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Biomedical subjects

C Trautwein

Publications and source records attributed to C Trautwein.

At least 19 recordsLinked to original sources
PubMed2006

[Elevated concentrations of fecal calprotectin in patients with liver cirrhosis].

UNLABELLED: BACKGROUND AND OBJECTION: Bacterial translocation from the gut lumen is considered to play an important role in the development of infectious complications in patients with liver cirrhosis. This translocation might be increased by inflammation of the gut mucosa. Calprotectin is a cytoplasmatic protein of neutrophilic granulocytes and is an established marker for the assessment of localized intestinal inflammation. It was the aim of the current study to systematically evaluate a localized intestinal inflammation in patients with liver cirrhosis by means of fecal calprotectin concentrations. PATIENTS AND METHODS: Fecal calprotectin concentrations were determined in 53 consecutive patients with liver cirrhosis and in 18 subjects without intestinal or liver diseases, who were comparable with respect to age and gender. Patients with diarrhoea, inflammatory bowel disease and a positive stool test for occult blood were excluded from the study. Fecal calprotectin concentrations were measured by a sandwich ELISA. The systemic inflammatory reaction of the patients was assessed by C-reactive protein, white blood cells counts and the serum concentrations of the cytokines IL-6, IL-8 and IL-10. RESULTS: Fecal calprotectin concentrations were significantly increased in patients with liver cirrhosis (median 37.0 mg/kg) compared to controls patients (median 2.2, P < 0.0001). There were no significant correlations of calprotectin concentrations with systemic inflammatory parameters, like CRP, white blood cell count or serum cytokines. However, fecal calprotectin concentrations were significantly associated with the stage of liver cirrhosis as expressed by the Child-Pugh score ( P < 0.001). A trend towards higher concentrations of calprotectin was found in patients with alcoholic liver cirrhosis ( P = 0.1). CONCLUSIONS: Patients with liver cirrhosis display elevated fecal calprotectin concentrations as a potential sign of intestinal inflammation. Further studies are warranted to establish a role of calprotectin for the risk assessment of infectious complications secondary to bacterial translocation in patients with liver cirrhosis.

Adult↗
PubMed2006

[Therapy of hepatitis B virus infection].

In the last years there was a continuous improvement in the therapy of hepatitis B virus infection. Meanwhile different therapeutic options are available. Therefore the indication for the different treatment options can be chosen dependent on clinical, biochemical, virological and histological parameters. Therapy with interferon alpha or PEG-interferon alpha should be started if positive prognostic parameters and lack of contraindications are present in a patient. Especially therapy with PEG-interferon alpha in recent studies showed good response rates. As an alternative nucleosides/nucleotides like lamivudine, adefovir or entecavir are available. During lamivudine therapy there is an increased risk for the selection of resistant strains, while the selection of resistant strains is less frequent during the medication of adefovir or entecavir. However at present the end of treatment for all nucleosides/nucleotides--especially in HBeAg negative patients--is not clearly defined. In patients with liver cirrhosis (Child B and C) only nucleos(t)ides should be used. In the future combination therapy for the treatment of chronic HBV infection seems very attractive. However at present combination therapy is not approved yet and therefore these options should only be used in clinical studies. Especially, as it seems possible that synergistic, but also antagonistic effects may exist between different drugs.

