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A Stary

Publications and source records attributed to A Stary.

At least 19 recordsLinked to original sources
PubMed2003

Xeroderma pigmentosum variant and error-prone DNA polymerases.

Replicative DNA synthesis is a faithful event which requires undamaged DNA and high fidelity DNA polymerases. If unrepaired damage remains in the template DNA during replication, specialised low fidelity DNA polymerases synthesises DNA past lesions (translesion synthesis, TLS). Current evidence suggests that the polymerase switch from replicative to translesion polymerases might be mediated by post-translational modifications involving ubiquitination processes. One of these TLS polymerases, polymerase eta carries out TLS past UV photoproducts and is deficient in the variant form of xeroderma pigmentosum (XP-V). The dramatic proneness to skin cancer of XP-V individuals highlights the importance of this DNA polymerase in cancer avoidance. The UV hypermutability of XP-V cells suggests that, in the absence of a functional poleta, UV-induced lesions are bypassed by inaccurate DNA polymerase(s) which remain to be identified.

Animals↗
PubMed2002

Cost effectiveness of screening for Chlamydia trachomatis: a review of published studies.

OBJECTIVE: Screening for Chlamydia trachomatis in the lower genital tract may contribute to the prevention of pelvic inflammatory disease in women. The purpose of this review was to critically appraise, and summarise studies of the cost effectiveness of screening for C trachomatis. METHODS: A literature search was conducted on Medline and in Health Star from 1990-2000. Keywords were C trachomatis, screening, cost effectiveness. Bibliographies of reviewed articles were also searched. The population studied was asymptomatic sexually active women under 30 years of age in a primary care setting. The intervention assessed was screening for lower genital tract infection with C trachomatis and the outcomes studied were cases of C trachomatis detected, cases of PID prevented, and associated costs. Studies were assessed using the Drummond criteria for economic evaluations. They were assessed qualitatively as they were too heterogeneous to allow quantitative analysis. RESULTS: 10 studies were included. All were modelled scenarios and all found screening to be more cost effective than simply testing symptomatic women, although all were based on probabilities that were assumed. Six of the studies focused on DNA based testing, three of them using urine. The models showed screening to be cost effective at prevalences of 3.1-10.0%, and cost saving (overtesting symptomatic women) at a prevalence as low as 1.1%, if age was used as a selection factor and DNA based tests were used in urine samples. CONCLUSIONS: At the prevalence of infection expected in the target population, all studies suggest screening is cost effective. However, the assumptions used in the models have been difficult to confirm and there is a need for more data, particularly on the risk of complications in women with asymptomatic lower tract infection.

Chlamydia Infections↗
PubMed2001

Sexually transmitted infections and human immunodeficiency virus infection in Europe: the way ahead?

The incidence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) infection is increasing in Europe. The reasons for this are multifactorial but ease of travel is one of them. This is worrying in view of the established role of STIs in facilitating HIV transmission. Care of this group of infections is provided by a variety of doctors, often not following agreed guidelines. It is vital that doctors and their specialist societies engage in setting standards, in ensuring that STIs and HIV infection are moved up the healthcare agendas of all European countries and in making sure that access to care is rapid. Surveillance should be enhanced, interventions evaluated and the media engaged.

Adolescent↗
PubMed1999

Correct samples for diagnostic tests in sexually transmitted diseases: which sample for which test?

Amplified DNA technology such as the polymerase chain reaction (PCR) and ligase chain reaction (LCR) are new techniques for the diagnosis of genital chlamydial infections in both men and women. These tests are highly sensitive and specific in detecting chlamydial genes in different specimen types such as genital samples as well as in non-invasive specimens such as urine and vulval smears. Due to the advantage of a high reliability of these techniques even when they are performed on non-invasive specimen types, amplification tests allow chlamydial diagnosis for screening especially high risk persons as the basis of chlamydia control programs.

Chlamydia Infections↗
PubMed1999

The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes.

