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Biomedical subjects

G G Donders

Publications and source records attributed to G G Donders.

At least 19 recordsLinked to original sources

Pathogenesis of abnormal vaginal bacterial flora.

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.

Animals↗

Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion.

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.

Abortion, Spontaneous↗

Wet mount microscopy reflects functional vaginal lactobacillary flora better than Gram stain.

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.

Culture Media↗

Treatment of sexually transmitted bacterial diseases in pregnant women.

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.

Anti-Bacterial Agents↗

Accuracy of rapid antigen detection test for group B streptococci in the indigenous vaginal bacterial flora.

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.

Bacteriological Techniques↗

Vaginitis.

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Female↗

Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus-seronegative African women.

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.

Adult↗

Rapid antigen tests for Neisseria gonorrhoeae and Chlamydia trachomatis are not accurate for screening women with disturbed vaginal lactobacillary flora.

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.

Animals↗