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Gilbert GG Donders

1) Femicare clinical research for women, Lombardstraat 28, B-3300 Tienen
2) H Hart General Hospital Tienen, Belgium
3) University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium
4) Hôpital Citadelle, Université de Liège, Belgium
Gilbert.Donders@femicare.net

Femicare vzw, Secreatary / research assistance Gert Bellen, Gasthuismolenstraat 31, 3300 Tienen, Belgium. Tel: +32 16 808102, University Hospital Leuven +32 16 344204

Education:
Medical Doctor (1985): Universiteit Diepenbeek, Belgium, Leuven University, Belgium
Specialist in Gynecology (1990): Leuven University, Belgium
Docor in Biomedical Sciences (PhD thesis) (1997): Leuven University, Belgium

Current occupations:
-Consultant Infectious Diseases in Obstetrics and Gynaecology, Dept Obstet Gynaecol, U.Z. Gasthuisberg, Leuven, Belgium (since 1990)
-General Obstetrics and Gynaecology, Regionaal Ziekenhuis Heilig Hart Tienen, Belgium (since 1991)
-Academic consultant Katholieke Universiteit Leuven (since 2001)
-Responsible education program for postgraduates in training for gynaecology in the Department of Obstetrics and Gynaecology Regional Hospital Heilig Hart Tienen (since 2002)
-Director of Femicare vzw, an organisation promoting, supporting and managing clinical research projects for women
-Invited professor of the University of Liège, Belgium in cooperation with the Department of Gynaecology (since 2006)

Current affiliations with Societies
-President of the Flemish group for Research in Infection Diseases in Obesterics and Gynaecology
-Commissioner (Belgium) of the European Society of Infectious Diseases in Obstetrics and Gynecology. http://www.esidog.com
-Lid van Hoge Gezondheidsraad Belgium (Federal High Council of Health)
-Secretary to th International Infectious Disease Society in Obstetrics and Gynecology

Editorial activity:
Co-editor for Infectious Diseases in Obstetrics and Gynecology
Co-editor in Obstetrical and gynceological Investigation

Review activity:
Am J Ob Gyn, Br J Ob Gyn, Mycoses, J Perinat Med, Microb Ecol, Eur J Obst Gyn Repr Biol

Journal articles

2011
Camila Marconi, Bruna Ribeiro de de Ramos, José Carlos Peraçoli, Gilbert G G Donders, Márcia Guimarães da Silva (2011)  Amniotic Fluid Interleukin-1 Beta and Interleukin-6, but not Interleukin-8 Correlate with Microbial Invasion of the Amniotic Cavity in Preterm Labor.   Am J Reprod Immunol 65: 6. 549-556 Jun  
Abstract: Citation Marconi C, Ramos BRA, Peraçoli JC, Donders GGG, Silva MG. Amniotic fluid interleukin-1 betaand interleukin-6, but not interleukin-8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol 2011; 65: 549-556 Problem  We compared the frequency of intra-amniotic infection in preterm labor (PL) with women not in labor, and correlated infection with amniotic fluid (AF) cytokines. Detailed identification of species, especially mycoplasmata, was tried to improve our understanding of the pathogenesis of PL. Method of study  AF from 20 women with PL and 20 controls were evaluated. Infection was detected by PCR for Mycoplasma hominis, Ureaplasma urealyticum and 16S rRNA bacterial gene, which was cloned and sequenced for bacterial identification. Interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α levels were measured by ELISA. Results  Frequency of intra-amniotic infection is higher in PL (40.0%). Sequencing-based method identified Bacteroides fragilis, Prevotella bivia and Leptotrichia amnionii, in addition to Mycoplasma species detected by PCR. AF infection correlated with increased IL-1β and IL-6 levels. Conclusion  The frequency of intra-amniotic infection, especially M. hominis, in PL women who delivered with 7 days, is high and correlates with high IL-1β and IL-6 levels, but not IL-8.
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Jana Zodzika, Dace Rezeberga, Irina Jermakova, Olga Vasina, Natalija Vedmedovska, Gilbert Donders (2011)  Factors related to elevated vaginal pH in the first trimester of pregnancy.   Acta Obstet Gynecol Scand 90: 1. 41-46 Jan  
Abstract: To assess different bacterial and epidemiological factors associations with increased vaginal pH in the pregnant women population during the first trimester.
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Gilbert G G Donders, Ine Mertens, Gert Bellen, Sophie Pelckmans (2011)  Self-elimination of risk factors for recurrent vaginal candidosis.   Mycoses 54: 1. 39-45 Jan  
Abstract: Women suffering from recurrent vulvo-vaginal candidosis (RVC) often follow medical and non-medical advices to diminish the severity and frequency of the recurrences, but the impact of such interventions is unclear. The aim of this study was to identify differences in life style habits of women with RVC compared with normal women and to define which changes have influenced the frequency of recurrences in these women. Fifty-one women with RVC and 51 age-matched control women without a history of RVC were sent a questionnaire. History of allergic disease (OR 2.8) and use of corticoids (OR 5) were more frequent in patients with RVC than controls. When interrogated about beneficial changes introduced in their life style habits, lowering the intake of sugars, preventing perineum humidity and stopping contraceptive pills were factors offering substantial improvement. Apart from an increased risk of having an allergic constitution, no differences in the medical history or life style habits were evident between women with RVC and healthy women. However, women with RVC have introduced several changes in life style habits that proved beneficial to them. Among these changes, lowering intake of sugars, preventing perineum humidity and stopping oral contraceptives were the most important.
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Gilbert G G Donders, Judith Berger, Hélène Heuninckx, Gert Bellen, Ann Cornelis (2011)  Vaginal flora changes on Pap smears after insertion of levonorgestrel-releasing intrauterine device.   Contraception 83: 4. 352-356 Apr  
Abstract: The levonorgestrel intrauterine system (LNG-IUS) combines a uterine foreign body and the continuous release of low-dose levonorgestrel for contraception. Its influence on the rate of vulvovaginal infections and flora disturbance is insufficiently known, but important for contraceptive advice in women, especially those who develop recurrent vaginosis or Candida vulvovaginitis.
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Natalija Vedmedovska, Dace Rezeberga, Uldis Teibe, Ivars Melderis, Gilbert G G Donders (2011)  Placental pathology in fetal growth restriction.   Eur J Obstet Gynecol Reprod Biol 155: 1. 36-40 Mar  
Abstract: One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR.
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2010
Natalija Vedmedovska, Dace Rezeberga, Uldis Teibe, Ivars Melderis, Gilbert G G Donders (2010)  Microscopic lesions of placenta and Doppler velocimetry related to fetal growth restriction.   Arch Gynecol Obstet Dec  
Abstract: PURPOSE: The purpose of the study was to find an association between the uterine and umbilical arteries blood flow patterns in growth-restricted (FGR) and normal fetuses and placental microscopic lesions. METHODS: Fifty women with prenatally suspected and post-delivery confirmed FGR of singleton fetuses were enrolled in a case-controlled follow-up study from May 2007 to December 2008. Unselected patients with appropriately growing fetuses, matched for gestational age, served as controls. Uterine and umbilical Doppler waveforms were recorded before delivery. RESULTS: Compared with control group with normal Doppler, FGR women with abnormal Doppler velocimetry of uterine and umbilical arteries had more intervillous thrombi (p = 0.01 and p < 0.0001, respectively) and villous infarctions (p = 0.02 and p = 0.0003, respectively). Thickening of the basal membrane and villitis was clearly linked to the FGR (p = 0.006 and p = 0.01). Vasculitis, on the other hand, is linked to normal growth, without affecting Doppler velocities. CONCLUSIONS: Abnormal Doppler may predict hemorrhagic and ischemic placental lesions in FGR pregnancies and may lead to future improvement of the management of current and subsequent pregnancies.
