PubMed Health⌕ Search

Biomedical subjects

U Spengler

Publications and source records attributed to U Spengler.

At least 19 recordsLinked to original sources
PubMed2003

[Fatty liver and increased serum lactate in a woman with HIV].

HISTORY AND CLINICAL PRESENTATION: A 50-year-old woman with HIV who had undergone a 7-month course of antiretroviral treatment (stavudine, lamivudine, indinavir, ritonavir) was admitted to hospital with abdominal pain, nausea, vomiting and muscle pain. Physical examination revealed subfebrile body temperature and hepatomegaly. INVESTIGATIONS: Biochemical tests revealed moderate elevations of gamma GT, AST and ALT as well as marked hyperlactatemia. Abdominal computed tomography indicated pronounced hepatomegaly. Percutaneous liver biopsy was performed and demonstrated macro- and microvesicular hepatic steatosis on light microscopy. Electron microscopy showed mitochondrial damage. TREATMENT AND COURSE: Despite discontinuation of antiretroviral treatment serum lactate levels further increased initially and clinical symptoms were progressive. In the following weeks, a slow but steady recovery of laboratory values and physical condition was noted. CONCLUSION: Hyperlactataemia associated with abdominal pain can indicate the mitochondrial toxicity due to nucleoside reverse transcriptase inhibitors. After drug discontinuation, improvement of clinical symptoms and laboratory values is often delayed, frequently for several weeks.

Abdominal Pain↗
PubMed2003

IgA class antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and autoimmune hepatitis.

Antineutrophil cytoplasmic antibodies (ANCA) of IgG class have been described at high prevalence in autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Data on IgA class ANCA in these diseases are limited. The aim of this study was to determine the prevalence and fluorescence patterns of IgA class ANCA in AIH and PSC and to examine a relationship between the presence of IgA ANCA and clinical characteristics in these patients. Sera from 35 patients with PSC (21 with concomitant inflammatory bowel disease), 40 patients with AIH and 10 healthy controls were studied. ANCA were detected on ethanol-fixed neutrophils using an indirect immunofluorescence technique. ANCA of the IgA class were found in 20% of sera from patients with PSC and in 50% of AIH sera. The majority of AIH patients with IgA class ANCA showed a 'classical' perinuclear staining pattern, whereas the 'classical' and 'atypical' perinuclear fluorescence patterns were distributed equally in PSC. In sera containing IgG and IgA class ANCA simultaneously, IgG class ANCA showed an 'atypical' pANCA fluorescence pattern whereas IgA class ANCA produced a 'classical' perinuclear staining. The presence of IgA class ANCA was not associated with disease-specific clinical characteristics. IgA class ANCA are more frequently detected in sera of patients with AIH than PSC. The diversity of fluorescence patterns points to different target antigens of IgA class ANCA with distinct subcellular localizations.

Adolescent↗
PubMed2003

Portal hypertension is associated with increased mRNA levels of vasopressor G-protein-coupled receptors in human hepatic arteries.

BACKGROUND: The contractile response of human splanchnic vessels to different vasoconstrictors is attenuated in cirrhosis. Functional studies indicate a cellular signalling defect upstream of the G-protein level. The aim of the present study was to analyze expression and mRNA levels of the following most relevant vasopressor receptors in the smooth musculature of human hepatic arteries: alpha1 adrenoceptor (AR) subtypes a, b and d, angiotensin II type 1 receptor (AT1), arginine vasopressin receptor type 1a (V1a), endothelin receptor type A (ETA) and B (ETB). MATERIALS AND METHODS: Hepatic arteries were collected from 10 donors (noncirrhotic) and 14 recipients (cirrhotic) at liver transplantations. Real-time-PCR was performed to quantify steady-state levels of receptor mRNAs. RESULTS: alpha 1aAR mRNA levels showed no significant difference between the cirrhotic arteries and the controls while the mRNA levels of the other vasoactive receptors were significantly higher in the cirrhotic hepatic arteries (alpha 1bAR: 4-fold, P = 0.013; AT1: 16-fold, P = 0.024; V1a: 23-fold, P = 0.001; ETA: 4-fold, P = 0.02; ETB: 8-fold, P = 0.008). No mRNA for the alpha 1dAR was detected either in the donor or recipient hepatic arteries. CONCLUSION: We conclude that vascular hyporeactivity to the most relevant endogenous vasoconstrictors of cirrhotic hepatic arteries is not caused by a receptor down-regulation at mRNA levels. In contrast they were up-regulated.

