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In this paper, a key differential equation is proposed to formulate fatigue damage evolution in metallic alloys under multiaxial, multiblock, proportional loadings in high cycle fatigue (HCF) and very high cycle fatigue (VHCF) regimes. This differential equation possesses two main components: one is a stress function to accommodate the adopted fatigue criterion and the other one is a characteristic damage function that serves to capture the HCF response of alloys. Two distinct characteristic damage functions with three different multiaxial fatigue criteria, namely Sines, Crossland, and Dang Van criteria, are examined to develop six (out of many possible) variants of the presented damage accumulation model. As a validation measure, Chaboche’s HCF damage model is retrieved as a specific case of the developed formalism. For model parameters identification, an ad hoc two-level identification scheme is designed and numerically verified. It is demonstrated that endurance limit, which is determined from fully reversed HCF tests (i.e., R = −1), can be identified from fatigue tests with positive stress ratio (R > 0), thus making our development quite suitable for specimens prone to buckling under compression. Another salient feature of the devised identification scheme is its capability in extracting model parameters from noisy data.

I; This paper presents an identification procedure for the parameters of a thermodynamically based constitutive model for Shape memory Alloys (SMAs). The proposed approach is a gradient-based method and utilizes an analytical computation of the sensitivity matrix. For several loading cases, including superelasticity, that are commonly utilized for the model parameters identification of such a constitutivemodel, a closed-form of the total infinitesimal strain is derived. The partial derivatives of this state variable are developed to find the components of the sensitivity matrix. A LevenbergeMarquardt algorithm is utilized to solve the inverse problem and find the best set of model parameters for specific SMA materials. Moreover, a pre-identification method, based on the second derivative of the total strain components is proposed. This provides a suitable initial set of model parameters, which increases theefficiency of the inverse method. The proposed approach is applied for the simultaneous identification of the non-linear constitutive parameters for two superelastic SMAs. The comparison between experimental and numerical curves obtained for different temperatures shows the capabilities of the developedidentification approach. The robustness and the efficiency of the developed approach are then experimentally validated; International audience; This paper presents an identification procedure for the parameters of a thermodynamically based constitutive model for Shape memory Alloys (SMAs). The proposed approach is a gradient-based method and utilizes an analytical computation of the sensitivity matrix. For several loading cases, including superelasticity, that are commonly utilized for the model parameters identification of such a constitutivemodel, a closed-form of the total infinitesimal strain is derived. The partial derivatives of this state variable are developed to find the components of the sensitivity matrix. A LevenbergeMarquardt algorithm is utilized to solve the inverse problem and find the best set of model parameters for specific SMA materials. Moreover, a pre-identification method, based on the second derivative of the total strain components is proposed. This provides a suitable initial set of model parameters, which increases theefficiency of the inverse method. The proposed approach is applied for the simultaneous identification of the non-linear constitutive parameters for two superelastic SMAs. The comparison between experimental and numerical curves obtained for different temperatures shows the capabilities of the developedidentification approach. The robustness and the efficiency of the developed approach are then experimentally validated

HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels ( r = 0.80) and HCV RNA levels ( r = 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

International audience; Experimental and numerical analysis of the effect of stress-strain heterogeneities (due to elastic anisotropy, grain orientations and interactions) on martensitic transformation are investigated here for a Cu-Based SMA multicrystal. The shape and crystallographic orientation of each grain are measured successively by optical microscopy and Electron Back Scattered Diffraction (EBSD) technique. During a tensile loading at room temperature, the displacement field of the free surface is measured by Digital Image Correlation (DIC) with the software CORRELI-Q4 [Roux, Hild, 2006: Besnard et al., 2006]. The strain field is then derived numerically. A finite element model is designed. The shape of each grain is defined as a subdomain and meshed by three dimensional continuum elements. A behavior law, describing the thermomechanical response of a SMA single crystal, is adopted and implemented into the Abaqus (R) finite element code. It is based on a micromechanical approach and takes into account the various possible active martensitic variants. The study shows that the experimental and numerical results are in good agreement. Moreover, the stress state in grains is disturbed by the neighboring grains and this disturbance has a strong influence on the martensite variant activation. Finally, the study shows that the martensitic transformation mainly occurs in localized bands involving the well crystallographic oriented grains with respect to the loading direction.

We designed a pilot trial in cadaveric liver transplantation to determine whether induction with antithymocyte globulins (ATG) and sirolimus would allow immunosuppression withdrawal. Patients received ATG 3.75 mg/kg per day from day 1 to 5 after transplantation followed by sirolimus for 4 to 6 months. We monitored interleukin (IL)-7 serum levels, interferon (IFN)-gamma, and IL-2 mRNA accumulation in mixed leukocyte reaction and intragraft IFN-gamma mRNA expression. In the first three patients, immunosuppression discontinuation was followed by reversible acute rejection occurring on days 280, 246, and 163 posttransplantation, corresponding to days 140, 40, and 39 after drug withdrawal, respectively. At the time of rejection, blood CD8+ T-cells counts had returned to or above pretransplant levels in two of three patients, whereas CD4+ T-cell count remained low. IL-7 serum levels rose in all three patients in the first months after transplantation and IFN-gamma mRNA accumulated in mixed leukocyte reaction between recipient T cells and donor spleen cells at the time of rejection. High levels of IFN-gamma mRNA were consistently detected in liver biopsy performed at the time of rejection. In conclusion, lymphopenia-induced IL-7 production after induction with ATG and sirolimus might lead to emergence of IFN-gamma-secreting CD8+ T-cells responsible for acute rejection after immunosuppression withdrawal.

