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D Häussinger

Publications and source records attributed to D Häussinger.

At least 19 recordsLinked to original sources
PubMed2006

[Transient elastography for diagnosing liver cirrhosis].

BACKGROUND AND OBJECTIVE: Detection of liver cirrhosis has numerous implications because of the potential sequelae of cirrhosis. Transient elastography (Fibroscan), was evaluated as a novel, non-invasive means of assessing cirrhosis by measuring liver stiffness. METHODS: 147 consecutive patients with different forms of liver disease and histologically determined stages of liver fibrosis were prospectively studied by transient elastography. 48 patients had liver cirrhosis. RESULTS: The number of transient elastographic measurements per patient was 12+/-4 (range 6 - 30). Valid elastography measurements were available for 135 out of 147 patients (92 %). The results of transient elastography correlated positively with the histological score of liver fibrosis (r = 0.8; 95 % CI: 0.72 - 0.85; p < 0.001). Areas under the receiver operating characteristic curve (AUROC) were 0.91 for > or = F3 fibrosis (95 % CI: 0.85 - 0.96) and 0.94 for cirrhosis (95 % CI: 0.90 - 0.98). Using a cut-off value of 13 kPa for detection of liver cirrhosis a sensitivity of 90 %, a specificity of 82 %, a positive predictive value of 71 % and a negative predictive value of 95 % were obtained. CONCLUSIONS: Measuring liver stiffness by transient elastography proved to be an easy method to assess liver cirrhosis. In combination with clinical signs, ultrasound and biochemical markers noninvasive diagnosis of liver cirrhosis will be further improved.

Adolescent↗
PubMed2006

[Hepatic encephalopathy].

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which can develop in acute and chronic liver disease. It is functional in nature and potentially reversible. Signs of neurodepression characterize HE in chronic liver disease, whereas neuroexcitatory symptoms may prevail in fulminant hepatic failure. Manifest HE is graded into four severity stages, which range from mild personality changes to deep coma, and is distinguished from subclinical (latent) HE. Diagnosis of manifest HE is made on the basis of clinical symptoms, whereas psychometric or neurophysiological tests are required for detection of subclinical HE. However, the frequently employed paper-pencil tests are not sensitive enough to diagnose subclinical HE. A promising alternative is determination of critical flicker frequency (CFF), which picks up low grade HE as a continuum, but requires cooperation of the patient. HE is now seen as the clinical manifestation of a chronic low grade cerebral edema, which triggers alterations in astrocyte function with consequences for glioneuronal communication. Ammonia, inflammatory cytokines, benzodiazepines and electrolyte disturbances can trigger or aggravate glial swelling. This may explain why a variety of heterogenous conditions can precipitate episodes of HE, such as infections, drugs, trauma, bleeding etc. Diagnosis and rigorous treatment of these precipitating factors is the most important therapeutic measure, which is supported by dietary and drug treatment.

Astrocytes↗
PubMed2006

Evaluation of safety and efficacy of rosiglitazone in the treatment of HIV-associated lipodystrophy syndrome.

BACKGROUND: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class of thiazolidindiones might be effective in the treatment of LDS. PATIENTS AND METHODS: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients received 4 mg rosiglitazone once daily for a 24-week study period. Efficacy was assessed by measurement of metabolic and anthropometric parameters, total body DXA scan, CT scan of the abdomen, photo documentation and self-assessment. RESULTS: Rosiglitazone treatment was well tolerated. DXA scans demonstrated a highly significant increase in adipose tissue of the limbs (2644 +/- 1334 g vs 3380 +/- 1614 g, p < or = 0.001) without any change in total fat mass. Abdominal CT-scans revealed a significant increase in subcutaneous adipose tissue (113.7 +/- 82.4 cm(2) vs 125.3 +/- 83.7 cm(2), p = 0.04). Abdominal circumference decreased significantly (94.7 +/- 8.7 cm vs 92.2 +/- 8.45 cm, p = 0.03) without any relevant change of body weight or BMI. We observed an increase in serum cholesterol (248 vs 281 mg/dl, p = 0.006) and serum triglycerides (301 vs 351 mg/dl, p = 0.1). Furthermore, no side effects of clinical relevance were observed. The insulin sensitivity index improved without reaching statistical significance. Thirteen patients (65%) reported general improvement of LDS symptoms. Evaluation of photo documentation by five HIV-experts revealed poor concordance and no relevant change of LDS. CONCLUSIONS: The results of this study suggest that rosiglitazone is safe in the treatment of HAART-associated lipodystrophy and has moderate clinical efficacy. We found a trend towards improved insulin sensitivity and as a possible limiting factor an unfavorable increase in serum cholesterol and triglycerides.

