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1.
J Chem Phys ; 153(12): 124114, 2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-33003704

RESUMEN

Quantum Monte Carlo (QMC) belongs to the most accurate simulation techniques for quantum many-particle systems. However, for fermions, these simulations are hampered by the sign problem that prohibits simulations in the regime of strong degeneracy. The situation changed with the development of configuration path integral Monte Carlo (CPIMC) by Schoof et al. [Contrib. Plasma Phys. 51, 687 (2011)] that allowed for the first ab initio simulations for dense quantum plasmas [Schoof et al., Phys. Rev. Lett. 115, 130402 (2015)]. CPIMC also has a sign problem that occurs when the density is lowered, i.e., in a parameter range that is complementary to traditional QMC formulated in coordinate space. Thus, CPIMC simulations for the warm dense electron gas are limited to small values of the Brueckner parameter-the ratio of the interparticle distance to the Bohr radius-rs=r¯/aB≲1. In order to reach the regime of stronger coupling (lower density) with CPIMC, here we investigate additional restrictions on the Monte Carlo procedure. In particular, we introduce two different versions of "restricted CPIMC"-called RCPIMC and RCPIMC+-where certain sign changing Monte Carlo updates are being omitted. Interestingly, one of the methods (RCPIMC) has no sign problem at all, but it introduces a systematic error and is less accurate than RCPIMC+, which neglects only a smaller class of the Monte Carlo steps. Here, we report extensive simulations for the ferromagnetic uniform electron gas with which we investigate the properties and accuracy of RCPIMC and RCPIMC+. Furthermore, we establish the parameter range in the density-temperature plane where these simulations are both feasible and accurate. The conclusion is that RCPIMC and RCPIMC+ work best at temperatures in the range of Θ = kBT/EF ∼ 0.1…0.5, where EF is the Fermi energy, allowing to reach density parameters up to rs ∼ 3…5, thereby partially filling a gap left open by existing ab initio QMC methods.

2.
J Chem Phys ; 151(19): 194104, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31757143

RESUMEN

The study of matter at extreme densities and temperatures as they occur in astrophysical objects and state-of-the-art experiments with high-intensity lasers is of high current interest for many applications. While no overarching theory for this regime exists, accurate data for the density response of correlated electrons to an external perturbation are of paramount importance. In this context, the key quantity is given by the local field correction (LFC), which provides a wave-vector resolved description of exchange-correlation effects. In this work, we present extensive new path integral Monte Carlo (PIMC) results for the static LFC of the uniform electron gas, which are subsequently used to train a fully connected deep neural network. This allows us to present a representation of the LFC with respect to continuous wave-vectors, densities, and temperatures covering the entire warm dense matter regime. Both the PIMC data and neural-net results are available online. Moreover, we expect the presented combination of ab initio calculations with machine-learning methods to be a promising strategy for many applications.

3.
J Chem Phys ; 151(1): 014108, 2019 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-31272157

RESUMEN

Being motivated by the surge of fermionic quantum Monte Carlo simulations at finite temperature, we present a detailed analysis of the permutation-cycle properties of path integral Monte Carlo (PIMC) simulations of degenerate electrons. Particular emphasis is put onto the uniform electron gas in the warm dense matter regime. We carry out PIMC simulations of up to N = 100 electrons and investigate exchange-cycle frequencies, which are found not to follow any simple exponential law even in the case of ideal fermions due to the finite size of the simulation box. Moreover, we introduce a permutation-cycle correlation function, which allows us to analyze the joint probability to simultaneously find cycles of different lengths within a single configuration. Again, we find that finite-size effects predominate the observed behavior. Finally, we briefly consider an inhomogeneous system, namely, electrons in a 2D harmonic trap. We expect our results to be of interest for the further development of fermionic PIMC methods, in particular, to alleviate the notorious fermion sign problem.

4.
Phys Rev E ; 99(5-1): 053203, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31212426

RESUMEN

The dynamical structure factor (DSF) of strongly coupled ions in dense plasmas with partially and strongly degenerate electrons is investigated. The main focus is on the impact of electronic correlations (nonideality) on the ionic DSF. The latter is computed by carrying out molecular dynamics (MD) simulations with a screened ion-ion interaction potential. The electronic screening is taken into account by invoking the Singwi-Tosi-Land-Sjölander approximation, and it is compared to the MD simulation data obtained considering the electronic screening in the random phase approximation and using the Yukawa potential. We find that electronic correlations lead to lower values of the ion-acoustic mode frequencies and to an extension of the applicability limit with respect to the wave-number of a hydrodynamic description. Moreover, we show that even in the limit of weak electronic coupling, electronic correlations have a nonnegligible impact on the ionic longitudinal sound speed. Additionally, the applicability of the Yukawa potential with an adjustable screening parameter is discussed, which will be of interest, e.g., for the interpretation of experimental results for the ionic DSF of dense plasmas.