International audience; Dialog between the experiment and the numerical simulation for a shape memory alloy multicrystal. The aim of this study is to make dialog between the numerical simulation and the experiment in the case of the tensile test behavior for a CuAlBe shape memory alloy multicrystal. This dialog allows to compare qualitatively the distributions of martensitic transformation, observed through a long distance microscope, with obtained by Finite element simulation using a thermomechanical behavior law. The last is based on the description of martensitic transformation on a single crystal scale. It is implemented in the Abaqus(R) finite element code. The applied boundary conditions for modeling correspond to the measured ones at the edge of the area by a technique of digital image correlation. Geometrical and crystallographic properties of the various grains of the multicrystal are experimentally determined. The tensile test is carried out at room temperature where the alloy has a superelastic behavior. A good agreement between the experimental observation and numerical results is observed.

— In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58–70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61–77%), whereas subtypes 1a and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p

Background: Due to the organ shortage, marginal donors are increasingly used in liver transplantation (OLT). These grafts may be safely used in less critical recipients but, the real influence of extended donor criteria (EDC) remains uncertain when graft-recipient matching is not applied. Our study analyzed the impact of EDC on initial graft function within the Eurotransplant patient-driven allocation system. Patients and methods: We reviewed 70 OLT performed between 2004 and 2006. The impact of the following EDC were analyzed: age > 60; intensive care unit (ICU) stay > 4 days; peak serum Na+ > 160 mEq/L; body mass index (BMI) > 30; cardiac arrest with cardiopulmonary resuscitation, and high doses of vasopressors. Early graft function, as defined according to peak transaminase level and spontaneous prothrombin time within the first 5 posttransplant days, was compared between the donors with none or one criterion (group A = 39) and those with >1 criterion (group B = 31). Results: The most frequent EDC were high vasopressor use, ICU stay > 4 days and BMI > 30, were present in respectively 44%, 27%, and 16% of the donors. No EDC were present in 13 donors, one in 26, three in eight, and four in three. Demographics and origin and severity of the liver disease were similar in both groups. We failed to observe significant differences in initial graft function. Conclusion: The presence of EDC did not significantly affect early graft function in a population where donor and recipient were not matched. While this observation must be confirmed in a multicenter analysis, it tends to support the use of marginal liver grafts, even in patient-driven allocation systems. © 2007 Elsevier Inc. All rights reserved.

With the design of new devices with complex geometry and to take advantage of their large recoverable strains, shape memory alloys components (SMA) are increasingly subjected to multiaxial loadings. The development process of SMA devices requires the prediction of their thermomechanical response, for which the calibration of the material parameters for the numerical model is an important step. In this work, the parameters of a phenomenological model are extracted from tests performed on specimens with non-uniform geometry, which induce heterogeneous strain fields carried out on specimens with the same thermomechanical loading history. The digital image correlation technique is employed to measure the strain fields on the surface of the specimen and to analyze the strain paths of chosen points. Finite element analysis enables the computation of numerical strain fields using a thermodynamicalconstitutive model for shape memory alloys previously implemented in a finite element code. The strain fields computed numerically are compared with experimental ones obtained by DIC to find the model parameters which best match experimental measurements using a newly developed parallelized mixed genetic/gradient-based optimization algorithm. These numerical simulations are carried out in parallel using a supercomputer to reduce the time necessary to identify the set of model parameters. The major features of this new algorithm is its ability to identify the material parameters which describe the thermomechanical behavior of shape memory alloys from full-field measurements for various loading conditions (different temperatures, multiaxial behavior, heterogeneous test configurations). It is demonstrated that model parameters for the simulation of SMA structures are thus obtained based on a reduced number of heterogeneous tests at different temperatures.; International audience; With the design of new devices with complex geometry and to take advantage of their large recoverable strains, shape memory alloys components (SMA) are increasingly subjected to multiaxial loadings. The development process of SMA devices requires the prediction of their thermomechanical response, for which the calibration of the material parameters for the numerical model is an important step. In this work, the parameters of a phenomenological model are extracted from tests performed on specimens with non-uniform geometry, which induce heterogeneous strain fields carried out on specimens with the same thermomechanical loading history. The digital image correlation technique is employed to measure the strain fields on the surface of the specimen and to analyze the strain paths of chosen points. Finite element analysis enables the computation of numerical strain fields using a thermodynamicalconstitutive model for shape memory alloys previously implemented in a finite element code. The strain fields computed numerically are compared with experimental ones obtained by DIC to find the model parameters which best match experimental measurements using a newly developed parallelized mixed genetic/gradient-based optimization algorithm. These numerical simulations are carried out in parallel using a supercomputer to reduce the time necessary to identify the set of model parameters. The major features of this new algorithm is its ability to identify the material parameters which describe the thermomechanical behavior of shape memory alloys from full-field measurements for various loading conditions (different temperatures, multiaxial behavior, heterogeneous test configurations). It is demonstrated that model parameters for the simulation of SMA structures are thus obtained based on a reduced number of heterogeneous tests at different temperatures.

