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In recent years, the diagnosis of irreversible brain function loss in severely brain-damaged patients has gained in importance. Brain death, defined as an irreversible loss of the overall function of the cerebrum, cerebellum and brain stem, is a prerequisite for organ removal in the context of organ donation. The article presents the legal and organizational framework.Brain death is determined on the basis of the latest update of the guidelines of the German Medical Chamber (Bundesärztekammer) using a three-step scheme and consists of clinical and instrumental examinations. After the final diagnosis of brain death, the phase of organ-preserving treatment for the potential organ donor begins. In the case of patients who themselves or their relatives have not agreed to organ donation, the intensive care therapy must be terminated promptly. The legal framework for the determination of brain death and for the removal of organs from potential organ donors is provided by the Transplantation Act. The German Foundation for Organ Transplantation (DSO) is responsible for the coordination of organ donations in Germany. The DSO supports hospitals in many ways during the organ donation process, but also in training courses for medical staff on organ donation. The main contact person of the DSO is the transplant officer in the hospitals. The care of the relatives of a potential organ donor is of great importance.

ZusammenfassungIn den letzten Jahren hat die Diagnose des irreversiblen Hirnfunktionsausfalls bei schwer hirngeschädigten Patienten an Bedeutung gewonnen. Der Hirntod, definiert als nicht behebbarer Ausfall der Gesamtfunktion des Großhirns, des Kleinhirns und des Hirnstamms, ist Voraussetzung zur Organentnahme im Rahmen einer Organspende. Der Artikel stellt die gesetzlichen und organisatorischen Rahmenbedingungen vor.

Liver transplantation (LT) is the first-line therapy in patients with transthyretin (TTR) amyloidosis and progressive familial amyloid polyneuropathy (FAP). Explanted organs from these patients can be used for domino liver transplantation (DLT). After DLT, de novo amyloidosis may develop in domino recipients (DR). Data were collected prospectively in a transplant database. Electroneurography by nerve conduction velocity (NCV), quantitative sensory testing, heart rate variability (HRV), sympathetic skin response, orthostatic reaction (tilt table test), transthoracic echocardiography, cardiac MRI and organ biopsy results were evaluated. The cohort included 24 FAP- (11 Val30Met, 13 nonVal30Met) and 23 DR-patients. DR symptoms referred to post-DLT only, while those of FAP patients were both pre- and post-transplantation. Symptoms of TTR-amyloidosis in Val30Met and Non-Val30Met patients pre- and post-LT were similarly distributed. Biopsy-proven de novo amyloidosis occurred in 4/23 DR after a mean observation of 10 years. Analysis for manifestations of amyloidosis only included patients with available 5-year follow-up data (n = 13 FAP, n = 12 DR). Compared to Val30Met FAP patients pre-LT, Val30Met DR patients had better NCV (P = 0.04) and HRV (P = 0.015). In the Non-Val30Met group no differences were found between DR and FAP patients pre-LT. TTR-amyloidosis symptoms showed no differences in FAP patients pre- and 5 years post-LT, irrespective of Val30Met status. In DR patients, de novo amyloidosis occurred earlier than expected. Therefore, recipients for DLT need to be carefully selected and followed.

ZusammenfassungDie Leitlinie zur Prävention, Diagnostik und Therapie von Gallensteinen aktualisiert die Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie aus dem Jahr 2007. Die Leitlinie wurde interdisziplinär von Gastroenterologen und Chirurgen erstellt. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften für eine systematische evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S3 und berücksichtigt die klinische Anwendbarkeit der Studienergebnisse. Zudem werden Präventionsmöglichkeiten beschrieben, Qualitätsindikatoren definiert, ökonomische Auswirkungen berücksichtigt und Vorschläge zur sektorenübergreifenden Behandlung von Patienten mit Gallensteinerkrankungen formuliert.

Die Leitlinie zur Pravention, Diagnostik und Therapie von Gallensteinen aktualisiert die Leitlinie der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten und der Deutschen Gesellschaft fur Allgemein- und Viszeralchirurgie aus dem Jahr 2007. Die Leitlinie wurde interdisziplinar von Gastroenterologen und Chirurgen erstellt. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften fur eine systematische evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S3 und berucksichtigt die klinische Anwendbarkeit der Studienergebnisse. Zudem werden Praventionsmoglichkeiten beschrieben, Qualitatsindikatoren definiert, okonomische Auswirkungen berucksichtigt und Vorschlage zur sektorenubergreifenden Behandlung von Patienten mit Gallensteinerkrankungen formuliert.

