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1.
Br J Cancer ; 110(4): 1008-13, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24366305

RESUMO

BACKGROUND: In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice. METHODS: Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted. RESULTS: A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a 'scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813). CONCLUSION: Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting.


Assuntos
Colo/patologia , Neoplasias do Colo/patologia , Linfonodos/patologia , Neoplasias Retais/patologia , Reto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Antiporters/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/cirurgia
2.
Int J Med Robot ; 7(1): 7-16, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21341357

RESUMO

BACKGROUND: The surgical treatment of liver tumours relies on precise localization of the lesions and detailed knowledge of the patient-specific vascular and biliary anatomy. Detailed three-dimensional (3D) anatomical information facilitates complete tumour removal while preserving a sufficient amount of functional liver tissue. METHODS: We present an easy to use, clinically applicable navigation system for efficient visualization and tool guidance during liver surgery. Accurate instrument guidance within 3D planning models was achieved with a fast registration procedure, assuming a locally rigid and temporarily static scenario. After deformations occurring during the procedure, efficient means for registration updates are provided. Special focus was given to workflow integration and the minimization of overhead time. The navigation system was validated with nine clinical cases. RESULTS: Navigated surgical interventions were performed with a median time overhead of 16.5 min. The navigation technology had a median accuracy of 6.3 mm, improving anatomical orientation and the detection of structures at risk. CONCLUSIONS: Successful application of the navigation technology to open liver surgery was achieved by minimizing the procedural complexity and optimizing integration within the existing surgical environment. The assumption of locally rigid patient registration was validated, and clinical evaluation shows clear benefits for the surgeon.


Assuntos
Hepatectomia/instrumentação , Robótica/instrumentação , Cirurgia Assistida por Computador/instrumentação , Interface Usuário-Computador , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Oncogene ; 30(21): 2411-9, 2011 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-21258413

RESUMO

Glucocorticoids (GC) have important anti-inflammatory and pro-apoptotic activities. Initially thought to be exclusively produced by the adrenal glands, there is now increasing evidence for extra-adrenal sources of GCs. We have previously shown that the intestinal epithelium produces immunoregulatory GCs and that intestinal steroidogenesis is regulated by the nuclear receptor liver receptor homolog-1 (LRH-1). As LRH-1 has been implicated in the development of colon cancer, we here investigated whether LRH-1 regulates GC synthesis in colorectal tumors and whether tumor-produced GCs suppress T-cell activation. Colorectal cancer cell lines and primary tumors were found to express steroidogenic enzymes and regulatory factors required for the de novo synthesis of cortisol. Both cell lines and primary tumors constitutively produced readily detectable levels of cortisol, as measured by radioimmunoassay, thin-layer chromatography and bioassay. Whereas overexpression of LRH-1 significantly increased the expression of steroidogenic enzymes and the synthesis of cortisol, downregulation or inhibition of LRH-1 effectively suppressed these processes, indicating an important role of LRH-1 in colorectal tumor GC synthesis. An immunoregulatory role of tumor-derived GCs could be further confirmed by demonstrating a suppression of T-cell activation. This study describes for the first time cortisol synthesis in a non-endocrine tumor in humans, and suggests that the synthesis of bioactive GCs in colon cancer cells may account as a novel mechanism of tumor immune escape.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Glucocorticoides/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Células CACO-2 , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Cromatografia em Camada Fina , Neoplasias do Colo/patologia , Meios de Cultivo Condicionados/farmacologia , Regulação Neoplásica da Expressão Gênica , Glucocorticoides/farmacologia , Células HEK293 , Células HT29 , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fosfoproteínas/genética , Interferência de RNA , Radioimunoensaio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/citologia , Esteroide 11-beta-Hidroxilase/genética , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Timo/citologia
4.
Br J Surg ; 97(11): 1696-703, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20799294

