Chlamydial genital infections and laparoscopic findings in infertile women

Several studies have shown that previous chlamydial genital infection, reflected by serological markers, is strongly associated with tubal damage leading to tubal infertility. In 105 women undergoing laparoscopy, multiple samples were collected from the lower (urethra and cervix) and upper (endometrium, peritoneal fluid, tubal lumen) genital tract, in order to isolate Chlamydia trachomatis in cell culture. Chlamydia trachomatis was isolated from at least one site in 13 (30.9%) of 42 infertile women with tubal infertility, in 5 (12.1%) of 41 women with unexplained infertility, in 1 of 4 women affected by acute salpingitis and in 1 (5.5%) of 18 women with endometriosis or uterine malformations. The latter group was the control group. Thirteen (65%) of the 20 positive women harboured Chlamydia trachomatis in their upper genital tract alone and 16 women were positive in one or both tubes. Only one of the positive women showed laparoscopic signs of acute pelvic infection. Four of the 5 positive women with unexplained infertility harboured Chlamydia trachomatis in the tubal lumen. This study confirms that chlamydial infection is strongly associated with tubal damage. It suggests that cervical cultures are inadequate for excluding a tubal infection and that chlamydial colonization of the tubal mucosa is possible in the absence of symptoms and laparoscopic signs of active infection.     

Peritoneal washing cytology in gynecologic cancers: long-term follow-up of 355 patients

BACKGROUND: Microscopic evaluation of cells washed from the peritoneal cavity during surgery for gynecologic tumors is used to detect subclinical intraperitoneal metastases from these tumors. The prognostic significance of this test, however, has been questioned. PURPOSE: Stressing histologic correlation and pitfalls in interpretation, we previously reported that the sensitivity of intraoperative peritoneal washing cytology was lower than was suggested earlier. This study evaluates the clinical utility of this test in the long-term follow-up of our patients. METHODS: Staging (International Federation of Gynecology and Obstetrics [FIGO], 1971) and follow-up information was available for 355 unselected patients with primary tumors who had peritoneal washings performed during initial surgery at University Hospital-Stony Brook, NY, during the period from 1980 through 1989. There were 135 patients with endometrial carcinomas, 112 with ovarian carcinomas, 92 with cervical carcinomas, and 16 with borderline (i.e., of low malignant potential) ovarian tumors. The median follow-up of the patients was 57 months (range, 0-154 months). Follow-up data were obtained from the Tumor Registry at University Hospital-Stony Brook. Survival differences were determined by Kaplan-Meier analysis and were evaluated by two-tailed logrank test. RESULTS. Peritoneal washing cytology was positive at initial surgery for 120 (33.8%) of 355 patients, including 90 (80.4%) of 112 patients with ovarian carcinomas, five (31.2%) of 16 patients with borderline ovarian tumors, 17 (12.6%) of 135 patients with endometrial carcinomas, and eight (8.7%) of 92 patients with cervical cancers. For 203 patients with stage I tumors, the peritoneal cytology was positive in 29.4% of the patients with ovarian carcinomas, 18.2% with borderline ovarian tumors, 6.1% with endometrial carcinomas, and 5.2% with cervical carcinomas. By use of peritoneal histology as the standard, peritoneal cytology was highly specific (98.1%) but less sensitive (82.9%) in detecting intraperitoneal involvement. For patients with stage I tumors, 80.0% with ovarian carcinomas, 83.3% with endometrial carcinomas, and 100% with cervical carcinomas who showed positive cytology died of their cancer, compared with 25.0% with ovarian carcinomas, 13.0% with endometrial carcinomas, and 21.9% with cervical carcinomas who showed negative peritoneal cytology. Four (2.0%) patients with stage I tumors had positive peritoneal cytology but negative peritoneal histology. Of these patients, three (two with ovarian carcinoma and one with cervical carcinoma) died of their cancer, whereas one patient with a borderline ovarian tumor was free of disease at the last follow-up. Survival analysis indicated that peritoneal washing cytology stratified for stage provides better prognostic information for each primary cancer site studied than does stage alone. All patients with borderline ovarian tumors were alive at last follow-up, regardless of disease stage or peritoneal status. CONCLUSIONS: Regardless of FIGO stage, positive peritoneal washing cytology predicted poor prognosis for women with epithelial tumors of the genital tract, except for patients with borderline ovarian tumors. Patients in whom peritoneal cytology was the only evidence of intraperitoneal spread were few, but the disease in such patients was associated with poor outcome. IMPLICATIONS: Strict adherence to specialized cytologic criteria in peritoneal washing cytology allows for results that are highly predictive of survival. This information may be useful in stratifying women in therapeutic trials for treatment of genital tract carcinomas.     

