RESUMEN
BACKGROUND: After more than eight decades of electroconvulsive therapy (ECT) for pharmaco-resistant depression, the mechanisms governing its anti-depressant effects remain poorly understood. Computational anatomy studies using longitudinal T1-weighted magnetic resonance imaging (MRI) data have demonstrated ECT effects on hippocampus volume and cortical thickness, but they lack the interpretational specificity about underlying neurobiological processes. METHODS: We sought to fill in the gap of knowledge by acquiring quantitative MRI indicative for brain's myelin, iron and tissue water content at multiple time-points before, during and after ECT treatment. We adapted established tools for longitudinal spatial registration of MRI data to the relaxometry-based multi-parameter maps aiming to preserve the initial total signal amount and introduced a dedicated multivariate analytical framework. RESULTS: The whole-brain voxel-based analysis based on a multivariate general linear model showed that there is no brain tissue oedema contributing to the predicted ECT-induced hippocampus volume increase neither in the short, nor in the long-term observations. Improvements in depression symptom severity over time were associated with changes in both volume estimates and brain tissue properties expanding beyond mesial temporal lobe structures to anterior cingulate cortex, precuneus and striatum. CONCLUSION: The obtained results stemming from multi-contrast MRI quantitative data provided a fingerprint of ECT-induced brain tissue changes over time that are contrasted against the background of established morphometry findings. The introduced data processing and statistical testing algorithms provided a reliable analytical framework for longitudinal multi-parameter brain maps. The results, particularly the evidence of lack of ECT impact on brain tissue water, should be considered preliminary considering the small sample size of the study.
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Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Encéfalo/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (ß)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. ß-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.
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Colon/metabolismo , Estreñimiento/metabolismo , Diarrea/metabolismo , Fibras de la Dieta/farmacología , Absorción Intestinal , Xilanos , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Biopsia , Degranulación de la Célula/efectos de los fármacos , Colon/patología , Colon/fisiopatología , Estreñimiento/patología , Estreñimiento/fisiopatología , Diarrea/patología , Diarrea/fisiopatología , Femenino , Humanos , Masculino , Mastocitos/metabolismo , Mastocitos/patología , Permeabilidad/efectos de los fármacos , Estrés Psicológico/metabolismo , Estrés Psicológico/patología , Estrés Psicológico/fisiopatología , Xilanos/farmacocinética , Xilanos/farmacologíaRESUMEN
We conducted this study to determine if placement of infraclavicular catheters guided by ultrasound is quicker than placement guided by nerve stimulation. Infraclavicular brachial plexus catheters were inserted in 210 randomly allocated patients who were scheduled for elective hand or elbow surgery. Needle and catheter placement was guided by ultrasound (n = 105) or by nerve stimulation (n = 105). The primary outcome was time to sensory block success. Success rate was similar between the two techniques (83.2% vs 81.4%, p = 0.738). However, placement of ultrasound-guided catheters took less time (7.2 [2.5] vs 9.6 [3.6] min, p < 0 .001). Pain and satisfaction scores, and incidence of nerve deficit, were also similar with both techniques.
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Anestésicos Locales/administración & dosificación , Bloqueo del Plexo Braquial/métodos , Estimulación Eléctrica , Dolor/prevención & control , Ultrasonografía Intervencional , Codo/cirugía , Femenino , Mano/cirugía , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Satisfacción del Paciente/estadística & datos numéricos , Estudios Prospectivos , Método Simple Ciego , Resultado del TratamientoRESUMEN
Contemporary psychiatry uses a variety of complementary approaches which enrich one another. In this paper, we describe the development of a brief psychodynamic approach for hospitalized patients with major depression, as well as the recent commercialization of an atypical neuroleptic depot medication. In addition, we discuss electro-convulsotherapy which, despite it has been widely and understandably condemned on the basis of its abusive and non medical application in certain political contexts, deserves objective assessment on the basis of scientific data stemming from recent research suggesting it is in some contexts a valuable tool.
