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Tilman Sauerbruch

Publications and source records attributed to Tilman Sauerbruch.

102 records · Page 6Linked to original sources
PubMed2002

Imbalanced intrahepatic expression of interleukin 12, interferon gamma, and interleukin 10 in fulminant hepatitis B.

In murine models, overexpression of interleukin (IL)-12 and interferon (IFN)-gamma can induce severe liver damage, whereas IL-10 has anti-inflammatory and hepatoprotective properties. To analyze the potential role of these cytokines in human fulminant hepatitis B, we used immunohistochemistry to study expression of IL-12, IFN-gamma, and IL-10 in explant livers of 11 patients with fulminant hepatitis B, 5 patients with fulminant hepatitis due to other etiologies, 37 patients with chronic liver disease (CLD; hepatitis B virus, n = 15; hepatitis C virus, n = 10; primary biliary cirrhosis, n = 12), and 10 normal controls (NCs). Furthermore, cytokine messenger RNA (mRNA) levels were determined in the liver specimens by quantitative real-time polymerase chain reaction (PCR). In NCs, faint IL-12 expression was detected in only a few Kupffer cells, whereas sinusoidal endothelial cells, hepatic stellate cells, bile ducts, and lymphocytes expressed IL-12 in CLD and, more conspicuously, in fulminant hepatitis B. In contrast, expression of IFN-gamma and IL-10 was restricted to lymphocytes and Kupffer cells, respectively. In fulminant hepatitis B, numbers of IL-12- and IFN-gamma-positive cells markedly exceeded those found in CLD and NCs. A close correlation existed between IL-12 and IFN-gamma expression (r = 0.68; P <.001). In contrast, IL-10 expression was not significantly different in CLD and fulminant hepatitis. The quantitative differences in immunohistologic cytokine expression closely corresponded to the mRNA levels. In conclusion, our data indicate massive induction of the proinflammatory cytokines IL-12 and IFN-gamma in fulminant hepatitis B, which is apparently not counterbalanced by the anti-inflammatory cytokine IL-10. This cytokine imbalance may play an important role in promoting inflammatory reactions leading to massive liver damage in fulminant hepatitis B.

Acute Disease↗
PubMed2002

Arylamine N-acetyltransferase type 2 and glutathione S-transferases M1 and T1 polymorphisms in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) exhibits a variable phenotype even in carriers of the same adenomatous polyposis coli germline mutation. Xenobiotic-metabolizing enzymes such as N-acetyltransferases (NATs) and glutathione S-transferases (GSTs) were reported to modify the individual risk for colorectal cancer. We examined whether the polymorphisms of the NAT2, GSTM1, and GSTT1 enzymes affect age at diagnosis of first colorectal adenomas or extracolonic manifestations in 411 FAP patients. Neither age at diagnosis of colorectal adenomas nor occurrence of extra-intestinal tumors differed significantly between genotypes at the NAT2 and GSTM1 loci, whereas GSTT1 polymorphism showed an uncertain association with extra-intestinal manifestations. Combinations of supposed at risk genotypes of the three enzymes showed no significant differences either. Thus, NAT2, GSTM1, or GSTT1 are unlikely to modify the disease phenotype in FAP patients.

Adenomatous Polyposis Coli↗
PubMed2002

Prospective evaluation of a clinical score for 60-day mortality after transjugular intrahepatic portosystemic stent-shunt: Bonn TIPSS early mortality analysis.

OBJECTIVE: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) is increasingly used to treat complications of portal hypertension, but proven tools for risk assessment of early mortality are lacking. DESIGN: The prospective evaluation of a new 60-day mortality score. PATIENTS AND METHODS: In a tertiary medical centre, 30 consecutive TIPSS patients were analysed for early mortality predictors, such as Child-Pugh score, TIPSS urgency (elective: > or = 36 h or emergency: < 36 h after variceal bleeding), comorbidity (Acute Physiology and Chronic Health Evaluation [APACHE]-II) and clinical data. Main predictors (P< 0.01) in this group (group-1: Child-Pugh score 10A, 10B, 10C) were graded (1, 2 or 3 points representing low, medium and high risk, respectively) and summarized as a Bonn TIPSS early mortality (BOTEM) score. This score was then tested prospectively in the next 73 TIPSS patients (group-2: Child-Pugh score 14A, 42B, 17C). RESULTS: Group 1 early mortality (30%) depended primarily on bilirubin (P< 0.005), APACHE-II (P < 0.001) and TIPSS urgency (P< 0.001). Added risk points (1, 2, 3) for bilirubin (< 3 mg/dl, 3-6 mg/dl, > 6 mg/dl, respectively), APACHE-II (< 10, 10-20, > 20 points, respectively) and urgency (elective, emergency, active bleeding, respectively) represented individual BOTEM score points. BOTEM was the best mortality predictor (P< 0.001); < or = / > 6 score points was the optimal cut-off, with 56% sensitivity, 100% specificity, 100% positive predictive value, 84% negative predictive value and 87% accuracy. In group 2, early mortality (8.2%) was again best predicted by BOTEM (P < 0.01) with the same cut-off and 67% sensitivity, 99% specificity, 80% positive predictive value, 97% negative predictive value and 96% accuracy. CONCLUSION: BOTEM score based on bilirubin, comorbidity and TIPSS-urgency predicts rather reliably post-TIPSS 60-day mortality and might optimize TIPSS treatment.

