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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Triphasic spiral CT in the diagnosis of liver diseases: comparison with CT arteriography and CT arterio-portography].

PURPOSE: Assessment of the diagnostic efficacy of triphasic spiral-CT scanning (TPS-CT) for liver disease evaluation. CT arteriography (CTA) and CT arterio-portography (CTAP) were used as reference, methods which together have the highest sensitivity for detecting tumours and the perfusion conditions of the liver. MATERIAL AND METHODS: 50 TPS-CT and CTA/CTPA were performed in 49 patients. After an initial examination without enhancement the first scan was initiated 15-25s after the peripheral bolus injection of contrast medium, the second after an interscan delay of 20-25s. By this means the liver was imaged in different phases of perfusion. In the course of the CTA/CTPA-exam the imaging was carried out after selective, intraarterial application of contrast agent. RESULTS: The differentiation of the perfusion phases succeeded in 90% of the patients. When compared with standard CT, which images only the portal venous phase, the new technique, which additionally shows the arterial perfusion, accomplished an increase in sensitivity for hypervascular lesions (51% vs. 60%). Yet in comparison with CTA/CTPA fewer lesions could be detected (87 vs. 138). Furthermore, by documenting the contrast agent kinetics, characterisation of the lesion was also facilitated. CONCLUSION: DPS-CT is a valuable additional tool for imaging the liver, even if the information yield is less when compared to CTA/CTPA.

Adult↗
PubMed1996

Rare pre-core stop-codon mutant nt. 1897 predominates over wide-spread mutant nt. 1896 in an unusual course of chronic hepatitis B.

We present a patient with an unusual course of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B who had repeated reactivations of his disease progressing to cirrhosis with terminal liver failure. Each flare up presented like an acute hepatitis with very high titres of hepatitis B virus (HBV) and high inflammatory activity followed by rapid clearance of viraemia. The pre-core genome of HBV isolated from sera during 5 years of follow up was analysed. Direct sequencing of polymerase chain reaction (PCR) products derived from consecutive sera showed a rare pre-core stop-codon mutation at nucleotide (nt.) 1897 G --> A with an accompanying mutation nt. 1857 C --> T as well as a stop-codon mutation nt. 1896 G --> A. By cloning and sequencing of PCR products the mutant strain with mutation nt. 1897 was shown to predominate over viral strains with a mutation nt. 1896 during the course of disease, although the stop-codon mutation nt. 1896 in general is observed more frequently. Both mutations allow viral replication by stabilizing the encapsidation signal 'epsilon'. This allowed HBV replication at a very high level as observed during flare ups. The absence of HBeAg may be responsible for the massive cytotoxic T-cell response towards hepatocytes which might explain the rapid progression to liver cirrhosis although no, or very little, HBV replication was observed for long periods. However, there is no clear explanation as to why the nt. 1897 mutant strain overwhelmed the other virus strains.

Adult↗
PubMed1996

Ligase chain reaction (LCR) assay for semi-quantitative detection of HBV DNA in mononuclear leukocytes of patients with chronic hepatitis B.

A ligase chain reaction (LCR)-based approach to detect hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMC) is described. Using this new amplification technique, we determined semi-quantitatively the amount of a short HBV S-gene fragment in PBMC lysates of 25 patients with different forms of chronic hepatitis (group A (n = 8), hepatitis B s antigen (HBsAg)+/hepatitis B e antigen (HBeAg)+; group B (n = 9), HBsAg+/HBeAg-; group C (n = 8), HBsAg-/HBeAg-). The LCR results were compared with the findings obtained with polymerase chain reaction (PCR) amplification of three distinct HBV gene regions (preS1/2, S and C) and related to the serological profiles of the patients. Depending on the primer pair used for PCR amplification, sensitivity of HBV LCR in PBMC was equivalent or slightly superior to PCR. The highest positivity rate for HBV DNA was observed in the HBeAg+ and HBV DNA seropositive group (8/8) and was lower in the other patient groups B (4/9) and C (1/8). Interestingly, HBV gene sequences could also be detected in the lymphocytes of an HBsAg negative patient and in two patients from group B who were both negative for serum viral particles by PCR. The rapid LCR procedure represents a reliable alternative to PCR for the sensitive detection of HBV DNA in PBMC samples. In combination with the automated IMx(TM)-system the new amplification technique may be routinely used for screening for HBV in whole blood samples and thus may help to better evaluate the risk of HBV reinfection in liver transplant recipients.

Clinical Laboratory Techniques↗
PubMed1996

Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance.

