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Biomedical subjects

James H Segars

Publications and source records attributed to James H Segars.

At least 19 recordsLinked to original sources
PubMed2006

Ganirelix acetate causes a rapid reduction in estradiol levels without adversely affecting oocyte maturation in women pretreated with leuprolide acetate who are at risk of ovarian hyperstimulation syndrome.

BACKGROUND: Elevated estradiol (E(2)) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels and avoid cycle cancellation. METHODS: Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage. RESULTS: In the treatment group, there was a significant, reproducible reduction in serum E(2) levels. Mean E(2) at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy. CONCLUSIONS: GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E(2) without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS.

Adult↗
PubMed2006

The promise and perils of microarray analysis.

Microarray analysis has provided a novel means of identifying clues into the mechanisms of disease development. As a methodology, microarray analysis holds the promise for genome-wide screening in which 2 tissues (diseased and normal) are compared, and molecular pathways that defined the phenotype of the disease could be precisely defined. Alternatively, microarray experiments can be used to differentially compare pathologically similar diseased tissues to predict response to chemotherapy and risk of recurrence. However, the clinician should be aware that various sources of error can influence microarray analysis results. Sources of error can be minimized but not eliminated, explaining why meticulously conducted experiments in different laboratories or using different platforms result in different lists of genes. Confirmation and validation of genome-wide microarray results using ancillary methods remains a critical step. With proper confirmatory studies and cautious interpretation, microarray analysis represents a powerful tool for molecular discovery.

Female↗
PubMed2006

A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays.

This article will discuss some recent insights based on our microarray studies that have emphasized the role the extracellular matrix, transforming growth factor beta, and collagen structure in fibroid formation. These studies led to appreciation of molecular similarities between fibroids and keloids. Collectively, these observations suggest a model of fibroid development based on an abnormal response to tissue repair, resulting in disordered healing and formation of an altered extracellular matrix.

Extracellular Matrix↗
PubMed2006

Estrogen effects on the expression of Brx in the brain and pituitary of the mouse.

A member of the Dbl family of oncoproteins was discovered in breast cancer tissue extracts. This novel protein, designated Brx, contains an estrogen-receptor binding motif and is highly expressed in hormone-responsive breast tissue. Due to its ability to augment ligand-dependent activation of estrogen receptors, we analyzed the expression of Brx in the adult mouse brain and pituitary. Results indicated that Brx was expressed in specific regions of the brain and pituitary. Furthermore, the results indicate that differences exist in both brain and pituitary tissue of male and female mice with greater expression in the female. However, estrogen did not influence Brx expression in ovariectomized mice. The anatomical studies support a role for Brx in its association with the estrogen receptor and that Brx may be involved in neuronal and pituitary function in a sexually dimorphic manner.

Animals↗
PubMed2006

Rho family Guanine nucleotide exchange factor Brx couples extracellular signals to the glucocorticoid signaling system.

Glucocorticoids regulate many crucial biologic functions through their cytoplasmic/nuclear glucocorticoid receptors (GR). Excess, deficiency, or alteration in tissue sensitivity to glucocorticoids has been associated with major causes of human morbidity and mortality. Brx, a cytoplasmic Rho family guanine nucleotide exchange factor, binds to and influences the activity of several nuclear hormone receptors. We examined the functional and molecular interactions between GR and Brx. The glucocorticoid sensitivity of lymphocytes obtained from mice haplo-insufficient for Brx was significantly decreased. Conversely, GR-mediated transcriptional activity of a glucocorticoid response element (GRE)-mediated glucocorticoid-responsive promoter was enhanced by Brx in a guanine nucleotide exchange factor domain-dependent fashion. Brx interacted with GR, forming a ternary complex with RhoA. In a chromatin immunoprecipitation assay, Brx and RhoA were co-precipitated with GREs only in the presence of ligand-activated GR. Extracellularly administered lysophosphatidic acid, which activates its signaling cascade through a specific membrane GTP-binding protein (G-protein)-coupled receptor in a G-protein alpha(13)-, Brx-, and RhoA-dependent fashion, enhanced GR transcriptional activity, whereas depletion of endogenous Brx attenuated this effect. These findings suggest that glucocorticoid signaling and, hence, the tissue sensitivity to glucocorticoids, may be coupled to extracellular signals via Brx and small G-proteins. Nuclear Brx might act as a local GRE-GR-transcriptosome activator by mediating the effect of small G-proteins on glucocorticoid-regulated genes.