5.
Phys Rev E ; 98(2-1): 023207, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30253556

RESUMEN

The structural properties of strongly coupled ions in dense plasmas with moderately to strongly degenerate electrons are investigated in the framework of the one-component plasma model of ions interacting through a screened pair interaction potential. Special focus is put on the description of the electronic screening in the Singwi-Tosi-Land-Sjölander (STLS) approximation. Different cross-checks and analyses using ion potentials obtained from ground-state quantum Monte Carlo data, the random phase approximation (RPA), and existing analytical models are presented for the computation of the structural properties, such as the pair distribution and the static structure factor, of strongly coupled ions. The results are highly sensitive to the features of the screened pair interaction potential. This effect is particularly visible in the static structure factor. The applicability range of the screened potential computed from STLS is identified in terms of density and temperature of the electrons. It is demonstrated that at r_{s}>1, where r_{s} is the ratio of the mean interelectronic distance to the Bohr radius, electronic correlations beyond RPA have a nonnegligible effect on the structural properties. Additionally, the applicability of the hypernetted chain approximation for the calculation of the structural properties using the screened pair interaction potential is analyzed employing the effective coupling parameter approach.

6.
Phys Rev Lett ; 121(25): 255001, 2018 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-30608805

RESUMEN

The accurate description of electrons at extreme density and temperature is of paramount importance for, e.g., the understanding of astrophysical objects and inertial confinement fusion. In this context, the dynamic structure factor S(q,ω) constitutes a key quantity as it is directly measured in x-ray Thomson scattering experiments and governs transport properties like the dynamic conductivity. In this work, we present the first ab initio results for S(q,ω) by carrying out extensive path integral Monte Carlo simulations and developing a new method for the required analytic continuation, which is based on the stochastic sampling of the dynamic local field correction G(q,ω). In addition, we find that the so-called static approximation constitutes a promising opportunity to obtain high-quality data for S(q,ω) over substantial parts of the warm dense matter regime.

7.
Z Gastroenterol ; 54(9): 1047-53, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27612217

RESUMEN

BACKGROUND/PURPOSE: Endoscopic ultrasound-guided drainage (EUS-GD) of postoperative abdominal fluid collections (POFC) following pancreatic surgery is used as an alternative or complement to percutaneous drainage (PD) procedure. The present single-center retrospective study evaluates its efficacy and safety. METHOD: We included consecutive cases with POFC treated by EUS-GD between September 2009 and November 2014 in our department. Technical success, long-term clinical success, recurrence rate and need for surgery were analyzed. RESULTS: 24 procedures in 20 patients (95 % after pancreatic resection) were assessed. Indications for surgery included tumors/lesions located in the pancreas (15/20), chronic pancreatitis (3/20) and duodenal adenoma not completely resectable endoscopically (2/20). EUS-GD was performed within a median of 30 days (IQR: 8.25) for a median fluid collection size of 72.5 mm (IQR: 46.25), requiring a mean of 1.2 sessions with placement of a mean of 2.1 plastic stents (7 Fr/10 Fr) per patient for a mean of 89 days (IQR: 127). Microbiology of aspirated fluid revealed positive cultures in 13 patients, mostly polymicrobial, isolated positive for fungal and 3 multidrug-resistant gram negative (MRGN) in 4 cases. An additional transpapillary drainage was inserted in 1/20 patients. 4/20 patients received PD, mostly before EUS-GD. Technical and clinical success was achieved in 20/20 (100 %) and 18/20 (90 %) patients, respectively, while 2 patients required re-operation. During follow-up (median 630 days after stent removal, range: 45 - 2160), recurrence occurred in 1/18 (5.5 %) patient that was referred for surgery. No death or severe adverse events were noted. CONCLUSION: EUS-GD is an effective, minimally invasive and safe method for therapy of POFC after pancreatic surgery offering long-term remission in about 95 % of cases.