Adult↗
PubMed2006

1H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy.

PURPOSE: Mild swelling of astrocytes is proposed as a key event in the pathogenesis of hepatic encephalopathy. Proton MR spectroscopy ((1)H-MR spectroscopy), diffusion-weighted imaging (DWI), and magnetization transfer imaging were performed in patients with alcoholic and nonalcoholic liver cirrhosis and correlated with different clinical stages of hepatic encephalopathy to assess alterations in cerebral water metabolism in different subgroups of patients with cirrhosis. MATERIAL AND METHODS: Forty-five patients (26 alcoholics, 19 nonalcoholics [due to hepatitis C (n = 9), hemochromatosis (n = 2), primary chronic cholangitis (n = 2), hepatitis B (n = 1), Wilson disease (n = 1), cryptogenic cirrhosis (n = 4)]) and 18 controls underwent (1)H-MR spectroscopy, magnetization transfer imaging, and DWI of the basal ganglia and normally appearing occipital white matter (NAWM). N-acetylaspartate (NAA), choline (Cho), myo-inositol (mIns), and glutamine/glutamate (Glx) relative to creatine (Cr), the apparent diffusion coefficients (ADC), and the magnetization transfer ratios (MTR) were correlated to the neuropsychologic status, which was assessed by computerized psychometry and mental state grading, according to the West Haven criteria. RESULTS: Compared with controls, nonalcoholic subjects exhibited a gradual increase of Glx/Cr in the basal ganglia and NAWM; a decrease in mIns/Cr; a significant decrease of MTR in the thalamus, the putamen, the pallidum, and NAWM; and an increase in the ADC of the NAWM with increasing hepatic encephalopathy severity. In alcoholics, mIns/Cr of the basal ganglia and the NAWM, Cho/Cr of the basal ganglia, and MTR of all assessed regions were decreased. Glx/Cr of the basal ganglia and of the NAWM was increased, compared with that of controls; but no correlation to the clinical hepatic encephalopathy grading was found. ADC did not change significantly between the groups. CONCLUSIONS: Apart from a typical pattern of (1)H-MR spectroscopy alterations in hepatic encephalopathy, a gradual decrease in MTR and an increase of ADC was found correlating to clinical grading of hepatic encephalopathy in nonalcoholic patients with cirrhosis. In alcoholic patients with hepatic encephalopathy, there was no such correlation. Abnormalities detected by MR imaging may hint at different pathways of brain damage in alcohol-induced liver disease.

Diffusion Magnetic Resonance Imaging↗
PubMed2005

Increased incidence of cancer in adult Gaucher disease in Western Europe.

The adult form of Gaucher disease (type I GD) is associated with a high prevalence of hypergammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS). A significantly increased risk of cancer, especially of hematological types, has been found in Ashkenazi-Jewish GD type 1 patients. In this study, incidence and mortality of cancer were assessed in a total of 131 GD patients of mixed ancestry in a population from Western Europe, i.e. 2 Gaucher referral centers in Germany (Düsseldorf) and the Netherlands (Amsterdam). Standardized rate ratios were determined by indirect standardization, using age- and sex-specific incidence and mortality rates of the Dutch population. A total of 14 GD patients of non-Ashkenazi-Jewish descent were identified of whom 5 had a hematologic malignancy. These numbers correspond to an increased risk of cancer of 2.5 (95% CI 1.1-4.7) and an increased risk of hematologic cancer of 12.7 (95% CI 2.6-37.0) among GD patients compared to the general population. In particular, the incidences of multiple myeloma and hepatocellular carcinoma in absence of preexisting cirrhosis were highly elevated, with standardized rate ratios of 51.1 (95% CI 6.2-184) and 141.3 (95% CI 17.1-510.5), respectively. These strongly increased risks on developing cancer suggest that measures for early detection and prevention of hematological and hepatic malignancies in patients with Gaucher type I disease are mandatory.

Adolescent↗
PubMed2005

Prevalence of oral lesions and periodontal diseases in HIV-infected patients on antiretroviral therapy.