Fatal Zoonotic Viral Infection after Transplantation Evidence of Borna disease virus 1 infection in humans is limited; in this report, donor-derived Borna virus encephalitis is shown to occur in three solid-organ transplant recipients.

Organspenden sind in Deutschland immer noch recht selten. Das fuhrt nicht nur zu langen Wartelisten, sondern auch zu Unsicherheit bei behandelnden Arzten: Welcher Patient kommt als Spender infrage – und wie meldet man dies? Antworten finden Sie hier.

Patients with transthyretin amyloid polyneuropathy (TTR-FAP) and asymptomatic mutation-carriers have to be regularly followed-up in order to identify disease progression and the time point for starting or modifying therapy. In this case series we describe the potential suitability of different variables as progression markers. We retrospectively analyzed the follow-up charts of 10 TTR-FAP patients. Clinical examination included the Neuropathy Impairment Score of Lower Limb (NIS-LL), temperature perception thresholds, nerve conduction and autonomic function tests. The NIS-LL had the greatest value for a sensitive and correct follow-up for all TTR-FAP stages. All other examinations provided useful additional information but they were either less suited for advanced TTR-FAP, or had a higher test-retest variability. The results of this study provide preliminary evidence that a good clinical investigation is mandatory in TTR-FAP follow-up. Simple neuropathy scores like the NIS-LL might be as useful as technical investigations for TTR-FAP follow-up.

Background and aims: The introduction of a new type of small handheld ultrasound device brings greater portability and affordability in a different setting. The basic ultrasound approach with these handheld devices has been defined by European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) as “EchoScopy”. The current study aimed to assess the image quality, indications and limitations of a portable pocket “EchoScopy” performed first compared with a high-end ultrasound system (second) in abdominal diseases.Material and methods: Three hundred consecutive patients (158 males and 142 females, age 55±19 [18-96]) years) were included. The ultrasound examinations were performed firstly by an EchoScope (Vscan™ Dual Probe) and secondly with a high-end ultrasound system (HEUS, GE Logiq E9). Compared with the always excellent image quality using HEUS, the image quality of the EchoScope was graded as good, sufficient or non-sufficient.Results: Out of all 300 patients, 221 had focal lesions, 31 patients were found with diffuse pathological findings, 20 with ascites, 25 after liver puncture and 45 without any pathological findings. The image quality of the pocket device was considered as being good or sufficient to delineate the pathology in 265/300 (88%). The detection rate of the EchoScope for abdominal focal lesion was 172/221 (78%). The higher frequency of the Dual Probe was helpful in 35/300 (12%).Conclusions: EchoScopy has proven to display sufficient image quality to answer specific questions, e.g., detection of ascites, splenomegaly, bile duct enlargement, hydronephrosis and other pathological findings which can be judged by “yes/no”.

This guideline provides evidence-based key recommendations for the prevention, diagnosis and therapy of gallstones and upgrades the 2007 version. The guideline was developed by an interdisciplinary team of gastroenterologists and surgeons, and patient support groups under the auspice of the German Society for Gastroenterology and Metabolic Diseases and the German Society for General Surgery and Surgery of the Alimentary Tract. The guideline used structural S3 consensus-based methodology and includes statements on clinical practice, medical education, prevention, quality assurance, outcome analysis, and integration of outpatient and inpatient care for patients with gallstone diseases.Die Leitlinie zur Prävention, Diagnostik und Therapie von Gallensteinen aktualisiert die Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie aus dem Jahr 2007. Die Leitlinie wurde interdisziplinär von Gastroenterologen und Chirurgen erstellt. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften für eine systematische evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S3 und berücksichtigt die klinische Anwendbarkeit der Studienergebnisse. Zudem werden Präventionsmöglichkeiten beschrieben, Qualitätsindikatoren definiert, ökonomische Auswirkungen berücksichtigt und Vorschläge zur sektorenübergreifenden Behandlung von Patienten mit Gallensteinerkrankungen formuliert.

