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1.  A Tribute to Abe Mickal, 1912–2001 
PMCID: PMC2442816
3.  Abstracts 
PMCID: PMC2442803
4.  Editorial 
PMCID: PMC2442786
5.  Impaired Whole-Blood Polymorphonuclear Leukocyte Migration as a Possible Predictive Marker for Infections in Preterm Premature Rupture of Membranes 
Objectives: Steroids, used in pretermpremature rupture of membranes (pPROM), to reduce the risk of morbidity and mortality of the preterm neonate, impair the maternal polymorphonuclear leukocyte (PMN)-based immune system. In spite of combination with antibiotics, prenatal and postnatal bacterial infections of mother and child are frequent. This pilot study focuses on the influence of steroids in pPROM on maternal PMN functional capacity and subsequent infections.
Methods: After opting for expectant management, eight women with pPROM and no signs of infection were treated by steroids (betamethasone 5.7 mg, i.m. every 24 hours, for three days) and antibiotic therapy with either amoxicillin and clavulanic acid, piperacillin or ampicillin i.v. up to delivery. The conventional inflammation parameters of PMN blood count and C-reactive protein (CRP) were measured daily in parallel with PMN migratory capacity towards N-formyl-methionyl-leucyI-phenylalanine stimulation and under blank conditions, estimated by a whole blood membrane filter assay.
Results: In all patients PMN migration decreased during the application of steroids. Three patients showed a decrease in PMN migration below critical values and in spite of antibiotic prophylaxis acute pyelonephritis developed 2–6 days later. PMN count and CRP were not predictive of maternal infection.
Conclusion: Reduced PMN function, caused by steroid treatment in pPROM, is suggested to be a reason for serious bacterial infections in spite of antibiotic prophylaxis. PMN migration reflects individual PMN defensive capacity.
PMCID: PMC1784663  PMID: 11916180
6.  Candida lusitaniae as an Unusual Cause of Recurrent Vaginitis and its Successful Treatment With Intravaginal Boric Acid 
Increasing use of short-course antifungal therapies in patients with recurrent vulvovaginitis may enable the emergence of less-common, more resistant yeast strains as vaginal pathogens. We report the case of a patient with chronically symptomatic and repeatedly treated vaginal candidiasis whose infection was attributable to Candida lusitaniae, a previously unreported cause of candidal vaginitis .
PMCID: PMC1784662  PMID: 11916183
7.  Performance Characteristics of Putative Tests for Subclinical Chorioamnionitis 
Objective: To evaluate amniotic fluid glucose, matrix metalloproteinase (MMP)-9, interleukin (IL)-6, and IL-12 for diagnosing subclinical chorioamnionitis in women with preterm labor.
Methods: Forty-four women in preterm labor at 22–35 weeks gestation with suspected subclinical chorioamnionitis underwentamniocentesis.Amniotic fluid analysis included Gram stain, culture, and determination of glucose, MMP-9, IL-6, and IL-12 concentrations. Median values of these analytes were compared using the Mann-Whitney U test. Sensitivity, specificity, and positive and negative predictive values were calculated for tests using a positive amniotic fluid culture or delivery within 24 hours as the key outcome variables
Results: Amniotic fluid concentrations of glucose, MMP-9, and IL-6 correlated closely with positive culture or delivery within 24 hours. IL-12 concentrations did not correlate with either a positive culture or delivery within 24 hours.
Conclusions: Amniotic fluid glucose, MMP-9, and IL-6 reliably predict microbial invasion of the amniotic cavity or imminent delivery. IL-12 values did not correlate with amniotic fluid culture results or imminent delivery.
PMCID: PMC1784661  PMID: 11916177
8.  Influenza and Current Guidelines for its Control 
PMCID: PMC1784660  PMID: 11916174
9.  The Inhibitory Effect of Clindamycin on Lactobacillus in vitro 
Objective: To evaluate the in vitro effect of varying concentrations of clindamycin on Lactobacillus spp.
Methods: Concentrations of clindamycin ranging from 1.95–20 000 mg/ml were studied for their effect on the growth of six strains of Lactobacillus .
