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Background: Douching has been related to risk of pelvic inflammatory disease (PID)., Goal: To examine the association between douching and PID in a large, multicenter, clinical trial of PID after adjustment for race/ethnicity., Study Design: Interviews were conducted with 654 women who had signs and symptoms of PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained from all the women. Women with evidence of plasma cell endometritis and/or gonococcal or chlamydial upper genital tract infections were compared with women who had neither endometritis nor upper genital tract infection., Results: Women with endometritis or upper genital tract infection were more likely to have douched more than once a month or within 6 days of enrollment than women who never douched. These associations remained after adjustment for confounding factors, after analysis of black women only; and among women with normal or intermediate vaginal flora but not bacterial vaginosis., Conclusion: Among a predominantly black group of women with clinical PID, frequent and recent douching was associated with endometritis and upper genital tract infection.

Objective: The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction., Methods: We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls., Results: Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9 +/- 14.1 microg/mL versus 10.9 +/- 5.4 and 10.1 +/- 6.2 microg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3 +/- 2.5 microM versus <5.5 +/- 2.2 and 5.4 +/- 3.4 microM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine., Conclusions: The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.

Objective: To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin., Study Design: We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin., Results: We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids., Conclusion: Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.

In this study, the authors hypothesized that life event stress is associated with an increased risk of spontaneous abortion. Using a nested case-control design in an emergency department (N = 970), stress was measured using a life event inventory and a sample drawn from R. B. Ness et al.'s (1999) Early Pregnancy Study. Gestational age at time of fetal loss served as a marker of chromosomal status. Women experiencing more than one life event used more alcohol and public assistance. Spontaneous abortion at 11 weeks or greater was associated with more life event stress (adjusted odds ratio 2.9, 95% confidence interval 1.4-6.2), whereas spontaneous abortion at any gestational age was not, implying that life event stress increases the risk of chromosomally normal spontaneous abortion. An analysis of confounders showed tobacco use was associated with an increased risk of spontaneous abortion, whereas prenatal care was only associated with fetal loss at 11 weeks or greater.

Objective: To examine the relation between leisure-time physical activity and ovarian cancer., Methods: We used data from a population based case-control study. Cases (n = 767) were women 20-69 years of age in whom epithelial ovarian cancer was diagnosed during 1994-1998 and who resided in a defined region of Pennsylvania, New Jersey, or Delaware. Controls (n = 1367) were ascertained by using random-digit dialing and Health Care Financing Administration files and were frequency-matched to cases for age and county of residence. Information on lifetime leisure-time physical activity was obtained during in-person interviews., Results: Leisure-time physical activity was significantly associated with reduced occurrence of ovarian cancer (P =.01). After adjustment for age, parity, oral contraceptive use, tubal ligation, family history of ovarian cancer, race, and body mass index, women with the highest level of activity had an odds ratio of 0.73 (95% CI 0.56, 0.94) for ovarian cancer compared with women with the lowest level of activity. When the relation was analyzed by various recalled time periods during life, the odds ratios for the highest versus the lowest category of activity at ages 14-17, 18-21, 22-29, 30-39, 40-49, and >50 years ranged from 0.64-0.78., Conclusion: Leisure-time physical activity is associated with reduced occurrence of epithelial ovarian cancer.

Objective: Our purpose was to compare self-reported and biochemical measures for tobacco, marijuana, and cocaine exposures among women early in pregnancy., Study Design: Women who were in the early stages of pregnancy and were examined in an inner-city emergency department were enrolled. Tobacco, marijuana, and cocaine use was measured by self-report and urinalysis. Cocaine use was also assessed by hair analysis., Results: Data were available for 789 women. Among those reporting past use of tobacco, marijuana, and cocaine, 25.2%, 23.9%, and 22.7%, respectively, had positive results of urinary assays; among those reporting current use, 77.2%, 86.6%, and 75.9% had positive findings, whereas among those reporting never use 5.6%, 5. 7%, and 3.6% of results were positive. Hair analysis, in comparison with urine testing, for cocaine identified 4 times as many exposures among women who reported never using cocaine., Conclusions: Urinary assays were equally likely to be positive among women reporting never use and those reporting past use of tobacco, marijuana, or cocaine. Thus women with a positive biologic assay result were as likely to deny use of tobacco as they were to deny marijuana, or cocaine.