To determine whether liver function as determined by indocyanine green (ICG) clearance can be estimated quantitatively from hepatic magnetic resonance (MR) relaxometry with gadoxetic acid (Gd-EOB-DTPA). One hundred and seven patients underwent an ICG clearance test and Gd-EOB-DTPA–enhanced MRI, including MR relaxometry at 3 Tesla. A transverse 3D VIBE sequence with an inline T1 calculation was acquired prior to and 20 minutes post-Gd-EOB-DTPA administration. The reduction rate of T1 relaxation time (rrT1) between pre- and post-contrast images and the liver volume-assisted index of T1 reduction rate (LVrrT1) were evaluated. The plasma disappearance rate of ICG (ICG-PDR) was correlated with the liver volume (LV), rrT1 and LVrrT1, providing an MRI-based estimated ICG-PDR value (ICG-PDRest). Simple linear regression model showed a significant correlation of ICG-PDR with LV (r = 0.32; p = 0.001), T1post (r = 0.65; p

Ultrasound findings in autoimmune hepatitis (AIH) have not been reported systematically so far. The use of reliable and accurate noninvasive methods for determining fibrosis stage is important in evaluation of treatment efficacy and fibrosis regression in AIH. Imaging plays an important role in detection of complications and ruling out other possible causes of chronic liver diseases. Ultrasound elastography cut-off values in AIH patients are not the same as those in patients with chronic viral hepatitis or non-alcoholic fatty liver disease. AIH is characterized by wide fluctuations in inflammatory activity. Here we report on current knowledge of ultrasound findings in AIH.

Background Familial transthyretin amyloidosis is a life‐threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR‐FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Methods Twenty‐four patients with TTR‐FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross‐sectional design. Both groups were matched for gender and presence of pain. Quantitative sensory testing (QST), sympathetic skin response (SSR), heart rate variability (HRV), and nerve conduction studies (NCV) were performed. Both groups were compared using univariate analysis. In a stepwise discriminant analysis, discriminators between both neuropathies were identified. These discriminators were validated comparing TTR‐FAP patients with a cohort of patients with chemotherapy‐induced polyneuropathy (CIN) and chronic inflammatory demyelinating neuropathy (CIDP). Results TTR‐FAP patients scored higher in NDS and NIS and had impaired cold detection (CDT, p = .024), cold–warm discrimination (TSL, p = .019) and mechanical hyperalgesia (MPT, p = .029) at the hands, SSR (upper limb, p = .022) HRV and ulnar and sural NCS (all p

The purpose of this study was to evaluate the usefulness of Gd-EOB-DTPA-enhanced 3-T MRI to determine the hepatic functional reserve expressed by the model for end-stage liver disease (MELD) score.A total of 121 patients with normal liver function (NLF; MELD score ≤ 10) and 29 patients with impaired liver function (ILF; MELD score 10) underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 min after contrast injection. Relative enhancement (RE) between plain signal intensity and contrast-enhanced signal intensity was calculated and was used to determine Gd-EOB-DTPA uptake into the liver parenchyma for patients with different MELD scores.RE differed significantly (p ≤ 0.001) between patients with NLF (87.2 ± 29.5 %) and patients with ILF (45.4 ± 26.5 %). The optimal cut-off value for RE to differentiate NLF from ILF was 47.7 % (AUC 0.87). This cut-off value showed a sensitivity of 82.8 % and a specificity of 92.7 % for the differentiation of the analysed groups.Gd-EOB-DTPA uptake in hepatocytes is strongly affected by liver function. Gd-EOB-DTPA-enhanced MRI and assessment of RE during the hepatobiliary phase (HBP) may serve as a useful image-based test in liver imaging for determining regional and global liver function.Hepatic uptake of Gd-EOB-DTPA is strongly affected by liver function. Relative enhancement during HBP in GD-EOB-DTPA MRI correlates with the MELD score. Assessment of relative enhancement may help improve treatment in routine clinical practice.

