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.

Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis.

OBJECTIVE: We sought to determine potential risk factors for upper genital tract inflammation in women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis. STUDY DESIGN: In a case-controlled study we compared 111 women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis (the study group) with 24 women who had negative tests for each of these infections (the control group). We evaluated potential risk factors for upper genital tract inflammation by use of bivariate and then logistic regression analysis. RESULTS: We found plasma cell endometritis in 53 of 111 women in the study group and 3 of 24 controls (odds ratio = 6.4, 95% confidence interval 1.7 to 35.0). On logistic regression, the study group women who were in the proliferative phase had increased likelihood of plasma cell endometritis (odds ratio = 4.5, 95% confidence interval 1.6 to 12.4). CONCLUSION: The proliferative phase of the menstrual cycle seems to be the primary risk factor for ascending infection by organisms associated with pelvic inflammatory disease. This may be due to a hormonal effect or to the loss of the cervical barrier during menstruation.

[Prevalence of bacterial vaginosis in an obstetric population of Barcelona]. / Prevalencia de vaginosis bacteriana en una población obstétrica de Barcelona.

OBJECTIVES: To investigate the prevalence and risk factors of bacterial vaginosis (BV) in a pregnant population of Barcelona (Spain). MATERIAL AND METHODS: 301 pregnant women controlled in the Hospital Clinic i Provincial (HCP) of Barcelona were enrolled in the study. Complete epidemiological information, and vaginal samples were available in 293 women. BV was diagnosed by Gram stain of vaginal smear (Nugent's criteria). RESULTS: BV was detected in 22 pregnant women (7.5%; 95% CI: 4.6-10.5%). There was no association between race, parity, education, marital status, smoking and drug use, and the presence of BV. Non-use of birth control method (72.3% vs 34.4%; p < 0.0001), presence of sexually transmitted diseases (STD) during pregnancy (22.7% vs 3.7%; p < 0.0001), HIV seropositivity (13.6% vs 2.9%; p = 0.041) and presence of symptoms of vaginitis (40.9% vs 13.3%; p = 0.009) were significantly associated with the presence of BV. CONCLUSIONS: The prevalence of BV in a pregnant population of Barcelona (Spain) is 7.5%. Further work is needed to evaluate the usefulness of BV as a prescreening marker for STD and HIV infection. The Gram stain provides an inexpensive, fast and easy method to diagnose BV, and may allow us to screen, treat and prevent the morbidity and mortality associated with it.

Immunology of HIV and pregnancy. The effects of each on the other.

Infection with HIV may significantly affect the human immune response. Depletion of CD4 T cells directly or indirectly results in global immune dysfunction, including both cellular and humoral components of the immune system. Ongoing viral replication leads to progressive immune destruction despite apparent clinical latency. The end result, if left untreated, is CD4 T-cell depletion, severe immune compromise, opportunistic infection, and eventual death. Pregnancy has been purported to induce an altered immune state to protect the fetus from immune rejection that may leave the mother with impaired immunity. This theoretical risk has been overemphasized, and, in fact, only limited data suggest that certain infections may have worse presentations and outcomes during pregnancy. The mother maintains immunocompetence throughout gestation and is not overwhelmed with opportunistic infection. Women infected with HIV may experience some decline in CD4 T-cell percentages and possibly in function. It is not clear whether any of the effects will significantly affect long-term outcome. Infection with HIV may predispose pregnant women to a variety of adverse pregnancy outcomes, including preterm labor, prematurity, low-birth-weight infants, postpartum endometritis, and other infectious morbidity. Larger controlled studies are necessary to determine the frequency of these adverse outcomes and whether they will predominantly affect the severely immunocompromised HIV-infected pregnant women.

Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and immune function II: maternal factors influencing transmission.