Adenine↗
PubMed2006

Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10 % of patients. Cholangiography or endoscopic tissue sampling does not reliably distinguish between cholangiocarcinoma and a benign dominant bile duct stenosis. The aim of the present study was to assess the value of cholangioscopy for distinguishing between benign and malignant dominant stenoses in PSC patients. PATIENTS AND METHODS: Fifty-three PSC patients with dominant bile duct stenoses were prospectively studied. Transpapillary cholangioscopy and endoscopic tissue sampling were carried out in addition to endoscopic retrograde cholangiography (ERC). The cholangiography and cholangioscopic findings were classified as malignant or benign by the investigators. A final diagnosis of malignant stenosis was based on positive histology and/or cytology, whereas a benign condition was assumed in cases of negative tissue sampling and uneventful extended clinical follow-up. RESULTS: Twelve PSC patients (23 %) had dominant bile duct stenoses caused by cholangiocarcinoma, whereas 41 of the 53 patients (77 %) had benign dominant bile duct stenoses. Cholangioscopy was significantly superior to ERC for detecting malignancy in terms of its sensitivity (92 % vs. 66 %; P = 0.25), specificity (93 % vs. 51 %; P < 0.001), accuracy (93 % vs. 55 %; P < 0.001), positive predictive value (79 % vs. 29 %; P < 0.001), and negative predictive value (97 % vs. 84 %; P < 0.001). Transpapillary cholangioscopy is more sensitive and specific for characterizing malignant bile duct stenosis in comparison with endoscopic brush cytology. CONCLUSIONS: Transpapillary cholangioscopy significantly increases the ability to distinguish between malignant and benign dominant bile duct stenoses in patients with PSC.

Adolescent↗
PubMed2006

[Severe drug hepatitis caused by Chelidonium].

We report the case of a 58-year-old male patient who was admitted with severe acute cholestatic hepatitis. Liver biopsy showed signs of drug-induced hepatitis. Other causes of acute hepatitis were excluded. Therefore, the ingestion of a Chelidonium-containing preparation (celandine) was thought to be responsible for the hepatitis. Shortly after stopping the administration of Chelidonium, the highly pathological levels of several liver parameters began to normalise. As no autoantibodies were detectable, an idiosyncratic reaction as the cause of drug-induced hepatitis is probable. In cases of unknown hepatitis, herbal medications should be taken into account as a possible cause.

Chelidonium↗
PubMed2005

CREB/PKA sensitive signalling pathways activate and maintain expression levels of the hepatitis B virus pre-S2/S promoter.

BACKGROUND AND AIMS: CREB (cAMP response element binding protein) transcription factors are key regulators of homeostatic functions in the liver, and CRE binding is increased in hepatic inflammation. During chronic hepatitis B virus (HBV) infection, mutations or deletions in the pre-S region are frequently observed. These mutations can affect the pre-S2/S promoter controlling HBV envelope protein expression (hepatitis B surface antigen (HBsAg)) and have been associated with worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg expression. METHODS: The effect of the CREB inducer protein kinase A (PKA) was tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter gene constructs were cloned to identify novel regulatory regions for the HBV pre-S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and supershift experiments were conducted to confirm DNA transcription factor binding. RESULTS: Coexpression of HBV and PKA resulted in HBV-S mRNA induction and enhanced small envelope protein expression. We identified a CREB binding motif in the transcribed part of the pre-S2 region, contributing to basal S promoter activity via binding of activating transcription factor 2 (ATF2). A second CREB motif closely linked to the S-ATG showed a similar binding pattern involving ATF2 and CREB1, without appearing essential for basal promoter activity. Moreover, a sequence in the pre-S2 region is responsible for further transcriptional induction via CREB activators such as PKA and forskolin. EMSA experiments indicate that CREB1 and ATF4 are involved in complex formation conferring PKA dependent promoter activation. CONCLUSIONS: Our data suggest a novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of hepatocytes to enhance its HBsAg expression during homeostasis and hepatic inflammation.

Activating Transcription Factor 2↗
PubMed2005

Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1.

BACKGROUND AND AIMS: Transforming growth factor beta1 (TGF-beta1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-beta1. METHODS: MC were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (SCF) with or without TGF-beta1. Growth characteristics, phenotype, and immunological mediator release of MC were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. RESULTS: TGF-beta1 dose dependently (ED50 approximately = 0.1 ng/ml) inhibited SCF dependent growth of human intestinal MC by both enhancing apoptosis and decreasing proliferation. In parallel, TGF-beta1 increased the percentage of connective tissue-type MC expressing tryptase and chymase while downregulating expression of the receptors for IgE and SCF. Furthermore, TGF-beta1 dramatically changed the profile of mediators released by MC following IgE receptor crosslinking. Release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor alpha was strongly reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression were upregulated by TGF-beta1. CONCLUSIONS: Our data indicate that TGF-beta1 acts as a novel potent inhibitor and modulator of human intestinal MC effector functions. The change in MC mediator release profile and protease expression induced by TGF-beta1 might be of relevance for the control of MC associated disorders of the intestine such as allergic reactions, Crohn's disease, irritable bowel syndrome, and parasitic infection.