Aim: To evaluate the efficacy of early interferon alpha-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison. Patients: Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus. Results: There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1-7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 +/- 31 days) than in relapsers or non-responders (88 +/- 52 days) (P = 0.016). Conclusions: Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.

L’inhibition de la secretion acide est un objectif important pour traiter les œsophagites. Les inhibiteurs de la pompe a proton suppriment la secretion acide plus efficacement que les antagonistes des recepteurs H2.

Several surgical techniques have been developed to allow liver transplantation in cases of complete portal vein thrombosis in the recipient. Despite this, these transplantations remain associated with a significant complication rate. We report herein a case of liver transplantation in a patient with complete portal vein thrombosis, underlying the potential pitfalls and the risk of intestinal sutures in case of hepaticojejunostomy. We discuss the technical options and their relative indications in such cases.

Summary. Zusammenfassung. Der Empfanger eines Lebertransplantats entwickelte eine Infektion eines perihepatischen Hamatoms durch Trichoderma viride. Bevor der Befund erstellt war, erhielt der Patient immunsuppressive Medikation in hoher Dosis und uber einen langen Zeitraum antibakterielle und antimykotische Behandlung. Auch wenn der Tod des Patienten nicht in direktem Zusammenhang mit der Pilzinfektion stand, wurde der Erreger trotz vorheriger chirurgischer Drainage und intensiver Behandlung durch Amphotericin B und Fluconazol bei der Autopsie in groser Menge im perihepatischen Hamatom vorgefunden. A liver transplant recipient developed infection of a perihepatic haematoma due to Trichoderma viride. Before the infection was diagnosed, the patient received intense immunosuppressive and prolonged antibacterial and antifungal therapies. Although the death of the patient was not directly related to the fungal infection, abundant quantities of this pathogen were recovered in the haematoma at post-mortem examination, despite previous surgical removal and treatment with amphotericin B and fluconazole.

BACKGROUND Routine brush cytology is relatively insensitive for the diagnosis of biliary and pancreatic malignancy. Sensitivity can be improved by measuring DNA and proliferation. The goal of this study was to assess the discriminatory capacity of image cytometry using pancreaticobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography (ERCP). Analysis included morphometry, DNA quantification, and characterization of nuclear chromatin distribution and condensation. METHODS Brush cytology specimens were obtained during ERCP from 22 chronic pancreatitis specimens, 11 pancreatic adenocarcinoma specimens, 13 primary sclerosing cholangitis specimens, and 11 cholangiocarcinoma specimens and contrasted with 25 normal epithelia specimens. A SAMBA 2005 image processor was used to analyze Feulgen stained chromatin density and distribution. Discriminant analysis of 37 morphonuclear variables was performed to characterize differences between: 1) chronic pancreatitis and pancreatic adenocarcinoma, and 2) primary sclerosing cholangitis and cholangiocarcinoma. RESULTS Chronic pancreatitis was distinguished from pancreatic adenocarcinoma (P ≤ 0.001); sensitivity and specificity were both estimated to be 82%. Primary sclerosing cholangitis was distinguished from cholangiocarcinoma (P ≤ 0.01); sensitivity and specificity were estimated to be 82% and 85%, respectively. CONCLUSIONS Multiparameter image cytometry has potential as an adjuvant diagnostic technique in patients with pancreaticobiliary malignancy. Cancer (Cancer Cytopathol) 1998;84:119-26. © 1998 American Cancer Society.

Background/Aims: The current shortage of organs makes it desirable to establish the prognosis of patients with cirrhosis in order to assess priority for liver transplantation. Methods: We compared the utility of two exogenous tests (aminopyrine breath test and lidocaine metabolization test), two clinical parameters (encephalopathy, ascites), 18 endogenous tests and five scores (Pugh, Merkel, Orrego, Adler, Pignon) for predicting 1-year mortality in patients with parenchyma cirrhosis. Retrospective ( n =49 out of 63 patients) and prospective ( n =38 out of 46 patients) series were included. Univariate, multivariate, receiver operator curves and survival curves were employed. Results: We found that endogenous tests were more discriminant than exogenous tests. The best parameters of the univariate analysis (encephalopathy, bilirubin, alkaline phosphatase, cholinesterase and bile acids) and their 25th and 75th percentiles were included in an additive new score which turned out to be superior to the five other scores. Prospectively, the sensitivity of our new score compared to the Pugh score was 82% versus 95% (NS) and the specificity was 89% versus 56% ( p Conclusions: Our new simple score appears to be very powerful for predicting prognosis at 1 year for patients with cirrhosis and should be evaluated in other centers.