Adult↗
PubMed2003

Changes of lymphocyte apoptosis associated with sequential introduction of highly active antiretroviral therapy.

OBJECTIVE: To assess the effect of highly active antiretroviral therapy (HAART) on surrogate markers of lymphocyte apoptosis in HIV 1-infected individuals. METHODS: Ex vivo apoptosis was studied prospectively in 26 antiretroviral naive HIV-positive patients up to 12 weeks after sequential initiation of HAART [phase I: nucleoside reverse transcriptase inhibitor (NRTI), phase II: NRTI + protease inhibitor (PI)]. Apoptosis was assessed via CD95-, Apo2.7-expression and annexin-V-binding in peripheral CD4, CD8, B and NK-cells, and compared to changes in activation markers (HLA-DR, CD38) and viral loads. RESULTS: After introduction of HAART CD4-counts rose significantly mainly through cell redistribution, while activation markers decreased. Although Apo2.7 expression decreased throughout the study period, it was not possible to establish a correlation to the rise in CD4 cells. Unexpectedly, CD95 expression and annexin V binding were elevated during phase I of treatment without PI and began to decline only after the addition of a PI in phase II. Poor responders to antiretroviral therapy had significantly higher CD95 expression and annexin V binding in the initial phase of antiretroviral regimen. CONCLUSION: These data show divergent effects of HAART on surrogate markers of apoptosis, when treatment is initiated sequentially with NRTIs first. Partial suppression of HIV replication during treatment without PI may be associated with increased rates of apoptosis.

ADP-ribosyl Cyclase↗
PubMed2002

Enteric dysfunction in patients with asymptomatic HIV-infection versus patients with hypoproteinemia/hypalbuminemia and advanced HIV-infection.

BACKGROUND: It is unclear whether enteric dysfunction and protein losses contribute to hypoproteinemia, which heralds poor survival in HIV infection. METHODS: We investigated alpha-1-antitrypsin-clearance (AAT-CL), D-xylose resorption and total gut transition time in 14 HIV+ patients with hypoproteinemia (serum protein < 6 g/dl, albumin < 3 g/dl, median CD4-cell count 58/microl; (group I)), in 10 asymptomatic HIV+ patients (median CD4-cell count 290/microl, (group II)) and in 15 healthy volunteers (group III). RESULTS: AAT-CL in group I (16.5 (2.9 278.2) ml/d; median (range)) was higher than in groups II (9.5 (1.7 23.1) ml/d) and III (10.6 (0.8 19.5) ml/d; p = 0.0114). Likewise, D-xylose recovery was on average threefold lower in group I than in groups II (p = 0.0009) and III ( p < 0.0001), whereas total gut transition time was significantly shorter in both HIV-infected groups (group I: 49.8 h (23.5-72.7), p=0.0431; group II: 32.6 h (23-54.6), p=0.0104) than in the healthy controls (group III 61.6 h (39.1-87.7)). CONCLUSIONS: Thus, impaired intestinal resorption and enteral protein losses may contribute to hypoproteinemia in advanced HIV infection, whereas accelerated intestinal motility may be present already in asymptomatic stages of HIV infection.

Adult↗
PubMed2002

[Do polymorphisms of the SDF1 and CCR2b genes modify the course of hepatitis C or HIV/HCV co-infection?].

