Is endoscopic variceal band ligation more effective than propranolol for the prevention of esophageal hemorrhage?
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Comment↗
Biomedical subjects
Tilman Sauerbruch
Publications and source records attributed to Tilman Sauerbruch.
Pitfalls in the diagnosis of intestinal tuberculosis: a case report.
An 18-year-old long-term Norwegian resident of Somali origin was submitted to hospital with bloody diarrhoea, fever, weight loss and abdominal pain. On initial colonoscopy, colitis with segmental appearance was seen. Apart from a single polymerase chain reaction (PCR) from gastric aspirate staining, PCR and culture for acid-fast bacilli revealed negative results from the multiple samples taken including sputum, gastric fluid, stool, urine and intestinal mucosa. On physical examination and CT scan, there was no evidence of ascites, lymph node enlargement or pathologic pulmonary findings. Although the diagnosis was uncertain, tuberculostatic therapy was initiated. As the conformational testing of the PCR and the microbiological work-up remained negative and the patient's condition did not improve, tuberculostatic treatment was stopped and Crohn's disease was stated as the most likely diagnosis. Although the patient improved clinically under therapy with prednisolone, newly appearing fistulas deriving from the ascending colon were noted on follow-up. Thus tuberculostatic treatment was restarted. However, signs of an acute abdomen appeared and laparotomy was performed, thereby revealing a peritoneal spread of nodules. Resection of the ileum and ascending colon was performed. Diagnosis of intestinal tuberculosis with peritoneal spread was made by histology from resected bowel specimens showing caseating granulomas and a positive PCR result. The patient's condition improved after resection of the highly inflamed bowel segments and tuberculostatic therapy. Our case report shows the difficulty of proving intestinal tuberculosis by microbiological testing, macroscopic features on colonoscopy, histology, imaging such as CT scan and by empirical therapy. Therefore, in cases of colonic inflammation, where intestinal tuberculosis is an important differential diagnosis, a more aggressive diagnostic approach such as explorative laparoscopy should be considered.
Adolescent↗
Postinfantile giant cell hepatitis with autoimmune features following a human herpesvirus 6-induced adverse drug reaction.
Giant cell hepatitis (GCH) is frequently found in neonates, but rarely in adults. Diagnosis is made on the basis of the presence of hepatocellular multinucleate giant cells. The disease often takes a fulminant course with the development of cirrhosis within months, requiring transplantation or leading to death in a high percentage of cases. The aetiology and pathogenesis are unclear. Association with autoimmune disorders, viral infections and drug reactions, but also with congenital metabolic diseases such as alpha1-antitrypsin deficiency or haemosiderosis has been described. In some cases, no causative event has been found. Therefore, therapeutic options are controversially discussed. We present a patient with GCH with autoimmune features after a human herpesvirus 6 (HHV6)-induced adverse drug reaction, a combination that has not been reported before. High-dose immunosuppression led to dramatic improvements over the past year.
Adolescent↗
Vascular, hemodynamic and renal effects of low-dose losartan in rats with secondary biliary cirrhosis.
BACKGROUND: In cirrhosis, splanchnic and systemic vasodilatation induce a hyperdynamic circulatory dysfunction, portal hypertension and renal sodium retention. This vasodilatation is in part because of an impaired vascular response to alpha1-adrenoceptor agonists. Recently, the angiotensin II type 1-receptor antagonist losartan has been shown to attenuate portal hypertension. We hypothesized that losartan decreases portal pressure by counteracting the impaired vascular responsive to alpha1-adrenoceptor agonists. METHODS: We studied, in rats with secondary biliary cirrhosis and sham-operated rats, the effect of 0.5 and 10 mg losartan/kg x day on aortic responsiveness to alpha1-adrenoceptor stimulation with methoxamine and angiotensin II (myograph), splanchnic and systemic hemodynamics (colored microspheres), plasma noradrenaline levels and kidney function. RESULTS: In cirrhotic rats, 10 mg losartan/kg x day completely inhibited aortic contractility to angiotensin II, decreased vascular resistance and arterial pressure and induced renal failure. In contrast, 0.5 mg losartan/kg x day only partially inhibited aortic contractility to angiotensin II, but improved aortic contractility to methoxamine, increased splanchnic and systemic vascular resistance, decreased portal pressure, decreased plasma norepinephrine levels and induced natriuresis. CONCLUSIONS: In cirrhotic rats, losartan at a very low dose increases splanchnic vascular resistance, decreases portal pressure and improves kidney function, possibly by an increased vascular responsiveness to alpha1-adrenoceptor agonists.
Adrenergic alpha-Agonists↗
Hepatitis C-associated autoimmunity in patients coinfected with HIV.
BACKGROUND: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. METHODS: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. RESULTS: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). CONCLUSION: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.