Objective Splenic lesions are rare and characterization is difficult. Secondary spread is more frequent than primary malignant lesions. Thus clinical circumstances are important in the general work-up. Contrast enhanced ultrasound (CEUS) had high accuracy in recent studies but the positive predictive value is low. Biopsy is considered dangerous. Recent studies have brought back this method into focus showing an excellent efficacy and safety. The aim of this study was to estimate the rate of relevant biopsy results in patients with splenic lesions concerning the clinical circumstances. Design Patients with unclear splenic lesions which appeared progressively hypoenhancing in the late phase of CEUS with BR1 were included. Biopsy was performed with ultrasound guidance. Patients were sorted into 5 groups according to their clinical symptoms. Results 44 patients were enrolled, 59% had benign lesions. 73% were rated relevant. For the subgroups the rate was: patients with hints for hemato-oncological diseases 83%, patients without symptoms 38%, patients with infections of unknown origin 100%, patients with suspicion of metastases 33%, immunocompromised patients 100%. One bleeding could be managed conservatively, another bleeding was detected incidentally 2 weeks later. Conclusion Percutaneous biopsy of unclear splenic lesions which appear hypoenhancing in the late phase of CEUS with BR1 results in a high rate of relevant lesions. The results should be tested in larger numbers of patients.

Background and Aims: Despite increasingly sensitive and accurate blood tests to detect liver disease, liver biopsy remains very useful in patients with atypical clinical features and abnormal liver tests of unknown etiology. The aim was to determine those elevated laboratory liver parameters that cause the clinician to order a biopsy, and whether laboratory tests are associated with pathological findings on histology. Methods: 504 patients with unclear hepatopathy, admitted to the outpatient clinic of a university hospital between 2007 and 2010, were analyzed with respect to laboratory results, clinical data, and the results of liver biopsies. Results: Aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) levels above the normal range significantly increased the likelihood of recommending a liver biopsy by 81% [OR with 95% CI 1.81 (1.21-2.71), p = 0.004] and 159% [OR with 95% CI 2.59 (1.70-3.93), p < 0.001], respectively. AST values above normal were associated with fibrosis (63 vs. 40% for normal AST, p = 0.010). Elevated ferritin levels pointed to a higher incidence of steatosis (48 vs. 10% for normal ferritin, p < 0.001) and inflammation (87 vs. 62% for normal ferritin, p = 0.004). Conclusions: Our results indicate that elevated AST and GLDH were associated with a greater likelihood of recommending liver biopsy. Elevated AST and ferritin levels were associated with steatosis, inflammation and fibrosis on liver biopsies. Thus, AST and ferritin may be useful non-invasive predictors of liver pathology in patients with unclear hepatopathy., OA-Komponente aus Allianzlizenz

Die Oberbauchsonografie spielt in vielen medizinischen Disziplinen eine grose Rolle. Sie stellt haufig das erste bildgebende Verfahren dar, mit dem fruhzeitig wegweisende Diagnosen gestellt werden. Der Ultraschall ermoglicht nicht invasiv die Beurteilung vieler Organe, insbesondere der Leber, des hepatobiliaren Systems, der Milz und Nieren. Auch Berufseinsteiger konnen die Oberbauchsonografie durch praktisches Uben rasch lernen. Sie ermoglicht eine schnelle, zielfuhrende Diagnostik auf Station oder z. B. in der Notaufnahme. Wichtig ist, dass die einzelnen anatomischen Strukturen mit definierten Schallschnitten aufgesucht werden, um eine gute Vergleichbarkeit und Reproduzierbarkeit zu erreichen.

Durchfallerkrankungen sind haufige Erkrankungen des Gastrointestinaltrakts und eine der 5 haufigsten Todesursachen weltweit. Obwohl genaue epidemiologische Angaben fehlen, spielen Diarrhoen auch in entwickelten Landern eine zunehmende Rolle. Dabei werden akute von chronischen Diarrhoen unterschieden. Die haufigsten Ursachen fur eine akute Enteritis infectiosa sind virale und bakterielle Erreger. Im Fall einer bakteriellen Dysenterie sind antibiotikaassoziierte Durchfalle durch Clostridium difficle eine haufige nosokomiale Manifestation der Erkrankung. Bei den viralen Erregern sind Noroviren in etwa 90 % der Falle Ausloser einer akuten, innerhalb von 48-72 Stunden meist selbstlimitierenden Diarrho. Bakterielle Dysenterien werden, wenn notwendig, mit Antibiotika behandelt, wobei bei einigen Erregern zunehmende Resistenzentwicklungen zu beachten sind. Eine weiterfuhrende mikrobiologische oder endoskopische Diagnostik ist nicht immer notwendig. Die Therapie orientiert sich an den klinischen Symptomen und berucksichtigt im Allgemeinen die Pravention sekundarer Komplikationen.

