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Biomedical subjects

M S Rein

Publications and source records attributed to M S Rein.

At least 37 records · Page 2Linked to original sources
PubMed1993

Leuprolide acetate depot decreases the number of nucleolar organizer regions in uterine leiomyomata.

Women with symptomatic uterine myomas were randomized to receive LA depot or placebo for 12 weeks before myomectomy. Silver staining nucleolar organizer regions (AgNORs) per nuclei were assessed in the tissue obtained at the time of myomectomy. Myoma tissue from women treated with LA depot before myomectomy had significantly fewer AgNORs per nuclei than myoma tissue obtained from women treated with placebo. Leuprolide acetate depot may reduce the number of proliferating cells in myomas.

Adult↗
PubMed1993

Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors.

Uterine leiomyomas, which are myometrial smooth muscle tumors, secrete PRL. We investigated the actions of several hormones known to stimulate PRL secretion by the pituitary gland or decidua on PRL secretion by leiomyoma-derived smooth muscle cells (SMC) in monolayer culture. Cultures were verified to be SMC by immunostaining for smooth muscle alpha-action and desmin. Hormone treatments were performed in serum-free medium for 72 h. Medium was harvested every 24 h and assayed for PRL. 17 beta-Estradiol, progesterone, TRH, insulin-like growth factor-I, epidermal growth factor, and the GnRH agonist leuprolide did not affect PRL secretion by these SMC. Insulin caused a significant suppression of PRL secretion by 72 h, and this was accompanied by a 64% increase in total cell protein per well, which represented an increase in cell number. Cells were also plated at various densities to determine the effects of cell number on PRL secretion. The amount of PRL secreted per 1000 cells decreased significantly as cell number per well increased. Northern blot analysis identified PRL mRNA in fresh leiomyoma tissue. PRL mRNA in three independent cultures of SMC was then detected by reverse transcription and the polymerase chain reaction. Hybridization occurred only with the expected band of approximately 423 basepairs in size. We conclude that leiomyomas express PRL mRNA in vivo and that leiomyoma-derived SMC in culture continue to express the PRL mRNA and secrete PRL in the absence of ovarian steroids. PRL secretion by SMC in culture appears to be modulated primarily by changes in cell density.

Base Sequence↗
PubMed1993

A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri.

Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.

Adult↗
PubMed1993

The concentrations of collagen-associated amino acids are higher in GnRH agonist-treated uterine myomas.

OBJECTIVE: To test the hypothesis that the effects of estrogen reduction on uterine leiomyoma regression are mediated through changes in cell density or the extracellular matrix. METHODS: Uterine myomas were obtained from 20 women who had received randomly either the GnRH agonist leuprolide acetate depot for 3 months or placebo. The biochemical and morphologic characteristics studied included: total protein, DNA, and amino acid concentrations; histologic appearance; collagen content; and nuclear density. RESULTS: The absolute and relative concentrations of hydroxylysine, hydroxyproline, glycine, and proline were significantly greater (P < .05) in uterine myomas from patients pretreated with a GnRH agonist compared with placebo-treated controls. The GnRH agonist was also associated with trends toward increased mean total protein, DNA, and nuclear density, but the differences did not reach statistical significance. CONCLUSIONS: The concentrations of the amino acids contained in collagen were significantly greater in uterine myomas from patients treated with the GnRH agonist compared to myomas from placebo-treated controls. In addition, our observations suggest that the reduction in uterine myoma volume associated with GnRH agonist therapy is associated with alterations in the extracellular matrix.

Amino Acids↗
PubMed1993

Hysterosalpingography contrast media and chromotubation dye inhibit peritoneal lymphocyte and macrophage function in vitro: a potential mechanism for fertility enhancement.