Adult↗
Neutropenic enterocolitis in adults: systematic analysis of evidence quality.
OBJECTIVE: Neutropenic enterocolitis is a life-threatening complication occurring most frequently after intensive chemotherapy in acute leukaemias. The literature is heterogeneous and a systematic review is lacking. METHODS: Following a systematic search we categorised all relevant reports according to their quality and extracted evidence to answer the questions: Which diagnostic criteria are appropriate? What is the incidence of neutropenic enterocolitis? Are there good quality studies supporting specific interventions: Which empiric antimicrobial therapy is recommendable? Is neutropenic enterocolitis without surgical emergency complications an indication for bowel resection? RESULTS: We found and analysed 145 articles of these reports: 64 were reports of single cases, 30 papers reported of two or three cases, 13 were narrative reviews, 34 were retrospective case series of more than three cases and four were prospective diagnostic studies. There were no prospective trials or case control studies on the therapy of neutropenic enterocolitis. There was no consensus on diagnostic criteria. We discuss the difficulty to define diagnostic criteria without having a disease definition. Histology is mostly not available in the living patients. We suggest applying a combination of clinical and radiological criteria: fever, abdominal pain and any bowel wall thickening >4 mm detected by ultrasonography (US) or computed tomography. We calculated a pooled incidence rate from 21 studies of 5.3% (266/5058; 95% CI: 4.7%-5.9%) in patients hospitalised for haematological malignancies, for high-dose chemotherapy in solid tumours or for aplastic anaemia. CONCLUSIONS: This systematic review provides diagnostic criteria for neutropenic enterocolitis, presents a quantitative synthesis on its incidence and discusses its treatment recommendations. Prospective studies are clearly warranted.
Adult↗
MDRD equations for estimation of GFR in renal transplant recipients.
After renal transplantation monitoring and detection of slight-to-moderate changes in GFR is a prerequisite for an optimal patient management. Recently, several equations to estimate GFR were developed and verified in the MDRD study cohort. However, little is known about the application of the MDRD formulas in the setting of renal transplantation. We prospectively conducted a study of the GFR estimates of the Cockcroft and Gault (C&G), MDRD6-, MDRD7 and the abbreviated MDRD (aMDRD) with the true GFR as measured by (99m)Tc-DTPA clearance in 95 consecutive patients 6.5, 5.3-7.7 years (mean, 95% CI) after renal transplantation. On average the DTPA clearance was 37.4, 34.4-40.4 mL/min/1.73 m(2), which differed significantly from estimates of GFR by C&G (52.6, 48.3-56.9 mL/min/1.73 m(2)), MDRD7 (44.8, 40.7-49.0 mL/min/1.73 m(2)), MDRD6 (43.8, 39.9-47.7 mL/min/1.73 m(2)) and aMDRD (46.6, 42.4-50.9 mL/min/1.73 m(2)). Bias was lowest for MDRD6 (6.4 mL/min/1.73 m(2)) and highest for C&G (15.2 mL/min/1.73 m(2)). Precision was similar for MDRD7 and aMDRD (10.6 and 11.1 mL/min/1.73 m(2)) but significantly better for MDRD6 (8.6 mL/min/1.73 m(2); p < 0.035). Accuracy within 50% of real GFR was 55.8% for C&G, 83.2% for aMDRD, 87.4% for MDRD7 and 90.5% for MDRD6. MDRD equations perform significantly better than the commonly used C&G formula. Moreover, the MDRD6 equation provides the best diagnostic performance, and should therefore be preferred in renal transplant recipients.
Adult↗
The role of endoscopy in portal hypertension.
Endoscopy plays a major role in the management of gastrointestinal varices in portal hypertension. It is used for the prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Today not only nonselective betablockers, but also endoscopic band ligation is an option in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Acutely bleeding varices should be treated by ligation, pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding despite endoscopic and pharmacologic treatment is patient dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin level below 3 mg/dl, TIPS is a good option. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and due to hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.
Acute Disease↗
HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells.
HIV has evolved several strategies to evade recognition by the host immune system including down-regulation of major histocompatibility complex (MHC) class I molecules. However, reduced expression of MHC class I molecules may stimulate natural killer (NK) cell lysis in cells of haematopoietic lineage. Here, we describe how HIV counteracts stimulation of NK cells by stabilizing surface expression of the non-classical MHC class I molecule, HLA-E. We demonstrate enhanced expression of HLA-E on lymphocytes from HIV-infected patients and show that in vitro infection of lymphocytes with HIV results in up-regulation of HLA-E expression and reduced susceptibility to NK cell cytotoxicity. Using HLA-E transfected K-562 cells, we identified the well-known HIV T-cell epitope p24 aa14-22a as a ligand for HLA-E that stabilizes surface expression of HLA-E, favouring inhibition of NK cell cytotoxicity. These results propose HIV-mediated up-regulation of HLA-E expression as an additional evasion strategy targeting the antiviral activities of NK cells, which may contribute to the capability of the virus in establishing chronic infection.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Birt-Hogg-Dubé syndrome: germline mutation in the (C)8 mononucleotide tract of the BHD gene in a German patient.
