PubMed Health⌕ Search

Biomedical subjects

S C Bell

Publications and source records attributed to S C Bell.

At least 73 records · Page 4Linked to original sources
PubMed1999

Potential roles of metalloprotease mediated ectodomain cleavage in signaling by the endothelial receptor tyrosine kinase Tie-1.

The orphan receptor tyrosine kinase Tie-1 is expressed predominantly in endothelial cells. Expression of this receptor is increased in physiologic angiogenesis and pathologic situations including tumor growth and arteriovenous malformations. Tie-1 is essential for vascular development where it acts in later stages of angiogenesis to suppress endothelial activation and stabilize the newly formed vessel. Stimulation of protein kinase C in endothelial cells results in endoproteolytic cleavage of Tie-1, releasing the extracellular ligand-binding domain of the receptor. We show that this is mediated by a metalloprotease. Immunoprecipitation and immunoblotting of lysates prepared from human placentas confirm that Tie-1 truncation occurs in vivo. We propose cleavage of this receptor may be a mechanism for inducing vessel destabilization by preventing ligand-activated signaling through Tie-1. Using an antibody that recognizes the carboxy terminus of the intracellular domain, we show that the Tie-1 endodomain formed on cleavage persists as a cell-associated fragment for several hours. Subcellular fractionation reveals this tyrosine kinase containing receptor fragment to be localized in the membrane fraction of the cell. Immunoprecipitation with antibodies recognizing phosphotyrosine demonstrates that cleavage of Tie-1 stimulates association of newly generated endodomain with cellular phosphoproteins. Furthermore, there was a marked induction of tyrosine phosphorylation of several proteins after PMA-induced endodomain generation. These data indicate that ectodomain cleavage may be a mechanism for down-regulating ligand-induced signaling through Tie-1 while activating an alternative ligand-independent signaling pathway in endothelial cells. Ectodomain cleavage occurs in some other receptor tyrosine kinases. We suggest that rather than solely being a means of down-regulating receptor activity, ectodomain cleavage may be a novel way for a receptor to switch between two alternative signaling pathways.

Cells, Cultured↗
PubMed1998

Newborn acid-base status and umbilical cord morphology.

OBJECTIVE: To assess the relation between umbilical cord morphology and intrapartum fetal status and umbilical cord blood gases at birth. METHODS: In a prospective study of 134 consecutive newborns and their umbilical cords, relations were investigated between umbilical cord morphologic characteristics (umbilical cord length, number of vascular coils, coiling index, and vessel length index) and intrapartum fetal heart rate (FHR) decelerations, color of amniotic fluid, operative delivery for suspected fetal acidosis, umbilical vessel blood gases, and acid-base status. RESULTS: Statistically significant linear correlations were found between umbilical venous pH and the umbilical cord length (r = 0.30; 95% confidence interval [CI] 0.13, 0.46; P < .001), number of vascular coils (r = 0.27; 95% CI 0.10, 0.43; P = .001), coiling index (r = 0.15; 95% CI 0, 0.33; P = .05), and vessel length index (r = 0.30; 95% CI 0.13, 0.46; P < .001). Statistically significant negative linear correlations were found between the umbilical venous partial pressure of carbon dioxide (PCO2) and cord length (r = -0.34, 95% CI -0.49, -0.17; P < .001), number of vascular coils (r = -0.30, 95% CI -0.46, -0.13; P < .001), coiling index (r = -0.17, 95% CI -0.34, 0; P = .03), and vessel length index (r = -0.34, 95% CI -0.49, -0.17; P < .001). The umbilical artery pH was related to vessel length index and to the number of umbilical vascular coils (r = 0.17, 95% CI 0.03, 0.36; P = .04 and r = 0.17, 95% CI 0.02, 0.35; P = .047, respectively). No relation was found between umbilical cord indices and intrapartum FHR decelerations, meconium staining of the amniotic fluid, or mode of delivery. Placental weight also correlated with umbilical cord length and vessel length index (95% CI 0.15, 0.46; P < .001 and 95% CI 0.05, 0.38; P = .01, respectively), but not with the number of umbilical cord coils or the coiling index. CONCLUSION: Umbilical venous pH and PCO2 and umbilical artery pH are related to umbilical cord morphology. Associated variations in placental morphology or placental blood flow affecting maternal-fetal gas exchange may explain these findings.

Acid-Base Equilibrium↗
PubMed1998

Nutrition in adults with cystic fibrosis.

