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.

Microvascular destruction in renal transplant rejection.

In normal kidneys, peritubular and glomerular capillaries can be readily identified by their intense expression of HLA class I and class II compared to other cells within the graft. This high density of expression of MHC, plus their exposure to activated circulating lymphocytes, makes these cells the likely early and primary target of rejection responses. The fate of these capillaries during renal allograft rejection was examined using an indirect immunoperoxidase staining technique and monoclonal antibodies to class I and class II MHC antigens as well as other antigens on capillary endothelium including ICAM-1, LFA-3, and a novel antigen identified by E1.5. Expression of HLA-DR by peritubular capillaries was decreased during rejection, and this disappearance of peritubular capillaries with severe rejection was confirmed by loss of other markers of microvascular endothelium. These studies suggest peritubular capillaries may be the major target of the acute rejection response, and the techniques described allow assessment of degree of damage to these structures in renal allograft biopsies.

Isolation of Chlamydia trachomatis from sexually abused female adolescents.

Cultures for Chlamydia trachomatis were obtained from 127 female adolescents (13-17 years of age) evaluated for reported sexual abuse. The rate of positive cultures for C trachomatis in this population was 14% (18 of 127). Neisseria gonorrhoeae was found in 12% (15 of 127) of these patients. All but two of the culture-positive patients admitted sexual activity before the abuse, and it is likely that most of the infections were acquired during this previous sexual activity. Concomitant infection with N gonorrhoeae was found in seven adolescents positive for C trachomatis. No adolescents in this study exhibited a positive VDRL. Victims of abuse should be tested for both gonococcal and chlamydial infection. These data show that if antibiotic prophylaxis is used for the sexually abused adolescent, it should be directed against both C trachomatis and N gonorrhoeae.

Amoxicillin therapy for Chlamydia trachomatis in pregnancy.

For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate. There is no alternate therapy. Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed. For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy. In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base. Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody. In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group. These differences were not significant. The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so. However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P less than .006). These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy.

Pelvic inflammatory disease in human immunodeficiency virus-infected women.

OBJECTIVE: To determine whether the clinical course of pelvic inflammatory disease differs between women with human immunodeficiency virus (HIV) infection and seronegative controls. METHODS: All admissions for acute pelvic inflammatory disease from January 1, 1986 to December 31, 1992 at San Francisco General Hospital were reviewed, identifying 23 HIV-seropositive women. Their clinical course was compared with a control group of 108 seronegative women admitted for acute pelvic inflammatory disease. RESULTS: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease had significantly lower abdominal tenderness scores (P < .05), lower admission and discharge white blood cell counts (WBC) (P < .01, P < .05), and fewer gonococcal infections (odds ratio 0.3, 95% confidence interval [CI] 0.1-0.9; P < .05) than the seronegative controls. There were no significant differences in duration of treatment, length of hospitalization, or incidence of tubo-ovarian abscess. Significantly more HIV-positive women with acute pelvic inflammatory disease required surgical intervention than seronegative women (odds ratio 5.5, 95% CI 1.0-29.3; P < .05). CONCLUSION: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease may have an altered immune response, resulting in inadequate response to antimicrobial agents and the need for more surgical intervention. Future studies must include larger numbers of HIV-infected women, and the results must be stratified for CD4 counts, clinical HIV stage, and other measures of immunocompromise.

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.

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.

Differential diagnosis of appendicitis and pelvic inflammatory disease. A prospective analysis.

Diagnosis of the cause of lower abdominal pain in women may be difficult because appendicitis and pelvic inflammatory disease often present similarly. In a prospective study of 118 women, we found that several criteria are useful in establishing this differential. These include (1) duration of symptoms, (2) the presence of nausea, vomiting or both, (3) a history of venereal disease, (4) cervical motion tenderness, (5) adnexal tenderness, and (6) isolated peritoneal signs in the right lower quadrant. Although no single finding can define the diagnosis, the history and physical findings reported herein provide a number of criteria which, when taken together, will usually allow a confident diagnosis of either appendicitis or pelvic inflammatory disease to be made. Attention to these items can improve precision in diagnosis and lessen the incidence of unnecessary laparotomy, which carries a well-documented complication rate of 10 to 20 percent.

The immunology of HIV disease and pregnancy and possible interactions.

HIV infection may impair a large portion of the human immune response. Infection of CD4+ T cells results in depletion of this population, leading to dysfunction of T-cell-dependent activities. Numerous other immune functions are directly or indirectly impaired, including the function of CD8+ T cells and decreases in total lymphocytes, IL-2 secretion, IL-2R expression, proliferative response to mitogens, NK activity, ADCC, and several other measures. Immune alterations seen in normal pregnancy include decreases in CD4 and T cells, the proliferative response to mitogen, IL-2 secretion, and NK activity. These changes are largely cellular and usually are not apparent clinically. Normal pregnant women are immunocompetent. When pregnancy is complicated by asymptomatic HIV infection, the obstetric outcome does not seem to be adversely affected. Preliminary studies show that the course of HIV disease may not be adversely affected in these women, but this matter is the subject of intense investigation.