RESUMO

BACKGROUND: Non-operative management (NOM) of blunt splenic injuries is nowadays considered the standard treatment. The present study identified selection criteria for primary operative management (OM) and planned NOM. METHODS: All adult patients with blunt splenic injuries treated at Berne University Hospital, Switzerland, between 2000 and 2008 were reviewed. RESULTS: There were 206 patients (146 men) with a mean(s.d.) age of 38.2(19.1) years and an Injury Severity Score of 30.9(11.6). The American Association for the Surgery of Trauma classification of the splenic injury was grade 1 in 43 patients (20.9 per cent), grade 2 in 52 (25.2 per cent), grade 3 in 60 (29.1 per cent), grade 4 in 42 (20.4 per cent) and grade 5 in nine (4.4 per cent). Forty-seven patients (22.8 per cent) required immediate surgery. Transfusion of at least 5 units of red cells (odds ratio (OR) 13.72, 95 per cent confidence interval 5.08 to 37.01), Glasgow Coma Scale score below 11 (OR 9.88, 1.77 to 55.16) and age 55 years or more (OR 3.29, 1.07 to 10.08) were associated with primary OM. The rate of primary OM decreased from 33.3 to 11.9 per cent after the introduction of transcatheter arterial embolization in 2005. Overall, 159 patients (77.2 per cent) qualified for NOM, which was successful in 143 (89.9 per cent). The splenic salvage rate was 69.4 per cent. In multivariable analysis age at least 40 years was the only factor independently related to failure of NOM (OR 13.58, 2.76 to 66.71). CONCLUSION: NOM of blunt splenic injuries has a low failure rate. Advanced age is independently associated with an increased failure rate.


Assuntos
Baço/lesões , Ferimentos não Penetrantes/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Métodos Epidemiológicos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Baço/cirurgia , Suíça/epidemiologia , Resultado do Tratamento , Ferimentos não Penetrantes/etiologia , Adulto Jovem
5.
Am J Transplant ; 9(9): 2197-202, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19706026

RESUMO

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis.


Assuntos
Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Transplante de Fígado/efeitos adversos , Recidiva , Sulfassalazina/farmacologia , Vancomicina/farmacologia , Artrite/tratamento farmacológico , Hipersensibilidade a Drogas , Eosinofilia/induzido quimicamente , Proteína Ligante Fas/biossíntese , Evolução Fatal , Granzimas/metabolismo , Humanos , Falência Hepática Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndrome , Linfócitos T Citotóxicos/imunologia
6.
Br J Surg ; 96(1): 104-10, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19109805

RESUMO

BACKGROUND: Little is known about the clinical importance of concomitant injuries in polytraumatized patients with high-grade blunt liver injury. A retrospective single-centre study was performed to investigate the safety of non-operative management of liver injury and the impact of concomitant intra- and extra-abdominal injuries on clinical outcome. METHODS: Some 183 patients with blunt liver injury were admitted to Berne University Hospital, Switzerland, between January 2000 and December 2006. Grade 3-5 injuries were considered to be high grade. RESULTS: Immediate laparotomy was required by 35 patients (19.1 per cent), owing to extrahepatic intra-abdominal injury (splenic and vascular injuries, perforations) in 21 cases. The mortality rate was 16.9 per cent; 22 of the 31 deaths were due to concomitant lesions. Of 81 patients with high-grade liver injury, 63 (78 per cent) were managed without surgery; liver-related and extra-abdominal complication rates in these patients were 11 and 17 per cent respectively. Grades 4 and 5 liver injury were associated with hepatic-related and extra-abdominal complications. CONCLUSION: Concomitant injuries are a major determinant of outcome in patients with blunt hepatic injury and should be given high priority by trauma surgeons. An algorithm for the management of blunt liver injury is proposed.


