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Roberto Romero

Publications and source records attributed to Roberto Romero.

At least 37 records · Page 2Linked to original sources
PubMed2006

Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery.

This article addresses the question of whether the uterine cavity is normally sterile and reviews the difficulties in conducting microbiologic studies of the endometrium, the limitations of conventional microbiologic techniques (cultivation-dependent), and the potential contribution of molecular microbiology to examine microbial diversity and burden of the endometrium. Issues pertaining to the diagnosis of chronic endometritis and the need for information about the prognostic value of this finding in subsequent pregnancies are discussed. The results of a randomized clinical trial of antibiotic administration versus placebo in women with a previous preterm birth are reviewed and commentary is provided. The emerging picture is that microbial-host interactions in the endometrial cavity are important for reproductive success. This is a US government work. There are no restrictions on its use.

Anti-Bacterial Agents↗
PubMed2006

The role of cervical cerclage in obstetric practice: can the patient who could benefit from this procedure be identified?

This editorial critically examines the definition of "cervical insufficiency." The definition, the clinical ascertainment, efforts to develop an objective method of diagnosis, as well as the nature of cervical disease leading to spontaneous mid-trimester spontaneous abortion and preterm delivery are reviewed. The value and limitations of cervical sonography as a risk assessment tool for spontaneous preterm delivery are appraised. The main focus is on the role of cervical cerclage to prevent an adverse pregnancy outcome. The value of assessing the presence or absence of endocervical inflammation in the outcome of cerclage placement is discussed.

Abortion, Spontaneous↗
PubMed2006

The transcriptome of the uterine cervix before and after spontaneous term parturition.

OBJECTIVE: This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor. STUDY DESIGN: The transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus 2 microarrays. Samples were collected from patients at term not in labor (n = 7) and after spontaneous labor (n = 9). Microarray statistical analysis included robust multiarray average, reduction of invariant probes, and permutation analysis for differential expression. Real-time quantitative reverse transcriptase-polymerase chain reaction assays of selected genes were performed on a new set of samples from term patients without labor (n = 10) and patients after spontaneous labor (n = 9). RESULTS: (1) The cervical transcriptome of term patients without labor was dramatically different from that of patients who underwent labor; (2) unique genes (n = 1192) were differentially expressed in the cervical tissue from patients after spontaneous labor, compared with that of the term patients without labor (false discovery rate less than 0.05, absolute fold change greater than 2); (3) Gene Ontology analysis indicated that multiple "Biological Process" categories were enriched, including "response to biotic stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of major interest, genes involved in neutrophil chemotaxis were dramatically up-regulated in specimens from women after spontaneous labor; (5) real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of interleukin-8, interleukin-6, and vascular endothelial growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3 and Toll-like receptor-5 showed decreased gene expression in patients after spontaneous labor. This was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. CONCLUSION: (1) Cervical dilatation in term labor is associated with a stereotypic gene expression pattern determined by microarray, which is characterized by overexpression of genes involved in neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially regulated during spontaneous parturition at term; and (3) this study provides an unbiased and comprehensive description of the changes in the cervical transcriptome before and after spontaneous term labor.

Adolescent↗
PubMed2006

Fetal macrophages are not present in the myometrium of women with labor at term.

OBJECTIVE: The basic mechanisms responsible for human parturition remain to be elucidated. The influx of fetal leukocytes into the myometrium has been recently proposed to be a crucial event in the onset of murine parturition. Surfactant protein-A has been implicated in the initiation of labor. In mice, it is thought that surfactant protein-A induces migration and subsequent activation of amniotic fluid macrophages of fetal origin, which then invades the myometrium. The present study was conducted to determine whether fetal macrophages invade the myometrium of women in labor. STUDY DESIGN: Placental bed biopsy specimens were obtained from patients in labor who delivered male neonates at term (n = 7). Myometrial sections of postpartum hysterectomy specimens obtained from women who delivered of male neonates (n = 3) were also analyzed. Formalin-fixed, paraffin-embedded sections were immunostained for CD68 or CD14 (which are markers for macrophages); immunoreactive myometrial macrophages were specifically procured by laser capture microdissection. Sex typing was done by polymerase chain reaction for the amelogenin gene with genomic DNA that was isolated from the macrophages. Chromogenic in situ hybridization with a Y chromosome-specific probe was also performed on paraffin-embedded histologic sections. RESULTS: Amelogenin allelotypes of the macrophages were consistent with female alleles in all cases that were tested, indicating a maternal origin. Chromogenic in situ hybridization demonstrated the absence of Y chromosome-positive mononuclear cells in the myometrium in all cases. CONCLUSION: These observations, from a limited number of cases, suggest that migration of fetal macrophages from the amniotic cavity or the chorioamniotic membranes into the myometrium does not occur during human labor. The trafficking of fetal macrophages in labor seems to be different in humans and mice.