A Kinase Anchor Proteins↗
PubMed2006

Treatment with gonadotropin-releasing hormone (GnRH) antagonists in women suppressed with GnRH agonist may avoid cycle cancellation in patients at risk for ovarian hyperstimulation syndrome.

Forty-seven patients at high risk for ovarian hyperstimulation syndrome because of markedly elevated serum E2 levels on either long-luteal or microdose flare leuprolide acetate regimens were treated with ganirelix acetate. Despite being pretreated with GnRH agonist and without withholding gonadotropins, serum E2 decreased by 49.5% and 41.0% of pretreatment values (long luteal and microdose flare, respectively) after initiation of ganirelix, and 68.1% of the patients became pregnant.

Adult↗
PubMed2006

The second National Institutes of Health International Congress on advances in uterine leiomyoma research: conference summary and future recommendations.

OBJECTIVE: To summarize the proceedings of the Advances in Uterine Leiomyoma Research: 2nd NIH International Congress, which was convened on February 24-25, 2005 by the Department of Health and Human Services (DHHS), National Institutes of Health (NIH) in Bethesda, Maryland. DESIGN: Scientific information was presented at a 2-day conference, which was a collaborative effort of agencies across the DHHS and members of the academic, clinical, and medical communities involved in uterine leiomyoma research. CONCLUSION(S): The conference brought together scientists in biomedicine, epidemiology, basic research, therapeutics, and translational medicine and fostered an exchange of scientific information among members of the uterine leiomyoma research and health care communities. This document summarizes this exchange and outlines research needs and recommendations for future research directions.

Animals↗
PubMed2005

A suboptimal endometrial pattern is associated with a reduced likelihood of pregnancy after a day 5 embryo transfer.

This retrospective study examined the association of endometrial pattern and pregnancy after a day 5 ET. The pregnancy rate of women with a triple-line ultrasound endometrial pattern on the day of hCG administration was significantly higher than the pregnancy rate of women with the other ultrasound patterns. This observation suggests that, in a subset of patients, a suboptimal endometrial lining may interfere with assisted reproductive technology success.

Adult↗
PubMed2005

Anthrax vaccine does not affect semen parameters, embryo quality, or pregnancy outcome in couples with a vaccinated male military service member.

Anthrax vaccination has been used in an effort to prevent infection should anthrax be used as a biological weapon, and widespread use has been considered in the event of another anthrax attack on American soil, but the long-term impact of anthrax vaccination on reproductive outcome is unknown. We found that exposure to the anthrax vaccine by males who were undergoing assisted reproduction did not negatively impact semen parameters, fertilization rate, embryo quality, or clinical pregnancy rates.

Adult↗
PubMed2005

Embryo afterloading: a refinement in embryo transfer technique that may increase clinical pregnancy.

OBJECTIVE: Given the importance of ET technique during assisted reproductive technology cycles, we evaluated the effect of embryo afterloading subsequent to placement of the ET catheter on pregnancy rates vs. a standard direct ET. DESIGN: Retrospective cohort analysis. SETTING: University-based assisted reproductive technology program. PATIENT(S): Patients undergoing a fresh nondonor day 3 ET by a single provider over a 1-year period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): One hundred twenty-seven patients met inclusion criteria, and the overall pregnancy rate was 46.5%. There was no difference between the two groups with respect to age, basal FSH, or number of embryos transferred. The ET method used was at the discretion of the provider. There was no difference between the two groups in the presence of blood on the transfer catheter. However, there were significantly more transfer catheters with mucus contamination in the direct transfer group (25.58% vs. 5.95%). The clinical pregnancy rate in the group with ET using the afterloading technique was higher than in the direct ET group (52.4% vs. 34.9%). CONCLUSION(S): There was a trend toward an increase in pregnancy rate when an embryo afterloading technique was used. A prospective randomized trial is needed to examine this issue.