Results: Clindamycin concentrations between 1.95–31.25 mg/ml had no statistically significant effect on growth of lactobacilli (p > 0.05). Concentrations 125 and 250 mg/ml had a bacteriostatic effect. The mean minimum inhibitory concentration (MIC) for studied Lactobacillus strains was determined as 1000 mg/ml.
Conclusion: High concentrations of clindamycin achieved in the vagina by intravaginal application might be inhibitory for Lactobacillus .
PMCID: PMC1784659  PMID: 11916182
10.  Differentiation Between Women With Vulvovaginal Symptoms Who are Positive or Negative for Candida Species by Culture 
Objective: To investigate whether clinical criteria could differentiate between women with vulvovaginitis who were culture positive or negative for vaginal Candida species.
Methods: Vulvovaginal specimens were obtained from 501 women with a vaginal discharge and/or pruritis. Clinical information and wet mount microscopy findings were obtained. All specimens were sent to a central laboratory for species identification.
Results: A positive culture for Candida species was obtained from 364 (72.7%) of the specimens. C. albicans was identified in 86.4% of the positive cultures, followed by C. glabrata in 4.5%, C. parapsilosis in 3.9%, C. tropicalis in 2.7% and other Candida species in 1.4%.Women with a positive Candida culture had an increased utilization of oral contraceptives (26.1% vs. 16.8%, p = 0.02) and antibiotics (8.2% vs. 0.7%, p = 0.001), and were more likely to be pregnant (9.1% vs. 3.6%, p = 0.04) than the culture-negative women. Dyspareunia was more frequent in women without Candida (38.0% vs. 28.3%, p = 0.03) while vaginal erythema (p = 0.01) was more common in women with a positive Candida culture.
Conclusions: Although quantitative differences were observed, the presence of vaginal Candida vulvovaginitis cannot be definitively identified by clinical criteria.
PMCID: PMC1784657  PMID: 11916179
11.  Urinalysis and Urinary Tract Infection: Update for Clinicians 
Dysuria is a common presenting complaint of women and urinalysis is a valuable tool in the initial evaluation of this presentation. Clinicians need to be aware that pyuria is the best determinate of bacteriuria requiring therapy and that values significant for infection differ depending on the method of analysis. A hemocytometer yields a value of ≥ 10 WBC/ mm3 significant for bacteriuria, while manual microscopy studies show ≥ 8 WBC/high-power field reliably predicts a positive urine culture. In cases of uncomplicated symptomatic urinary tract infection, a positive value for nitrites and leukocyte esterase by urine dipstick can be treated without the need for a urine culture. Automated urinalysis used widely in large volume laboratories provides more sensitive detection of leukocytes and bacteria in the urine.With automated microscopy, a value of > 2 WBC/hpf is significant pyuria indicative of inflammation of the urinary tract. In complicated cases such as pregnancy, recurrent infection or renal involvement, further evaluation is necessary including manual microscopy and urine culture with sensitivities.
PMCID: PMC1784655  PMID: 11916184
12.  Prevalence of Human Immunodeficiency Virus, Hepatitis B and Hepatitis C Virus Antibodies and Hepatitis B Antigen Among Commercial Sex Workers in Japan 
Objective: To investigate the prevalence of antibodies to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and of hepatitis B surface (HBs) antigen in commercial sex workers (CSW) who attended a sexually transmitted disease (STD) clinic in Tokyo.
Methods: Surveys were conducted on 308 CSW and 384 control subjects for HIV antibody or 241 control subjects for HBs antibody and antigen and HCV antibody.
Results: HIV antibodywas not detected in either CSW or control subjects. The positive rates for HBs antigen and antibody were 0.6 and 23.4%, respectively, in the CSW group, and 0.4 and 71.8% in the control group. The HCV antibody positive rate was 3.2% in the CSW group and 0.4% in the control group.
Conclusion: A statistically significant difference between the two groups was observed only in HCV antibody positive rate. STD checkup for CSW alone is inadequate – STD health education and screening for the general public are also required.