Female↗
PubMed2006

Uterine transcriptomes of bacteria-induced and ovariectomy-induced preterm labor in mice are characterized by differential expression of arachidonate metabolism genes.

OBJECTIVE: The purpose of this study was to identify changes in gene expression that are associated with preterm labor induced by either bacteria or ovariectomy. STUDY DESIGN: Pregnant mice (14.5 days of gestation) were allocated to: (1) intrauterine injection of heat-inactivated Escherichia coli; (2) media alone; (3) ovariectomy; or (4) sham operation. The uterine transcriptome was studied with photolithographic, very short oligonucleotide-based microarrays, and arachidonate metabolism genes were assayed with quantitative reverse transcriptase-polymerase chain reaction. Significance was determined by analysis of variance. RESULTS: Microarray-based gene expression changes in the arachidonate metabolism pathway are associated globally with bacteria-induced preterm labor (P < or = .0031) and ovariectomy-induced preterm labor (P < or = .00036). Quantitative real-time reverse transcriptase-polymerase chain reaction measurements demonstrated that bacteria-induced preterm labor substantially increased the expression of genes involved in prostaglandin synthesis. In contrast, ovariectomy-induced preterm labor increased the expression of genes involved in lipoxin, leukotriene, and hydroxyeicosatetraenoic acid synthesis. CONCLUSION: Bacteria-induced and ovariectomy-induced preterm labor each express a different balance of genes that are required for the synthesis of prostaglandins, lipoxins, leukotrienes, and hydroxyeicosatetraenoic acids.

Animals↗
PubMed2006

A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery.

OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. STUDY DESIGN: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. RESULTS: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). CONCLUSION: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intra-amniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery.

Adult↗
PubMed2006

Analysis of microarray experiments of gene expression profiling.

The study of gene expression profiling of cells and tissue has become a major tool for discovery in medicine. Microarray experiments allow description of genome-wide expression changes in health and disease. The results of such experiments are expected to change the methods employed in the diagnosis and prognosis of disease in obstetrics and gynecology. Moreover, an unbiased and systematic study of gene expression profiling should allow the establishment of a new taxonomy of disease for obstetric and gynecologic syndromes. Thus, a new era is emerging in which reproductive processes and disorders could be characterized using molecular tools and fingerprinting. The design, analysis, and interpretation of microarray experiments require specialized knowledge that is not part of the standard curriculum of our discipline. This article describes the types of studies that can be conducted with microarray experiments (class comparison, class prediction, class discovery). We discuss key issues pertaining to experimental design, data preprocessing, and gene selection methods. Common types of data representation are illustrated. Potential pitfalls in the interpretation of microarray experiments, as well as the strengths and limitations of this technology, are highlighted. This article is intended to assist clinicians in appraising the quality of the scientific evidence now reported in the obstetric and gynecologic literature.

Algorithms↗
PubMed2006

Apparent role of dynein in glucose-6-phosphate dehydrogenase trafficking in neutrophils from pregnant women.

To better understand the mechanisms of metabolic microcompartmentalization associated with neutrophil hexose monophosphate shunt activity during pregnancy, we have studied the intracellular trafficking of glucose-6-phosphate dehydrogenase (G6PDase). Microtubule motor proteins colocalize with G6PDase. Dynein inhibitors block G6PDase accumulation at the microtubule-organizing center in pregnancy cells. On this basis, we conclude that microtubule motor proteins participate in hexose monophosphate shunt enzyme transport within leukocytes.

