Search PubMed⌕ Search

Biomedical subjects

D L Olive

Publications and source records attributed to D L Olive.

At least 73 records · Page 4Linked to original sources
PubMed1996

Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube.

OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1 alpha, tumor necrosis factor-alpha, and transforming growth factor-beta enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-beta 1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 +/- 89 vs 25 +/- 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-beta alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-alpha alone or in combination with interleukin-1 alpha enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies.

Adult↗
PubMed1996

The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program.

OBJECTIVE: To investigate the effect of endometriosis on implantation. DESIGN: Case-control study from Yale University IVF-ET program. PATIENTS: Two hundred eighty-four consecutive IVF cycles were analyzed retrospectively. Patients with endometriosis only (n = 35; 89 cycles) were compared with an age-matched control group with tubal infertility (n = 70; 147 cycles) and also to a group with unexplained infertility (n = 15; 48 cycles). Data from the endometriosis group was analyzed further in subgroups of minimal-mild (43 cycles) and moderate-severe (46 cycles). RESULTS: No difference was found in the number and the quality of oocytes retrieved and fertilization rates between the endometriosis, the tubal infertility, and the unexplained infertility groups. The quality and the number of embryos transferred in each group were comparable. A trend toward reduced pregnancy rate per transfer (14.8%) in the endometriosis versus tubal or unexplained infertility groups (25.7% and 23.3%, respectively) was observed. Implantation rate (gestational sac per transferred embryo) was significantly lower in the endometriosis versus the tubal infertility group (3.9% versus 8.1%; unexplained infertility group, 7.2%). Analysis of first cycles only across all groups revealed that the implantation rate also was significantly lower in the endometriosis versus the tubal infertility group (3.1% versus 9%; unexplained infertility group, 6.7%). Within the endometriosis group, although the pregnancy rate per cycle and per transfer were similar in subgroups, patients with minimal-mild endometriosis had the lowest implantation rate. CONCLUSION: We conclude that, in patients with endometriosis, implantation rate is low. Abnormal implantation, which may be secondary to endometrial dysfunction or embryotoxic environment, is a factor in endometriosis-associated subfertility.

Adult↗
PubMed1996

Peritoneal fluid from women with moderate or severe endometriosis inhibits sperm motility: the role of seminal fluid components.

OBJECTIVE: To examine the mechanism of sperm motility inhibition by peritoneal fluid (PF) from women with endometriosis. DESIGN: Prospective, randomized study. SETTING: University-based andrology laboratory. PATIENTS: Women with and without endometriosis. INTERVENTIONS: Fresh semen or Percoll-purified sperm fractions were combined with PF from women with endometriosis (n = 20), from fertile women without endometriosis (n = 10), or with physiological saline. MAIN OUTCOME MEASURE: Sperm motility parameters were determined with computer assisted semen analysis. Data were evaluated by the analysis of variance and the Student's t-test. RESULTS: Peritoneal fluid from women with minimal or mild endometriosis did not inhibit sperm motility in semen. Peritoneal fluid from women with moderate or severe endometriosis caused approximately 40%, 50%, and 80% declines in sperm motility and in percent progressive motile sperm after 4,7, and 24 hours, respectively. Sperm velocity was inhibited by approximately 30% and 60% after 7 and 24 hours, respectively. However, in the Percoll-purified sperm fractions the same PF did not inhibit sperm motility within the 4- to 7-hour time frame, and only a 17% to 42% inhibition occurred after the overnight incubation. Sperm velocity was not affected. CONCLUSION: Cellular components of seminal fluid appear to mediate the inhibitory action of PF. Assuming that the leukocyte components of semen and PF are common, the cell-mediated inhibition of sperm motility is a likely contributor to endometriosis related infertility.

Adult↗
PubMed1996

Growth-regulated alpha expression in the peritoneal environment with endometriosis.

