Objective: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated.Methods and results: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of immunodeficient Pfp/Rag2(-/-) mice with or without prior hepatocyte differentiation in vitro. Donor-derived human cells engrafted in the mouse host liver predominantly in the periportal region of the liver lobule. They expressed HepPar1 and albumin, typical features of differentiated human hepatocytes, in the otherwise negative mouse liver background. Engraftment was significantly more efficient using hAT-MSCs pre-differentiated to hepatocyte-like cells in vitro as compared with undifferentiated cells.Conclusions: Pre-differentiation of human MSCs from adipose tissue into hepatocyte-like cells in vitro facilitates long term functional hepatic integration in vivo.

BACKGROUND:The course of Crohn's disease prior to the establishment of the diagnosis is widely unknown. Therefore, we instigated a survey amongst newly diagnosed patients.PATIENTS AND METHODS:Patients diagnosed with CD less than 12 months before enrollment were included. Data on demography, social status, time interval to diagnosis, symptoms, and health care service use were collected in a retrospective, web-based, census. Patients were contacted in cooperation with two organizations: a German patients' organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung e.V. [DCCV]) and a professional organization of German gastroenterologists (Berufsverband der Niedergelassenen Gastroenterologen Deutschlands e.V. [bng]). Study participation was anonymous by use of a transaction number.RESULTS:The median interval period between onset of first symptoms and diagnosis was 13 months. During this time, participants reported having five doctor consultations on average, with 44% of them having a mean of 1.5 hospitalizations. 65% were unfit for work with a 14 day median (2 to 480 days) due to their symptoms. A mean (+/-SD) of 8.6 (+/-7.1) diagnostic tests were performed before the diagnosis was established. Overall health state was judged as temporarily bad or very bad by 84% of the participants. Age at diagnosis, characteristic symptoms, and localization of the disease for the participants did not differ from previously reported international data.DISCUSSION:This web-based survey shows a substantial time interval of over one year until diagnosis of Crohn's disease amongst the study participants. This period is characterized by both psychological stress and impaired ability to work.

BACKGROUND:Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma.PATIENTS AND METHODS:A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle.RESULTS:Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial.CONCLUSION:Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Lebererkrankungen sind in Deutschland die häufigste krankheitsbedingte Todesursache unter den 30- bis 45-Jährigen. Sie verlaufen meist chronisch; rechtzeitige Präventiv- und Therapiemaßnahmen könnten manifeste Erkrankungen oder zumindest Folgeschäden vermeiden. Die derzeitige Frühdiagnostik konzentriert sich auf krankheitsspezifische Risikogruppen wie Patienten mit Alkoholabusus, Verwandte eines Patienten mit einer genetischen Erkrankung oder hepatitisinfektionsgefährdete Personen. Für einige Erkrankungen laufen aber bereits Studien, die die Praktikabilität eines Screenings größerer Bevölkerungsgruppen testen. Erfolgreich angewandt wird heute schon das Screening für Hepatitis B und C bei Blutspendern. Auch bei fortgeschrittenen Lebererkrankungen wird eine Frühdiagnostik empfohlen: hier dient sie der Früherkennung der Zirrhose und ihrer Komplikationen wie Varizen und hepatozelluläres Karzinom.

History and clinical findings: In a 39-year-old man with increasing spasmodic epigastric pain, nausea and vomiting, varices of the esophagus and the gastric fundus were found endoscopically.Investigations: A portal vein thrombosis and a consecutive thrombosis of the splenic vein were diagnosed by colour dopplersonography and angio CT. A protein S deficiency (59%) was found to be the underlying illness.Treatment and course: The thrombosis and the resulting clinical symptoms completely resolved shortly after starting therapeutic heparinization. For six months, the patient has been without complaints or clinical symptoms.Conclusion: Hence, an isolated protein S deficiency can be the cause for a portal vein thrombosis.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Konsens Eine Hepatitis ist eine Entzundung der Leber, die durch eine variable Kombination von rundzelliger, vorwiegend lymphozytarer entzundlicher Infiltration, hepatozellularer Schadigung sowie Regeneration der Hepatozyten charakterisiert wird. Die morphologischen Kriterien der Chronizitat sind eine portale Pradominanz der entzundungszelligen Infiltration und jeweils fakultativ eine portale Faservermehrung und die so genannte Grenzzonen-(„Interface“-)Hepatitis (Empfehlungsklasse* B).1 Erlauterung Die Definition beinhaltet die Aussage, dass unabhangig von der klinischen und serologischen Konstellation die Diagnose einer Hepatitis (d. h. manifesten Leberentzundung) nur dann zu stellen ist, wenn ein hepatozellularer Zellschaden oder zumindest eine adaquate entzundungszellige Infiltration nachweisbar ist. Der alleinige Nachweis viraler Nukleinsauren oder Antigene sichert lediglich die virale Infektion, ist jedoch fur die Diagnose einer Hepatitis nicht ausreichend. Andererseits kann histologisch durchaus die Diagnose einer chronischen Hepatitis auch bei normwertigen oder nahezu normwertigen Serumwerten (Aminotransferasen; insbesondere bei chronischer Hepatitis C) gestellt werden. Ferner kann eine Hepatitis nur dann diagnostiziert werden, wenn der hepatozellular-schadigende Charakter der Entzundung im Vordergrund steht. Entzundungen, die vorwiegend andere Leberstrukturen betreffen (z. B. Gallengange, Gefase), sollten auch beim Vorliegen einer geringergradigen hepatozellular-schadigenden Komponente nicht als Hepatitis bezeichnet werden. Zur Frage der Chronizitat s. unten.

