Expression of complement regulatory proteins-CD 35, CD 46, CD 55, and CD 59-in benign and malignant endometrial tissue.

OBJECTIVE: Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples. METHODS: A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin-biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system. RESULTS: For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens (P < 0.0001) was observed. CONCLUSIONS: Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis.

Experimental gestational pyelonephritis induces preterm births and low birth weights in C3H/HeJ mice.

Urinary tract infections (UTIs) are associated with approximately 27% of premature births. Escherichia coli is the most frequent causal agent of UTIs and expresses virulence factors, including surface adhesins that recognize specific host tissue receptors. We have reported that E. coli Dr adhesin recognizes decay-accelerating factor as the host tissue receptor and that these receptors are increased during pregnancy. Induction of pathogenesis is a cumulative effect of the host-pathogen relationship involving specific host factors and virulence characteristics of the invading organism. Recently, an experimental model of chronic pyelonephritis has been developed with E. coli bearing Dr adhesin (E. coli Dr(+)) in nonpregnant lipopolysaccharide hyporesponder C3H/HeJ mice. In this study, we investigated the role of E. coli Dr(+) on the outcome of pregnancy in C3H/HeJ mice. Groups of pregnant mice were infected with E. coli Dr(+) or its isogenic mutant which does not bear the Dr adhesin (E. coli Dr(-)) by urethral catheterization. Nearly 90% of pregnant mice infected with E. coli Dr(+) delivered preterm (before 90% gestation) compared to 10% of mice infected with E. coli Dr(-) and none of the mice treated with phosphate-buffered saline (PBS). Also, there was a significant reduction in fetal birth weight in the E. coli Dr(+)-infected group compared to the E. coli Dr(-)- and PBS-treated groups (P = 0.003). This experimental model of E. coli Dr(+)-induced preterm delivery in mice may help in understanding the molecular mechanisms involved in UTI-induced preterm labor involving bacterial adhesins.

Comparison of once-daily and twice-daily dosing of 0.75% metronidazole gel in the treatment of bacterial vaginosis.

BACKGROUND AND OBJECTIVES: Bacterial vaginosis is the most common cause of vaginal symptoms in women and has potential complications. Efforts to improve treatment of this disease process are warranted. GOAL OF THIS STUDY: The goal of this study was to compare the safety and efficacy of once-daily intravaginal administration of 0.75% metronidazole gel for 5 days to the established twice-daily regimen in the treatment of bacterial vaginosis. STUDY DESIGN: Nonpregnant women with bacterial vaginosis diagnosed by accepted clinical criteria at 14 geographically diverse general gynecology clinics were enrolled in this prospective, randomized, investigator-blind, parallel study. They were treated with either once-daily or twice-daily 0.75% metronidazole gel 5 g intravaginally for 5 days and were reevaluated at 7 to 12 days and 28 to 35 days after completing treatment. Efficacy was determined by clinical criteria. Adverse drug reactions were monitored. RESULTS: Of the 514 evaluable women enrolled, bacterial vaginosis was cured at the first return visit among evaluable patients in 153 of 199 (77%) of those who received the once-daily and in 157 of 196 (80%) of those who received the twice-daily administration. Bacterial vaginosis was cured among evaluable patients at the final visit in 104 of 180 (58%) of those who received once-daily and 109 of 178 (61%) of those who received the twice-daily regimen. Intent-to-treat analysis showed cure at 1 month in 118 of 207 (57%) of those treated once daily and 129 of 209 (62%) of those treated twice daily. Side effects were mild, and none caused treatment discontinuation. CONCLUSIONS: Once-daily dosing of 0.75% metronidazole gel 5 g for 5 days yields efficacy, safety, and tolerance equivalent to the currently used twice-daily dosing in the treatment of bacterial vaginosis, adding another competitive choice to the available therapeutic options for this condition.

Penetration of trovafloxacin into gynecologic tissues.

BACKGROUND: This randomized open-label study assessed the penetration into gynecologic tissues of trovafloxacin, a new broad-spectrum, fourth-generation fluoroquinolone with in vitro activity against anaerobes, gram-positive, gram-negative, and atypical pathogens. METHODS: Women undergoing hysterectomy or hysterectomy and adnexectomy received 200 mg trovafloxacin orally before surgery as a single dose or as multiple doses. Samples of genital tract tissue and serum were obtained simultaneously during surgery. RESULTS: In the single-dose group, trovafloxacin concentrations in genital tract tissues were measurable for up to 30 hours. Tissue concentrations of trovafloxacin after multiple doses were comparable to those after single doses. Mean tissue: serum concentration ratios after a single dose were greatest in the ovary (1.6 microg/g) and comparable in uterus, myometrium, cervix, and fallopian tubes (0.5 to 0.7 microg/g). Adverse events after a single dose were minor. CONCLUSIONS: A daily dose of 200 mg trovafloxacin produces gynecologic tissue concentrations that persist for up to 30 hours at levels necessary to prevent or treat pelvic infections. This dosing regimen is well tolerated.