We measured bound and free leptin levels in preeclamptic and matched normal pregnant and never-pregnant women to determine whether the free component of leptin is increased during pregnancy and further increased in preeclampsia. Two milliliters of serum was obtained from 18 normal and 18 preeclamptic patients matched by pre-pregnancy body mass index (BMI), and from 18 never-pregnant women matched by BMI with the pregnant groups. The sample was subjected to gel filtration using Sephadex G-100. Radioimmunoassay (RIA) was performed on all fractions, and the proportions of bound and free leptin were determined by analyzing the areas under the curve of the chromatographic profile. The total maternal serum leptin concentration was significantly higher in normal pregnancy compared with the nonpregnant state and was further increased in preeclampsia (33.8 +/- 4.1 v 15.2 +/- 1.8 ng/mL, P = .002, and 48.1 +/- 5.6 ng/mL, P = .02, respectively). Free leptin was increased in normal pregnant compared with never-pregnant women (25.9 +/- 4.1 v 11.0 +/- 2.0 ng/mL, respectively, P = .01), while the increase of total leptin in preeclampsia was exclusively in the free fraction that was significantly higher versus the normal pregnant group (41.8 +/- 5.6 v25.9 +/- 4.1 ng/mL, respectively, P = .01). The bound leptin fraction, by contrast, was significantly increased in the normal pregnant group compared with the preeclamptic group and the never-pregnant group (7.9 +/- 0.56 v 6.2 +/- 0.36 and 4.1 +/- 0.36 ng/mL, respectively, P = .009 and P = <.0001). In conclusion, the free leptin concentration increases in normal pregnancy and is further increased in preeclampsia. This supports the hypothesis that biologically active leptin is elevated in normal pregnancy and is increased more in women with preeclampsia.

We examined ovarian cancer risk in relation to use of phenolphthalein-containing laxatives in 410 epithelial ovarian cancer cases and 713 controls. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of ovarian cancer (odds ratio, OR, 1.1, 95% confidence interval, CI, 0.9-1.4). Risk was slightly, but not significantly, higher with more frequent use (OR 1.2 for 75 or more days of use). When women who used non-phenolphthalein containing laxatives was used as the reference group, the associations were slightly, but not significantly larger (OR 1.4 for any use of phenolphthalein-containing laxatives and OR 1.5 for 75 or more days of use)

Although past studies have shown that oral contraceptives with 50 microg or more of estrogen reduce the risk of ovarian cancer, it is not clear whether newer, lower-dose formulations do as well. We conducted a population-based, case-control study in the Delaware Valley to assess the impact of dose of oral contraception on risk of ovarian cancer. Cases aged 20-69 years with a diagnosis of epithelial ovarian cancer ascertained between May 1994 and July 1999 (n = 767) were compared with community controls (n = 1,367). Compared with never users, the adjusted risk of ovarian cancer was reduced by 40% for oral contraceptive users overall, with longer duration of use affording greater protection. The ovarian cancer risk reduction was similar for women who initiated oral contraception before 1972, when high-dose pills dominated the market; between 1972 and 1980; and after 1980, when newer, lower-dose pills dominated. Oral contraceptive estrogen and progestin content were compared for cases and controls after adjustment for current age, number of pregnancies, race, and family history of ovarian cancer. Use of low-estrogen/low-progestin pills afforded an estimated risk reduction (odds ratio = 0.5, 95% confidence interval: 0.3, 0.6) that was identical to that for high-estrogen/high-progestin pills (odds ratio = 0.5, 95% confidence interval: 0.3, 0.7).

Background and Methods: Prevailing hypotheses about the causes of ovarian carcinogenesis predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of epithelial ovarian cancer. However, the scant available evidence suggests that they may actually be at lower risk. To resolve this issue, we pooled data from eight studies involving 2859 parous women with epithelial ovarian cancer (case patients) and 7434 parous women without ovarian cancer (control women). In addition to assessing their history of multiple births (and the sex of the children, where available), we obtained information on age, parity, oral contraceptive use, and other reproductive factors for each woman. Details of tumor histology were available for all case patients. We estimated the relative risks of various histologic types of ovarian cancers associated with multiple births by using multivariable logistic regression analysis, adjusting for matching and confounding variables., Results: Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%) had a history of multiple births. The adjusted summary odds ratio (OR) for developing all types of epithelial ovarian cancer that are associated with multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no evidence that risks associated with multiple births differed among women with borderline or invasive tumors and among women with same-sex and opposite-sex offspring from multiple births. The risk reductions appeared specific for nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]); in contrast, associations with mucinous tumors (n = 406) were heterogeneous across studies., Conclusions: Parous women with nonmucinous ovarian cancer are no more likely to have a history of multiple births than other parous women, counter to the predictions of current hypotheses for causes of ovarian cancer.

