Cervical Fluid Research Articles

The influence of cotinine on interleukin 6 expression in smokers with cervical preneoplasia

Several epidemiological investigations have shown that cigarette smoking leads to increased serum IL-6 levels and is a risk factor for cervical cancer. We examined the levels of interleukin 6 (IL-6) and the amount of cotinine in the cervical fluid of 78 women and compared the presence of human papillomavirus (HPV) in smokers and nonsmokers. The results of our study showed that IL-6 levels were higher in the cervical mucus of smokers than in nonsmokers. Fourteen percent of smokers were in the category with highest IL-6 levels compared to 6% of nonsmokers. However, our IL-6 results were not significant as they were probably influenced by the higher rates of HPV infection in smokers (17 cases) than in nonsmokers (4 cases). Significant findings showed that smokers had a higher prevalence of squamous intraepithelial lesions (SILs) than nonsmokers. Smokers' cotinine levels also exceeded those of nonsmokers: 13.95 ng/ml compared with 5.00 ng/ml. However, less IL-6 activity was evident in smokers with high-grade SILs and HPV infection of high-risk types. Our results suggest that smoking has a stimulatory effect on the production of IL-6 in the cervix. Furthermore, smokers show a higher genital HPV infection rate and a higher prevalence of SILs.

Interleukin 6 determinations in cervical fluid have diagnostic and prognostic value in preterm premature rupture of membranes

Objective: Our aim was to determine whether interleukin-6 concentrations in cervical fluid samples are of value in the identification of microbial invasion of the amniotic cavity, prediction of the duration of the latency period, and assessment of the risk of neonatal complications in preterm premature rupture of membranes. Study Design: A cohort study was performed in 86 patients with preterm premature rupture of membranes. Amniotic fluid and cervical fluid were collected. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Interleukin 6 was measured by a sensitive and specific immunoassay. The receiver operating characteristic curve, logistic regression, and survival techniques were used for analysis. Results: (1) Patients with a positive amniotic fluid culture had a significantly higher median cervical fluid interleukin 6 concentration than those with negative results (median, 528 pg/mL; range, 174-825 pg/mL; vs median, 169 pg/mL; range, 8-986 pg/mL; P < .0001). (2) A cervical fluid interleukin 6 concentration of >350 pg/mL had a sensitivity of 92% and a specificity of 78% in the identification of a positive amniotic fluid culture. (3) Patients with a cervical fluid interleukin 6 concentration of >350 pg/mL had a significantly shorter median interval to delivery and higher rate of funisitis, preterm delivery within 2 days and 7 days, and the occurrence of significant neonatal morbidity than did those with a cervical fluid interleukin 6 concentration of <350 pg/mL ( P < .05 for each). (4) The increased perinatal morbidity remained significant after adjustment for gestational age ( P < .05). (5) There was a strong correlation between cervical fluid concentrations and amniotic fluid concentrations of interleukin 6 ( P < .001). Conclusion: Cervical fluid interleukin 6 determinations are of value in the assessment of the likelihood of microbial invasion of the amniotic cavity, impending preterm delivery, and the occurrence of significant neonatal complications in the setting of preterm premature rupture of membranes. (Am J Obstet Gynecol 2000;183:868-73.)

Partial improvement of headache in a patient with spontaneous cervical cerebrospinal fluid (CSF) leakage after lumbar blood patch

Partial improvement of headache in a patient with spontaneous cervical cerebrospinal fluid (CSF) leakage after lumbar blood patch

Detection of fetal fibronectin in twin pregnancies in relation to gestational age.

The presence of fetal fibronectin in the cervix or vagina has been investigated as a possible marker for the risk of preterm birth. Fetal fibronectin in cervical fluid can provide direct evidence of pathologic changes at the interface of fetal and maternal tissues. To evaluate the presence of fetal fibronectin as a predictor of premature delivery in twin pregnancies in relation to gestational age. Accuracy study. University referral unit. 52 pregnant women with twin pregnancies and gestational age of between 24 and 34 weeks. Sensitivity, specificity, predictive values and relative risk ratios of the correlation between fetal fibronectin and preterm birth before 34 and 37 weeks using an immediate-reading membrane test on cervicovaginal secretions obtained from participants. The sensitivity varied between 66.7% and 85.7%, whereas the specificity was from 58.3% to 81.8% according to gestational age at the time of sampling. The relative risk of spontaneous preterm birth after a positive fetal fibronectin test, as compared with a negative fetal fibronectin test, rose from 2.8 at 24-26 weeks to 4.1 at 27-30 weeks. Analyses of the risk of delivery before 34 weeks were not statistically significant. Fetal fibronectin in the cervicovaginal secretions of patients with twin pregnancies is a useful tool for the early identification of twin pregnancies likely to deliver before 37 weeks. However, the clinical value of the fibronectin test is limited because of low indices for prediction of delivery before 34 weeks. The best period for performing the fetal fibronectin test in twin pregnancies to predict preterm delivery is between 27 and 30 weeks.

