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Biomedical subjects

D Häussinger

Publications and source records attributed to D Häussinger.

At least 55 records · Page 3Linked to original sources
PubMed2003

Socioepidemiological data on hepatitis delta in a German university clinic--increase in patients from Eastern Europe and the former Soviet Union.

BACKGROUND AND AIMS: The relevance of chronic hepatitis delta results from its high morbidity leading frequently to rapid cirrhosis progression. The aim of the present study was the socioepidemiological characterization of patients with hepatitis delta, in order to identify patients at risk for hepatitis delta. PATIENTS AND METHODS: Clinical parameters of 36 consecutive patients with chronic hepatitis delta, seen between 1989 and 2002 at the University Hospital in Düsseldorf, were evaluated for the present study. Socioepidemiological parameters, available in 31 of these patients who returned a questionnaire, were compared to data of the population of Nordrhein-Westfalen (NRW). RESULTS: Liver cirrhosis was found in 33.3% of patients. There was a mean delay of 3 years between the diagnosis of hepatitis B and D. Patients with delta hepatitis were characterized by lower education, were more frequently unemployed, exhibited less qualified work and had less property compared to the population of NRW. 86.1% of hepatitis delta patients were immigrants to Germany. Before 1995 hepatitis delta infections were mainly seen in patients from Southern Europe (75%), whereas after 1996 predominantly patients from Eastern Europe and the former Soviet Union (53.6%; p < 0.04) contributed to the newly diagnosed cases of hepatitis delta. CONCLUSIONS: The present data underline that hepatitis delta is a severe disease. It seems reasonable to intensify screening for hepatitis delta among patients with low socioeconomic status, especially among immigrants of Eastern Europe and the former Soviet Union.

Adolescent↗
PubMed2002

[Hepatocellular carcinoma: rising incidence of hepatitis C virus-associated cases at a university clinic in Germany].

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) ranks eighth among malignant tumors worldwide. Western countries belong to areas of low HCC prevalence, but incidence of HCC is rising. The aim of the present, retrospective study was to determine changes in the incidence rates and risk factors for HCC in Germany based on the data of a single center. PATIENTS AND METHODS: Epidemiological data of 205 consecutive patients with HCC (163 males, 42 females, mean age 64+/-1 years), admitted to the University clinic Düsseldorf between January 1988 and December 2001, were evaluated. For comparison this time period was divided into two equal intervals (1988 - 1994 and 1995 - 2001). RESULTS: The number of newly diagnosed HCC has more than doubled in the years 1995 - 2001 compared to the years 1988 - 1994. Chronic hepatitis C (HCV), hepatitis B (HBV), and chronic alcohol abuse accounted for almost 80 % of HCC. The number of HCV-associated HCC increased from 31.0 % in the years 1990 - 1995 to 44.6 % (p < 0.04) in the years 1996 - 2001, whereas the proportion of HBV-associated HCC decreased. There were no changes in the Okuda tumor stage, tumor diameter and alpha-fetoprotein levels at the time of HCC diagnosis throughout the years 1988 - 2001. More than 65 % of HCC were non-resectable at the time of HCC diagnosis due to tumor diameter or number of tumor lesions. CONCLUSION: Screening for HCC, possibly rising in its incidence, should be further improved, taking into account that chronic HCV infection is the major risk factor for HCC in Germany.

Adult↗
PubMed2002

[Hepatic encephalopathy].

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops during chronic or acute liver disease. It is functional in nature and potentially reversible and symptoms range from subtle personality changes to deep coma. Diagnosis of manifest HE is made on a clinical basis, whereas psychometric tests are required to diagnose subclinical HE (SHE). Paper-pencil tests are frequently used for diagnosing SHE, but they may be inferior to measurements of critical flicker frequency, which pick minimal and low grade manifest HE as a continuum. Pathogenetically, HE is seen as clinical manifestation of low grade chronic cerebral edema, which is accompanied by alterations in glioneuronal communication. Different factors such as ammonia, inflammatory cytokines, benzodiazepines and electrolyte imbalances may precipitate or aggravate glia edema, thereby explaining precipitation of HE episodes by a variety of unrelated factors. Recognition and rigorous treatment of these precipitating factors is the most important measure in HE therapy, which may be augmented by dietary and medical approaches.

Combined Modality Therapy↗
PubMed2002

Cortical origin of mini-asterixis in hepatic encephalopathy.

