Search PubMed⌕ Search

Biomedical subjects

A A Murphy

Publications and source records attributed to A A Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1996

Treatment of endometriosis with the antiprogesterone mifepristone (RU486)

OBJECTIVE: To evaluate the safety and efficacy of an antiprogesterone (mifepristone, RU486; Roussel-Uclaf, Romaineville, France) on endometriosis. DESIGN: An open, prospective clinical trial. SETTING: The clinical practice of an academic faculty. PATIENTS: Nine women with endometriosis were studied. INTERVENTIONS: RU486 (50 mg/d) was administered for 6 months. MAIN OUTCOME MEASURES: Daily symptom inventories and urinary steroid metabolites were assessed before, during, and after treatment. Blood for hormone analysis was obtained weekly for 4 weeks and monthly thereafter. The extent of endometriosis, bone mineral density, circadian rhythm of cortisol, and LH pulsatility were determined before and after treatment. Safety laboratory measurements were made before and at 1, 2, and 6 months of treatment. RESULTS: Pelvic pain and uterine cramping improved in all patients. Endometriosis regressed by 55%. All patients exhibited endocrine features of anovulatory amenorrhea without hypoestrogenism. A rise in serum LH and T levels was observed during the first month of treatment and one patient developed an elevation of liver transaminases during the last month of treatment. All other measurements were unchanged. CONCLUSION: RU486 appears to be effective in improving the symptoms and causing regression of endometriosis in the absence of significant side effects.

Adolescent↗
PubMed1996

Inhibition of oxidative modification of proteins by RU486.

OBJECTIVES: To elucidate further the antioxidant properties of RU486. We determined whether it can protect biologic molecules such as proteins (albumin, low-density lipoprotein [LDL] and oxidized LDL) from damage by pre-existing lipid peroxides. DESIGN: In vitro study. INTERVENTIONS: We tested the effects of RU486 on the formation of fluorescent oxidatively modified proteins by pre-existing lipid peroxides. We used two model systems, the incubation of oxidized linoleic acid with serum albumin and the incubation of human LDL with copper. MAIN OUTCOME MEASURES: The formation of modified protein was established by determining fluorescence at excitation wavelength of 330 nm and emission wavelength between 390 and 500 nm. Modified protein has a characteristic emission between 425 and 430 nm. RESULTS: The addition of increasing amounts of RU486 inhibited the formation of fluorescent oxidatively modified protein products in both model systems. CONCLUSION: These results provide evidence that RU486 not only can prevent the formation of lipid peroxide, but also can block the formation of fluorescent protein adducts in the presence of pre-existing lipid peroxides.

Antioxidants↗
PubMed1995

Effect of RU-486 and related compounds on the proliferation of cultured macrophages.

PROBLEM: Macrophages are implicated in the pathophysiology of endometriosis and are influenced by anti-inflammatory steroids as well as anti-oxidants. METHODS: We tested the effect of RU-486, an antiprogesterone, antiglucocorticoid and an antioxidant, on the proliferation of RAW macrophages. RESULTS: The incorporation of 3H-thymidine was significantly inhibited by both progesterone and RU-486. Progesterone and RU-486, in combination, synergistically inhibited macrophage growth. In contrast, dexamethasone-stimulated growth was antagonized by RU-486 in a dose dependent manner. ZK 112,993 which is structurally related to RU-486 but lacks antioxidant properties, also inhibited thymidine incorporation. The synergistic effect of RU-486 and ZK 112,993 with progesterone implicate a mechanism of action separate from receptor bound antagonists. A cell permeable antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the incorporation of 3H-thymidine into cells. CONCLUSIONS: These results suggest novel therapeutic modalities in the management of endometriosis via antiglucocorticoid as well as antioxidant mechanisms.

Antioxidants↗
PubMed1995

Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) is superior to oxidized regenerated cellulose (Interceed TC7+) in preventing adhesions.

OBJECTIVE: To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington, TX) on the development of postsurgical adhesions. DESIGN: A multicenter, nonblinded, randomized clinical trial. SETTING: University medical centers. INTERVENTIONS: Each barrier was allocated randomly to the left or right sidewall of every patient. PATIENTS: Thirty-two women with bilateral pelvic sidewall adhesions undergoing reconstructive surgery and second-look laparoscopy. MAIN OUTCOME MEASURES: Adhesion score (on a 0- to 11-point scale), the area of adhesion (cm2), and the likelihood of no adhesions. RESULTS: The use of both barriers was associated with a lower adhesion score and area of adhesion postoperatively. However, those sidewalls covered with PTFE had a significantly lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM) and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions were present on the contralateral sidewall, the number of sidewalls covered with PTFE without adhesions was greater than those covered with oxidized regenerated cellulose (16 versus 2). CONCLUSION: Expanded polytetrafluoroethylene was associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized regenerated cellulose.