The Preterm Prediction Study: Failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth

Objective: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. Study Design: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks’ gestation and selected control subjects delivered at ≥37 weeks’ gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks’ to 24 weeks 6 days’ gestation. Results: The mean ± SD sialidase activities were similar in case patients and control subjects (0.64 ± 1.60 vs 0.41 ± 0.94 nmol · mL –1 · min –1 , P = .21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P = .8) nor sialidase activity above the 95th percentile (7.9% vs 4.8%, P = .3) of control specimens (>1.43 and >2.23 nmol · mL –1 · min –1 , respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar ( P ≥ .63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 ± 1.87 vs 0.03 ± 0.14 nmol · mL –1 · min –1 , P < .0001). Conclusions: Elevated cervical fluid sialidase activity at 22 to 24 weeks’ gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth. (Am J Obstet Gynecol 1999;180:1151-4.)

Fetal Fibronectin, Endotoxin, Bacterial Vaginosis and Cervical Length as Predictors of Preterm Birth and Neonatal Morbidity in Twin Pregnancies

Objective To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. Participants One–hundred and twenty–one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. Methods Cervical or vaginal fluid was sampled and determined for fetal fibronectin ( 0.05 μg/mL was used as cutoff), endotoxin ( 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. Main outcome measures Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. Results All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI2.2–145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6–15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P= 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4–11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1–4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. Conclusions Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Cervical cotinine and macrophage-Langerhans cell density in the normal human uterine cervix.

Cotinine levels in blood and cervical fluid of smokers and non-smokers were analysed using capillary-column gas chromatography. These levels were not related to numerical cell densities of intraepithelial S100-protein- and LN2-positive Langerhans cells or to MAC-387-positive macrophages in the stroma of the transformation zone of normal uterine cervices. A decrease in the number of Langerhans cells was noted in smokers, especially in those using oral contraceptives (OCs). Macrophages were more numerous in the endocervical stroma of smokers, suggesting a local response to smoke constituents. These findings may indicate a synergistic suppression of local cervical immunity by smoking and OCs.

Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid.

Cotinine levels in blood, urine and cervical fluid of smokers and nonsmokers were analyzed by capillary-column gas chromatography. The sensitivity of this method appeared to be 100%. The specificity was lower (87.5% in blood, 25% in urine and 75% in cervical fluid). Nonsmokers exposed to smoke by others had low but detectable cotinine levels in the three body fluids. The highest cotinine levels in cervical fluid were detected during the proliferative phase of the cycle. Cotinine levels in cervical fluid and blood correlated well, but the correlation was less during the proliferation phase. Cotinine measurement in cervical fluid proves to be a reliable method to quantify exposure to tobacco smoke, even when induced by others.

Rapid diagnosis of premature rupture of membranes using a new kit employing anti-AFP monoclonal antibody

A kit using mouse monoclonal antibody against human alpha-fetoprotein (anti-AFP kit) has been developed. Cervical secretion (n = 34) and vaginal fluid (n = 15) was obtained from 30 pregnant volunteers. All 31 specimens obtained from women with intact membranes tested negative while all 18 specimens from women with premature rupture of membranes (PROM) tested positive. The newly developed kit allowed rapid and accurate diagnosis. We compared the kit results with those obtained by pH determination (nitrazine, bromthymol blue test) and measurement of AFP concentrations by enzyme-linked immunoassay (EIA).