Asunto(s)
Ascitis/mortalidad , Ascitis/cirugía , Drenaje/mortalidad , Endoscopía/estadística & datos numéricos , Pancreatectomía/mortalidad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/cirugía , Causalidad , Comorbilidad , Drenaje/estadística & datos numéricos , Endoscopía/mortalidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía/estadística & datos numéricos , Cuidados Posoperatorios , Prevalencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Ultrasonografía Intervencional
8.
Phys Rev Lett ; 115(13): 130402, 2015 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-26451539

RESUMEN

The uniform electron gas at finite temperature is of key relevance for many applications in dense plasmas, warm dense matter, laser excited solids, and much more. Accurate thermodynamic data for the uniform electron gas are an essential ingredient for many-body theories, in particular, density-functional theory. Recently, first-principles restricted path integral Monte Carlo results became available, which, however, had to be restricted to moderate degeneracy, i.e., low to moderate densities with r_{s}=r[over ¯]/a_{B}≳1. Here we present novel first-principles configuration path integral Monte Carlo results for electrons for r_{s}≤4. We also present quantum statistical data within the e^{4} approximation that are in good agreement with the simulations at small to moderate r_{s}.

9.
Rehabilitation (Stuttg) ; 52(3): 196-201, 2013 06.
Artículo en Alemán | MEDLINE | ID: mdl-23761208

RESUMEN

Aim of the study was to explore meaning and consequences for patients for having their illness experiences published in the internet. Patients who participated in the establishment of a research-based internet website on illness experiences were interviewed about their experiences of taking part in the project. 14 patients with diabetes and 29 patients with chronic pain participated in the follow-up. They were interviewed with an open narrative and semi-structured approach about their motives and experiences of taking part in the project and the impact of the publication on them. Interview transcripts were coded and aggregated in a computer-assisted thematic analysis. Patients unanimously evaluated their participation positively. Many of them reported that it had been an intense and relevant experience, which equalled an intervention. They conveyed that the special effort of the researchers to establish a trustful and caring relationship had proven of value and led to a high identification of the participants with the aims of the website.


Asunto(s)
Dolor Crónico/rehabilitación , Diabetes Mellitus/rehabilitación , Difusión de la Información/métodos , Internet , Entrevistas como Asunto , Terapia Narrativa/métodos , Participación del Paciente/psicología , Adulto , Anciano , Dolor Crónico/psicología , Diabetes Mellitus/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Narración , Satisfacción del Paciente , Resultado del Tratamiento
10.
Gesundheitswesen ; 75(3): e18-22, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23361407

RESUMEN

INTRODUCTION: Health literacy is gaining increasing importance in prevention and health care. This is the case for patients and for health-care professionals. Information and risk communication should comply with defined criteria and strengthen health literacy as they are a prerequisite for informed decision making. METHODS: In this study, we analyse the content of the printed information material (brochures and pamphlets) on mammography screening for consumers that were distributed in Austria in 2011. RESULTS: The evaluation of the 11 brochures shows that the content does not comply with the prerequisites for informed decision making. CONCLUSIONS: Since the last study - published in 2004 - the situation has only slightly improved. The authors reemphasise the need for a targeted multimodal information campaign. This is particularly important as a systematic national mammography screening program in compliance with the guidelines of the European Commission will be introduced in Austria in 2013.


Asunto(s)
Neoplasias de la Mama/prevención & control , Medicina Basada en la Evidencia , Comunicación en Salud/normas , Consentimiento Informado/normas , Mamografía/normas , Tamizaje Masivo/normas , Folletos , Austria/epidemiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Femenino , Adhesión a Directriz , Guías como Asunto , Alfabetización en Salud , Promoción de la Salud , Humanos , Difusión de la Información
13.
Chirurg ; 83(8): 719, 722-5, 2012 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-22878577

RESUMEN

Bleeding and perforation in esophageal cancer patients are rare but associated with a high morbidity and mortality. Because of disappointing results after primary surgical exploration and resection endoscopic intervention was introduced as the primary treatment option with an improved outcome. Aortoesophageal and esophagobronchial fistulas may occur spontaneously or secondary to stenting of the esophagus. They are uncommon but fatal if untreated. The first option is prompt placement of a stent graft as a bridging solution followed by surgical treatment.