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Gilbert G G Donders, Gert Bellen, Werner Mendling (2010)  Management of recurrent vulvo-vaginal candidosis as a chronic illness.   Gynecol Obstet Invest 70: 4. 306-321 10  
Abstract: For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate 'don't do's', unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists.
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Natalija Vedmedovska, Dace Rezeberga, Uldis Teibe, Jana Zodzika, Gilbert G G Donders (2010)  Preventable maternal risk factors and association of genital infection with fetal growth restriction.   Gynecol Obstet Invest 70: 4. 291-298 10  
Abstract: Maternal risk factors may interfere with mechanisms regulating fetal growth. The aim of the present study was to determine which sociodemographic and reproductive risk factors may be related to fetal growth restriction (FGR), with a special focus on determinants possible for preventive intervention.
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Christophe E Depuydt, Elke Leuridan, Pierre Van Damme, Johannes Bogers, Annie J Vereecken, Gilbert G G Donders (2010)  Epidemiology of Trichomonas vaginalis and human papillomavirus infection detected by real-time PCR in flanders.   Gynecol Obstet Invest 70: 4. 273-280 10  
Abstract: The goal of this cross-sectional laboratory-based study is to investigate the association between Trichomonas vaginalis (TV) and human papillomavirus (HPV) infections in cervical samples in Flanders.
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G G G Donders, B Van Bulck, P Van de Walle, R R Kaiser, G Pohlig, S Gonser, F Graf (2010)  Effect of lyophilized lactobacilli and 0.03 mg estriol (Gynoflor®) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study.   Gynecol Obstet Invest 70: 4. 264-272 10  
Abstract: To evaluate the efficacy of lyophilized lactobacilli in combination with 0.03 mg estriol when compared to metronidazole in the treatment of bacterial vaginal infections. Setting: Multicenter, randomized, single-blind, active-controlled pilot study in 3 independent gynecological practices in Belgium.
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Gilbert G G Donders, Camila Marconi, Gert Bellen (2010)  Easiness of use and validity testing of VS-SENSE device for detection of abnormal vaginal flora and bacterial vaginosis.   Infect Dis Obstet Gynecol 2010: 10  
Abstract: Accessing vaginal pH is fundamental during gynaecological visit for the detection of abnormal vaginal flora (AVF), but use of pH strips may be time-consuming and difficult to interpret. The aim of this study was to evaluate the VS-SENSE test (Common Sense Ltd, Caesarea, Israel) as a tool for the diagnosis of AVF and its correlation with abnormal pH and bacterial vaginosis (BV). The study population consisted of 45 women with vaginal pH ≥ 4.5 and 45 women with normal pH. Vaginal samples were evaluated by VS-SENSE test, microscopy and microbiologic cultures. Comparing with pH strips results, VS-SENSE test specificity was 97.8% and sensitivity of 91%. All severe cases of BV and aerobic vaginitis (AV) were detected by the test. Only one case with normal pH had an unclear result. Concluding, VS-SENSE test is easy to perform, and it correlates with increased pH, AVF, and the severe cases of BV and AV.
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Gilbert G Donders, Christel Van Calsteren, Gert Bellen, Reinhilde Reybrouck, Thierry Van den Bosch, Ine Riphagen, Stephan Van Lierde (2010)  Association between abnormal vaginal flora and cervical length as risk factors for preterm birth.   Ultrasound Obstet Gynecol Jan  
Abstract: AIM.: To study the relationship between abnormal vaginal flora (AVF) in the first trimester as a risk factor for shortening cervix length (CL) at second and third trimester, and to assess the combination of these factors in predicting preterm delivery. METHODS.: 1026 unselected low risk women seen before 16 weeks of pregnancy underwent sampling of vaginal fluid for wet mount microscopy at a central laboratory blinded to clinical data. Disappearance of lactobacilli and bacterial vaginosis (BV) were scored according to standardized definitions. Specific cultures were performed for M hominis, U urealyticum, aerobic vaginitis (AV) and vaginal colonization with Candida. CL was measured by transvaginal ultrasound at 10-14, 20-24 and at 30-34 weeks, and gestational age at delivery was recorded. RESULTS.: Short cervix (CL below the lower quartile) at 10-14 weeks is related to a lower CL at 20-24 and 30-34 weeks of gestation (p=0.01, p=0.005 respectively). Short cervix at 20-24 weeks, but not at 10-14 weeks, was predictive for preterm birth. In patients with M. hominis and/or with severe AV at 10-14 weeks, the cervix appeared shorter at 20-24 and at 30-34 weeks than in other women. Increased risk for preterm birth in women with a shorter cervix at 10-14 weeks and AVF could not be proved by this study. DISCUSSION.: Presence of AV or M. hominis is associated with a shorter cervix at 20-24 and 30-34 weeks. Although a short cervix at 10-14 weeks increases the likelihood of having a short cervix later in pregnancy, it was not a prerequisite for AVF to be associated with preterm delivery. Therefore, in the pathogenesis of preterm birth, certain types of AVF may be involved directly in the process of cervical shortening, rather than being exposed to the intrauterine cavity more readily by a short cervix in the early stages of pregnancy. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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2009
G G G Donders, P G Larsson, J J Platz-Christensen, A Hallén, W van der Meijden, P Wölner-Hanssen (2009)  Variability in diagnosis of clue cells, lactobacillary grading and white blood cells in vaginal wet smears with conventional bright light and phase contrast microscopy.   Eur J Obstet Gynecol Reprod Biol 145: 1. 109-112 Jul  
Abstract: Study the reproducibility of wet smear interpretation of clue cells, lactobacillary grades and leukocyte dominance with conventional bright light and phase contrast microscopy.
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E Biagi, B Vitali, C Pugliese, M Candela, G G G Donders, P Brigidi (2009)  Quantitative variations in the vaginal bacterial population associated with asymptomatic infections: a real-time polymerase chain reaction study.   Eur J Clin Microbiol Infect Dis 28: 3. 281-285 Mar  
Abstract: The real-time polymerase chain reaction (PCR) quantification of several vaginal bacterial groups in healthy women and patients developing asymptomatic bacterial vaginosis (BV) and candidiasis (CA) was performed. Statistical analysis revealed that the BV condition is characterised by a great variability among subjects and that it is associated with a significant increase of Prevotella, Atopobium, Veillonella and Gardnerella vaginalis, and a drop in Lactobacillus. On the contrary, the vaginal microflora of healthy women and patients developing CA was found to be homogeneous and stable over time.
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G G Donders, K Van Calsteren, G Bellen, R Reybrouck, T Van den Bosch, I Riphagen, S Van Lierde (2009)  Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy.   BJOG 116: 10. 1315-1324 Sep  
Abstract: Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors.
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2008
Dace Rezeberga, Gunta Lazdane, Juta Kroica, Ludmila Sokolova, Gilbert G G Donders (2008)  Placental histological inflammation and reproductive tract infections in a low risk pregnant population in Latvia.   Acta Obstet Gynecol Scand 87: 3. 360-365  
Abstract: To investigate the correlation of reproductive tract infections (RTI) and endogenous vaginal flora at first antenatal consultation with placental histological inflammation.