BACKGROUND AND OBJECTIVE: Complementary to the CCR5-Delta32 mutation polymorphisms in the genes of CCR2b (CCR2b-V64 I) and stromal derived factor (SDF)-1 (SDF-1 3'A) affect the course of the human immunodeficiency virus (HIV) infection. While the CCR5-Delta32 mutation is also increased in chronic hepatitis C virus (HCV) infection it is unclear, whether the CCR2b-V64 I and the SDF-1 3'A polymorphisms also are associated with chronic HCV infection. METHODS: We analyzed the frequencies of the CCR2b-V64I and SDF1 - 3'A mutation in patients with HIV/HCV coinfection (n = 130), HIV infection (n = 105), HCV infection (n = 153) and 112 healthy blood donors. We stratified each group into homozygous mutations, heterozygous mutations and homozygous wild types, respectively. The resulting subsets were compared with respect to HIV and HCV loads, CD4 and CD8 cell counts. RESULTS: The mutant SDF1 - 3'A allele was found at 20.3 % frequency in patients with HCV infection and at 20.4 % frequency in patients with HIV/HCV coinfection, respectively. It was present in 27.1 % of the patients with HIV infection and 27.9 % of the healthy controls (not significant). The number of SDF-1 3) A homozygous patients was highest in patients with HIV/HCV coinfection and significantly different compared to the Hardy-Weinberg equilibrium (p = 0.010, chi (2) = 9.15). However, CD4- and CD8-cell counts or viral loads were not affected by this mutation. The frequency of the CCR2b-V64 I allele was similar in all patient groups. However, CCR2b-V64 I heterozygous patients showed HIV loads that were threefold lower than in CCR2b wildtype patients (22.9 x 103 vs. 6.4 x 103 copies/ml, not significant). Furthermore, hepatitis C viral loads were reduced roughly by 30 %. CONCLUSION: These results suggest that the SDF1 - 3'A and CCR2b-V64I mutations do not affect the course of HCV and HIV/HCV infection in the same manner as does the CCR5-Delta32 mutation.

Adolescent↗
PubMed2002

Renal functional reserve is well maintained in patients with advanced liver cirrhosis and ascites.

BACKGROUND: Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in healthy humans can be induced by amino acid stimulation. The rise in GFR from baseline to maximum is referred to as the renal functional reserve (RFR). Recently, we showed that the RFR is preserved in patients with compensated cirrhosis despite impaired renal function. In the present study, we evaluated RFR in decompensated cirrhotics with ascites. METHODS: Steady-state inulin- and para-aminohippurate (PAH) clearances were performed at rest and during amino acid infusion in 22 patients with decompensated liver cirrhosis and ascites. RESULTS: Baseline GFR and ERPF (means +95% confidence intervals) were: GFR 25.2 (21.1-29.2) ml min(-1), ERPF 266.6 (229.7-303.5). Amino acid infusion significantly increased GFR by 67% (38.3-95.8) to 34.6 (29.2-40.0) ml min(-1) (means + (95% confidence intervals), P < 0.001) and ERPF by 29% (11.9-46.3) to 326.3 (274.1-378.5) ml min(-1) (P = 0.002). Renal vascular resistance dropped by 13.4% (3.3-23.5) from 29.4 (24.8-33.9) mmHg ml(-1) min(-1) to 26.4 (22.0-30.7) mmHg ml(-1) min(-1) (P = 0.036). The improved kidney function was accompanied by a decrease in systemic aldosterone levels (P < 0.05). CONCLUSION: In patients with liver cirrhosis and ascites, amino acid infusion improves kidney function. Trials are warranted to test the long-term effects of amino acid infusions in patients with hepatorenal syndrome.

Aldosterone↗
PubMed2001

Intrahepatic MxA expression is correlated with interferon-alpha expression in chronic and fulminant hepatitis.