Background: Women constitute an increasing proportion of physicians in the United States. Historically, inequities have existed between male and female physicians in professional advancement, but evidence has suggested that disparities in salary are resolving., Objective: To examine the current state of salary equity among male and female internists., Design: Population-based survey mailed to all Board-certified female internists and a matched group of male internists who had graduated from medical school 10 to 30 years ago and were currently practicing., Setting: Pennsylvania., Participants: 232 male and 213 female internists for whom data were complete., Measurements: Respondents answered questions about demographic characteristics, training, practice type and setting, status within the practice, family life, and salary., Results: Women were more likely to be involved in the least lucrative practice arrangements. They were more likely to be in low-paying specialties, to not be a partner in the practice, and to be salaried employees; they also spent fewer hours per week seeing patients. Even after adjustment for these differences, hourly earnings were significantly higher (14%) among men than among their female colleagues. Men's earnings significantly exceeded women's earnings among physicians with no academic affiliation, those in high-earning specialties, and those in general internal medicine., Conclusions: Significant salary differentials exist between male and female internists overall and in various medical practice settings.

Objective: To test the hypothesis that postmenopausal women with a history of eclampsia manifest a more high risk lipid profile than postmenopausal women with a history of normal pregnancy., Setting: The Department of Obstetrics and Gynaecology, National University Hospital, Reykjavik, Iceland, and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA., Participants: Thirty Icelandic women with a history of eclampsia, aged between 50 and 67 years at the time of re-examination (cases) were individually matched for current age, and for age and parity at index pregnancy, to 30 unrelated Icelandic women with a history of normal pregnancy (controls)., Methods: The participating women completed a health and family history questionnaire and underwent a physical examination. Fasting plasma low density lipoprotein diameter, serum lipids, insulin, and glucose were measured., Results: Mean low density lipoprotein size was significantly smaller and apolipoprotein B concentration was higher in women with prior eclampsia. The percentage of cases receiving blood pressure medication (33%) was significantly greater than controls (6.7%). Thirteen cases had had hypertensive complications in at least one other pregnancy (recurrent subgroup); postmenopausally, these women displayed significantly increased diastolic blood pressures, smaller-sized low density lipoprotein, increased apolipoprotein B, decreased high density lipoprotein2 (HDL2) cholesterol, and increased total cholesterol: HDL cholesterol ratio compared with their controls. Fourteen cases were normotensive in all other pregnancies (nonrecurrent); these showed no differences from their controls., Conclusions: Dyslipoproteinaemia is more prevalent among postmenopausal women with prior eclampsia, especially with recurrent hypertension in pregnancy, than in postmenopausal women with prior normal pregnancies.

Objectives: We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer., Methods: We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained., Results: Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density., Conclusions: These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.

We examined whether the previously observed lower risk of ovarian cancer among African-American women might be the result of differences in known risk factors. In a population-based, case-control study, sociodemographic, reproductive, and physical risk factors among white (669) and African-American (84) women aged 20 through 69 years with a recent diagnosis of epithelial ovarian cancer (study subjects) were compared with white (1110) and African-American (204) community control subjects. African-American women were more likely to have five or more pregnancies and to have a hysterectomy, whereas white women were more likely to have a family history of ovarian cancer. Yet, the risk and protective factors for ovarian cancer were similar among white and African-American women. As compared with white women, the odds of ovarian cancer among African-American women was significantly lower (odds ratio 0.7, 95% confidence interval [CI] 0.5 to 0.9) and remained somewhat lower after adjusting for known, important risk factors (odds ratio 0.8, 95% CI 0.6 to 1.0). Differences in the obstetric and gynecologic experiences of African-American and white women may explain some of the observed racial variability in ovarian cancer risk, but ovarian cancer risk remained lower among African-American women even after adjustment for these factors.

Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.