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Gilbert G G Donders, Maria Gabrovska, Gert Bellen, Joachim Van Keirsbilck, Thierry Van Van Bosch, Ine Riphagen, Marcel Verjans (2008)  Knowledge of cervix cancer, human papilloma virus (HPV) and HPV vaccination at the moment of introduction of the vaccine in women in Belgium.   Arch Gynecol Obstet 277: 4. 291-298 Apr  
Abstract: To test the knowledge of women, attending a gynecology clinic, on HPV, cervix cancer awareness and the knowledge and willingness to use HPV vaccine for themselves or their children.
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G G G Donders, O Babula, G Bellen, I M Linhares, S S Witkin (2008)  Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis.   BJOG 115: 10. 1225-1231 Sep  
Abstract: PRECIS: Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes.
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2007
Gilbert G G Donders, Tinne Caeyers, Priska Tydhof, Ine Riphagen, Thierry van den Bosch, Gert Bellen (2007)  Comparison of two types of dipsticks to measure vaginal pH in clinical practice.   Eur J Obstet Gynecol Reprod Biol 134: 2. 220-224 Oct  
Abstract: OBJECTIVES: To assess the practical use of two dispsticks for measuring vaginal pH with a range 4-7 (Merck and Macherey Nagel in the diagnosis of vaginal infections. STUDY DESIGN: Routine gynaecological clinic in the General Hospital H Hart in Tienen and vulvo-vaginitis clinic in the University Hospital Gasthuisberg in Leuven, Belgium. After oral consent was obtained, 101 unselected consecutive women presenting for gynaecologic examination between 15 January 2004 and 15 February 2004 were included in an observational study. Vaginal smears were taken from the upper vaginal wall for pH measurement and for fresh wet mount examination by phase contrast microscopy for diagnosing lactobacillary grades and presence of pathogens. The observed color change of two different pH strips were compared with the color scale provided by the company by a junior investigator who was not familiar with the technique, nor with the pathology of the patient. The difficulty of the measurement was scored semi-quantitatively by assessing the time and effort necessary to decide on the correct pH. RESULTS: Using the Macherey-Nagel method, the mean pH score was lower in women with normal flora and in women with vaginal infections than when the Merck method was used, but the difference was not significant. The pH became progressively more abnormal with increasing lactobacillary grades, a correlation that was similar for both tests. The reading of the pH sticks was significantly simpler and quicker with Macherey-Nagel than with Merck. Although difficult readings with Merck strips were four times more frequent in the group of women with abnormal flora than in women with normal flora, this difference was not significant. CONCLUSION: (1) In both tests (Macherey-Nagel and Merck) the pH was more abnormal (higher) with increasing lactobacillary grades (declining number of lactobacillary morphotypes). (2) The Macherey-Nagel sticks are more user-friendly than Merck's.
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Jaak Ph Janssens, José Russo, Irma Russo, Luc Michiels, Gilbert Donders, Marcel Verjans, Ine Riphagen, Thierry Van den Bossche, Marijke Deleu, Peter Sieprath (2007)  Human chorionic gonadotropin (hCG) and prevention of breast cancer.   Mol Cell Endocrinol 269: 1-2. 93-98 Apr  
Abstract: Animal and 'in vitro' experiences learned that human chorionic gonadotropin (hCG) is capable to protect from breast cancer. Receptors for hCG/luteinizing hormone (LH) are present on human female and male breast cancer cells. hCG decreases proliferation and invasion of breast cancer MCF-7 cells by inhibiting NF-kappa B, AP-1 activation and other genes. Doxorubicin toxicity is enhanced by conjugation with beta-hCG in MCF-7 cells. All these pieces of evidence suggest that hCG is active in human breast cancer. Direct proof however is missing. We performed a pilot study phase I trial for testing the inhibitory effects or recombinant hCG (rhCG) on primary breast cancer. Twenty-five postmenopausal women with newly diagnosed breast cancers of more than 1.5 cm were biopsied before randomization to receive either 500 microg rhCG (n=20) or placebo. After 2 weeks, surgery was done and tissues were analysed with regard to morphological, immunohistochemical and biochemical changes in tissues and plasma. rhCG reduces significantly the proliferative index and the expression of both the oestrogen receptor and progesterone receptor. rhCG does not modify the hormonal level of estradiol, progesterone, inhibin and follicle stimulating hormone (FSH) but increases significantly the level of LH. In a second pilot study, we tested the clinical efficacy through an open-label single centre study in 13 postmenopausal women with metastatic breast cancer. A 500 microg rhCG once every 2 days shows activity in postmenopausal metastatic breast cancer. The time to progression is relatively short. Response to previous hormonal treatment is indicative for rhCG activity. Given the data in primary and metastatic breast cancer rhCG further large scale investigation is highly warranted. rhCG can be an realistic option in (chemo-) prevention trials.
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Beatrice Vitali, Ciro Pugliese, Elena Biagi, Marco Candela, Silvia Turroni, Gert Bellen, Gilbert G G Donders, Patrizia Brigidi (2007)  Dynamics of vaginal bacterial communities in women developing bacterial vaginosis, candidiasis, or no infection, analyzed by PCR-denaturing gradient gel electrophoresis and real-time PCR.   Appl Environ Microbiol 73: 18. 5731-5741 Sep  
Abstract: The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.
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Gilbert G G Donders (2007)  Definition and classification of abnormal vaginal flora.   Best Pract Res Clin Obstet Gynaecol 21: 3. 355-373 Jun  
Abstract: Studying the vaginal microflora is not only fascinating, with many discoveries to be made, it is also a very practical way to help women get rid of bothersome and sometimes dangerous infections. Gram-stained vaginal preparations, Pap smears, specific cultures, and nucleic acid detection techniques can be used to diagnose the constituents of the vaginal flora, but in trained hands office-based microscopy of a fresh vaginal smear, preferably using a x400 magnification phase-contrast microscope, allows almost every diagnosis and combination of diagnoses imaginable. In this chapter I will address the pros and cons of the tools that are in use to study vaginal flora, and discuss the different types of bacterial flora and the difficulties encountered in reaching the correct diagnosis of pathological conditions. The 'intermediate flora' is addressed separately, and a new entity--'aerobic vaginitis'--is discussed. Future research should focus on the interaction between infecting microorganisms and host defence mechanisms, as both together generate the pathogenicity of these conditions.
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2006
Gilbert G G Donders (2006)  Management of genital infections in pregnant women.   Curr Opin Infect Dis 19: 1. 55-61 Feb  
Abstract: PURPOSE OF REVIEW: To examine and evaluate ways of managing genital infections in pregnant women. RECENT FINDINGS: The need to screen for sexually transmitted diseases during pregnancy depends on the prevalence of the condition, its pathogenesis and the cost-benefit analysis for a population or risk group. For a few genital infections with severe impact on the outcome of the pregnancy, such as syphilis and gonorrhoea, a 'screen and treat' policy is almost always cost-effective. SUMMARY: Genital infections often remain unnoticed during pregnancy, as their signs and symptoms may be seen as part of the normal discomfort of pregnancy. Also it is sometimes not clear whether there are multiple partners or whether the partners have been treated, making re-infection after treatment highly likely. Partner tracing may be difficult, but the 'screen and treat' policy is usually the best solution.