Assuntos
Fígado/lesões , Traumatismo Múltiplo/mortalidade , Ferimentos não Penetrantes/mortalidade , Traumatismos Abdominais/complicações , Traumatismos Abdominais/mortalidade , Traumatismos Abdominais/terapia , Acidentes por Quedas/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Adulto , Algoritmos , Feminino , Humanos , Escala de Gravidade do Ferimento , Laparotomia , Fígado/cirurgia , Masculino , Traumatismo Múltiplo/complicações , Traumatismo Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia
7.
Ann Surg Oncol ; 15(4): 1239-48, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18247094

RESUMO

BACKGROUND: This study aims to assess postoperative hepatic growth of colorectal adenocarcinoma metastasis and peritumoural macrophage counts after laparoscopy in an experimental animal model. METHODS: Thirty male syngenic WAG/Rij rats were randomised into two surgical groups: laparoscopy (LS; n = 15) using CO(2) at 12 mmHg and laparotomy (LT; n = 15; negative control) during an operating time of 90 min. At 45 min after setup, CC531s colon adenocarcinoma cells were injected into two liver lobes. Postoperative tumour volumes were determined by abdominal magnetic resonance imaging (MRI) and computed three-dimensional volumetry. Peritumoural macrophages were counted by local stereology using a confocal laser-scanning fluorescence microscope. RESULTS: The median postoperative tumour volume was significantly higher after LS in both lobes (L): after 10, 15 and 20 days in L2 and L5: 24/12, 54/38, 275/62 mm(3) and 0/0, 15/11, 55/24 mm(3) (LS/LT). Significantly fewer peritumoural macrophages were found after LS at all postoperative time points (Mann-Whitney: p < 0.05). CONCLUSIONS: Increased hepatic growth of colorectal adenocarcinoma metastasis and impaired cellular antitumoural defence after LS cast doubt on the use of LS in colorectal cancer and needs further clinical investigation.


Assuntos
Adenocarcinoma/fisiopatologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/fisiopatologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Animais , Contagem de Células , Linhagem Celular Tumoral , Modelos Animais de Doenças , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Macrófagos , Masculino , Ratos
8.
Gut ; 56(12): 1725-35, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17641081

RESUMO

BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.


Assuntos
Transplante de Medula Óssea/métodos , Hiperbilirrubinemia Hereditária/terapia , Regeneração Hepática , Condicionamento Pré-Transplante/métodos , Animais , Bilirrubina/metabolismo , Diferenciação Celular , Modelos Animais de Doenças , Sobrevivência de Enxerto , Hepatócitos/patologia , Hiperbilirrubinemia Hereditária/metabolismo , Hiperbilirrubinemia Hereditária/patologia , Circulação Hepática , Ratos , Ratos Gunn , Traumatismo por Reperfusão/patologia , Resultado do Tratamento
9.
Br J Surg ; 94(5): 599-603, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17330858

RESUMO

BACKGROUND: This study aimed to determine the incidence of pulmonary embolism (PE) following laparoscopic surgery and its potential risk factors. METHODS: Data concerning 44 453 patients from 114 surgical institutions were collected by the Swiss Association of Laparoscopic and Thoracoscopic Surgery. The incidence of postoperative PE despite thromboprophylaxis was evaluated and potential risk factors were assessed singly, and then in a consecutive stepwise logistic multiple regression analysis. RESULTS: Among 44 453 patients assessed, 55.8 per cent were female and 44.2 per cent were male. Interventions included cholecystectomy (52.8 per cent), hernia repair (17.7 per cent), appendicectomy (12.4 per cent), colonic surgery (4.6 per cent) and oesophageal surgery (5.5 per cent). Postoperative PE occurred in 86 patients (0.2 per cent), and the incidence tended to decrease during this study (P = 0.016). A total of 149 patients died (0.3 per cent) of which nine (6.0 per cent) were due to PE. Significant predictive risk factors were female sex (P < 0.001), age (P < 0.001), weight above 90 kg (P < 0.001), emergency procedure (P < 0.001) and operating time exceeding 150 min (P < 0.001). CONCLUSION: The low incidence of PE after laparoscopy, with a further decrease over the past decade, suggests a tendency towards improved perioperative thromboembolic risk management.