The hepatitis B virus (HBV) is a major causative agent of chronic liver disease and subsequent liver cirrhosis worldwide. The reduced sensitivity of virus-infected liver cells to apoptosis may play a role in the failure to remove virus-infected cells and eventually promote viral chronicity. The purpose of our study was to investigate whether survival factors induced during compensatory liver regeneration may protect hepatocytes against apoptosis. We evaluated the serum levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in HBV-infected patients and found significant increases in HGF and EGF in patients with active virus infection. In primary human hepatocytes we show that HGF and EGF have a protective effect against CD95-mediated apoptosis and cytotoxic T-cell killing. Simultaneous treatment with both regeneration factors enhanced the cytoprotective effect. The PI 3-K/Akt kinase inhibitor, wortmannin, and the STAT3 pathway inhibitor, Tyrphostin AG490, both effectively attenuated the cytoprotective effect of HGF and EGF. Furthermore, we show an EGF/HGF-dependent upregulation of beta(1)-integrin chains, increased adhesion to extracellular matrix and an increase in focal adhesions, suggesting outside-in signaling from the extracellular matrix as an additional cytoprotective mechanism. Our study demonstrates that HGF and EGF can interfere with CD95-mediated apoptosis and the action of cytotoxic T-cells through multiple mechanisms in human hepatocytes. Together our results argue that a survival mileau generated by activation of liver regeneration factors may be a risk factor for establishing viral persistence.

There is a paucity of data on the sonographic criteria for the diagnosis of intestinal tuberculosis. The purpose of this study was to further characterize the potential sonographic signs of intestinal tuberculosis and to increase the diagnostic sensitivity and specificity of ultrasound.Seven patients with a final diagnosis of gastrointestinal tuberculosis and a control group of 18 patients suffering from tuberculosis limited to the lungs were prospectively evaluated for sonographic criteria of intestinal tuberculosis and the findings were compared with those in 50 healthy controls.The following signs of intestinal tuberculosis were detectable: asymmetric thickened bowel wall (100%), intramural abscesses (86%), fistula (43%), extramural abscesses (29%), mesenteric thickening (29%), "white bowel" sign (29%), hypoechoic edema of Kerckring's folds with mesenterial thrombosis (14%), enlarged mesenteric lymph nodes with inhomogeneous echotexture and circumscribed hypoechoic spots3 mm (86%), ascites (29%) and enlarged spleen (14%). These signs were exclusively present in patients with intestinal tuberculosis as compared with patients with tuberculosis limited to the lungs or with healthy controls. We could confirm the endoscopically reported right-sided prevalence of these wall thickenings. In contrast to the reported literature, a much higher prevalence of these sonographic signs was found as they were present in all patients. Six of 7 patients (86%) showed enlarged mesenteric lymph nodes. This was particularly interesting as mesenteric lymph nodes have not been described as being enlarged in the majority of other differential diagnoses of the ileocecal region.The combination of bowel-wall thickening of the ileocecal region with intramural abscesses with or without fistula, abscesses and mesenteric thickening accompanied by enlarged mesenteric lymph nodes was highly predictive of intestinal tuberculosis.

Background Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. Methods Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). Results Adoptive transfer of ex vivo activated alloreactive host T cells (aHLI) led to the control and complete resolution of severe GvHD without inducing allograft rejection. Conclusions aHLI opens a novel therapeutic window to control solid-organ transplant-associated GvHD while preserving allograft integrity.

