 1040-5, 2006 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-16479392

RESUMEN

INTRODUCTION: Bacterial infections represent a large proportion of emergencies in hand surgery. In some cases, pyoderma gangrenosum and mycobacterial infection may present with the same symptoms of swelling, pain, and purulent secretion. In these cases, operative treatment would be harmful. Therefore two cases-pyoderma gangrenosum and tuberculosis-are presented here in relation to common bacterial hand infection. METHODS: Using two case reports of diseases that only rarely affect the hands, their relevance to differential diagnosis is shown with reference to the literature. RESULTS: In both cases, we found clinical symptoms of bacterial hand infection with negative bacterial smear tests. After several debridements, pyoderma gangrenosum of the dorsum of the hand was diagnosed in one patient after pyodermiform lesions at the thigh and the nasal septum were detected and pre-existing colitis ulcerosa was taken into consideration. Corticoid therapy induced complete remission. The second patient with similar clinical symptoms had been operated on at another hospital several times before being transferred to our institution. The presumptive diagnosis of pyoderma gangrenosum was made, and under treatment with prednisone the symptoms quickly improved. After 2 weeks, the wound conditions and the patient's condition rapidly worsened. Following amputation at the upper arm level, the patient died of septic multiple organ failure. Autopsy studies revealed tuberculous sepsis originating from the hand. DISCUSSION: Patient history should be evaluated carefully because of its value to correct diagnosis. In case of negative smear tests, especially from immunocompromised, elderly patients and in patients with a history of pulmonary tuberculosis, Ziehl-Neelsen staining should be obtained. In case of multilocular affection or pre-existing chronic inflammatory bowel disease, the presumptive diagnosis of pyoderma gangrenosum can be confirmed by biopsies from the lesions margin. In both cases, unnecessary traumatizing operations could thus be avoided and treatment optimized.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Celulitis (Flemón)/diagnóstico , Mano , Piodermia Gangrenosa/diagnóstico , Tuberculosis Miliar/diagnóstico , Adulto , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Infecciones Bacterianas/cirugía , Celulitis (Flemón)/cirugía , Desbridamiento , Diagnóstico Diferencial , Fijadores Externos , Resultado Fatal , Femenino , Mano/cirugía , Humanos , Osteonecrosis/diagnóstico , Osteonecrosis/cirugía , Piodermia Gangrenosa/cirugía , Colgajos Quirúrgicos , Tuberculosis Miliar/cirugía , Articulación de la Muñeca/cirugía
14.
J Craniomaxillofac Surg ; 44(7): 882-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27193476

RESUMEN

INTRODUCTION: Bacterial resistance against antibiotics has become an increasing challenge in the treatment of cutaneous infections. Consequences can be severe, especially in infected wounds following previous local radiotherapy. Certain endogenous peptide antibiotics, the host defence peptides (HDPs), exhibit broad-spectrum antimicrobial activity and promote wound healing. Their use as supplements to conventional antibiotics is a current topic of discussion; however, knowledge of their quantities in healthy and compromised tissue is a prerequisite for such discussion. To date, no data concerning HDP quantities in irradiated skin are available. METHODS: Expression profiles of the genes encoding HDPs, namely human beta-defensin-1 (DEFB1, hBD-1), beta-defensin-2 (DEFB4A, hBD-2), beta-defensin-3 (DEFB103, hBD-3) and S100A7, were assessed in samples of non-irradiated and irradiated neck. RESULTS: A reduction in the expression of all of the examined genes was observed in irradiated skin when compared with non-irradiated skin (statistically significant in the case of S100A7, P = 0.013). Immunohistochemistry revealed differences in HDP distribution with respect to the epithelial layers. CONCLUSION: The study demonstrates a significant reduction in HDP gene expression in neck skin as a result of radiotherapy. These findings might represent a starting point for novel treatments of cutaneous infections in irradiated patients, such as topical supplementation of synthetic HDP.