Apoptosis↗
PubMed2005

Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake.

BACKGROUND AND AIMS: Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces apoptosis in transformed cells and is considered as an agent for cancer therapy. As there is evidence that TRAIL is also essential for apoptosis in animal models of liver injury, we investigated the role of TRAIL in viral hepatitis and after alcohol consumption. METHODS: Expression of TRAIL was determined by western blot analysis in the liver of patients with chronic hepatitis C virus (HCV) infection as well as in experimental acute adenoviral hepatitis and after alcohol intake in the liver of mice. To investigate the effect of FasL and TRAIL expression, we used low dose adenoviral gene transfer. Apoptosis and steatosis were assessed by TUNEL and fat red staining, and by caspase assays. RESULTS: TRAIL was overexpressed in the liver of patients with HCV associated steatosis while acute adenoviral hepatitis resulted in upregulation of TRAIL-DR5. In contrast with FasL, TRAIL expression was harmless to healthy livers. However, in virally infected livers, TRAIL expression induced apoptosis and steatosis whereas expression of FasL only resulted in apoptosis of hepatocytes without steatosis. After alcohol intake, TRAIL expression led to hepatic steatosis, without apoptosis of hepatocytes, indicating that TRAIL mediated apoptosis and steatosis may be independently modulated after viral infection and alcohol intake. In viral hepatitis and after alcohol intake, Ad-TRAIL mediated steatosis can be inhibited by injection of a neutralising TRAIL antibody. CONCLUSIONS: We identified TRAIL as a new mediator of hepatic steatosis in viral hepatitis and after alcohol intake. Consequently, TRAIL mediated hepatotoxicity has to be considered in patients with viral hepatitis and alcoholic liver disease.

Alcohol Drinking↗
PubMed2004

[Encoding of diagnosis by medical documentation assistant or ward physician. Influence on the mapping of Diagnostic Related Group (DRG) performance].

BACKGROUND AND OBJECTIVE: Starting in 2004 the patient budget in Germany will be calculated according to the Diagnosis Related Group (DRG) system, by which system the monetary reward of a unit will be directly related to the quality of documentation e. g. diagnosis and procedures. The aim of this study was to compare the quality of documentation by a medical documentation assistant (MDA) with the usual practice of documentation by the ward physician (WP). Additionally, the effect of introducing a completely changed organizational process was tested. METHODS: In a prospective study on the ward of a gastroenterology unit two different approaches of medical documentation were compared. In a first six-month period diagnosis and procedures were encoded by WP. In the following six months an MDA was introduced and involved in the encoding process. RESULTS: In the first six months 221 patients (mean age 55 +/- 16,2 years, 55,7 % males) were evaluated, whereas in the following six months 305 patients (mean age 53 +/- 15,4 years, 59,9 % males) were included. The introduction of an MDA improved medical documentation and economical reference numbers: with an increase of diagnosis per case to 7,43 (in first six months 5,53), patient complexity and comorbidity level (PCCL) to 2,5 (in first six months 2,13), case-mix index to 1,04 (in first six months 0,98). Additionally the medial hospitalization time decreased from 11,2 to 8,1 days. The average daily reimbursement increased in the MDA group from 423 Euro to 603 Euro. This was calculated on the basis of a basic case factor of 2900 Euro. CONCLUSION: Introduction of an MDA in a gastroenterology ward increases the quality of documentation and results in an improved presentation of DRG-relevant efforts with a better reimbursement of medical costs.