Interferon-alpha (IFN-alpha) has potent pro-inflammatory and anti-viral functions. It exerts its effects by inducing intracellular proteins such as MxA. To analyse the role of intrahepatic interferon activation, IFN-alpha and MxA expression was studied by immunohistochemistry in explant livers of 20 patients with fulminant hepatic failure (FHF), 41 patients with chronic liver disease (CLD), and ten normal controls (NCs). In NCs only small numbers of Kupffer cells, but no hepatocytes, showed IFN-alpha and MxA expression. In contrast, significantly enhanced numbers of IFN-alpha- and MxA-positive Kupffer cells, along with small numbers of MxA-positive and larger numbers of IFN-alpha-positive lymphocytes, were found in CLD and in FHF. MxA protein was also expressed on hepatocytes and bile ducts in the vicinity of IFN-alpha-positive inflammatory infiltrates (hepatocytes: NCs: 0%, CLD: 8%, FHF: 68%; bile ducts: NCs: 19%, CLD: 46%, FHF: 83%). A significant correlation was found between the numbers of IFN-alpha- and MxA-positive cells (r=0.67, p<0.001). Thus, large amounts of IFN-alpha are released in the livers of patients with FHF, which is likely to contribute to immune-mediated liver cell damage. Intrahepatic MxA expression corresponds to IFN-alpha produced particularly by infiltrating inflammatory cells, rather than by hepatocytes themselves.

Antiviral Agents↗
PubMed2001

Natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) is not impaired in patients suffering from chronic hepatitis C.

BACKGROUND/AIMS: Recent observations suggest that natural killer (NK) cell activity might be impaired in chronic hepatitis C. However, to date antibody-dependent cellular cytotoxicity (ADCC) has not been studied in chronic hepatitis C in detail. METHODS: Therefore, we investigated spontaneous and cytokine-induced (interleukin-2 and interferon-gamma) natural cytotoxicity and ADCC in 29 patients suffering from chronic hepatitis C and 19 healthy controls. Cytotoxicity was determined with a flow-cytometric assay, which can also assess monocyte cytotoxicity. As target cells we used the colorectal tumor cell line HT29 and the lymphoma cell line Raji. RESULTS: We found no significant differences with respect to spontaneous cytotoxicity (HCV versus healthy controls (32 vs. 46%) and 17-1A specific ADCC (59 vs. 48%), even if isolated monocytes or NK cells were studied. Preincubation and stimulation of effector cells with cytokines increased both natural cytotoxicity and ADCC by 20-30%. However, natural cytotoxicity and ADCC after stimulation did not differ between the two groups. CONCLUSIONS: Our data obtained with a long-term cytotoxicity assay do not reveal impaired cytolytic capacity of the innate immune system in chronic hepatitis C, even when isolated monocytes and NK cells were studied as effector cells.

Adult↗
PubMed2001

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients.

BACKGROUND/AIMS: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. METHODS: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. RESULTS: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. CONCLUSIONS: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load--and therefore minimizes the risk of adverse events--may result in clinical efficacy should be investigated.

Adult↗
PubMed2001

Plasma antioxidant capacity of HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate containing antioxidant polyphenols.

OBJECTIVE: To investigate whether antioxidant polyphenols from fruit juices or a fruit-vegetable-concentrate increase the plasma antioxidant capacity in HIV-infected and healthy subjects. DESIGN: Twenty-three HIV-seropositive and 18 seronegative adults were randomized to ingest either 1 l of fruit juice or 30 ml fruit-vegetable-concentrate per day over 16 weeks in addition to their normal Western diet. METHODS: Plasma antioxidant capacity was determined as Trolox equivalent antioxidant capacity (TEAC) at baseline, after 1 and 16 weeks of intervention, and after a 6 week washout. RESULTS: There was no difference in plasma antioxidant capacity between HIV-infected and healthy subjects at baseline (P=0.1). After 16 weeks of intervention TEAC increased in HIV-positive subjects with both types of polyphenol supplementation (juice, 1.38+/-0.07 to 1.42+/-0.04 mM, P=0.034; concentrate, 1.40+/-0.09 to 1.46+/-0.08 mM, P=0.025). TEAC was not altered by either type of supplementation in HIV-seronegative subjects. CONCLUSION: Plasma antioxidant capacity can be increased by long-term ingestion of polyphenols from fruit juices or fruit-vegetable-concentrate in HIV-seropositive but not in HIV-seronegative subjects. SPONSORSHIP: This study was supported by a grant and Cellagon aurum from HG Berner GmbH, Altenholz, and fruit juices from Eckes Granini GmbH & Co. KG, Nieder-Olm.

