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Biomedical subjects

R P Heine

Publications and source records attributed to R P Heine.

At least 19 recordsLinked to original sources

Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.

Adult↗

Self-collection of vaginal swabs for the detection of Chlamydia, gonorrhea, and trichomoniasis: opportunity to encourage sexually transmitted disease testing among adolescents.

BACKGROUND: Many sexually transmitted diseases (STDs) are prevalent among adolescents, yet compliance to undergo STD testing by this population is suboptimal. Efforts to enhance compliance with testing among at-risk youth are needed. GOAL: To determine the feasibility and acceptability of self-collection of vaginal swabs for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among high-school students attending a school health clinic. STUDY DESIGN: Enrolled in the study were 228 female students between the ages of 15 and 19 years. Each student self-collected a single vaginal swab that was tested for C trachomatis, N gonorrhoeae, and T vaginalis by polymerase chain reaction amplification. Acceptability of self-collection of vaginal swabs was assessed. RESULTS: The prevalence of any STD was 18%. Trichomoniasis, chlamydia, and gonorrhea were diagnosed in 10%, 8%, and 2% of students, respectively. Nearly 13% of females who had never previously had a gynecologic examination tested positive for an STD, and 51% of infected students would not have pursued testing by traditional gynecologic examination if self-collection was not offered. Self-collection of vaginal swabs was almost uniformly reported as easy to perform (99%) and preferable to a gynecologic examination (84%). Nearly all (97%) stated that they would undergo testing at frequent intervals if self-testing were available. CONCLUSIONS: Self-collected vaginal swabs for STD testing can be easily implemented in a high-school setting with high acceptability among students, enabling the detection of many STDs that would otherwise remain undetected and untreated.

Adolescent↗

Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. METHODS: To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. RESULTS: Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit. CONCLUSIONS: The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes.

Adult↗

Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

Adult↗

Vaginal fetal fibronectin measurements from 8 to 22 weeks' gestation and subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the range of fetal fibronectin values in the vagina from 8 to 22 weeks' gestation, the factors associated with both low and high values, and whether high values are associated with gestational age at birth. STUDY DESIGN: Vaginal fetal fibronectin was quantitatively determined in a prospective cohort study of 13,360 women being evaluated for participation in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit treatment trials for bacterial vaginosis and Trichomonas vaginalis. Fetal fibronectin values were correlated with gestational age at screening, race, the presence of bacterial vaginosis and Trichomonas vaginalis, and gestational age at delivery. RESULTS: Vaginal fetal fibronectin values at each gestational age ranged from unmeasurable to >1000 ng/mL, with median values always being <10 ng/mL. Fetal fibronectin values declined progressively with increasing gestational age at sampling. Bacterial vaginosis and black race were associated with higher values, whereas nulliparity was associated with lower values. High values after 13 weeks' gestation were associated with a 2- to 3-fold increased risk of subsequent spontaneous preterm birth overall and a 4-fold increased risk of very early preterm birth. CONCLUSION: Elevated vaginal fetal fibronectin levels from 13 to 22 weeks' gestation are associated with a significantly increased risk of spontaneous preterm birth.

Black People↗

Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections.

OBJECTIVE: Secretory leukocyte protease inhibitor contributes resistance to primary human immunodeficiency virus infection in the oral cavity. However, the levels of this inhibitor in the genital tract of women with sexually transmitted diseases or vaginitis are not well described. The objective was to determine vaginal inhibitor levels in women with symptomatic and asymptomatic genital infections. STUDY DESIGN: We tested 207 nonpregnant women for Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, Candida species, and bacterial vaginosis by standard methods. A second group of symptom-free pregnant women (N = 231) was also studied. Secretory leukocyte protease inhibitor was measured by enzyme-linked immunosorbent assay, and results were compared by nonparametric methods. RESULTS: Vaginal levels of secretory leukocyte protease inhibitor in both groups were significantly lower in women with any sexually transmitted disease than in those without infection (P<.0001). Patients with bacterial vaginosis and those with bacterial vaginosis with yeast vaginitis also had decreased levels (P<.025). CONCLUSIONS: Levels of secretory leukocyte protease inhibitor in vaginal fluid are decreased in women with lower genital tract infection. This may represent a common mechanism of increasing susceptibility to infection with human immunodeficiency virus.