Aged↗
PubMed2002

Vanishing bile duct syndrome associated with elevated pancreatic enzymes after short-term administration of amoxicillin.

Amoxicillin is a widely used antibiotic, rarely being considered a cause of hepatic injury. We report the case of a 45-year-old woman who developed a vanishing bile duct syndrome 8 weeks after initiation of amoxicillin therapy. Liver biopsy showed destruction and loss of preformed bile ducts together with an inflammatory infiltrate involving eosinophilic leucocytes. Cholestasis was progressive despite prednisolone treatment and was accompanied by elevation of pancreatic enzymes. The patient died after 18 months from progressive liver failure. This case illustrates that amoxicillin alone can be a cause of progressive and ultimately fatal vanishing bile duct syndrome.

Amoxicillin↗
PubMed2002

Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid.

Ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency. Here, a possible link between these ratios and biliary secretion rates of cholesterol was investigated. Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones. Seven were treated with ursodeoxycholic acid (UDCA) (1,000 mg/d). Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers, who received either placebo or UDCA (750 mg/d). Biliary cholesterol secretion was significantly lower, whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA. A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed. In volunteers, administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios. Even 4 weeks after discontinuing UDCA administration, campesterol and sitosterol were still significantly higher than pretreatment levels, which was also true for the campesterol-cholesterol ratio after 8 weeks. The results suggest that the ratios of cholestanol, campesterol, and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates.

Adult↗
PubMed2002

Impact of the continuous infusion of Levovist on color Doppler sonography in portal hypertension.

OBJECTIVE: This study was undertaken to investigate to what extent continuous infusion of a galactose-based microbubble contrast agent (Levovist) allows evaluation of the portal vascular system in patients with portal hypertension and for whom baseline unenhanced color Doppler sonography was nondiagnostic. SUBJECTS AND METHODS: We performed color Doppler sonography at baseline and during IV Levovist infusion (4 g, 300 mg/min). First, we measured the duration of portal vein visualization during Levovist infusion in 15 patients in whom unenhanced color Doppler sonography failed to show the portal confluence from a subcostal view. This duration of improved portal conspicuity was termed "diagnostic window." We then compared in 30 patients enhanced color Doppler sonographic findings with conventional imaging methods, including portography (n = 14), helical CT (n = 4), or gadolinium-enhanced MR angiography (n = 12), and we recorded the investigator's confidence in the color Doppler sonographic result before and after Levovist infusion. RESULTS: The diagnostic window achieved by the Levovist infusion was 13.6 +/- 0.9 min. At baseline, color Doppler sonography was nondiagnostic in 19 patients. The diagnostic confidence level was low in all the remaining 11 patients. During Levovist infusion, color Doppler sonography remained nondiagnostic only in two of 30 patients. The confidence level was low in five patients and high in 23 patients. In 26 of these 28 patients, echo-enhanced color Doppler sonographic findings were confirmed by reference methods. CONCLUSION: The continuous infusion of Levovist achieved a sufficient echo enhancement from the portal vascular bed and allowed a valid diagnostic color Doppler sonographic examination in portal hypertensive patients for whom color Doppler sonography would otherwise be nondiagnostic.

Adult↗
PubMed2002

HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C.

AIM: Cytokine release by macrophages critically determines the type of immune response to an antigen. Therefore, we studied hepatitis C virus (HCV)-specific induction of interleukins-1 beta, -10, -12 (IL-1 beta, IL-10, IL-12), and tumor necrosis factor-alpha (TNF-alpha) in monocytes. METHODS: Intracellular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C, 14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear cells with recombinant core, NS3, NS4, NS5a and NS5b proteins. RESULTS: Patients with HCV viremia revealed greater spontaneous expression of IL-1beta, TNF-alpha, and IL-10. Furthermore, greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups (P<0.05). In contrast, neither IL-12 nor TNF-alpha was induced preferentially. CONCLUSION: In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction - not counterbalanced by antiviral type 1 cytokines. This may contribute to persistent viral replication.

Adult↗
PubMed2002

[Guidelines of the German Society of Gastroenterology for the treatment of gallstones].