A cross-sectional study examining oral manifestations was carried out in HIV-infected patients of a general HIV-specialized unit to provide prevalence data on oral lesions and periodontal diseases. The occurrence of oral lesions was correlated with demographic and clinical characteristics, immunologic and virologic parameters. Among 139 patients 86% presented any oral lesions with a prevalence of 76% of any periodontal diseases. Most periodontal lesions were classified as conventional gingivitis (28%) or periodontitis (30%). Dental plaque formation was associated with a higher prevalence of periodontal diseases (p = 0.01) and periodontal inflammation scores were higher in patients with more reduced CD4-counts (p = 0.03). Prevalence for HIV-specific oral lesions was 29% with a proportion of 9% of linear gingival erythema (LGE), 3.6% of necrotizing and ulcerative gingivitis (NUG) or periodontitis (NUP), 7% of oral candidiasis, 3.6% of oral hairy leucoplakia (OHL) and single other lesions. HIV-specific lesions (NUG/NUP, oral candidiasis and OHL) were found predominantly in patients with advanced immunosuppression and elevated viral load. Compared with data of oral diseases of the pre-HAART era prevalence of HIV-specific lesions was markedly reduced. Especially frequently known lesions such as oral candidiasis and OHL were less common seen. We noticed a shift of prevalence towards periodontal diseases. Lack of oral hygiene determined by plaque formation and reduced CD4-counts with pronounced periodontal inflammation can be seen as risk factors for periodontal disease. Overall high prevalence of manifestations underlines the importance of oral examination for the general practitioner and visits by oral specialists should become a routine procedure in HIV-patients care.

Adult↗
PubMed2005

[Current treatment of hepatitis C virus infection].

New strategies have led to better results in the treatment of HCV infection during the last few years. At present the recommended treatment for patients with chronic hepatitis C is a combination of pegylated interferon and ribavirin. The sustained virological response rate of this combination therapy is 42 - 48 % for patients with genotype 1 after a course of 48 weeks and 80 % for patients with genotype 2 or 3 after a course of 24 weeks. New nucleoside analogs may lead to a better tolerance and better outcomes. A new approach is the long term monotherapy with pegylated interferon in order to reduce the progression of fibrosis and the incidence of cirrhotic complications. At present the effectivity of protease inhibitors and of a therapeutic immunisation with the E1 envelope protein of the hepatitis C virus are being examined. Because the optimal treatment strategy for patients with an acute hepatitis C infection is still unclear, these patients should be included in clinical studies.

Acute Disease↗
PubMed2005

Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients.

OBJECTIVES: The insulin-sensitizer rosiglitazone is under investigation for therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about pharmacological interactions with antiretroviral (ARV) drugs. METHODS: Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective study before and at day 28 after start of treatment with 4 mg of rosiglitazone for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1, 2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for analysis. RESULTS: Twelve males and six females were assessed; mean age was 50.7 years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside reverse transcriptase inhibitors in all cases. After administration of rosiglitazone, no significant differences in Cmax, Cmin and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax of nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI) -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the geometric mean ratio (GMR) of Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9-1.0; GMR of Cmin 0.89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01). CONCLUSIONS: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is likely to reduce the bioavailability of nevirapine. Thus, routine TDM is recommended for patients treated with rosiglitazone and nevirapine. A therapy consisting of efavirenz or lopinavir seems to be without negative impact. Further studies on the interaction of rosiglitazone with ARV drugs are necessary.

Anti-HIV Agents↗
PubMed2005

Atazanavir for treatment of HIV infection in clinical routine: efficacy, pharmacokinetics and safety.

INTRODUCTION: Atazanavir (ATV) is a novel protease inhibitor that has been recently introduced into therapy of HIV infection. Currently there is little data on ATV therapy from daily practice. METHODS: In this retrospective study, we report on ATV efficacy and safety in clinical routine. Drug monitoring was performed consisting of unscheduled single measurements and a 4-hour-profile. Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were regarded as sufficient. RESULTS: Between May 2003 and April 2004, ATV treatment was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was discontinued in 10% due to side effects or malignant diseases. No significant influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell-count, and HI-viral load was seen. Virologic failure occurred in 13% of patients, all of them were PI-experienced. Pharmacokinetic data are available for 32 patients, all patients had sufficient trough levels. 30% with unboosted ATV and 21% with boosted ATV had peak plasma concentrations below the level defined as sufficient. Mean trough levels, plasma profile and AUC did not differ significantly between groups with non-boosted versus boosted ATV regimes but showed a wide inter-patient variability. CONCLUSIONS: ATV treatment of HIV-infected patients with or without a RTV booster was safe and effective in clinical routine. Drug levels were sufficient in the majority of cases. The variability of pharmacokinetic results in our sample supports therapeutic drug monitoring in patients treated with ATV.

Anti-HIV Agents↗
PubMed2005

Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis.