Adult↗
PubMed2005

Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions.

OBJECTIVE: To evaluate adhesion reformation after laparoscopic excision of endometriosis and adhesiolysis in women with chronic pelvic pain. DESIGN: Prospective clinical trial. SETTING: University hospital. PATIENT(S): Thirty-eight women with endometriosis and chronic pelvic pain. INTERVENTION(S): A primary and second-look laparoscopy with adhesiolysis and excision of endometriotic lesions with a neodymium-yttrium argon garnet surgical laser technologies (SLT) contact laser. MAIN OUTCOME MEASURE(S): Adhesion formation and character (thin, thin and thick, or thick). Location of adhesions at a first laparoscopy was compared with de novo or reformation of adhesions and the location of adhesions at a second surgery. RESULT(S): Adhesions or adhesions combined with endometriotic lesions were significantly more likely to reform at second surgery compared with sites having only an endometriosis lesion. Thick adhesions were associated with a significantly increased likelihood of an adhesion reforming, compared with thin adhesions or thin and thick adhesions. Lesions or adhesions involving the ovary were more likely to be associated with adhesions at a subsequent surgery, compared with lesions in the adjacent ovarian fossa or fallopian tube. CONCLUSION(S): Most patients developed adhesions after radical surgical excision of endometriosis for pelvic pain. The high incidence of adhesion formation after surgery for endometriosis underscores the importance of optimizing surgical techniques to potentially reduce adhesion formation.

Adult↗
PubMed2004

Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.

Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41-fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma:myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor-beta3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a molecular link between the leiomyoma and keloid phenotypes.

Adult↗
PubMed2004

Assessment of resident competency in the performance of sonohysterography: does the level of training impact the accuracy?

OBJECTIVE: The objective of this study was to examine the true-positive rates by level of training of the operator and to determine whether the accuracy of the procedure differed by the level of education after formalized training. STUDY DESIGN: This was a retrospective analysis. The records of patients who underwent surgery for the indication of an abnormal saline sonohysterography were reviewed from January 2001 to April 2003 (n=73 patients). The nature of the saline sonohysterography abnormality, the intraoperative findings, and the level of training of the provider were recorded. Findings at saline sonohysterography were compared with findings at hysteroscopy or surgery. Statistical significance was determined by chi(2) test. RESULTS: The overall true-positive rate was 86.3% (63/73 patients). The true-positive rates for nurse practitioners, second- and fourth-year residents, and fellows were 84%, 80%, 90%, and 89%, respectively. There was no significant difference among providers (P=.96). CONCLUSION: The true-positive rates for saline hysterography were comparable among different provider levels.

Clinical Competence↗
PubMed2004

Prognostic use of mean ovarian volume in in vitro fertilization cycles: a prospective assessment.

OBJECTIVE: To determine the predictive value and to define prognostic threshold measurements for mean ovarian volume (MOV) in patients undergoing IVF. DESIGN: Prospective cohort analysis. SETTING: Tertiary care center. PATIENT(S): Two hundred sixty-seven patients. INTERVENTION(S): Transvaginal ultrasound before starting gonadotropins. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, basal hormone levels, and cycle outcomes. RESULT(S): The MOV for the population was 4.78 +/- 2.6 cm(3) (range 0.9-21.1 cm(3)). The MOV significantly correlated with the majority of prestimulation and poststimulation IVF parameters. Threshold analysis demonstrated a lower pregnancy rate associated with a MOV of <2 cm(3) (31.6% vs. 55.6%). Threshold analysis revealed a trend toward higher cancellation rate associated with a MOV of <2 cm(3) (21.1% vs. 7.3%). CONCLUSION(S): Although MOV correlated with IVF stimulation parameters, its use as an adjunct in counseling patients during IVF appears to be of limited value. A MOV <2 cm(3) was associated clinically with a higher cancellation rate (21.1%) and a lower pregnancy rate (31.6%) in those cycles not cancelled. However, these values do not deviate far from the mean national IVF outcome rates. There was no absolute MOV that was predictive of pregnancy outcome or cycle cancellation.