Cell Compartmentation↗
PubMed2006

The effect of continuous morphine administration on maternal plasma oxytocin concentration and uterine contractions after open fetal surgery.

OBJECTIVE: A major complication of open fetal surgery is prematurity. We propose that fetal and maternal stress/pain after surgery may affect the concentration of circulating oxytocin and the frequency of uterine contractions, thus increasing the risk of preterm delivery. The objective of this study was to test whether continuous morphine sulfate administration after open fetal surgery has an effect on maternal plasma oxytocin concentration and the frequency of uterine contractions. METHODS: An established time-pregnant primate model for open fetal surgery was used. From the time of surgery until the end of the three-day study period, three animals received prophylactic antibiotics, a bolus of indomethacin, and a bolus of morphine sulfate (group I). Three other animals received the same prophylactic antibiotics and an i.v. bolus of indomethacin, as well as a continuous i.v. infusion of morphine sulfate throughout the entire study period (group II). Maternal blood samples were collected to determine oxytocin plasma concentrations. Oxytocin was measured by radioimmunoassay. Uterine activity was continuously recorded through an amniotic fluid catheter and quantified as number of contractions (10 mmHg increase from base line in intrauterine pressure) per hour (UCs/h). RESULTS: The mean maternal plasma oxytocin concentration was higher (p < 0.01) and the number of uterine contractions more frequent (p < 0.05) in the group of animals with intermittent doses of morphine than in the group that received morphine continuously. CONCLUSIONS: These data suggest that maternal plasma oxytocin concentration and uterine activity after open fetal surgery may be related to inadequate maternal/fetal analgesia/sedation.

Analgesics, Opioid↗
PubMed2006

Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?

OBJECTIVE: To determine whether broad-spectrum antibiotic administration to patients with preterm labor and intact membranes is associated with an improvement in neonatal and maternal outcomes, particularly in patients with microbial invasion of the amniotic cavity (MIAC) or endocervical inflammation (ECI). METHODS: A prospective clinical trial was conducted in which women in premature labor were alternately allocated to receive either antibiotics or placebo, and information about MIAC and ECI collected. Eighty-four pregnant women between 24 and 34 weeks of gestation with spontaneous preterm labor were enrolled. Exclusion criteria were cervical dilatation greater than 3 cm, clinical chorioamnionitis, abruption, rupture of membranes, vaginal bleeding, and several additional fetal and maternal conditions that may influence perinatal outcome. Amniocentesis was offered to all patients and the cervix and vagina were sampled for microbiological and cytological studies. Eligible patients were allocated to receive either clindamycin-gentamycin or placebo for 7 days. Corticosteroids and tocolysis with beta-adrenergic agents were used according to the standard management of our institution. MIAC was defined as the presence of a positive amniotic fluid culture obtained by trans-abdominal amniocentesis. ECI was diagnosed when a significant increase in the white blood cell count of the endocervical secretions was found. A composite neonatal morbidity/mortality outcome was created, including severe neonatal morbidity (respiratory distress syndrome, asphyxia, sepsis, pneumonia, intraventricular hemorrhage) and mortality. RESULTS: Thirty-nine women received antibiotics and 40 received placebo. The prevalence of ECI and MIAC in both groups was comparable (antibiotic group ECI 61.5% (24/39) and MIAC 20.5% (8/39); placebo group ECI 62.5% (25/40) and MIAC 20% (8/40); p > 0.05). Overall, there were no significant differences in maternal infections and composite neonatal outcomes between antibiotic and placebo groups. Women who received antibiotics had a lower rate of subsequent rupture of membranes compared to patients who received placebo (2.6% (1/39) vs. 25% (10/40), respectively; p = 0.007). A sub-analysis showed that among patients with ECI, antibiotic administration was associated with a lower rate of composite neonatal morbidity/mortality outcome compared to those who received placebo (4.2% (1/24) vs. 28% (7/25), respectively; p < 0.05). This association was also present in patients with ECI without MIAC (0% (0/16) vs. 27.8% (5/18); p < 0.05), but not in patients with ECI and MIAC (antibiotic group 12.5% (1/8) vs. placebo group 28.6% (2/7); p > 0.05). CONCLUSIONS: The combination of antibiotics used in this study did not improve maternal or perinatal outcome in patients with preterm labor and intact membranes. Further studies are required to determine if women with endocervicitis presenting with preterm labor and intact membranes may benefit from antibiotic administration.

