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G Herrmann

Publications and source records attributed to G Herrmann.

At least 55 records · Page 3Linked to original sources

Local immunosuppression with budesonide after liver transplantation in the rat: a preliminary histomorphological analysis.

BACKGROUND: In this study we have analyzed the local immunosuppression with budesonide, a topically selective glucocorticosteroid, in rats after orthotopic liver transplantation. Because of its high first-pass hepatic clearance budesonide can be given orally, achieving high intrahepatic and low systemic concentrations. METHODS: Using an acute rejection model from Dark Agouti (DA) to Lewis rats, the histomorphological degree of rejection was assessed on histological sections at the ninth postoperative day. RESULTS: Livers of the DA to Lewis study group without immunosuppression revealed severe allograft rejection with vast cellular infiltrates, massive endothelialitis, and hepatocyte necrosis. In the three budesonide study groups (250 microg, 500 microg, and 1 mg/kg/day) a moderate to mild liver allograft rejection was seen. Rejection was most prominent in the 250 microg group, whereas the 1 g group showed almost no signs of rejection, similar to the Lewis to Lewis control group. Aspartate and alanine transaminase (sGOT, sGPT) as well as alkaline phosphatase serum levels correlated with the degree of rejection, achieving highest levels in the DA to Lewis group without immunosuppression. Animals treated with 1 g of budesonide had serum levels similar to Lewis to Lewis control animals. CONCLUSIONS: These results implicate a beneficial effect of local immunosuppression with budesonide in rats based on the histomorphological degree of liver allograft rejection.

Acid Phosphatase↗

A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks.

Eukaryotic DNA ligases are ATP-dependent DNA strand-joining enzymes that participate in DNA replication, repair, and recombination. Whereas mammalian cells contain several different DNA ligases, encoded by at least three distinct genes, only one DNA ligase has been detected previously in either budding yeast or fission yeast. Here, we describe a newly identified nonessential Saccharomyces cerevisiae gene that encodes a DNA ligase distinct from the CDC9 gene product. This DNA ligase shares significant amino acid sequence homology with human DNA ligase IV; accordingly, we designate the yeast gene LIG4. Recombinant LIG4 protein forms a covalent enzyme-AMP complex and can join a DNA single-strand break in a DNA/RNA hybrid duplex, the preferred substrate in vitro. Disruption of the LIG4 gene causes only marginally increased cellular sensitivity to several DNA damaging agents, and does not further sensitize cdc9 or rad52 mutant cells. In contrast, lig4 mutant cells have a 1000-fold reduced capacity for correct recircularization of linearized plasmids by illegitimate end-joining after transformation. Moreover, homozygous lig4 mutant diploids sporulate less efficiently than isogenic wild-type cells, and show retarded progression through meiotic prophase I. Spore viability is normal, but lig4 mutants appear to produce a higher proportion of tetrads with only three viable spores. The mutant phenotypes are consistent with functions of LIG4 in an illegitimate DNA end-joining pathway and ensuring efficient meiosis.

Amino Acid Sequence↗

Coagulation activation in patients undergoing directional coronary atherectomy.

Restenosis is a major problem of percutaneous transluminal coronary angioplasty (PTCA) and related procedures. To better understand the underlying pathophysiologic mechanisms, coagulation and fibrinolytic variables were analysed prospectively in 35 patients after directional coronary atherectomy (DCA) and in 20 control patients undergoing diagnostic heart catheterisation and coronary angiography. Blood samples were taken before and 1 h, 24 h and 48 h after the procedure. No subacute thrombosis or unstable angina were documented in any patient. In 8 out of these 35 patients late restenosis was diagnosed during follow-up angiography 3-6 months after DCA. In these 8 patients prothrombin fragments (F1 + 2) rose from 0.7 to 0.9 nmol/l (P < 0.01) and thrombin-antithrombin III complexes (TAT) from 2.9 to 6.0 micrograms/l (P < 0.01), but not significantly in 27 patients without restenosis and in the control patients. In patients with late restenosis plasminogen activator inhibitor (PAI-1) also increased from 2.4 to 4.9 U/ml (P < 0.05) 24 h after DCA while there were no significant changes in patients without restenosis and in control patients. D-Dimer/TAT ratio reflecting the balance between clotting activation and fibrinolysis was significantly lower after 24 h in restenosis patients. The findings suggest that coagulation activation and hypofibrinolysis during 48 h after DCA might be associated with the development of late restenosis.

