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Biomedical subjects

M Schröter

Publications and source records attributed to M Schröter.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence, incidence, and clinical relevance of the reverse transcriptase V207I mutation outside the YMDD motif of the hepatitis B virus polymerase during lamivudine therapy.

The reverse transcriptase V207I mutation within the hepatitis B virus (HBV) polymerase is associated with resistance to lamivudine in vitro. The prevalence of this mutation in treatment-naive patients was 1% (1/96). A follow-up of the patient carrying this mutation prior to treatment revealed no loss of sensitivity of HBV to lamivudine in vivo.

Amino Acid Sequence↗
PubMed2002

[Hepatitis C. Virology, transmission modes, clinical aspects, prevention and therapy].

Of the various forms of chronic viral hepatitis, in Germany 60-70% are caused by the hepatitis C virus (HCV). The virus arrives inconspicuously, i.e. an acute infection only leads to an increase in transaminases in 40% of cases and to an increase in bilirubin in only 20%. However, approximately 90% of infections take a chronic course and in 20% this leads to cirrhosis after only 20 years. The infection rate of medical personnel is not significantly higher than in the general population. The transmission of HCV from patients to medical personnel, e.g. by needle stick injuries, is very rare and the risk of infection is less than 1%. Even less frequently transmission of HCV in the reverse direction from medical personnel to patients occurs. An active or passive prophylactic immunization is not possible and protective immunization is not yet foreseeable. Recently, progress has been made with chemotherapeutical treatment of HCV. The present state-of-the-art is pegylated interferon-a in combination with ribavirin. The success rate in HCV genotypes 2 and 3 is clearly higher with 70-80% than in genotypes 1 and 4 with approximately 40%. Both drugs have significant side-effects but better forms of medication are not yet available.

Genotype↗
PubMed2002

Prevalence of SENV-H viraemia among healthy subjects and individuals at risk for parenterally transmitted diseases in Germany.

The prevalence of a newly described DNA virus (SENV-H) was examined in a population of 599 individuals by polymerase chain reaction (PCR). All individuals were assigned to a nonrisk or a risk group depending on the presence of historical or serological factors indicating an increased risk for parenterally transmitted diseases. In a group of 226 healthy blood donors, 38 (16.8%) were found to be SENV-H viraemic. The highest prevalence of SENV-H viraemia was observed among patients infected by HIV (28 of 63; 44.4%). Contrarily, of 78 individuals on maintenance haemodialysis, only 10 (12.8%) were found positive in the SENV-H PCR. Our results demonstrate that SENV-H viraemia is widespread in the general population. Therefore, it seems to be questionable if parenteral transmission is the main route for spreading SENV-H. The hepatitis-inducing capacity of SENV-H is unclear. However, taking our clinical and epidemiological data into account it seems unlikely that this virus is responsible for hepatitis.

Adolescent↗
PubMed2001

20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype adw.

We investigated subtype-dependent development of lamivudine resistance in hepatitis B virus (HBV) longitudinally in 26 consecutive patients (13 adw and 13 ayw carriers) during antiviral treatment of chronic hepatitis B. Lamivudine resistance developed in seven adw carriers and one ayw carrier. Risk of lamivudine resistance was significantly higher for adw carriers than for ayw carriers (p=0.03). We believe that the adw subtype of HBV is associated with a high risk of lamivudine resistance, which might be linked to simultaneous changes of the HBsAg that occurs with the emergence of resistance.

Adult↗
PubMed2001

Strategies for reliable diagnosis of hepatitis C infection: the need for a serological confirmatory assay.

The aim of the study was to examine whether the diagnosis of Hepatitis C (HCV) infection can be obtained reliably without using an immunoblot-based confirmation assay. 1,708 EIA-reactive serum samples were examined retrospectively for (i) optical density value in the screening assay, (ii) reactivity in an immunoblot assay, and (iii) result by RT PCR. In 1,394 (81.0%) samples positive results were obtained by both the HCV EIA and the confirmation assay. OD-values > or = 2.2 were observed in 1026 of these samples, but covered the range from 0.4 to 2.1 in the other 368 samples. The combination of HCV EIA reactivity and indeterminate immunoblot assay was observed in 134 (7.8%) serum samples. HCV RNA was detected in 58 cases by PCR. The OD-values of these 58 samples ranged from 0.4 to >2.2. Especially reactivity against the core recombinant protein was indicative of PCR positivity. The reactivity by the HCV EIA could not be confirmed by immunoblot assay or PCR in 180 (10.5%) sera. These false reactive sera showed OD values by EIA from 0.3 to 2.1. It is concluded that no threshold values can be defined which would allow differentiation between positive, indeterminate, and false reactive result by HCV EIA without producing an unacceptably high number of false negative diagnoses. Not using immunoblot-based confirmation would result in many additional PCR examinations. Therefore, confirmation of reactive HCV EIA results by a serological confirmatory assay must remain an essential part of the diagnostic procedure.