Administration, Oral↗
PubMed2006

Tissue microarray: an effective high-throughput method to study the placenta for clinical and research purposes.

OBJECTIVE: Tissue microarray (TMA) technology allows simultaneous examination of the expression of many molecular markers (protein, mRNA, DNA, etc.) with high-throughput. The application of this technology, to date, has been largely confined to the study of cancer. Placental pathology poses unique challenges because of the size of the organ, its complex anatomy, as well as its histological heterogeneity. The objective of this study was to assess the feasibility and efficiency of TMAs for immunohistochemistry and in situ hybridization of placental tissues. STUDY DESIGN: TMAs were constructed using an automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used. Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in each block. Five mum-thick TMA sections underwent immunohistochemical analysis of both cytoplasmic and nuclear antigens using a panel of antibodies against a variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF), and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens. mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in situ hybridization for the Y chromosome (DYZ1) were also performed. RESULTS: Validation of TMA immunoreactivity demonstrated comparable results with corresponding whole sections. When a two-tiered scoring system (positive/negative) was employed, there was agreement between two and three cores and whole tissue sections (kappa>0.7). When a three-tiered scoring system (negative, weak-positive, or strong-positive) was used, the data from three cores showed the highest agreement with whole tissue sections (kappa >0.7). In situ hybridization experiments for mRNA and DNA were also successful in that the signals were readily detectable. Successful transfer from the donor block to the recipient block differed according to the anatomical compartment. The transfer efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were 96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. CONCLUSION: TMA is a practical and effective tool for high-throughput molecular analysis of the human placenta. Duplicate and triplicate cores offer agreement with whole tissue sections for two-category distinction immunostaining. TMA also affords relevant results from in situ hybridization experiments for mRNA and DNA. The major advantages are the conservation of tissues and reagents, simultaneous comparison of molecular markers in different anatomical compartments of the placenta, and reduction of experimental error.

Biomarkers↗
PubMed2006

Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in pregnancy and term parturition.

OBJECTIVE: To examine if changes in fetal plasma concentrations of cortisol or dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term parturition. METHODS: Umbilical cord plasma cortisol and DHEAS concentrations were measured in 374 singleton pregnancies that delivered at term in the following six groups: group 1, cordocentesis for clinical indications before 36 weeks of gestation (n = 93); group 2, cordocentesis for clinical indications after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective cesarean section (CS) at term without labor (n = 140); group 4, cord blood sampling after CS at term with early labor (cervical dilatation < or =3 cm, n = 18); group 5, cord blood sampling after CS at term with active labor (cervical dilatation 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal delivery at term (n = 88). Corticosteroids were not administered before blood collection. RESULTS: (1) Fetal plasma cortisol remained unchanged until 36 weeks of gestation and increased thereafter to term; (2) active labor was associated with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS increased at term gestation (>36 weeks) but did not increase during active labor; (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation and with active labor at term. CONCLUSIONS. Human parturition at term is associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS ratio, but not in DHEAS.

Adult↗
PubMed2006

A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome).