Assuntos
Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Embolia Pulmonar/epidemiologia , Toracoscopia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Embolia Pulmonar/etiologia , Fatores de Risco , Suíça/epidemiologia
10.
Br J Surg ; 93(11): 1390-3, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16862615

RESUMO

BACKGROUND: The effectiveness of various appendiceal stump closure methods has not been evaluated systematically. The aim of this study was to compare the morbidity of stump closure by stapling or use of endoloops. METHODS: A non-concurrent cohort study of prospectively acquired data was performed. The primary outcome variable was the rate of intra-abdominal surgical-site infection. Secondary outcome measures were complications, duration of intervention, hospital stay, rate of readmission to hospital and the difference in direct costs of the operation. RESULTS: Staples were used in 60.5 per cent and endoloops in 39.5 per cent of 6486 patients operated on for suspected appendicitis between January 1995 and December 2003. Among 4489 patients with acute appendicitis the rate of intra-abdominal surgical-site infection was 0.7 per cent in the stapler group and 1.7 per cent in the endoloop group (P = 0.004). The rate of readmission to hospital was 0.9 and 2.1 per cent respectively (P = 0.001). CONCLUSION: Application of a stapler for transection and closure of the appendiceal stump in patients with acute appendicitis lowered the risk of postoperative intra-abdominal surgical-site infection and the need for readmission to hospital.


Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura , Adulto , Apendicectomia/economia , Estudos de Coortes , Custos e Análise de Custo , Humanos , Tempo de Internação , Complicações Pós-Operatórias/economia , Estudos Prospectivos , Grampeamento Cirúrgico/economia , Infecção da Ferida Cirúrgica/economia , Infecção da Ferida Cirúrgica/etiologia , Técnicas de Sutura/economia , Resultado do Tratamento
11.
Surg Endosc ; 19(11): 1475-82, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16222470

RESUMO

BACKGROUND: Portal venous and mesenteric blood flow are reduced by 40-60% in humans and animals during laparoscopic surgery compared to laparotomy. Little is known about whether these intraabdominal micro- and macrocirculatory changes are associated with alterations in the hepatic energy metabolism. METHODS: We operated on male Sprague-Dawley rats, performing either laparoscopy (CO2, 6 mmHg; n = 27) or laparotomy (n = 28), and compared the results with two control groups: intraperitoneal (i.p.) endotoxin administration (n = 28, positive control) and anesthesia only (n = 28, negative control). We investigated the impact of the two different surgical techniques on daily food intake, body weight gain, glycogen content in the liver, levels of blood glucose, and liver function tests (LFTs) on postoperative days 1, 2, 4, and 8. Local (hepatic) and systemic inflammatory responses (interleukin-6 and tumor necrosis factor-alpha) during the postoperative time course were also determined. Data were analyzed using the Kruskal-Wallis test or univariate analysis of variance. RESULTS: Body weight gain, food intake, liver and spleen weights, as well as LFTs [except aspartate aminotransferase (AST)] did not differ among the four groups. The significant increase in the AST level following laparoscopy compared to the anesthesia-only group was found on postoperative days 1 and 2; however, a similar difference was not detected after laparotomy or i.p. endotoxin injection. Laparoscopy showed no alterations in the hepatic glycogen stores compared to anesthesia only, whereas laparotomy and endotoxinemia significantly reduced the hepatic glycogen stores on postoperative days 2 and 4. The systemic postoperative inflammatory response did not differ between laparotomy and laparoscopy, but it was higher in both groups than in anesthesia only. In rats treated with endotoxin, the systemic inflammatory response was even higher than in the two surgical groups. The hepatic inflammatory response did not differ between the four groups. CONCLUSION: This study shows a significant postoperative decrease in the hepatic glycogen content after laparotomy and i.p. endotoxin injection but not after laparoscopy. Food intake and inflammatory response cannot explain this difference between the two surgical groups, which suggests that alterations in the postsurgical hormonal stress response are the most likely explanation for these findings.