DNA, Viral↗
PubMed2001

Correlation of hepatitis B virus load with loss of e antigen and emerging drug-resistant variants during lamivudine therapy.

It remains unclear whether sequential assessment of hepatitis B virus (HBV) load during lamivudine therapy can predict the loss of hepatitis B e antigen or emergence of drug-resistant variants. Therefore, a longitudinal study was carried out in 28 consecutive patients with chronic hepatitis B who started lamivudine therapy for a median of 12 months (range, 6-31). HBV DNA copy numbers were determined at 3-month intervals. From month 6 onward, HBV viral load below the detection limit of the PCR was predictive of the loss of envelope antigen (P = 0.043). Continuously detectable HBV DNA during the first 12 months of treatment indicated emergence of drug-resistant variants (P = 0.034). These data suggest that the goal of lamivudine therapy should be complete suppression of serum HBV DNA.

Administration, Oral↗
PubMed2001

Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients.

BACKGROUND: Resistance-associated mutations in HIV-1 evolve even under highly active antiretroviral therapy. OBJECTIVE: To evaluate the clinical efficacy of genotypic-resistance testing (GRT), to estimate the potential of a given antiretroviral therapy for prevention of further resistance mutations. STUDY DESIGN: Ten patients were treated prospectively with drugs, according to the results of a GRT. Five patients were allocated to group I in which antiretroviral therapy could be switched to an effective regimen (consisting of at least three sensitive drugs, from at least two different classes of antiretroviral substances). Five patients (group II) had no option for effective therapy, and continued to be treated non-effectively (at least one applicated substance class only intermediately sensitive, or resistant). GRT and quantitative viral cultures were performed longitudinally for 8 months. Also, plasma HIV-1 RNA, total CD4+ cells, and rates of productively infected CD4+ cells were determined. RESULTS: All the patients in group I showed a significant decrease of HIV-RNA of >1 log/ml (mean, -1.35 log/ml, P=0.025). The mean increase of CD4+ cells was 46 (not significant). The rate of productively infected CD4+ cells decreased significantly (mean, -16 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04). In this group no further resistance mutations were detected after 8 months. In group II, none of the patients showed a significant decrease of HIV-1 RNA (mean, +0.05 log/ml), total CD4+ cells decreased (mean, -35, not significant), the rate of productively infected CD4+ cells increased significantly (mean, +124 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04), and 4 of 5 patients had additional mutations in the RT gene conferring multi-drug resistance within 8 months (P=0.048). CONCLUSIONS: GRT is predictive of the efficacy of a therapeutic regimen, in particular regarding evolution of further resistance mutations.

Adult↗
PubMed2001

Comparison of three HCV genotyping assays: a serological method as a reliable and inexpensive alternative to PCR based assays.

BACKGROUND: Determination of hepatitis C virus (HCV) genotypes and subtypes is of rising clinical importance. In times where also an increasing need for cost effectiveness can be observed, the demand for fast and easy performable assays grows. OBJECTIVES: To evaluate and compare different genotyping methods regarding their reliability, practicability, and expense in the daily routine. METHODS: Sera of 39 patients infected with different HCV subtypes were examined by a serological genotyping assay (NS-4 IBA), by the widely used INNO-LiPA HCV II, and by a nucleotide sequencing method. RESULTS: The tests performed equally well in terms of HCV subtyping and no different results were obtained. However, the serotyping assay provided the results in less than half the time needed by the other two assays. Significant differences were also observed regarding the 'hands on' times and the costs. The technical equipment which was necessary to perform the assays is significantly reduced using the serological assay. CONCLUSION: Our study demonstrates that the serological test offers the opportunity to determine HCV genotypes and subtypes reliably, fast, easy, and cost effective.

Genotype↗
PubMed2001

Relevance of reactivity in commercially available hepatitis C virus antibody assays.

Sera from 2,148 patients were tested with a third-generation microparticle enzyme immunoassay (MEIA), a confirmatory assay, and a reverse transcription-PCR. Overall, 85.6% of reactivities were confirmed, 13.2% were shown to be unspecifically reactive, and 1.2% were indeterminate. The rate of confirmed MEIA reactivities clearly depended on the strength of the reactivity.