"HPV effect" in the female lower genital tract. A community study

OBJECTIVE: To determine the distribution of "human papillomavirus (HPV) effect" and intraepithelial neoplasia in the lower female genital tract in one community with a prospective study. STUDY DESIGN: In a family practice setting, colposcopy was offered to all women presenting for a routine cervical cytologic smear. Directed biopsies were taken from areas staining abnormally with acetic acid or iodine. RESULTS: This study of 224 women showed a high incidence of HPV effect in the lower genital tract (68%), including 18% on the vulva. The age distribution suggests a coital influence. A five-year review showed persistence of HPV effect on the vulva or vagina in only one patient. One other woman developed cervical intraepithelial neoplasia (CIN) 1. CONCLUSION: HPV effect is common in the lower genital tract of women under the age of 30 years. Colposcopic study suggested that HPV effect on the vulva and vagina is transient. The relatively high incidence of HPV effect on the vulva may explain why cervical HPV and CIN generally appear only after coitarche, as a consequence of physical transfer. This may help explain why women with a single lifetime sexual partner are not exempt from the risk of cervical cancer or its precursors.     

Antibodies and antibody-secreting cells in the female genital tract after vaginal or intranasal immunization with cholera toxin B subunit or conjugates

We studied the antibody response including antibody-secreting cells (ASC) in the female genital tract of mice after mucosal immunizations with the recombinant B subunit of cholera toxin (rCTB) perorally, intraperitoneally, vaginally, and intranasally (i.n.). The strongest genital antibody responses as measured with a novel perfusion-extraction method were induced after vaginal and i.n. immunizations, and these routes also gave rise to specific immunoglobulin A (IgA) and IgG ASC in the genital mucosa. Specific ASC in the iliac lymph nodes, which drain the female genital tract, were seen only after vaginal immunization. Progesterone treatment increased the ASC response in the genital tissue after all mucosal immunizations but most markedly after vaginal immunization. We also tested rCTB as a carrier for human gamma globulin (HGG) and the effect of adding cholera toxin (CT) as an adjuvant for the induction of systemic and genital antibody responses to HGG after vaginal and i.n. immunizations. Vaginal immunizations with HGG conjugated to rCTB resulted in high levels of genital anti-HGG antibodies whether or not CT was added, while after i.n. immunization the strongest antibody response was seen with the conjugate together with CT. In summary, vaginal and i.n. immunization give rise to a specific mucosal immune response including ASC in the genital tissue, and vaginal immunization also elicits ASC in the iliac lymph nodes. We have also shown that rCTB can act as an efficient carrier for a conjugated antigen for induction of a specific antibody response in the genital tract of mice after vaginal or i.n. immunization.     

Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men

Two women, aged 28 and 32, presented with primary infertility and severe dysmenorrhea. The younger woman developed recalcitrant and recurrent firm vaginal, cervical and possibly endometrial lesions over a period of six years; the older patient had similar material in the cervix, endometrium and a fallopian tube. The lesions were composed of amorphous eosinophilic hyaline or necrotic material, shown by histochemical and immunoperoxidase stains to be partly fibrin. Pathologic examination showed that the lesions were similar to those of ligneous (pseudomembranous) conjunctivitis, a rare disease that may occasionally affect the lower female genital tract. However, neither patient had eye disease, and ligneous conjunctivitis has not previously been reported to involve the upper genital tract. Endometrial and tubal involvement could readily explain primary infertility and dysmenorrhea in these patients.     

Children with chronic arthritis: the management of transition to adulthood

Primary fallopian tube carcinoma represents less than 1% of all gynecologic malignancies and is therefore one of the less common malignancies of the female genital tract. Fallopian tube carcinoma is rarely diagnosed preoperatively and is often mistaken for benign pelvic disease or ovarian cancer. Compared with ovarian carcinoma, fallopian tube cancer more often presents in early stage but seems to have a worse prognosis, stage for stage. Treatment consists of surgical debulking followed by chemotherapy, adjuvant or otherwise. New studies are needed to better delineate the clinical course, prognostic factors, and appropriate chemotherapy recommendations.     

Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and vagina

PROBLEM: The tissues of the human female reproductive tract (Fallopian tube, uterus, cervix, and vagina) may play different roles in the provision of mucosal immunity. The purpose of this study was to develop a uniform method suitable for quantitative comparison of the leukocytes from all these tissues. METHOD OF STUDY: Tissues, typically 0.5-1.0 g, were dispersed by enzyme treatment. A flow cytometric gating procedure based on CD45-positivity and low far-red autofluorescence permitted unfractionated, freshly dispersed cells to be phenotyped with respect to T lymphocytes, B lymphocytes, macrophages, and granulocytes. RESULTS: Reproductive tract tissues contain leukocytes that represent approximately 6-20% of the total number of cells, with the Fallopian tubes and uterus containing a higher proportion of leukocytes than the cervix and vagina. The uterine endometrium from post-menopausal women has fewer leukocytes than does uterine endometrium from pre-menopausal women. T lymphocytes are a major constituent (30-60%) of leukocytes from all tissues. The Fallopian tube contains granulocytes as another major constituent; granulocytes are significantly less numerous in the other tissues. All tissues contain B lymphocytes and macrophages as clearly detectable but minor components. CONCLUSIONS: Three-color flow cytometry is an appropriate method for quantitative comparison of leukocytes from the different tissues of the female reproductive tract, during all phases of the menstrual cycle and within post-menopausal samples. Results indicate that the tissues differ from each other, particularly with respect to the large number of granulocytes in the Fallopian tubes.     

A locus coding for putative non-ribosomal peptide/polyketide synthase functions is mutated in a swarming-defective Proteus mirabilis strain

We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K = 10(10)M-1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (> = 130 and 100 kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.     

Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi

A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.     

Lower genital tract neoplasia in women with HIV infection

Women who are infected with human immunodeficiency virus (HIV) are at greater risk for the development of lower genital tract neoplasia than are HIV-negative women. Among HIV-positive women, those who are more severely immunosuppressed appear to be at higher risk for cervical intraepithelial neoplasia (CIN), also known as squamous intraepithelial lesions (SILs). Women who are HIV-positive also are more likely than HIV-negative women to have multifocal lower genital tract neoplasia. Cervical cancer is one of the most important acquired immune deficiency syndrome (AIDS)--related malignancies in women. Cancer and intraepithelial neoplasia of the lower genital tract can be persistent, progressive, recurrent, and difficult to treat in HIV-positive women. The most effective method for treating SILs has not been determined. Regular performance of Pap smears in HIV-positive women is of critical importance, as is careful examination of the entire lower genital tract. Also, women with high-grade intraepithelial or cervical cancer should be tested for HIV.     

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.     

Reconstruction of posterior mandibular defects with soft tissue using the rectus abdominis free flap

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. We studied the presence of NO synthase activity in human nasal mucosa and nasal polyp tissues obtained from patients undergoing septoplasty or polypectomy, respectively. NO synthase activity was quantified in tissue homogenates using citrulline release assay and was located in tissue sections using NADPH-diaphorase histochemistry. The results indicated that nasal polyps contain higher levels of total NO synthase activity than nasal mucosa tissue. In addition, nasal polyps contained mainly inducible NO synthase activity whereas all NO synthase activity detected in the nasal mucosa was in constitutive form. In both cases, NO synthase activity was localized in epithelial cells. In view of these results, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production.     

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.     

Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women

To determine which mucosal immunization routes may be optimal for induction of antibodies in the rectum and female genital tract, groups of women were immunized a total of three times either orally, rectally, or vaginally with a cholera vaccine containing killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit. Systemic and mucosal antibody responses were assessed at 2-week intervals by quantitation of CTB-specific antibodies in serum and in secretions collected directly from mucosal surfaces of the oral cavity, rectum, cervix, and vagina with absorbent wicks. The three immunization routes increased levels of specific immunoglobulin G (IgG) in serum and specific IgA in saliva to similar extents. Rectal immunization was superior to other routes for inducing high levels of specific IgA and IgG in rectal secretions but was least effective for generating antibodies in female genital tract secretions. Only vaginal immunization significantly increased both specific IgA and specific IgG in both the cervix and the vagina. In addition, local production of CTB-specific IgG in the genital tract could be demonstrated only in vaginally immunized women. Vaginal immunization did not generate antibodies in the rectum, however. Thus, generation of optimal immune responses to sexually transmitted organisms in both the rectal and the genital mucosae of women may require local immunization at both of these sites.     

Cervical intraepithelial neoplasia in HIV seropositive patients

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.     

Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle

Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.     