The authors investigated 12 patients with cirrhosis who had hepatic encephalopathy (HE): six with continuous mini-asterixis and six with subclinical HE without asterixis. They studied the coupling between hand-muscle electromyography (EMG) recordings and brain activity recorded by magnetoencephalography. On forearm elevation, patients with tremor developed excessive coupling between activity in the motor cortex (M1) and contralateral hand-muscle EMG recordings at the frequency of mini-asterixis, which was not found in controls. The corticomuscular coupling demonstrates the involvement of M1 in asterixis and may reflect a pathologically slowed and synchronized motor cortical drive.

Adult↗
PubMed2002

Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy.

The clinical efficacy of both oral and parenteral L-ornithine-L-aspartate (OA) was confirmed by randomized, placebo-controlled, double-blind studies in patients with manifest hepatic encephalopathy and hyperammonemia. The drug was able to reduce high blood ammonia levels induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis per se. Furthermore, OA improved performance in Number Connection Test-A as well as mental state gradation. In contrast to the positive effects observed in patients with more advanced hepatic encephalopathy, oral OA does not seem to affect minimal hepatic encephalopathy. In a recent trial, OA decreased protein breakdown and stimulated protein synthesis in muscle. The therapy had little side effects, increasing with higher intravenously administered dosages, and was well tolerated after oral and parenteral administration.

Ammonia↗
PubMed2002

Multi-slice CT-colonography in low-dose technique--Preliminary results.

PURPOSE: Assessment of Multi-Slice CT-colonography (MSCTC) with standard and low-dose technique in comparison to conventional colonoscopy (CC). MATERIALS AND METHODS: After standardized bowel cleansing, 28 men and 24 women (mean age 60,3 years) underwent CC within two hours after MSCTC had been performed (4 x 2.5 mm collimation, 3 mm slice width, 17.5 mm table feed, 120 kVp). In 19 patients, MSCTC was performed with 120 mAs (CTDI w, eff : 11.28 mGy), and in 33 patients with 10 mAs (CTDI w, eff : 0.94 mGy), respectively. After noise reduction using mathematical algorithms by a dedicated software (ECCET), images were analyzed by two blinded readers in simultaneously displayed 2D- and 3D-modes. Findings in MSCTC were compared to the results obtained with CC. RESULTS: Calculated effective doses ranged between 9 and 12 mSv for 120 mAs, and between 0.75 and 1 mSv for the low-dose technique. In standard dose MSCTC, 20 of 25 lesions (80 %) were found: all 7 tumors (100 %), one large polyp (> 10 mm; 100 %), 6 of 7 medium sized polyps (9.9 to 5 mm; 86 %) and 6 of 10 small polyps (< 5 mm; 60 %). In low-dose MSCTC, 32 of 44 lesions (73 %) were seen: all three large polyps (100 %), 13 of 14 medium sized polyps (93 %) and 16 of 27 small polyps (59 %). An overall sensitivity of 78 % with a specificity of 68 % was calculated. False positive findings were seen mostly for small lesions (12 for standard dose, 11 for low-dose). CONCLUSION: Despite a 12-fold reduction of radiation exposure, MSCTC in low-dose technique performs comparably well to standard dose MSCTC. After mathematical noise reduction, more than 90 % of polyps larger than 5 mm can be detected.

Algorithms↗
PubMed2002

[The use of colour-coded duplex sonography increases diagnostic accuracy of abdominal ultrasound].

UNLABELLED: Colour Doppler sonography (CDS) avoids misinterpretation of abdominal ultrasonography. Differential diagnosis of pathological structures found by grey-scale sonography can be difficult in many cases. AIM: The present study aimed to determine how often additional colour Doppler sonography could be of benefit to avoid misinterpretation of grey-scale ultrasound images. METHODS: 1350 abdominal sonograms were examined. The sonographic examination was performed using a Toshiba SSA-140 A-ultrasound machine (3.75 MHz and 2.5 MHz-transducer). Findings which could be misinterpreted in grey-scale images, e. g. structures suspicious of lymph nodes, small areas of ascites, hydronephrosis, cysts or cholestasis, were examined by additional colour Doppler sonography. RESULTS: 327 findings (= 24 % of the cases) were classified as requiring additional examination by colour Doppler sonography. In 73 of these cases (= 22 % of cases having additional CDS), CDS identified blood flow in the pathological structure, which avoided misinterpretation of the grey-scale imaging. CONCLUSION: Additional CDS avoids misinterpretation of grey-scale sonography especially in patients with portal hypertension.

Abdomen↗
PubMed2001

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements.