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Psiquiatría/tendencias , Antipsicóticos/uso terapéutico , Depresión/terapia , Terapia Electroconvulsiva/ética , Terapia Electroconvulsiva/métodos , Terapia Electroconvulsiva/estadística & datos numéricos , Humanos , Isoxazoles/uso terapéutico , Mitología , Palmitato de Paliperidona , Palmitatos/uso terapéutico , Psiquiatría/métodos , Psicoterapia/métodos , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
BACKGROUND: Serum tumour markers correlate with biological tumour behaviour and prognosis of patients. We collected prospective data of melanoma patients in tumour stage III before radical lymph node dissection. MATERIALS AND METHODS: Between 2003 until 2007 we collected 231 tumour stage III patients and analysed the preoperative serum tumour markers S100 (S100 calcium binding protein), NSE (Neuron specific enolase, Enolase 2), Albumin, LDH (Lactate dehydrogenase) and CRP (C-reactive protein) and evaluated the correlation to clinical and pathological data. We divided patients into a group with only a positive sentinel lymph node (group 1; n = 109) and a second with further lymph node metastases (group 2; n = 122). RESULTS: Patients of group 2 had a significant higher T level (p < 0.0001) and Breslow index (p < 0.0001). Patients with a higher Breslow index had a higher S100 serum level (p = 0.021). Patients of group 2 displayed a significant higher level of serum S100. The serum level of CRP correlated with increasing number of lymph node metastases. CONCLUSIONS: A higher Breslow index in tumour stage III patients seems to have an influence on lymph node metastases and on S100 serum level. Patients with more than a positive sentinel lymph node do have a higher S100 level.
Asunto(s)
Biomarcadores de Tumor/sangre , Metástasis Linfática/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Anexina A2/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Melanoma/sangre , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfopiruvato Hidratasa/sangre , Pronóstico , Estudios Prospectivos , Proteínas S100/sangre , Albúmina Sérica/análisis , Neoplasias Cutáneas/sangreRESUMEN
BACKGROUND: We collected the data of 288 patients with malignant skin tumours. We analysed the postoperative pain assessed by a visual analogue scale (VAS) to evaluate the quality of our standard peri-operative pain therapy after a radical inguinal and iliacal lymph node dissection (RILND) as well as the influence of postoperative surgical complications on the level of pain. MATERIALS AND METHOD: The postoperative level of pain of 85 patients with malignant skin tumours who underwent a RILND between August 2003 and December 2007 was recorded prospectively. Patients received a standardised perioperative pain therapy according to level I or II of the World Health Organisation (WHO) ladder of pain. The efficiency of our pain therapy was registered via VAS in the morning of the first three postoperative days. RESULTS: Using our standard pain therapy, we determined a VAS < 30 in rest during the first three postoperative days, but significantly more pain (VAS median 50-30) (p < 0.001) under stress. Patients with surgical complications in the postoperative period (n = 71) had significantly more pain in the postoperative period compared to patients with a regular postoperative course (p = 0.047). CONCLUSIONS: Immediately after a RILND, an analgesic therapy according to level I or II of the WHO pain ladder does not seem to be effective enough. Postoperative surgical complications lead to a higher VAS level of pain in the postoperative period.
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Escisión del Ganglio Linfático , Dimensión del Dolor , Dolor Postoperatorio , Complicaciones Posoperatorias , Adulto , Anciano , Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Axila , Tos/complicaciones , Femenino , Ingle , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , CaminataRESUMEN
BACKGROUND: The surgical radical inguinal / iliacal lymph node dissection (RLND) is the procedure of choice in patients presenting with lymphatic metastasis of melanoma of the lower extremity or the lower part of the trunk. The perioperative morbidity of patients includes not only local wound complications, seroma formation or lymphatic fistula but also leg oedema, deep venous thrombosis and neuralgic disorders postoperatively. The aim of this prospective study was the evaluation of postoperative morbidity in patients undergoing radical inguinal/iliacal RLND in a standardised surgical fashion. PATIENTS AND METHODS: 67 patients suffering from malignant melanoma of the lower extremity or the lower trunk with metastatic lymph nodes in the groin or the iliacal region underwent a combined RLND of the inguinal / iliacal region or the groin alone between 2003 and 2006. All operations were performed in a standardised technique. The main criterion of the study was the incidence of postoperative wound complications. Minor endpoints included the incidence of lymphatic fistula, the length of hospital stay, and the development of temporary or permanent leg oedema. RESULTS: 64 patients underwent inguinal / iliacal and 3 patients only inguinal LND (lymph node dissection). All patients tolerated the procedure well. The overall wound complication rate was 34 %. One patient died on the 21st postoperative day due to a pulmonary embolism and a simultaneous cerebral apoplexy. Lymphatic fistula occurred in 22 (33 %) patients whereas seroma resulted in 23 (34 %) patients. The length of hospital stay was 15 (3-41) days. A relevant leg oedema was observed in 9 (13 %) patients. CONCLUSION: Even with a proper perioperative management and a precise wound care management, one-third of the patients undergoing radical inguinal / iliacal lymphadenectomy suffer from a complication requiring medical or interventional treatment. Our data demonstrate that most of these complications can be treated sufficiently by conservative treatment. A fitted surgical support hose could prevent long-term complications.