Improved survival has been associated with better nutritional status in patients with cystic fibrosis (CF). In this study we examined the relationship between nutritional state and other measures of clinical severity in adult patients with CF, attending a regional centre. Eighty-one patients (median age 21 years) were studied. Patients with CF were significantly under weight, compared to healthy individuals but were of similar height. Measurements of lung function, FEV1 and FVC were significantly related to body mass index. Lung function was poorer in patients with chronic pseudomonal infection but body weight and body mass index were not significantly different compared to those without such infection. In 53 patients who were alive 4 years later, FEV1 had declined by -10.5 (2.1)% (P < 0.001) but there was no significant change in body weight 1.5 (6.5) kgs. In 23 patients who died or had lung transplantation the change from 1994 to the date of death or transplantation the FEV1 was reduced by -7.9 (11.2)% (P = 0.004) and body weight -2.8 (4.4) kgs (P < 0.01). In 12 patients who had supplemental enteral feeding, the median increase in body weight was 7|kgs over a period of 12 months. This study confirms that young adult patients with CF are significantly under weight and declining health is associated with significant weight loss. In patients with severe malnutrition significant improvement can be achieved by enteral feeding.

Adolescent↗
PubMed1998

Endometrial responses to hormone replacement therapy: histological features compared with those of late luteal phase endometrium.

We evaluated the histological features of the endometrium in relation to the bleeding pattern in a group of women receiving oral cyclical combined hormone replacement therapy (HRT), and compared the histological features with those of luteinizing hormone (LH)-dated endometrial biopsies obtained from healthy women at the time of sterilization. A total of 103 women completed 6 months of HRT therapy. All received a regimen of 2 mg oestradiol valerate daily, with 1 mg norethisterone added for the last 12 days of every 28-day cycle. Endometrial biopsies were scheduled for the end of the study (days 27-29 of the last cycle of therapy). Using the classical histological criteria, secretory endometrial changes were demonstrated in the majority (n = 89) of cases. The remaining were insufficient or inactive (n = 12), proliferative (n = 1) or atrophic (n = 1). Forty-nine women had a mean cycle length of less than 29 days (early bleeders), 50 women experienced cycles of more than 29 days (late bleeders) and four did not experience any bleeding. When the individual histological structures were examined, using image analysis, there were no statistically significant differences in the histological features when the long cycles in early bleeders were compared with those in late bleeders. LH-dated endometrium showed a high degree of homogeneity that was consistent with cycle day as described by the classic criteria, but HRT-treated endometrium exhibited a wide range of variability. HRT-treated endometrium from the subset of women who bled on or after day 29, and whose biopsies were obtained before the onset of bleeding, differed significantly from the endometrium taken at the corresponding phase of the physiological cycle. We conclude that the use of classical histological criteria, which are used in relation to the physiological cycle, in the study of HRT-treated endometria is inappropriate.

Endometrium↗
PubMed1998

Circulating immunoreactive interleukin-6 in cystic fibrosis.

We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1-antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation, after antibiotic treatment, and in clinically stable patients with cystic fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was to determine the compartmental patterns of a proinflammatory and anti-inflammatory cytokine compared with other markers of inflammatory activity in cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p = 0.007, and p = 0.01, respectively, in a stable group of patients compared with those at the end of an exacerbation. IL-6 and CRP concentrations were related (r = 0.836, p < 0.0001), and both were greater than in matched control subjects (p < 0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment were positively related to FEV1 and FVC and inversely related to concentrations of neutrophil elastase. The separation between patients and healthy subjects, and the reduction of IL-6 after antibiotic treatment indicates it could be used as a marker of inflammation, but its relationship to other markers depends on the compartment in which it is measured.

Adult↗
PubMed1998

Regulation of the glycosylated beta-lactoglobulin homolog, glycodelin [placental protein 14:(PP14)] in the baboon (Papio anubis) uterus.