Adolescent↗
PubMed1995

Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect.

OBJECTIVE: To study the response of uterine leiomyomata to three daily doses of RU486 (5, 25, and 50 mg). DESIGN: Prospective nonrandomized trial of women with symptomatic leiomyomata. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS: Ten patients with symptomatic leiomyomata previously reported after treatment with 50 mg of RU486 daily for 3 months. Eleven patients treated with 25 mg of RU486 daily and nine patients placed on 5 mg of RU486 daily for 12 weeks. MAIN OUTCOME MEASURES: Changes in leiomyomata volume as measured with vaginal ultrasounds at baseline and monthly thereafter. Frequent blood samples for hematology, chemistry, and hormone levels were obtained. Twenty-four-hour urine collections for free cortisol and creatinine were obtained at baseline and at 12 weeks. RESULTS: All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% +/- 4.8% of baseline at 4 weeks, 60.5% +/- 6.6% at 8 weeks, and 51.0% +/- 9.2% after 12 weeks of treatment. Regressive response in patients treated with 25 mg of RU486 daily was 76.3% +/- 5.0% of baseline at 4 weeks, 54.0% +/- 5.1% at 8 weeks, and 44.0% +/- 5.0% after 12 weeks. At 5 mg of RU486 leiomyomata volume was 80.6% +/- 8.3% of baseline after 4 weeks, 63.7% +/- 14.6% after 8 weeks, and 74.4% +/- 19.8% after 12 weeks of therapy. CONCLUSIONS: Although acyclicity is seen at all three doses, an effective dose to cause a clinically significant (50%) decrease in leiomyomata volume appears to be 25 mg daily.

Adolescent↗
PubMed1995

Endometrial effects of long-term low-dose administration of RU486.

OBJECTIVE: To examine endometrial response to long-term low-does RU486 administration. DESIGN: Retrospective controlled study of women with endometriosis treated for 6 months with 50 mg RU486 daily for 6 months. Controls consisted of women in the follicular phase of a spontaneous cycle undergoing endometrial biopsy. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS AND INTERVENTIONS: Nine patients treated with long-term low-dose RU486 and nine normal cycling controls undergoing hysterectomy or endometrial biopsy for benign disease. MAIN OUTCOME MEASURES: Changes in endometrial morphology and immunohistochemical analysis for estrogen receptor (ER) and progesterone receptor (PR) protein. RESULTS: All patients treated with RU486 exhibited abnormal endometrial morphology. The endometrial glands were irregular in size and shape. The stroma was varied but consisted predominantly of dense cellular stroma with frequent mitotic figures. The glands were lined by a combination of epithelial types some of which were secretory. No cytologic atypia was seen. Levels of ER immunoreactivity, as determined by image analysis, were greater in the stroma with no difference in PR immunoreactivity compared with controls. No difference in ER and PR immunoreactivity were seen in the glands compared with normal controls. CONCLUSION: The generalized cystic changes demonstrated are consistent with a chronic unopposed estrogen effect and are concordant with hormonal data showing early to midfollicular phase levels of estrogens. They also are consistent with our findings of increased ER immunoreactivity in the stroma. Evidence of minimal P agonist effect was noted.

Adolescent↗
PubMed1994

Clinical efficacy of the antiprogesterone RU486 in the treatment of endometriosis and uterine fibroids.