Budgets↗
PubMed2004

Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated.

INTRODUCTION: Lamivudine is a treatment option for the therapy of chronic hepatitis B with an excellent safety profile. Unfortunately, viral resistance to lamivudine is common in the course of therapy. The lamivudine resistant mutants are usually less pathogenic than the wild type, but development of viral resistance can also lead to acute exacerbation of the underlying hepatitis. The recently FDA approved nucleoside analogue adefovir dipivoxil has potent antiviral activity against lamivudine-resistant mutants and can prevent viral replication effectively. CASE REPORT: A 31-year-old man with pre-existing compensated liver cirrhosis developed resistance to lamivudine therapy leading to subacute liver failure. After referral adefovir dipivoxil 10 mg daily was initiated within an early access protocol. Since initiating therapy with adefovir dipivoxil progression of the subacute liver failure was delayed accompanied by a rapid decrease of ALT and decline of HBV viral load. Even so, the clinical course was not reverted but showed slower deterioration. This enabled the patient to undergo living-related liver transplantation. Adefovir dipivoxil was well tolerated in the acute phase of the disease and did not cause nephrotoxicity or favour the development of hepatorenal syndrome. CONCLUSION: Adefovir dipivoxil resulted in a delay of hepatic decompensation and enabled liver transplantation as final treatment option for this patient. Earlier initiation might even have prevented the need of liver transplantation. Thus, in patients with pre-existing liver cirrhosis an early switch to adefovir dipivoxil appears indicated after emergence of lamivudine resistance.

Adenine↗
PubMed2004

Analysis of factors contributing to higher erythropoietin levels in patients with chronic liver disease.

BACKGROUND: Dysregulated erythropoietin (EPO) plasma levels may play a role in the pathophysiology of chronic liver disease (CLD) because chronic anaemia is frequently observed in patients with liver cirrhosis. We aimed to identify the factors contributing to EPO regulation in patients with CLD. METHODS: Plasma EPO concentrations were correlated with clinical and laboratory parameters in 111 CLD patients and 220 healthy controls. RESULTS: Anaemia, though generally mild, was common in CLD patients, and thrombocytopenia and previous bleeding episodes were observed in two-thirds of the patients. Plasma EPO levels were significantly elevated in CLD patients (P < 0.001). EPO increased according to Child's stages of cirrhosis, independently of the aetiology of CLD. EPO correlated with haemoglobin (r= -0.498, P < 0.001). Additionally, EPO independently correlated with markers of liver dysfunction, e.g. prothrombin time, albumin concentration or cholinesterase activity, and platelet count. EPO was also significantly elevated in patients with a current bleeding tendency and with prior gastrointestinal haemorrhages. EPO levels were increased in patients with impaired pulmonary function, e.g. decreased diffusion capacity, vital capacity or hyperventilation. Interestingly, plasma interleukin-6 (IL-6) concentrations positively correlated with EPO (r=0.277, P = 0.003), suggesting a possible mechanism of EPO upregulation in patients with CLD through IL-6 dependent pathways, e.g. binding of STAT transcription factors in the putative EPO promoter region. CONCLUSIONS: EPO is upregulated in patients with chronic liver diseases in response to anaemia, bleeding complications, impaired pulmonary function, thrombocytopenia and liver dysfunction. IL-6 dependent pathways could be involved in mediating elevated EPO levels in CLD patients.

Adolescent↗
PubMed2004

Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo.