Cohort Studies↗
PubMed2004

Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium.

OBJECTIVE: To examine the ultrastructural characteristics of extracellular matrix and mature collagen fibrils in uterine leiomyomas and compare them with those in adjacent normal myometrium. DESIGN: Analysis of paired leiomyoma-myometrium in surgical specimens. SETTING: Research center and tertiary care center. SUBJECT(S): Women undergoing medically indicated hysterectomy for symptomatic uterine leiomyomas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Appearance and spatial orientation of the collagen fibrils in leiomyomas compared with myometrium. RESULT(S): Observation of specimens at x 12,500 magnification indicated that collagen fibrils were more abundant, loosely packed, and arrayed in a nonparallel manner in leiomyomas compared with myometrium. Random areas were examined at x 6,500 to x 64,000 magnification and revealed collagen fibrils of equal diameter in both leiomyomas and myometrium. However, an ordered and regular barbed appearance was present in collagen fibrils from myometrium but was lacking in leiomyomas. CONCLUSION(S): Leiomyomas contain an abnormal collagen fibril structure and orientation, which suggests that the well-regulated fibril formation in myometrium is altered in leiomyomas. Alterations in collagen genes may play a role in the pathogenesis of leiomyomas.

Adult↗
PubMed2003

New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2.

In the post-Genome era, new concepts emerge about the growth regulation of uterine leiomyomata. Screening of leiomyoma and myometrial tissues with DNA arrays revealed numerous genes up-regulated in leiomyomata that were not known to be expressed in the human uterus. GluR2, a subunit of a ligand-gated cation channel, is up-regulated in leiomyomata relative to myometrium by 15- to 30-fold at the protein and mRNA level and is localized in endothelial cells. GluR2 pre-mRNA in leiomyoma and myometrial tissues is nearly 100% edited at the Q/R site, indicative of low Ca(2+) permeability of the ion channels. In spontaneous leiomyomata in women or leiomyomata induced in the guinea pig model, there is a likely synergism linking increased production of estradiol and all-trans retinoic acid with up-regulation of nuclear receptor PPARgamma and RXRalpha proteins to support tumor growth. GluR2 might be coupled to this synergism directly or via interleukin-17B, kinesin KIF5 or related genes also up-regulated in leiomyomata. GluR antagonists should be tested as inhibitors of leiomyoma growth.

Female↗
PubMed2003

A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles.

OBJECTIVE: To determine the predictive value and define threshold values for basal antral follicle count in patients undergoing IVF. DESIGN: Prospective cohort analysis. Tertiary care center. Two hundred eighty-nine patients. Transvaginal ultrasonography before starting gonadotropin administration. MAIN OUTCOME MEASURES: Number of oocytes retrieved, basal hormone levels, and cycle outcomes. RESULTS: Pregnant patients had significantly more antral follicles (13.8 +/- 7.5 vs. 12.4 +/- 10.0). Patients in whom cycles were canceled had significantly fewer antral follicles (7.6 +/- 4.8 vs. 13.7 +/- 8.8). Antral follicle count significantly correlated with most prestimulation and poststimulation IVF variables. Threshold analysis demonstrated a lower pregnancy rate (23.5% vs. 57.6%) and a higher cancellation rate (41% vs. 6.4%) associated with having four or fewer antral follicles. CONCLUSION(S): The basal antral follicle count identified patients who responded poorly to IVF stimulation. Having four or fewer antral follicles was associated with a high cancellation rate (41%) and, in patients without a cancelled cycle, a low pregnancy rate (23%). However, no antral follicle count absolutely predicted pregnancy or cycle cancellation.

Cohort Studies↗