Background: Data regarding the prevalence of SBP in patients with ascites or the diagnostic and therapeutic management of SBP in Germany are lacking.Patients and methods: In a multicenter study (40 hospitals), retrospective, then prospective data were collected investigating the prevalence of SBP in patients with ascites and the pertinent diagnostic and therapeutic management. In 272 prospectively entered patients with ascites (cirrhosis/malignant ascites/other: n = 227/42/ 3) a diagnostic paracentesis was performed and SBP diagnosed using the ascitic neutrophil count. History, clinical symptoms and laboratory findings were recorded and potential risk factors analysed by univariate analysis and stepwise logistic regression. SBP was treated with a standard dose of a third-generation cephalosporin.Results: In the retrospective study, SBP was diagnosed in 648 of 4,697 patients with ascites (14%). Employed diagnostic and therapeutic pathways were not effective in several hospital departments. In the prospective trial, SBP was found in 134 of 272 patients with ascites (49,3%). Frequency of symptoms was significantly different in patients either with or without SBP, as were macroscopic aspect of ascites, urine excretion and several biochemical parameters. However, their diagnostic precision was unsatisfactory. Predictive factors for SBP were previous paracentesis, endoscopic procedures and a history of abdominal pain. Treatment was effective in 83,5% of cases. Inhospital mortality was 10%.Conclusion: The prevalence of SBP in hospitalised patients with ascites in Germany is similar to that in southern Europe and USA. Symptoms alone lack sufficient diagnostic accuracy. Third-generation cephalosporin is an effective antibiotic in SBP. Pertinent diagnostic and therapeutic management calls for improvement.

HISTORY AND CLINICAL FINDINGS:In a 39-year-old man with increasing spasmodic epigastric pain, nausea and vomiting, varices of the esophagus and the gastric fundus were found endoscopically.INVESTIGATIONS:A portal vein thrombosis and a consecutive thrombosis of the splenic vein were diagnosed by colour Doppler sonography and angio CT. A protein S deficiency (59 %) was found to be the underlying illness.TREATMENT AND COURSE:The thrombosis and the resulting clinical symptoms completely resolved shortly after starting therapeutic heparinization. For six months, the patient has been without complaints or clinical symptoms.CONCLUSION:Hence, an isolated protein S deficiency can be the cause for a portal vein thrombosis.

Es ist von Ärzten, namentlich Funktionären der ärztlichen Selbstverwaltung, aber auch von Präsidenten wissenschaftlicher Fachgesellschaften so viel Kluges und auch weniger Inspiriertes über die stürmischen Zeiten und die unberechenbare Gesundheitspolitik gesprochen und geschrieben worden, dass es mir müßig erscheint, in dieses vielchörige Lamento einzufallen: Eine neue Stimme dazu gibt es ohnehin nicht mehr. Es wäre höchstens darauf hinzuweisen, dass es neben der Politik auch Patienten, Ärzte und hochverwaltete Krankenkassen waren und noch sind, die dieses wenig sturmfeste, planwirtschaftliche Gesundheitssystem durch Ansprüche und Hypochondrie und durch eine seltsame Mischung aus Maximalversorgungsdenken, Halbwissen, (notwendigem) Gewinnstreben und ausufernder Bürokratie in den Ruin treiben. Nur durch diese groteske Gemengelage ist es möglich, dass einerseits zur Abklärung einer Transaminasenerhöhung zugewiesene Patienten anstandslos vergütete CTs und MRTs mitbringen und andererseits Krankenkassen die Übernahme der Kosten von in Studien als wirksam erwiesenen, aber nebenwirkungsarmen und damit nicht rezeptpflichtigen Medikamenten ablehnen können. Zu meinen, dieses System könnte u. a. durch Abschreckung vor dem Arztberuf durch einen weiteren Zuwachs an nichtärztlicher Tätigkeit und schlechte Bezahlung nachhaltig saniert werden, ist zynisch und dumm.