Treatment of acute gynecologic infections with trovafloxacin. Trovafloxacin Surgical Group.

BACKGROUND: Trovafloxacin, a broad-spectrum fourth-generation quinolone with gram-positive and gram-negative aerobic and anaerobic bacterial activity, is available in oral and intravenous formulations. The objective of this prospective, multicenter, double-blind, randomized study was to compare the efficacy of trovafloxacin with that of cefoxitin, an approved drug for treatment of acute gynecologic infections, together with amoxicillin/clavulanic acid as oral follow-on treatment. METHODS: Patients with a clinical diagnosis of acute pelvic infection received either intravenous alatrofloxacin with oral trovafloxacin follow-on (trovafloxacin) or a combined regimen of cefoxitin followed by amoxicillin/clavulanic acid for a maximum of 14 days. The primary endpoint was clinical response to therapy on follow-up at day 30. RESULTS: Clinical success rates were comparable between the trovafloxacin (n = 107) and comparative (n = 119) groups at study end (90% vs. 86%, respectively; 95% confidence interval, -4.5, 12.5). Among clinically evaluable patients, clinical success rates for infections involving Enterococcus species were higher with trovafloxacin than with the comparative regimen at the end of treatment (96% and 85%) and at study end (96% and 86%). CONCLUSION: Intravenous alatrofloxacin followed by oral trovafloxacin for a maximum of 14 days of total therapy was efficacious in the treatment of acute pelvic infections.

Tissue penetration of Meropenem in patients undergoing gynecologic surgery.

The purpose of this study was to assess the tissue-penetrating ability of a new beta-lactam antibiotic, meropenem, in 64 patients undergoing elective gynecologic surgery. Patients received a single 500-mg dose intravenously before surgery. Plasma and tissue concentrations of meropenem were highest at approximately 1 hour, and good tissue penetration was seen in the variety of specimens evaluated. The median plasma concentration at approximately 1 hour was 13.3 micrograms/mL. The median fluid and tissue concentrations at approximately 1 hour were as follows: cervix, 8.5 micrograms/g; endometrium, 2.3 micrograms/g; fallopian tube, 1.9 micrograms/g; myometrium, 3.6 micrograms/g; ovary, 2.3 micrograms/g; and uterus, 2.3 micrograms/g. These tissue concentrations exceed the MICs of meropenem for 90% of typical pathogens associated with gynecologic infections. Meropenem readily penetrates gynecologic tissue. A single 500-mg dose provides adequate tissue concentrations for treatment of gynecologic infections caused by susceptible pathogens.

A multicenter study comparing intravenous meropenem with clindamycin plus gentamicin for the treatment of acute gynecologic and obstetric pelvic infections in hospitalized women.

We conducted a multicenter trial to compare the efficacy and safety of meropenem with the efficacy and safety of clindamycin plus gentamicin in the treatment of 515 hospitalized patients with acute gynecologic and obstetric pelvic infections. At the end of treatment, the rates of satisfactory clinical and bacteriologic response were high (88%) in both treatment groups: the rates of response were 90% for the meropenem group and 86% for the clindamycin/gentamicin group. No serious adverse events occurred. The most frequently reported drug-related adverse clinical events in the meropenem group were nausea and injection-site reactions (> 1% of patients), and the most common drug-related laboratory abnormality was thrombocythemia. Similar patterns of adverse events occurred in the clindamycin/gentamicin group; however, the incidence of diarrhea and eosinophilia was higher in this group. In summary, this trial demonstrated that meropenem is an effective and safe alternative to the combination of clindamycin plus gentamicin for the treatment of women with acute gynecologic and obstetric pelvic infections.

Gestational pyelonephritis--associated Escherichia coli isolates represent a nonrandom, closely related population.

OBJECTIVE: A select group of Escherichia coli strains known as uropathogenic cause pyelonephritis in nonpregnant individuals. We investigated whether Escherichia coli from gestational pyelonephritis represent a random population or possess common uropathogenic characteristics. STUDY DESIGN: Repetitive element sequence-based polymerase chain reaction, plasmid profiles, hemolysin, and O serotypes were assayed from Escherichia coli isolates of 57 pregnant patients with acute pyelonephritis at different gestational ages. RESULTS: The majority of the first trimester isolates fell primarily into repetitive element sequence-based patterns 1 and 3 and O6, O15, and O75 serotypes. Second-trimester isolates had multiple patterns with high-frequency repetitive element sequence-based polymerase chain reaction 1 and 5 and an unknown (OX) serotype. Pattern 3, predominantly O75 serotype, was found primarily among third-trimester isolates. CONCLUSION: It is likely that Escherichia coli associated with acute pyelonephritis during different trimesters of pregnancy represents nonrandom closely related isolates, and some of these strains may be characteristic in pregnant patients only.