The risk of mother-to-child transmission of HIV ranges from 15-35 percent depending on the population under study (Fowler and Rogers 1996, Peckham and Gibb 1995). The recent finding that zidovudine treatment during pregnancy can reduce the risk of mother-to-child transmission of HIV by as much as two-thirds in some populations (CDC 1994, Connor et al. 1994), raises the question of which maternal, fetal, viral, immunologic, and placental factors play the greatest role in vertical transmission. It is clear that not only does the transmission rate vary dramatically by geographical distribution, but both the prevalence of infection and susceptibility of the uninfected may be higher in parts of the developing world. The transmission rate is significantly higher in the developing world presumably due to numerous factors including coinfection with other STD's, very little economic support for prevention, education, health maintenance or improving nutritional contributions to curb the spread of HIV. Furthermore, the strategies to reduce vertical transmission in industrialized countries are often not feasible in the developing world. Providing widescale availability of antivirals may not be feasible in areas where, to date, vitamin deficiencies often still exist. The healthcare budget in many of these developing countries cannot even pay for basic medical or prenatal services. The future directions in reducing the rate of mother-to-infant transmission must focus on strategies applicable to the developing world as well as industrialized countries. The vast majority of HIV in the pediatric age group is the result of vertical transmission of the virus. A number of maternal immunologic factors have been associated with vertical transmission. This paper offers a brief review of the extant knowledge with regard to the role of maternal factors in vertical transmission of HIV infection.

Interleukin-6 secretion in vitro is up-regulated in ectopic and eutopic endometrial stromal cells from women with endometriosis.

An in vitro model developed to compare human endometrial and endometriosis stromal cells was used to examine basal and stimulated expression of interleukin (IL-6). Stromal cells isolated from normal endometrium (NE) exhibited the lowest level of IL-6 secretion (84 pg/10(6) cells-48 h), whereas those cells isolated from endometriosis implants (EI) secreted the highest concentration of this inflammatory cytokine (46,284 pg/10(5) cells-48 h; P < 0.01). Eutopic endometrial stromal cells from women with endometriosis (EE) expressed an intermediate concentration of IL-6 (831 pg/10(6) cells-48 h). Stimulation of the various cultures with IL-1 beta dramatically augmented stromal cell production of IL-6. The mean concentrations of stimulated IL-6 secretion were 16,257, 37,800, and 264,290 pg/10(5) cells-48 h for NE, EE, and EI cells, respectively (P < 0.03). Exposure of the cell cultures to 10 nmol/L estradiol had little direct effect on IL-6 production. The results indicate that endometrial stromal cells isolated from tissues of women with and without endometriosis express IL-6 under basal and cytokine-stimulated conditions. Differential responsiveness among the three cell sources indicates that NE, EE, and EI cells have intrinsic quantitative differences in cytokine regulation.

Commonly used diagnostic criteria for pelvic inflammatory disease have poor sensitivity for plasma cell endometritis.

BACKGROUND: The majority of women with tubal damage do not have a history of acute pelvic inflammatory disease. The prevalence of upper genital tract inflammation was evaluated in women deemed not to have pelvic inflammatory disease by common diagnostic criteria. GOAL OF THIS STUDY: To compare clinical signs and laboratory tests used to diagnose pelvic inflammatory disease with endometrial biopsy histopathology. STUDY DESIGN: Endometrial biopsy and commonly used physical and laboratory tests were performed on 52 women with pelvic tenderness, 51 with vaginosis or cervicitis, and 22 control subjects who had no evidence of infection with Neisseria gonorrhoeae or Chlamydia trachomatis and who tested negative for bacterial vaginosis using vaginal swab Gram's stain. RESULTS: Thirty-six of 52 patients (69%) with pelvic tenderness, compared with 22 of 51 patients (43%) with vaginosis or cervicitis and two of 22 control subjects (9%), had plasma cell endometritis. The Centers for Disease Control and Prevention minimal diagnostic criteria for pelvic inflammatory disease had a sensitivity of 33% for plasma cell endometritis. CONCLUSIONS: The clinical diagnosis of pelvic inflammatory disease using published criteria correlates poorly with plasma cell endometritis.

Gynecologic disease in women infected with human immunodeficiency virus type 1.

Gynecologic disease is commonly encountered in women infected with the human immunodeficiency virus (HIV). The clinical course of cervical intraepithelial neoplasia, invasive cervical cancer, pelvic inflammatory disease, syphilis, and vaginal candidiasis may be altered by HIV infection and may be refractory to standard treatment, especially with increasing degrees of immune suppression. Careful screening for gynecologic disease and vigilant surveillance for treatment failure are important in the care of women infected with HIV.

Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling.

The alpha v beta 6 integrin was identified in cultured epithelial cells and functions as a fibronectin receptor. We have now used monoclonal antibodies to determine in vivo expression patterns of the beta 6 subunit in normal and pathological human or primate tissues, and during experimental wound healing or induced lung injury. The results indicate that beta 6 expression is restricted to epithelia and is up-regulated in parallel with morphogenetic events, tumorigenesis, and epithelial repair. During development of the kidney, lung, and skin, we found that beta 6 is expressed by specific types of epithelial cells, whereas it is mostly undetectable in normal adult kidney, lung and skin. In contrast, we detected high-level expression in several types of carcinoma. For example, beta 6 is almost invariably neo-expressed in squamous cell carcinomas derived from the oral mucosa, often focally localized at the infiltrating edges of tumor islands. Expression of beta 6 is also upregulated in migrating keratinocytes at the wound edge during experimental epidermal wound healing. Similarly, beta 6 expression is induced in type II alveolar epithelial cells during lung injury caused by injection of live bacteria. We also observed beta 6 expression in adult lungs and kidneys at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys. From these findings and earlier results, we hypothesize that alpha v beta 6 affects cell spreading, migration and growth during reorganization of epithelia in development, tissue repair, and neoplasia.

Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis.

OBJECTIVE: To investigate the presence of interleukin-8 (IL-8), a macrophage-derived angiogenic factor, in peritoneal fluid (PF) of women with and without endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENTS: Eighteen women with laparoscopic findings of mild to severe endometriosis, and nine women with no visual evidence of pelvic pathology. MAIN OUTCOME MEASURES: Peritoneal fluid IL-8 levels were determined using an ELISA. Interleukin-8 concentrations were compared among women with and without endometriosis. Correlation between PF IL-8 concentration and endometriosis stage was investigated. RESULTS: Interleukin-8 was detectable in the PF of a majority of women (67%). Interleukin-8 concentrations were higher in the PF of women with endometriosis than in matched normal controls. A significant correlation between PF IL-8 concentration and endometriosis stage was noted. CONCLUSIONS: We hypothesize that IL-8 is an important angiogenic factor that contributes to the pathogenesis of endometriosis by promoting the neovascularization of ectopic endometrial implants.

Plasma cell endometritis in women with symptomatic bacterial vaginosis.

OBJECTIVE: To evaluate the endometrial microbiology and histopathology in women with symptomatic bacterial vaginosis but no signs or symptoms of upper genital tract disease or other vaginal or cervical infections. METHODS: Endometrial biopsies were performed on 41 women complaining of vaginal discharge or pelvic pain at a sexually transmitted disease clinic. These women had neither culture nor serologic evidence of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Twenty-two women with bacterial vaginosis diagnosed by Gram stain examination of vaginal fluid, but with neither signs nor symptoms of upper genital tract infection, were compared with 19 women who had no evidence of bacterial vaginosis on vaginal fluid Gram stain. Endometrial biopsies were evaluated for histopathologic evidence of plasma cell endometritis and were cultured for N gonorrhoeae, C trachomatis, aerobic and anaerobic bacteria, Mycoplasma species, and Ureaplasma urealyticum. RESULTS: Ten of 22 women with bacterial vaginosis had plasma cell endometritis, compared with one of 19 controls (odds ratio [OR] 15, 95% confidence interval [CI] 2-686; P < .01). Bacterial vaginosis-associated organisms were cultured from the endometria of nine of 11 women with and eight of 30 women without plasma cell endometritis (OR 12.4, 95% CI 2-132; P = .002). CONCLUSION: Plasma cell endometritis was frequently present in women with bacterial vaginosis and without other vaginal or cervical infections. This suggests the possibility of an association between bacterial vaginosis and nonchlamydial, nongonococcal, upper genital tract infection.

Features of HIV-1 that could influence maternal-child transmission.