OBJECTIVE: To determine the effects of hysterosalpingography (HSG) contrast media (CM) and chromotubation dye on peritoneal lymphocyte proliferation and macrophage phagocytosis in vitro. DESIGN: Peritoneal fluid (PF) lymphocytes and macrophages were isolated from 40 subfertile women undergoing diagnostic laparoscopy and 12 fertile women having laparoscopic tubal ligation. Dilutions of renografin, ethiodol, methylene blue, and indigo carmine were added to peritoneal lymphocyte and macrophage cultures. Tissue culture media alone served as control. Lymphocyte proliferation was assessed by hemocytometer counts and 3H-thymidine incorporation. Macrophage function was determined by phagocytosis of fluorescent microspheres. RESULTS: Peritoneal lymphocyte proliferation and macrophage phagocytosis were significantly inhibited by renografin, ethiodol, methylene blue, and indigo carmine in a dose-dependent manner. CONCLUSION: Inhibition of PF immune cell function by HSG CM and chromotubation dye may provide a potential mechanism for fertility enhancement after these diagnostic procedures.

Cell Survival↗
PubMed1993

The reproducibility of the revised American Fertility Society classification of endometriosis.

OBJECTIVE: To assess the degree of intraobserver and interobserver variability in endometriosis staging using the revised American Fertility Society (AFS) classification of endometriosis. DESIGN: Videotapes of laparoscopies of 20 patients with endometriosis were each scored twice by five observers. SETTING: The reproductive endocrine unit of a tertiary care, university-affiliated hospital. SUBJECTS: Five subspecialty-certified reproductive endocrinologists. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Variability in assigned score was measured for each of the five components of the AFS classification, as well as total scores and stage of endometriosis. RESULTS: There was considerable variability in the scores assigned to each videotape, both by the same observer and by different observers. The grand total score, which ranged from 0 to 90, varied with an SD of 13.44 when a single patient was rated twice by the same observer and varied with an SD of 17.12 when a single patient was rated by two different observers. Among individual components of the score, the greatest variability occurred in endometriosis of the ovary and cul-de-sac obliteration, with less variability observed for peritoneum endometriosis and for ovarian and tubal adhesions. Comparison of intraobserver and interobserver scores resulted in a change in endometriosis stage in 38% and 52% of patients, respectively. There were statistically significant differences in mean endometriosis scores among the observers in four of the five anatomic categories examined. CONCLUSIONS: Intraobserver and interobserver variability was high for ovarian endometriosis and cul-de-sac subscores using the revised AFS classification of endometriosis.

Endometriosis↗
PubMed1992

Interleukin-4 fails to inhibit interferon-gamma-induced activation of human colostral macrophages.

IL-4 abrogates the IFN-gamma-mediated activation of peripheral blood monocytes (M. Lehn, W. Y. Weiser, S. E. Engelhorn, S. Gillis, and H. G. Remold, 1989, J. Immunol. 143, 3020). In contrast, in colostral macrophages IL-4 fails to inhibit IFN-gamma-induced increase of H2O2 production and of antileishmanial activity. Flow cytometric analysis shows that the number of IL-4 receptors (IL-4R) is 2.4 times higher on colostral macrophages than on peripheral blood monocytes and that 23% of the colostral macrophages have detectable IL-4R in contrast to 2% of the blood monocytes. Thus, colostral macrophages are functionally different from peripheral blood monocytes in their response to IL-4 and in the numbers of IL-4R. This difference could reflect specific requirements for their protective performance in the neonatal intestine.

Animals↗
PubMed1992

Recurrence of myomas after myomectomy in women pretreated with leuprolide acetate depot or placebo.

The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a randomized, double-blind, P-controlled study of the efficacy of LA depot before myomectomy. After 27 to 38 months of follow-up, the recurrence of myomas was found to be greater when at least four myomas were resected. Myoma recurrence was not associated with pretreatment or preoperative uterine volume, resected myoma mass, or preoperative medical therapy.

Adult↗
PubMed1992

The appearance of one-pronuclear human oocytes is associated with a better ovulation-induction response and successful pregnancy outcome.