In vitro studies indicate that glycodelin (PP14) synthesis by the human endometrium increases dramatically at the time of implantation and early pregnancy. It has been postulated that this protein may have an immunosuppressive function. Due to the limitations associated with in vivo studies in the human, this study was undertaken to study the regulation of the baboon glycodelin homolog in vivo during the menstrual cycle and early pregnancy. In nonpregnant baboons, between days 10-12 postovulation (n = 3) the mid and apical regions of the glandular epithelium showed a distinct punctate staining pattern, which increased between days 12-18 of pregnancy (n = 3). Between days 25-60 of pregnancy, staining intensity in the glandular epithelium decreased. The decrease was more apparent at the implantation site compared with the nonimplantation site. The immunostaining correlated with the synthesis of radiolabeled baboon glycodelin in explant culture. Northern blot analysis demonstrated two messenger RNA (mRNA) transcripts [1.0 and 1.7 kilobases (kb)] in the baboon uterus compared with a single 1.0-kb transcript in the human, and mRNA expression was consistent with protein localization and synthesis. The protein and mRNA expression was consistently higher in the deeper glands of the functionalis and basalis during early pregnancy. Because the increased expression of glycodelin in the baboon endometrium coincided with peak levels of CG, a simulated pregnant baboon model was used to confirm hormonal regulation. Exogenous human CG (hCG) followed by estrogen and progesterone treatment in intact and ovariectomized baboons up-regulated glycodelin expression between days 18-25 postovulation (n = 10). By day 32 postovulation (n = 3), glycodelin synthesis decreased. Estrogen and progesterone treatment in the absence of exogenous hCG did not result in an increase of glycodelin synthesis. Analysis of uterine flushings from hCG-treated animals revealed that a minimum of 7 days of hCG treatment was required for glycodelin to be detectable in the uterine lumen. These studies indicate that a posttranslationally modified glycodelin homolog is synthesized by the baboon uterus during early pregnancy and appears to be regulated directly by CG. This pattern of synthesis is comparable with that observed with in vitro studies in the human. Because glycodelin expression is associated with CG secretion, we suggest that this protein may have a functional role during implantation in the primate. Thus, the baboon may serve as a nonhuman primate model to elucidate the function of this protein in vivo.

Amino Acid Sequence↗
PubMed1998

Uterine surveillance of asymptomatic postmenopausal women taking tamoxifen.

The aim of this study was to assess the ability of transvaginal sonography (TVS) and office hysteroscopy with sharp curettage to characterize the morphological changes in the uteri of asymptomatic postmenopausal women taking long-term tamoxifen for breast cancer. The overall acceptability of a single-visit screening clinic for these women was also evaluated. Fifty-eight women were recruited from patients undergoing regular follow-up at the Leicester Royal Infirmary for breast cancer. A single-visit clinic was acceptable to 94.8% of these women. Transvaginal sonography detected endometrial thickness of greater than 5 mm in 84.5% of cases, but there was no relationship between total tamoxifen exposure and endometrial thickness. Transvaginal sonography also detected uterine lesions such as fibroids and endometrial cysts in 34.5% of cases. Hysteroscopy detected the latter uterine lesions in 53.4% of cases, with three cases (5.2%) of endometrial polyps also being identified in these women. Sharp curettage sampling of the endometrium produced specimens sufficient for diagnosis in 84.5% of cases; 70.7% of specimens were reported as showing types of 'quiescent' endometrium with 13.8% of specimens showing 'active' endometrium. In the latter group, there was a case of complex hyperplasia detected and also a case with granulomatous endometritis. For each histopathological diagnosis identified, there was a wide range of endometrial thickness recorded by TVS. A single-visit screening clinic involving TVS and hysteroscopy with sharp curettage was acceptable to asymptomatic women taking tamoxifen. However, hysteroscopy was more effective than TVS in detecting endometrial lesions such as polyps, fibroids and cystic areas. Although TVS detected endometrial thickness greater than 5 mm in the majority of cases, there were no malignancies detected and, for each histopathological classification, there was a wide range of endometrial thickness associated. Thus, the isolated use of TVS is insufficient for screening the endometria of these women.

Curettage↗
PubMed1997

The Leicester Endometrial Needle Sampler: a novel device for endometrial and myometrial junctional zone biopsy.

A 48-cm-long, fine (16 gauge) needle was purpose-built to our design for full-thickness endometrial sampling. It is driven by a high-speed cutting device that has a two-step action-loaded spring, and is adjusted to a penetration depth of 16 mm. Pain and tolerance were assessed on a visual analogue scale. The histologic diagnosis obtained by this device, the Leicester Endometrial Needle Sampler, was compared with that of Pipelle endometrial sampling in 40 patients at the end of panoramic hysteroscopy under local anesthesia. The patients' mean age was 51 years (range 39-60) and the mean parity was 2.4 (range 0-6). The mean (+/-standard deviation) pain score was 3.7 +/- 2.2 and the mean tolerability score was 4.4 +/- 3.6. The technique helped to procure a full-thickness endometrial biopsy in all cases, from targeted areas including the myometrial junctional zone, with 100% efficiency.