Asunto(s)
Adenocarcinoma/cirugía , Urgencias Médicas , Fístula Esofágica/cirugía , Neoplasias Esofágicas/cirugía , Perforación del Esófago/cirugía , Hemorragia Gastrointestinal/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/mortalidad , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/mortalidad , Fístula Bronquial/diagnóstico , Fístula Bronquial/mortalidad , Fístula Bronquial/cirugía , Fístula Esofágica/diagnóstico , Fístula Esofágica/mortalidad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Perforación del Esófago/diagnóstico , Perforación del Esófago/mortalidad , Esofagoscopía/métodos , Esofagoscopía/mortalidad , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidad , Humanos , Pronóstico , Reoperación/métodos , Reoperación/mortalidad , Stents , Tasa de Supervivencia , Fístula Vascular/diagnóstico , Fístula Vascular/mortalidad , Fístula Vascular/cirugía
14.
Br J Dermatol ; 167(5): 1179-83, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22639938

RESUMEN

Anti-p200 pemphigoid is a rare subepidermal blistering disease associated with autoantibodies against a 200-kDa protein, reportedly corresponding to laminin γ1. However, direct evidence of the pathogenic potential of these antibodies has not been proven. For 5 years we have followed up a patient with anti-p200 pemphigoid. During this period she experienced a total of three generalized relapses. Quantifying our patient's autoantibody concentrations against laminin γ1 by enzyme-linked immunosorbent assay throughout the course of her disease we demonstrated a clear correlation with disease activity, thus providing the first evidence of the possible pathogenic role of antibodies against laminin γ1 in anti-p200 pemphigoid. Further analysis by Western blotting revealed the occurrence of additional autoantibodies against the α3 chain of laminin 332, 1·5 years after diagnosis, suggestive of intermolecular epitope spreading. Yet, the clinical appearance was unchanged and mucous membranes remained unaffected at any stage of the disease.


Asunto(s)
Autoanticuerpos/sangre , Epítopos/inmunología , Laminina/inmunología , Penfigoide Ampolloso/inmunología , Anciano de 80 o más Años , Autoantígenos/inmunología , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estudios Longitudinales , Penfigoide Ampolloso/patología
15.
Endoscopy ; 44(6): 572-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22528672

RESUMEN

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has been shown to be the most accurate test for locoregional staging of upper gastrointestinal tumors; however, recent studies have questioned its accuracy level in daily clinical application. The present retrospective study analyzes the accuracy of EUS in guiding interdisciplinary treatment decisions. PATIENTS AND METHODS: 123 primarily operated patients (63 % men, mean age 61.4 years) were included; only cases with tumor-free resection margins and without evidence of distant metastases were selected. EUS and histopathological findings were compared. Main outcome parameter was the distinction between tumors to be primarily operated (T1 /2N0) and those to be treated by neoadjuvant or perioperative chemotherapy (T3/4, or any N + ), based on an assumed algorithm for treatment stratification. RESULTS: Overall staging accuracy of EUS was 44.7 % for T and 71.5 % for N status irrespective of tumor location. Overstaging was the main problem (44.9 % for T, 42.9 % for N staging). The overall EUS classification was correct in 79.7 % (accuracy), with a sensitivity 91.9 % and specificity 51.4 %; only 19 out of 37 cases with histopathological T1/2N0 were correctly classified by EUS. Positive and negative predictive values of EUS in diagnosing advanced tumor stage for assignment to neoadjuvant therapy were 81.4 % and 73.1 %, respectively. CONCLUSIONS: Whereas EUS has a high sensitivity in the diagnosis of locally advanced gastric cancer, endosonographic overstaging of T2 cancers appears to be a frequent problem. EUS stratification between local (T1 /2N0) and advanced (T3/4 or any N + ) tumors would thus result in incorrect assignment to neoadjuvant treatment in half of cases.


Asunto(s)
Carcinoma/diagnóstico por imagen , Carcinoma/patología , Endosonografía , Escisión del Ganglio Linfático , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma/terapia , Quimioterapia Adyuvante , Femenino , Gastrectomía , Humanos , Masculino , Mediastino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Neoplasias Gástricas/terapia
16.
BMJ Open ; 2(1): e000369, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22307096

