Biomedical subjects

Thomas Watkins-Riedel

Publications and source records attributed to Thomas Watkins-Riedel.

7 recordsLinked to original sources

PubMed2005

Lack of impact of ABO blood group or corresponding isoantibodies on the immune response after rabies vaccination.

Demand for rabies hyperimmunoglobulin has increased recently, requiring optimization of vaccination schemes for immunized plasma donors. Possible resemblance of rabies vaccine to blood group antigens and consequential association of the immune response to rabies vaccine and blood group or corresponding isoantibodies has not yet been investigated. We analyzed antirabies antibodies after rabies vaccination and ABO blood group in 142 individuals, and isoantibody titers in 92 of those individuals. We did not find any correlation of the immune response with blood group or isoantibody levels. There was also no correlation with the sex of individuals, but there was a weak correlation between age and rabies-specific antibody level. Rabies vaccination schemes for immunized donors cannot be optimized on the basis of blood groups or isoantibody titers.

ABO Blood-Group System↗

PubMed2004

Early prediction of hepatitis C virus (HCV) infection relapse in nonresponders to primary interferon therapy by means of HCV RNA whole-blood analysis.

BACKGROUND: Routine analysis of serum and/or plasma specimens for hepatitis C virus (HCV) RNA does not always correctly reflect the response to antiviral therapy. Analysis of whole-blood specimens for detection of viral RNA should provide more-accurate prognostic information. METHODS: Whole-blood, serum, and plasma specimens (268 sample sets) were obtained from 56 patients who did not respond to initial interferon (IFN)- alpha 2b monotherapy (5 MU every 2 days for 3 months). Specimens were analyzed for HCV RNA by 4 different types of reverse-transcriptase polymerase chain reaction (RT-PCR) (Cobas Amplicor HCV-2.0 [Roche], LightCycler real-time PCR [Roche], and 2 in-house RT-PCRs) to determine whether specimen type can predict the rate of virologic response to high-dose treatment with IFN (10 MU every 2 days) and ribavirin (1-1.2 g/day). RESULTS: Of the 56 patients who provided specimens, serum and plasma obtained from 18 tested negative for HCV RNA at the end of treatment, indicating a complete virologic response. In contrast, analysis of whole-blood specimens obtained at the same time revealed the presence of viral RNA in 12 of these 18 patients. All 12 subjects had relapse of HCV in serum and plasma: 11 relapsed a median of 4 weeks after the end of treatment, and 1 relapsed 20 weeks after the end of treatment. None of these 12 patients--all of whom consistently had whole-blood specimens that tested positive and plasma and serum specimens that tested negative for HCV RNA up to 20 weeks before the end of treatment--showed a sustained virologic response (P=.0002). CONCLUSIONS: Results of whole-blood tests for detection of HCV RNA were highly predictive of viral relapse (positive predictive value, 100%) and thus may be useful tools for monitoring and tailoring IFN/ribavirin therapy. Testing of only serum or plasma specimens underestimates the true circulating HCV load and leads to an overestimation of antiviral response rates.

Adult↗

PubMed2004

Physical state and expression of HPV DNA in benign and dysplastic cervical tissue: different levels of viral integration are correlated with lesion grade.

OBJECTIVE: Human papillomavirus (HPV) infection is the most important event in the malignant transformation of human cervical epithelium. Several high-risk (HR-)HPV subtypes have been identified, which lead to CIN and subsequently to invasive carcinoma. The reason for this phenomenon is still unknown, but it seems to be related to the physical state of HPV DNA. METHODS: Digene HC II test was used to identify HR- and/or low-risk (LR-)HPV infections in cervical swabs of 275 women attending our clinic for routine cytological screening and/or colposcopy because of an abnormal Pap smear comprising low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL). Specific HR (16, 18, 31, 33, 52b, 58) and LR (6, 11) subtypes were characterized in cervical biopsies of 10 women with benign cellular changes and of 68 women with CIN I-III by the PCR-restriction enzyme method. The physical state of HPV DNA (episomal, mixed and integrated form) was analyzed by bi-dimensional (2D)-gel electrophoresis. In addition, mRNA expression of E6/E7 genes was analyzed by RT-PCR. Furthermore, the relative virus load was determined in nine selected cases. The physical state and transcriptional activity of HPV DNA were then correlated to histopathological results. RESULTS: LR-HPV infection [27 cases (9.8%)] and HR-HPV infection [121 cases (44%)] of cervical swabs were clearly correlated to the degree of SIL. Further HPV typing in cervical biopsies of 78 women showed that HPV6 and 11 were restricted to benign cellular changes, CIN I and II, whereas HPV16 and 18 were observed predominantly in CIN III/CIS (P=0.01). No clear distribution pattern was observed for HPV31, 33, 52b and 58. Expression of HPV E6 and E7 transcripts was uniformly correlated with the different physical state of HPV DNA. Analyzing the physical state of these HPV subtypes, HPV6 and 11 could only be detected as an episomal form, independent of SIL grade. In normal epithelium and in CIN I and II, HPV16 and 18 were exclusively found in the episomal form. In CIN III/CIS, 15 of 30 cases of HPV16 (50%) and 16 of 17 cases of HPV18 (94%) were exclusively integrated into the host genome. Like HPV16/18, HPV31, 33, 52b and 58 were also present in the episomal form in normal epithelium and in CIN I and II, but were integrated in 80% of the CIN III/CIS (4/5) cases. CONCLUSION: Absent integration of HPV16 DNA in some CIN III/CIS suggests that integration is not always required for progression early dysplastic lesions. In contrast, integration of HPV type 18 and others appears to be of major importance for the transforming efficacy of cervical dysplasia. The applied method represents a sensitive instrument to assess the physical state of HPV and is useful to predict the progression of disease.