Biopsy, Needle↗
PubMed1997

A cross-sectional study of changes in fetal renal size with gestation in appropriate- and small-for-gestational-age fetuses.

This cross-sectional study aimed to determine whether there are differences in kidney size and shape in small- and appropriate-for-gestational-age fetuses at different gestations. In the Fetal Growth Clinic of a large university hospital in England, 219 singleton fetuses were studied cross-sectionally at different gestational ages from 22 to 38 weeks. At each gestational age, the fetal kidney length, circumference and anterior-posterior and transverse diameters were measured using an Aloka 650 SL machine. At birth, the fetuses were classified as small or appropriate for gestational age, depending on the birth weight centile; the various kidney measurements for the two groups were compared. The kidney lengths at different gestational ages were similar in the two groups. The circumference and transverse and anterior-posterior diameters were significantly greater in the appropriate-for-gestational-age fetuses from about 28 weeks' gestation. We conclude that differences in fetal kidney size with gestation manifest from as early as 26-28 weeks. The differentially smaller anterior-posterior and transverse kidney diameters in small-for-gestational age fetuses, resulted in altered renal morphology, producing sausage-shaped kidneys.

Adult↗
PubMed1997

Localization of fibrillin-1 in human endometrium and decidua during the menstrual cycle and pregnancy.

We have examined the existence and distribution of fibrillin-1 within the endometrium and decidua to ascertain the effect of decidualization upon its synthesis, and its relationship to other extracellular matrix proteins. Formalin-fixed, paraffin-embedded tissues were stained using monoclonal antibodies to collagen IV, elastin, fibrillin-1 and laminin, by immunocytochemistry. Fibrillin-1 was present throughout the menstrual cycle and appeared to be cell-associated. Similar staining for fibrillin-1 was detected within the Fallopian tube of ectopic pregnancy material. In first trimester, second trimester and term decidua, staining for fibrillin-1 was more intense than that during the menstrual cycle and was detected as a thick layer encapsulating decidual cells, but also in fibrillar form inter-connecting these cells. In comparison with the association of collagen IV and laminin with all basal laminae, fibrillin-1 was absent from the vascular and glandular elements of pregnancy endometrium. Elastin was absent in all tissues examined. Hence, fibrillin-1 exists within the uterus in association with basal lamina components rather than with elastin-containing fibrils, where its presence in the endometrium and decidua could be of functional significance.

Antibodies, Monoclonal↗
PubMed1997

Distribution of integrins and the extracellular matrix proteins in the baboon endometrium during the menstrual cycle and early pregnancy.

Integrins are heterodimeric glycoproteins that have been found to undergo dynamic temporal and spatial changes in distribution in the endometrium during the menstrual cycle in women. Likewise the extracellular matrix (ECM) ligands for these receptors are likely to play a role in the establishment of a receptive endometrium. To develop primate models to study the role of these molecules in the cascade of molecular events leading to implantation, integrin expression and associated changes in ECM were investigated during the menstrual cycle and in early pregnancy in the baboon. Antibodies specific for the integrins (alpha(1-6) and alpha(v); beta1, beta3, and beta4) and ECM (laminin, collagen IV, fibronectin) were utilized. In addition, cytokeratin and alpha-smooth muscle actin were used as epithelial, stromal, and smooth muscle cell markers, respectively. Endometrium was obtained in duplicate or triplicate during the menstrual cycle and early pregnancy. Changes observed during the natural menstrual cycle were confirmed using ovariectomized, steroid-treated animals. Constitutively expressed integrins on the endometrial epithelium included the collagen/laminin receptors: alpha2, alpha3, alpha6, and beta4. The pattern of expression correlated well with the distribution of ECM in this tissue. Collagen IV was confined to the basement membrane of glandular epithelium and blood vessels. Laminin immunostaining was found in the basement membrane, mostly in the stroma of the basal region, in the glandular endometrium and vasculature. Fibronectin was present throughout the stroma but not in the basement membrane. The collagen receptor alpha1 beta1 and fibronectin receptor alpha4 beta1 appeared in the glandular epithelium in the luteal phase. As in the human, alpha1 and alpha4 disappeared from the glandular epithelium with the establishment of pregnancy. In contrast, the alpha4 beta3 vitronectin receptor appeared in the glandular epithelium only in pregnancy or following long-term steroid treatment with estrogen and progesterone but not during the time of uterine receptivity associated with the initial period of embryo attachment. Osteopontin, an ECM ligand for alpha(v) beta3, was coexpressed with this integrin in invading cytotrophoblasts, glandular epithelium, and decidualizing stromal cells. Decidualization in the baboon was associated with changes in integrin expression similar to those found in humans: there was an increase in alpha1, alpha3, alpha6, beta1, and alpha(v) beta3 in the decidualized stromal cells. Laminin and collagen IV expression also increased at the implantation site and throughout the endometrium. In contrast, fibronectin expression was most evident at the implantation site and corresponded to alpha5 expression on the invading cytotrophoblasts. In summary, marked similarities were found in the expression of ECM and the integrin receptors between the baboon and the human endometrium throughout the menstrual cycle and in pregnancy. Cycle-specific integrins, alpha1, and alpha4, were present on epithelial cells during the secretory phase. Delayed expression of alpha(v) beta3 in baboon endometrial glands correlated closely with the time of enhanced glandular secretory activity in this primate. The baboon appears to be an excellent model for the investigation of the role of integrins and ECM leading to successful implantation.