OBJECTIVE: To investigate the presence and modulation of growth-regulated alpha, a member of the chemokine family with neutrophil chemotactic activity, in the peritoneal fluid of women with or without endometriosis. METHODS: Peritoneal fluid samples were obtained at laparoscopy from 63 women with endometriosis and 19 fertile women without endometriosis. Endometrial tissue was obtained from uteri after hysterectomy for reasons other than endometrial disease or from endometrial biopsies of reproductive-age women. Cellular RNA was extracted and northern blots were hybridized with an oligonucleotide probe complementary to a specific sequence of growth-regulated alpha messenger RNA. Growth-regulated alpha in peritoneal fluid and culture supernatant was quantified using enzyme-linked immunosorbent assay. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney tests. RESULTS: The median (range) concentration of growth-regulated alpha in peritoneal fluid samples from 19 normal fertile women was 27 pg/mL (0-108), from 24 women with moderate endometriosis 34 pg/mL (8-150), and from seven with severe endometriosis was 73 pg/mL (10-221) (P = .04, P = .01, respectively). In the moderate and severe endometriosis groups, the levels of growth-regulated alpha were significantly higher in the peritoneal fluid of women with untreated endometriosis (73 pg/mL [10-221]) than in women with medically treated endometriosis (25 pg/mL [8-47]). In mesothelial and endometrial stromal cells in culture, growth-regulated alpha messenger RNA and protein were detectable constitutively; however, both interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of growth-regulated alpha messenger RNA and protein in a dose- and time-dependent manner. CONCLUSIONS: Growth-regulated alpha levels are elevated in the peritoneal fluid of women with moderate and severe endometriosis. This chemotactic factor, which acts via the interleukin-8 receptor, may play a role in the pathogenesis of endometriosis.

Adult↗
PubMed1996

Evaluation and management of chronic pelvic pain.

Evaluating patients with chronic pelvic pain is complex. A detailed medical history should be ideally supplemented by psychologic evaluation and assessment of the woman's social background. At the time of physical examination, the location and intensity of the pain should be mapped. Assessment of pain relief with the administration of a local anesthetic to trigger points or selected nerves may be useful in predicting the potential efficacy of surgical interventions such as uterosacral nerve ablation. Appropriate tests include pelvic ultrasound and magnetic resonance imaging. Ultimately, laparoscopy may provide the final diagnosis. Management should address the underlying cause(s) of pain; when this cannot be done, it should focus on treating the pain itself. When appropriate, empiric administration of antidepressants may be considered. In selected women, therapeutic goals may be achieved by electrical stimulation of nerves.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Office microlaparoscopy under local anesthesia for chronic pelvic pain.

STUDY OBJECTIVE: To investigate the utility, tolerance, and costs associated with a program of office laparoscopy under local anesthesia using fiberoptic microlaparoscopes (<2 mm) and accessory instrumentation (<2 mm) for the evaluation of patients with chronic pelvic pain (CPP). DESIGN: Prospective, nonselected cohort study. SETTING: Office-based free-standing faculty practice at a tertiary care referral center. PATIENTS: All women with a history of CPP from February to June 1995 who required diagnostic laparoscopy were compared with a cohort of patients undergoing in office diagnostic laparoscopy for the evaluation of infertility during the same period. INTERVENTIONS: All patients underwent diagnostic office microlaparoscopy under local anesthesia (OLULA) with supplemental intravenous sedation, as well as conscious pain mapping. MEASUREMENTS AND MAIN RESULTS: A specific questionnaire was developed to follow all aspects of patient acceptance and tolerance of the procedures, and all patients were queried preoperatively, and 30 minutes and 1 week postoperatively. Pain was evaluated with a modification of the McGill pain inventory. A subset of questions evaluated the length of time until usual activities were resumed, anxiety level, and general acceptance of the procedure including set-up, operative time, and recovery time until discharge. Overall, there was a high degree of patient acceptance and satisfaction with OLULA; however, women with CPP experienced greater intraoperative and postoperative pain than those with infertility. Some patients with CPP had a generalized visceral hypersensitivity to pain; all areas of the pelvis and bowel were sensitive, and pain was not completely blocked with local anesthesia. Average procedure length was similar for the two groups. Patients with CPP required greater postoperative analgesia and took longer to return to work. Conscious pain mapping identified a focal source of pain in three patients and generalized visceral hypersensitivity in a majority of patients with CPP. Neither of these were found in patients with infertility. Compared with traditional laparoscopy there was almost an 80% reduction in costs. CONCLUSION: Office laparoscopy under local anesthesia is safe and effective for the evaluation of patients with CPP and is less expensive than traditional laparoscopy. Although the procedure is better tolerated by women undergoing infertility evaluation, it was well tolerated by both groups. Conscious pain mapping helps identify potential areas of pelvic pain and helps further characterize patients with CPP.