The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restriction were studied with 15 peptide-specific CD4+ T cell lines and 23 T cell clones isolated from liver tissue and peripheral blood of 12 patients with chronic hepatitis C. It was demonstrated that the peptide-specific response of CD4+ T cells was restricted to the presence of autologous accessory cells and HLA-DR and -DP molecules. Eight peptide-specific T cell lines and five T cell clones derived from liver tissue and peripheral blood, released interferon-gamma (200-6600 pg/ml) and tumor necrosis factor-alpha (100-400 pg/ml) and no or little interleukin-4 (< 140 pg/ml) after peptide-specific or mitogeneic stimulation, thus resembling a Th1-like cytokine profile. Patients with active liver disease showed significantly higher proliferative responses to hepatitis C virus core peptides than asymptomatic hepatitis C virus carriers or complete responders to interferon therapy. In conclusion, class II-restricted CD4+ T cell responses to some immunodominant epitopes within the hepatitis core region correlated with disease activity in chronic hepatitis C virus infection. Functionally, liver-infiltrating and peripheral blood T cells released Th1-like cytokines in response to the specific stimulus. Thus, it can be suggested that CD4+ T cells can mediate the pathogenesis of chronic hepatitis C virus induced liver disease.

Amino Acid Sequence↗
PubMed1996

Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis.

In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post-infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20-70% of all hepatocytes. Post-infantile giant cell hepatitis was defined histopathologically. The clinical course of all four patients markedly improved after immunosuppressive treatment. Further improvement was observed with the addition of ursodeoxycholic acid. Follow-up liver biopsies during treatment showed reduced inflammation and a decreased number of giant cells. One patient, who initially was admitted to the hospital with liver cirrhosis died five years later due to a sepsis. The clinical course of the other three patients remained stable during the observation period, and no progression of liver fibrosis was recorded as long as immunosuppressive treatment was continued. Cholestasis and autoimmunity seem to be two important mechanisms triggering hepatic giant cell formation in post-infancy. In the reported cases long-lasting cholestasis in primary sclerosing cholangitis together with features of autoimmune hepatitis seem to have triggered the formation of syncytial hepatic giant cells.

Adrenal Cortex Hormones↗
PubMed1996

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

Adult↗
PubMed1996

[HIV and pregnancy: risks of transmission and therapeutic possibilities].

In Europe, transmission of HIV-1 during pregnancy occurs in 14% of children born to HIV-infected women. Risk factors for transmission are (1) virus load measured by p-24 antigenemia and HIV RNA level, (2) low CD4+ lymphocyte counts (below 600/microliter, (3) placental membrane inflammation and (4) time interval between membrane rupture and delivery. Breast feeding and vaginal delivery increase the risk of transmission of HIV infection. Antiretroviral therapy with zidovudine (Retrovir) at a dose of 500 mg/day reduces the transmission of HIV infection by two thirds. No malformation of the newborn due to zidovudine has been reported so far, but the possibility of unknown long-term adverse effects on children exposed to zidovudine must be weighed against the benefit of a considerable decrease in HIV transmission. Pregnancy is not associated with a higher rate of progression to AIDS, and HIV infection has no adverse effect on the pregnancy outcome in asymptomatic women.

Anti-HIV Agents↗
PubMed1996

Long-term follow-up of patients with chronic hepatitis B after interferon treatment.

We investigated the long-term effect of interferon-alpha treatment in patients with chronic hepatitis B with regard to the response status during treatment. 97 patients with chronic hepatitis B, including 18 patients with active cirrhosis Child A, were followed for 12-110 months (mean: 40.5 months) after interferon-alpha treatment. At the end of treatment complete response with loss of HBeAg and HBV-DNA was observed in 32 patients, partial response with loss of HBV-DNA in 30 patients and non-response with persistence of HBeAg and HBV-DNA in 35 patients. Overall, delayed virological improvement was observed in 43% of the 97 patients during follow-up. Delayed clearance of HBsAg occurred more frequently in complete responders (25%) than in partial responders (13%, P = n. s.) and non-responders (3% p = 0.0217). 39% of the partial and non-responders lost HBeAg during the follow-up period. HBsAg and HBeAg clearance rates were increased in female patients compared to males (HBsAg: 21% vs. 12%, p = n. s.; HBeAg: 47% vs. 32%, p = 0.0045). Reactivation of the disease was seen in 28% of the complete responders. In the 18 patients with active cirrhosis, short- and long-term response rates were impaired. Only, 4/18 patients had a complete response during treatment and two of these patients suffered reactivation during follow-up. One patient underwent liver transplantation and five patients died due to complications of cirrhosis. Thus, in patients without apparent cirrhosis interferon-alpha treatment has a considerable long-term effect with regard to the enhanced rate of HBsAg and HBeAg clearance during prolonged follow-up.