Background. We report on a pilot study investigating the feasibility of early immunosuppression withdrawal after liver transplantation (LT) using antithymocyte globulin (ATG) induction and rapamycin. Methods. LT recipients received 3.75 mg/kg per day ATG from days 0 to 5 followed by rapamycin-based immunosuppression. In the absence of acute rejection (AR), rapamycin was withdrawn after month 4. Immunomonitoring included analysis of peripheral T-cell phenotypes and clonality, cytokine production in mixed lymphocyte reaction, and characterization of intragraft infiltrating cells. Results. Ten patients were enrolled between October 2009 and July 2010. In the first three patients, complete withdrawal of immunosuppression after month 4 led to AR. No further withdrawals of immunosuppressive were attempted. Two AR occurred in the remaining seven patients. ATG induced profound T-cell depletion followed by CD8(+) T-cell reexpansion exhibiting memory/effector-like phenotype associated with progressive oligoclonal T-cell expansion (VA/HPRT ratio) and gradually enhanced anti-cytomegalovirus and anti-Epstein-Barr virus T-cell frequencies. Patients developing AR were characterized by decreased TCAIM expression. AR were associated with increased donor-specific production of interferon (IFN)-gamma and interleukin (IL)-17, increased intragraft expression of IFN-gamma mRNA, and significant CD8(+) T-cell infiltrates colocalizing with IL-17(+) cells. Conclusion. High-dose ATG followed by short-term rapamycin treatment failed to promote early operational tolerance to LT. AR correlates with expansion of memory-type CD8(+) T cells and increased levels of IFN-gamma and IL-17 in mixed lymphocyte reaction and in the graft. This suggests that resistance and preferential expansion of effector memory T-cell in lymphopenic environment could represent the major barrier for establishment of tolerance to LT in approaches using T-cell-depleting induction.

Der nachfolgende Beitrag stellt Covenants, allen voran Financial Covenants (Finanzkennzahlen), aus juristischer Sicht dar und geht dabei auf die Auspragung von Covenants in Kreditvertragen sowie Anleihen ein. Die Herleitung der rechtlichen Grundlagen erfolgt dabei auf Basis der in Kreditvertragen verwendeten Covenants und deren rechtlicher Einordnung und Ausgestaltung und ubertragt diese dann auf Anleihen. Dieser Aufbau folgt dabei der ursprunglichen Anwendung und Entwicklung der Covenants fur Kreditvertrage und deren nachfolgende Ubertragung auf Anleihetransaktionen.

International audience; In this work, a method for the identification of the transformation surface of Shape Memory Alloys based on full field measurements is presented. An inverse method coupled with a gradient-based algorithm has been developed to determine the characteristic parameters of the transformation surface. The constitutive equations of the chosen model that capture the macroscopic behavior of Shape Memory Alloys are first presented. The material parameters, to be identified, that are characteristic of the tension-compression asymmetry of the alloy are detailed. The identification algorithm, based on full field measurements obtained by Digital Image Correlation (DIC) and numerical simulation by Finite Element Analysis are introduced. The identification algorithm is validated using a numerically generated strain field on a Meuwissen-type specimen.

In an SMC composite two damage processes are observed: fiber fracture and interfacial debonding. Local criteria of damage initiation were introduced in a micro-mechanical model to reproduce these phenomena and predict the material behavior. The model is based on the stiffness prediction by the Mori and Tanaka approach. Tensile stress-strain curves until total failure were simulated. The evolution with damage of the elastic constants is compared with ultrasonic and mechanical measurements and with micro-mechanical calculations. In an Al SiCp composite damage was identified to be particle fracture. A statistical local criteria of particle fracture is then introduced into the model. Tensile behaviors including plasticity are simulated with or without damage and compared with experimental results. Moreover, to model the very local anisotropy due to damage, we develop the equivalent anisotropic undamaged inhomogeneity (EAUI) method.

BACKGROUND AND STUDY AIMS: The evolution of primary sclerosing cholangitis (PSC) is difficult to predict, and ERCP may be helpful in diagnosing its complications and treating them. Few descriptions of cholangiographic findings during the course of the disease have yet appeared. We report here on our experience in the management and follow-up by ERCP of six patients with deteriorating PSC. PATIENTS AND METHODS: Between 1981 and 1992, PSC was diagnosed in 18 patients. Clinical, biochemical, and cholangiographic findings were recorded during the follow-up period. An initial group of 12 patients had a good clinical and biochemical course (mean 56 months) and did not require systematic control ERCPs. A second group of six patients, showing cholangiographic features similar to those of the first group at presentation, developed clinical and biochemical deterioration within a mean period of 43 months (range 6-96). RESULTS: These six patients had a significant elevation of serum bilirubin and at ERCP showed worsening bile duct lesions, with marked strictures and a subsequent increase in the maximum duct diameter in both the extrahepatic and intrahepatic ducts compared to the initial ERCPs. In two of these six patients, the strictures were due to a superimposed cholangiocarcinoma. Endoscopic drainage was unsuccessful, transplantation impracticable due to extrahepatic spread, and both patients died three and five months, respectively, after diagnosis of cholangiocarcinoma. By contrast, four patients with dominant extrahepatic duct involvement benefited from endoscopic procedures (mean follow-up 19 months) without any recurrence of cholangitis and without requiring long-term antimicrobial treatment. The follow-up checks included regular ERCPs performed every six months for duct and stent assessment, and cytology brushing. CONCLUSIONS: Since there are no effective means of early and accurate detection of cholangiocarcinoma, the use of ERCP to compare the course of cholangiographic lesions over time may be of interest. Patients with extrahepatic duct involvement may benefit from endoscopic therapy. By contrast, in patients with dominant intrahepatic duct disease and a deteriorating clinical status, attempts at endoscopic therapy are not helpful, and liver transplantation needs to be considered promptly.