Asunto(s)
Neoplasias de la Boca/radioterapia , Proteínas S100/biosíntesis , Piel/metabolismo , beta-Defensinas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Radioterapia/efectos adversos , Proteína A7 de Unión a Calcio de la Familia S100 , Proteínas S100/genética , beta-Defensinas/genética
16.
Burns ; 31(2): 168-74, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15683687

RESUMEN

BACKGROUND: The breakdown of skin microcirculation is assumed to play a key role in the pathophysiology after burn injury. The aim of the present study was to develop a burn model, which allows repetitive quantitative in vivo analysis of the microcirculation after a burn injury, focusing on the interaction between leukocytes and the endothelium. MATERIALS AND METHODS: Experiments were carried out on male hairless mice. Deep partial thickness burns were inflicted with a no-touch-technique to the ears. Intravital fluorescent microscopy in combination with FITC-dextran as a plasma marker was used to assess microcirculatory parameters. Leukocytes were stained with rhodamine 6G. Preburn baseline data was obtained before as well as 1, 3, 7 and 14 days subsequent to the burn injury. RESULTS: The non-perfused area decreased significantly over the observed period and perfusion was almost completely restored at day 14. The functional vessel density was characterized by reduction of perfused vessels immediately after burn and an increase after 24h. Leukocyte endothelium interaction significantly increased immediately after injury; baseline values were reached 1 day later. The extravasation of the plasma marker into the surrounding tissue increased immediately after burn, decreased at day 1 and remained at this level during the following observation time. The venular as well as the arterial blood flow increased immediately subsequent to the burn injury, decreased after 1 day and reached baseline values at day 3. CONCLUSION: The presented burn model allows quantitative assessment of the dynamics of microcirculatory disturbances after thermal trauma by high quality visualization of both plasma stained microvessels and leukocyte-endothelium interaction.


Asunto(s)
Quemaduras/fisiopatología , Piel/irrigación sanguínea , Animales , Arterias/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Quemaduras/patología , Modelos Animales de Enfermedad , Endotelio Vascular/fisiopatología , Leucocitos/fisiología , Masculino , Ratones , Ratones Pelados , Microcirculación/fisiología , Microscopía Fluorescente/métodos , Piel/patología , Piel/fisiopatología , Vénulas/fisiopatología
17.
Burns ; 31(2): 159-67, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15683686

RESUMEN

INTRODUCTION: It is well known that in patients suffering from major burn injuries of more than 15% of total body surface area (TBSA), capillary leak and loss of proteins including immunoglobulins (Ig) lead to cardiovascular failure and significantly elevated risk of infections. However, knowledge of the resulting protein profiles is limited. In order to elucidate quantitative and qualitative protein loss in human burn wounds we compared wound fluid (WF) protein content with serum protein levels. MATERIAL AND METHODS: Eleven patients suffering from second degree burns of 18-68% TBSA were enrolled in the study. Immediately after admission burn wounds were enclosed in cutaneous vinyl wound chambers covering a 2.25 cm(2) wound surface area. WF and serum samples were harvested every 8 h with a follow up of 48 h and analyzed for total protein content, albumin and the immunoglobulins A, E, G and M. RESULTS: Protein levels in serum were significantly lower as compared to physiological levels while WF protein levels were elevated and remained high. Total protein (TP) and albumin (AL) accumulated in high concentrations on the wound surface (average accumulation on 10% burnt TBSA within 8 h: TP=16.59+/-8.86 g; AL=12.39+/-5.87 g). The albumin fraction in WF showed increasing values (24 h: 69%; 32 h: 86%) although the serum albumin fraction remained nearly unchanged (55%). Peak values were initially found for all immunoglobulins both in serum and WF. IgA, E and M reached a steady state 32 h post-trauma, whereas IgG continuously decreased until 40 h. IgG values in serum were significantly below physiological levels at all time points. CONCLUSIONS: This study qualifies and quantifies a significant protein loss in second degree burn wounds. Protein concentrations in wound fluid correlate highly with serum concentrations until 48 h post-burn. A patient's entire amount of serum proteins accumulates in wound fluid in a 20% TBSA burn within approximately 24h. In contrast to capillary leak theory proteins and immunoglobulins extravasate to wound fluid even after 48 h post-trauma.


Asunto(s)
Quemaduras/metabolismo , Proteínas/análisis , Adulto , Albúminas/análisis , Proteínas Sanguíneas/análisis , Superficie Corporal , Quemaduras/sangre , Proteína C-Reactiva/análisis , Humanos , Inmunoglobulinas/análisis , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Albúmina Sérica/análisis
19.
Shock ; 15(4): 272-7, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11303725