Female↗

Accuracy of salivary estriol testing compared to traditional risk factor assessment in predicting preterm birth.

OBJECTIVE: The objective was to compare the predictive accuracy (percentage of correct vs incorrect predictions) of salivary estriol levels (SalEst; Biex, Inc, Dublin, Calif) with that of the modified Creasy score for predicting preterm labor followed by preterm delivery. STUDY DESIGN: A triple-blinded prospective trial was conducted at 8 US centers. RESULTS: Among 601 evaluable patients, serial salivary estriol testing correctly predicted the appropriate outcome 91% of the time and the Creasy scoring method correctly predicted the appropriate outcome 75% of the time (McNemar test P <. 001). Among subjects with Creasy scores >/=10 (high-risk group, n = 152), use of salivary estriol testing correctly predicted the end point 87% of the time, compared with only 7.2% correctly predicted by modified Creasy scoring (McNemar test P <.001). CONCLUSION: Salivary estriol assessment was more accurate in predicting outcome than was modified Creasy scoring.

Estriol↗

Defensins impair phagocytic killing by neutrophils in biomaterial-related infection.

The implantation of foreign material carries a risk of infection which frequently is resistant to all treatment short of removing the implant. We have previously shown that these materials activate neutrophils by contact, leading to production of oxygen free radicals accompanied by release of granule products. Such activation further results in depletion of local host defenses, including the capacity of biomaterial-activated neutrophils to kill bacteria. Among the granule products released from neutrophils are small cationic antibacterial peptides (human neutrophil peptides [HNP]) known as defensins. Here we tested the hypothesis that defensins, released from activated neutrophils onto the surface of biomaterials, might play a role in the deactivation of subsequent neutrophil populations. Incubation of neutrophils with purified HNP resulted in a dose-related impairment of stimulus-induced oxygen radical production and of phagocytic killing. Furthermore, fresh neutrophils added to biomaterial-associated neutrophils exhibited impaired phagocytic killing. This impairment could be abrogated by antibody to HNP but not by an irrelevant antibody. Taken together, these observations support the idea that neutrophils activated at a material surface can create, by means of HNP release, an environment hostile to their microbicidal function and that of their infiltrating brethren.

Anti-Bacterial Agents↗

Levels of antimicrobial molecules defensin and lactoferrin are elevated in the cerebrospinal fluid of children with meningitis.