RESUMEN

OBJECTIVE: The primary objective was to evaluate the capacity of first-referral health facilities in Tanzania to perform basic surgical procedures. The intent was to assist in planning strategies for universal access to life-saving and disability-preventing surgical services. DESIGN: Cross-sectional survey. SETTING: First-referral health facilities in the United Republic of Tanzania. PARTICIPANTS: 48 health facilities. MEASURES: The WHO Tool for Situational Analysis to Assess Emergency and Essential Surgical Care was employed to capture a health facility's capacity to perform basic surgical (including obstetrics and trauma) and anaesthesia interventions by investigating four categories of data: infrastructure, human resources, interventions available and equipment. The tool queried the availability of eight types of care providers, 35 surgical interventions and 67 items of equipment. RESULTS: The 48 facilities surveyed served 18.6 million residents (46% of the population). Supplies for basic airway management were inconsistently available. Only 42% had consistent access to oxygen, and only six functioning pulse oximeters were located in all facilities surveyed. 37.5% of facilities reported both consistent running water and electricity. While very basic interventions (suturing, wound debridement, incision and drainage) were provided in nearly all facilities, more advanced life-saving procedures including chest tube thoracostomy (30/48), open fracture management (29/48) and caesarean section delivery (32/48) were not consistently available. CONCLUSIONS: Based on the results in this WHO country survey, significant gaps exist in the capacity for emergency and essential surgical services in Tanzania including deficits in human resources, essential equipment and infrastructure. The information in this survey will provide a foundation for evidence-based decisions in country-level policy regarding the allocation of resources and provision of emergency and essential surgical services.

17.
Br J Dermatol ; 164(1): 76-82, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20854435

RESUMEN

BACKGROUND: Anti-p200 pemphigoid is a subepidermal blistering skin disease characterized by autoantibodies against a 200-kDa protein (p200) of the dermal-epidermal junction. The laminin γ1 chain has recently been identified as target antigen in this disease and the C-terminus was described as an immunodominant region of laminin γ1. Diagnosis of anti-p200 pemphigoid requires detection of serum IgG at the dermal side of 1 mol L(-1) salt-split skin by indirect immunofluorescence microscopy and labelling of a 200-kDa protein by Western blotting of dermal extract. However, preparation of dermal extract is not widely available, limiting the possibility of diagnosing this disease to a few laboratories. OBJECTIVES: To develop a simple, sensitive and specific diagnostic tool for anti-p200 pemphigoid. METHODS: Sera from patients with anti-p200 pemphigoid (n = 35), bullous pemphigoid (BP, n = 101), epidermolysis bullosa acquisita (EBA, n = 10), antilaminin 332 mucous membrane pemphigoid (MMP, n = 14), pemphigus vulgaris (PV, n = 51) and healthy volunteers (HV, n = 131) were tested by a novel enzyme-linked immunosorbent assay (ELISA) that employed a recombinant monomeric C-terminal fragment of human laminin γ1 (hLAMC1-cterm) expressed in Escherichia coli. RESULTS: Serum reactivity with hLAMC1-cterm was detected in sera from 24 of 35 (69%) patients with anti-p200 pemphigoid, two of 101 (2%) with BP, 0 of 10 with EBA, two of 14 (14%) with anti-laminin 332 MMP, 0 of 51 with PV, and 0 of 131 HV. CONCLUSIONS: This novel ELISA will facilitate the diagnosis of anti-p200 pemphigoid.


Asunto(s)
Autoanticuerpos/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Laminina/inmunología , Penfigoide Ampolloso/diagnóstico , Oxidorreductasas de Alcohol/inmunología , Área Bajo la Curva , Autoanticuerpos/sangre , Autoantígenos/sangre , Autoantígenos/inmunología , Western Blotting , Proteínas de Unión al ADN/inmunología , Electroforesis en Gel Bidimensional , Ensayo de Inmunoadsorción Enzimática/normas , Epidermólisis Ampollosa Adquirida/diagnóstico , Epidermólisis Ampollosa Adquirida/inmunología , Humanos , Penfigoide Ampolloso/inmunología , Sensibilidad y Especificidad , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/inmunología
18.
Endoscopy ; 41(2): 166-74, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19214899

RESUMEN

Traditionally abdominal abscesses have been treated with either surgical or radiologically guided percutaneous drainage. Surgical drainage procedures may be associated with considerable morbidity and mortality, and serious complications may also arise from percutaneous drainage. Endoscopic ultrasound (EUS)-guided drainage of well-demarcated abdominal abscesses, with adjunctive endoscopic debridement in the presence of solid necrotic debris, has been shown to be feasible and safe. This multicenter review summarizes the current status of the EUS-guided approach, describes the available and emerging techniques, and highlights the indications, limitations, and safety issues.