To evaluate the long-term effects of treatment with RU486 and to test its efficacy in endometriosis, a 3-month trial was conducted to evaluate the effects of daily administration (100 mg/day or approximately 2 mg/kg/day) on the functional activity of the reproductive axis, as well as implants, in patients with symptomatic pelvic endometriosis. All women became amenorrhoeic and acyclic. However, ovarian suppression was incomplete. In 24 h sampling studies, mean luteinizing hormone (LH) and LH pulse amplitude were increased without a change in LH pulse frequency. Additionally, an antiglucocorticoid effect was demonstrated. Treatment resulted in improvement in pelvic pain in all subjects without significant changes in the extent of disease as evaluated by laparoscopy. We also attempted to reduce the growth of uterine fibroids by using 50 mg/day of RU486 for 3 months in 10 patients. Myoma size decreased approximately 22% at 4 weeks, 39% at 8 weeks and 49% at 12 weeks. Serum concentrations of LH, androstenedione and testosterone increased in the first 3 weeks of treatment and then returned to baseline. In conclusion, daily administration of RU486 resulted in ovarian inhibition and menstrual acyclicity and in an improvement in the pain associated with pelvic endometriosis and decreased the size of uterine fibroids. This ovarian inhibition was achieved without oestrogen deprivation and may provide a novel long-term approach to the treatment of ovarian steroid-dependent disease processes.

Abdominal Pain↗
PubMed1994

Antioxidant: a new role for RU-486 and related compounds.

RU-486 (17 beta-hydroxy-4-dimethylaminophenyl-17-alpha-propenyl estrone 4,9 diene-3-one; mifepristone) is suggested to act by binding to progesterone and glucocorticoid receptors. Based on its chemical nature, we anticipated that RU-486 may have potent antioxidant properties. We used the oxidation of LDL as our model system. RU-486 and a similar compound, onapristone, at 1-5-microM concentrations, decreased the formation of oxidized LDL. LDL isolated from plasma of subjects who were orally supplemented with RU-486 was resistant to oxidation, as compared to LDL isolated from control plasma. The antioxidant effect of RU-486 appears to reside in the dimethylaminophenyl side chain moiety. Reduction of the A-ring of the steroid molecule had no effect on its antioxidant property. Analogs of RU-486 which lack the dimethylaminophenyl group, were without antioxidant activity. Levonorgestrel, which lacks the dimethylaminophenyl group failed to inhibit the oxidation of LDL even at 100-microM levels. In contrast, ethinylestradiol and estradiol which do not possess the dimethylamino group, were able to inhibit the oxidation of LDL by virtue of their phenolic steroid "A" ring. Thus RU-486, with its long half life, high plasma concentrations, association with lipoproteins, and ability to readily enter the cell may have additional intra- and extra-cellular antioxidant effects.

Animals↗
PubMed1994

RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri.

More than a decade after the serendipidous discovery of RU486, numerous antiprogestins have been synthesized and studied. Interest in how antiprogestins exert their antagonist effect has led to novel information about the molecular mechanisms of progesterone action. The pivotal role that progesterone plays in reproductive biology has led to research in many areas where a potential role for these compounds may be found in health and disease. RU486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Uterine leiomyomata show a significant reduction in size after administration of RU486 for 3 months. Although much research remains to be carried out, RU486 appears promising as alternative therapies for these diseases.

Endometriosis↗
PubMed1994

The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study.

OBJECTIVE: Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume. STUDY DESIGN: Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography. RESULTS: Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. CONCLUSION: Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery.

Female↗
PubMed1993

Rapid regression of uterine leiomyomas in response to daily administration of gonadotropin-releasing hormone antagonist.

OBJECTIVE: The efficacy of acute and sustained pituitary gonadotropin down-regulation by the Nal-Glu GnRH antagonist (Nal-Glu) was evaluated in the treatment of uterine leiomyomas. DESIGN: Prospective, open clinical trial. PATIENTS: Seven normally cycling women with symptomatic leiomyomas. INTERVENTIONS: Nal-Glu (50 micrograms/kg per day) was administered subcutaneously for 3 months. MAIN OUTCOME MEASURES: Baseline ultrasound examinations were obtained and repeated monthly throughout treatment. Each leiomyoma was mapped and measured in three dimensions. Blood samples were drawn daily for 7 days, weekly for 4 weeks, and monthly for the remaining 2 months. RESULTS: Mean leiomyoma size decreased 52.8 +/- 7.3% (means +/- SD) after 1 month of therapy and remained unchanged for the remainder of the study. Serum levels of E2 (35.9 +/- 11.8 to 9.3 +/- 0.8 pg/mL, 131.7 +/- 43.3 to 34.0 +/- 1.4 pmol/L), estrone (37.3 +/- 7.5 to 13.0 +/- 2.5 pg/mL, 138.1 +/- 27.7 to 48.1 +/- 9.1 pmol/L), and P (1.6 +/- 1.1 to 0.3 +/- 0.01 ng/mL, 5.0 +/- 3.6 to 0.9 +/- 0.04 nmol/L) declined rapidly (within 48 hours) and remained suppressed throughout treatment. Serum LH, FSH, androstenedione, T, and DHEA levels did not change significantly. In two subjects who did not have surgical removal, leiomyomas grew to original size within the 1st month off drug. Six patients remained amenorrheic and the other subject spotted during the last 2 months of therapy. CONCLUSIONS: Continuous treatment with Nal-Glu induces immediate and sustained pituitary-gonadal down-regulation that results in regression in leiomyoma size. By circumventing GnRH agonist-induced pituitary-ovarian up-regulation, GnRH antagonists may prove to be superior tools in the medical management of leiomyomas.