OBJECTIVE: To measure levels of defensins and lactoferrin in the cerebrospinal fluid (CSF) of children with meningitis. STUDY DESIGN. Prospective descriptive study involving children undergoing lumbar puncture during evaluation for meningitis. METHODS: CSF concentrations of defensins and lactoferrin were determined using enzyme-linked immunosorbent assays on 19 children with bacterial meningitis, 31 children with aseptic meningitis, and 32 control children found to have normal CSF during evaluation for meningitis. Pertinent clinical and laboratory data were gathered on all children. RESULTS: CSF concentrations of both defensins and lactoferrin were elevated markedly in children with bacterial and aseptic meningitis, compared with control children. No control subject had detectable levels of defensins in the CSF. Lactoferrin was undetectable in the CSF of 31 of 32 control subjects. Defensin and lactoferrin levels were significantly higher in the CSF of children with bacterial meningitis than in those with aseptic meningitis. Defensin levels in the CSF of children with bacterial meningitis ranged from 128 ng/mL to 99 430 ng/mL with a mean of 30 311 ng/mL (SD +/- 28 865) and a median of 23 042 ng/mL. Defensin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 1675 ng/mL with a mean of 227 ng/mL (SD +/- 433) and a median of 23 ng/mL. A significant correlation was found between defensin levels in the CSF and the total leukocyte count and the absolute neutrophil count in the CSF of children with bacterial meningitis. Lactoferrin levels in the CSF of children with bacterial meningitis ranged from 184 ng/mL to 31 412 ng/mL with a mean of 13 209 ng/mL (SD +/- 9644) and a median of 10 382 ng/mL. Lactoferrin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 2715 ng/mL with a mean of 1042 ng/mL (SD +/- 878) and a median of 852 ng/mL. No correlation was found between lactoferrin level in the CSF and the total leukocyte count or the absolute neutrophil count in the CSF of children with bacterial meningitis. In our study population, the sum total of CSF defensins and lactoferrin was found to be highly sensitive and specific in delineating bacterial from aseptic meningitis when compared with standard CSF studies. CONCLUSIONS: Significant elevations of defensins and lactoferrin, indicative of endogenous local antimicrobial peptide and polypeptide release, are found in the CSF of children with meningitis. We speculate that elevations in these antimicrobial molecules may reflect the intensity of the host response. Defensins seem to parallel neutrophil activation more closely than lactoferrin. Cumulative levels of CSF defensins and lactoferrin clearly distinguished bacterial meningitis from aseptic meningitis and control patients. Further investigation is warranted to determine the usefulness of measuring defensins and lactoferrin as a diagnostic tool and therapeutic monitor in the evaluation of children with meningitis.

Anti-Infective Agents↗

Metastatic complete hydatidiform mole with a surviving coexistent twin. A case report.

BACKGROUND: Complete hydatidiform molar pregnancy with a coexistent live fetus is a rare clinical entity with poor fetal survival and an uncertain maternal risk. CASE: A twin gestation consisting of a complete molar pregnancy as one twin and a normal second "twin" was identified in the second trimester. The patient was managed expectantly until 28 weeks' gestation, at which time evidence of metastatic trophoblastic disease was identified. She delivered a healthy infant by cesarean section and received postoperative single-agent chemotherapy. She was disease free six months after treatment. CONCLUSION: Patients with documented complete molar pregnancies and coexistent live fetuses present several complex clinical issues. Though successful in some instances, expectant management should be used with caution in these patients.

Adult↗

The use of once-daily dosing of gentamicin in obstetrics and gynecology.

Gentamicin is a widely-used antimicrobial agent for obstetric and gynecologic infections. Renewed excitement in this antibiotic has arisen from recent information supporting less frequent dosing. In this symposium, we will describe the pharmacokinetics of gentamicin and review new information advocating the use of once-daily administration of gentamicin.

Bacterial Infections↗

The pharmacokinetics of once-daily dosing with gentamicin in women with postpartum endometritis.

OBJECTIVE: To evaluate the pharmacokinetics and cost of once-daily dosing with gentamicin in women with postpartum endometritis. METHODS: Gentamicin in a single daily dose of 4.5 mg/kg was administered intravenously to 10 women with postpartum endometritis. Peak and trough gentamicin levels were measured, and nephrotoxicity and clinical ototoxicity were monitored. Pharmacokinetic data were analyzed, and a cost analysis of once-daily gentamicin administration was performed. RESULTS: The mean elimination constant was 0.105 +/- 0.008 L/h, and the mean volume of distribution was 0.34 +/- 0.07 L/kg. Mean peak gentamicin levels exceeded 11 mg/L, and all trough levels were < 0.3 mg/L. Cost savings of 44% were achieved with once-daily dosing of gentamicin, compared with traditional thrice-daily dosing. CONCLUSIONS: Once-daily dosing with gentamicin in women with postpartum endometritis achieves therapeutic peak levels without drug accumulation. Substantial cost savings are realized with this dosing regimen.

Adolescent↗

Fetal fibronectin as a marker to discriminate between ectopic and intrauterine pregnancies.