OBJECTIVE: To study the relationship between the presence of one-pronuclear oocytes in in vitro fertilization (IVF) patients and ovulation-induction response, oocyte and embryo development, and clinical outcome. DESIGN: Retrospective analysis of 535 consecutive IVF retrievals. Retrievals in which one or more oocytes exhibited one pronucleus were compared with retrievals in which no one-pronuclear oocytes (control) were observed. The following one-pronuclear versus control subgroups were also examined: leuprolide acetate/human menopausal gonadotropin (LA/hMG) ovulation inductions, high estradiol (E2) response cases, and retrievals in which a large number of oocytes (greater than or equal to 15) were recovered. SETTING: Brigham and Women's Hospital, a tertiary care, university-affiliated hospital. PATIENTS: Three hundred forty-six IVF patients were treated between January 1989 and May 1991. MAIN OUTCOME MEASURES: Parameters examined included E2 concentration and number of follicles with maximum diameter greater than or equal to 12 mm on day of human chorionic gonadotropin administration; number of total and mature oocytes retrieved; total fertilization rates; number of embryos; and percent per retrieval of embryo transfers (ETs), clinical pregnancies, and ongoing-livebirths. RESULTS: The one-pronuclear patients had higher E2 levels and larger number of follicles, yielded significantly more total and mature oocytes, had a higher overall fertilization rate, produced more embryos, and had higher ET, clinical pregnancy and ongoing-livebirth rates per retrieval than did the control patients. Analysis of the subgroup populations revealed no significant differences in the majority of the main outcome measures studied; however, the one-pronuclear patients yielded significantly more total and mature oocytes per retrieval. CONCLUSIONS: Although there was an increase in the clinical and ongoing-livebirth pregnancy rates (PRs) in one-pronuclear patients, this was probably associated with an improved ovulation-induction response in the one-pronuclear patients. They achieved significantly higher E2 levels, recruited a larger number of follicles, and yielded more oocytes and embryos per retrieval than the control patients. When only the LA/hMG, E2 greater than or equal to 1,500 pg/mL, or the greater than or equal to 15 oocytes/case retrievals were analyzed, the PRs were no longer different; however, the one-pronuclear patients still yielded significantly more total and mature oocytes per retrieval than the controls. Therefore, the appearance of one-pronuclear oocytes is probably associated with the maturation stage of the oocytes obtained and is indicative of an ovulation induction in which a large number of preovulatory, metaphase II oocytes have been recruited.

Cell Nucleus↗
PubMed1992

The effect of baseline complex ovarian cysts on in vitro fertilization outcome.

STUDY OBJECTIVE: To determine the effect of baseline complex ovarian cysts on controlled ovarian hyperstimulation and in vitro fertilization (IVF) outcome. DESIGN: Retrospective analysis with stratification by stimulation regimen and the presence or absence of surgically documented endometriosis. PATIENTS: Two hundred sixty-one women undergoing IVF from May 1, 1989 to December 31, 1990. MAIN OUTCOME MEASURES: The outcome measures assessed were the maximum estradiol (E2) concentration on day of human chorionic gonadotropin (hCG) administration, number of follicles with maximum diameter greater than or equal to 15 mm, number of follicles with maximum diameter greater than or equal to 12 mm, number of days to hCG administration, number of ampules of human menopausal gonadotropin (hMG) used, number of oocytes retrieved and fertilized, number of embryos transferred, and pregnancy and cycle cancellation rates. RESULTS: There were no statistical differences between cyst and noncyst groups in any of the above parameters of IVF performance. In a single subgroup, patients with endometriosis stimulated with hMG and patients with cysts had significantly lower E2 concentrations than patients without cysts. CONCLUSION: The presence of a complex cyst on a baseline ultrasound does not appear to adversely affect IVF cycle outcomes.

Endometriosis↗
PubMed1991

Cytogenetic abnormalities in uterine leiomyomata.