Asunto(s)
Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Melanoma/secundario , Complicaciones Posoperatorias/etiología , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Conducto Inguinal/cirugía , Tiempo de Internación , Ganglios Linfáticos/patología , Masculino , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Posoperatorios , Complicaciones Posoperatorias/mortalidad , Reoperación , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Medias de Compresión , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/mortalidad , Dehiscencia de la Herida Operatoria/cirugía , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/mortalidad , Infección de la Herida Quirúrgica/cirugíaRESUMEN
BACKGROUND: Effects of intraoperative application of fibrin glue following combined radical inguinal and iliacal lymph node dissection (RILND) on the amount of postoperative lymphatic secretion are discussed controversially. To detect whether fibrin glue application results in a decreased lymphatic secretion following RILND a randomized patient blinded clinical trial was conducted. METHOD: Between September 2003 and September 2006 58 patients with stage IV melanoma underwent therapeutic RILND and were randomized into two groups. 29 Patients received 4 cc fibrin glue after RILND whereas 29 patients were only irrigated with saline 0.9 percent. Postoperatively all patients received two inguinal and one iliacal closed suction drain. The main outcome criteria were the duration of drain placement in the wound. Minor criteria were the total amount of secretion and the length of hospital stay. RESULTS: There was no difference between the treatment and the control group in the duration of drain placement (fibrin group: 4 days (1-27); control group 5 days (1-26); p=0.64). The total amount of fluid was 310 cc (30-6005) in the fibrin group vs. 365 cc (30-3945 cc) in the control group (p=0.9) and the length of hospital stay 10 days (3-41) (group 1) compared to 11 days (3-41) (p=0.99) were not different between both groups either. CONCLUSION: Intraoperative application of 4 cc fibrin glue does not reduce the length of drain placement, drain output or hospitalisation of patients undergoing RILND with melanoma metastasis to the lymph node basin.
Asunto(s)
Adhesivo de Tejido de Fibrina/farmacología , Escisión del Ganglio Linfático/efectos adversos , Melanoma/patología , Neoplasias Cutáneas/patología , Adhesivos Tisulares/farmacología , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anciano , Drenaje , Femenino , Ingle , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios ProspectivosRESUMEN
OBJECTIVES: "Fast-track" rehabilitation is a multimodal perioperative treatment concept for accelerating postoperative recovery which has been already used successfully in visceral surgery. Of its use in thoracic surgery however, almost no data exist and the relevance of this concept for pulmonary operations is unknown. PATIENTS AND METHODS: In this prospective study we examined a new perioperative fast-track treatment concept for thoracic surgery and evaluated the results. This program employs detailed information of patients, intensive perioperative respiratory therapy, thoracic peridural analgesia, forced mobilization, and an early start of postoperative normal food intake. RESULTS: Fifty consecutive patients with benign or malignant diseases of the lung aged an average of 64 years (range 22-78) were operated on thoracoscopically (n=15) or with thoracotomy (n=35) and treated perioperatively using the fast-track program. All patients were mobilized beginning 4 h postoperatively and had normal food. The incidence of general postoperative complications was 0% in this study. Postoperative stay lasted 4.5 days (range 1.5-28.5). There was no increase in surgical complications, and 6% of the patients were readmitted. The patients' acceptance of this concept was high. CONCLUSION: Fast-track rehabilitation resulted in a decreased rate of general complications and accelerated rehabilitation in thoracic surgery.