Preterm labor and maternal hypoxia in patients with community-acquired pneumonia.

OBJECTIVE: We sought to determine if preterm labor is associated with the degree of maternal hypoxia in pregnant women with community-acquired pneumonia but no other maternal diseases. METHODS: We retrospectively reviewed the medical records of all antepartum patients admitted with a diagnosis of community-acquired pneumonia to an inner-city university hospital between 1983 and 1987. Included in this review were only the patients with radiologically confirmed diagnose of pneumonia and documented arterial blood gases on room air at the time of admission, but no other maternal diseases. RESULTS: A total of 22 cases were identified. There was no maternal mortality, but there were 2 patients (9%) who developed respiratory failure requiring mechanical ventilation. Bacteremia with Streptococcus pneumoniae was documented in 1 patient (5%). Preterm labor complicated 5 cases (23%) and led to preterm delivery in 3 patients (14%). Terbutaline tocolysis was instituted in 3 patients, but was discontinued in 1 patient who was allowed to deliver because of her worsening condition. Preterm labor was associated with the WBC count on admission, usually > 18,000/mm3, but no statistically significant correlation with the severity of maternal hypoxia was noted. Five patients (23%) were incorrectly diagnosed at the time of admission, 4 with an initial diagnosis of pyelonephritis and 1 with an initial diagnosis of cholecystitis. CONCLUSIONS: Community-acquired pneumonia in the antepartum period is responsible for significant maternal and fetal complications even in the absence of other maternal diseases. Preterm labor and delivery remain frequent, and tocolysis should be used cautiously. At the time of admission, the diagnosis may be difficult. The degree of maternal hypoxia on admission does not correlate with the presence of preterm labor.

Gonococcal infection in a nonhuman host is determined by human complement C1q.

Human C1q displayed a dose-dependent protection of gonococcal cells (GC) from the bactericidal effect of newborn rat serum. All rat pups injected with C1q-preincubated GC developed bacteremia, while none of the animals injected with GC only were infected. After clearance of bacteremia at day 6, live GC could still be recovered from tested organs, including the liver. Preincubation of GC with higher concentrations of C1q was associated with increased morbidity. In contrast to human serum as a source of C1q, rat, rabbit, and mouse sera did not increase the in vivo virulence of Neisseria gonorrhoeae. C1q-deficient human serum, heat-inactivated C1q or human serum, type IV collagen, and complement C3 were inefficient in inducing infection. Experimental infection by C1q-preincubated GC was inhibited by anti-C1q antibodies in a dose-dependent fashion, demonstrating a causal effect of C1q function. This report demonstrates the novel finding that human C1q, a component of the human immune system with a general function for elimination of infection, may increase GC virulence and result in the development of disseminated infection in a nonhuman host.

Development of wound infection or separation after cesarean delivery. Prospective evaluation of 2,431 cases.

Wound infections are a common surgical complication, often requiring a prolonged hospital stay and leading to increased costs. Over a one-year period, 2,431 patients were followed after cesarean delivery with prompt evaluation and culture of all suspicious wounds. Seventy subjects (2.8%) developed confirmed wound infection, and 42 (1.7%) developed noninfected open surgical wounds. Seven (0.3%) fascial dehiscences were diagnosed, requiring surgical repair. Forty of 63 (64%) infected wounds had positive bacterial cultures, with Staphylococcus epidermidis (29%), Enterococcus faecalis (17%), Staphylococcus aureus (17%), Escherichia coli (11%) and Proteus mirabilis (10%) the most frequent isolates. Only 7 of 42 (17%) noninfected wounds had positive cultures, with only S aureus, S epidermidis and Corynebacterium species isolated. Ninety-five percent of the noninfected wounds had blood or serous collections present. Rupture of membranes lasting longer than six hours, emergency cesarean delivery and morbid obesity were associated with a statistically increased likelihood of the development of infected wounds. Emergency cesarean delivery and morbid obesity, but not prolonged rupture of membranes, were associated with an increased likelihood of the development of noninfected wounds. Therefore, it appears that at least two mechanisms are responsible for the development of postcesarean open wounds: (1) increased amniotic fluid and wound colonization due to prolonged rupture of membranes, resulting in a wound infection containing one or more bacterial species derived from the cervicovaginal flora, and (2) increased exogenous bacterial contamination and flora consistent with skin species or breaks in sterile technique, often accompanying difficult or emergency surgery.

Chlamydia trachomatis: management in pregnancy.