Assuntos
Metabolismo dos Carboidratos , Laparoscopia , Laparotomia , Fígado/metabolismo , Animais , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley
12.
Transplant Proc ; 37(10): 4211-4, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16387080

RESUMO

BACKGROUND: Fabry's disease (FD) is an inborn error of glycosphingolipid catabolism with progressive systemic deposition of globotriaosylceramide thereby leading to renal and cardiac failure. Current therapy involves symptomatic medical management, dialysis, enzyme replacement therapy, kidney transplantation (KTx), and more recently gene therapy. Case fatalities occur in the fourth decade of life resulting from uremia unless dialysis or KTx is undertaken. STUDY DESIGN: This is a retrospective study aimed at determining the effect of KTx on the long-term outcome of patients with FD. RESULTS: Between 1964 and 1998, ten patients with FD received KTx at our institutions. Actuarial patient and graft survivals were 100% and 90% at 5 years; 76% and 66% at 10 years. One kidney graft was lost due to rejection. Patient survival data compared favorably at 5 years with survival of FD patients on hemodialysis alone (41%, P < .05). Five patients are alive at the time of this study, and five patients died with median survival time after KTx of 128 months (range: 74-160 months). CONCLUSIONS: This study demonstrates an excellent outcome in patients with FD in the first decade after KTx. In the absence of a severe contraindication, we advocate KTx to improve the overall prognosis of patients with renal failure due to FD. Based on the data, enzyme replacement therapy after KTx seems indicated, as FD progresses posttransplant, leading to case fatalities in the second decade after KTx.


Assuntos
Doença de Fabry/cirurgia , Transplante de Rim/fisiologia , Adolescente , Adulto , Doença de Fabry/mortalidade , Seguimentos , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Eur Surg Res ; 36(3): 142-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15178902

RESUMO

Activation of the classical complement pathway is crucially involved in complement-mediated endothelial cell damage in ischemia-reperfusion injury. C1 inhibitor is the only known physiological inhibitor of classical complement pathway activation. Transgenic mice overexpressing human C1 inhibitor were used in a surgical lower torso and a liver ischemia-reperfusion model. Organ-specific endothelial disruption was determined by 125I-tagged albumin extravasation. In the lower torso ischemia-reperfusion model, transgenic mice overexpressing the C1 inhibitor were protected in the muscle and the lungs from endothelial cell damage. In the liver ischemia-reperfusion model, endothelial cell integrity was preserved in transgenic animals in the liver, the gut and the lungs. Our data indicate that inhibiting complement activation by a transgenic approach is effective in protection against ischemia-reperfusion injury.


Assuntos
Proteínas Inativadoras do Complemento 1/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Albuminas/farmacocinética , Animais , Permeabilidade Capilar , Proteínas Inativadoras do Complemento 1/genética , Via Clássica do Complemento , Endotélio Vascular/lesões , Endotélio Vascular/fisiopatologia , Expressão Gênica , Humanos , Radioisótopos do Iodo , Fígado/irrigação sanguínea , Fígado/lesões , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/fisiopatologia
14.
Biochem Biophys Res Commun ; 288(1): 156-64, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11594767

RESUMO

Recently it was shown that a population of cells in the bone marrow-expressing hematopoietic stem cell antigens could differentiate into hepatocytes. However, explicitly committed hepatocyte progenitors, which exhibit highly differentiated liver functions, immediately upon isolation, have not yet been isolated from bone marrow. After studying common antigens on blast-like cells in fetal and adult regenerating cholestatic rat livers and human regenerating and malignant livers, we hypothesized that beta-2-microglobulin-negative (beta(2)m(-)) cells might represent dedifferentiated hepatocytes and/or their progenitors. Utilizing a two-step magnetic bead cell-sorting procedure, we show that in bone marrow from rat and human, beta(2)m(-)/Thy-1(+) cells consistently express liver-specific genes and functions. After intraportal infusion into rat livers, bone marrow-derived hepatocyte stem cells (BDHSC) integrated with hepatic cell plates and differentiated into mature hepatocytes. In a culture system simulating liver regeneration and containing cholestatic serum, these cells differentiated into mature hepatocytes and metabolized ammonia into urea. This differentiation was dependent on a yet nondescript humoral signal existing in the cholestatic serum. Transmission electron microscopy and three-dimensional digital reconstruction confirmed hepatocyte ultrastructure of cultured BDHSC.