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.

[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.

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.

Current trends in the diagnosis and treatment of tuboovarian abscess.

Tuboovarian abscess is a well-recognized complication of acute salpingitis and has been reported in as many as one third of hospital admissions for acute salpingitis. The incidence of tuboovarian abscess is expected to increase as a result of the current epidemic of sexually transmitted diseases and their sequelae. Patients with tuboovarian abscess most commonly present with lower abdominal pain and an adnexal mass(es). Fever and leukocytosis may be absent. Ultrasound, computed tomographic scans, laparoscopy, or laparotomy may be necessary to confirm the diagnosis. Tuboovarian abscess may be unilateral or bilateral regardless of intrauterine contraceptive device usage. Tuboovarian abscess is polymicrobial with a preponderance of anaerobic organisms. An initial conservative antimicrobial approach to the management of the unruptured tuboovarian abscess is appropriate if the antimicrobial agents used can penetrate abscesses, remain active within the abscess environment, and are active against the major pathogens in tuboovarian abscess, including the resistant gram-negative anaerobes such as Bacteroides fragilis and Bacteroides bivius. However, if the patient does not begin to show a response within a reasonable amount of time, about 48 to 72 hours, surgical intervention should be undertaken. Suspicion of rupture should remain an indication for immediate operation. Once operation is undertaken, a conservative approach with unilateral adnexectomy for one-side tuboovarian abscess is appropriate if future fertility or hormone production is desired.

Anti-infective drugs in obstetrics and gynecology.

Prophylactic and therapeutic options for reproductive infections are continually shifting. In this review, highlights from the recent literature of anti-infective drugs in obstetrics and gynecology are presented. Several articles offer new insights into the basic pathophysiology of common infections. Others provide novel strategies in prophylaxis for women with recurrent infections and for those undergoing surgical procedures. In the therapy arena, refinements in dosing schedules favor lower doses and shorter courses for some infections. Intriguing data regarding infrequently discussed infectious processes are presented. Finally, as new, more sophisticated agents flood the market, they are compared against the gold standards of treatment.

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.

Tubo-ovarian abscess: contemporary approach to management.

Two hundred and thirty-two patients with tubo-ovarian abscesses (TOAs) were evaluated. Ruptured TOAs were documented in seven (3%) of the patients. One hundred and seventy-five patients with TOAs were treated with antibiotics alone; for 15 of these patients, TOAs were confirmed by laparoscopy. The remaining 57 patients required surgical intervention: drainage (five patients), unilateral salpingo-oophorectomy (19) and total abdominal hysterectomy and bilateral salpingo-oophorectomy (33). A unilateral TOA was present in 163 patients (70%). Seventy-six patients with TOAs used intrauterine contraceptive devices, and in this group, 54 (71%) patients had unilateral TOAs. The most common microorganisms that were recovered from these TOAs were Escherichia coli, Bacteroides fragilis, Bacteroides species, Peptostreptococcus, Peptococcus, and aerobic streptococci. Sixty-eight percent of the patients treated with an antimicrobial regimen that included clindamycin had a decrease in the size of the TOA, while only 36.5% of those receiving antimicrobial regimens without clindamycin had a decrease in the size of the TOA (P less than .01). Long-term follow-up information (two to 10 years) was available for 58 of the patients treated with antibiotics alone. Eighteen (31%) required subsequent surgery; 12 had persistent TOAs; and six, chronic salpingo-oophoritis. Intrauterine pregnancy was documented in eight (13.8%) patients. Of the 19 patients treated with unilateral adnexectomy, two ultimately required hysterectomy and contralateral adnexectomy, while three patients in this group subsequently became pregnant (one ectopic and two intrauterine).

Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis.

A role for both the cellular and humoral components of the immune response has been established for chlamydial infection. The significance of helper (L3T4) T cells was evaluated by using a Chlamydia trachomatis murine salpingitis model for upper genital tract chlamydial infection. Mouse oviducts were inoculated with C. trachomatis by using the mouse pneumonitis agent (MoPn) or control medium. Mice depleted of L3T4-bearing lymphocytes had significantly higher (P less than 0.05) numbers of organisms recovered at day 7 postinoculation. The rate of hydrosalpinx formation was significantly higher in the mice depleted of L3T4-bearing lymphocytes (27 of 31 [87%] ) than in the infected undepleted group (8 of 16 [50%] ) (P less than 0.01). The geometric mean antichlamydial immunoglobulin G titers at day 54 postinoculation were significantly higher in the L3T4-depleted mice (mean titer, 2,030) than in the undepleted group (mean titer, 776; P less than 0.05). The rate of fertility was lower in the L3T4-depleted group (2 of 31 [6%]) than in the infected, undepleted mice (2 of 16 [13%]), but this difference did not reach statistical significance. In conclusion, the greater persistence of organisms in the oviduct and higher rates of hydrosalpinx formation in mice depleted of L3T4-bearing cells suggests that these cells play a role in the clearing of organisms following infection and thus in reducing the degree of oviduct obstruction and damage.