The purpose of this report is to evaluate the association between lower genital tract inflammation and objectively diagnosed endometritis. We analyzed the first 157 patients enrolled in the PEACH study, a multicenter randomized clinical trial designed to compare the effectiveness of outpatient and inpatient therapy for PID. Women less than 38 years of age, who presented with a history of pelvic discomfort for 30 days or less and who were found to have pelvic organ tenderness (uterine or adnexal tenderness) on bimanual examination, were initially invited to participate. After recruitment of the first 58 patients (group 1) we added the presence of leukorrhea, mucopurulent cervicitis, or untreated positive test for N. gonorrhoeae or C. trachomatis to the inclusion criteria (group 2, N = 99). We compared rates of endometritis in the two groups and calculated the sensitivity, specificity, and predicted values of the presence of white blood cells in the vaginal wet preparation. The rate of upper genital tract infection in group 1 was 46.5% (27/58) compared to 49.5% (49/99) in group 2. Microbiologic evidence of either N. gonorrhoeae or C. trachomatis increased from 22.4% in group 1 to 38.3% in group 2. The presence of vaginal white blood cells or mucopus has a high sensitivity (88.9%), but a low specificity (19.4%) for the diagnosis of upper genital-tract infection. Assessment of the lower genital tract for evidence of infection or inflammation is a valuable component of the diagnostic evaluation of pelvic inflammatory disease. The presence of either mucopus or vaginal white blood cells is a highly sensitive test for endometritis in patients with pelvic pain and tenderness.

Epidemiological studies have demonstrated associations between maternal tobacco smoke exposure and consumption of alcohol during pregnancy and increased risk of pediatric malignancies, particularly infant leukemias. Molecular evidence also suggests that somatic mutational events occurring during fetal hematopoiesis in utero can contribute to this process. As part of an ongoing multi-endpoint biomarker study of 2000 mothers and newborns, the HPRT T-lymphocyte cloning assay was used to determine mutant frequencies (Mf) in umbilical cord blood samples from an initial group of 60 neonates born to a sociodemographically diverse cohort of mothers characterized with respect to age, ethnicity, socioeconomic status, and cigarette smoke and alcohol exposure. Non-zero Mf (N = 47) ranged from 0.19 to 5.62 x 10(-6), median 0.70 x 10(-6), mean +/- SD 0.98 +/- 0.95 x 10(-6). No significant difference in Mf was observed between female and male newborns. Multivariable Poisson regression analysis revealed that increased HPRT Mf were significantly associated with maternal consumption of alcohol at the beginning [Relative Rate (RR) = 1.84, 95% CI = 0.99-3.40, P = 0.052) and during pregnancy (RR = 2.99, 95% CI = 1.14-7.84, P = 0.026). No independent effect of self-reported active maternal cigarette smoking, either at the beginning or throughout pregnancy, nor maternal passive exposure to cigarette smoke was observed. Although based on limited initial data, this is the first report of a positive association between maternal alcohol consumption during pregnancy and HPRT Mf in human newborns. In addition, the spectrum of mutations at the HPRT locus was determined in 33 mutant clones derived from 19 newborns of mothers with no self-reported exposure to tobacco smoke and 14 newborns of mothers exposed passively or actively to cigarette smoke. In the unexposed group, alterations leading to specific exon 2-3 deletions, presumably as a result of illegitimate V(D)J recombinase activity, were found in five of the 19 mutants (26.3%); in the passively exposed group, two exon 2-3 deletions were present among the seven mutants (28.6%); and in the actively exposed group, six of the seven mutants (85.7%) were exon 2-3 deletions. Although no overall increase in HPRT Mf was observed and the number of mutant clones examined was small, these initial results point to an increase in V(D)J recombinase-associated HPRT gene exon 2-3 deletions in cord blood T-lymphocytes in newborns of actively smoking mothers relative to unexposed mothers (P = 0.011). Together, these results add to growing molecular evidence that in utero exposures to genotoxicants result in detectable transplacental mutagenic effects in human newborns.

Objective: We assessed tobacco exposure in nulliparous women with preeclampsia compared with that in control subjects by measuring urinary cotinine to confirm the reduced risk of preeclampsia associated with tobacco exposure during pregnancy., Study Design: A case-control study group of 50 women with preeclampsia after 35 weeks of gestation and a group of 50 control subjects matched for gestational age, date of delivery, and body mass index were selected from the project database. Urine obtained on admission was assayed for cotinine. Self-reported smoking information was blinded during patient selection and laboratory assay., Results: Thirty-five patients had detectable urinary cotinine levels, 11 (22%) with preeclampsia and 24 (48%) control women. Mean cotinine concentrations among exposed women were 331 ng/mL for those with preeclampsia and 540 ng/mL for control subjects. The odds ratio of preeclampsia developing in an exposed woman was 0.31 (95% confidence interval, 0.12-0.79)., Conclusion: These findings, obtained by using laboratory assay, confirm the reduced risk of developing preeclampsia with tobacco exposure.

Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

Objectives: To test the hypothesis that the common missense mutation of 5,10-methylenetetrahydrofolate reductase (MTHFR) (677 C to T, ala to val) is more prevalent among nulliparous preeclamptic women compared with control and transient hypertension of pregnancy patients. The correlation of the MTHFR T677/T677 genotype in mothers and fetuses was also investigated to test for possible maternal-fetal interactions. Lastly, possible differences in serum folate concentrations between control and preeclampsia patients and the possibility of a correlation between serum folate and MTHFR genotype were investigated as well., Methods: The MTHFR genotype was determined for 114 control subjects, 99 preeclamptic patients, and 24 patients with transient hypertension of pregnancy by a polymerase chain reaction/restriction fragment length polymorphism (PCR) method. To ensure homogeneity of ethnic background, only samples from white women were analyzed. Results were analyzed with a chi 2 test for homogeneity. Serum folate was determined by radioimmunoassay (RIA)., Results: The prevalence of the MTHFR T677/T677 genotype was not significantly different between the populations studied. There was no significant difference in the prevalence of the MTHFR T677/T677 genotype between the infants of preeclamptic and control mothers. Furthermore, there was no difference in serum folate concentrations between control and preeclampsia patients, and there was no correlation between serum folate and MTHFR genotype., Conclusion: These data suggest that contrary to previous published reports, the C677T missense mutation of MTHFR is not a risk factor for preeclampsia in this nulliparous patient population. Furthermore, this mutation is not related to serum folate status in late pregnancy.

Background: Cigarette smoking and cocaine use may be risk factors for spontaneous abortion, but data supporting such a link are limited., Methods: We studied the associations between cocaine and tobacco use and spontaneous abortion among pregnant adolescents and women (age range, 14 to 40 years) who sought care at an inner-city emergency department. A total of 400 adolescents and women had spontaneous abortions either at study entry or during follow-up (which lasted until 22 weeks' gestation), and 570 adolescents and women remained pregnant past 22 weeks' gestation. Cocaine use was measured at base line by self-reports and analysis of urine and hair samples. Cigarette smoking was measured by self-reports and urine analysis., Results: The adolescents and women in both groups were predominantly black and of lower socioeconomic status. Among those who had spontaneous abortions, 28.9 percent used cocaine on the basis of hair analysis and 34.6 percent smoked on the basis of a urine cotinine assay, as compared with 20.5 percent and 21.8 percent, respectively, of the adolescents and women who did not have spontaneous abortions. The presence of cocaine in hair samples was independently associated with an increase in the occurrence of spontaneous abortion (odds ratio, 1.4; 95 percent confidence interval, 1.0 to 2.1) after adjustment for demographic and drug-use variables. However, the use of cocaine as measured by self-reports and by urine analysis was not. The presence of cotinine in urine was also independently associated with an increased risk of spontaneous abortion (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.6). Twenty-four percent of the risk of spontaneous abortion could be related to cocaine or tobacco use., Conclusions: Cocaine and tobacco use were common in our study population and were associated with a significant risk of spontaneous abortion.

Objective: We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress., Study Design: Antepartum blood samples were collected >/=6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde., Results: The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P <. 04). Similarly, plasma malondialdehyde (P <.001), triglyceride (P <. 001), and cellular fibronectin (P <.006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P =.97) or creatinine (P =.28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P =.61), malondialdehyde (P =.32), or triglyceride (P =.89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P <. 0001, and r = 0.50, P <.004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P =.03, r = 0.32)., Conclusions: Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration.

We sought to identify factors that discriminate between women with a lower genital tract infection and women with a lower genital tract infection and endometritis. This study enrolled women at risk for or having a lower genital tract infection with Chlamydia trachomatis or Neisseria gonorrhoeae and measured behavioral and clinical factors. Women were identified through contact tracing of male partners, presentation with cervicitis, or presentation with symptoms of pelvic inflammatory disease and classified as (1) having a lower genital tract infection without endometritis, (2) having a lower genital tract infection with endometritis, (3) having no lower genital tract infection with endometritis, and (4) having neither a lower genital tract infection nor endometritis. The primary comparison was between women having a lower genital tract infection without endometritis to women having a lower genital tract infection and endometritis. Women with a lower genital tract infection and endometritis were older and reported a history of more sexually transmitted diseases (70.0% vs. 56.7%), abdominal pain (82.2% vs. 60.0%), and use of barrier methods of contraception (28.9% vs. 8.6%) than women with a lower genital tract infection alone. The regression model found that women with a lower genital tract infection and endometritis were 7.1 times (95% CI = 2.2-23.0) more likely to report abdominal pain and 4.6 times (95% CI = 1.5-14.9) more likely to use barrier methods of contraception than women with a lower genital tract infection alone. These results suggest that behavioral factors, in addition to symptoms, can be used to identify women with and without upper genital tract involvement.