Adult↗
PubMed1996

The range of normal.

One of the primary aspects of any test is its capacity to distinguish "normal" from "abnormal." However, the issue of what normal truly is remains complex. There are two categories: correlated normality and isolated normality. Each has numerous advantages and disadvantages, but the latter is much more common for defining normal. The method of establishing limits of normal varies depending on whether correlated or isolated normality is utilized. With correlated normality, the limits are dependent on whether the purpose of the test is discovery, exclusion, or confirmation. Isolated normality limits are frequently based on the consequences of being termed abnormal. It is imperative that normal limits be based on values of an appropriate reference group: the normal group should be healthy equivalents of the individual being tested. Finally, both intrapersonal and menstruational variations that result when multiple tests are performed on the same individual should be accounted for.

Diagnostic Tests, Routine↗
PubMed1996

Regression analysis and multivariate analysis.

Proper evaluation of data does not necessarily require the use of advanced statistical methods; however, such advanced tools offer the researcher the freedom to evaluate more complex hypotheses. This overview of regression analysis and multivariate statistics describes general concepts. Basic definitions and conventions are reviewed. The types of regression analysis are then discussed, including simple regression, multiple regression, multivariate multiple regression, and logistic regression. The various steps required to perform these analyses are described, and the advantages and disadvantages of each is detailed.

Analysis of Variance↗
PubMed1996

Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells.

Interleukin-8 (IL-8) is a chemoattractant and activating factor for human neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with endometriosis has been shown to have increased neutrophil chemotactic activity. We postulate that IL-8 may be an important modulator in the pathogenesis of endometriosis and adhesion formation. We first investigated IL-8 concentrations in the peritoneal fluid of women with or without endometriosis, then assessed peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1 pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1 alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml) for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1 alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time-dependent manner. Non-treated mesothelial cells in culture also produced and secreted IL-8 protein quantified by ELISA, but again higher concentrations were induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8 concentrations were elevated in peritoneal fluids from women with endometriosis. Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL-8 protein. The regulated expression of this angiogenic factor may play a role in pathogenesis of endometriosis.

Ascitic Fluid↗
PubMed1996

Cytokine induction of heat shock protein in human granulosa-luteal cells.