Adult↗

[Severe acute cholestatic viral hepatitis E in a non-pregnant woman].

HISTORY AND CLINICAL FINDINGS: During a journey in Germany a 25-year-old French woman, who had been living in India for 6 months, developed a severe acute hepatitis with marked jaundice and transitory liver failure. INVESTIGATIONS: Serum titres for anti-hepatitis E virus immunoglobulins G and M were markedly raised during hospitalisation, proving acute hepatitis E, a rare disease in Central Europe. TREATMENT AND COURSE: Within two weeks symptomatic treatment brought about almost complete regression of the initially greatly increased parameters of abnormal liver function (GPT 2277 U/l, GOT 1497 U/l, GLDH 39.2 U/l); reduction of the total bilirubin level from initially 11.7 to 1.0 mg/dl). Indicators of decreased liver synthesis, such as antithrombin III, partial thromboplastin time and coagulation factors II, V and VII, quickly became normal. Flue-like and gastrointestinal symptoms and arthralgia, improved within a few days. CONCLUSION: This case documents the sporadic occurrence in Germany and the course of severe acute hepatitis E, associated with marked liver damage. It demonstrates that the disease can take a fulminant course even in non-pregnant women, leading to severe impairment of liver function and the danger of hepatic coma.

Acute Disease↗

Enlargement of perihepatic lymph nodes in relation to liver histology and viremia in patients with chronic hepatitis C.

Inflammatory processes in organs frequently lead to hyperplasia of regional lymph nodes. In the present study, we investigated whether lymph node enlargement within the hepatoduodenal ligament may reflect the inflammatory activity within the liver of patients chronically infected with the hepatitis C virus (HCV). In 114 patients with chronic hepatitis C and 49 healthy controls, the total lymph node volume within the hepatoduodenal ligament was prospectively investigated by ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the same occasion, and specimens were semiquantitatively evaluated by the histological activity index (HAI). Hepatitis C viremia was assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%) and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected in all patients with chronic hepatitis C and in 33 of 45 controls. The mean perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than in HCV-infected patients with mild to moderate inflammatory activity, severe inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4 mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P < 10(-6)). No correlation was found between the total lymph node volume within the hepatoduodenal ligament, HCV genotypes, and liver function test results. In conclusion, enlargement of perihepatic lymph nodes in patients with chronic hepatitis C is predictive for the presence of severe inflammatory activity. The mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown but appears to be related to viral replication within the liver and the immune-mediated inflammatory response of the host.

Adult↗

[Endomyocardial biopsy--helpful in differential diagnosis between myocarditis and dilated cardiomyopathy. A case report].

Endomyocardial biopsy is an established technique to distinguish between myocarditis and dilated cardiomyopathy. Even when clinical symptoms for myocarditis are lacking, immunohistologic findings may establish a clear diagnosis. For treatment, however, an early diagnosis is mandatory. We report on a 44 year old patient who was admitted with the echocardiographic diagnosis of dilated cardiomyopathy. He underwent diagnostic angiocardiography and endomyocardial biopsy. The latter demonstrated an active myocarditis. At the time of read-mission, 2 weeks later, the patient had deteriorated. Now, additional to a symptomatic therapy, prednisolone, azathioprine and human immunoglobulin G were given and patient conditions improved dramatically. The use of endomyocardial biopsy seems recommendable in order to define patients diagnosis and their results may be necessary to decide patients therapy.

Adult↗

Prevalence and clinical and histological manifestation of hepatitis G/GBV-C infections in patients with elevated aminotransferases of unknown etiology.