Animals↗
PubMed1997

Automated blood pressure measurement as a predictor of proteinuric pre-eclampsia.

OBJECTIVES: To investigate the relation between antenatal clinic, obstetric day unit and 24-hour ambulatory blood pressure measurements and 24-hour proteinuria levels in hypertensive pregnancies. DESIGN: An observational study. PARTICIPANTS: Forty-eight women presenting with new hypertension after 20 weeks of gestation. RESULTS: The closest relation was found between ambulatory blood pressure measurements and 24-hour proteinuria levels. No significant relation was found between the conventional diastolic blood pressure threshold of 90 mmHg and 24-hour proteinuria levels. CONCLUSIONS: Ambulatory blood pressure measurement gives better information about disease status in pre-eclampsia as assessed by proteinuria than does conventional sphygmomanometry.

Adolescent↗
PubMed1996

Major secretory product of the mesometrial decidua in the rat, a variant of alpha-2-macroglobulin, binds insulin-like growth factor I via a protease-dependent mechanism.

Decidualization-associated protein (DAP), the quantitatively major secretory product of the mesometrial decidua in the rat, is a pl variant of the liver-derived acute-phase reactant, alpha-2-macroglobulin (alpha 2M). Alpha 2M, a broad spectrum protease inhibitor, has been demonstrated in the human to bind a variety of cytokines and growth factors. In humans, the quantitatively major secretory product of decidual tissue is an insulin-like growth factor (IGF) binding protein. In this study, we have therefore tested the ability of liver- and decidual-derived alpha 2M in the rat to bind IGF-I. Alpha 2M purified from acute-phase plasma and DAP purified from cytosolic extracts of decidual tissue and medium from tissue incubations both bound radiolabeled IGF-I. The binding of IGF-I was principally dependent upon the coincubation of the protein with a proteinase. Therefore, it occurred during the conversion of the "slow" to the "fast" form of alpha 2M. Pretreatment with proteinase to produce the fast form before addition of the IGF-I reduced the binding. Binding was enhanced at a ratio protein:proteinase of 1:1. Results from gel electrophoretic analysis were consistent with the covalent linkage of IGF-I to alpha 2M during the cleavage of the "bait region." A saturable displacement by increasing concentrations of unlabeled IGF-I suggested high affinity interaction. Under conditions of demonstrated binding to purified proteins binding in acute-phase plasma, decidual tissue extracts and tissue incubation medium were associated with a high molecular weight species which was confirmed to represent alpha 2M and DAP, respectively. Our studies demonstrate that IGF-I may now be added to the list of regulatory peptides which alpha 2M may bind and that, in rat decidua, DAP may represent the functional homolog of decidual IGFBP-1 in the human and regulate growth factor function during placental development.

Animals↗
PubMed1996

Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth.

1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 +/- 2.5 mm compared with 19.8 +/- 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestation-age group (274.4 +/- 32.9 mu-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 +/- 28.3 mu-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = -0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = -0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26-34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs.

Birth Weight↗
PubMed1996

Endometrial responses to hormone replacement therapy: the bleeding pattern.