The human XPB DNA helicase is a subunit of the DNA repair/basal transcription factor TFIIH, involved in early steps of the nucleotide excision repair pathway. Two distinct clinical phenotypes, xeroderma pigmentosum associated with Cockayne's syndrome (XP/CS) and trichothiodystrophy (TTD), can be due to mutations in the XPB gene. In the present work, we studied cellular DNA repair properties of skin fibro-blasts from two patients mutated in the XPB gene: an XP/CS patient cell (XPCS2BA) with a T296C (F99S) transition and a TTD patient cell (TTD6VI) exhibiting an A355C (T119P) transversion. Both cells are clearly associated with different levels of alterations in their response to UV light. To establish the relationship between the relative expression level of these two alleles and DNA repair properties, we transfected SV40-transformed XPCS2BA (XPCS2BASV) cells with a plasmid (pTTD6VI) carrying the XPB-A355C cDNA and examined DNA repair properties after UV irradiation (cell survival, unscheduled DNA synthesis and kinetics of photoproduct removal) in stable transfectants. We isolated three clones, which express the XPB-A355C gene (Cl-5) or the XPB-T296C gene (Cl-14) or both genes (Cl-19). This con-stitutes a model system allowing us to correlate the relative expression levels of the XPB-A355C (TTD) and XPB-T296C (XP/CS) genes with various DNA repair properties. Overexpression of the XPB-A355C (TTD) gene in an XP/CS cell gives rise to a cellular phenotype of increased repair similar to that of TTD6VI cells, while equal expression of the two mutated genes leads to an intermediate cellular phenotype between XP/CS and TTD.

Cell Line, Transformed↗
PubMed1998

Cyclobutane pyrimidine dimers are the main mutagenic DNA photoproducts in DNA repair-deficient trichothiodystrophy cells.

We have used the replicating shuttle vector pR2 to determine the role of ultraviolet C (UVC)-induced cyclobutane pyrimidine dimers (CPDs) and nondimer photoproducts in mutagenesis in human trichothiodystrophy (TTD) cells and in their repair-proficient counterparts obtained after complementation with the wild-type XPD/ERCC2 repair gene (TTD + ERCC2 cells). Before transfection in human cells, the UVC-irradiated vector DNA was treated with Anacystis nidulans photolyase [photoreactivation (PR) procedure] that selectively removed CPDs, leaving nondimer photoproducts intact. The mutant frequency of the UV-irradiated pR2 plasmid treated by PR was similar after replication in TTD or in TTD + ERCC2 cells. This result indicates that TTD cells were able to repair nondimer photoproducts as efficiently as TTD cells complemented with the wild-type repair gene and that in TTD cells, CPDs were the major photoproducts generating an increased mutant frequency after UVC irradiation. Sequence analysis of > 300 mutant plasmids indicated that PR of the DNA increased the relative level of tandem mutations and decreased the relative level of multiple mutations in TTD cells. In both cell lines, we observed that CPDs mostly led to GC-AT transitions; whereas only nondimer photoproducts were responsible for the induction of GC-TA transversions in TTD and TTD + ERCC2 cells.

Base Sequence↗
PubMed1998

Urethritis. Diagnosis of nongonococcal urethritis.

Nongonococcal urethritis (NGU) frequently occurs in men after infection of the lower genital tract with a genital pathogen and is mostly associate with complaint of a scanty, thin discharge and urinary symptoms. Management of NGU includes clinical examination, microbiological diagnosis of genital pathogens, and efficient treatment as well as contact tracing. Diagnosis, especially of the Chlamydia trachomatis, the most frequent cause of NGU, has improved by using amplification assays for the detection of DNA or rRNA. These new methods have the advantage of a higher sensitivity especially for specimens with a low number of infectious agents. In addition, they enable the use of urine as a noninvasive specimen type.

Bacteriuria↗
PubMed1998

Performance of transcription-mediated amplification and ligase chain reaction assays for detection of chlamydial infection in urogenital samples obtained by invasive and noninvasive methods.

Based on the amplification of chlamydia-specific rRNA sequences and the ligase chain reaction (LCR), the performance characteristics of the Gen-Probe Chlamydia trachomatis transcription-mediated amplification (TMA) assay were evaluated with endocervical, urine, and vulval specimens from women and urethral and urine specimens from men and were compared with those for cultures on endocervical, vulval, and urethral swabs. Of the 308 women and 240 men tested, 25 (8.1%) and 44 (18.3%), respectively, were shown to be infected. By using the infected individual as the expanded "gold standard" for calculations, the TMA assay and LCR gave similar performances for the sensitivity of male urethral (93.2%) and urine (88.6 and 86.4%) samples, while culture detected only half of the 44 infected men. In women, the sensitivities of the TMA assay for endocervical and vulval samples were 88 and 92%, respectively, compared to values of 92% for the LCR on both sample types and of 52 and 8%, respectively, for culture. By using first-void urine for chlamydial diagnosis in women, LCR detected 24 (96%) and TMA assay detected 19 (76%) infected individuals, showing a significantly lower sensitivity for urine in women (P = 0.0253). The results indicate a high overall agreement for both amplifying techniques for all examined specimen types, except for female urine. Furthermore, they confirm the previous observation that vulval swabs are an effective alternative noninvasive sample type for the detection of C. trachomatis infection in women by nucleic acid-based amplification technologies.