Evaluation of immunoglobulin A1 (IgA1) protease and IgA1 protease-inhibitory activity in human female genital infection with Neisseria gonorrhoeae

Immunoglobulin A1 (IgA1) protease, an enzyme that selectively cleaves human IgA1, may be a virulence factor for pathogenic organisms such as Neisseria gonorrhoeae. Host protection from the effects of IgA1 protease includes antibody-mediated inhibition of IgA1 protease activity, and it is believed that the relative balance between IgA1 protease and inhibitory antibodies contributes to the pathogenesis of disease caused by IgA1 protease-producing organisms. We have examined the levels of these two opposing factors in genital tract secretions and sera from women with uncomplicated infection with N. gonorrhoeae. When IgA1 in cervical mucus was examined by Western blotting, no evidence of cleavage fragments characteristic of IgA1 protease activity was seen in gonococcus-infected or control patients. Cleavage fragments typical of IgA1 protease were detected, however, after the addition of exogenous IgA1 protease to cervical mucus. Degraded IgA1 was detected in some vaginal wash samples, but the fragment pattern was not typical of IgA1 protease activity. All N. gonorrhoeae isolates from the infected patients produced IgA1 protease in vitro. All but two serum samples and 16 of 65 cervical mucus samples displayed inhibitory activity against gonococcal IgA1 protease, but there was no significant difference in the level of inhibitory activity between gonococcus-infected and noninfected patients in either cervical mucus or serum. There was no difference in the levels of IgA1 protease-inhibitory activity in serum or cervical mucus collected from patients at recruitment and 2 weeks later. These results suggest that cleavage of IgA1 by gonococcal IgA1 protease within the lumen of the female lower genital tract is unlikely to be a significant factor in the pathogenesis of infections by N. gonorrhoeae.     

A simple technique for the long-term non-polarised and polarised culture of human fallopian tube epithelial cells

Fallopian tubes were obtained from 25 women undergoing abdominal hysterectomy. Pieces of fallopian tube mucosa were placed in culture flasks containing minimum essential medium in Earle's salts supplemented with fetal bovine serum. First passage was carried out after 7-10 days and subcultures in 4-5 days. For polarised cell culture, epithelial cells were seeded onto an extracellular matrix system. New epithelial cells were seen on day 2-3 of the primary culture and epithelial patches on day 7-10. Cells reached confluence in 4-5 days in subcultures. The cells could be subcultured for 7-11 passages with a life span of 42-60 days. Epithelial origins of the cells were confirmed by immunofluorescence staining with anti-cytokeratin antibody. Polarised cells showed a columnar pattern, microvilli on their apical surface and basally located nucleus whereas non-polarised cells were flat. It was concluded that the human fallopian tube epithelial cells can be cultured in vitro to create non-polarised and polarised cell layers by using a simple and reproducible technique and this system can be a potential model to study function of the fallopian tube.     

Effects of head-down tilt on atrial natriuretic peptide and the renin system in pregnancy

We studied the effects of head-down tilt to 10 degrees for 30 minutes on plasma atrial natriuretic peptide and the renin-aldosterone system in 8 preeclamptic pregnant women, 8 healthy pregnant women, and 11 nonpregnant women of fertile age. Mean arterial blood pressure did not change in the pregnant groups but increased significantly in the nonpregnant control subjects. Heart rate decreased significantly in preeclamptic women but remained unchanged in both control groups. Baseline atrial natriuretic peptide concentration was significantly higher in both preeclamptic (66 +/- 4 pmol/L) and pregnant (54 +/- 6 pmol/L) control subjects compared with nonpregnant subjects (40 +/- 2 pmol/L), but the difference between the pregnant groups was not significant. Head-down tilting induced a significant increase in atrial natriuretic peptide only in healthy pregnant women. Baseline plasma renin activity and aldosterone concentrations were significantly higher in pregnant control subjects compared with both the preeclamptic and nonpregnant groups. The differences between the preeclamptic and nonpregnant control groups were nonsignificant. After head-down tilting, plasma renin activity decreased significantly only in nonpregnant control subjects, whereas aldosterone decreased significantly in preeclamptic and nonpregnant control subjects. In preeclampsia, atrial natriuretic peptide release followed blood pressure and not changes in cardiac output. When all 27 women were studied, a correlation between atrial natriuretic peptide and mean arterial pressure was found in the left lateral supine position. The results suggest that pregnant women developing preeclampsia lose their usual hemodynamic control and show reactions resembling the nonpregnant state when subjected to head-down tilt.