Intact actin microfilaments are required for insulin-regulated glucose transporter isoform 4 (GLUT4) translocation to the plasma membrane. Lipoxygenase (LO) metabolites have recently been shown to contribute to the regulation of actin cytoskeleton rearrangement. In the present investigation, ventricular cardiomyocytes were used to study the effects of two structurally different LO inhibitors (esculetin and nordihydroguaiaretic acid) on insulin signalling events, glucose uptake, GLUT4 translocation and the actin network organization. Insulin stimulation increased glucose uptake 3-fold in control cells, whereas LO inhibition completely blocked this effect. This was paralleled by a slight reduction in the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt/protein kinase B in response to insulin. Addition of 12(S)-hydroxyeicosatetraenoic acid almost completely restored the insulin action in cells exposed to nordihydroguaiaretic acid. Insulin stimulation increased cell surface GLUT4 2-fold in control cells, whereas LO inhibition abrogated the insulin-stimulated GLUT4 translocation. LO inhibition induced a prominent disassembly of actin fibres compared with control cells. In conclusion, we show here that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of the actin network in cardiomyocytes. LO inhibition blocks GLUT4 translocation without affecting downstream insulin signalling. These data suggest that LO metabolites participate in the regulation of glucose transport by contributing to a rearrangement of actin cytoskeletal elements.

Actins↗
PubMed2001

The inhibitory effect of IL-1 beta on IL-6-induced alpha 2-macroglobulin expression is due to activation of NF-kappa B.

The cross-talk between the signal transduction of simultaneous acting cytokines largely determines the final impact of cytokines on their target genes. Both NF-kappaB and STAT3 are transcription factors well known to be activated by many stimuli and to mediate transcriptional activation by binding to specific enhancer sequences. In this study, it is analyzed how IL-1beta inhibits IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. It is shown that IL-1beta prevents STAT3 binding to the two STAT3-responsive sites within the alpha(2)-macroglobulin promoter by association of IL-1beta-activated NF-kappaB to this region. The observation that inhibition of IL-6-induced transcriptional activation of this promoter by IL-1beta is reversed by cotransfection with I-kappaBalpha provides evidence that NF-kappaB activation by IL-1beta is responsible for inhibition of IL-6-mediated trans activation of the alpha(2)-macroglobulin gene. Accordingly, cotransfection of the NF-kappaB subunits p50 or p65 themselves inhibited activation of the alpha(2)-macroglobulin promoter by IL-6. Introduction of point mutations in each of the two NF-kappaB sites overlapping the two STAT3 binding sites within the alpha(2)-macroglobulin promoter provides evidence that each of these two sites counteracts transcriptional activation via STAT3. Most interestingly, at least one functional NF-kappaB consensus site is essential for the IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. Additional data are provided indicating that the activation of NF-kappaB by IL-1beta is also responsible for the inhibition of other IL-6-inducible genes, such as the alpha(1)-antichymotrypsin gene as well as the suppressor of cytokine signaling 3 gene, suggesting a more general relevance of this mechanism for transcriptional regulation.

Animals↗
PubMed2001

[Ru(HNO)('py(bu)S4')], the first HNO complex resulting from hydride addition to a NO complex ('pybuS4'2-=2,6-Bis(2-mercapto-3,5-di-tert-butylphenylthio)dime thylpyridine(2-1)).

Treatment of the nitrosyl complex [Ru(NO)('pybuS4')]Br (1a) with NaBH4 in CH3OH yielded [Ru(HNO)('pybuS4')](2), which could be completely characterized. The X-ray structure determination of 2 confirmed the N coordination of the HNO ligand. Density functional theory calculations enabled us to assign the nu(NO) IR band of 2, which appears in KBr at 1358cm(-1) and in THF at 1378 cm(-1). The unprecedented hydride addition to nitrosyl complexes yielding HNO complexes fills a white spot on the map of chemical reactions, represents the as yet unknown counterpart to the well-established formyl complex formation from CO complexes and hydrides, and distinctly differs from the formation reaction of [Os(HNO)(CO)Cl2(PPh3)2], the only other HNO complex characterized structurally. The HNO complex 2 is oxidized stepwise by [Cp2Fe]PF6 in the presence of NEt3 and directly by Bronsted acids to give [Ru(NO)('pybuS4')]+ in 2e- oxidations. H+/D+ exchange indicates acidity of the HNO proton.

Journal Article↗
PubMed2001

Modulation of the heme oxygenase HO-1 expression by hyperosmolarity and betaine in primary rat hepatocytes.