Little information is available concerning the response of the endometrium to exogenous sex steroid therapy, particularly in the post-menopausal state. In this study we examined the variability of the bleeding pattern in 103 post-menopausal women receiving cyclical sequential combined hormone replacement therapy (HRT) over 6 months. All patients kept menstrual diary cards to record the onset, duration and subjective assessment of the severity of bleeding. We defined a cycle as starting from the commencement of treatment till the day of onset of bleeding. Two groups were identified amongst 99 women who experienced bleeding: those with a mean cycle length of 29 or more days (late bleeders, n = 50) and those with shorter mean cycle length (early bleeders, n = 49). The former were characterized by less variability in cycle length and bleeding that was of shorter duration. Four women experienced no bleeding. There were no significant differences between the two groups in age, year since the menopause, weight, height, body mass index (BMI), parity, or in the previous use of HRT. The only significant difference was in their smoking habits. This suggests a possible link of a hypo-oestrogenic state to poor cycle control.

Adult↗
PubMed1996

The effects of the antihormones RU486 and tamoxifen on fetoplacental development and placental bed vascularisation in the rat: a model for intrauterine fetal growth retardation.

OBJECTIVE: To examine the effect of administration of the antihormones RU486 and tamoxifen in early pregnancy during the period of maximal decidual development in the rat upon fetoplacental and placental bed development. DESIGN: Case-control study in an experimental animal model. SETTING: Academic department of obstetrics and gynaecology in a UK medical school. ANIMALS: Small laboratory animal-the rat-exhibiting haemochorial placentation. INTERVENTION: Administration of antiprogesterone or antioestrogen (RU486 and tamoxifen respectively) during early pregnancy. MAIN OUTCOME MEASURES: Weight of the whole pregnancy implant, fetus, mesometrial decidua and placenta; incidence of intrauterine fetal death: and histological changes in the placental bed. RESULTS: RU486 produced resorption of all implants when administered above a threshold dose, below which it had no effect upon subsequent fetoplacental development. Tamoxifen treatment on days 9 to 11 resulted in significant reduction of decidual weight (35.1% on day 12 of pregnancy, P < 0.001). This was associated with a higher rate of implants or fetuses weighing below the 10th centile (59.6% and 5.7% on day 12, P < 0.001; 42.9% and 7% on day 16, P < 0.001; 25.4% and 7.6% on day 20, P < 0.001 in treated and control animals, respectively). This was also associated with a higher rate of intrauterine fetal death (30.7% on day 16 compared with 4.5% in controls, P < 0.001; 47.8% on day 20 compared to 0.83% in controls, P < 0.001). Histologically, the placental bed of treated animals failed to develop a dilated uteroplacental artery although trophoblast cells migrated endovascularly to a level equivalent to untreated animals. CONCLUSIONS: RU486 had an all or none dose-dependent effect on fetoplacental development, resulting in either abortion or normal development of pregnancy. Tamoxifen produced significant impairment of decidual development, which was associated with altered blood vessel transformation in the placental bed, impaired fetoplacental development and higher incidence of growth retarded fetuses and fetal death.

Abortifacient Agents, Steroidal↗
PubMed1996

Fetal fibronectin in cervicovaginal secretions as a predictor of preterm birth.

OBJECTIVE: To determine whether fetal fibronectin detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labour is a predictor for preterm birth. DESIGN: A blind prospective observational study. SETTING: A teaching hospital. PARTICIPANTS: One hundred and forty-one women presenting to the delivery suite between 24 and 37 weeks of gestation (112 were between 24 and 34 weeks of gestation) with symptoms suggestive of preterm labour, with intact membranes and cervical dilation of < 2 cm. INTERVENTION: Specimens of cervicovaginal secretions were collected from the ectocervix and posterior fornix. Fetal fibronectin levels were measured by an ELISA and samples were considered positive if the level of fetal fibronectin present was > or = 0.05 microgram/ml. MAIN OUTCOME MEASURES: Gestation at birth and sampling-birth interval. RESULTS: The preterm birth (before 37 weeks of gestation) rate in the population studied was 19.1%. Fetal fibronectin predicted preterm birth with sensitivity of 63%, specificity of 95.6%, positive predictive value of 77.3%, and negative predictive value of 91.6%. Analysis of the data from women at less than 34 weeks of gestation showed similar results. A negative test accurately excluded (97.9%) the chance of subsequent birth during the three weeks interval following sampling. CONCLUSIONS: The presence of fetal fibronectin in the cervicovaginal secretions of women admitted with symptoms suggestive of preterm labour indicates a significant risk for subsequent preterm birth. The absence of fetal fibronectin in this group is a very strong indication that subsequent preterm birth is unlikely to occur. Fetal fibronectin test, if combined with clinical findings, has a potentially important role in clinical management of women with symptoms suggestive of preterm labour.

Adult↗