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J Verguts, B Bronselaer, G Donders, M Arbyn, J Van Eldere, M Drijkoningen, W Poppe (2006)  Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation.   BJOG 113: 11. 1303-1307 Nov  
Abstract: OBJECTIVES: The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. DESIGN: Prospective follow-up study. SETTING: Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. POPULATION: Seventy-two women treated with conisation for CIN2 or CIN3. METHODS: Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. RESULTS: In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. CONCLUSION: Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence.
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2005
2003
Gilbert G G Donders, Annie Vereecken, Eugene Bosmans, Bernard Spitz (2003)  Vaginal cytokines in normal pregnancy.   Am J Obstet Gynecol 189: 5. 1433-1438 Nov  
Abstract: OBJECTIVE: The purpose of this study was to determine whether the vaginal cytokine concentration varies during the course of uncomplicated pregnancy. STUDY DESIGN: Prenatal visits of healthy women to University Hospital Gasthuisberg, Leuven, Belgium were considered. Cytokine levels in vaginal washings from 30 unselected healthy women with uncomplicated pregnancies were monitored during pregnancy and compared with those from 62 nonpregnant healthy control subjects. Exclusion criteria included bacterial vaginosis, moderate or severe aerobic vaginitis, Trichomonas vaginalis, Candida vaginitis (wet mount or culture), gonorrhea, and Chlamydia. Interleukin-6, interleukin-8, interleukin-1beta, interleukin-1-receptor antagonist, leukemia inhibitory factor, and tumor necrosis factor were measured. Nonparametric Kruskal-Wallis and Welch tests were used for univariate analysis, and the Spearman rank test was used for multivariate analysis. RESULTS: Compared with concentrations in nonpregnant women, interleukin-1beta concentrations were similar, but interleukin-1-receptor antagonist production was depressed throughout pregnancy. Vaginal interleukin-6 and interleukin-8 were less often discovered during pregnancy than outside pregnancy and dipped significantly in the middle trimester, to rise again to prepregnancy levels in the third trimester. Leukemia inhibitory factor was lower during the beginning of pregnancy (P=.038) but otherwise did not differ from nonpregnant values throughout pregnancy nor did tumor necrosis factor. Sexual activity could not explain these findings. CONCLUSION: Vaginal cytokine levels, especially interleukin-1 receptor antagonist, from pregnant women may differ from nonpregnant values; some levels, such as interleukin-6 and interleukin-8, may fluctuate during normal pregnancy. These spontaneous variations during pregnancy must be taken into account when mucosal immunologic responses to infection of the lower genital tract are being studied.
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2002
T Van den Bosch, G G G Donders, I Riphagen, P Debois, L Ameye, J De Brabanter, S Van Huffel, D Van Schoubroeck, D Timmerman (2002)  Ultrasonographic features of the endometrium and the ovaries in women on etonogestrel implant.   Ultrasound Obstet Gynecol 20: 4. 377-380 Oct  
Abstract: OBJECTIVE: To evaluate the ultrasound features of the endometrium and ovaries in women on etonogestrel implant, and to correlate these features with the bleeding pattern. METHODS: Observational study including 188 consecutive women presenting for follow-up transvaginal ultrasound examination after insertion of an etonogestrel implant contraceptive device. Thirty women had more than one follow-up examination. The bleeding pattern was considered abnormal if, in the last 3 months, there were more than five episodes of vaginal bleeding, or there was prolonged bleeding exceeding 14 consecutive days. RESULTS: At first follow-up examination, the mean age was 29.7 years and 47% of women had an abnormal bleeding pattern. Most bleeding episodes were of less intensity than menses. The mean endometrial thickness (ET) on ultrasound was 2.9 mm (standard deviation, 2.0). Ovarian follicle growth exceeding 5 mm was observed in 60% of the cases. Ovulation was demonstrated in one woman. Univariate analysis showed a positive association (P < 0.01) between ET, bleeding pattern, and bleeding intensity. Follicle growth was positively associated (P < 0.01) with ET, bleeding pattern, and interval between insertion and examination. Multivariate analysis showed that the ET was on average 1.25 mm greater in women with abnormal bleeding (P = 0.0001). The odds of finding follicle growth were 2.8 times higher (95% confidence interval, 1.2-6.2) in women presenting with a three-layer type of endometrial morphology. There was no association between the other patients' characteristics and the bleeding pattern. CONCLUSIONS: Abnormal uterine bleeding in women on etonogestrel implant was associated with follicle growth and a thicker, three-layer type of endometrium, suggesting incomplete ovarian inhibition and estrogen stimulation of the endometrium.
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Gilbert G G Donders, Hans Prenen, Geert Verbeke, Reinhilde Reybrouck (2002)  Impaired tolerance for glucose in women with recurrent vaginal candidiasis.   Am J Obstet Gynecol 187: 4. 989-993 Oct  
Abstract: OBJECTIVE: The purpose of this study was to determine whether nondiabetic women with recurrent vaginal candidiasis have an impaired glucose metabolism. STUDY DESIGN: A case-control study of 62 otherwise healthy women who were attending a vaginitis clinic > or =3 times a year for symptoms of Candida vaginitis, positive microscopy, and at least one positive Candida culture and of 32 Candida-negative control subjects, all of whom were undergoing standardized oral glucose tolerance testing. RESULTS: Women with recurrent bacterial vaginal infections did not differ from women without infections, so both groups comprised the control group. Women with recurrent vaginal candidiasis had a greater mean body mass index than the control subjects (23.5 vs 21.4, P =.001). They had no more incidences of overt or preclinical diabetes mellitus than the control subjects (6/62 vs 0/32 incidents), but a greater proportion of them had at least one glucose concentration above the 95th percentile (36% vs 12%, P =.016). Glucose concentrations were higher in recurrent vaginal candidiasis cases than in control subjects at 0 (89 vs 85 mg/dL,P =.049), 30 (139 vs 126 mg/dL, P =.05), and 60 minutes (123 vs 102 mg/dL, P =.009) after the intake of 75 g of glucose. Fasting concentration of glycosylated hemoglobin was 25% higher in women with recurrent vaginal candidiasis (5 vs 4 g/dL, P =.0006), even after correction for body mass index. Compared with control subjects, ingestion of 75 g of glucose led to a 15% increase of serum glucose levels in women with recurrent vaginal candidiasis (P =.01). As expected, most of these differences were largely mediated by an increased body mass index. CONCLUSION: The tolerance to glucose in nondiabetic women with recurrent vaginal candidiasis is discretely impaired. Glucose tolerance testing is of value in women with recurrent vaginal candidiasis, but the interpretation of the obtained values should not be limited to the diagnosis of preclinical diabetes mellitus.