Endotoxin and interleukin-1α in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis

The purpose of our study was to determine the concentrations of endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women who either did or did not have bacterial vaginosis. Samples of cervical mucus and vaginal fluid were collected from women in early pregnancy who had signs of bacterial vaginosis and from healthy control subjects. The samples were analyzed for the concentrations of endotoxin and interleukin-1 alpha. In addition, wet mounts were examined for signs of inflammation indicated by increased numbers of leukocytes. Both endotoxin and interleukin-1 alpha occurred in much higher concentrations (p < 0.0001, p < 0.0002) in both the cervical mucus and the vaginal fluid of women with signs of bacterial vaginosis than they did in healthy control subjects. A correlation was found between the interleukin-1 alpha concentrations in the vaginal fluid and the number of leukocytes as judged by a semi-quantitative evaluation of wet mounts (p = 0.0365). The concentrations of endotoxin correlated with those of interleukin-1 alpha in both fluids (vaginal fluid, p < 0.01; cervical mucus, p < 0.01). Our study shows that concentrations of endotoxin and interleukin-1 alpha in cervical mucus and vaginal fluid of women in early pregnancy who have bacterial vaginosis are significantly higher than the corresponding levels in control subjects.

Complement in human reproduction: activation and control.

The behaviour of the complement system during human reproduction is now the focus of much scientific attention. The presence of antisperm antibodies in the reproductive tracts of some infertile individuals, and of complement in cervical and ovarian follicular fluid, suggests that complement-mediated damage of spermatozoa is involved in some cases of infertility. Further, deposition of maternal IgG and of complement in the extrafetal tissues indicates that complement activation occurs within the fetoplacental unit. Recently, three complement-regulatory proteins--decay-accelerating factor, membrane cofactor protein and CD59--have been detected on spermatozoa and in the extrafetal tissues. It is likely that these inhibitors are essential for normal reproductive function. This article reviews current understanding of the interaction of the complement system with cells and tissues involved in reproduction, with emphasis on the nature and function of the controlling proteins.

A CASE OF DENTAL INFECTION ASSOCIATED WITH MEDIASTINITIS

We experienced a patient with dental infection associated with mediastinitis. The patient, a 41-year-old man, developed dental infection 9 days before admission to our hospital. On admission cervical swelling was noted, and chest X-ray examination revealed an enlargement of the mediastinum, mediastinal emphysema and retention of fluid in the pleural cavity. Drainage and lavage of the pleural cavity were immediately performed, followed by debridement of the neck. Culture of the cervical purulent fluid and of the fluid in the pleural cavity yielded gram-positive and -negative bacteria and anaerobes. Chemotherapy with various drugs was performed. Though mediastinitis and empyema improved after thoracic drainage and washing, he developed multiple organ failure and died en 33rd day after admission. Mediastinitis due to dental infection frequently develops from the oral cavity to the neck and further to the mediastinum, showing a descending spread of inflammation. Although the pyogenic bacteria vary, the infection is frequently caused by anaerobes. It is therefore important for the treatment of such a condition, as in the present case, to use antibiotics to which the bacteria are highly sensitive and to perform surgery in an early stage.

Abnormal cervical cytology leading to the diagnosis of gastric cancer

Abstract There have been nine cases reported in the English literature in which the finding of malignant cells on cervical/vaginal cytology led to the diagnosis of primary gastric cancer. We report on a patient with gastric carcinoma, metastatic to the cervix, in which the diagnosis was suspected by the finding of signet ring cells on a Papanicolaou smear of the cervix. Prior to treatment of this patient, concordance of signet ring carcinoma on cervical and ascitic fluid cytology and on cervical and gastric biopsies was documented; this has not been reported previously. Thirty-four additional cases of gastric carcinoma metastatic to the cervix are reviewed. This paper is presented to remind the clinician that, however rare, metastases from the gastrointestinal tract to the Uterine Cervix do occur.

Abnormal cervical cytology leading to the diagnosis of gastric cancer

There have been nine cases reported in the English literature in which the finding of malignant cells on cervical/vaginal cytology led to the diagnosis of primary gastric cancer. We report on a patient with gastric carcinoma, metastatic to the cervix, in which the diagnosis was suspected by the finding of signet ring cells on a Papanicolaou smear of the cervix. Prior to treatment of this patient, concordance of signet ring carcinoma on cervical and ascitic fluid cytology and on cervical and gastric biopsies was documented; this has not been reported previously. Thirty-four additional cases of gastric carcinoma metastatic to the cervix are reviewed. This paper is presented to remind the clinician that, however rare, metastases from the gastrointestinal tract to the Uterine Cervix do occur.