Adult↗

PubMed2003

Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load.

Early interferon (IFN) therapy prevents viral persistence in acute hepatitis C, but in view of the resulting costs and morbidity patients who really need therapy have to be identified. Twelve consecutive patients with acute hepatitis C (9 women, 3 men, mean age: 39.5 +/- 18.8 y, genotype 1: 7, genotype 3a: 3, 2 could not be genotyped) were studied. The sources of infection were medical procedures in 6, sexual transmission in 3, and intravenous drug abuse in 3 patients. Viral load was measured by Cobas Amplicor HCV Monitor v2.0 (Roche Diagnostic Systems, Branchburg, NY). The time from infection to clinical symptoms was 43.3 +/- 8.6 (mean +/- SD) days. Eight patients cleared hepatitis C virus (HCV) spontaneously and remained HCV-RNA negative with a follow-up of 9.0 +/- 3.9 months. In these patients viral load declined fast and continuously. The time from exposure to HCV-RNA negativity was 77.4 +/- 25.3 and from the first symptoms was 34.7 +/- 22.1 days. In 4 patients HCV-RNA levels remained high or even increased. Two of them became sustained responders to treatment initiated after a 6-week observation period. The 2 remaining patients were not treated (one because of contraindications for IFN, the other declined therapy) and are still HCV-RNA positive. In conclusion, patients with acute icteric hepatitis C have a high rate of spontaneous viral clearance within the first month after the onset of symptoms. IFN therapy appears only needed in patients who fail to clear the virus within 35 days after onset of symptoms. By this approach, IFN therapy was not necessary in two thirds of patients with acute hepatitis C.

Acute Disease↗

PubMed2002

Detection of hepatitis C virus (HCV) RNA in normal cervical smears of HCV-seropositive patients.

The presence of hepatitis C virus (HCV) in normal cervical smears (CS) obtained from 22 HCV-seropositive and 50 HCV-seronegative patients was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR). The presence of HCV in serum was established by use of enzyme-linked immunosorbent assay, Western blot test, and RT-PCR. HCV was detected in 36.4% (n=8) of CS cells recovered from 22 HCV-seropositive patients, but not in CS samples obtained from 50 HCV-seronegative patients. Furthermore, cells from the CS of 2 seropositive/smear-positive patients and 1 seropositive/smear-negative patient were isolated; HCV RNA was detectable in the cervical lymphocytes of the 2 smear-positive patients, but not in epithelial cells or granulocytes. HCV RNA is detectable in the CS of some HCV-seropositive women. The clinical importance of these data requires further study.

Adult↗

PubMed2002

Rapid diagnosis of enterovirus infections by real-time PCR on the LightCycler using the TaqMan format.

A 2 h single-tube, reverse-transcription(RT)-PCR/hybridization assay using the TaqMan format for rapid diagnostic screening of enterovirus (EV) infections was optimized for the real-time LightCycler (LC) technology. For low EV load clinical samples an additional 30 min reamplification step using a novel primer-mix/probe design resulted in a 100% concordance with AMPLICOR EV PCR Test and in-house RT-PCR. Combined with maximum specificity, the sensitivity of LC-PCR was 10- to 100-fold higher compared to AMPLICOR EV Test.

Enterovirus↗

PubMed2002

Hepatitis C viral dynamics: basic concept and clinical significance.

Viral dynamics is a concept analyzing the time course of treatment-induced changes in blood virion concentration (kinetics) to derive conclusions of where, when and how in the living organism virions are produced or eliminated. Originally applied to human immunodeficiency virus type 1 and hepatitis B virus, it has elucidated mechanisms of antiviral therapy in hepatitis C virus infection as well. This review summarizes key aspects of mathematical modeling as well as important clinical applications, namely induction therapy and prediction of virologic response to treatment. Furthermore, limitations of currently available quantitative assays will be discussed.

Antiviral Agents↗