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Donders (2002)  Lower Genital Tract Infections in Diabetic Women.   Curr Infect Dis Rep 4: 6. 536-539 Dec  
Abstract: The influence of glucose metabolism is seen in many infectious diseases, making diabetic patients more vulnerable to sepsis and other serious sequelae of bacterial invasion. Vaginal candidiasis is a common problem if the glycemia is poorly controlled. The level of glucose concentration in the blood after ingestion of sugar seems to explain an increased likelihood of recurrent infection. Specific immune aberrations, such as an elevated T-helper 2 response and a blunted T-helper 1 response, leading to tolerance, may result in chronic recurrent vulvovaginal candidiasis. In such patients, a low-grade infection with frequent exacerbations is seen, and treatment should be based on 24-hour glycemic control and long intermittent treatment with antifungals. Besides candidiasis, there is also evidence of an increased likelihood of cystitis. Upper urinary tract infections (UTIs) are also a frequent result of bladder colonization. Lethal emphysematous nephritis due to Candida albicans or gas-forming bacteria such as Escherichia coli, Klebsiella, Proteus, streptococci, or enterococci are known to occur in diabetic patients. Furthermore, UTIs in diabetic patients are difficult to eradicate and need longer and intense antibiotic therapy. Awareness of the increased likelihood of UTIs, frequent screening, and prolonged treatment in case of cystitis are warranted. For the prevention of UTI and bacterial vaginal infections (bacterial vaginosis, vaginal atrophy with bacterial colonization, aerobic vaginitis) estrogen therapy may be as important as antibiotic therapy. Catheterization should be limited since it promotes infection more in diabetic patients than in nondiabetic patients. In the case of recurrent vaginal candidiasis, tight control of glycemia is crucial, in addition to prolonged, intermittent therapy with antifungals.
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U Forsum, T Jakobsson, P G Larsson, H Schmidt, A Beverly, A Bjørnerem, B Carlsson, P Csango, G Donders, P Hay, C Ison, F Keane, H McDonald, H Moi, J - J Platz-Christensen, J Schwebke (2002)  An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.   APMIS 110: 11. 811-818 Nov  
Abstract: An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.
Notes:
2001
2000
P R Koninckx, G Donders, H Vandecruys (2000)  Umbilical endometriosis after unprotected removal of uterine pieces through the umbilicus.   J Am Assoc Gynecol Laparosc 7: 2. 227-232 May  
Abstract: We reviewed the frequency of umbilical endometriosis after laparoscopic-assisted subtotal hysterectomy with unprotected removal of uterine segments through the umbilical incision. Retrospective analysis of surgical records was followed by recall and clinical examination of 10 patients. Two women developed umbilical endometriosis. One was the only patient operated during menstruation. The other was one of two women operated in the late luteal phase and with subsequent adequate exposure to endogenous or exogenous estrogens. From 1976-1997, 22 reports of umbilical endometriosis were published: 18 cases were spontaneous, 2 occurred after ring sterilization, and 2 after diagnostic laparoscopy. These data lend support to the concept that implantation and the potential development of menstrual endometrium are increased after surgery. It is speculated that procedures that expose menstrual endometrial cells to nonepithelialized areas could be associated with an increased risk of endometriosis.
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G G Donders, A Vereecken, A Dekeersmaecker, B Van Bulck, B Spitz (2000)  Wet mount microscopy reflects functional vaginal lactobacillary flora better than Gram stain.   J Clin Pathol 53: 4. 308-313 Apr  
Abstract: AIM: The status of vaginal lacto-bacillary flora, an indicator of possible genital infection and pregnancy complications, can be assessed on wet mount or Gram stained specimens. The former is quick, the latter more routine. The accuracy of the two preparative techniques to detect normal vaginal lacto-bacillary microflora was compared for 646 patients. The effect of delay in transport medium before Gram staining was also investigated. METHODS: Patients presented with infectious vaginitis or for a routine prenatal visit. After placement of a speculum, duplicate smears were taken from the upper vaginal vault and examined fresh or after Gram staining. Lacto-bacillary grades from both methods were compared with lactate concentration in vaginal rinses. In a subgroup of 238 patients, Gram staining was performed both on fresh smears and those that had been transported in Stuart's growth medium. RESULTS: Higher lacto-bacillary grades (more disrupted flora) were diagnosed 2.9 times more frequently on Gram stained specimens than on wet mounts (p < 0.0001), a difference even more pronounced after transport in Stuart's medium (relative risk, 4.2; p < 0.0001). Lacto-bacillary grades assessed on wet mounts correlated better with vaginal lactate concentration than those assessed on Gram stains. CONCLUSIONS: Easier recognition of lacto-bacillary morphotypes on wet mounts than on Gram stains might result from the loss of lactobacilli by the process of fixation or Gram staining. Wet mount microscopy of vaginal smears for assessment of lacto-bacillary grades, rather than Gram staining, is strongly recommended.
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G G Donders, B Van Bulck, J Caudron, L Londers, A Vereecken, B Spitz (2000)  Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion.   Am J Obstet Gynecol 183: 2. 431-437 Aug  
Abstract: OBJECTIVE: This study was undertaken to investigate a possible link between first-trimester diagnosis of bacterial vaginosis and cessation of pregnancy at < or =20 weeks' gestation. STUDY DESIGN: Women (n = 228) who received routine prenatal care in Flanders, Belgium, during the first trimester (14 weeks' gestation) and had a living singleton fetus were examined for microbiologic flora of the vagina. Bacterial vaginosis was assessed either clinically (Amsel et al criteria), microscopically (clue cells), or by culture of bacterial vaginosis-associated bacteria. Data were analyzed univariately (relative risk) and multivariately. RESULTS: The presence of bacterial vaginosis at the first prenatal visit was strongly associated with subsequent early pregnancy loss (relative risk, 5.4; 95% confidence interval, 2.5-11). After multivariate analysis bacterial vaginosis, Mycoplasma hominis, and Ureaplasma urealyticum but not other microorganisms remained associated with an increased risk of miscarriage. CONCLUSION: Bacterial vaginosis and mycoplasmas may play causative roles in spontaneous abortion and early pregnancy loss.
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G G Donders (2000)  Treatment of sexually transmitted bacterial diseases in pregnant women.   Drugs 59: 3. 477-485 Mar  
Abstract: Testing for and treating sexually transmitted diseases (STDs) in pregnant women deserves special attention. Treatment possibilities are limited because of potential risks for the developing fetus, and because effects can differ in pregnant compared with non-pregnant women, re-infection may be missed because of the intrinsic delicacy of contact-tracing during pregnancy and because pregnant women are more reluctant to take the prescribed medication in its full dose, if at all. However, the devastating effects of some of these genital infections far outweigh any potential adverse effects of treatment. Although active syphilis has become a rarity in most Western countries, it is still prevalent in South America, Africa and South-East Asia. Benzathine benzylpenicillin (2.4 million units once or, safer, twice 7 days apart) is the treatment of choice, although patients with syphilis of longer standing require 3 weekly injections as well as extensive investigation into whether there has been any damage due to tertiary syphilis. Despite declining rates of gonorrhea, the relative rate of penicillinase-producing strains is increasing, especially in South-East Asia. The recommended treatment is intramuscular ceftriaxone (125 or 250 mg) or oral cefixime 400 mg. Despite good safety records after accidental use, fluoroquinolones are contraindicated during pregnancy. An alternative to a fluoroquinolone in pregnant women with combined gonorrhea and chlamydial infection is oral azithromycin 1 or 2 g. Azithromycin as a single 1 g dose is also preferable to a 7 day course of erythromycin 500 mg 4 times a day for patients with chlamydial infection. Eradication of Haemophilus ducreyi in patients with chancroid can also be achieved with these regimens or intramuscular ceftriaxone 250 mg. Trichomonas vaginalis, which is often seen as a co-infection, has been linked to an increased risk of preterm birth. Patients infected with this parasite should therefore received metronidazole 500 mg twice daily for 7 days as earlier fears of teratogenesis in humans have not been confirmed by recent data. Bacterial vaginosis is also associated with preterm delivery in certain risk groups, such as women with a history of preterm birth or of low maternal weight. Such an association is yet to be convincingly proven in other women. The current advice is to treat only women diagnosed with bacterial vaginosis who also present other risk factors for preterm delivery. The treatment of choice is oral metronidazole 1 g/day for 5 days. The possible reduction of preterm birth by vaginally applied metronidazole or clindamycin is still under investigation. In general, both test of cure and re-testing after several weeks are advisable in most pregnant patients with STDs, because partner notification and treatment are likely to be less efficient than outside pregnancy and the impact of inadequately treated or recurrent disease is greater because of the added risk to the fetus. Every diagnosis of an STD warrants a full screen for concomitant genital disease. Most ulcerative genital infections, as well as abnormal vaginal flora and bacterial vaginosis, increase the sexual transmission efficiency of HIV, necessitating even more stringent screening for and treating of STD during pregnancy.