BACKGROUND: Interleukin 18 (IL-18) is a cytokine with pleiotropic activity that augments T helper 1 responses and cytotoxic activity of natural killer cells. METHODS: To assess the function of IL-18 in vivo, we generated IL-18 transgenic (IL-18 Tg) mice under the control of a CD2 promoter/enhancer construct. RESULTS: Macroscopically, IL-18 Tg mice showed reduced relative liver weight compared with wild-type littermates. TUNEL assays demonstrated increased hepatocyte apoptosis, and primary hepatocytes isolated from IL-18 Tg mice exhibited an increased spontaneous apoptosis rate. Furthermore, cross linking of Fas increased significantly the apoptosis rate in hepatocytes isolated from wild- type mice but to a much lesser extent in IL-18 Tg mice, suggesting spontaneous activation of the Fas pathway in the latter mice. In fact, in vivo blockade of Fas signal transduction by an adenovirus overexpressing the dominant negative form of the Fas associated death domain rescued hepatocytes from undergoing apoptosis. Finally, adoptive transfer of CD4(+) T cells from IL-18 Tg mice but not from wild-type littermates in SCID mice resulted in severe liver failure with massive periportal fibrosis due to hepatocyte apoptosis. CONCLUSION: IL-18 plays a fundamental role in regulating hepatocyte apoptosis. Furthermore, our transgenic model provides a novel tool to study the mechanisms of IL-18 dependent liver injury in vivo.

Adoptive Transfer↗
PubMed2002

[Therapy of chronic hepatitis B infection].

Around 350 million people worldwide are chronically infected with the hepatitis B virus. In adults around 5% and during perinatal contact around 100% of the infections become chronic. The main complications of chronic HBV infection are liver cirrhosis and hepatocellular carcinoma. Therefore after chronic HBV infection has been diagnosed early therapy has to be considered. At present two drugs are available: Interferon-alpha and lamivudine. Therapy with Interferon-alpha is successful in 30-40% of the patients. In contrast, the initial response rate during lamivudine therapy is very good. However, in many of the patients mutant HBV strains are selected. Therefore in each patient it has to be considered individually which of the two drugs should be used. In this review these questions will be addressed and a special focus will be the use of lamivudine. Additionally future treatment options will be discussed.

Adult↗
PubMed2002

A patient with autoimmune hepatitis type I, Addison's disease, atrophic thyroiditis, atrophic gastritis, exocrine pancreatic insufficiency, and heterozygous alpha1-antitrypsin deficiency.

This report describes a 60-yr-old white male presenting with decompensated liver cirrhosis. He had a history of Addison's disease for 36 yr, primary hypothyroidism for 5 yr, and moderate alcohol consumption. His laboratory studies and a liver biopsy supported the diagnosis of autoimmune hepatitis. Furthermore, he was found to be heterozygous for the piZ allele of the alpha1-antitrypsin gene with normal serum alpha1-antitrypsin levels and absence of pulmonary affection. Mucosal biopsies revealed moderately severe atrophic gastritis; however, signs of pernicious anemia were missing. An association of autoimmune hepatitis with endocrine disorders and atrophic gastritis has been described. Long term hydrocortisone therapy for his adrenal insufficiency may have prevented a faster course of the liver disease, whereas the heterozygous alpha1-antitrypsin deficiency and moderate alcohol consumption constituted additional risk factors ultimately leading to the development of cirrhosis.

Addison Disease↗
PubMed2001

Treatment of acute hepatitis C with interferon alfa-2b.

BACKGROUND: In people who are infected with the hepatitis C virus (HCV) chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection. METHODS: Between 1998 and 2001, we identified 44 patients throughout Germany who had acute hepatitis C. Patients received 5 million U of interferon alfa-2b subcutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. RESULTS: The mean age of the 44 patients was 36 years; 25 were women. Nine became infected with HCV through intravenous drug use, 14 through a needle-stick injury, 7 through medical procedures, and 10 through sexual contact; the mode of infection could not be determined in 4. The average time from infection to the first signs or symptoms of hepatitis was 54 days, and the average time from infection until the start of therapy was 89 days. At the end of both therapy and follow-up, 43 patients (98 percent) had undetectable levels of HCV RNA in serum and normal serum alanine aminotransferase levels. Levels of HCV RNA became undetectable after an average of 3.2 weeks of treatment. Therapy was well tolerated in all but one patient, who stopped therapy after 12 weeks because of side effects. CONCLUSIONS: Treatment of acute hepatitis C with interferon alfa-2b prevents chronic infection.

Acute Disease↗