Die Sekundar sklerosierende Cholangitis (SSC) ist eine cholestatische Lebererkrankung, welche bei Patienten nach einem Langzeitintensivaufenthalt mit einer schweren Sepsis und ARDS auftreten kann. Die SSC ist charakterisiert durch eine progressive Fibrose und Destruktion der intra- und extrahepatischen Gallenwege, biliare Casts und Cholangitis. Bisher gibt es nur wenig Erfahrung bezuglich der Resultate nach einer Lebertransplantation (LTx). Patienten und Methoden: Zwischen 11/04 und 04/13 erhielten 22 SSC-Patienten (49 ± 11J.; 21 m; mittlerer labMELD: 25 ± 10) eine LTx im Universitatsklinikum Regensburg. Zwolf Patienten hatten die SSC nach einem schweren Polytrauma mit multiplen Knochenfrakturen, Sepsis und ARDS entwickelt und 10 Nicht-Trauma-Patienten akquirierten die SSC nach einem Langzeitaufenthalt wegen einer Sepsis mit ARDS. Die Diagnosestellung der SSC wurde mittels einer ERCP gestellt und im Explantat bestatigt. Ergebnisse: Die mittlere Nachbeobachtungszeit lag bei 37 ± 36 Monaten. Das 1- und 5-Jahresuberleben der SSC-Patienten nach LTx betrug 63% und 63%. Ein Patient wurde 19 Tage nach der ersten LTx retransplantiert ('initiale Nichtfunktion'). Acht von 22 SSC-Patienten starben innerhalb von 8 Monaten post-LTx, 6 davon an einer Sepsis. Ein Patient starb 2 Monate nach der LTx im hamorrhagischen Schock (Aneurysmaruptur der A. hepatica) und ein Patient starb 2 Tage post-LTx aufgrund einer hyperakuten Abstossung mit einer fulminanten zentralen pontinen Myelinolyse. Vier von 6 SSC-Patienten starben nach der LTx an einer Sepsis bedingt durch eine Infektion mit multi-resistenten Bakterien: Vancomycin-resistenter Enterococcus faecium (n = 2) bzw. Klebsiella pneumoniae (ESBL) (n = 2). Alle uberlebenden Patienten (14/22) haben eine gute Lebensqualitat nach der LTx. Schlussfolgerung: Die LTx stellt fur Patienten mit einer SSC eine relativ gute Therapieoption dar. Die Haupttodesursache innerhalb der ersten 8 Monate post-LTx war die Sepsis.

Background It has been shown that interaction of anti-PR-3 antibodies with human endothelial cells (EC) leads to an activation of EC in vitro, i.e. induction of adhesion molecules like E-selectin, VCAM-1 and tissue factor. The aim of this study was to investigate the effect of anti-PR-3 antibodies on endothelial IL-8 expression. Materials and methods EC were cultured in 96-well plates and stimulated with TNF-α and IL-1β for 1 h to induce membrane expression of endothelial PR-3. Anti-PR-3 antibodies were purified from sera from patients with clinically active Wegener's granulomatosis. Purified anti-Ro, anti-centromere, anti-dsDNA antibodies and a monoclonal anti-PR-3 antibody (WGM2) served as controls. Induction of IL-8 mRNA was detected by RT-PCR. IL-8 was measured in the supernatant of EC by ELISA. In addition, induction of NFκB was investigated by PAGE of nuclear extracts of EC and Western blot with ab against p65. Results In contrast to controls, interaction of anti-PR-3 antibodies (patients and WGM2) with cytokine activated EC led to the highest amount of IL-8 synthesis. Priming of EC with cytokines alone induced a markedly lower IL-8 level. The lowest levels of IL-8 could be measured after incubation of unprimed EC with anti-PR-3 antibodies. Anti-PR-3 antibody induced endothelial IL-8 expression could be inhibited by cycloheximide. In addition, we established that the activation of NF-κB is critically involved in anti-PR-3 antibody induced endothelial IL-8 production. Conclusion In summary, we were able to show that anti-PR-3 antibodies induce endothelial IL-8 synthesis by activating NF-κB. As IL-8 represents a powerful neutrophil chemoattractant, our data provide further evidence for a direct pathogenic effect of anti-PR-3 antibodies in ANCA related diseases.