Assuntos
Células-Tronco Hematopoéticas/fisiologia , Hepatócitos/química , Hepatócitos/transplante , Albuminas/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Hepatócitos/citologia , Separação Imunomagnética , Fígado/metabolismo , Regeneração Hepática , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Antígenos Thy-1/análise , Antígenos Thy-1/imunologia , Microglobulina beta-2/análise , Microglobulina beta-2/imunologia
15.
ASAIO J ; 47(1): 56-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11199316

RESUMO

Veno-venous bypass (VVBP) is increasingly used to avoid acute venous hypertension and low cardiac output after clamping the vena cava. Air embolism upon accidental decannulation of the inflow line and endothelial damage due to suction of the blood collecting cannula to the vessel wall are known complications specific to the currently used roller and centrifugal pumps, because they generate negative pressure at the inflow site of the pump. The Affinity pump has a unique chamber design with an occlusive segment, that collapses in low filling states preventing negative pressure at the inflow site of the pump chamber. This device was tested for VVBP in three pigs (each weighing 52.3 +/- 5.1 kg) with hepatic vascular exclusion. Blood was pumped from the femoral and portal veins to the external jugular vein and perfusion was maintained for 6 hours. The hemodynamic state of the animals was assessed by recording heart rate; systolic, mean arterial, and diastolic pressure; as well as central venous pressure. Mean pump flow during the experiment was 1,629.3 +/- 372.2 ml/min. After clamping, the inflow line of the pump mean arterial pressure significantly decreased (from 69.5 +/- 4.4 to 43.1 +/- 3.5 mm Hg), and mean pressure in the femoral vein increased significantly (from 16.1 +/- 2.6 to 26.8 +/- 5.9 mm Hg), whereas the mean pressure in the internal jugular vein did not significantly change (from 6.0 +/- 1.7 to 5.0 +/- 2.1 mm Hg). There was no suction by the blood collecting cannula on the vessel wall, and neither bubbles nor air emboli were detected and no operator intervention was needed. In conclusion, the Affinity pump eliminates device related complications due to negative pressure generated at the inlet, and guarantees stable hemodynamics. Its application is simple and safe and minimal operator intervention is needed, making the Affinity pump particularly suited for veno-venous bypass.


Assuntos
Ponte Cardiopulmonar/instrumentação , Hipertensão/prevenção & controle , Bombas de Infusão , Fígado/cirurgia , Pressão Venosa , Animais , Baixo Débito Cardíaco , Ponte Cardiopulmonar/métodos , Embolia Aérea/prevenção & controle , Veia Femoral , Frequência Cardíaca , Coração Auxiliar , Hepatectomia , Veias Jugulares , Fígado/irrigação sanguínea , Suínos , Veia Cava Inferior/cirurgia
17.
Biochem Biophys Res Commun ; 273(1): 129-35, 2000 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-10873574

RESUMO

In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were up-regulated early after induction of liver failure (6-12 h). In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.


Assuntos
Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Regeneração Hepática , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Transativadores/antagonistas & inibidores , Transativadores/metabolismo , Animais , Antígenos CD/metabolismo , Proteínas de Transporte/genética , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Receptor gp130 de Citocina , DNA/biossíntese , DNA/genética , DNA/metabolismo , Hepatectomia , Fator de Crescimento de Hepatócito/farmacologia , Interleucina-6/sangue , Interleucina-6/farmacologia , Janus Quinase 2 , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Falência Hepática Aguda/cirurgia , Regeneração Hepática/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Necrose , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-6/metabolismo , Fator de Transcrição STAT3 , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Schweiz Med Wochenschr ; 128(38): 1408-13, 1998 Sep 19.
Artigo em Alemão | MEDLINE | ID: mdl-9783356