OBJECTIVE: Our purpose was to determine the accuracy of fetal fibronectin values for diagnosing ectopic pregnancies. STUDY DESIGN: We obtained vaginal swabs from women with pregnancies of < or = 12 weeks' gestation to perform enzyme-linked immunosorbent assays for fetal fibronectin. Fetal fibronectin values were compared among groups categorized on the basis of clinical and laboratory criteria into (1) ectopic pregnancies, (2) threatened abortions, (3) incomplete/complete abortions, and (4) uncomplicated intrauterine pregnancies. RESULTS: Mean fetal fibronectin values ranged from 0.08 microg/mL in women with ectopic pregnancies to 0.33 microg/mL in women with threatened abortions. Comparing these two diagnostic categories, a negative fetal fibronectin test (at a cutoff level of 0.300 microg/mL) predicted ectopic pregnancy with a sensitivity of 94%, specificity of 28%, positive predictive value of 62%, and negative predictive value of 78%. CONCLUSION: Although fetal fibronectin is low in women with ectopic pregnancies, a negative test is not sufficiently sensitive and specific to be used clinically for the diagnosis of ectopic pregnancy.

Abortion, Incomplete↗

Amniotic fluid defensins: potential markers of subclinical intrauterine infection.

Human neutrophil peptides 1-3 (defensins) are granule constituents released from activated neutrophils. We hypothesized that amniotic fluid (AF) defensin levels are elevated in preterm labor (PTL) patients with subclinical intrauterine infection (IUI). AF samples were obtained from 203 pregnant patients with varying clinical characteristics. Defensin levels were measured by enzyme-linked immunosorbent assay. Median AF defensin levels were fourfold to 24-fold higher in patients with IUI than in preterm and term controls. Among patients with subclinical IUI, the degree of AF defensin elevation was greater in those with a positive AF culture. AF defensin levels increased exponentially with increasing severity of histologic chorioamnionitis. An AF defensin level of > 2,500 ng/mL identified 88% of patients with a positive AF culture, whereas a level of > 400 ng/mL identified 85% of all infected patients. AF defensin levels accurately identify patients with subclinical IUI, as defined by a positive AF culture or placental histology.

Amniotic Fluid↗

Cysteine proteases of Trichomonas vaginalis degrade secretory leukocyte protease inhibitor.

Sexually transmitted diseases, including trichomoniasis, are risk factors for acquisition of human immunodeficiency virus (HIV) infection. Enhancement mechanisms are unknown. Secretory leukocyte protease inhibitor (SLPI) from saliva appears to prevent transmission of HIV through inhibition of virus entry into monocytic cells in vitro. This study was undertaken to determine if secreted cysteine proteases of Trichomonas vaginalis degrade SLPI and render it nonfunctional. It was determined if SLPI levels were decreased in vaginal fluids from pregnant women infected with T. vaginalis. Isolated proteases were incubated with recombinant human SLPI, and the degradation was followed by Western analysis with SLPI antiserum. SLPI levels were measured by ELISA in vaginal fluids from women infected with T. vaginalis and uninfected controls. Cysteine proteases cleaved SLPI and rendered it nonfunctional. Median levels of SLPI from infected patients were 26% of those of controls (P <.005). The degradation of SLPI in association with trichomonal infection may increase the risk of HIV acquisition.

Animals↗

Polymerase chain reaction analysis of distal vaginal specimens: a less invasive strategy for detection of Trichomonas vaginalis.

We compared polymerase chain reaction (PCR) analysis of specimens obtained from the distal vagina with wet mount microscopy and culture of specimens from the posterior vaginal fornix. One or all three techniques revealed that 61 (20.3%) of 300 women tested were positive for Trichomonas vaginalis. PCR analysis of distal vaginal specimens detected 56 (91.8%) of 61 infections, while wet mount microscopy and culture detected 49 (80.3%) of 61 infections. Results of this study may impact the approach to testing for T. vaginalis by eliminating the requirement of a vaginal speculum examination. The distal vagina is an appropriate testing site for T. vaginalis by PCR analysis.