BACKGROUND/AIMS: Hepatitis G virus (HGV) and hepatitis GB virus-C (GBV-C) are recently identified non-A-E hepatitis-associated viruses. The prevalence of HGV/GBV-C in the general population is high (1.0-1.7%), but data on the clinical and histological manifestations of the new viruses are sparse. In the present study we investigated the prevalence and clinical and histological manifestation of HGV/GBV-C infections in patients with elevated aminotransferase levels of unknown etiology. METHODS: In 52 of 630 consecutive patients referred for evaluation of elevated aminotransferases the underlying liver disease remained unknown. Serum samples of these 52 patients with elevated aminotransferase levels of unknown etiology were tested for HGV/GBV-C RNA by reverse transcription-polymerase chain reaction (RT-PCR) using primers deduced from nonstructural regions. Cloned PCR products were sequenced and compared by phylogenetic analysis. RESULTS: HGV/GBV-C RNA was consistently detected in 7 of the 52 patients (13%). Sequence and phylogenetic analysis revealed the presence of only one subtype, with nucleotide sequence homologies between 86 and 91%. All seven patients had persistent viremia for at least 9 months. In six patients liver function test results normalized, and alanine aminotransferase levels remained persistently elevated in only one patient. Four HGV/GBV-C positive and ten HGV/GBV-C negative patients consented to a liver biopsy, which revealed similar results with minimal to mild chronic hepatitis and mild portal fibrosis. CONCLUSIONS: The prevalence of HGV/GBV-C infections in patients with elevated aminotransferases of unknown etiology is low. Since clinical, biochemical and histomorphologic features of patients with elevated aminotransferases of unknown etiology with and without HGV/GBV-C infection are indistinguishable, the role of HGV/GBV-C in the pathogenesis of chronic liver disease appears insignificant.

Adult↗

Evidence for the development of macrophage-like cells in long-term culture of bovine aortic endothelial cells.

Macrophages are known to be derived from monocytes which proliferate in the bone marrow. The proliferation of monocytes may occur in other places as well. In the present study, we describe the morphological behaviour of macrophage-like cells in endothelial cell cultures obtained from bovine aorta. These cells resembled hemopoietic clones containing progenitor-like cells. Immature and mature macrophage-like cells were rich in acid phosphatase activity, and expressed the CD18 molecule using immunolocalisation. Mature cells contained intracellular lipid droplets. "Actin" globules were apparent only in the peripheral cell areas without lamellipodia or filipodia. At the ultrastructural level, the mature cells were crowded with granules which could be lysosomes, phagolysosomes, or endocytotic vesicles. Multinuclear giant cells which behaved in a different way to the macrophage-like cells were observed. The development and maintenance of macrophage-like cells appears to be dependent on the coculture with endothelial cells. It may signify that endothelial cells are involved in the proliferation of monocytes outside the bone marrow.

Acid Phosphatase↗

Detection of the adrenal glands by endoscopic or transabdominal ultrasound.

BACKGROUND AND STUDY AIMS: The value of transabdominal and endoscopic ultrasound (EUS) in detecting normal adrenal glands is not yet established. The aim of our study was to evaluate whether these techniques can be routinely used to visualize the adrenal glands in patients without suspected adrenal pathology. PATIENTS AND METHODS: Transabdominal ultrasound was validated by examination of 10 corpses and was performed in 80 healthy volunteers (3.5 and 5 MHz). EUS of the left adrenal gland was performed in 154 consecutive patients referred for various other reasons. In 20 patients we attempted to visualize the right adrenal gland as well. RESULTS: Both adrenal glands were correctly identified in all of the 10 corpses once they were opened. In healthy volunteers, the right adrenal gland was visualized by transabdominal ultrasound in 79/80 patients (99 %) and the left adrenal gland in 55/80 patients (69 %). EUS allowed detection of the left adrenal gland in 151/154 patients (98%). In three patients EUS failed because of grossly distorted anatomy. In 6/20 patients we were also able to detect the right adrenal gland by EUS, which was obvious in two cases because of incidentalomas. CONCLUSION: Visualization of the right adrenal gland is almost always possible by transabdominal ultrasound, while its detection by EUS is successful only in some cases. The left gland is more difficult to detect by transabdominal ultrasound, while it can nearly always be seen using EUS. Therefore, a combined transabdominal and endoscopic ultrasonographic approach is useful for visualization of the adrenal glands and may enable diagnosis of even small adrenal masses.

Adrenal Glands↗

Detection of normal mediastinal lymph nodes by ultrasonography.