Adolescent↗
PubMed2001

Prevalence of a novel DNA virus (TTV) among patients on maintenance hemodialysis.

BACKGROUND/AIMS: A recently detected DNA virus (TTV) has been assumed to be responsible for posttransfusion hepatitis in humans. Until now it is unclear whether patients on maintenance hemodialysis are at increased risk of acquiring TTV. METHODS: Serum samples derived from 143 chronically hemodialyzed patients were examined for TTV viremia by nested PCR. All serum specimens were also investigated for viremia and for the presence of antibodies of hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) by PCR and serological assays, respectively. RESULTS: The prevalence of TTV was determined to be 18.8% (n = 27), for HCV a prevalence of 15.4% (n = 22) and for GBV-C/HGV of 8.4% (n = 12) could be demonstrated. Parallel infection by TTV and HCV was detected in only 1.4% (n = 2) of the patients. In no serum sample could TTV and GBV-C/HGV be detected in parallel. None of the solely TTV-viremic individuals had clinical or biochemical signs of liver disease. CONCLUSION: From our data we conclude that TTV viremia is widespread among hemodialysis patients and can be detected in 18.8%. Since no viremic patient had clinical or biochemical signs of liver disease, the hepatitis-inducing capacity of TTV remains unclear.

Adult↗
PubMed2001

Area under the viraemia curve versus absolute viral load: utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients.

A novel approach to predicting symptomatic cytomegalovirus (CMV) infections combines the level and the duration of viraemia in a single parameter. Sixty-four kidney transplant recipients were monitored by quantitative shell vial culture, pp65 antigenaemia, and polymerase chain reaction (PCR) of leucocytes. The area under the curve (AUC) of each parameter was determined from the onset of viraemia to the beginning of antiviral treatment. The AUC values were significantly higher in symptomatic than in asymptomatic patients. For antigenaemia and PCR, optimal AUC thresholds for predicting symptomatic CMV infections were determined. They were superior to standard cutoff levels of absolute viral load in sensitivity, specificity, and positive and negative predictive value. In 8 of the 23 patients who became symptomatic, impending clinical features were indicated earlier by the AUC thresholds than by standard viral load. In conclusion, the concept of the AUC should facilitate identification of patients at risk of symptomatic CMV infection.

Area Under Curve↗
PubMed2000

In vivo dynamics and pathogenicity of wild-type and resistant Hepatitis B virus during long-term lamivudine monotherapy - a clinical note.

BACKGROUND: Genotypic resistance of Hepatitis B virus (HBV) against lamivudine evolves within months after onset of therapy. OBJECTIVES: To determine the longitudinal order in which resistance mutations appear and to compare the kinetics and pathogenicity of wild-type and resistant HBV. STUDY DESIGN: In a longitudinal study, consecutive samples were drawn over a period of 28 months from a patient with chronic hepatitis B, and resistance mutations were followed by sequencing a part of the polymerase region of HBV. These data were compared with HBV copy numbers, HBsAg and ALT levels, and results of consecutive liver biopsies. RESULTS: After 21 weeks of treatment, a silent mutation at codon 528 (CTG to TTG) occurred. Significant genotypic resistance was detectable after 68 weeks, indicated by a substitution of isoleucine for methionine at residue 552 (M552I). Nineteen weeks later, the virus exhibited additional resistance-associated mutations (L528M and I552V). The resulting high-level resistance was reflected by an increase of serum HBV copies of 4.7 log(10). The turnover of wild-type and resistant HBV was 2.6x10(6) and 1.8x10(6) virions/day, respectively. HBsAg and ALT levels were lower within the period when resistant HBV was detectable. During treatment the progress of liver fibrosis was arrested. CONCLUSIONS: The in vivo replicative capacities and dynamics of wild-type and resistant HBV were similar. However, resistant HBV seemed to exhibit reduced pathogenicity.

Base Sequence↗
PubMed2000

Fas-dependent tissue turnover is implicated in tumor cell clearance.