RESUMEN

Skin is an especially attractive target for genetic manipulation because it is readily accessible and easily monitored for both the presence and the expression of inserted genes. This study was designed to assess the feasibility of particle mediated gene transfer to burned skin and to compare the transfection efficiency, anatomic distribution, and duration of transgene expression achievable in normal versus burned skin. Two days following scald injury of varying depths in 60 degrees C water (10 s: superficial partial; 20 s: deep partial; 40 s: full thickness) reporter gene (beta-galactosidase) constructs were delivered using a gene gun at various helium pressures (200-600 psi) to normal and burned skin. A time course study was performed to examine the kinetics of transgene expression. Animals received a superficial partial thickness burn and were sacrificed 12 h, 1, 3, 5, 7, 14, or 21 days after gene transfer. India Ink injection and immunohistochemistry were used to assess the depth of the scald injury. Transfection efficiency was measured in skin homogenates 24 h after gene transfer by morphometric and chemoluminescent assays. We found that the extent of tissue damage was directly related to the duration of heat source exposure. Reporter gene activity was significantly higher in superficial partial thickness burns compared to normal controls and gradually declined with increasing tissue injury. No activity was seen in the full thickness burn group. Beta-galactosidase activity reached a maximum level 12 h after gene transfer in both normal and superficial partial thickness burned skin with no levels seen after 5 days post-transfection. These findings indicate that particle-mediated gene transfer in thermally injured skin is feasible and may provide a means of introducing biologic agents into injured tissue capable of enhancing bacterial clearance and improving wound healing.


Asunto(s)
Biolística , Quemaduras/terapia , Terapia Genética , Animales , Quemaduras/patología , ADN Recombinante/administración & dosificación , Estudios de Factibilidad , Expresión Génica , Genes Reporteros , Vectores Genéticos/administración & dosificación , Oro , Operón Lac , Mediciones Luminiscentes , Masculino , Microesferas , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/análisis , Organismos Libres de Patógenos Específicos , Transfección , Transgenes , beta-Galactosidasa/análisis
20.
Eur J Med Res ; 9(9): 449-54, 2004 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-15546810

RESUMEN

AIM: Antiseptics are commonly used in clinical practice to disinfect tissue and to avoid infections. However, topical antiseptics are assumed to have an influence on skin microcirculation, per se. Thus, the aim of the study was to analyse the influence of topically applied antiseptics on the microcirculation of intact skin in vivo. MATERIALS AND METHODS: The investigation was carried out on ears of male hairless mice (SKH-1hr, n = 25). The influence of four antiseptics was examined. Sodium chloride 0.9% served as control. An alcohol-based solution with a mixture of ethanol, 2-propanol and purified water (Softasept), an antiseptic with octenidine dihydrochloride and phenoxyethanol as the main active agents (Octenisept), as well as hexamethylenbiguanide (Lavasept) and 70% ethanol were tested. Intravital fluorescence microscopy in combination with intravenous injection of the fluorescence dyes FITC-Dextran as plasma marker and Rhodamine 6G (leukocyte staining) allowed a quantitative analysis of standard microcirculatory parameters (vessel diameter, functional capillary density, red blood cell velocity, FITC-leakage and leukocyte endothelium interaction). Recordings of the microcirculation in several regions of interest (ROI) were made prior to application and after 10 min exposure time and 60 min after the baseline data. Data were evaluated off-line with aid of computer assisted analysis. RESULTS: The diameter of arterioles decreased after the treatment with the alcoholic solutions. The other two antiseptics (Octenisept and Lavasept) caused a significant increase. Functional capillary density (FCD) was significantly reduced after application of ethanol and Softasept. There was no reduction of FCD following application of Octenisept. After treatment with ethanol and Softasept there was a significant decrease in red blood cell velocity (RBCV). The use of Lavasept revealed a decrease of FCD and RBCV. In the Octenisept treated group RBCV shows a mild increase after 10 minutes. The application of ethanol, Softasept and Lavasept was characterized by a significant increase of leukocyte endothelium interaction (LEI). After treatment with saline and Octenisept LEI remained constant. All used antiseptics except of Octenisept caused a significant leakage of FITC-Dextran. CONCLUSION: The antiseptics used in this study all showed an influence on skin microcirculation. As expected, our findings show that the alcoholic solutions are most aggressive to skin microcirculation.


Asunto(s)
Antiinfecciosos Locales/farmacología , Fluoresceína-5-Isotiocianato/análogos & derivados , Piel/irrigación sanguínea , Administración Tópica , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Comunicación Celular/fisiología , Dextranos , Endotelio Vascular/fisiología , Eritrocitos/fisiología , Colorantes Fluorescentes , Leucocitos/fisiología , Masculino , Ratones , Ratones Pelados , Microcirculación/efectos de los fármacos , Microcirculación/efectos de la radiación , Microscopía Fluorescente
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