Hepatic encephalopathy is characterized by disturbances of motor and cognitive functions involving the basal ganglia. So far no standards for assessment of neuropsychiatric abnormalities (disorders of sleep, mood, anxiety and personality) in subclinical hepatic encephalopathy have been defined. Using an animal model of mild (subclinical) hepatic encephalopathy we investigated now striatum-related behaviors and cortico-striatal synaptic plasticity in rats 2 months after introduction of a portacaval shunt and sham-operated matched controls. In a novel open field portacaval shunt rats displayed less locomotor activity; unlike controls they also showed no habituation to the field and no recall of the field environment after 24 h, indicative of cognitive deficit. The elevated-plus maze test indicated no differences in fear/anxiety in the portacaval shunt animals. Tetanic stimulation of cortical afferents in magnesium-free solution evoked an N-methyl-D-aspartate-dependent long-term potentiation in sham-operated animals. In portacaval shunt animals long-term potentiation was significantly impaired. Histamine, a potent modulator of cortico-striatal transmission, induced a larger long-term depression of field potentials in control compared with portacaval shunt rats. In conclusion, a combination of electrophysiological and behavioral approaches has revealed functional changes in cortico-striatal transmission. These data are relevant for understanding the mechanisms of motor and cognitive dysfunctions in hepatic encephalopathy patients and for the development of precise psychometric tests, evaluating cognitive deficits in subclinical hepatic encephalopathy.

Animals↗
PubMed2005

[Transjugular intrahepatic portosystemic stent shunt: indications and long-term outcome].

The transjugular intrahepatic portosystemic stent shunt has replaced surgical shunt procedures as the standard therapy for complications of portal hypertension such as refractory ascites and recurrent variceal bleeding. However, reinterventions due to TIPS stenosis are necessary in 25-50 %. Major complications are the manifestation or worsening of hepatic encephalopathy. Recent studies using PTFE covered stents have shown lower stenosis rates and a trend towards prolonged survival.

Ascites↗
PubMed2005

Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.

BACKGROUND AND AIMS: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. PATIENTS AND METHODS: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. RESULTS: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response. CONCLUSIONS: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

Adult↗
PubMed2004

[Infection with Gnathostoma spinigerum as a cause of eosinophilic oesophagitis].

HISTORY AND ADMISSION FINDINGS: A 63-year-old man, who had travelled extensively in Asia and had lived in South Africa, presented with increasing dysphagia. Physical examination showed no abnormalities. EXAMINATIONS: Upper gastrointestinal endoscopy showed a concentric oesophageal stenosis, 5 cm long, consisting of thickening of the wall without any sign of malignancy or mucocutaneous lesions. The histological examination of this lesion demonstrated infiltrations of eosinophilic cells. Serology was positive for Gnathostoma spinigerum. TREATMENT AND CLINICAL COURSE: After treatment with albendazole 400 mg per day for 3 weeks the clinical, histological and serological symptoms resolved completely. CONCLUSION: In case of any eosinophilia or local infiltrations of eosinophilic cells, parasitic disease have to be considered.

Albendazole↗
PubMed2004

Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany.

BACKGROUND: Resistance against antiretroviral drugs in previously untreated HIV-infected persons is of growing relevance. The aim of the study is to determine the prevalence of resistance-associated mutations in this patient group. METHODS: In a prospective multicenter-study in Nordrhein-Westfalen, Germany, genotypic resistance testing was performed in untreated HIV-positive patients before administration of first-line highly active antiretroviral therapy (HAART). RESULTS: Between January 2001 and August 2002 resistance testing was performed in 184 therapy-naive individuals. HAART was initiated in 143 patients, who were included into the study. 70.6 % were males, mean age was 39 years, mean duration of diagnosis of HIV-infection was 1.5 years. The proportion of cases at CDC stage C was 45.4%, mean CD4-cell count was 199 /ml, mean viral load was 206,855 copies/ml. Resistance-associated mutations were detected in 20 patients (14.0%). 10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor- (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q), 2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated resistance (V82A, L90M), respectively. Multi-class-resistance was found in 2.1%, mutations indicating revertant variants of resistant strains were found in 4.2% (T215C/E/L/S). 86.7% of the isolates showed secondary mutations in the protease gene. No significant difference in the distribution of the parameters age, sex, duration of HIV diagnosis, CDC stage, CD4-cell count, and viral load, between groups with and without resistance was identified. CONCLUSION: The prevalence of primary resistant virus strains can be estimated at 14% in chronically infected HAART-naive HIV-patients in Germany. The majority of these cases show NRTI-associated resistance. Resistance against NNRTI or PI as well as multi-class-resistance is of low prevalence. No risk factor of predictive value can be identified for the diagnosis of resistance mutations in the individual. In conclusion, routine genotypic resistance testing in untreated HIV-positive patients should be performed before administration of first-line HAART in this region.

Adult↗