RESUMO

Patients with unresectable supramesenteric malignancies often suffer from intractable pain. The supramesenteric viscera are supplied by the greater splanchnic nerve. Surgical options to effectively denervate the supramesenteric area are coeliac ganglionectomy, open or percutaneous coeliac ganglion block or transhiatal bilateral splanchnicotomy. The surgical minimally invasive alternative is thoracoscopic splanchnicectomy. In 7 patients pain was scored on a scale from 1 (no pain) to 10 (maximal pain) before and after surgery and weekly thereafter. Five bilateral and 2 left-sided thoracoscopic splanchnicectomies were performed. Operation time was 17 +/- 3 min for each side. The mean pain score dropped from preoperatively (under morphine sulphate medication) 7.4 +/- 0.6 to 4.9 (2.5-8.25) 1 week postoperatively (p = 0.02) and to 4.9 (2.5-6.75) 7 weeks postoperatively (p = 0.02). The relief from back pain was immediate and complete, but abdominal pain tended to recur. Six of our 7 patients and their general practitioners rated the intervention as a success. Thoracoscopic splanchnicectomy affords excellent palliation in patients with unresectable supramesenteric tumour, offering reliable pain control.


Assuntos
Neoplasias Abdominais/fisiopatologia , Endoscopia , Dor Intratável/cirurgia , Cuidados Paliativos , Nervos Esplâncnicos/cirurgia , Toracoscopia , Denervação , Humanos , Medição da Dor
19.
J Invest Surg ; 11(2): 115-22, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9700619

RESUMO

Current treatment of obstructive jaundice includes endoscopic stenting and open surgical bypass. To combine the advantages of surgical bypass with the minimal invasive approach of endoscopic stenting we developed a laparoscopic technique, transient endoluminally stented anastomosis (TESA). As shown previously, small-diameter anastomoses (e.g., hepaticojejunostomy) by TESA technique can be performed reliably in growing domestic swine. This further preclinical trial was designed to exclude growth of the animals as the main reason for these excellent results. After ligation of the common bile duct, a laparoscopic Roux-en-y hepaticojejunostomy was performed 7 days later by TESA with a reabsorbable radiopaque polyglycolic acid stent. In group A (n = 7) growing domestic pigs and in group B (n = 5) adult minipigs were operated on. Laboratory parameters were controlled weekly. Stent degradation was followed by weekly abdominal x-ray. At necropsy 6 months after surgery, cholangiography was performed and the anastomoses were measured. Mean weight gain was 140.7 +/- 10.9 kg in domestic pigs versus 5.8 +/- 1.6 kg in minipigs. Cholestasis normalized within 7 days postoperatively. Duration of stenting was not significantly different between groups. Cholangiography at necropsy showed immediate runoff through the anastomoses in both groups. The diameter of the anastomosis was 4.7 +/- 0.5 mm in group A versus 3.0 +/- 0.4 mm in group B (p = 0.03). In conclusion, functionality of the small-diameter TESA hepaticojejunostomy is not related to age and growing factors in pigs, justifying its application in human as the next step of investigation.


Assuntos
Anastomose Cirúrgica/métodos , Ductos Biliares Intra-Hepáticos/cirurgia , Jejunostomia/métodos , Laparoscopia , Anastomose Cirúrgica/instrumentação , Animais , Estudos de Avaliação como Assunto , Crescimento , Humanos , Jejunostomia/instrumentação , Laparoscópios , Stents , Suínos , Porco Miniatura
20.
Artigo em Alemão | MEDLINE | ID: mdl-9931946

RESUMO

This article summarizes our experience with renal transplantation over the past 33 years and shows progressive improvement of the clinical outcome over time. In parallel we observed an increasing proportion of elderly recipients and diabetics. The increasing shortage of cadaver grafts was compensated by using donor hearts from legally dead donors (heart no longer beating) and establishing a living donor program.


Assuntos
Transplante de Rim/tendências , Adulto , Idoso , Cadáver , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Suíça , Doadores de Tecidos/provisão & distribuição , Resultado do Tratamento
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