Improved penetration of spermatozoa into uterine fluids of women with abnormal postcoidal tests

Cervical mucus-uterine fluid cross-penetration of husbands' and control sperm was assessed in 13 couples with poor or negative postcoital tests. Cervical mucus scoring and tray agglutination test identified six women with sperm-agglutinating antibodies and seven women with cervical dysmucorrhea. All males were normozoospermic, with penetration into control cervical mucus and control uterine fluids. Control sperm penetrated into cervical mucus and uterine fluids of three and five of the women with sperm-agglutinating antibodies and cervical dysmucorrhea, respectively. Penetration of husbands' spermatozoa into uterine fluids of patients with sperm-agglutinating antibodies was lower than that of control semen (P less than .05). Control and husbands' sperm penetration into uterine fluids of women with cervical dysmucorrhea were identical. In both groups, husbands' and control sperm penetrated uterine fluids more frequently than cervical mucus (75 versus 12%; P less than .001). On a six-month follow-up and midcycle intrauterine inseminations, six patients (46%) conceived. We conclude that uterine fluids of patients with sperm-agglutinating antibodies and cervical dysmucorrhea may provide a better milieu for spermatozoa than cervical mucus. This observation suggests a rationale for intrauterine inseminations to achieve pregnancy.

ABC of AIDS. Development of the epidemic.

The 1st recognized cases of the acquired immunodeficiency syndrome (AIDS) occurred in the summer of 1981 in America. HIV has been isolated from semen cervical secretions lymphocytes cell free plasma cerebrospinal fluid tears saliva urine and breast milk. Particularly infectious are semen blood and possibly cervical secretions. The commonest mode of transmission of the virus is by sexual intercourse. Other methods of transmission are through the receipt of infected blood or blood products and donated organs and semen and through the sharing or reuse of contaminated needles by injecting drug abusers or for therapeutic procedures and from mother to child. There is no well documented evidence that the virus is spread by saliva. It is not spread by casual or social contact. By March 1987 31526 adult cases of AIDS had been reported in the US plus an additional 456 pediatric cases. There is a wide geographical variation. New York for example has a rate of 991/million. The US as a whole has a rate of 140/million. In the US and the UK the 1st wave of the epidemic occurred in homosexual men the next and current wave is among intravenous drug abusers and after this it might affect the heterosexual population. Transmission into the heterosexual population will occur through bisexual men intravenous drug abusers and prostitutes. In Africa strong evidence shows that HIV is spread mainly by heterosexual intercourse. The advent of an effective antibody test in 1984 has allowed for a clearer understanding of the changing prevalence and natural history of HIV infection. Surveys show that the proportion of individuals infected must be high before cases of AIDS start to become apparent. AIDS is the most major public health problem in the world this century.

Characterization of a Monoclonal Antibody to a Conserved Epitope on Human Seminal Vesicle-Specific Peptides: A Novel Probe/Marker System for Semen Identification1

A novel sperm-coating antigen from the human seminal vesicles was discovered. We identified a monoclonal antibody MHS-5, recognizing an epitope with characteristics of a forensic semen marker: conservation in all vasectomized or normal semen samples tested (421); absence in all human tissues or biological fluids other than semen; and immunolocalization on the surface of ejaculated sperm. Western blots of ejaculates allowed to liquefy for 5 min demonstrated the MHS-5 epitope to be located on peptides of a wide range of molecular masses from 69 to 8 kDa. After 15 h of semen liquefaction, immunoreaction peptides of higher molecular mass were undetectable in semen, while peptides of lower molecular mass from 8 to 21 kDa retained antigenicity. Three peptides of 10, 11.9, and 13.7 kDa were the most immunoreactive species in semen liquified for 15 h. Using the MHS-5 monoclonal, an enzyme-linked immunosorbent assay (ELISA) was developed sensitive to 1 ng of seminal protein. This assay showed that the MHS-5 antigen was undetectable in semen of common domestic animals and monkeys but was present in chimpanzee, gorilla, and orangutan semen. ELISA of homogenates from human organs and reproductive tissues demonstrated the antigen only in samples of seminal vesicles. Epididymal sperm obtained at vasovasostomy lacked the MHS-5 epitope, a fact that, together with immunolocalization on ejaculated sperm, demonstrated that the MHS-5 antigen functions as a "sperm-coating antigen." The MHS-5 monoclonal detected semen in sexual-assault evidence obtained six months previously and in mixtures of semen with vaginal or cervical fluid. Assay systems employing the MHS-5 monoclonal may be useful for identification of semen in sexual-assault casework. The MHS-5 epitope resides on novel seminal vesicle-specific peptides whose functions, aside from sperm coating, are uncharacterized.

