http://repub.eur.nl/res/aut/6788/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/31500/ 1997-04-01T00:00:00Z Objective: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection in immunocompetent individuals. Methods: 739 patients with a history of recurrent genital HSV infection received either oral valaciclovir (500 mg twice daily) or aciclovir (200 mg five times daily) for 5 days for treatment of their next recurrent episode in a controlled, randomised, double blind trial. Patients self initiated therapy at the first signs and/or symptoms of the HSV recurrence, then were assessed in clinic on five occasions over 7 days, and twice weekly thereafter until lesions had healed. Safety was evaluated through adverse experience reports and haematology and biochemistry monitoring. Results: No significant differences were detected between valaciclovir and aciclovir for the primary endpoint, the duration of all signs and symptoms which included lesion healing and pain/discomfort. The hazard ratio [95% confidence interval] for valaciclovir v aciclovir was 0 93 [0.79, 1.08]. Lesion healing time was similar in each treatment group (hazard ratio valaciclovir v aciclovir 0.96 [0.80, 1.14]). The odds ratio of valaciclovir v aciclovir in preventing the development of vesicular/ulcerative lesions was 1-08 [0.82, 1.42]. Percentages of patients in whom all HSV cultures were negative were similar in the valaciclovir and aciclovir groups at 59% and 54% respectively; for patients having equal to or more than one positive culture result after treatment initiation, cessation of virus shedding was similarly rapid for the two treatments (hazard ratio 0-98 [0.75, 1 .27]). The safety profiles of valaciclovir and aciclovir were comparable with adverse experiences being infrequent and generally mild. Conclusion: This study has demonstrated that valaciclovir 500 mg twice daily is equivalent in efficacy to aciclovir 200 mg five times daily as episodic treatment of recurrent genital HSV infection. Valaciclovir maintains the established efficacy and safety of aciclovir but offers a much more convenient twice daily dosing regimen. http://repub.eur.nl/res/pub/8744/ 1997-01-01T00:00:00Z The prognostic value of detection of human papillomavirus (HPV) type 16 DNA in histologically cancer free lymph nodes was assessed in left obturator lymph nodes from cervical cancer patients with HPV-16 positive primary tumours. HPV-16 DNA was detected by polymerase chain reaction in 12 of 35 patients with histologically cancer free lymph nodes. Of these 12 patients, only one developed a recurrence, suggesting HPV-16 DNA detection in cancer free lymph nodes has no prognostic value. http://repub.eur.nl/res/pub/8635/ 1996-01-01T00:00:00Z We have compared the efficacies of three general primer pairs for the detection of human papillomavirus (HPV) DNA in formaldehyde-fixed paraffin-embedded carcinomas. The use of these primer pairs leads to underestimates of the HPV prevalence (GP5/6, 61.1%; CPI/IIG, 57.4%; MY09/11, 46.9%; combined, 72.8%). The efficacy of each primer pair seemed to be inversely correlated to the length of the amplimer produced. By using newly developed type-specific primer pairs (amplimer length, approximately 100 bp), an increase in HPV DNA detection (87.6%) was found. http://repub.eur.nl/res/pub/8539/ 1995-01-01T00:00:00Z AIMS--To investigate the correlation between antibodies to the transforming protein E7 of human papillomavirus (HPV) type 16 and clinicopathological indices in women with cervical squamous carcinoma. METHODS--A synthetic peptide of the HPV type 16 E7 protein (amino acids 6 to 35) was used to screen sera from 29 children, 130 women with cervical intraepithelial neoplasia, 443 women with cervical cancer, and 222 controls, for antibodies against this viral antigen. Bivariate and multivariate analyses were used to investigate the correlation between the serological status in the pretreatment sera and clinicopathological indices (size of the lesions, histological grade, stomal infiltration, vascular invasion, and nodal spread). Survival analysis was done using the Cox regression model for all FIGO stages and stages IB and ILA. RESULTS--Cervical carcinoma patients had a significantly higher prevalence of antibodies to synthetic peptide E7/6-35 than women with cervical intraepithelial neoplasia (17.7% v 7%, p < 0.005) or controls (17.7% v 11%, p < 0.05). Bivariate analysis of the data on the presence of anti-E7/6-35 antibodies in the pretreatment sera from these patients and clinicopathological indices showed a significant correlation between the presence of anti-E7/6-35 antibodies and the size of the lesion (p = 0.0009), histological grade (p = 0.0031), and lymph node metastasis (p = 0.01). 