9th European Symposium on Martensitic Transformations (ESOMAT 2012), St Petersburg, RUSSIA, SEP 09-16, 2012; International audience; The thermomechanical behavior of Shape Memory Alloys (SMAs) is described by many micromechanical and phenomenological models. The first ones have material parameters whose physical meaning is based on the crystallography of the phase transformation related to the studied alloy. In contrast, phenomenological models often have material parameters whose physical meaning is not obvious and that makes them difficult to identify, some of which are based on mathematical considerations. In this paper, we propose to use the formulation of the phenomenological model of Chemisky et al., and to consider the particular case of a superelastic SMA. In this case, the constitutive equation should be easily expressed analytically through the strain tensor as a function of applied load direction and material parameters. The behavior is then characterized by a complete and proportional loading. This analytical model contains 7 material parameters, 1 related to the elasticity and 6 to the phase transformation. Based on several isothermal tensile tests at various temperatures, material parameters of this model are identified using the Levenberg-Marquardt algorithm and an analytical calculation of the sensitivity matrix. Their physical meaning and their influence on the thermomechanical behavior of the studied alloy are highlighted and discussed.

Listeria is an uncommon cause of hepatitis in adults. We report the case of a liver transplant recipient who presented with a clinical picture of acute hepatitis, 8 months after grafting. Blood cultures yielded Listeria monocytogenes. The patient made a full clinical recovery after adequate antimicrobial therapy (ampicillin and gentamicin intravenously for 4 weeks). Hepatitis was attributed to the Listeria infection. We believe this is the first reported case of Listeria hepatitis in an organ transplant recipient.

International audience; This paper deals with the experimental and numerical analysis of the effect of stress-strain heterogeneities due to elastic anisotropy, grain orientations and their effects on martensitic transformation for a Cu-Based SMA multicrystal. The shape of each grain is measured successively by optical microscopy and Electron Back Scattered Diffraction technique. During a tensile loading at room temperature, the displacement field of the free surface is measured by Digital Image Correlation. The considered shape for the finite element analysis is designed on the basis of the experimental characterization of the shape of each grain. The model is intended to simulate the behaviour of the multicrystal. The experimentally obtained data, such as the actual applied boundary conditions at the edge of the area, crystallographic orientation, and some material parameters of the literature chosen to be in conformity with our case, are introduced in the numerical model designed by the Abaqus finite element code. A SMA micromechanical constitutive law, implemented in this FE code, is considered for the behaviour description of each grain. It describes the effect of a martensitic transformation on the behaviour of a single crystal by taking into account the possible activation of various martensite variants. The study shows that the experimental and numerical results are in good agreement. Moreover, numerical results show the stress state in grains is disturbed by the neighboring grains and this disturbance has a strong influence on the martensite variant activation.

Minimization or withdrawal of immunosuppressive treatments after organ transplantation represents a major objective for improving quality of life and long-term survival of grafted patients. Such a goal may be reached under some clinical conditions, particularly in liver transplantation, making these patients good candidates for tolerance trials. In this context in liver transplantation, the central questions are (1) how to promote the natural propensity of the liver graft to be accepted, (2) which type of immunosuppressive drug should be used for induction and maintenance, and (3) which biomarkers could be used to discriminate tolerant patients from those requiring long-term immunosuppression. Induction therapies using aggressive T-cell-depleting agents may favor graft acceptance. However, persistent and/or rapidly reemerging cell lines, such as memory-type cells or CD8(+) T cells, could represent a significant barrier for induction of tolerance. The type of maintenance drugs also remains questionable. Calcineurin inhibitors may be eventually deleterious in the context of tolerance protocols, through inhibitory effects on regulatory T cells, that are not observed with rapamycin. In conclusion, significant efforts must be made to achieve reliable strategies for immunosuppression minimization or withdrawal after organ transplantation into the clinics.

Fifty-three patients suffering from dysphagia because of suspected esophageal motor disorders were treated by pneumatic dilatation using the Rider-Moeller technique. Fifteen had achalasia demonstrated by manometric studies. Forty-nine of them had remarkable clinical improvement after the procedure. During the mean period of follow-up (average 5 years, range 1–11), 75% of the patients needed a new dilatation, with a delay of two years. The results of the dilatation were excellent or good in 80% of the cases. Early complications consisted in two esophageal perforations surgically treated. There was no mortality. We did not observe late complications of the procedure. We conclude that pneumatic dilatation should be the initial procedure in the treatment of dysphagia in suspected esophageal motor disorders.