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G G Donders, E Bosmans, A Dekeersmaecker, A Vereecken, B Van Bulck, B Spitz (2000)  Pathogenesis of abnormal vaginal bacterial flora.   Am J Obstet Gynecol 182: 4. 872-878 Apr  
Abstract: OBJECTIVE: This study was undertaken to determine the relationships between microscopy findings on wet mounts, such as lactobacillary grade or vaginal leukocytosis, and results of vaginal culture, lactate and succinate content of the vagina, and levels of selected cytokines. STUDY DESIGN: In a population of 631 unselected women seeking treatment at an obstetrics and gynecology outpatient clinic, vaginal fluid was obtained by wooden Ayre spatula for wet mounting and pH measurement, by high vaginal swab for culture, and by standardized vaginal rinsing with 2 mL 0.9% sodium chloride solution for measurements of lactate, succinate, interleukin 1beta, interleukin 8, leukemia inhibitory factor, and interleukin 1 receptor antagonist concentrations. Lactate and succinate levels were measured by gas-liquid chromatography and the cytokine concentrations were measured by specific immunoassays. Both univariate analysis (Student t test, Welch test, chi(2) test, and Fisher exact test) and multivariate regression analysis (Cox analysis) were used. RESULTS: Increasing disturbance of the lactobacillary flora (lactobacillary grades I, IIa, IIb, and III) was highly correlated with the presence of Gardnerella vaginalis, Trichomonas vaginalis, enterococci, group B streptococci, and Escherichia coli. Vaginal pH and interleukin 8 and interleukin 1beta concentrations increased linearly with increasing lactobacillary grade, whereas lactate concentrations and the presence of epithelial cell lysis decreased. A similar pattern of associations with increasing leukocyte count was clear, but in addition there was an increase in leukemia inhibitory factor concentration. Multivariate analysis of vaginal leukocytosis, lactobacillary grades, and the presence of positive vaginal culture results showed that interleukin 1beta concentration was most closely related to the lactobacillary grade, leukemia inhibitory factor concentration was most closely related to the lactobacillary grade and positive culture results, interleukin 8 concentration was most closely related to positive culture results, and interleukin 1 receptor antagonist concentration was most closely related to vaginal leukocytosis and positive culture results. The concentration ratio of interleukin 1beta to interleukin 1 receptor antagonist remained stable, except when vaginal leukocytosis increased. In its most severe form, with >10 leukocytes per epithelial cell present, a decompensation of the vaginal flora with a collapse in interleukin 1beta and interleukin 1 receptor antagonist concentrations was seen, but there was a concurrent sharp increase in leukemia inhibitory factor concentration. This pattern was completely different from the course of the cytokine concentrations associated with a lactobacillary grade increase. CONCLUSION: Both disturbed lactobacillary grade and the presence of increasing vaginal leukocytosis were correlated with lactobacillary substrate (lactate) concentration, pH, and the concentrations of a variety of cytokines. There was a remarkably linear increase in these cytokines as either leukocytosis or lactobacillary grade became more severe. In circumstances in which leukocytosis was extreme, however, interleukin 1beta was no longer produced but leukemia inhibitory factor concentrations increased. We speculate that in extreme inflammation the body tries to limit the damage that can be done by exaggerated cytokine production.
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1999
G G Donders, A Vereecken, G Salembier, B Spitz (1999)  Accuracy of rapid antigen detection test for group B streptococci in the indigenous vaginal bacterial flora.   Arch Gynecol Obstet 263: 1-2. 34-36 Nov  
Abstract: OBJECTIVE: To test the sensitivity of the rapid group B streptococci (GBS) antigen test ICONR and compare its accuracy in women with vaginal enterococci or with non-specific disturbance of the lactobacillary flora. STUDY DESIGN: The ICONR, aerobic culture and a microscopic wet mount evaluation were done on a vaginal sample in 254 unselected women presenting for routine gynecologic care in an academic hospital in Flanders, Belgium and tested by Chi2 [diagnostic odds ratio (DOR) and its 95 percent confidence limits]. RESULTS: Sensitivity of the test was 70%, specificity 99.5%. Prevalence of GBS was 10.6% overall, 23% in the group with abnormal vaginal flora and 7% in the normal group (p=0.002). Accuracy of the ICONR was not affected by abnormal vaginal flora, but was significantly lower in the presence of enterococci: the DOR decreased from 490 to 58, and the positive predictive value from 94 to 80%. CONCLUSION: With a sensitivity of 70% the enzyme immunoassay ICONR does not appear to be suitable as a practical screening tool for detecting GBS carriage in normal or preterm laboring women. In the presence of enterococci the test performed less well, with a DOR falling by 8 to 9 fold. We presume this is due to lower specificity in vivo in the presence of enterococci, as non-specific disturbance of the lactobacillary flora did not interfere with test results.
Notes:
1998
1997
G G Donders, J Desmyter, P Hooft, G H Dewet (1997)  Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus-seronegative African women.   Sex Transm Dis 24: 2. 94-101 Feb  
Abstract: BACKGROUND: Syphilis remains a major cause of premature birth, fetal and perinatal death, and congenital syphilis in South Africa, despite systematic antenatal screening by rapid plasma reagin and treatment with 2.4 million U of benzathine penicillin G. GOAL: To determine whether one injection of 2.4 million of U of benzathine penicillin G, as recommended by the 1993 Centers for Disease Control and Prevention guidelines, is sufficient treatment for early syphilis during pregnancy. STUDY DESIGN: Outcome of pregnancy was prospectively analyzed after zero to three weekly intramuscular injections of benzathine penicillin G in 180 of 212 human immunodeficiency virus-seronegative black urban women with syphilis in Pretoria, South Africa. RESULTS: One hundred eight women receiving two or three weekly intra-gluteal injections of benzathine penicillin G had a favorable pregnancy outcome. However, after only one injection, lower birth weight, increased immaturity, prematurity, and total preterm birth rate resulted. Total pregnancy loss and perinatal mortality were also increased. After exclusion of patients treated with oral penicillin derivatives and adjustment for the estimated duration of treponemicidal levels at 3 weeks after injection, the perinatal outcome was reanalyzed. Treponemicidal coverage of 3 weeks or less resulted in decreased birth weight (2,748 vs. 3,130 g, P = 0.004) compared with treponemicidal coverage lasting longer than 3 weeks. In addition, the relative risks for prematurity (relative risk [RR], 8.5; 95% confidence interval [CI95], 2.5-28), perinatal mortality (RR, 20.5; CI95, 2.3-184), and congenital syphilis (RR 2.0; CI95-0.6-6.8) were increased when coverage was less then 3 weeks. These results were comparable to those obtained when no treatment was given. Most of the incompletely treated women delivered at less than 4 weeks after they received their injection. These also had the worst neonatal outcome. Impaired outcome due to short treatment clustered in early attenders of prenatal care (before the 28th week of gestation) and when the initial rapid plasma reagin titer was higher than 16. Although numbers were small for a firm conclusion, incompletely treated and untreated women who had taken intercurrent oral ampicillin had an improved birth weight, lower prematurity rate, and lower fetal rate. CONCLUSIONS: One intramuscular injection of 2.4 million U benzathine penicillin G or treponemicidal concentrations lasting 3 weeks or less is not sufficient therapy for pregnant women with syphilis. Although fetal outcome is clearly improved at birth with more than one injection, without follow-up of the neonates, complete cure cannot be predicted from these data. To obtain treponemicidal activity for longer than 3 weeks, the authors recommend administration of two injections of 2.4 million U benzathine penicillin at least 1 week apart, if possible at 4 weeks or more before delivery. This therapy is especially important for patients who attend prenatal care before 28 weeks of pregnancy or when the rapid plasma reagin titer is higher than 16.