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Tiempo de Internación , Enfermedades Pulmonares/cirugía , Neoplasias Pulmonares/cirugía , Grupo de Atención al Paciente , Neumonectomía/rehabilitación , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios/métodos , Analgesia Epidural , Anestesia General , Ambulación Precoz , Alemania , Humanos , Dolor Postoperatorio/etiología , Alta del Paciente , Satisfacción del Paciente , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Toracoscopía , Toracotomía/rehabilitaciónRESUMEN
BACKGROUND: Despite the growing clinical use of the percutaneous dilatational tracheostomy data concerning their first line application are still lacking. METHODS: Retrospective analysis of the intra- and postinterventional morbidity of a modified dilatational tracheostomy in a surgical intensive care unit of a German university hospital over a 2-year period. RESULTS: A total of 107 elective dilatational tracheostomies were performed in 105 patients. There were no intraoperative complications. 2 accidental decannulations occurred in the postoperative period. One conventional tracheostomy had to be performed secondary. Stoma side bleeding or clinical relevant infection had not been observed. After definite decannulation wound closure was spontaneous in all patients. CONCLUSIONS: The first line application of the dilatational tracheostomy has a low morbidity.
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Traqueostomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Traqueostomía/efectos adversos , Traqueostomía/mortalidadRESUMEN
OBJECTIVE: There is experimental evidence that oxygen-derived free radicals (Superoxide (O(2)(-))) play a key role in tissue damage in ischemia-reperfusion injury. Among various antioxidants tested in vitro, natural polyphenols like Epigallocatechine gallate (EGCG) show a 164-fold higher scavenging activity for O(2)(-) than ascorbic acid We therefore conducted an animal study in order to investigate the impact of EGCG on O(2)(-) production during reperfusion after defined periods of ischemia in the muscle tissue of the rat, using a recently developed cytochrome c-based biosensor for on-line in vivo monitoring of O(2)(-). MATERIALS AND METHODS: Femoral artery and vein were dissected below the inguinal ligament in male Wistar rats. The cytochrome c-based biosensor was placed in the gastrocnemius muscle. Ischemia was induced by clamping the femoral vessels. Ischemia times were either 60 (n = 14) or 120 (n = 14) minutes. Six animals in each group received 4 mg/kg body weight EGCG intravenously at the time of reperfusion, another six animals in each group served as controls (no treatment). Additionally, two animals in each group received the same volume of saline instead of EGCG. The current response of the biosensor corresponding to the O(2)(-) concentrations in vivo was recorded on a PC. The gastrocnemius muscles were harvested for histological evaluation. RESULTS: The average maximum O(2)(-) concentration after 60 minutes of ischemia was 188, 18 nmol/L (23 pA) compared to 90 nmol/L (11 pA) (P <.01) with EGCG application. The mean O(2)(-) value after 120 minutes was 220 nmol/L (27 pA) versus 135 nmol/L (16.5 pA) (P <.01) with EGCG, respectively. Histological analysis showed advanced muscle cell injury and neutrophil infiltration in the group without EGCG. No O(2)(-) reduction could be verified administering saline instead of EGCG. CONCLUSION: For the first time the scavenging activity of an antioxidant was verified in vivo on-line. EGCG significantly diminished O(2)(-) tissue concentrations after 60 or 120 minutes of ischemia by an average of nearly 50%, suggesting its therapeutic potential.
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Antioxidantes/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Daño por Reperfusión/prevención & control , Animales , Modelos Animales de Enfermedad , Arteria Femoral , Vena Femoral , Cinética , Masculino , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Ratas , Ratas Wistar , Superóxidos/metabolismoRESUMEN
OBJECTIVE: to investigate in a pig model whether small diameter ePTFE grafts will sustain a confluent endothelial cell layer formed in vitro under shear stress conditions. MATERIALS AND METHODS: thirteen ePTFE (4 mm) grafts were implanted end to end in the right femoral artery of; 8 grafts had been endothelialized in vitro. Grafts were left in situ for 6 weeks then evaluated with ultrasound and histology. RESULTS: seven endothelialized graft were patent with confluent endothelial cell lining. None of the control grafts were patent or showed evidence of an endothelial lining. CONCLUSION: in this pig model ePTFE grafts sustained for 6 weeks a confluent endothelial cell layer formed in vitro under shear stress.