OBJECTIVE: To evaluate the biological and serological properties of the human immunodeficiency virus type 1 (HIV-1) for factors potentially involved in the mother-to-child transmission of HIV-1. DESIGN: Isolates of HIV-1 were recovered from the blood of 12 of 44 nontransmitting mothers and six of eight transmitting mothers and their corresponding infants. These 24 HIV-1 isolates were compared for their biological and immunologic properties to discern any parameters that correlate with vertical transmission of HIV-1. MAIN OUTCOME MEASURES: Replication capabilities of the above-mentioned HIV-1 isolates in human peripheral blood mononuclear cells (PBMCs), human macrophages, and various T-cell lines and the susceptibilities of the viruses to neutralization or enhancement by anti-HIV-1 antibodies in autologous serum samples from mothers and infants. SETTING: San Francisco Bay Area, California. PARTICIPANTS: A cohort of 52 HIV-1-infected women and their infants in a prospective study on perinatal HIV transmission by the Bay Area Perinatal AIDS Center. RESULTS: The viral isolates from the transmitting mothers and their infants differed from the isolates from the nontransmitting mothers in their efficient replication in human PBMCs and in their ability to infect one or more human T-lymphocytic cell lines. All the HIV-1 isolates were able to infect human macrophages with only low-level replication and were unable to form syncytia in the MT-2-lymphocytic cells. No correlation between transmission and reactivity of maternal serum samples to the peptide corresponding to the principal neutralization domain of the third hypervariable region of the viral envelope was observed. However, the majority (9/12) of maternal isolates from the nontransmitters were neutralized by their autologous serum samples compared with only two among six in the transmitter group (P < .07). Moreover, five infant isolates were resistant to neutralization by their respective mother's serum samples, and one was sensitive to infection enhancement by the mother's serum. Another infant isolate was enhanced by his autologous serum. CONCLUSIONS: Viral factors that appeared to correlate with mother-to-child transmission of HIV-1 observed in a small cohort included rapid or high-titered replication in human PBMCs, T-cell line tropism, and resistance to neutralization or a sensitivity to enhancement of infection by the maternal serum.

Human fetal antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Human fetal antibody-dependent cellular cytotoxicity (ADCC) has not been reported previously. Most investigations have failed to document any cytolytic activity among fetal lymphocytes. The purpose of this study was to investigate ADCC activity in the human fetus and identify and characterize the effector cell populations in the fetus. Fetal spleen cells were separated into single-cell suspensions and assayed with 51Cr-labeled herpes simplex 1-infected Chang liver target cells. Significant ADCC activity was detected in 19 of 26 (73%) of freshly assayed fetal spleen cell preparations from fetuses of 17-24 wk gestational age. This activity, however, was significantly less than concurrently run adult peripheral blood mononuclear cells. After plastic adherence the fetal spleen ADCC activity from nonadherent cells was not significantly different from whole spleen preparations. Surprisingly, ADCC activity in nonadherent fetal cells dropped significantly after exposure to latex beads, an effect not seen in nonadherent adult lymphocytes. Thus, either fetal monocyte-derived (macrophages) fetal spleen cells do not efficiently adhere to plastic or a unique nonadherent population of latex-sensitive immunocytes is capable of mediating ADCC activity in the fetus. We suspect the former conclusion to be the more plausible; however, fluorescence-activated cell sorter staining of fetal cells was not sufficient to confirm these suspensions by fluorescence-activated cell sorter analysis.

Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis.

OBJECTIVE: Endometriosis is a common gynecologic disorder in which the concentration and activation of peritoneal macrophages are increased. The goal of this study was to quantify pelvic fluid concentrations of two cytokines involved in macrophage recruitment and activation. STUDY DESIGN: A case-control study of women undergoing pelvic surgery was conducted by collecting peritoneal fluid from 12 women without evidence of endometriosis (controls), 12 with mild, and 12 with moderate to severe endometriosis. Concentrations of RANTES and interferon gamma, soluble cytokines known to recruit and activate macrophages, were quantified by enzyme-linked immunosorbent assays. RESULTS: Pelvic fluid concentrations of RANTES are elevated in women with endometriosis and the levels correlate with the severity of disease. By contrast, concentrations of interferon gamma appear unaffected by the presence of or severity of endometriosis. CONCLUSION: The findings indicate that RANTES, a cytokine with potent chemotactic activity for human monocytes, may play an important role in the recruitment of peritoneal macrophages in endometriosis.