The forming behaviour of type 304 stainless steel sheet has been investigated. The strain-hardening behaviour has been characterised in uniaxial tension tests, and the forming limits at necking and at fracture have been determined using the Marciniak punch test. The results, complemented by measurements of the fraction of martensite formed by plastic straining, have been compared with the predictions derived from the constitutive laws proposed by Iwamoto and Tsuta [Iwamoto, T., Tsuta, T., 2000. Computational simulation of the dependence of the austenitic grain size on the deformation behaviour of trip steels. Int. J. Plasticity 16, 791–804; Iwamoto, T., Tsuta T., 2002. Computational simulation on deformation behaviour of CT specimens of trip steel under mode I loading for evaluation of fracture toughness. Int. J. Plasticity 18, 1583–1606] for steels exhibiting transformation induced plasticity, and from a flow localisation analysis developed along the lines of the model of Marciniak and Kuczinski [Marciniak, Z., Kuczynski, K., 1967. Limit strains in the processes of stretch-forming sheet metal. Int. J. Mech. Sci. 9, 609–620]. A good account of the whole results can be obtained by considering the limits to ductility imposed by ductile fracture.

Transplantation may be considered for patients with advanced cirrhosis, however, adequate criteria for evaluating survival in those patients are ill-defined. The aim of the present study was to select, among several clinical and functional variables those that could best predict survival at one year. The data collected from 91 consecutive patients with parenchymal cirrhosis hospitalized in our center from February 1984 to January 1986 were subjected to stepwise logistic regression analysis. Death occurring during the first year following entry into the study was considered as a failure. During that period, there were no censored patients. Of 19 variables that entered into the analysis, only two were significant (P less than 0.01): presence (1: moderate; 2: severe) or absence (0) of ascites (A) and breath test (BT: % aminopyrine activity of administered dose at 2 hr). The logistic equation was: 1n (P/1 - P): - 1.95 A + 1.64 BT - 0.393, where P represented the probability of survival at one year. For each patient, P was calculated according to his A and BT values. Using a 0.7 probability cut-point to separate success from failure, 93% (70/75) of successes, 81% (13/16) of failures, and 91% (83/91) of both successes and failures could be correctly predicted. Predictive equations like the present preliminary one can be used in the future to better assess the risk of mortality in patients with parenchymal cirrhosis in whom liver transplantation is considered.

OBJECTIVES: Pyogenic liver abscesses remain an important and life-threatening clinical problem but their causes and management have changed over the last two decades. The aim of this study was to assess the feasibility and the impact of an endoscopic approach in the management of liver abscesses with suspected biliary origin. METHODS: We reviewed the records of 16 patients suffering from pyogenic liver abscess, who underwent endoscopic retrograde cholangiopancreatography (ERCP) in the setting of biliary diseases between January 1995 and December 2004. Nine patients had an underlying neoplastic disease; 13 had a history of biliary endoscopic maneuvers. When the collections were communicating with the biliary tree, an endoscopic drainage of the abscess was performed either by sphincterotomy, dilation, insertion of a nasobiliary catheter, or stenting. In noncommunicating liver abscesses associated with bile duct abnormalities, biliary decompression was obtained by insertion or replacement of biliary stents. RESULTS: Fourteen patients had liver abscesses communicating with the biliary system and underwent an endoscopic drainage of the cavity. Ten of these patients had an exclusive endoscopic drainage of the abscess, while four cases required additional percutaneous drainage. The two noncommunicating abscesses were associated with previous insertion of biliary stents; these were cured percutaneously after endoscopic stent replacement. Among the 16 patients, 13 had a rapid resolution of symptoms (81%). CONCLUSION: This initial clinical experience suggests that ERCP can demonstrate communications between the biliary tract and liver abscesses, and that an internal drainage of the cavity is feasible and safe.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease usually presents with high spiking fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and a high serum level of ferritin with a low glycosylated fraction [1]. Abnormalities in liver tests, like a moderate elevation of transaminases and cholestasis, are common but usually resolve either spontaneously or rapidly under medical treatment [2]. However, rare cases of severe liver dysfunction in AOSD have been reported [2]. We describe a case of fulminant liver failure (FLF) in a patient with a recently diagnosed AOSD who was successfully treated with molecular absorbent recirculating system (MARS), followed by urgent liver transplantation (LT).

Age does not spare the liver. We reviewed here the essential actual knowledge about age related modifications of this organ. Liver volume and blood flow decrease with age. Aging is also associated with a decline in the intrinsic metabolic activity of the hepatic parenchyma, and in the gene expression of proteins involved in intermediary metabolism, mitochondrial respiration and drug metabolism. Aged hepatocytes accumulate oxidative DNA damage, responsible for the increase in mutations, particularly in the mitochondrial genome. Histologically, aged hepatocytes are characterized by accumulation of ageing pigments into the cytoplasm and by pseudocapillarization of the sinusoid. Age is also of importance at the time of HCV infection: fibrosis progression is faster when the virus is acquired after 40 years. In liver transplantation, an old transplanted liver is now an identified cause of primary non-function of the graft and an independent cause of mortality after transplantation. The age of the donor is also a predictive factor of the severity of recurrent liver HCV-related disease on the graft.

OBJECTIVE: The purpose of our study was to assess the usefulness of manganese dipyridoxyl diphosphate (Mn-DPDP)-enhanced T1-weighted MR cholangiography for evaluating patients with biliary-enteric anastomoses. CONCLUSION: Mn-DPDP-enhanced T1-weighted MR cholangiography may provide useful functional information and may aid in the assessment of the patency of biliary-enteric anastomoses.