Uterine leiomyomata are thought to be monoclonal tumors; however, the factors involved in the neoplastic proliferation of uterine leiomyomata are unknown. The purpose of the present study was to characterize uterine leiomyomata using cytogenetic techniques. Thirteen leiomyoma specimens were obtained by hysterectomy or myomectomy. Short-term cultures were successfully established for all specimens, and metaphase spreads were prepared by conventional techniques. Clonal chromosome rearrangements were detected in seven leiomyoma specimens (54%). These rearrangements involved chromosome bands 12q14-15 in five specimens, including three tumors with a specific translocation, t(12;14)(q14-15;q23-24). Chromosome rearrangements involving chromosome band 7q22 were identified in two specimens. A normal 46,XX karyotype was observed in six specimens. Myometrial specimens from two patients with abnormal leiomyoma karyotypes were normal cytogenetically. These results suggest that spontaneous chromosome rearrangements may be responsible for the initiation and proliferation of leiomyoma growth.

Adult↗
PubMed1990

Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis.

Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment. Leiomyomas are common, estrogen-sensitive, benign neoplasms that decrease in size by 40% to 50% during gonadotropin-releasing hormone agonist treatment. During gonadotropin-releasing hormone agonist therapy most women are amenorrheic. After discontinuation of gonadotropin-releasing hormone agonist treatment, uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs. Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy. This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin "add-back" treatment as a potential long-term medical therapy for women with symptomatic leiomyomas. Finally, an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues, is presented.

Buserelin↗
PubMed1990

Fasting serum growth hormone and insulin-like growth factor-I and -II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo.

Eighteen patients with leiomyomata uteri were randomized to receive either leuprolide acetate depot (n = 9) 3.75 mg intramuscularly (IM) or placebo (n = 9) IM every 4 weeks for four injections. Leuprolide acetate treated patients demonstrated a reduction in mean uterine volume of 34% and a decrease in serum estradiol (E2) concentrations from 120 +/- 21 pg/mL (mean +/- standard error) to 16 +/- 9 pg/mL. Leuprolide acetate treated patients also demonstrated significant decreases in serum growth hormone (GH) (3.0 +/- 0.4 ng/mL versus 1.4 +/- 0.4 ng/mL) and insulin-like growth factor-I (IGF-I) concentrations (3.3 +/- 0.4 U/mL versus 1.3 +/- 0.2 U/mL) over the 12 week treatment period. Serum IGF-II levels did not change. Mean uterine volume and serum E2, GH, IGF-I, and IGF-II concentrations did not change in placebo-treated patients. These data suggest that hypoestrogenism is associated with decreases in circulating GH and IGF-I.

Adult↗
PubMed1990

Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist.

Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion.

Antineoplastic Agents↗
PubMed1990

Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate.

The reduction in uterine and fibroid volume associated with the chronic administration of a gonadotropin-releasing hormone agonist (GnRH-a) is thought to be secondary to the analogue induced hypoestrogenic state. Our hypothesis was that the concentration of bioactive estrogen receptors (ER) and progesterone receptors (PR) may be important in the regulation of fibroid growth. The purpose of this study was to determine ER and PR content in fibroids and myometria from women pretreated with GnRH-a compared with controls. Tissue was obtained from 20 premenopausal women with uterine fibroids who were randomized to receive either leuprolide acetate depot, 3.75 mg intramuscularly every 28 days for four injections (n = 10) or placebo (n = 10) before myomectomy. The mean fibroid ER and PR content was significantly greater than the mean myometrial ER and PR content. The mean fibroid ER content for GnRH-a-treated patients was significantly greater than in placebo-treated patients (143.3 +/- 22.8 versus 36.1 +/- 14.3 fmol/mg). The mean fibroid PR and the mean myometrial ER and PR content were not significantly different between treatment groups. Clinically, the significant increase in fibroid ER may be an explanation for the rapid regrowth of fibroids observed after the cessation of GnRH-a therapy.

Antineoplastic Agents↗
PubMed1990

The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist.

The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