Adult↗
PubMed2001

Differentiation of antineutrophil nuclear antibodies in inflammatory bowel and autoimmune liver diseases from antineutrophil cytoplasmic antibodies (p-ANCA) using immunofluorescence microscopy.

Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) directed against cytoplasmic proteins of neutrophils have been studied extensively in patients with systemic vasculitides. Recent data indicate that antineutrophil antibodies in sera from patients with chronic inflammatory bowel diseases (IBD) or autoimmune liver disorders, currently called 'atypical p-ANCA', recognize a nuclear target antigen, rendering the term 'ANCA' inaccurate. Specific microscopic criteria to distinguish atypical p-ANCA from p-ANCA are lacking. We used planar and confocal laser scanning indirect immunofluorescence microscopy to examine the labelling characteristics of ethanol-, methanol- and formaldehyde-fixed neutrophils by antineutrophil antibodies in 153 serum samples from patients with IBD, autoimmune liver disorders, systemic vasculitides or healthy blood donors. On ethanol- or methanol-fixed neutrophils, multiple intranuclear fluorescent foci together with either a rim-like peripheral nuclear staining ('type A') or a combined cytoplasmic and peripheral nuclear staining ('type B') was noted exclusively with atypical p-ANCA in sera from patients with IBD or autoimmune liver disorders. Intranuclear foci, which probably corresponded to invaginations of the nuclear envelope, were not labelled by p-ANCA from patients with microscopic polyangiitis or cytoplasmic ANCA (c-ANCA) from patients with Wegener's granulomatosis. On formaldehyde-fixed neutrophils, atypical p-ANCA gave a fine rim-like staining of the nuclear periphery, whereas ANCA diffusely labelled the cytoplasm. To distinguish reliably between the patterns produced by atypical p-ANCA or p-ANCA, particularly p-ANCA, careful indirect immunofluorescence microscopy on ethanol- as well as on formaldehyde-fixed neutrophils is necessary, with particular emphasis on the presence of multiple intranuclear fluorescent foci.

Adolescent↗
PubMed2001

Lipidation of T helper sequences from hepatitis C virus core significantly enhances T-cell activity in vitro.

Successful elimination of the hepatitis C virus (HCV) during acute infection has been linked to strong HCV-specific in vitro T-cell proliferation, whereas T cells from patients with chronic hepatitis C respond only weakly to HCV antigens. Lipid-coupled peptides are immunostimulants, which might provide a basis for novel therapeutic strategies against HCV. Therefore, in 20 patients with chronic hepatitis C, we studied whether tri-palmitoyl-S-cysteine-coupled peptides could modify in vitro T-cell proliferation (by [3H]thymidine uptake) in response to virus core and NS4. The lipopeptides corresponded to five immunodominant T helper epitopes of HCV core. Contrary to unmodified peptides, the lipopeptides specifically enhanced [3H]thymidine uptake in response to HCV antigens but not to a non-HCV related control antigen. They increased the frequency of responders (stimulation index, SI > or = 4) to core (13/20 versus 2/20; p = 0.0008) and NS4 (20/20 versus 7/20; p < 0.0001) among our patients with chronic hepatitis C. This immunostimulatory effect was dose-dependent, and was observed specifically with lipopeptides corresponding to the HCV epitopes. Our data demonstrate that the poor in vitro T-cell proliferation of patients with chronic hepatitis C can be improved when T cells are co-stimulated with HCV core-derived T helper lipopeptides, while the same peptides in unlipidated form had no effects. Thus, lipopeptides corresponding to HCV T-cell epitopes may offer novel immunomodulatory strategies against HCV.