Adult↗
PubMed1996

Antigen-processing polymorphisms in chronic hepatitis C infection.

BACKGROUND: Cytotoxic T cell (CTL) responses may influence the course of a hepatitis C infection. CTL recognize viral peptides on HLA class I molecules. Antigenic peptides for class I presentation are generated by proteasomes and transported into the endoplasmic reticulum by the TAP proteins. It is unknown whether polymorphisms of the antigen-processing genes might influence the development of chronic hepatitis C. METHODS: 75 patients with chronic hepatitis C and 99 unrelated controls were typed for TAP and LMP2 polymorphisms. Typing was done by allele-specific PCR techniques and PCR with subsequent single-stranded confirmation polymorphism (SSCP) analysis. RESULTS: Apart from minor increases of the TAP2*0101 allele and LMP2 heterozygotes in the chronic hepatitis group there were no statistically significant differences between the two groups. CONCLUSIONS: These findings suggest, that disease association for chronic hepatitis C does not extend beyond the HLA-DQ locus. Although TAP and LMP play an important role in the processing of viral antigens, their limited polymorphisms do not show any association with the development of chronic hepatitis C.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Proliferative response of CD4+ T cells and hepatitis B virus clearance in chronic hepatitis with or without hepatitis B e-minus hepatitis B virus mutants.

To assess the significance of cell-mediated immunity, T cells were derived from the peripheral blood and liver tissue of hepatitis B virus (HBV)-infected patients and controls. The analysis of the 3H-thymidine-uptake in response to a panel of recombinant HBV antigens revealed that peripheral blood mononuclear cells (PBMC) of the 25 viremic patients with inflammatory active, chronic hepatitis B, 16 with wild-type and nine with HBe-minus HBV mutant infection, showed stronger proliferative responses to HBc and HBe antigens than 16 asymptomatic nonviremic HBsAg carriers with normal aminotransferase levels (HBc: SI 19.3 +/- 3.9 vs. 13.0 +/- 3.2 vs. 8.0 +/- 1.2; P < .01 and HBe: SI 16.6 +/- 4.0 vs. 10.7 +/- 3.5 vs. 6.9 +/- 1.5; P < .05). In 15 patients with acute self-limited hepatitis B, however, significantly stronger HBc antigen-specific T-cell responses were observed during HBV clearance and HBe/anti-HBe seroconversion, whereas in nine completely HBV-immunized patients only minor proliferative responses to HBV antigens were observed. Six HBe/HBcAg- and two HBeAg-specific CD4+ T-cell lines could be expanded from liver tissue and peripheral blood of six viremic patients with chronic hepatitis B. Irrespectively of HBV mutations the HBV-specific activation of the T-cell lines was restricted by the presence of HLA-DR molecules and resulted in the release of Th1-like cytokine patterns. Follow-up of interferon (IFN) recipients showed simultaneous short-term increase of HBc/HBe-specific T-cell reactivities in responder patients during HBV clearance and HBe/anti-HBe seroconversion, whereas in nonresponders high virus load and HBV-specific immune responses were in imbalance.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1995

HCV replication in mononuclear cells stimulates anti-HCV-secreting B cells and reflects nonresponsiveness to interferon-alpha.

Recently, it was demonstrated in chronic hepatitis C that the release of IgG and IgM anti-HCV antibodies by mononuclear cells (PBMCs) correlated with inflammatory activity, HCV persistence in serum, and negative outcome from antiviral therapy. Thus, persistent antigenic stimulation of the antibody-secreting B cells has been suggested. In this study, PBMCs were derived from 13 patients with chronic hepatitis C. Nucleic acids were extracted by the guanidine-thiocyanate-method, and plus- and minus-stranded HCV-RNAs were determined using primers from the 5'-untranslated region of HCV. Simultaneously, unstimulated PBMCs were cultured for 8 days and anti-HCV antibodies were detected in the supernatants by EIA and RIBA. Seven patients (53.8%) had both plus- and minus-stranded HCV-RNA in PBMCs, while anti-HCV antibodies were secreted in vitro. One of 2 patients with plus- but not minus-stranded HCV-RNA in PBMCs was anti-HCV positive in vitro, whereas 4 patients without HCV-infected PBMCs were anti-HCV negative in vitro. Eight patients received antiviral therapy with interferon-alpha 2b. Four nonresponders and 1 partial responder had plus- and minus-stranded HCV-RNA in PBMCs and anti-HCV secretion in vitro. On the other hand, 2 complete responders and another partial responder showed neither HCV infection of PBMCs nor anti-HCV secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Posttransfusional, LKM-1-autoantibody-positive hepatitis C virus infection, cryoglobulinemia, and aplastic anemia.