PURPOSE: The detection by US (in contrast to CT) of lymph nodes of any size in the mediastinum is usually considered to be a pathological finding. The aim of this study was to find out whether it was possible to detect normal lymph nodes by high-resolution mediastinal US. MATERIAL AND METHODS: Six different mediastinal regions in 80 healthy asymptomatic volunteers and in 20 human cadavers were examined by means of US (with colour Doppler imaging) to assess US access to the respective regions and to demonstrate the number and size of detectable lymph nodes. All the cadaveric lymph nodes that were detected were examined histologically to exclude inflammatory or malignant infiltration. RESULTS: In almost all subjects, we obtained US access to the supra-aortic (100%), paratracheal (95%), prevascular (99%), and pericardial (98%) regions, and to the aorticopulmonary window (98%). US access to the subcarinal region was more difficult (75%). In the healthy subjects, lymph nodes were detected in the paratracheal region (in 35% of these subjects, mean lymph-node diameter 12 x 7 mm), in the aorticopulmonary window (45%, 14 x 8 mm), and in the subcarinal region (13%, 13 x 7 mm). In the cadavers, histologically normal lymph nodes were detected frequently in the paratracheal region (85%, mean size 11 x 6 mm) and in the aorticopulmonary window (90%, 11 x 5 mm). CONCLUSION: These results indicate that normal lymph nodes (and not only pathological lymph nodes) can be demonstrated by high-resolution mediastinal US.

Adult↗

Multiple coronary artery-left ventricular fistulae: haemodynamic quantification by intracoronary Doppler ultrasound.

Multiple coronary artery-left ventricular fistulae involving all three major coronary arteries are extremely rare. Clinical findings are heterogeneous but include a history of typical or atypical angina pectoris in most cases. Coronary arteriography in a 65 year old woman who presented with chest pain at rest revealed multiple fine fistulae arising from the left anterior descending, left circumflex, and right coronary arteries. Left-to-left shunt was estimated by measurements of coronary artery flow velocity with intravascular Doppler ultrasound.

Aged↗

Nonmalignant epithelial cells, potentially invasive in human endometriosis, lack the tumor suppressor molecule E-cadherin.

Endometriosis is one of the most frequent diseases in gynecology. It is a histologically defined nonmalignant disease in which endometrium-like tissue is found outside the uterus (for example, peritoneum, gut, or lung). The pathogenesis of endometriosis is unknown, but invasive mechanisms have been implicated in the development of the disease. Indeed, primary cells from human endometriotic biopsies but not from human endometrial biopsies are invasive in an in vitro collagen invasion assay. In this study, these in vitro invasive endometriotic cells were found to be nonmalignant epithelial cells lacking E-cadherin, which acts as an invasion suppressor molecule in carcinomas. Immunocytochemistry showed that the E-cadherin-negative epithelial cell type was increased in sections of endometriosis tissue as compared with sections of eutopic endometrium. On the basis of these data we propose that the E-cadherin-negative invasive endometriotic cells seen in vitro represent the cell population that migrates to ectopic (extrauterine) locations and thus causes endometriosis in vivo. Accordingly, the loss of E-cadherin expression is postulated to constitute a crucial mechanism in the pathogenesis of endometriosis.

Cadherins↗

[Liver transplantation and splenectomy in idiopathic portal hypertension].

Idiopathic portal hypertension (IPH) was diagnosed in a 30-year-old man. Clinical signs were splenomegaly, leucothrombocytopenia, and esophageal varices of fourth degree. The histology of the liver biopsy showed portal fibrosis with no evidence of cirrhosis. No causing agent or known disease could be found for the histopathological and clinical features. Due to a severe deterioration of general condition and a decline of synthetic liver function, liver transplantation and splenectomy were performed. The histological examination of the explanted liver revealed features of IPH, demonstrating portal fibrosis and dilated vessels adjacent to portal tracts; no cirrhosis was found. The postoperative recovery was without any severe complications. The duration of hospitalization was 28 days. Following liver transplantation, the esophageal varices disappeared and leucocytes, platelets as well as parameters of hepatic synthesis reached normal values. Initially, the immunosuppression was composed of prednisolon, tacrolimus, and antibodies against IL-2 receptors (BT 563) and was later continued with prednisolon and tacrolimus. Within the follow-up observation of 26 months, there was no evidence for graft rejection, severe infection, or occurrence of portal hypertension. Up till now the patient is in good condition with normal graft function. Liver transplantation may be a curative therapy for patients with advanced disease of IPH but the long-term follow-up after transplantation has to show whether IPH can reoccur.

Adult↗

Sonographic detection of focal changes in the liver hilus in patients receiving corticosteroid therapy.