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Prótesis Vascular , Endotelio Vascular/citología , Politetrafluoroetileno , Estrés Mecánico , Animales , Células Cultivadas , Femenino , Modelos Biológicos , Porcinos , Factores de Tiempo , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: The inhibition of tumorangiogenesis may be of importance in the additive treatment of various cancers. Leflunomide, a drug which has been approved in Germany for the therapy of rheumatoid arthritis, inhibits the activity of several growth factors in vitro. The aim of this study was to investigate the effects of the drug on tumor angiogenesis in a nude mouse model. MATERIALS AND METHODS: A total of 40 nude mice were injected with human colon carcinoma cells. Following randomization in 4 groups, therapy started on day five. Group 1 was treated daily with orally administered Leflunomide (35 mg/kg) dissolved in 1.5% Carboxymethylcellulose (CMC). Group 2 served as a control group and received 1 ml CMC orally per day. The animals of group 3 were treated daily with 35 mg Leflunomide/kg KG and 500 mg Uridine/kg dissolved in 1 ml Nacl 0.9% intraperitoneally. The 4th group again served as a control group and received only 500 mg Uridine/kg intraperitoneally each day. The main outcome criterion was the angiogenesis score (AS). In addition, the tumor volume and tumor weight were also assessed. The AS was determined by immunohistochemistry using an antibody against factor VIII related antigen. RESULTS: All animals tolerated the procedure well. In the Leflunomide and the Leflunomide/Uridine group the angiogenesis score (p < 0.01), the tumor volume (p < 0.01) and the tumor weight (p < 0.01) were lower compared to the respective control groups. CONCLUSION: The administration of Leflunomide leads to a significant reduction of tumor weight and tumor volume following subcutaneous injection of human colon carcinoma cells in a nude mouse model. This could be due to the reduction of tumor angiogenesis. Following further experimental and clinical studies, Leflunomide may come to play a role in the additive treatment of colonic carcinoma.
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División Celular/efectos de los fármacos , Neoplasias del Colon/irrigación sanguínea , Isoxazoles/farmacología , Neovascularización Patológica/patología , Administración Oral , Animales , Capilares/efectos de los fármacos , Capilares/patología , Neoplasias del Colon/patología , Células HT29/efectos de los fármacos , Células HT29/patología , Humanos , Inyecciones Intraperitoneales , Leflunamida , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Distribución Aleatoria , Uridina/farmacologíaRESUMEN
Earlobe keloids are benign, fibrous proliferations that show a high rate of recurrence of up to 80% following surgical excision. Traumas to the earlobe such as ear piercing, burns or surgical interventions are important in the pathogenesis of the disease. In addition to surgical keloid excision and reconstruction of the earlobe, several adjuvant therapeutic concepts have been described to prevent recurrence. Here we present the case of a female patient who suffered from severe bilateral keloid development after piercing of both ears. The report gives an overview of the relevant therapeutic concepts in the treatment of earlobe keloids and their possible complications. In addition, the question of written informed consent before ear piercing is discussed.
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Oído Externo/cirugía , Queloide/cirugía , Complicaciones Posoperatorias/cirugía , Terapia Combinada , Femenino , Humanos , Queloide/radioterapia , Persona de Mediana Edad , Complicaciones Posoperatorias/radioterapia , Radioterapia Adyuvante , Recurrencia , ReoperaciónRESUMEN
Photodynamic therapy is an effective palliative treatment of esophageal cancer. Minor complications associated with this therapy include pleural effusions, fever or esophageal strictures. In addition to this major complications such as respiratory-esophageal fistula and bronchus perforation have been described. We report here our experience with a patient who developed a complete esophageal necrosis and perforation of the left main bronchus following photodynamic therapy. The surgical and intensive care management of the patient is described and the literature discussed.