Adult↗
PubMed2001

Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism.

Splanchnic vasodilatation and vascular hyporesponsiveness to vasopressors are characteristic features of patients with cirrhosis. Although the vascular response to different vasopressors has been shown to be attenuated in cirrhosis, alterations on the receptor level are discussed controversially. Thus, impaired postreceptor signaling has been postulated. However, so far this has not been studied in human splanchnic vessels. Therefore, we assessed the vascular response of human hepatic arteries after activating the G-protein-dependent signal transduction pathway by stimulation with angiotensin II, the thromboxane A(2) analog U46619, or by G-protein activation with NaF/AlCl(3). After endothelium denudation, cumulative isometric concentration contraction curves were obtained for hepatic arteries from 32 cirrhotic patients undergoing liver transplantation and from 40 organ donors after stimulation with either angiotensin II (10(-11)-10(-5) mol/L), U46619 (10(-10)-10(-6) mol/L) or AlCl(3) (30 micromol/L)/NaF (10(-4)-3 x 10(-2) mol/L). Hepatic arteries from cirrhotic patients were markedly less responsive to angiotensin II (P <.0001) than those from organ donors. Both stimulation of the G-protein phospholipase C pathway via the thromboxane A(2) receptor and receptor-independent G-protein stimulation with AlCl(3)/NaF, induced an intact contractile response. In conclusion, the G-protein-dependent signal transduction system itself is unaltered in cirrhosis. Hence, the cause of the hyporesponsiveness to some vasoconstrictors in cirrhosis appears to be a receptor-specific phenomenon localized upstream from the G-protein level.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Virus-like particles in a case of acute hepatitis with human GB virus-C viraemia.

BACKGROUND/AIMS: It is still controversial whether the human GB virus-C can cause liver injury, as in situ demonstration of the virus is still inconclusive. METHODS: Here we describe the case report of a patient with two episodes of severe acute hepatitis, who had a meticulous clinical, immunological and microbiological work-up, including human GB virus-C RNA detection by in situ hybridization and electron microscopy. RESULTS: Human GB virus-C viraemia was found as the only potential cause of hepatitis in this patient. Furthermore, virus-like particles could be demonstrated in the cytoplasm of single hepatocytes by electron microscopy and human GB virus-C RNA was detected in the liver by in situ hybridization. CONCLUSION: The presence of human GB virus-C RNA in serum together with the demonstration of human GB virus-C RNA in the liver, favour acute human GB virus-C infection as the cause of liver injury in this patient. Thus virus-like particles and hepatic human GB virus-C RNA should be specifically looked for by electron microscopy and in situ hybridization, especially during the diagnostic work-up of patients with unexplained hepatitis.

Acute Disease↗
PubMed2001

Transient loss of T-cell reactivity in a patient with hepatitis C virus reinfection.

BACKGROUND/AIMS: Self-limited acute hepatitis C virus (HCV) infection with spontaneous recovery is only rarely observed in clinical practice. All existing studies correlate strong cellular immune responses to the recovery from HCV infection. CASE REPORT: Here, we present a 49-year-old haemophiliac, who had successfully recovered from an acute hepatitis, which was classified retrospectively as HCV infection based on his antibody profiles. This patient was reinfected with HCV 18 years later from an exogenous source, and successfully recovered from this reinfection within 2 months. After his first hepatitis the patient displayed strong cellular responses against recombinant HCV proteins. During reinfection, T-cell proliferation was markedly reduced, while HCV antibody titres increased. However, E2 antibodies were consistently not detectable. T-cell proliferation returned to the pre-reinfection level only several months after loss of viraemia. DISCUSSION: Our observations resulted in the unexpected finding that our patient cleared HCV reinfection despite an apparent loss of his pre-existing T-cell reactivity in the peripheral blood.

Hemophilia A↗