Animals↗

Neutrophil activation in preeclampsia. Are defensins and lactoferrin elevated in preeclamptic patients?

OBJECTIVE: To determine if human defensins and lactoferrin, both markers of neutrophil activation, are elevated in preeclamptic plasma. STUDY DESIGN: Blood samples were obtained from 18 preeclamptic and 29 normal pregnant women in the third trimester. Demographic and clinical data were obtained from the medical record. No patient had evidence of labor and/or infection when blood was drawn. Preeclamptic patients were defined by elevated blood pressure, 140/90 mm Hg, proteinuria of > 300 mg in a 24-hour collection and hyperuricemia. Human defensins and lactoferrin were measured by enzyme immunoassay of plasma samples diluted 1:100 and 1:10, respectively. Standard curve values ranged from 0.25 to 16 ng/mL. Data for human defensins and lactoferrin are presented as median values +/-SE. Statistical analysis included Student's t test for comparison of clinical data, Mann-Whitney U test for comparison of absolute values between groups and Fisher's exact test, when appropriate. RESULTS: There was no difference in age or estimated gestational age between the two groups. There were more nulliparous patients in the preeclamptic group. Human defensin levels were significantly elevated (P = .005) in plasma of preeclamptic patients (25.1 ng/mL +/- 16.2) as compared to normal controls (9.0 ng/mL +/- 8.9). Nine of 18 (50%) preeclamptic patients and 2 of 29 (7%) normal controls had defensin levels above the low point on the standard curve (P = .001). There was no difference in lactoferrin levels between the two groups. CONCLUSION: Our results suggest that preeclampsia is associated with neutrophil activation. The biologic effect of elevated human defensins in preeclamptic plasma remains to be determined.

Adult↗

Transferrin increases adherence of iron-deprived Neisseria gonorrhoeae to human endometrial cells.

OBJECTIVE: Our purpose was to study the effects of iron deprivation with and without human transferrin supplementation on the adherence and invasion of Neisseria gonorrhoeae to human endometrial cells. STUDY DESIGN: N. gonorrhoeae grown with our without iron was placed in media alone or media containing 2.5 mg/ml saturated human transferrin or unsaturated transferrin. N. gonorrhoeae was inoculated onto polarized human endometrial carcinoma cell (HEC 1-B) monolayers, and at various intervals monolayers were washed and incubated with media containing gentamicin or media alone. Colony-forming units per milliliter of N. gonorrhoeae associated with HEC 1-B cells were then determined. N. gonorrhoeae strains tested included both a transferrin receptor-positive (wild-type) and a transferrin receptor-negative mutant. Differences in percent of original inoculum remaining at varying time points were analyzed by the Mann-Whitney U test. Transmission electron microscopy using a primary endometrial cell line was used to verify findings. RESULTS: Iron-negative N. gonorrhoeae exhibited less adherence than did iron-positive N. gonorrhoeae. No difference in HEC 1-B adherence was seen when either saturated transferrin or unsaturated transferrin was added to the iron-positive N. gonorrhoeae. With iron-negative N. gonorrhoeae addition of either saturated transferrin or unsaturated transferrin significantly increased N. gonorrhoeae adherence although unsaturated transferrin did not permit growth of iron-negative N. gonorrhoeae in tissue culture media alone. Transmission electron microscopy confirmed increased adherence of iron-negative N. gonorrhoeae supplemented with unsaturated transferrin. An iron-negative N. gonorrhoeae mutant lacking the transferrin receptor exhibited no adherence regardless of addition of saturated transferrin or unsaturated transferrin. Invasion could not be quantitated reliably because of persistence of gentamicin effect. CONCLUSION: Iron and transferrin increased attachment of N. gonorrhoeae to human endometrial cells.

Bacterial Adhesion↗