Familial amyloidosis: Great progress for an orphan disease Ana Paula Barreiros1,2,*, Gerd Otto3, Bita Kahlen1, Andreas Teufel1,2, Peter R. Galle1 1Department of Internal Medicine I, Universitatsmedizin of the Johannes Gutenberg-University Mainz, Germany; 2Department of Internal Medicine I, Universitatsklinikum of the University Regensburg, Germany; 3Department of Hepatobiliary and Transplantation Surgery, Universitatmedizin of the Johannes Gutenberg-University Mainz, Germany. *Corresponding author. Address: Universitatsklinikum Regensburg, Department of Internal Medicine I, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany. Tel.: +49 941-944-7021. E-mail address: Ana.Barreiros@ukr.de (A. P. Barreiros).

Summary A retrospective multicenter study has been conducted to evaluate domino liver transplantations (DLTs) in Germany. The study provides insight into survival and features having an impact on the assessment of neuropathy after DLT. In addition, a neurologic follow-up program with a scheme to estimate the likelihood of de novo amyloidosis is presented. A series of 61 DLTs at seven transplant centers in Germany was enrolled. The mean age of domino recipients at the time of transplantation was 58 years, 46 of them being men, and 15 being women. The median follow-up was 46 months. The overall 1-, 3-, and 5-year survival of domino recipients was 81.6%, 70.8% and 68.8%, respectively. Causes of death were primarily not related to familial amyloidosis. The main indication of DLT was hepatocellular carcinoma. Two of the reported domino recipients developed symptoms and signs of de novo amyloidosis within 10 years after transplantation. A total of 30 domino graft recipients (49.18%) presented with diabetes post transplantation. In conclusion, an advanced follow-up program is crucial to evaluate the risk of transmitting familial amyloidosis by DLT and to establish more strict selection criteria for domino recipients.

Summary Since the introduction of model for end-stage liver disease (MELD) in 2006, post-orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006–December 2007) were included. Recipient data were analyzed for their influence on 1-year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow-up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis-C (17.1%), Hepatitis-B (9.5%), primary sclerosing cholangitis (5.6%) and late graft-failure after first OLT before December 2006 (8.7%). 1-year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57–6.78, 12-month survival = 52.6%, c-statistic = 0.669], hyponatremia (OR = 2.07), and pre-OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.

To The Editor: Perineal or perianal ultrasound (PNUS) is an effective, inexpensive, easily available and not painful but as of now rarely applied diagnostic tool important in the hands of gastroent...

Long term immunosuppression and therapy of acute rejections result in a 20-120-fold increased risk to develop Non Hodgkin lymphoma (NHL). Since immunosuppressive therapy and immunological disorders are major risk factors for the development of NHL in the non-transplant population we aimed to analyze risk factors for PTLD in our cohort of liver transplanted (LT) patients.We analyzed retrospectively 431 patients liver transplanted between 1998 and 2008.PTLD was diagnosed in eleven of 431 patients (2.6%). PTLD, especially late PTLD, was significantly more frequent in patients who received steroids before LT (Kaplan-Meier: p0.001). Moreover PTLD in immunocompromised patients with preoperative steroid treatment occurred at a significantly younger age (49.5+/-4.7 years) compared to patients without steroids (60.6+/-5.1 years; p=0.006). Multivariate analysis revealed pretransplant steroid treatment and liver transplantation for autoimmune hepatitis as main risk factors for the development of PTLD after liver transplantation (p0.001).Liver transplanted patients who received steroids before LT due to immunological disorders and patients with autoimmune hepatitis seem to be at particular high risk to develop PTLD. Prospective cohort studies including immunoepidemiologic investigations of abnormalities of cellular, humoral and innate immunity should be carried out to identify predictive factors and patients at risk.