Adult↗
PubMed1993

Regression of uterine leiomyomata in response to the antiprogesterone RU 486.

Uterine leiomyomata are steroid hormone dependent tumors which possess receptors for estrogen (ER) and progesterone (PR). We reasoned that an antiprogesterone (RU 486) may induce regression of leiomyomata by withdrawal of progesterone action and/or by its interference of estrogen action. Accordingly, we examined the effects of daily administration of RU 486 (50 mg) for a period of 3 months in 10 patients with uterine leiomyomata and regular menstrual cycles. Baseline ultrasound examinations were obtained and repeated monthly during treatment as a measure of leiomyomata volume. Hormonal parameters were monitored by blood samples obtained prior to treatment and daily for 7 days, weekly for 4 weeks and monthly for the duration of therapy. Myomectomy or hysterectomy was performed in 6 of 10 patients at the end of treatment. Leiomyomata and myometrial tissue was obtained for immunocytochemical analysis of ER and PR protein. Amenorrhea was induced in all patients during treatment. Leiomyomata volume (mean +/- SE) decreased 21.9 +/- 4.8% after 4 weeks, 39.5 +/- 6.6% (P < 0.001) after 8 weeks, and 49.0 +/- 9.2% (P < 0.001) after 12 weeks of treatment compared to pretreatment measurements. Serum LH levels (P < 0.005), but not FSH levels, more than doubled during the first 3 weeks of treatment with a concomitant increase in serum androstenedione (P < 0.006) and testosterone (P < 0.0001) levels. These elevated hormonal levels returned to baseline at 4 weeks without further changes during the remainder of treatment. A significant rise in serum dehydroepiandrosterone sulfate (P < 0.0001) and cortisol (P < 0.01) was seen at 12 weeks, suggesting an antiglucocorticoid effect of RU 486 has occurred. Serum estradiol, estrone, progesterone, sex hormone binding protein, thyroid-stimulating hormone, and PRL were unchanged from early follicular phase values. PR but not ER immunoreactivity was significantly reduced in both leiomyomata and myometrium after RU 486 treatment compared with tissues from untreated patients, suggesting that regression of tumors may be attained through a direct antiprogesterone effect. However, an alteration in ER functionality cannot be excluded. We conclude that RU 486 is well tolerated, safe, and effective; thus, it may prove to be a novel mode of management for uterine leiomyomata.

Adolescent↗
PubMed1992

Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial.

STUDY OBJECTIVE: To compare prospectively operative laparoscopy to laparotomy in the management of hemodynamically stable patients with ectopic pregnancy (EP). DESIGN, PATIENTS, Intervention: Patients with suspected EP presenting to a university-based residency teaching program were prospectively allocated to laparoscopy (n = 26) or laparotomy (n = 37) on alternating months for operative management. RESULTS: Operative times between laparoscopy and laparotomy did not differ significantly. Laparoscopy-treated patients had a significant reduction in estimated intraoperative blood loss, postoperative hospital stay, narcotic requirement, time to normal activity, and total hospital cost. There was no statistical difference in intrauterine pregnancy rates or in EP rates. CONCLUSIONS: In a university-based residency program, operative laparoscopy is a safe alternative for the management of appropriately selected patients with suspected EP.

Female↗
PubMed1992

Pediatric and adolescent gynecologic endocrinology.