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DNA Primers↗
Detection of Klatskin's tumor in extrahepatic bile duct strictures using delayed 18F-FDG PET/CT: preliminary results for 22 patient studies.
UNLABELLED: Detection of cholangiocarcinoma in extrahepatic bile duct strictures is a continuing challenge in clinical practice because brush cytology taken at endoscopic retrograde cholangiography has an average sensitivity of 50%. The aim of this study was to evaluate the effectiveness of dual-modality PET/CT using (18)F-FDG for noninvasive differentiation of extrahepatic bile duct strictures. METHODS: Twenty-two PET/CT studies were performed on 20 patients (10 women, 10 men; mean age +/- SD, 63 +/- 14 y) with extrahepatic bile duct strictures on endoscopic retrograde cholangiography. PET imaging was started 101 +/- 22 min after injection of 369 +/- 48 MBq of 18F-FDG. Blood glucose was 100 +/- 20 mg/dL. PET images were reconstructed iteratively with attenuation correction based on a rescaling of the CT image. CT was performed within 1 min before the PET study, with the patient in the same position. CT was used to place a volume of interest 5 cm in diameter at the liver hilus for quantitative evaluation of PET images by means of standardized uptake values (SUVs). RESULTS: Final diagnosis was histologically proven cholangiocarcinoma in 14 cases and benign causes of strictures in 8 cases without evidence of malignancy during a follow-up of 18 +/- 3 mo. All patients with cholangiocarcinoma presented with focal increased uptake in the liver hilus with an SUV of 6.8 +/- 3.3 (range, 3.9-15.8), compared with 2.9 +/- 0.3 (range, 2.5-3.3) in patients with benign causes of strictures (P = 0.003). There was a clear cutoff SUV of 3.6 for detection of malignancy in the liver hilus. CONCLUSION: 18F-FDG PET/CT provided high accuracy for noninvasive detection of perihilar cholangiocarcinoma in extrahepatic bile duct strictures.
Adult↗
Does intubation really equal death in cirrhotic patients? Factors influencing outcome in patients with liver cirrhosis requiring mechanical ventilation.
OBJECTIVE: It is not known whether the poor outcome of ventilated cirrhotic patients is related to the severity of the underlying liver disease or to the severity of the acute illness for which ICU care is required. This study examines parameters both of chronic liver disease and of acute illness with regard to their influence on outcome in mechanically ventilated cirrhotic patients. DESIGN AND SETTING: Retrospective observational case series in a 9-bed medical ICU in an academic tertiary care center. PATIENTS AND MEASUREMENTS: Seventy-six consecutive cirrhotic patients who received mechanical ventilation were identified. Clinical and laboratory parameters were compared between ICU survivors and ICU deaths. RESULTS: There were 45/76 (59%) patients who died during their ICU stay. By univariate analysis, the Child-Pugh score, its components (serum bilirubin, prothrombin time), ALT, creatinine concentration, a clinical suspicion of infection, and the APACHE II score, but not the acute physiology score (APS), differed significantly between ICU survivors and ICU non-survivors. The Child-Pugh score was highly correlated to ICU mortality both in logistic regression analysis and receiver-operating characteristics analysis. Conversely, markers of acute illness, in particular the APS component of the APACHE II score, did not predict ICU survival. CONCLUSIONS: Markers of advanced chronic liver disease but not of the severity of acute illness are correlated to ICU outcome in ventilated cirrhotic patients. The outcome of advanced cases (Child-Pugh score of 12 and above) is poor.
Adolescent↗
Primary immunisation of hepatitis C virus (HCV)-specific antibody producing B cells by lipidated peptides.
We analysed whether hepatitis C virus (HCV)-specific antibody producing B lymphocytes can be induced in vitro with HCV-derived lipopeptides containing different T helper cell epitopes. HCV-specific antibody producing B cells were detected by ELISPOT at the single cell level. HCV-derived lipopeptides, but not their corresponding unlipidated peptides, induced B lymphocytes, which produced antibodies mainly reacting with the HCV-derived lipopeptides. The number of antigen-specific B cells was dependent on the number of added autologous T helper lymphocytes during the incubation period. Thus, HCV lipopeptides are more immunogenic than unmodified peptides and can induce HCV-reactive B lymphocytes in antigen-naïve lymphocytes.