Aplastic anemia is occasionally caused by viral hepatitis, hepatitis C virus being the most important factor. Pathogenetically, decreased bone marrow function, abnormalities of the bone marrow microenvironment, and immune-mediated suppression of hematopoiesis are important. Hepatitis C virus infection is associated with a variety of extrahepatic manifestations including autoimmune features like cryoglobulinemia, Sjögren's syndrome, and autoimmune hepatitis. Here we report the case of a 42-year-old man with aplastic anemia due to posttransfusional hepatitis C virus infection associated with cryoglobulinemia and LKM-1 autoantibodies. Following a triple immunosuppressive therapy, there was a complete reconstitution of the bone marrow. Serum HCV-RNA as well as plus- and minus-stranded HCV-RNA in peripheral blood mononuclear cells (PBMC) were detected before immunosuppressive therapy. After therapy, serum HCV-RNA persisted. Furthermore, PBMC now were positive for plus-stranded RNA only. However, in bone marrow-derived precursor cells we failed to demonstrate HCV molecules after therapy. This would argue for reconstituted PBMC from newly generated uninfected precursor cells. It remains unclear as to whether the autoimmune character of the disease or the hepatitis C virus infection itself have contributed to the pathogenesis of the aplastic anemia.

Adult↗
PubMed1995

Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge.

BACKGROUND/AIMS: Kupffer cells are involved in local immunoregulation in the liver by secretion of cytokines and direct cellular contact. They are able to influence the function of other liver cells, i.e. sinusoidal endothelial cells, Ito cells and hepatocytes. The three known major functions of Kupffer cells are clearance of endotoxin from the portal circulation, release of soluble mediators and presentation of antigen. METHODS: Human Kupffer cells were isolated by collagenase perfusion followed by centrifugal elutriation and analyzed for cytokine secretion after 3 days in culture. RESULTS: We found that freshly isolated human Kupffer cells secreted the anti-inflammatory cytokine interleukin-10 in response to stimulation with lipopolysaccharide. The release of interleukin-10 was maximal 12-24 h after lipopolysaccharide challenge. Furthermore, we could show that exogenous interleukin-10 downregulated the release of the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha by Kupffer cells after lipopolysaccharide stimulation. The release of interleukin-6 was maximal 24 h after stimulation and interleukin-10 inhibited interleukin-6 release after 6 h. Tumor necrosis factor alpha showed maximal secretion 6 h after stimulation and exogenous interleukin-10 also downregulated the tumor necrosis factor alpha release after 6 h. CONCLUSIONS: Kupffer cells are exposed physiologically to lipopolysaccharide present in portal venous blood. Given the known anti-inflammatory effect of interleukin-10, our findings of secretion of interleukin-10 by Kupffer cells in response to lipopolysaccharide and suppression of interleukin-6 and tumor necrosis factor alpha release by Kupffer cells in vitro through exogenous interleukin-10 suggest an important role for interleukin-10 in the regulation of the local immune response in the liver sinusoid.

Cytokines↗
PubMed1995

[Pulmonary manifestations in HIV patients: role of thoracic radiography, CT and HRCT].

AIM: To determine the prevalence of pulmonary changes on chest radiographs and computed tomography (CT/HRCT) in HIV patients and their relation to pulmonary symptoms. MATERIAL AND METHOD: 64 HIV patients were examined prospectively. 15 had no respiratory symptoms (group I), 30 had non-specific respiratory symptoms (group II), 19 complained of dyspnoea (group III). Chest radiographs and CT were performed within a week. In patients with positive findings, bronchoscopy was carried out with bacteriological and histological examinations. RESULTS: In group 1, 13% of chest radiographs and 40% of CTs showed infiltrative changes. In group II, the figures were 27% and 57% respectively. In group III, abnormalities were found in all cases by both examinations. CONCLUSIONS: In the absence of pulmonary symptoms, imaging is not indicated since it has no clinical consequences. In the presence of pulmonary symptoms, CT/HRCT should be performed whether the chest radiograph is normal or not, since it may reveal additional information.

Adult↗