Asunto(s)
Enfermedades Bronquiales/etiología , Carcinoma/terapia , Neoplasias Esofágicas/terapia , Perforación del Esófago/etiología , Cuidados Paliativos , Fotoquimioterapia/efectos adversos , Enfermedades Bronquiales/diagnóstico por imagen , Enfermedades Bronquiales/cirugía , Cuidados Críticos/métodos , Perforación del Esófago/diagnóstico por imagen , Perforación del Esófago/patología , Perforación del Esófago/cirugía , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Radiografía , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/terapiaRESUMEN
Thalidomide, an angiogenesis inhibitor is currently used in clinical trials in the US and Europe in combination with chemotherapy for the treatment of various solid tumors. The prognosis of patients suffering from small-cell lung cancer (SCLC) is poor. A 73-year-old female with extensive disease of SCLC was given six courses of chemotherapy with adriamycine, cyclophasphamide and oncovine, which led to complete remission of the disease. Following written informed consent, the patient has been treated with thalidomide 200 mg orally on a daily basis for 2 years and 5 months. There has been no sign of tumor recurrence during the follow-up. This case underlines the possible role of additional treatment with angiogenesis inhibitors in combination with traditional chemotherapy in the therapy of SCLC. Although there is no proof that thalidomide contributed to this good outcome and no conclusions can be drawn from this treatment in a single patient, further studies may determine the role of thalidomide as an adjuvant antiangiogenic agent in the therapy of SCLC.
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Inhibidores de la Angiogénesis/farmacología , Carcinoma de Células Pequeñas/mortalidad , Metástasis de la Neoplasia/tratamiento farmacológico , Talidomida/farmacología , Anciano , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/secundario , Femenino , Humanos , SobrevivientesRESUMEN
Angiogenesis is a prerequisite for solid tumor growth and metastasis. Elucidation of the signaling pathways that control tumor angiogenesis constitutes the basis for a rational antiangiogenic tumor therapy. Here we show that the production of vascular endothelial growth factor (VEGF) in HeLa and HL-60 cells is directed by the constitutive photomorphogenesis 9 signalosome (CSN). The CSN is a kinase complex that cooperates with the ubiquitin/26S proteasome system in regulating the stability of proteins involved in signal transduction. VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1. Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75%. The removal of the inhibitor from the cells led to a time-dependent recovery of endogenous c-Jun that is paralleled by increasing VEGF production. Elevated cellular CSN activity induced by CSN subunit 2 overexpression causes increased VEGF production in HeLa cells. A competitor of CSN-dependent c-Jun phosphorylation, the NH(2)-terminal c-Jun fragment Deltac-Jun(1-226), inhibits VEGF production in HeLa cells. The transcription factors AP-2 and SP-1 act independently of the CSN. They contribute less than a quarter to basal VEGF production. Under our experimental conditions, hypoxia-inducible factor 1alpha protein was not detected. Overexpression of the tumor suppressor p53 reduces VEGF production in HeLa cells. p53 competes with c-Jun for CSN-specific phosphorylation with the consequence of c-Jun destabilization. We conclude that CSN-directed c-Jun signaling mediates high VEGF production in HeLa and HL-60 cells. The data provide an explanation for the known antiangiogenic and antitumorigenic activities of curcumin. Because the CSN regulates the major part of VEGF production in the tested tumor cells, it constitutes a potentially important target for tumor therapy.
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Factores de Crecimiento Endotelial/biosíntesis , Linfocinas/biosíntesis , Proteínas/fisiología , Complejo del Señalosoma COP9 , Proteínas de Unión al ADN/metabolismo , Células HL-60/enzimología , Células HL-60/metabolismo , Células HeLa , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/fisiología , Complejos Multiproteicos , Péptido Hidrolasas , Transducción de Señal/fisiología , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-2 , Factores de Transcripción/metabolismo , Proteína p53 Supresora de Tumor/farmacología , Proteína p53 Supresora de Tumor/fisiología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The most commonly injected materials in high-pressure injection injury to the hand include paint, automotive grease, solvents and diesel oil. High-pressure injection injuries are a frequently mismanaged problem, as they are often not recognized and treated early, which may result in a compromised function of the hand or even the amputation of a digit. Early diagnosis is an important factor, as well as the type and amount of injected material and the injection pressure at appliance. We present one case of high-pressure injection injury to the hand with the surfacer Caparol Accord. This report describes the principles of treatment and gives an overview of the literature about tissue injuries caused by components of different substances encountered in high-pressure injection injuries.