Asunto(s)
Absceso Abdominal/cirugía , Drenaje/métodos , Endosonografía , Absceso Abdominal/patología , Desbridamiento/instrumentación , Desbridamiento/métodos , Drenaje/instrumentación , Endoscopios , Humanos , Necrosis/microbiología , Necrosis/cirugía
19.
Oncogene ; 26(33): 4850-62, 2007 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-17297450

RESUMEN

In the present study, we have analysed the effects of transforming growth factor-beta (TGF-beta) signaling on the growth behavior of pancreatic carcinoma cells in vitro and on their tumorigenicity in vivo. Ectopic expression of dominant-negative mutants of the TGF-beta type II receptor or type I receptor/activin receptor-like kinase 5 (ALK5) in TGF-beta-sensitive pancreatic ductal adenocarcinoma PANC-1 cells prevented the TGF-beta-induced activation of transfected Smad-responsive reporter genes and growth arrest. The growth-inhibitory effect was mimicked by stable expression of kinase-active ALK5 (ALK5-T204D), and was dependent on ALK5's ability to activate Smad signaling, as a ALK5-derived mutant with an intact kinase domain but deficient in its ability to activate Smads (RImL45) failed to suppress proliferation in the absence of added TGF-beta. Moreover, this mutant often displayed opposite effects to those of ALK5-TD and blocked various ligand-induced responses in vitro, indicating that it acts in a dominant-negative fashion to inhibit endogenous wild-type receptors. ALK5-TD-, but not RImL45-TD-transduced cells underwent epithelial-to-mesenchymal transition, exhibited a higher ratio of thrombospondin-1 to vascular endothelial growth factor-A expression and upregulated various metastasis-associated genes. Upon orthotopic transplantation of PANC-1 clones into immunodeficient mice, ALK5-TD, but not RImL45-TD, greatly reduced tumor size and induced the formation of liver metastases in otherwise non-metastatic PANC-1 cells. These results suggest a causal, dominant role for the endogenous Smad2/3 signaling pathway in the tumor suppressor and prometastatic activities of TGF-beta in pancreatic tumor cells.


Asunto(s)
Receptores de Activinas Tipo I/fisiología , Adenocarcinoma/patología , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Receptores de Factores de Crecimiento Transformadores beta/fisiología , Receptores de Activinas Tipo I/genética , Receptores de Activinas Tipo I/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Immunoblotting , Ratones , Ratones SCID , Mutación , Metástasis de la Neoplasia , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteínas Serina-Treonina Quinasas , Ratas , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Smad/metabolismo , Transfección , Factor de Crecimiento Transformador beta/farmacología , Carga Tumoral
20.
Endoscopy ; 38(12): 1235-40, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17163325

RESUMEN

BACKGROUND AND STUDY AIMS: Precut is a well-known technique that is used if repeated attempts at common bile duct (CBD) cannulation fail. Opinions on the complication rate of precut are conflicting, however. The aim of the present study was to compare the efficacy and complication rate of precut used as a primary method of CBD access with the efficacy and safety of the conventional technique. PATIENTS AND METHODS: During the 19-month study period, consecutive patients who were scheduled for first-time endoscopic sphincterotomy (ES) for a variety of biliary disorders were randomized into two groups: patients in group A underwent conventional wire-guided biliary cannulation followed by ES (with precut being performed only when this failed); in patients in group B precut was used as a primary technique to gain biliary access, followed by wire-guided ES. We used a specially designed, modified Erlangen type of sphincterotome for precutting. RESULTS: A total of 291 patients (100 men, 191 women; mean +/- SD age 65 +/- 17.5 years) were recruited: 146 patients were assigned to group A (conventional approach) and 145 to group B (primary precut approach). The indications for ES were comparable in the two groups. In group A, wire-guided cannulation of the CBD failed in 42 patients. Secondary precut was successful in 41 of these patients, leading to an overall success rate of 99.3 %. In group B, the ES success rate using primary precut was 100 % at the first attempt. The mean time to successful deep CBD cannulation was 8.3 +/- 2.1 minutes in group A and 6.9 +/- 1.8 minutes in group B ( P < 0.001). The incidence of mild to moderate pancreatitis was similar in the two groups (2.9 % in group A vs. 2.1 % in group B, P > 0.05). Mild bleeding occurred in only one patient (from group A) and this was controlled by epinephrine injection. None of the study patients developed severe pancreatitis or perforation. CONCLUSIONS: In experienced hands, an approach using primary precut appears to be at least as successful and safe as a conventional approach using guide-wire-based CBD cannulation followed by ES, and might also be a quicker method.


Asunto(s)
Conductos Biliares/cirugía , Esfinterotomía Endoscópica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo/efectos adversos , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esfinterotomía Endoscópica/efectos adversos , Resultado del Tratamiento
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