PMCID: PMC1784653  PMID: 11916178
13.  Prevalence of Sexually Transmitted Infections (Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Human Papillomavirus) in Female Attendees of a Sexually Transmitted Diseases Clinic in Ulaanbaatar, Mongolia 
Background: Epidemiological data suggest that the prevalence of syphilis, gonorrhea and trichomoniasis has increased in both urban and rural areas of Mongolia. These data are primarily substantiated by notifications of cases of clinically apparent disease in both rural and urban areas, plus laboratory diagnoses from the AIDS/STD Reference Center,Ulaanbaatar. In the past 5 years, however, there has been a marked decline in the total number of patients being screened for sexually transmitted infections (STIs). An assessment of true prevalence of STIs in a female population attending an urban sexually transmitted diseases (STD) clinic was therefore commenced.
Methods: Consecutivewomen attending an STD clinic in Ulaanbaatar had genital samples collected by the insertion and immediate removal of a tampon, which was then tested for the presence of Neisseria gonorrhoeae , Chlamydia trachomatis, human papillomavirus (HPV) and Trichomonas vaginalis , using polymerase chain reaction (PCR) amplification.
Results: A total of 110 women were studied (mean age 26.7 years). Overall, 58 (53%) patients had one or more pathogens identified; 43 (39%) had a single pathogen, while 15 (14%) had mixed pathogens. C. trachomatis was found in 15 (14%), N. gonorrhoeae in 12 (11%), T. vaginalis in nine (8%) and HPV in 39 (36%). Among the 39 HPV-positive patients, oncogenic genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52) were found in 17 (44%) patients.
Conclusions: Sexually transmitted infections as defined by PCR were common, and found in 53%of female attendees of an urban STD clinic in Mongolia. As infections with conventional STIs increase the risk of human immunodeficiency virus (HIV) transmission, it is imperative that strategies be introduced to reduce the prevalence of STIs. Furthermore, detection of oncogenic HPV was common, indicating that it is vital that a strategy to reduce cervical cancer such as a pre-cancer cervical cytology screening program also be introduced.
PMCID: PMC1784652  PMID: 11516062
14.  Differences in Innate Immunologic Response to Group B Streptococcus Between Colonized and Noncolonized Women 
Objective: To evaluate the functional capacity of granulocytes and monocytes from pregnant and nonpregnant women in relation to group B streptococcus (GBS) colonization status.
Methods: Engulfment of fluorescent GBS by peripheral blood phagocytes from GBS-colonized and noncolonized women was measured by flow cytometry. Intracellular superoxiode generated in response to GBS challenge to monocytes and granulocytes enriched from peripheral blood of these women was also measured by flow cytometry, and extracellular superoxide was determined by colorimetric assay.
Results: Monocytes and granulocytes from pregnant, GBS-colonized women engulfed significantly greater numbers of GBS than phagocytes from pregnant, noncolonized women. No difference in intracellular superoxide production was detected between any of the groups of women; however, monocytes from pregnant, colonized women released significantly more superoxide into the extracellular milieu than did granulocytes from the same women. No differences in extracellular release of superoxide were observed among noncolonized women whether they were pregnant or not.
Conclusions: Monocytes from pregnant, colonized women engulf more GBS and release more of the superoxide into the extracellular environment, where it is unlikely to be an effective defense mechanism against intracellular bacteria. This suggests that components of the innate immune system that should serve in a protective role may function suboptimally, thereby contributing to the colonization process by GBS.
PMCID: PMC1784651  PMID: 11516060
15.  Candida Sepsis Following Transcervical Chorionic Villi Sampling 
Background: The use of invasive devices and broad spectrum antibiotics has increased the rate of candidal superinfections.Candida sepsis associated with pregnancy is rare. Candida sepsis following chorionic villi sampling (CVS) has never been reported.
Case: A 31-year-old pregnant woman presented with signs of sepsis one day after undergoing transcervical CVS. Blood culture and curettage material yielded C. albicans. She was treated with 400 mg of fluconazole daily for 4 weeks and completely recovered.
Conclusion: Candida sepsis should be considered in the differential diagnosis of sepsis following CVS.