OBJECTIVE: While diffuse deposition of fat may occur with corticosteroid (CS) administration both in the liver and in other organs, comparatively little is known about focal changes in the liver under corticosteroid medication. Therefore, we evaluated pattern and extent of focal hepatic steatosis by ultrasound (US) in patients receiving corticosteroids. SUBJECTS AND METHODS: 93 patients with known inflammatory bowel disease (IBD) received corticosteroids during a period of at least six weeks prior to the ultrasound examination and 28 IBD-patients had no corticosteroids within the last three years. 13 additional patients received corticosteroids for other reasons than IBD for > 1 year. 80 healthy volunteers served as controls. Focal changes of the liver as assessed by high resolution ultrasound (Acuson 128, 3.5 and 5 MHz) were defined as areas of brighter echogenicity compared to the general aspect of the liver. The size of the hyperechoic areas was documented (photoprint). RESULTS: 40/93 IBD-patients with corticosteroids (43%) had definite areas of brighter echos in the hilus region of the liver. In IBD-patients without corticosteroids only one patient showed a focal brighter echogenicity, whereas in the non-IBD group with corticosteroids 8/13 had focal lesions (62%). In the control group only four healthy subjects showed brighter areas (5%). CONCLUSION: Bright focal areas in the liver hilus occur in > 40% of IBD-patients during corticosteroid medication. This phenomenon occurs in IBD-patients as frequently and as intense as in other patients with longstanding corticosteroid therapy. There is a hilar area of the liver with typical size and location which reacts to corticosteroid administration with hyperechoic reflexes at ultrasound investigation. This is important to know when it comes to the differential diagnosis of focal changes.

Adrenal Cortex Hormones↗

Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology.

Nucleotide sequence analysis of hepatitis C virus (HCV) strains showed substantial variability leading to a classification into several genotypes and subtypes. The data correlating HCV genotypes and subtypes with hepatitis C viremia levels, demographic characteristics of patients (age, mode of transmission, duration of infection), and severity of liver disease are conflicting. The interpretation of several studies is further complicated because the molecular methods used lacked specificity for genotyping/subtyping and underestimated viremia levels, especially in patients infected with HCV genotypes 2 and 3. In the present study we investigated 97 consecutive patients with chronic hepatitis C using molecular "gold standard" methods. HCV subtyping was performed by sequence and phylogenetic analysis of the nonstructural (NS)-5 region and serum HCV-RNA concentration was assessed by a validated genotype-independent quantitative reverse-transcription-polymerase chain reaction assay using an internal RNA standard. Patients infected with subtypes HCV-1b, HCV-2a-c, and HCV-4 were older than patients infected with HCV-1a and HCV-3a. Serum HCV-RNA levels ranged from 1.5 x 10(4) to 1.0 x 10(8) copies/mL with no significant differences between median serum HCV-RNA concentrations in patients infected with different genotypes/subtypes. Although patients infected with HCV-1b were older, no biochemical or histological evidence was obtained that this subtype is associated with more severe liver disease. Furthermore, the present study showed a lack of correlation between the serum HCV-RNA concentration, biochemical parameters, and liver histology. The median serum HCV-RNA levels in patients with chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis were 5.0 x 10(6) copies/mL, 2.5 x 10(6) copies/mL, and 5.0 x 10(6) copies/mL, respectively. These differences were not significant. In conclusion, using optimized and validated molecular techniques, the present cross-sectional study showed no correlation between HCV genotypes/subtypes, viremia, liver function test results, and histology.

Adult↗

Do long-term results justify bridging to heart transplantation in patients with multi-organ dysfunction?

This retrospective study was performed to determine the influence of multi-organ dysfunction and the type of preoperative hemodynamic support on mortality after heart transplantation. All patients undergoing heart transplantation during a 6 year period were divided into 3 groups: group A patients (n = 110) had stable hemodynamics on oral medication, group B recipients (n = 41) received continuous i.v. catecholamine application, and in group C (n = 21) mechanical hemodynamic support was necessary. In groups B and C elevated serum creatinine and transaminase levels-reflecting renal and hepatic dysfunction-were detected more often and the survival rate was worse during the first six months (A: 85%, B: 71%, C: 52%, p < 0.01). In group C the prognosis of patients with multi-organ dysfunction was significantly worse compared to patients with normal renal and hepatic function (38% vs. 75%; p < 0.01). In recipients surviving for six months, there was no difference in long-term prognosis between the groups studied. It is concluded that heart transplantation in patients with multi-organ dysfunction on invasive hemodynamic support bears a significantly increased risk in the early postoperative period. In view of the current donor shortage the condition of other organs should be improved before transplantation as far as possible, even using long-term mechanical support.

Adult↗