The infiltration of leukocytes is a characteristic feature of luteolysis in humans. Leukocytes are known to generate physiological inducers of cell stress such as cytokines which have been implicated as mediators of functional luteal regression. In cells exposed to stress, a response characterized by an increase in heat shock protein (HSP) synthesis occurs. Recently, the induction of HSP-70 in rat luteal cells has been shown to inhibit luteinizing hormone (LH) and cAMP-sensitive progesterone production, possibly by interfering with the translocation of cholesterol to the mitochondrial cytochrome P450scc. We therefore investigated whether HSP-70 is induced in human granulosa-luteal cells and its relationship to steroidogenesis. [35S]Methionine labelling showed an increase in a 70 kDa protein after heat treatment which was demonstrated to be HSP-70 by Western analysis using monoclonal antibodies against the constitutive and inducible forms of HSP-70. Induction of HSP-70 in human granulosa-luteal cells was also seen with interferon (IFN) gamma (10 ng/ml), tumour necrosis factor (TNF)-alpha (100 ng/ml) and a combination of IFN gamma/TNF-alpha (10/50 ng/ml). Interleukin-1 beta (IL-1 beta) (30 ng/ml) showed minimal induction of HSP-70 above control values. An increase in activated heat shock factor, which binds to the heat shock transcriptional control element, was detected after heat shock, IFN/TNF, and IFN treatment. Coincident with the induction of HSP-70 by heat shock was the inhibition of progesterone production compared with non-shocked granulosa-luteal cells. Heat shock inhibition of progesterone synthesis was partially reversed by the cell- and mitochondria-permeant cholesterol analogue, 22R-hydroxycholesterol. Cell viability was unaffected by heat treatment. White blood cell-depleted granulosa-luteal cell cultures treated with IFN demonstrated a significant reduction in progesterone production. Treatment with IFN/TNF, TNF, and IL-1 also decreased progesterone secretion, although statistical significance was not achieved. These findings provide evidence that a stress response occurs in human granulosa-luteal cells in response to heat and cytokines. The inhibition of gonadotrophin-sensitive steroidogenesis coincident with the induction of HSP-70 synthesis by physiological agents which are present in the corpus luteum implicates HSP-70 as a potential mediator of luteolysis in the human.

Animals↗
PubMed1996

Transvaginal uterine cervical dilation with fluoroscopic guidance: preliminary results in patients with infertility.

PURPOSE: To assess efficacy of uterine cervical dilation performed with fluoroscopic guidance to treat patients with infertility who have cervical stenosis, false channels within the endocervical canal, or both. MATERIALS AND METHODS: Fifteen patients in whom infertility was diagnosed were referred because the uterine lumen could not be accessed. Three of the patients had endometriosis. With fluoroscopic guidance, the cervix was cannulated and the endocervical canal was dilated with an angioplasty balloon or with dilators. Five patients underwent simultaneous fallopian tube recanalization. Five of 15 patients who underwent dilation subsequently underwent in vitro fertilization for embryo transfer (IVF-ET) or intrauterine insemination. RESULTS: Four patients became pregnant. Of those four, one underwent IVF-ET and one underwent intrauterine insemination. Two patients became pregnant spontaneously. In the five patients who underwent IVF-ET or intrauterine insemination and in the remaining eight patients, the cervix could be easily cannulated up to 7 months after dilation. CONCLUSION: Dilation of the uterine cervix may provide options for treatment in selected patients with infertility. The effect of dilation on patients with other sequelae of cervical obstruction such as endometriosis remains uncertain.

Adult↗
PubMed1996

Interleukin-8 expression and modulation in human preovulatory follicles and ovarian cells.

Just before the time of ovulation, the number of neutrophils increases markedly in the thecal layer of the leading follicle. A preovulatory rise in chemotactic activity for neutrophils in human follicular fluid has also been detected. We hypothesized that interleukin-8 (IL-8), a neutrophil chemoattractant/activating factor and a potent angiogenic agent, may be an important modulator of leukocyte chemotaxis in ovulatory function. In this regard we investigated the expression and modulation of IL-8 in human follicular fluid samples from patients undergoing in vitro fertilization-embryo transfer therapy and in ovarian stromal and granulosa-lutein cell cultures. The concentration of IL-8 in pre-hCG follicular fluid samples (n = 4) was 16 +/- 12 (mean +/- SEM) pg/ml, and that in post-hCG samples (n = 101) was 262 +/- 45 pg/ml (P = 0.001). In post-hCG samples, the concentration of IL-8 in an individual follicle correlated with the size of that follicle (r = 0.61; P = 0.02). We also observed a correlation between serum IL-8 levels (22 +/- 3 pg/ml) and follicular fluid levels (303 +/- 143 pg/ml), with a 14-fold gradient (r = 0.71; P = 0.01) in 11 patients tested for both. IL-8 messenger RNA (mRNA) and the protein were expressed constitutively in ovarian stromal cell cultures, and the level was increased by IL-1 alpha and tumor necrosis factor-alpha in a time- and concentration-dependent manner. hCG and LH induced higher levels of IL-8 mRNA expression and protein production. Granulosalutein cells also expressed IL-8 mRNA and protein, and the levels were increased by IL-1 alpha and tumor necrosis factor-alpha. Importantly, progesterone suppressed both basal and IL-1 alpha-stimulated IL-8 expression in stromal and granulosa-lutein cell types. In summary, we found that IL-8 levels are elevated in periovulatory follicular fluid, and both granulosa-lutein and ovarian stromal cells express the mRNA and produce the protein. The modulation of IL-8 in these cell cultures by steroid and trophic hormones suggests that IL-8 may play an important role in the physiology of ovulation, such as timely follicular rupture and neovascularization of the corpus luteum.