PMCID: PMC1784650  PMID: 11516063
16.  Female Genital Warts: Global Trends and Treatments 
The increasing incidence of human papillomavirus (HPV) infection and HPV-associated conditions such as genital warts in women is a global concern. Genital warts are a clinical manifestation of HPV types 6 and 11, and are estimated to affect 1% of sexually active adults aged between 15 and 49. HPV infection is also strongly associated with cervical cancer, and is prevalent in as many as 99% of cases. The psychological stress of having genital warts is often greater than the morbidity of the disease, and therefore successful treatment is crucial. Current treatments are patient-applied and provider-administered therapies. Imiquimod 5% cream, a patient-applied therapy, is an efficacious treatment with tolerable side-effects and a low recurrence rate, and has the potential to be an effective strategy for the management of genital warts.
PMCID: PMC1784648  PMID: 11516064
17.  Human Papillomavirus Typing in HIV-Positive Women 
PMCID: PMC1784646  PMID: 11495554
18.  Adhesion Development and the Expression of Endothelial Nitric Oxide Synthase 
Objective: This study was conducted to determine whether nitric oxide (NO), a potent vasodilator and inhibitor of thrombus formation, is involved in the formation and maintenance of adhesions.
Methods: Skin, subcutaneous tissues, peritoneum and adhesions were collected from surgical patients and total RNA was isolated. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was performed to quantitate endothelial nitric oxide synthase (eNOS) and β-actin mRNA levels.
Results: eNOS mRNA levels for skin, subcutaneous tissue, peritoneum and adhesions were ≤ 3.12 × 10-4, ≤ 3.12 × 10-4, 6.24 × 10-4 and 2.5 × 10-3 attomoles/μl, respectively. β-actin mRNA levels for all tissues were between 1.25 × 10-1 and 6.25 × 10-2 attomoles/μl.
Conclusion: eNOS mRNA can be identified in tissue adhesions, and may therefore play a role in adhesion formation and maintenance.
PMCID: PMC1784645  PMID: 11495551
19.  Acyclovir Suppression to Prevent Clinical Recurrences at Delivery After First Episode Genital Herpes in Pregnancy: An Open-Label Trial 
Objective: To continue evaluation of the use of acyclovir suppression in late pregnancy after first episode genital herpes simplex virus (HSV) infection, using an open-label study design.
Methods: Ninety-six women diagnosed with genital herpes for the first time in the index pregnancy were prescribed suppressive acyclovir 400 mg orally three times daily from 36 weeks until delivery in an open-label fashion. Herpes cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise a Cesarean delivery was performed. NeonatalHSV cultures were obtained and infants were followed clinically. Rates of clinical and asymptomatic genital herpes recurrences and Cesarean delivery for genital herpes were measured, and 95% confidence intervals were calculated.
Results: In 82 patients (85%) compliant with therapy, only 1% had clinical HSV recurrences at delivery. In an intent to treat analysis of the entire cohort, 4% had clinical recurrences (compared with 18–37% in historical controls). Asymptomatic shedding occurred in 1% of women without lesions at delivery. Two of the four clinical recurrences were HSV-culture positive. No significant maternal or fetal side-effects were observed.
Conclusions: In clinical practice the majority of patients are compliant with acyclovir suppression at term. The therapy appears to be effective at reducing clinical recurrences after a first episode of genital herpes complicating a pregnancy.
PMCID: PMC1784644  PMID: 11495557
20.  The Classic Approach to Diagnosis of Vulvovaginitis: A Critical Analysis 
Objective: To correlate the symptoms, signs and clinical diagnosis in women with vaginal discharge, based on the combined weight of the character of the vaginal discharge and bedside tests, with the laboratory diagnosis.
Methods: Women presenting consecutively to the women's health center with vaginal discharge were interviewed and examined for assessment of the quantity and color of the discharge. One drop of the material was then examined for pH and the whiff test was done; a wet mount in saline and in 10% KOH was examined microscopically. The clinical diagnosis was based on the results of these assessments. Gram stain and cultures of the discharge were sent to the microbiology laboratory.