This paper describes the PID Evaluation and Clinical Health Study (PEACH), a multicenter, randomized clinical trial designed to compare treatment with outpatient and inpatient antimicrobial regimens among women with pelvic inflammatory disease (PID). PEACH is the first trial to evaluate the effectiveness and cost-effectiveness of currently recommended antibiotic combinations in preventing infertility, ectopic pregnancy, chronic pelvic pain, recurrent PID, and other health outcomes. It is also the largest prospective study of PID ever conducted in North America. We describe the PEACH study's specific aims, study organization, patient selection criteria, conditions for exclusion, data collected upon entry, randomization and treatment, adherence measures, follow-up activities, quality-of-life measures, outcomes, and statistical analyses. In the first 11 months of enrollment (March 1996-January 1997), 312 women were randomized. Of eligible women, 59% consented to enroll. Participating women are primarily black (72%) and young (mean age 24 years). After a median of 5.5 months of follow-up, we were in contact with 95% of study participants. The PEACH study will provide a rationale for selecting between inpatient and outpatient antibiotic treatment, the two most common treatment strategies, for PID.

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

Objective: Few previous studies have examined the role that acute Chlamydia trachomatis lower genital tract infection plays in the development of spontaneous abortion. This study evaluated cervical C. trachomatis infections among 52 women experiencing spontaneous abortion and 59 controls., Methods: Pregnant women at less than 22 weeks of gestation who sought medical care in an emergency department in West Philadelphia were eligible for enrollment. Urine samples from enrolled women were tested for chlamydia using ligase chain reaction DNA amplification. All women were followed up to 22 weeks of pregnancy to ascertain the outcome of spontaneous abortion., Results: The proportion of women with chlamydial infection was 3.8% among spontaneous abortion cases and 8.5% among controls. After adjustment for potentially confounding factors, there was no substantial difference in the rate of chlamydial infection between women with and without spontaneous abortion (odds ratio 1.8, 95% confidence interval 0.3-10.7)., Conclusion: These data do not support a relationship between acute C. trachomatis infection and the development of spontaneous abortion.

Purpose: There has been much publicized concern about difficulty with minority recruitment into research studies, particularly since minority inclusion in randomized clinical trials was mandated by the 1993 National Institutes of Health Revitalization Act. We reviewed recruitment data in published reports from clinical studies to assess the actual degree of success in recruiting minorities versus whites and to identify barriers to recruitment., Methods: We abstracted articles published between September 1993 and February 1995 that reported detailed results of participant recruitment for studies conducted in the United States., Results: Of 65 articles meeting our eligibility criteria (median sample size, 1323), only one (1.5%) reported the racial/ethnic composition of potential study participants. Only two articles (3.1%) provided information about the racial/ethnic composition of eligible subjects, and only one (1.5%) provided information about the racial/ethnic composition of refusing subjects. For enrolled subjects, race/ethnicity was less likely to be reported (58.5%) than were age (90.8%) or gender (80.0%)., Conclusions: The published literature currently contains insubstantial data to either refute or prove that there are differential recruitment rates among minorities as compared with whites. Changes in reporting will be needed in order to track progress in this area.

Objective: To critically assess the possibility that gonorrhea or chlamydia causes male infertility., Design: Comprehensive literature review structured to evaluate the epidemiologic tenets for causality, including biologic plausibility, strength of association, dose response, consistency, temporality, and treatment effect., Result(s): It is biologically plausible that gonorrhea and/or chlamydia could cause male infertility. There is clinical and pathologic evidence linking these pathogens to urethritis, linking urethritis to epididymo-orchitis, and linking epididymo-orchitis to infertility. Retrospective epidemiologic results also support an association between chlamydia serologies and male infertility, which in most of these small studies does not reach the level of statistical significance. However, there is no consistent epidemiologic evidence that these pathogens alter sperm characteristics. We discuss the methodologic limitations of previous epidemiologic studies and suggest strategies for future research., Conclusion(s): Whether gonorrhea and/or chlamydia cause male infertility is currently unclear. Sound methodologic research strategies must be applied to future studies.