Adult↗
PubMed1996

The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: a potential role in human implantation.

Leukemia inhibitory factor (LIF) is a multifunctional glycoprotein strongly associated with normal implantation in the mouse. We have recently determined that LIF is expressed in the human endometrium in a menstrual cycle dependent manner. Maximal expression is observed between days 19 and 25 of the menstrual cycle, coinciding with the time of human implantation. In this study we have utilized purified cultures of human cytotrophoblasts to examine the effects of LIF on several morphologic and biochemical markers of the trophoblastic differentiation. We purified human cytotrophoblasts from term placentae and cultured them with and without LIF (10 ng/mL). The secretion of human CG, oncofetal fibronectin, and progesterone were measured at 24, 48, 72, and 96 h. Northern blot analysis was used to assess messenger RNA (mRNA) expression of beta hCG and oncofetal fibronectin. We found that LIF markedly decreased trophoblast production of hCG protein at 72 and 96 h, as well as expression of beta hCG mRNA. LIF also significantly increased the expression of oncofetal fibronectin mRNA and secretion of the protein. LIF did not affect steroidogenic activity of cultured trophoblasts, as determined by progesterone production. These biochemical changes are characteristic of cytotrophoblast differentiation toward an anchoring extravillous phenotype. Thus, LIF appears to be an important regulator of human embryonic implantation by directly modulating trophoblast differentiation.

Blotting, Northern↗
PubMed1995

Similarities and differences between anonymous and directed candidates for oocyte donation.

PURPOSE: To compare anonymous and directed candidates for oocyte donation within a single program. METHODS: 75 consecutive candidates for oocyte donation (49 anonymous and 26 directed) were studied using a semistructured interview to collect data on demographics, psychosocial history, motivation, and candidate views on disclosure to a potential child. RESULTS: Donor groups were similar with regard to race, religion and education. Anonymous donors (mean age 27.33 years, SD 4.17) were significantly younger than directed donors (mean age 37.54 years, SD 4.94), (t = -4.83, df = 73, p < 0.001). Marital duration was significantly longer for directed donors (6.92 years, SD 5.64) versus (2.57 years, SD 3.96) for anonymous donors (t = -3.50, df = 38.47, p = .001). Forty-one percent of anonymous and 69% of directed donors had previous pregnancies (X2 = 4.60, p < .05). A greater percentage of anonymous donors (34.7%) felt that the potential child should be informed of his or her origins, compared to 19% of directed donors, but this difference fell short of statistical significance. CONCLUSIONS: There were more similarities than differences among groups of potential donors with the exception of age, marital status, and previous pregnancies. Differing views about disclosure were suggested in both groups with anonymous donors tending to opt for disclosure.

Adult↗
PubMed1995

The role of gonadotropins in ovulation induction.

Currently two types of gonadotropin preparations are commercially available for ovulation induction: menotropins and follicle-stimulating hormone (FSH). Proper use of these agents is directed by many factors. Concern about the FSH-luteinizing hormone ratio and the bioconsistency of the preparations suggests the use of FSH in most situations. Regimens based on short-term incremental increases in gonadotropin dose (based on frequent sonographic and biochemical monitoring) seem to produce the highest pregnancy rates. Individualization of the patient's ovulation induction course on the basis of history of medication use and the reasons for ovulation induction therapy are also essential to optimize outcomes.

Female↗