Cervix Uteri↗
PubMed1998

Fluconazole in the treatment of tinea corporis and tinea cruris.

BACKGROUND: Results of topical dermatomycosis treatment are often unsatisfactory, particularly in patients with extended or multiple infection sites. OBJECTIVE: Given the high fluconazole concentrations attainable in the stratum corneum and the long elimination half-life of fluconazole, we investigated whether efficacy is satisfactory when using fluconazole at once weekly doses of 150 mg. METHODS: In an open, noncomparative study, tinea corporis and cruris patients were treated with once weekly fluconazole 150 mg over 2-4 weeks. Clinical (pruritus, erythema, scaling, burning/pain, vesiculation) and mycologic (culture and microscopy) assessments were performed before treatment, at weekly intervals until the end of treatment and 3 weeks after treatment. All adverse events were recorded. RESULTS: The total severity scores of clinical symptoms were reduced from 7.1 before to 1.5 after treatment (p = 0.001, n = 100 patients). Seven patients experienced adverse events. CONCLUSIONS: Fluconazole 150 mg once weekly for 2-4 weeks is an efficacious and safe regimen in the treatment of tinea corporis and cruris.

Antifungal Agents↗
PubMed1997

[Xeroderma pigmentosum].

MAIN CLINICAL FEATURES: Xeroderma pigmentosum is a rare, recessive disorder clinically characterized by extreme photosensitivity, pigmented abnormalities of the skin-exposed areas, and frequent ocular and neurological abnormalities. Xeroderma pigmentosum syndrome is associated with an estimated 2000-fold increase in the risk to develop skin cancer (basal cell carcinoma, squamous cell carcinoma and melanoma). A HETEROGENEOUS DISEASE: Skin or blood cells from Xeroderma pigmentosum patients are hypersensitive to killing by ultraviolet and hypermutable after ultraviolet C treatment Cell fusion experiments based on complementation of repair synthesis have recognized the presence of seven Xeroderma pigmentosum groups which exhibit various defects in the initial steps of the DNA nucleotide excision repair pathway. A variant Xeroderma pigmentosum form has been found to be normal in nucleotide excision repair but abnormal in a poorly to be normal in nucleotide excision repair but abnormal in a poorly understood postreplication repair process. PATHOPHYSIOLOGY: The Xeroderma pigmentosum complementation groups differ in terms of severity of clinical, cellular and genetic features. Molecular and biochemical studies of the Xeroderma pigmentosum syndrome have led to a better understanding of the mechanisms of ultraviolet-induced sensitivity and the mechanism of cancer development after ultraviolet exposure.

Humans↗
PubMed1997

Mycoplasma hominis and Ureaplasma urealyticum in patients with sexually transmitted diseases.

Mycoplasma hominis and Ureaplasma urealyticum can be isolated with considerable frequency from the human urogenital tract and are thought to cause various syndromes such as nongonococcal urethritis, pelvic inflammatory disease, pyelonephritis or infertility. The aim of this study was the evaluation of the presence of different genital pathogens in patients with sexually transmitted diseases (STD) and, in particular, the detection of mycoplasmas in individuals infected with genital microbes and an assessment of the presence of genital microorganisms in patients harbouring Mycoplasma hominis or Ureaplasma urealyticum. Furthermore, the occurrence of mycoplasmas in women with bacterial vaginosis was established. Specimens were collected from a total of 41,980 persons attending the Outpatients' Centre for Infectious Venero-Dermatological Diseases in Vienna from 1994 to 1996. Of all genital pathogens, Ureaplasma urealyticum was cultured most frequently in men and women. Mycoplasma hominis and Ureaplasma urealyticum were detected more often in the vaginal fluid than in the male urethra. By contrast, infection rates with Neisseria gonorrhoeae and Chlamydia trachomatis were higher in men than in women. In both men and women, trichomoniasis increased colonisation with Mycoplasma hominis, while mycoplasmas occurred less frequently together with genital candidiasis. Mycoplasma hominis was cultivated significantly more often in women with bacterial vaginosis than in those without. In contrast to urethral infections in men, cervical infections with Neisseria gonorrhoeae or Chlamydia trachomatis raised the incidence of Mycoplasma hominis in the vaginal fluid.

Adult↗
PubMed1997

Comparison of ligase chain reaction and culture for detection of Neisseria gonorrhoeae in genital and extragenital specimens.