Although an increased risk of coronary heart disease has been demonstrated among women with high gravidity/parity, the mechanism by which this association may be mediated is unclear. One possible pathway that has been suggested is that pregnancy and child rearing may result in changes in factors such as stress or lifestyle. This hypothesis was tested in a sample of 541 middle-aged women who participated in a prospective study of the effects of menopause on behavioral and biological cardiovascular risk factors. Married women generally reported less chronic stress, less perceived stress, and more structural support than did unmarried women. However, the findings in this study indicated no consistent relationship between parity and stress or parity and social support in this group of middle-aged women. Only unmarried women with more children reported a higher number of life events than did women with fewer children.

Women's health research provides an opportunity to focus on the mechanisms underlying health and disease in both men and women. We propose that differences in risk between men and women and among individual women are primarily determined by biologic factors, such as sex steroid hormone metabolism, anatomy, immunologic function, genetic influences, and the effects of reproduction, interacting with external influences, such as psychologic development, sociocultural environment, and economic status. We provide examples whereby a comparison of disease frequencies between men and women and among women allows a focus on underlying mechanisms of disease. We then demonstrate the importance of posing questions about the genesis of differences in disease frequency.

Objective: Oral contraceptive use has been associated with a lower risk of symptomatic pelvic inflammatory disease but a higher risk of chlamydial cervicitis. To explain these seemingly contradictory findings, we asked whether oral contraceptive use was more common among women with unrecognized endometritis than among women with recognized endometritis., Study Design: A multicenter case-control study was performed. Women without signs of pelvic inflammatory disease were ascertained through contact tracing of partners with sexually transmitted diseases or through presentation with cervicitis. Women with symptomatic pelvic inflammatory disease met a set of standard clinical criteria. We compared the 43 cases without signs of pelvic inflammatory disease but with endometritis ("unrecognized endometritis") with the 111 controls with recognized pelvic inflammatory disease and endometritis ("recognized endometritis")., Results: Women with unrecognized endometritis were 4.3 times (95% confidence interval 1.6 to 11.7) more likely than women with recognized endometritis to use oral contraceptives., Conclusion: Future studies need to fully characterize the risks and benefits of oral contraceptives in relation to sexually transmitted diseases.

The cause of preeclampsia remains elusive in spite of many attempts to understand its biologic characteristics and to characterize its predictors. We suggest that there are distinct origins of preeclampsia, each with its own pathologic characteristics and natural history. One genesis is the result of reduced placental perfusion, which we will call placental, and another results from maternal disorders preexisting (but sometimes not evident before) pregnancy. These preexisting maternal disorders comprise predisposing factors for cardiovascular disease such as hypertension, renal disease, overweight, and diabetes. A critical review of the epidemiologic and pathologic literature is presented, which supports the hypothesis that preeclampsia is the result of heterogeneous causes. The implications of this hypothesis are discussed, particularly its impact on the development of rules to predict the occurrence of preeclampsia.

Diagnostic uncertainty, particularly prior to the receipt of test results, is common in medicine. When randomized trials are being conducted to evaluate therapies in these situations, patients must be randomized in the absence of a definitive diagnosis. This article explores some of the implications of diagnostic uncertainty for the design and analysis of randomized clinical trials, using specific therapeutic examples to illustrate the important points.

We examined the association between number of children and coronary heart disease risk among men in two large prospective cohort studies. Data from the Framingham Heart Study comprised a group of 1,632 men who were followed for 30 years; data from the first National Health and Nutrition Examination Survey National Epidemiologic Follow-up Study included 2,584 men who were followed for 3-5 years. We found no relation between number of children and coronary heart disease incidence in these cohorts. This lack of association in men contrasts with the previous positive association found between pregnancy and coronary heart disease in women.

The relationship between parity and body fat distribution was investigated in a sample of 1,590 Mexican American, 411 Cuban American, and 657 Puerto Rican women, aged 20-74 years. Participants were interviewed and examined as part of the Hispanic Health and Nutrition Examination Survey, a cross-sectional study of a representative sample of Hispanic populations residing in the United States. In each ethnic group, there was an increase with greater parity in overall body fat (body mass index [BMI], or triceps plus subscapular skinfolds), central vs. peripheral skinfold thicknesses (subscapular/triceps ratio), and upper vs. lower body skinfold thicknesses (subscapular/calf ratio). These positive associations remained after adjusting for age, income, marital status, smoking, menopausal status, and education. They were statistically significant only in the Mexican American group. After controlling for the BMI, the association between parity and the subscapular/ calf ratio remained significant in Mexican Americans, suggesting a relationship between parity and upper body fat distribution independent of body size. © 1995 Wiley-Liss, Inc., (Copyright © 1995 Wiley-Liss, Inc., A Wiley Company.)