Chlamydia trachomatis is a sexually transmitted disease (STD) commonly diagnosed in pregnancy. C. trachomatis has been linked to several pregnancy complications including premature rupture of membranes (PROM), preterm labor and birth, low birth weight, intrauterine growth retardation, and postpartum endometritis. Infants born to mothers through an infected birth canal are at risk for acquiring C. trachomatis pneumonitis, conjunctivitis, and nasopharyngeal infection. The standard treatment of C. trachomatis in pregnancy is erythromycin. Recently, amoxicillin and clindamycin have been added as alternative regimens for those patients intolerant of erythromycin. This paper reviews the effectiveness and tolerance of the alternative regimens compared with erythromycin and the success of antepartum treatment of chlamydia in preventing the poor pregnancy outcome and neonatal morbidity associated with C. trachomatis.

Decay-accelerating factor is expressed in the human endometrium and may serve as the attachment ligand for Dr pili of Escherichia coli.

PROBLEM: We evaluated the hypothesis that different tissue substructures in uteri may express decay accelerating factor (DAF), a complement regulatory protein that also may serve as ligand for bacterial attachment. METHOD: Purified Dr pili, anti-Dr pili IgG, anti-DAF (SCR-3) IgG, and fluorescein-isothiocyanate-conjugated secondary IgG were used for binding and inhibition experiments. RESULT: We observed staining of endometrial glands, spiral arterioles, and myometrial arteries with Dr adhesin (pili) and anti-DAF (SCR-3) IgG, and found variation in distribution and amount of Dr ligands in different individuals. Anti-DAF (SCR-3) IgG blocked the binding of Dr pili to the endometrium. CONCLUSION: Presence of DAF in endometrium may protect tissues from complement-induced damage. Differences between individuals in DAF density in the endometrium may affect sensitivity to attachment of Dr-bearing E. coli and/or complement activation.

Incidence of the prozone phenomenon in syphilis serology.

OBJECTIVE: To determine the rate of the prozone phenomenon in our patient population. METHODS: Sera from 4328 patients--3504 females (2065 pregnant, 1439 nonpregnant) and 824 males--were tested for syphilis by the rapid plasma reagin (RPR) test, and then rechecked with serial twofold dilutions of up to 16-fold to detect the prozone phenomenon. Chi-square analysis with Yates correction was used, with P < or = .05 considered significant. RESULTS: The total positivity rate in females was 6% (213 patients); 13% (27) of the positive tests were false-positive reactions as confirmed by a negative anti-treponemal antibody test. Only one prozone reaction was detected, in serum from a male subject, but it was not missed on initial screening. CONCLUSION: The rate of prozone phenomenon is very low (95% confidence interval 0-0.4%), and routine serial dilutions are not cost effective.

False-negative syphilis screening due to change in temperature.

BACKGROUND AND OBJECTIVES: Inaccurate test results for syphilis may cause an individual to experience serious effects. GOAL OF THE STUDY: Investigate potential sources of error and test limitations causing false-negative reactions. STUDY DESIGN: In 5 months, two laboratories screened 2,232 patients for syphilis by the Rapid Plasma Reagin (RPR) test. RESULTS: The hospital laboratory reported 5.3% (64/1,210) of patients' test as reactive on initial screening, and the research laboratory found 6.4% (78/1,210) reactive. Fourteen reactive patients were incorrectly reported negative by the hospital laboratory, as confirmed by both laboratories. A refrigerated centrifuge in the hospital laboratory possibly caused sera to be cooled before testing, producing false-negative results. When its temperature was adjusted from 4 degrees C to 27 degrees C, an additional 1,022 samples tested were consistent between the two laboratories. CONCLUSION: Cold temperature produces false-negative reactions for syphilis screenings in patients' samples with titers < 1:4 dilution. Patients' samples with titers > or = 1:16 dilution were not affected. According to this study, incorrect temperatures for test sera can alter testing outcomes. Therefore, test manufacturer's directions must be strictly followed.

Toxic shock syndrome mimicking pelvic inflammatory disease presumably resulting from tattoo.

The female patient with a variety of genital tract symptoms offers a distinct challenge to the gynecologist. We report a case that on initial examination was thought to be pelvic inflammatory disease (PID). After further evaluation, our patient was found to be suffering from toxic shock syndrome, which in many ways may resemble PID. This case demonstrates the importance of a careful and thorough evaluation of the gynecologic patient who has several nonspecific signs and symptoms.

Antibiotics in pregnancy.

Because it is known that antibiotics given to the mother may reach and affect the fetus, when prescribing antibiotics during pregnancy, one must take into consideration both maternal and fetal well-being. Therapy should be directed toward the maternal disease but also be safe for the fetus. The volume of distribution is increased during pregnancy, and dosages may need to be adjusted to accommodate this change. Because it is difficult to monitor the toxicity in the fetus, the physician must make careful choices when prescribing antibiotic treatment for the pregnant patient.