In addition to the urogenital tract, Neisseria gonorrhoeae infects extragenital sites such as the pharynx and anorectal canal. Culture and a ligase chain reaction (LCR)-based assay were compared for their performance for the diagnosis of N. gonorrhoeae infection with specimens from various urogenital and extragenital sites of 200 men and 125 women. The sensitivity and specificity of the LCR assay with male urethral swabs were both 100%, compared to values of 95.9 and 100%, respectively, for culture of urethral swabs or 98.0 and 100%, respectively, for LCR with first-void urine (FVU). For women, LCR with FVU showed the highest sensitivity (94.7%), and culture of urethral samples showed the lowest sensitivity (63.2%) (P < 0.05). In a selected subgroup of 47 men and 22 women at increased risk, the rates of pharyngeal infection were 15 and 18%, respectively, and those of anorectal infection were 13 and 45%, respectively. The sensitivity of LCR was greater than that of culture for both pharyngeal and anorectal specimens. Thus, the overall performance of LCR testing with swabs or FVU was better than that of culture for the diagnosis of genital or extragenital gonorrhea.

Bacterial Typing Techniques↗
PubMed1997

Vulval swabs as alternative specimens for ligase chain reaction detection of genital chlamydial infection in women.

A ligase chain reaction (LCR)-based assay was recently shown to be highly sensitive and specific for the detection of Chlamydia trachomatis not only in cervical specimens but also in first-void urine (FVU) specimens form women. The suitability of using vulval swabs as an alternative specimen that can be obtained by noninvasive means for the diagnosis of genital chlamydial infection by LCR was investigated. In a first study of 169 women, vulval, endocervical, and urethral swabs were tested by LCR, culture, and a combination of enzyme immunoassay (EIA) followed by confirmation by direct fluorescent-antibody assay (DFA), and the results were compared with those obtained by testing FVU specimens by LCR and EIA-DFA by using a specimen from an infected patient as a reference standard. Of the 169 women tested, 27 (16%) were shown to be infected. Whereas LCR showed high sensitivities with all specimen types (85.2% for vulval, urine, and endocervical specimens; 92.6% for urethral swabs), the sensitivities of culture and EIA-DFA were high only with endocervical swabs (74.1 and 70.4%, respectively), being 22.2 and 40.7%, respectively, with vulval swabs. In addition, urine testing by EIA-DFA also showed a poor sensitivity (48.1%). In order to further compare LCR performance with vulval specimens to that with FVU specimens, a second study was carried out with specimens from 312 women, of whom 26 were infected. Comparable sensitivity was obtained by LCR with vulval swabs (88.5%; 23 of 26) and FVU specimens (92.3%; 24 of 26). The results indicate that vulval swabs may serve as suitable alternative to specimens that can be obtained by noninvasive means for the detection of C. trachomatis by LCR.

Bacterial Typing Techniques↗
PubMed1997

Differences in the sensitivity of the Amplicor Chlamydia trachomatis PCR assay.

PURPOSE: To evaluate the use of the Amplicor PCR assay in two European centres (Amsterdam and Vienna) as a standard for amplification assays in comparative studies. STUDY DESIGN: Both centres used the Amplicor PCR assay and their own standard diagnostic methods as the reference assay. Discrepant results were further analysed by an Omp1-PCR assay. In total 805 female patients and 614 male patients were included in the studies. RESULTS: The prevalence of Chlamydia trachomatis infections in female patients was 10.0% in Amsterdam and 2.5% in Vienna and in male patients 13.7% and 10.8%, respectively. The mean sensitivity of the Amplicor PCR assay with cervical specimens from female patients was 92.5% and the mean specificity was 99.2%. For the reference assays the mean values were 87.5% and 100.0% respectively. The mean sensitivity of the Amplicor PCR assay with urine specimens from male patients was 70.3% and the mean specificity was 97.6%. For the reference assays these values were 64.9% and 100.0% respectively. The mean sensitivity of the Amplicor PCR assay with urethral specimens from male patients was 67.6% and the mean specificity was 98.5%. For the reference assays these values were 62.2% and 100.0% respectively. Of all specimens together, 1.0% showed an OD value between 0.25 and 0.5 in the Amplicor PCR assay and had to be retested. The sensitivity of the Amplicor PCR assay was less than could be expected from previous studies comparing amplification assays under similar conditions. Also, the sensitivity of the Amplicor PCR assay varied considerably between study centres using urine specimens from male patients-45.9% and 94.6%, respectively. CONCLUSION: The Amplicor PCR assay cannot be considered as a standard for amplification assays in comparative studies.

Austria↗