The vast majority of gallbladder stones are cholesterol stones. The natural course taken by these stones is benign. Only patients with symptomatic gallstones require treatment, mostly in the form of laparoscopic cholecystectomy. Unlike gallstones, bile duct stones are treated during their symptomatic and asymptomatic stages. Endoscopic sphincterotomy is the treatment of choice for cholecystectomised patients. If patients have concomitant gallstones they should receive endoscopic sphincterotomy first (therapy splitting), at least according to the German consensus. Obstructive cholangitis should always be treated with endoscopic drainage procedures first.

Cholecystectomy↗
PubMed2002

Phospholipid autoantibodies and the antiphospholipid antibody syndrome: diagnostic accuracy of 23 methods studied by variation in ROC curves with number of clinical manifestations.

BACKGROUND: We analyzed the diagnostic accuracies for the diagnosis of antiphospholipid syndrome (APS) of 23 antiphospholipid antibody (APL-Ab) assays targeted at different antigen preparations and immunoglobulin isotypes. METHODS: In 144 patients with suspected APS, anti-cardiolipin (aCL) and anti-beta2-glycoprotein I (abeta2GPI) antibodies were measured with 23 different ELISAs from three manufacturers. Data were analyzed by ROC curves. In the absence of an accepted criterion standard, the endpoint "diagnosis of APS" was varied according to the number (two through five) of signs and symptoms of APS. RESULTS: Although the presence of lupus anticoagulant was associated significantly with APL-Ab in 10 of 23 assays (P = 0.01-10(-4)) and recurrent arterial or venous occlusions were significantly associated with APL-Ab of IgM isotype in 5 of 6 assays (P = 0.02-10(-4)), sensitivity for detection of APS did not exceed 67%. With the exception of IgA APL-Ab, the diagnostic accuracy of the assays improved when the diagnosis of APS was based on an increasing number of simultaneous features of APS. For most methods, areas under the ROC curves were >0.8 irrespective of the method's subclass specificity and antigen preparation (aCL or abeta2GPI), if the clinical diagnosis of APS was based on four or more signs and symptoms of APS. CONCLUSION: Despite considerable heterogeneity in the individual test results, a single test of IgG or IgM isotype targeted at either aCL or abeta2GPI antibodies has excellent diagnostic accuracy when the criterion for diagnosis requires four or more typical manifestations of APS.

Adult↗
PubMed2001

Generation of activated and antigen-specific T cells with cytotoxic activity after co-culture with dendritic cells.

Co-culturing of immunological effector cells with antigen-pulsed DC leads to an increase of cytotoxic activity against antigen-expressing tumour cells. Using this approach, we could detect up to 2.8% antigen-specific CTLs after co-culture with antigen-pulsed DC. However, the required high effector cell numbers remain a major obstacle in immunotherapy. In this study, we show an approach for generating activated and antigen-specific effector cells that enables us to decrease effector to target cell ratios. We used an interferon-gamma secretion assay to enrich activated effector cells after co-culture with antigen-pulsed dendritic cells (DC). Purified immunological effector cells lysed 58.3% of antigen-expressing tumour cells at an effector to target ratio of 1:1. Furthermore, using MHC-IgG complexes, we enriched effector cells expressing antigen-specific T-cell receptor after co-culture with DC. Performing ELISpot, flow cytometry and TCR analysis, we could show a significant increase of activated and specific TCR-expressing effector cells after co-culture with DC.

Antigen Presentation↗
PubMedDate not supplied

Prediction of glomerular filtration rate in renal transplant recipients: cystatin C or modification of diet in renal disease equation?

BACKGROUND: To overcome disadvantages of serum creatinine two strategies have been suggested to identify patients with reduced glomerular filtration rate (GFR). On the one hand, the Modification of Diet in Renal Disease (MDRD) equation is now recommended to classify the stage of chronic kidney disease. On the other hand, cystatin C (Cys C) has been investigated in numerous studies, finding a higher sensitivity than creatinine in detecting diminished GFR. To date, no comparison of both strategies in patients after renal transplantation has been performed. METHODS: One hundred and five consecutive renal transplant recipients underwent (99m)Tc-DTPA-- clearance measurement. Simultaneously, MDRD estimates were calculated and Cys C serum levels were determined. ROC analyses were performed at different decision points from 20 to 70 mL/min/1.73 m(2). RESULTS: Although the area under the curve did not differ significantly between MDRD and Cys C within the tested GFR range, the AUC for Cys C tended to be higher when GFR exceeded 55 mL/min/1.73 m(2). A significantly higher diagnostic accuracy for Cys C compared with MDRD (p = 0.045 at 65 mL/min/1.73 m(2)) was found when investigating the subgroup of patients with well-functioning grafts (GFR>40 mL/min/1.73 m(2)). CONCLUSION: MDRD equation is equivalent to Cys C measurement in renal transplant recipients. As availability of MDRD is superior to Cys C, we recommend GFR estimation using the MDRD equation. Nevertheless, Cys C may serve as a confirmation test of high MDRD estimates in patients with well-functioning grafts because of superior accuracy in these patients.

Adult↗