The apoptosis-inducing Fas receptor has been shown to be down-regulated in various types of tumors, while its ligand (FasL) appears to be frequently up-regulated. Here we provide evidence that there is a strong selective pressure in vivo against Fas-expressing, tumorigenic NIH3T3 cells, favoring survival, proliferation and eventually tumor formation by Fas-negative cells. Importantly, re-expression of Fas in these cells results in either the complete abolishment of tumor development, or in a significant extenuation of the latency period of tumor outgrowth. In addition, we found that environmental conditions which prevail during tumorigenesis, such as limiting amounts of survival factors and the lack of cell adhesion, are markedly sensitizing tumor cells to Fas-mediated suicide. Our data suggest that in addition to T cell-mediated immune responses, mechanisms of Fas-dependent tissue turnover are also centrally implicated in tumor cell clearance.

3T3 Cells↗
PubMed2000

Cytomegalovirus cultured from different major leukocyte subpopulations: association with clinical features in CMV immunoglobulin G-positive renal allograft recipients.

Cytomegalovirus (CMV) cultured from peripheral blood mononuclear cells (PBMCs) was shown to be associated more closely with clinical manifestations than infectious CMV in polymorphonuclear leukocytes (PMNLs) of renal allograft recipients with secondary CMV infection. Shell vial culture was carried out with ficoll-purified PBMCs and PMNLs of 71 CMV IgG-positive patients after kidney transplantation. Thirty-six patients experienced active CMV infections. Of these, 17 developed clinical symptoms. The diagnostic value of PMNLs and PBMCs viremia was determined in comparison to pp65 antigenemia, leukoDNAemia, plasma DNAemia, and detection of cytomegalic endothelial cells. In both PMNLs and PBMCs (with or without detectable endothelial cells), frequencies and levels of viremia were significantly higher among symptomatic patients. Regarding the occurrence of clinical CMV manifestations, the sensitivity of culture from PMNLs and from PBMCs fractions was 100%. Viremia in PBMCs, however, was far more specific (94%) than in PMNLs (74%). Cutoff values established previously for pp65 antigenemia and leukoDNAemia, standard markers in the laboratory, had similar specificity (96% each) to PBMCs viremia, but were less sensitive (88% each). Plasma DNA-emia was both less sensitive (82%) and less specific (69%) than PBMCs viremia. Detection of endothelemia showed maximal specificity (100%), but inferior sensitivity (47%). All patients had PBMCs viremia before the onset of symptoms. In conclusion, infectious CMV present in PBMCs may prove to be a determinant of clinical CMV manifestations in seropositive immunocompromised individuals. Factors involved in PBMCs tropism may help to understand the pathogenetic mechanisms of CMV dissemination in this group of patients.

Cells, Cultured↗
PubMed2000

[Surgical therapy of colonic diverticulitis--how reliable is primary anastomosis?].

INTRODUCTION: The aim of the study was to evaluate the modern principles of surgery in diverticulitis, e.g. early elective resection and primary anastomosis. METHODS: The data of 445 consecutive patients were retrospectively analysed after classifying all cases in four subgroups according to a modified Hinchey classification (stages 0-III). RESULTS: Within our study group the morbidity was 26.5% (n = 118) and the mortality was 1.6% (n = 7). In 96% (n = 425) of all cases and in 64% (21/33) of patients with perforated diverticulitis and peritonitis (stage III), a primary anastomosis was performed. Four patients of the study group showed insufficient anastomosis (0.9%). No leakage was observed from any of the anastomoses performed in stage III diverticulitis. Stage of inflammation and age of patient correlate with morbidity and mortality. Some 53% (94/177) of the patients in stage II and 67% (22/33) of the patients in stage III had never showed symptoms of diverticulitis before. CONCLUSION: Prophylactic surgery to avoid life-threatening situations, including abscess formation or perforation, is not possible in many cases. However, especially patients at risk (age, coexisting illness) should undergo early surgery. Primary anastomosis can be performed safely even at an advanced stage.

Adult↗
PubMed2000

Detection of TT virus DNA and GB virus type C/Hepatitis G virus RNA in serum and breast milk: determination of mother-to-child transmission.

To investigate the vertical transmission of the newly described TT virus (TTV), serum and breast milk samples from 46 women as well as sera from their 47 newborns were examined for the presence of TTV DNA by PCR. TTV DNA was detected in 47.8% (n = 22) of the women. All but one child born to these women were also viremic for TTV from the first sample onward. TTV DNA was found in 73.9% (n = 17) of the breast milk samples derived from TTV viremic mothers. The one TTV-negative child born to a viremic mother remained negative during follow-up, although it was breast-fed. Our data show that TTV is highly effectively transmitted from mothers to their children during pregnancy. Although the majority of breast milk samples from viremic mothers are positive by TTV PCR, there is no need to discourage women from breast-feeding, because most children are TTV viremic even before breast-feeding begins.

Animals↗