The influence of hyperosmotic shrinkage and the osmolyte betaine on heme oxygenase HO-1 expression was studied in cultured rat hepatocytes. Hyperosmolarity transiently suppressed HO-1 induction in response to hemin or medium addition at the levels of mRNA and protein expression. Pretreatment of the cells with betaine largely restored induction of both HO-1 mRNA and protein under hyperosmotic conditions. Exposure of HO-1-expressing hepatocytes to cycloheximide unraveled a hyperosmotic acceleration of HO-1 degradation which was counteracted by betaine and the proteolysis inhibitor MG-132. The HO-1 mRNA stability remained unaffected by hyperosmolarity and betaine as shown by application of the transcription inhibitor actinomycin D. The data suggest a modulation of HO-1 expression by hyperosmolarity and betaine at the transcriptional level and at the level of proteasomal degradation. Hyperosmotic suppression of HO-1 expression was accompanied by a moderate but significant loss of hepatocyte viability, which was prevented by betaine. The hyperosmotic impairment of hepatocyte viability was insensitive to betaine in presence of the heme oxygenase inhibitor zinc protoporphyrin IX. However, treatment of the hepatocytes with bilirubin or 8-Br-cGMP improved hepatocyte viability under hyperosmotic conditions to the control niveau. Thus, stabilizing HO-1 expression may contribute to hepatocyte protection against hyperosmotic stress by organic osmolytes.

Animals↗
PubMed2001

Cell hydration controls autophagosome formation in rat liver in a microtubule-dependent way downstream from p38MAPK activation.

Autophagic proteolysis in rat liver is under the control of the cellular hydration state. Because the morphological site of swelling-dependent proteolysis regulation has not yet been identified, the formation of autophagosomes was investigated with transmission electron microscopy in slices from perfused livers. In livers from fed rats, hypo-osmotic exposure (185 mosmol/l) led within 30 min to a decrease in fractional cytoplasmic autophagosome volume that was sensitive to colchicine and p38(MAPK) inhibition. Similarly, the decrease in autophagosome volume, but not the increase in cell volume caused by insulin or glutamine/glycine, was strongly inhibited by colchicine and SB 203580, an inhibition of p38(MAPK) activation. Immune complex assays from perfused liver showed that hypo-osmotic activation of p38(MAPK) was not inhibited by colchicine. Further, experiments using confocal laser microscopy in cultivated hepatocytes incubated with mouse-derived anti-(alpha-tubulin) showed that microtubular structures were not influenced by the inhibition of p38(MAPK) by SB 203580. It is concluded that the sequestration of autophagic vacuoles is a major site of proteolysis regulation by cell hydration. Swelling-induced activation of p38(MAPK) is required for this process and occurs upstream of the putative microtubule regulation site.

Animals↗
PubMed2001

[Diagnosis and therapy of Gaucher disease. Current recommendations of German therapy centers in the year 2000].

BACKGROUND: Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multisystem disease, the prevalence of which is about 1:40,000 in central Europe and up to 1:2,000 in some other countries (e.g. Israel). The acute and chronic neuronopathic forms of the disease (formerly defined as Gaucher types 2 and 3) account for only 5 to 10% of all Gaucher patients in Central Europe and Germany and are thus less frequent than the non-neuronopathic disease (formerly defined as Gaucher type 1). Gaucher's disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications, and several corresponding hematological and laboratory abnormalities. In 5 to 10% of the patients there are also central nervous symptoms such as myoclonic seizures, oculomotoric apraxia and a slight mental retardation. METHODS: Four specialized centers care for more than 2/3 of all German Gaucher patients today. These centers present their consensus recommendations for state-of-the-art diagnosis and treatment of Gaucher's disease. RESULTS: Recent epidemiological data indicate that only 10 to 20% of all Gaucher patients are correctly diagnosed (and treated) in Germany. The diagnosis today can be done in all patients by noninvasive methods, i.e. determination of the glucocerebrosidase activity in peripheral leukocytes and of the genetic defect. The current enzyme replacement therapy with glucocerebrosidase has proven effective to improve and often normalize hematological abnormalities, hepatosplenomegaly, skeletal complications and quality of life, provided that the therapy is started early and is given at adequate dosages. CONCLUSION: In view of the availability of an effective therapy, efforts should be made to increase the awareness of Gaucher's disease in differential diagnosis, to help to diagnose the disease with noninvasive techniques at early stages, and to provide practical guidelines for adequate treatment.

Chromosome Aberrations↗
PubMed2001

[Nonsurgical therapy methods in hepatocellular carcinoma].

The incidence of the hepatocellular carcinoma (HCC) is increasing in western countries mainly due to chronic hepatitis C. Therapy is dependent on the size and localization of the tumors as well as age and condition of the patient. If resection or transplantation are not possible, smaller tumors can be treated with local therapy either by percutaneous ethanol instillation, radiofrequency ablation or laser thermocoagulation. Larger tumors can be treated by transarterial chemoembolization which can also be combined with the methods named above. The results of systemic chemotherapy and medical treatment are disappointing. With early diagnosis and individualized therapeutic strategies prolongation of life or healing may be reached in many patients.

Carcinoma, Hepatocellular↗