Background Increasing numbers of cases and organ shortage justify reconsidering the global therapeutic approach for hepatocelluar carcinoma in cirrhotic patients. Methods Recent literature was reviewed, focused on new therapeutic technologies such as radiofrequency. Results For small tumors, liver transplantation offers theoretically the best chance for cure. However, organ shortage may eliminate this advantage, because of tumor progression while waiting for a graft. For small tumors, arising on compensated cirrhosis, resection or radiofrequency ablation may provide efficient local tumor control without precluding subsequent transplantation in case of tumor recurrence and/or cirrhosis decompensation. Conclusions For small tumors and compensated cirrhosis, resection or radiofrequency could represent acceptable first line treatments. In addition to permit safe and immediate tumor control, this strategy would allow a preferential redistribution of grafts to patients with decompensated cirrhosis in whom transplantation is the only possibility. J. Surg. Oncol. 2003;84:36–44. © 2003 Wiley-Liss, Inc.

Background. We report a case of domino liver transplantation using the liver harvested from a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria (PH). Method. A cadaveric liver transplantation was performed in a 19-year-old man with PH. In a second step, the PH liver harvested from the first patient was transplanted in a 69-year-old man with hepatitis C-related cirrhosis, not a candidate for a classic liver graft owing to multifocal hepatocellular carcinoma. Results. At 8 months after transplantation, the domino recipient has normal hepatic function and no signs of tumoral recurrence, but he progressively developed hyperoxalemia, hyperoxaluria, and renal insufficiency. Conclusion. Regarding the favorable postoperative clinical evolution, domino liver transplantations using livers from PH patients may represent a new opportunity for marginal candidates for liver transplantation. However, the progressive renal insufficiency expected in such domino recipients should limit this procedure to selected cases.

A 21-year-old woman with Crohn's disease of the colon developed a skin rash after 3 weeks of treatment with sulfasalazine. Administration of sulfasalazine was discontinued. When mesalazine was instituted 1 week later, she developed a severe hypersensitivity reaction characterized by fever, diarrhea, skin rash with subsequent desquamation, marked atypical lymphocytosis, and severe hepatotoxicity. Recovery was complete. The clinical and biological features as well as liver pathology of this case bear a striking resemblance to earlier reports of hypersensitivity reaction with severe hepatotoxicity to sulfasalazine. The authors urge caution when mesalazine is given to a patient with known hypersensitivity to sulfasalazine.

The MELD score has now been implemented in the United States for liver allocation, but it has not been validated in Europe. Its association with posttransplant outcome is unclear. Optimal cutoff values of MELD and Child-Pugh scores to predict death on the liver waiting list were defined in a series of 137 cirrhotic patients listed for liver transplantation. Six-month actuarial survival while on the waiting list was 90% with a Child-Pugh11 and MELD17, whereas it decreased progressively to 40% at 6 months after listing for those having a Child-Pugh and MELD score10 and16. Analysis of a series of 112 patients (85 chronic liver disease and 27 hepatocellular carcinoma) revealed no change in MELD value at the time of transplantation compared to the score at the time of listing (mean +/- SD: 15.5 +/- 7.7 vs 15 +/- 5.8) with a mean waiting time of 118 days. Using either the optimal cutoff for MELD score (17 or16) or seven different strata (3 to 7, 8 to 10, 11 to 13, 14 to 16, 17 to 19, 20 to 22, 23 to 39), whether measured at listing or just before liver transplantation, there was no significant difference (chi(2) 4.97, P = .58) in survival: 82.7% and 63% at 6 and 60 months, overall. Our data confirm that the MELD score with only three parameters is as good as the Child-Pugh score to predict mortality on the Eurotransplant waiting list. The optimal cutoff to assess higher priority for the bad category is16. There was no negative impact on short- or long-term prognosis of the bad categories of MELD.

From January 1985 to January 1995, 125 adult patients underwent 135 liver transplantations (OLT). Hundred of them survived more than 3 months.

Background: We report our current experience using endoscopic retrograde cholangiography in the management of post-transplantation biliary tract complications. Methods: Twenty-three patients among 109 adult liver transplant recipients underwent retrograde cholangiography because of cholestasis (18 patients) or bile leaks (5 patients). Results: Eleven of 18 patients developed anastomotic strictures, all successfully dilated by plastic stents; one patient required Roux-en-Y revision due to recurrent cholangitis while stented. Three had biliary calculi extracted following sphincterotomy. Two developed intrahepatic ductal strictures secondary to severe rejection. One patient had hepatic artery thrombosis with a hilar stricture. One cholangiogram was normal.Three patients developed bile peritonitis following T-tube removal, all treated by sphincterotomy and nasobiliary drainage. Choledochal perforation resulting from an impacted T-tube limb was detected in two patients, both treated with sphincterotomy and nasobiliary drainage. Conclusions: Strictures within 3 months of surgery required 3 months of stenting; those occurring later required longer periods of time to respond. Bile leaks responded uniformly and rapidly to drainage. Endoscopic retrograde cholangiography is a useful diagnostic and therapeutic intervention for posttransplantation biliary tract complications. (Gastrointest Endosc 1995;42:527-34.)