Die konstituierende Sitzung der Arbeitsgruppe fand am 6.9.2001 im Universitätsklinikum Frankfurt/Main statt. Auf dem zweiten Treffen am 11.3.2002 während des 25. Deutschen Krebskongresses in Berlin wurden die Herren Blum (Freiburg), Fleig (Halle/Saale), Gregor (Tübingen), Oettle (Berlin) sowie vor seinem Wechsel nach Salzburg Herr Berr aus Leipzig als Mitglieder der Leitgruppe gewählt. Gegenwärtiger Sprecher der Arbeitsgruppe ist Herr Prof. Dr. W. E. Fleig. Seit ihrer Gründung hat die Arbeitsgruppe bisher in halbjährlichen Abständen getagt.

BACKGROUND:Data regarding the prevalence of SBP in patients with ascites or the diagnostic and therapeutic management of SBP in Germany are lacking.PATIENTS AND METHODS:In a multicenter study (40 hospitals), retrospective, then prospective data were collected investigating the prevalence of SBP in patients with ascites and the pertinent diagnostic and therapeutic management. In 272 prospectively entered patients with ascites (cirrhosis/malignant ascites/other: n = 227/42/3) a diagnostic paracentesis was performed and SBP diagnosed using the ascitic neutrophil count. History, clinical symptoms and laboratory findings were recorded and potential risk factors analysed by univariate analysis and stepwise logistic regression. SBP was treated with a standard dose of a third-generation cephalosporin.RESULTS:In the retrospective study, SBP was diagnosed in 648 of 4,697 patients with ascites (14 %). Employed diagnostic and therapeutic pathways were not effective in several hospital departments. In the prospective trial, SBP was found in 134 of 272 patients with ascites (49,3 %). Frequency of symptoms was significantly different in patients either with or without SBP, as were macroscopic aspect of ascites, urine excretion and several biochemical parameters. However, their diagnostic precision was unsatisfactory. Predictive factors for SBP were previous paracentesis, endoscopic procedures and a history of abdominal pain. Treatment was effective in 83,5 % of cases. Inhospital mortality was 10 %.CONCLUSION:The prevalence of SBP in hospitalised patients with ascites in Germany is similar to that in southern Europe and USA. Symptoms alone lack sufficient diagnostic accuracy. Third-generation cephalosporin is an effective antibiotic in SBP. Pertinent diagnostic and therapeutic management calls for improvement.

Diagnostik und Therapie der oberen gastrointestinalen Blutung sind interdisziplinär. Bei bewusstseinsgetrübten Patienten wird eine Aspiration durch frühzeitige Intubation vermieden. Bei der Notfallendoskopie verbessert die Gabe von Erythromycin 20 min vor dem Eingriff die Sicht.

Upper gastrointestinal hemorrhage calls for a team approach. Early endotracheal intubation of unconscious patients helps to prevent aspiration. Erythromycin i.v. 20 min. before emergency endoscopy improves the diagnostic yield. Patients without increased risk of rebleeding may be treated on an outpatient basis. Band ligation is the gold standard for acute variceal bleeding. Terlipressin, somatostatin and octreotide are equally effective but require additional measures for prevention of late recurrence. Somatostatin and analogues used as adjunct to ligation slightly reduce the risk of rebleeding but not of death. Three to seven days of prophylactic antibiotics decrease the risk of uncontrolled or recurrent bleeding. Therapeutic failures are rescued by transjugular intrahepatic portosystemic shunting (TIPS). Patients with nonvaricose bleeding should only be treated when active hemorrhage or a "visible vessel" is found. First line treatment is endoscopic injection of diluted adrenalin or isotonic saline. Thermal coagulation is an alternative. Tissue-destructing sclerosants should be avoided. Clipping and injection of fibrin glue are second and third line measures. Proton pump inhibitors improve endoscopic hemostasis, however, it is unclear whether high i.v. doses are required. H. pylori must be eradicated to prevent late recurrence. Rebleeding is treated endoscopically with angiographic intervention or surgery as rescue measures.