Cervical mucocele (plunging ranula): An unusual case of mucous extravasation cyst

An unusual case of a mucous extravasation cyst that manifest itself solely as a cervical swelling is reported. As a result of this unusual symptom, diagnosis and appropriate treatment were delayed, and the condition finally resolved after the ipsilateral sublingual salivary gland was excised and the cervical fluid was aspirated. Cervical mucoceles have also been reported in dogs, and the veterinary literature pertaining to this is briefly reviewed.

Cervicovaginal peroxidases: sex hormone control and potential clinical uses

Thirty-one normal women were studied daily in 41 cycles. Venous blood samples were taken for measurements of luteinizing hormone (LH), estradiol (E2), and progesterone (P), and vaginal examinations were done to obtain cervical mucus and vaginal fluid. The specific activity of guaiacol peroxidase (GP), extracted from cervicovaginal secretions with 0.5 M CaCl2, was determined in the vaginal samples. In the follicular phase, from day -7 to day 0 (the LH +1 day, when ovulation presumably occurred), there was a strong negative correlation between GP and the rising E2 (r = -0.94). On days 1 to 10 after ovulation, there was a strong positive correlation between GP and P (r = 0.84). In nine ovulatory cycles in which P levels did not exceed 8 ng/ml on any day, indicating possible luteal phase inadequacy, there were significantly lower GP levels than in another 32 ovulatory cycles with higher P (P = 0.04). These results suggest that (1) at midcycle, E2 seems to "down-regulate" the GP specific activity; and (2) in the luteal phase, serum P levels parallel those of GP activity, even in the presence of high luteal E2. GP activity profiles during the menstrual cycle can be used to define the fertile period, may prove useful in diagnosing pregnancy, and may be a simple, convenient test for an inadequate corpus luteum.

Collagen sponge as vaginal contraceptive barrier: Critical summary of seven years of research

Extensive testing of collagen sponge as a vaginal contraceptive (mechanical and chemical) showed that the original expectations regarding the safety, convenience, and efficacy were not met. The collagen sponge was tested both as a cylinder and as a diaphragm and used as such or impregnated with spermicidal detergent or with zinc salt. The collagen sponge must be larger that 6 cm in diameter in order to serve as a mechanical barrier that will not be dislodged during physical activity. This creates problems with the ease of insertion and with the partners' awareness of the barrier. When the collagen sponge containing ejaculate is left in the vagina >48 hours, it develops an offensive odor. The original acidity of the collagen sponge (pH 3.5, 0.1 mol/L) is soon neutralized by the large volume of alkaline vaginal secretions. In vitro studies showed that up to 10 mg of nonoxynol 9 per milliliter of growth medium did not inhibit the growth of Staphylococcus aureus. These effects, as well as the large surface area of the resilient sponge, present a potential risk for growing staphylococci within the collagen sponge. The capacity of the collagen sponge to absorb a large volume of cervical and vaginal fluid produced two symptoms that were annoying to the volunteers: an awareness of either vaginal dryness during intercourse or, conversely, saturation of the sponge from the vagina. Postcoital studies showed viable spermatozoa in the cervical mucus in 25% of the tests with the nonmedicated cylindrical sponge but in only 6% of tests with the sponge containing nonoxynol 9. The results of clinical trials conducted at four centers support the view that collagen sponge as a vaginal contraceptive barrier method is inconvenient to both partners, not effective enough to compete with present methods of vaginal contraception, and possibly might be unsafe because of the capacity to grow bacteria. Despite the negative end result of this goal-oriented research, we believe that our studies have contributed to a better understanding of vaginal physiologic features, the safety and effectiveness of spermicidal detergents, and the mechanisms of vaginal malodor. Although the acceptability study showed some advantages of the collagen sponge over the rubber diaphragm, the overall acceptability of the collagen sponge diaphragm was no better than that of the rubber diaphragm. For all these reasons, including the possible risk of an increased incidence of toxic shock syndrome, we have discontinued further testing of either type of collagen sponge as a vaginal barrier method.