BACKGROUND: 'Mirror syndrome' (Ballantyne's syndrome) refers to the association of fetal hydrops with placentomegaly and severe maternal edema. Preeclampsia occurs in approximately 50% of these cases. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), an anti-angiogenic factor, has been implicated in the pathophysiology of preeclampsia (PE). OBJECTIVE: The objective of this study was to determine if the maternal plasma concentration of sVEGFR-1 is elevated in patients with mirror syndrome. STUDY DESIGN: This case-control study included patients with uncomplicated pregnancies (n = 40) and those with mirror syndrome (n = 4) matched for gestational age. Mirror syndrome was defined as fetal hydrops and severe maternal edema. Maternal plasma sVEGFR-1 concentrations were determined using specific enzyme-linked immunosorbent assays. Immunohistochemistry of sVEGFR-1 on villous trophoblasts was also performed in samples from one patient with mirror syndrome and compared with those from a patient with spontaneous preterm delivery matched for gestational age. Non-parametric statistics were used for analysis (p < 0.05). RESULTS: (1) The median maternal plasma concentration of sVEGFR-1 was significantly higher in patients with mirror syndrome than in the control group (median: 3974 pg/mL, range: 3083-10 780 vs. median: 824 pg/mL, range: 260-4712, respectively; p < 0.001). (2) All patients with mirror syndrome had sVEGFR-1 concentrations above the 95th percentile for gestational age. Syncytiotrophoblast, especially syncytial knots, showed strong staining with antibodies against sVEGFR-1 in placental samples from the patient with mirror syndrome, but not in those from the patient with spontaneous preterm delivery. CONCLUSION: High maternal plasma concentrations of sVEGFR-1 were observed in mirror syndrome. We propose that this anti-angiogenic factor may participate in the pathophysiology of this syndrome. Thus, maternal plasma determination of sVEGFR-1 may help to identify the hydropic fetus that places the mother at risk for preeclampsia.

Adult↗
PubMed2006

Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation.

OBJECTIVE: Funisitis is the histologic counterpart of the fetal inflammatory response syndrome, which is a multisystemic disorder associated with impending preterm delivery and adverse neonatal outcome. The purpose of this study was to examine the relationship between funisitis and the microbiologic status of amniotic fluid (AF) and AF white blood cell (WBC) count in patients at term. METHODS: The relationship between the presence of funisitis, AF culture, and AF WBC count was examined in 832 consecutive patients who delivered a term neonate within 72 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly. AF WBC count was analyzed in a hemocytometer chamber. Nonparametric statistics were used for data analysis. RESULTS: Funisitis was present in 4% (30/832) of cases. A positive AF culture was more common in cases with funisitis than in those without funisitis (17% vs. 5%; p < 0.05). Patients with funisitis had a significantly higher median AF WBC count than those without funisitis (median >1000 cells/mm3 vs. median 2 cells/mm3; p < 0.001). The frequency of funisitis and of a positive AF culture was 1% in women without labor and with intact membranes and the frequencies and the median AF WBC count increased in the presence of labor or rupture of membranes. CONCLUSION: Funisitis is present in 4% of women at term and is associated with microbial invasion of the amniotic cavity (MIAC) and inflammation as reflected by increased AF WBC count.

Adult↗
PubMed2006

Evidence for interleukin-10-mediated inhibition of cyclo- oxygenase-2 expression and prostaglandin production in preterm human placenta.

PROBLEM: Interleukin-10 (IL-10) is thought to be a key cytokine for the maintenance of pregnancy. Here we examined the expression profiles of IL-10 and cyclo-oxygenase-2 (COX-2), and the effect of IL-10 on COX-2 expression and prostaglandin release in the human placenta from preterm labor deliveries associated with chorioamnionitis. METHOD OF STUDY: Placental tissues from preterm labor and term labor deliveries were processed for ex vivo placental explant culture system. IL-10 expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. COX-2 expression was evaluated by IHC, Western blotting and reverse transcriptase-polymerase chain reaction. Prostaglandin E2 (PGE2) release was measured by ELISA. RESULTS: IL-10 was significantly reduced in chorioamnionitis-associated preterm labor as well as in term labor placental tissues compared with second trimester normal pregnancy samples obtained from elective terminations. Similar results were obtained with freshly isolated cytotrophoblasts from these deliveries. As expected, COX-2 mRNA was detected at significant levels in tissues from term and preterm labor deliveries compared with no labor term deliveries. Importantly, IL-10 inhibited COX-2 expression in cultured placental explants from preterm labor deliveries, but not from term labor samples. Inhibition of COX-2 expression coincided with reduced PGE2 release. CONCLUSION: These results demonstrate the importance of IL-10 in countering inflammation associated with preterm labor, and suggest that term and preterm parturition may, in part, represent different conditions.

Adolescent↗