0.011). In addition, the Cox regression model, analysing four risk factors which can be determined before treatment, showed a significant correlation between the presence of anti-E7/6-35 antibodies and a worse prognosis (p = 0.003). Survival analysis revealed that both for all FIGO stages (p = 0.0005) and for stages IB and IIA alone (p = 0.0021), anti-E7/6-35 positive patients before treatment had a significantly shorter life expectancy. CONCLUSIONS--The presence of antibodies against E7/6-35 in pretreatment sera from patients with cervical carcinoma correlates with the size of the lesions, lymph node involvement, and a worse prognosis. http://repub.eur.nl/res/pub/8549/ 1995-01-01T00:00:00Z In the present study, it was demonstrated that the sensitivity of the PCR for the detection of Chlamydia trachomatis is influenced by the volume of the clinical sample which is processed in the PCR. An adequate sensitivity for PCR was established by processing at least 4%, i.e., 80 microliters, of the clinical sample volume per PCR. By using this preparation procedure, 1,110 clinical samples were evaluated by PCR and by cell culture, and results were compared. After discordant analysis, cell culture resulted in a sensitivity of 79.1% and PCR resulted in a sensitivity of 92.7%. Furthermore, it was shown that treatment with antibiotics immediately resulted in negative cell culture results but that PCR could give positive results up to 2 weeks posttreatment. http://repub.eur.nl/res/pub/8591/ 1994-01-01T00:00:00Z The Gen-Probe PACE 2 assay (GP) in combination with a modified collection system was compared with cell culture (CC) for the detection of Chlamydia trachomatis in urethral specimens from males. Analysis of discordant results was performed by PCR. The modifications, i.e., application of a more rigid swab type and a 50% reduction in the amount of transport medium, were made to improve the sensitivity of the assay. By using the modified GP on 302 urethral specimens from males, a sensitivity of 89.5% and a specificity of 100% were determined. In addition, performance of a probe competition assay on all GP samples with a result > 0.6 and < 1.0 times the cutoff factor (gray zone) detected three more true-positive samples. The sensitivity of GP in combination with the probe competition assay increased to 94.9%, with a specificity of 100%. This was identical to the performance of CC. The modified GP offers a very sensitive and specific alternative to CC. http://repub.eur.nl/res/pub/8598/ 1993-01-01T00:00:00Z The Clearview Chlamydia test (CV; Unipath Ltd., Bedford, United Kingdom), the Magic Lite Chlamydia test (ML; CIBA Corning, Medfield, Mass.), a polymerase chain reaction (PCR), and cell culture (CC) were evaluated for detection of Chlamydia trachomatis in urogenital specimens. Specimens were collected from 283 men and 724 women visiting the outpatient clinic for Sexually Transmitted Diseases at the University Hospital Rotterdam, Rotterdam, The Netherlands. ML, PCR, and CC were all performed on the same sample to prevent swab-to-swab variability. CV was performed on a separate sample. Analysis of discordant results was performed by application of the following confirmatory assays: first, PCR on the CC, second, ML was repeated, and third, PCR was repeated by using a different DNA extraction protocol. If more than one test was positive, the sample was considered true positive. If only one test was positive, which was confirmed by the confirmatory assay, the sample was also considered true positive. By using these interpretations, the following results were obtained. The sensitivity and specificity of CV for samples from men were 60.4 and 86.3%, respectively. For samples from women, these values were 62.3 and 99.7%, respectively. The low specificity for samples from men was caused by unidentified substances in the swab that was used. The use of CV on samples from men is not recommended by the manufacturer. For samples from women, the specificity of CV was high, but the low sensitivity of CV limits its use for diagnostic purposes. The sensitivities of ML were low for samples from both men and women (68.8% and 50.9% respectively), while specificities were excellent for samples from both groups (100 and 99.9%, respectively). The low sensitivity of ML limits its diagnostic value. The PCR technique was highly specific for samples from both men (99.6%) and women (99.9%). The sensitivity of PCR, however, was unexpectedly low for samples from both groups (men, 87.5%; women, 79.2%), most likely because of the sample treatment method used. The sensitivity and specificity values of CC for samples from men were 95.8 and 100%, respectively. For samples from women, these values were 100 and 99.9%, respectively. In the present study, CC was the most reliable technique for the detection of C. trachomatis. http://repub.eur.nl/res/pub/26242/ 1974-12-11T00:00:00Z In 1971 an investigation into the epidemiological, clinical, bacteriological and therapeutic aspects of gonorrhoea was started in collaboration with the Bacteriological Laboratory of the University Hospital/Medical Faculty Rotterdam. Jn the framework of this investigation, the data were recorded on optically readable forms. These forms could be processed to punched cards and fed to a computer for storage and processing, and could also be used as such for filing purposes. Jn order to make efficient use of these forms, it now became necessary to standardize the questioning technique used for collection of the epidemiological data, and the methods of clinical examination, bacteriological investigation and treatment. This thesis deals with a part of the data covered by the abovementioned investigation - mainly those parts relating to the diagnostic aspects of gonorrhoea. However, in order to place these aspects in the total framework of the investigation and in order to allow better comprehension of further publications resulting from this thesis, a full description is given of the methods of examination, treatment and follow-up (Chapter I ) , the methods of bacteriological investigation (Chapter II) and the registration and processing of the data (Chapter III). The epidemiological data on the gonorrhoea patients covered by this investigation are also summarized (Chapter IV).