Best described as a transformation from the infantile state to an accentuated dimorphic adult state, puberty is a sequence of events characterized by the secretion of gonadal hormones leading to the development of secondary sexual characteristics, gametogenesis, and reproductive function. In girls, the first signs of puberty may be evident at age 8, with the process largely completed by age 16; in boys, puberty commonly begins between ages 10 and 12 and is largely completed by age 18. Adrenarche, the secretion of adrenal androgens, starts between ages 6 and 8 and is clinically accompanied by pubarche. Premature pubarche should be diagnosed as either typical or atypical. In atypical premature pubarche, corticotropin testing is recommended to determine nonclassical adrenal enzyme deficiency of steroidogenesis. Children with either type of premature pubarche should be under continued follow-up throughout puberty. The trigger of the onset of puberty is still unknown. The presence of gonadotropin activity and possible circadian rhythm in the prepubertal years allows for new understanding in possible triggering mechanisms of puberty. Precocious puberty, which is associated with significant psychologic implications and possible pathology, must be categorized as complete precocious puberty with activation of the hypothalamic-pituitary axis or incomplete precocious puberty without activation of the central axis as effective therapies are so different. The categorization does not yield diagnoses, as there are multiple etiologies within each category. The treatment of central precocious puberty with gonadotropin-releasing hormone agonists will postpone pubertal progression to a more appropriate age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The effect of tetracycline on levels of oral contraceptives.

Despite the widespread use of tetracycline for treatment of dermatologic disorders and sexually transmitted diseases, the pharmacodynamics of oral contraceptive use in the presence of tetracycline has not been studied. Seven normal women ingested an oral contraceptive containing ethinyl estradiol 35 micrograms and norethindrone 1 mg in the follicular phase of the menstrual cycle. On day 0 baseline ethinyl estradiol and norethindrone levels were obtained at 0, 1/2, 3/4, 1, 2, 4, 12, and 24 hours after oral contraceptive administration. On day 1 tetracycline 500 mg was given orally every 6 hours while the oral contraceptive was continued. Tetracycline, ethinyl estradiol, and norethindrone levels were determined at the same time intervals as on day 0. Oral contraceptive and tetracycline were continued for up to 10 days, and additional concentrations of ethinyl estradiol, norethindrone, and tetracycline were determined between days 5 and 10. Four additional normal women ingested tetracycline for 5 to 10 days. Tetracycline levels were determined at the time intervals noted above on day 1 and days 5 to 10. No significant decrease in plasma ethinyl estradiol or norethindrone concentration was seen with either short-term (24 hours) or long-term (5 to 10 days) ingestion of tetracycline. Similarly, levels of tetracycline do not significantly decrease with ingestion of a low-dose oral contraceptive.

Adolescent↗
PubMed1991

Laparoscopic cautery in the treatment of endometriosis-related infertility.

Life table analysis and the two-parameter exponential method have been applied to pregnancy rates in 72 patients undergoing laparoscopic cautery exclusively. Patients with male factor infertility were excluded. Estimated cure rates for patients with stage I and II disease were 98.2% and 76.6%, respectively (not significantly different). No significant difference was seen when anovulation complicated the endometriosis (68.6%). When greater than one infertility factor was present, a significant difference was observed (50.6%). Patients with stage I disease had an average fecundity of 10.30% with decreasing values observed in stage II (7.59%), anovulation (6.67%), and more than one infertility factor (3.33%). We conclude that laparoscopic cauterization is an effective mode of therapy for the treatment of stage I and II endometriosis associated with infertility.

Adult↗
PubMed1991

Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis.

OBJECTIVE: To examine endocrine and clinical responses to long-term administration of RU486 in patients with endometriosis. DESIGN: Prospective open trial. SETTING: Faculty practice of the authors. PATIENTS, PARTICIPANTS: Six normally cycling women with endometriosis were recruited. INTERVENTIONS: Subjects received RU486 100 mg/d for 3 months. MAIN OUTCOME MEASURE(S): Hormonal changes during RU486 were compared with control data obtained in the preceding cycle during the early follicular phase. Clinical responses were determined by patient assessment and second-look laparoscopy. RESULTS: All women became amenorrheic, and daily urinary levels of ovarian steroid metabolites remained acyclic. Mean luteinizing hormone (LH) (P less than 0.02) and LH pulse amplitude (P less than 0.05) were increased without changes in LH pulse frequency. An antiglucocorticoid effect was demonstrated by an increase in serum cortisol (P less than 0.01) and adrenocorticotropic hormone (P less than 0.05) levels. Treatment resulted in an improvement in pelvic pain in all subjects without significant change in the extent of disease as evaluated by follow-up laparoscopy. CONCLUSIONS: Daily administration of RU486 results in acyclic ovarian function and improvement in the subjective painful symptoms of endometriosis.

Adolescent↗