Results: One hundred and fifty-threewomen with vaginal discharge with a clinical diagnosis of vulvovaginitis participated in the study. Fifty-five (35.9%) had normal flora and the other 98 (64.1%) had true infectious vulvovaginitis (k agreement = 18%). According to the laboratory, the principal infectious micro-organism causing the vulvovaginitis was Candida species. Candida infection was associated with pH levels of less than 4.5 (p < 0.0001, odds ratio = 4.74, 95% confidence interval: 2.35–9.5, positive predictive value 68.4%). The whiff test was positive in only a small percentage of bacterial vaginosis (BV) (p = not significant (NS)). Clue cells were documented in 53.3% of patients with a laboratory diagnosis of BV (p < 0.02, positive predictive value 26.7%).
Conclusions: The current approach to the diagnosis of vulvovaginitis should be further studied. The classical and time-consuming assessments were shown not to be reliable diagnostic measures.
PMCID: PMC1784643  PMID: 11495550
21.  Molecular Diagnosis of Human Papillomavirus: Comparison Between Cervical and Vaginal Sampling 
Background: Human papillomavirus (HPV) is the most significant cause of cervical cancer. In view of the number of drawbacks associated with endocervical sampling, the gold standard for HPV detection, this study examined the utility and specificity of vaginal sampling as an alternative for endocervical sampling for the routine detection of HPV.
Case study: The study comprised 51 women who tested positive and 54 women who tested negative for endocervical HPV by polymerase chain reaction (PCR), confirmed by histopathology. At the time of specimen collection, both (speculum-assisted) endocervical and vaginal (no speculum) scrapings were isolated from HPV positive and negativewomen, and HPV DNA was assessed by PCR using the MY09/MY11 primer system;HPV type was identified by hybridization of PCR products with type-specific biotinylated DNA probes. Each participant served as her own control. HPV was detected in vaginal and cervical scrapes from all HPV-positive but not HPV-negative women. In HPV-positive women the same HPV type was found in vaginal and endocervical scrapings (positive predictive value = 1.0).
Conclusion: Correlation between vaginal and endocervical sampling methods was excellent in detecting the presence of HPV DNA and for identifying distinct HPV genotypes. Utilization of vaginal testing for routine HPV detection, and for the long-term follow-up of persistent HPV infection, is therefore recommended.
PMCID: PMC1784642  PMID: 11495553
22.  Candidiasis During Pregnancy May Result From Isogenic Commensal Strains 
Objective: Our laboratory previously demonstrated that asymptomatic vaginal colonization during pregnancy is a factor predisposing patients to subsequent symptomatic vulvovaginal candidiasis. It is unknown whether symptoms result from strain replacement or a change in host relationship to the original colonizing strain. This study was undertaken to determine whether Candida albicans isolates from asymptomatic women could be responsible for subsequent symptomatic vaginitis.
Methods: We retained isolates of C. albicans from women followed longitudinally through pregnancy, and identified six pairs of cultures from women who were colonized without symptoms and who later became symptomatic (average time 14 weeks). We used a random amplification of polymorphic DNA (RAPD) analysis to determine whether isolates from our study patients were genetically similar or dissimilar.
Results: Analysis of these pairs of yeast strains by RAPD revealed that five of the six women had symptoms apparently due to the same yeast strain that was found initially as a commensal strain. To increase the power of these observations, we also performed RAPD analysis on six randomly selected yeast strains from other women in this study who had not become symptomatic to determine whether any of these unrelated strains matched strains from those women who became symptomatic.
Conclusion: Symptomatic yeast vaginitis is usually due to strains of C. albicans already carried in the lower genital tract, underscoring the need to understand regulation of growth and virulence of the organism in vivo.
PMCID: PMC1784641  PMID: 11495556
23.  Human Papillomavirus Typing in HIV-Positive Women 
Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear.
Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis.
Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes.
Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.
PMCID: PMC1784640  PMID: 11495559
24.  Vaginal Mucormycosis: A Case Report 
Although Zygomycetes cause life-threatening, opportunistic infections in immunocompromised hosts, the first case of vaginitis caused by Mucor species in a healthy woman is reported. Mucor vaginitis, which caused mild symptoms only, was refractory to conventional azole therapy and resistant to flucytosine. Cure was achieved with topical amphotericin B.
PMCID: PMC1784639  PMID: 11495552
25.  Hepatitis B Virus Immunization Today 
PMCID: PMC1784638  PMID: 11495555

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