Adult↗
Agmatine (decarboxylated arginine), a modulator of liver cell homeostasis and proliferation.
Agmatine interferes with polyamine metabolism and cell growth in cell culture. When absorbed from the gastrointestinal tract, it is accumulated in the liver. Based on these facts, the aim of the present study was to investigate the effects of agmatine on the proliferation of rat and human hepatoma cells and on regeneration of rat liver after partial two-thirds hepatectomy. In cultured cells of the rat and human hepatoma cell lines McRH7777 and HepG2 respectively, agmatine reduced ATP and protein contents (50% inhibition in the range of 169-569 microM) which were determined as estimates for the cell number. This antiproliferative action was not due to an effect on ornithine decarboxylase antizyme, since its intracellular concentration was not significantly changed by agmatine. In addition, agmatine metabolism by diamine oxidase seems not to be involved in the inhibition of cell growth and proliferation because the diamine oxidase inhibitor aminoguanidine did not alter agmatine's antiproliferative action. After two-thirds hepatectomy, daily administration of 250 mg and 500 mg agmatine to rats for 6 days by gavage reduced the weight gain of the remnant liver on day 7 by 19.5+/-0.9% and 22.3+/-1.5% respectively. The decrease in regeneration correlated with a pronounced accumulation of agmatine in the liver. Hence, the present data provide evidence of an involvement of agmatine in liver cell growth.
Agmatine↗
Hepatitis C virus-derived lipopeptides differentially induce epitope-specific immune responses in vitro.
We studied the induction of T cell responses against hepatitis C virus (HCV)-related cytotoxic T cell (CTL) epitopes in lymphocytes from human leukocyte antigen (HLA)-A2-positive, HCV-naive individuals. Peptide and lipopeptides corresponding to the epitope at amino acids (aa) 1073-1081 induced equivalent numbers of tetramer-positive CD8+ T cells and detectable interferon-gamma and granzyme B spot-forming cells (sfcs). Epitope aa 35-44 induction of CTLs was not achieved, despite detectable tetramer-positive CD8+ T cells. IFN-gamma sfcs could only be induced with lipopeptide aa 20-44 but not by conventional antigens, which indicates that lipopeptides may alter T cell functions, depending on the epitope.
Adult↗
Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma.
Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2'-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C --> T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific DNA repair enzymes in tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed hepatocellular carcinoma. 8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P =.003) elevated in ntu tissue (median, 129 fmol/microg DNA) as compared to tu tissue (median, 52 fmol/microg DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic iron concentration and malondialdehyde levels were significantly (P =.001) higher as compared to tu tissue. Glutathione content, glutathione peroxidase activity and manganese superoxide dismutase messenger RNA (mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P =.014) higher hMTH1 mRNA expression compared to ntu tissue. In contrast, hMYH mRNA expression was significantly (P <.05) higher in ntu tissue. No difference in hOGG1 mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic inflammation contribute to human hepatocarcinogenesis. The role of DNA repair enzymes appears to be of reactive rather than causative manner.
Adult↗
Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis.
In this randomized controlled multicenter trial, we compared endoscopic variceal banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal varices (diameter >5 mm) without prior bleeding were randomized to VBL (n = 75) or PPL (n = 77). The groups were well matched with respect to baseline characteristics (age 56 +/- 10 years, alcoholic etiology 51%, Child-Pugh score 7.2 +/- 1.8). The mean follow-up was 34 +/- 19 months. Data were analyzed on an intention-to-treat basis. Neither bleeding incidence nor mortality differed significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10% (PPL). It was associated with the ligation procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL were similarly effective for primary prophylaxis of variceal bleeding. VBL should be offered to patients who are not candidates for long-term PPL treatment.
Actuarial Analysis↗
Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients.
Highly active antiretroviral therapy (HAART) has improved the life expectancy of HIV-infected patients, allowing orthotopic liver transplantation as a reasonable treatment option for selected patients with terminal liver disease. Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements of HAART, give rise to substantial drug-to-drug interactions with immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given. To avoid toxic drug levels, we used an orally available cyclosporine A formulation prepared from the commercial available intravenous solution, which enabled dose adjustments in 1-mg increments. Under ritonavir-boosted HAART, cyclosporine A levels showed markedly altered absorption/elimination characteristics with more or less constant blood-levels throughout the dosing interval and prolonged elimination half-lives up to 38 hours. To obtain equivalent areas under the curve of cyclosporine A, daily doses were reduced to 5-20% of the individual standard doses given before initiation of ritonavir-boosted HAART. Because of the flat absorption/elimination profiles under ritonavir-boosted HAART cyclosporine A, dosing could be reliably monitored long term by measuring cyclosporine A trough-levels.
Adult↗