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G G Donders, S Gordts, A Cornelis, P Moerman (1997)  Intrauterine candidiasis in a twin pregnancy after myomectomy, in vitro fertilization and embryo transfer.   Arch Gynecol Obstet 259: 4. 201-204  
Abstract: A IVF twin pregnancy in a patient who had previously undergone a myomectomy ended in a intrauterine infection, placental abruption and fetal losses at 21 weeks. Intrauterine Candidiasis may have played a role in the pathogenesis of the unsuccessful outcome.
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1996
G G Donders, V van Gerven, H G de Wet, A M van Straten, F de Boer (1996)  Rapid antigen tests for Neisseria gonorrhoeae and Chlamydia trachomatis are not accurate for screening women with disturbed vaginal lactobacillary flora.   Scand J Infect Dis 28: 6. 559-562  
Abstract: We studied the accuracy of the rapid antigen detection tests Gonozyme and Chlamydiazyme in high-risk women in an outpatient prenatal clinic, Kalafong University Hospital, Pretoria, South Africa. Women (n = 433) presenting with uneventful pregnancy (n = 324), unavoidable miscarriage (n = 41) or infertility of 1 year's duration (n = 68) had a Pap smear for lactobacillary grading and detection of pathogens like Candida albicans or Trichomonas vaginalis, a swab for culture of Neisseria gonorrhoeae, and a swab for Gonozyme, Chlamydiazyme and Chlamydia immunofluorescence collected from the endocervix. Specificities of both antigen tests were high, but sensitivities and positive predictive values were disappointingly low. Chlamydial antigen was recovered in only 37% of samples with positive immunofluorescence, gonococcal antigen was detected in only 50% of samples with positive culture for N. gonorrhoeae. Although prevalence of N. gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis was higher in women with disturbed lactobacillary grades on the Pap smears, sensitivities of the antigen tests were lower in this group. We conclude that detection of endocervical antigens of C. trachomatis and N. gonorrhoeae lacked sensitivity in pregnant and infertile women living in an area with high prevalence of chlamydial cervicitis, gonorrhoea and Trichomonas vaginitis. Furthermore, the rapid antigen tests lack accuracy when the lactobacillary flora is disturbed and are, therefore, not suitable for detection of C. trachomatis or N. gonorrhoeae in pre-screened patients.
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G G Donders, A Vereecken, G Salembier, B Van Bulck, B Spitz (1996)  Assessment of vaginal lactobacillary flora in wet mount and fresh or delayed gram's stain.   Infect Dis Obstet Gynecol 4: 1. 2-6  
Abstract: The assessment of the vaginal lactobacillary flora helps to direct further diagnostic microbiologic investigations in genital infectious disease and seems to represent a powerful tool in predicting infectious morbidity and preterm labor during pregnancy. In the absence of a "gold standard," we studied the variations in assessing lactobacillary morphotypes according to the method used.
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1994
1993
G G Donders, J Desmyter, P Goubau, F A van Assche (1993)  Attitude towards serological tests for infection during pregnancy.   Arch Gynecol Obstet 252: 4. 161-167  
Abstract: In anticipation of systematic prenatal screening at the antenatal clinic of Gasthuisberg University Hospital, Leuven, Belgium, the attitude of 500 successive pregnant women towards testing for rubella, toxoplasmosis, hepatitis B virus, HIV and syphilis was studied by means of written questionnaires. All tests were well accepted, toxoplasmosis and rubella being most (92 and 91%), syphilis and HIV being least (79 and 82%) favoured. Refusal was generally associated with lower education, but refusal for syphilis and HIV was associated with high education. Ninety-four percent wanted to be informed of the results of the tests. Only one woman (0.2%) of those who agreed with testing did not want to know her HIV test result. Pregnant doctors were more reluctant about screening, in particular for sexually transmitted diseases, whereas nurses were in favour of it. Written information failed to increase the acceptance rate, but lowered the number of women without an opinion.
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G G Donders, J Desmyter, D H De Wet, F A Van Assche (1993)  The association of gonorrhoea and syphilis with premature birth and low birthweight.   Genitourin Med 69: 2. 98-101 Apr  
Abstract: OBJECTIVE--Provide evidence from prospective data that Neisseria gonorrhoeae may be an important cause of premature delivery and low birth weight in areas with high prevalence of genital infections. SETTING--Department of Obstetrics and Gynaecology, Kalafong University Hospital, Pretoria, South Africa in collaboration with the Departments of Microbiology and of Gynaecology and Obstetrics, Katholieke Universiteit, Leuven, Belgium. SUBJECTS--Two hundred and fifty six consecutive black pregnant women were examined during the first antenatal visit, and one to four weeks later a second culture for N gonorrhoeae was taken at random in 67 of them. Hundred and sixty seven were analysable, 75 were lost to follow up. METHODS--After obtaining detailed clinical history, an endocervical specimen for N gonorrhoeae culture (Thayer-Martin) and C trachomatis antigen detection (Chlamydiazyme (R)) was taken. Syphilis was diagnosed when both reactive plasma protein (RPR) and T pallidum haemagglutination inhibition assay (TPHA) were positive. Prematurity was defined as delivery at less than 37 gestational weeks. RESULTS--Infection with N gonorrhoeae (n = 9) and untreated syphilis (n = 7) were both associated with prematurity and low birth weight. After multi-variate regression analysis, age-adjusted parity, late sexual debut, number of recent sexual partners, infection with N gonorrhoeae and infection with syphilis revealed significant associations with low birth weight. However, infection with C trachomatis, presence of abundant vaginal discharge, social class, Trichomonas vaginalis infection, gestational weeks at first antenatal visit and number of previous miscarriages did not reveal such an association. Attributable risk of untreated gonorrhoea for premature birth was 72% and routine cultures were cost-benefit efficient. CONCLUSIONS--At least in countries where the prevalence is high, genital infections as well as the risk factors for acquiring them (young age, late sexual debut, number of recent partners) play a major role in the aetiogenesis of prematurity and low birth weight. N. gonorrhoeae is a main contributor, and in high prevalence areas it should be routinely looked for and treated for during pregnancy.