Variceal bleeding carries high early mortality, especially after failure of conventional treatments such as endoscopic injection therapy. The present study analyses the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) in cirrhotic patients after failure of sclerotherapy for variceal bleeding.Twenty-four consecutive patients underwent TIPS in this indication.The procedure was successful in all patients, with reduction of size or disappearance of varices in 96% of them. Four patients (17%) developed encephalopathy and six (25%) rebled during the follow-up period (median 5 months; range 1-19). Thirty-day mortality was only 17% and 29% during the follow-up period. Deaths were mainly due to liver failure, especially after procedures performed in emergency. Significant decrease in liver function was observed in the days following the procedure. To maintain long-term patency of the shunt, revision was required in nine patients (38%).TIPS seems to be a promising salvage therapeutic procedure after failed sclerotherapy, but this needs to be addressed in controlled trials.

The authors report a scoring system based on cell image analysis of specimens obtained during endoscopic retrograde cholangiopancreatography from either the biliary or pancreatic duct epithelium. Nine normal, 20 inflammatory, and 19 malignant epithelia were assessed using a cell-image processor that permits determination of morphometric (nuclear area), densitometric (nuclear DNA content), and textural (chromatin distribution) parameters on Feulgen-stained nuclei. The score is based on three densitometric parameters: the DNA histogram type, the nuclear DNA content, and the percent proliferating cell population. These parameters permit distinction of normal and inflammatory from malignant epithelium with 95% sensitivity and 100% specificity. Cell-image analysis of specimens obtained during endoscopic retrograde cholangiopancreatography is a useful clinical tool in the detection of malignant lesions of the pancreas and biliary epithelia.

In a previous study we demonstrated at light microscopical level the presence of variable amounts of type IV collagen in the areas of periductal and interstitial elastosis in breast cancer. The present work was directed towards a further study by immunoelectron microscopy of the distribution of type IV collagen in the areas of periductal elastosis. The semithin sections showed a distinct immunoreactivity of all basement membranes for type IV collagen but no staining of the interstitial stroma. Corresponding ultrathin sections demonstrated a broad basement membrane with immunoreactivity for type IV collagen at its outer side. Many punctiform deposits of type IV collagen were observed in the areas of periductal elastosis but not around normal ducts or vessels. Recently the role of type IV collagen as a structural component on anchoring plaques between the basement membrane and the underlying stroma in the dermis has been emphasized. The results of this study demonstrate the presence of type IV collagen deposits below a thickened basement membrane in breast cancer.

Variceal haemorrhage in cirrhotic patients carries a high early mortality even when balloon tamponade or emergency sclerotherapy are applied. The aim of this study to identify patients dying within six weeks of their first variceal haemorrhage. One hundred and twenty one patients with parenchymal cirrhosis presenting with the first variceal bleeding episode between June 1983 and December 1988 were studied. Nineteen patients were excluded for various reasons. Emergency sclerotherapy was carried out in cases of active bleeding or where there were endoscopic signs of recent bleeding, and then regularly repeated afterwards. Of the 24 variables studied and included in a multivariate analysis using a logistic regression model, three had an independent prognostic value: encephalopathy, prothrombin time, and the number of blood units transfused within the 72 hours of time zero. The subsequent regression equation was able to predict 89% of the patients who will die and 97% of the patients who will still be alive six weeks after their first variceal haemorrhage treated by sclerotherapy. Pugh score was less discriminatory than these last three variables in terms of accuracy of adjustment, goodness of fit to the model, receiver operating characteristic curves, and percentage correct prediction. To measure the accuracy of the prediction rule, our model was applied to another series of 28 cirrhotic patients admitted with their first variceal bleeding during the next period (January 1989 to May 1990). Death and survival were correctly predicted in respectively 82% and 94% of the cases. The use of this score is recommended for the selection of patients with high early mortality after variceal bleeding despite sclerotherapy, and for the design of new therapeutic trials.

The aim of our study was to develop simple and highly effective scores to estimate prognosis at 1 year for patients with parenchymal cirrhosis and to define the optimum time for liver transplantation with the same degree of accuracy as the prognosis estimation for primary biliary cirrhosis. The prognostic value of 19 variables was studied retrospectively in 91 patients with parenchymal cirrhosis using multivariate analysis and logistic regression. The best prognostic index was obtained with two independent variables: ascites and aminopyrine breath test. Although the receiver operating characteristic (ROC) curve for these two variables was better than the ROC curve for Pugh score, the percentage of correct prediction was excellent for both indices: 92% and 87%, respectively. The critical cut-off value of the Pugh score was 8.8. The prognostic value of a Pugh score ≤ 8 or > 8 was confirmed in a prospective study of 145 cirrhotic patients with 78% correct prediction. During this period, 21 patients with parenchymal cirrhosis received transplants with a preoperative Pugh score of 9.5 ± 2.0 (mean ± SEM) and 60% 1- and 2-year survival. In conclusion in parenchymal cirrhosis, a Pugh score > 8 indicates a poor prognosis at 1 year. This is a simple, easy and highly effective tool to define the optimal time for liver transplantation in this category of patients.

Belgian Assoc Study Liver, Ghent, Belgium. Univ Hosp Gent, Ghent, Belgium. Ctr Biostat, Diepenbeek, Belgium.