Background and study aim Endoscopic-ultrasound-guided elastography (EUS-elastography) is a recently introduced imaging procedure that distinguishes tissues on the basis of their specific consistency. The aim of this prospective study was to investigate the role of this new technique in the characterization and differentiation of focal pancreatic lesions. Patients and methods This prospective study enrolled 70 patients with unclassified solid lesions of the pancreas and 10 controls with a healthy pancreas. In all patients elastography recordings were compared with cytology/histology findings as the gold standard. Results Adequate EUS-elastography of the pancreas was performed in all healthy controls but in only 56 % of patients with solid pancreatic lesions. The main limitation of elastographic image acquisition was incomplete delineation of the border of lesions greater than 35 mm in diameter (39 %) or of lesions at some distance from the transducer (10 %). Elastographic recordings were also hampered by the fact that the surrounding tissue, which is used as an internal reference standard for strain calculation, was insufficiently displayed in the case of larger lesions. The reduced ratio of target to surrounding tissue resulted in the formation of color artifacts and in impaired reproducibility. In contrast, the majority of lesions smaller than 35 mm in diameter were adequately and reproducibly evaluated by EUS-elastography (91 %). The clinical use for differential diagnosis, however, seems limited, since strain images from all kinds of pancreatic masses were found to be harder than the surrounding tissues, irrespective of the underlying nature of the lesion (i. e., malignant vs. benign). EUS-elastography predicted the nature of pancreatic lesions with poor diagnostic sensitivity (41 %), specificity (53 %), and accuracy (45 %). Conclusion EUS-elastography of the pancreas has the potential to obtain some complementary information that would improve tissue characterization. Its clinical utility, however, remains questionable, and it seems unlikely that the information provided will obviate the necessity of obtaining tissue samples for confirmation of a final pathologic diagnosis.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Química Quando se trata da qualidade de seus produtos e da adequação destes às especificações de seus clientes, as empresas empregam e investem muito no controle de qualidade e melhoria contínua do processo. Neste contexto é que se encontra o teste de Edge Soaking, cujo objetivo é reproduzir em laboratório a absorção de água que ocorre nas bordas do cartão durante o envase. Este teste é realizado exclusivamente em cartões utilizados em embalagem de alimentos líquidos ou pastosos (LPB - Liquid Package Board). O método atualmente utilizado pela Klabin para determinação do Edge Soaking tem se mostrado pouco repetitivo e percebem-se variações significativas quando realizado por operadores diferentes. Desta forma, este trabalho teve como objetivo adequar e padronizar o teste de Edge Soaking visando sua utilização para controle de processo. A partir da avaliação do método existente, determinaram-se algumas variáveis que podem ser controladas para minimizar as variações de resultado, tais como: perfil de amostragem, temperatura e volume de água de cada banho e tempo de imersão das amostras. Além disso, foi desenvolvido um suporte específico para este teste visando auxiliar sua execução. Resultados dos testes realizados indicaram maior uniformidade e confiabilidade a cada etapa do desenvolvimento do suporte. O desvio padrão encontrado para a metodologia desenvolvida ainda indica que existe um erro sistemático, mas este é inferior ao erro do método atual. Durante o estudo foram avaliados diferentes tipos de cartões e diferentes gramaturas e concluiu-se que além da cura da cola, a gramatura do papel e a distribuição da cola são fatores que exercem influência na absorção de água. When the topic is about the quality of its products and of the adequacy of these to the specifications of its customers, the companies use and invests in the quality control and continuous improvement of the process. In this context is the test of Edge Soaking, whose objective is to reproduce in laboratory the water absorption that occurs in the edges of the card in the filling machine. This test is carried through exclusively in cartons used in liquid or gummy food packing (LPB - Liquid Package Board). The method currently used by Klabin for determination of the Edge Soaking has shown little repetitive and notices significant variations when carried through by different operators. In this form, this work had as objective to adjust and to standardize the test of Edge Soaking to be used to control the process. For the evaluation of the existing method, some variable had been determined to be controlled and to minimize the result variations: profile of sampling, temperature and volume of water of each bath and time of immersion of the samples. In addition, a specific support for this test was developed to simply its execution. Results of the tests had indicated more uniformity and more trustworthiness to each stage of the development of the support. The standard deviation found for the developed methodology still indicates that exist a systematic error, but this is smaller than the error of the current method. During the study different types of cartons and different basis weigh had been evaluated and concluded that beyond the cure of the glue, the basis weigh and the glue are factors that exert influence in the water absorption.

1407 TTR MUTATIONS IN GERMAN PATIENTS WITH FAMILIAL AMYLOID POLYNEUROPATHY Y. Avsar, T. Todorov, A. Zibert, I. Kabar, V. Cicinnati, S. Beckebaum, C. Roecken, A. Barreiros, H.H.-J. Schmidt. Department of Transplantation Medicine, University Hospital Munster, Munster, Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Department of Gastroenterology and Hepatology, Johannes Gutenberg University Mainz, Mainz, Germany E-mail: yesim.avsar@gmx.net