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G Donders, H G De Wet, P Hooft, J Desmyter (1993)  Lactobacilli in Papanicolaou smears, genital infections, and pregnancy.   Am J Perinatol 10: 5. 358-361 Sep  
Abstract: Papanicolaou (Pap) smears taken at the first antenatal visit of black African women were examined for lactobacillary expression and its correlation with the prevalence of genital infections and with the outcome of pregnancy. Lactobacillary morphotypes were absent (grade III) in 52% of 256 women. Trichomonas, Chlamydia, gonococci, or syphilis was identified in 54% of grade III women, and in 17% of grade I + II women (p < 0.0001). There were partially independent positive associations of Trichomonas, Chlamydia, and gonococci and a negative association of Candida morphotypes with grade III. Absence of lactobacilli, whether or not in the context of bacterial vaginosis, is an indicator for the presence of other genital infections. Birthweight was 2000 gm or less in 5% of 82 children of grade I + II mothers, and in 16% of 83 children of grade III mothers (p = 0.02). Thus, there are populations in whom the grading of lactobacilli in routine Pap smears helps to direct further investigations and to predict the outcome of pregnancy.
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1992
G G Donders, D van Straeten, P Hooft, G H De Wet (1992)  Detection of Candida cell forms in Pap smears during pregnancy.   Eur J Obstet Gynecol Reprod Biol 43: 1. 13-18 Jan  
Abstract: In a prospective study of 124 urban black pregnant women, 43% had Candida isolated from endocervical cultures and 20% had Candida cell forms on cytological Pap-stained cervical specimens. The presence of Candida cell forms on Pap smears had a better correlation with Candida colonisation when normal lactobacillary flora was present, when Trichomonas vaginalis parasites were absent and when the infecting Candida species was C. albicans. Positive cultures were strongly related to a number of clinical signs and symptoms, but Pap smears were not. Neither Candida culture nor Candida cells in Pap smear revealed an association with premature delivery, birth weight, severe neonatal morbidity or mortality. We confirm that the routine cervical Pap smear is not a sensitive method for diagnosing symptomatic fungal infection. More specifically, some of the Pap smear characteristics, such as disturbed lactobacillary flora or co-infection with T. vaginalis, interfere with accurate diagnosis.
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1991
G G Donders, P Moerman, J Caudron, F A Van Assche (1991)  Intra-uterine Candida infection: a report of four infected fetusses from two mothers.   Eur J Obstet Gynecol Reprod Biol 38: 3. 233-238 Feb  
Abstract: Although Candida albicans is a frequent inhabitant of the female genital tract, chorioamnionitis is rarely caused by this fungal organism. In this report we present two cases with manifest Candida chorioamnionitis. The first case is a twin pregnancy with premature delivery and survival of both twins. The second case is a pregnancy with intra-uterine contraceptive device in situ ending in a midtrimester abortion, followed by the next pregnancy also ending in an abortion in the second trimester. Possible triggers responsible for the increased invasiveness of otherwise benign Candida vaginitis are discussed. Foreign intra-uterine bodies such as contraceptive devices and cerclage sutures necessitate repetitive search for Candida species infection, and prompt adequate antifungal treatment in cases of documented infection. Both cases of the present report add further substantial evidence to the hypothesis of amniotic infection by ascending transcervical infection. The frequent concomitant cervical infections with other infectious agents as well as antibiotherapy influencing the normal Lactobacillary defence mechanisms are both likely to increase the risk. Systemic debilitating diseases that promote invasiveness are briefly discussed.
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G G Donders, P Moerman, G H De Wet, P Hooft, P Goubau (1991)  The association between Chlamydia cervicitis, chorioamnionitis and neonatal complications.   Arch Gynecol Obstet 249: 2. 79-85  
Abstract: In a prospective study on genital infections, the influence of Chlamydial cervicitis on pregnancy outcome was evaluated. In eleven women with Chlamydial cervicitis perinatal outcome was recorded, the placenta was examined and the newborns were screened for Chlamydial conjunctivitis. They were compared with 13 women who were negative for Chlamydia and were delivered immediately after a Chlamydia positive woman. Compared to negative women, women with Chlamydia cervicitis were younger and presented for antenatal care at a later gestational age (difference not significant) and started having sexual intercourse at an earlier age (P less than 0.02). There was a significant association between Chlamydial infection and chorioamnionitis, lower birth weight and severe neonatal infection (P less than 0.05); but a contribution from concomitant genital pathogens could not be completely ruled out. Therefore a screening program for Chlamydia should include screening for other genital infections. While almost all cases of Chlamydia could have been suspected by this technique, a screening based on lactobacillary grades in Pap smears might be helpful for this purpose, even more so because it also facilitates tracing other genital pathogens. Detection of Chlamydial antigen from conjunctival swabs taken immediately after birth did not adequately reflect the risks of neonatal infection in this small group.
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1990
G G Donders, L Missiaen, F P Zuspan, F A Van Assche (1990)  Uterine norepinephrine levels are correlated with contraction force, but not with the occurrence of preeclampsia.   Gynecol Obstet Invest 30: 4. 207-211  
Abstract: The aim of the present experiments was to investigate a possible correlation between the occurrence of preeclampsia and the levels of norepinephrine in human myometrial biopsies obtained from the lower uterine segment at the time of cesarean section. Norepinephrine was measured directly by the technique of muscle CATS, and indirectly by measuring the effect of their release on the K(+)-induced force development of the myometrial strip. Two distinct types of force development depending on the level of endogenous norepinephrine were observed, but they were not correlated with the development of preeclampsia. This was confirmed by the absence of correlation between uterine norepinephrine levels and the occurrence of preeclampsia. Therefore, no correlation between myometrial catecholamine content and the development of preeclampsia could be demonstrated.
Notes:
1989
G G Donders, S D Delport, F Potze (1989)  Isolated complete congenital heart block diagnosed prenatally in Down's syndrome; a case report.   Eur J Obstet Gynecol Reprod Biol 31: 3. 283-287 Jun  
Abstract: A newborn with Down's syndrome complicated by complete atrioventricular (AV) block, despite normal cardiac anatomy, is described. The congenital AV block was diagnosed in utero, and the characteristics of Down's syndrome were recognised after birth. Pitfalls in antenatal diagnosis and management of complete AV block in the fetus are briefly outlined. Identification of fetal karyotype in case of isolated congenital AV block is recommended.
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1987
G Donders, P Moerman, H Devlieger, B Spitz, F A Van Assche (1987)  X-linked centronuclear myopathy as a cause of floppy baby.   Eur J Obstet Gynecol Reprod Biol 24: 1. 33-38 Jan  
Abstract: Two families with X-linked recessive centro-nuclear myopathy (XLR-CNM) are described. Evidence is accumulating that XLR-CNM forms a distinct entity, in contrast to the commoner later-onset forms. Family history often provides a clue to the diagnosis. Pregnancy is very often complicated by hydramnios and reduced fetal movements. We describe two families with five affected male babies who all died. An isolated case with severe fetal brady-arrhythmias in combination with acute increase in polyhydramnios is mentioned. The neonatal mortality in all recorded cases is 80 percent, with respiratory insufficiency as the cause of death. An attempt is made to establish early prenatal diagnosis and the possibility of carrier detection is briefly discussed.
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1986
R L De Wilde, G Donders (1986)  Scanning electron microscopic study of microvascular anastomoses on irradiated vessels: long-term effect of irradiation.   Microsurgery 7: 4. 156-157  
Abstract: A study was performed to determine the effect of preoperative irradiation on microvascular arterial anastomoses. The study focused on microthrombi and epithelial regeneration. Using scanning electron microscopy (SEM), a clear difference was seen comparing nonirradiated to irradiated vessels. No difference was found between short- and long-term effects of irradiation.
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