Objective: We prospectively evaluated the rate of adverse reproductive outcomes following pelvic inflammatory disease (PID) in a small cohort of American women., Methods: We enrolled 28 patients having either salpingitis confirmed by laparoscopy or endometritis confirmed by endometrial biopsy. The follow-up was maintained by clinic visits and telephone contact., Results: A median of 15.4 months of follow-up was accomplished for 82.1% of these women. Fifty-two percent (13/25) had unprotected sexual activity without conception for at least 6 months. Fully 55.6% (10/18) of the cohort were involuntarily infertile after at least 1 year of follow-up., Conclusion: In the first prospective cohort study of the reproductive outcomes of American women having had PID, high rates of infertility at 1 year of follow-up were experienced by these women.

Gravidity and parity have been hypothesized as possible protective factors for hypertension in women, but results of previous studies have been conflicting; none of three U.S. studies has clearly demonstrated this relation. We studied the association of number of pregnancies to blood pressure and hypertension in a cross-sectional study of 4,626 white women, ages 20-74 years, examined in the Second National Health and Nutrition Examination Survey. In univariate analyses, neither mean systolic blood pressure, mean diastolic blood pressure, nor prevalence of hypertension varied systematically with the number of pregnancies. In multivariate analyses that included age, body size, smoking, oral contraceptive use, education, poverty status, and alcohol use, systolic blood pressure declined modestly with greater gravidity. The association of gravidity with systolic blood pressure was stronger for younger premenopausal women. The odds of hypertension also declined with each additional pregnancy as compared with no pregnancies: there was an odds ratio of 0.90 (95% confidence interval = 0.81-0.99) for premenopausal women and an odds ratio of 0.95 (95% confidence interval = 0.92-0.98) for postmenopausal women. These findings indicate a slight negative relation of number of pregnancies to both blood pressure and hypertension.

Background: Whether increasing parity or gravidity is a risk factor for coronary heart disease has been debated, but the question remains unresolved., Methods: We tested the association between the number of pregnancies and a variety of cardiovascular end points in two groups of women who had completed childbearing. One group comprised 2357 women who were followed for 28 years through the Framingham Heart Study, and the other 2533 women followed for at least 12 years through the first National Health and Nutrition Examination Survey National Epidemiologic Follow-up Study (NHEFS)., Results: The rates of coronary heart disease were higher among multigravid women than among women who had never been pregnant, in both the Framingham Heart Study and the NHEFS, but in both studies, the higher rates were statistically significant only in women with six or more pregnancies. For the women in the Framingham Study, the rate ratio adjusted for age and educational level in the group with six or more pregnancies (as compared with women who had never been pregnant) was 1.6 (95 percent confidence interval, 1.1 to 2.2). For the women in the NHEFS, the same adjusted rate ratio was 1.5 (95 percent confidence interval, 1.1 to 1.9). Adjustments for other known cardiovascular risk factors, including weight, did not markedly alter this risk. The rate of total cardiovascular disease was also significantly higher among multigravid women in the Framingham Study than in the women who had never been pregnant., Conclusions: In two prospective American studies, having six or more pregnancies was associated with a small but consistent increase in the risk of coronary heart disease and cardiovascular disease. Whether gravidity itself or some other unmeasured factor accounts for the increase in risk that we observed requires further investigation.

Objective: To determine the impact on house staff recruitment of large numbers of patients with the acquired immunodeficiency syndrome (AIDS)., Design: Trends in yearly survey data from the National Resident Matching Program from 1983 to 1990 were examined for residency programs in New York City, NY, where AIDS is epidemic, in the four largest US cities with the fewest AIDS cases, and nationally. Within New York City, trends were compared for residency programs serving large numbers of AIDS patients (high AIDS) and for other programs (low AIDS)., Main Outcome Measures: Number of matches in each study year as compared with the baseline year of 1983 and the yearly percentage of positions offered that were filled by matches., Results: During the study period, New York City experienced a greater decline in US graduate matches than did the four low-AIDS cities or the nation. Within New York City, recruitment to municipal programs, all with large AIDS patient populations, dropped from 241 to 173 matches (28.2%) despite a 3.6% increase in positions. However, recruitment to both high-AIDS and low-AIDS voluntary programs improved in all years except 1990. After controlling for numbers of offered positions, high-AIDS and low-AIDS voluntary programs again showed similar trends until 1990., Conclusions: These observations cannot be attributed to AIDS alone. Multiple economic and social factors, including AIDS, may have contributed.