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Biomedical subjects

D R Meldrum

Publications and source records attributed to D R Meldrum.

At least 145 records · Page 8Linked to original sources
PubMed1990

Leuprolide acetate lowers circulating bioactive luteinizing hormone and testosterone concentrations during ovarian stimulation for oocyte retrieval.

Levels of immunoreactive luteinizing hormone (LH), bioactive LH, and testosterone (T) were determined in 52 women receiving human menopausal gonadotropins (hMG). In 26 women receiving leuprolide acetate (LA) preceding hMG, there was a significant suppression of immunoreactive LH and bioactive LH. The characteristic increase in serum levels of bioactive LH and T were absent. Follicular fluid estradiol and T concentrations, and serum progesterone were not different. The lower circulating levels of T may reflect reduced LH-stimulated androgen accumulation in smaller nonaspirated follicles and may account for the enhanced follicle recruitment observed during LA. The lack of premature luteinization despite marked rises of bioactive LH in the absence of LA is consistent with normal events during the menstrual cycle and was due to the early termination of hMG stimulation.

Chorionic Gonadotropin↗
PubMed1990

Oocyte donation.

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Female↗
PubMed1990

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate.

Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.

Adult↗
PubMed1990

Immunoprotective effect of a calcium channel blocker on macrophage antigen presentation function, major histocompatability class II antigen expression, and interleukin-1 synthesis after hemorrhage.

Hemorrhage induces a severe suppression of the immune system resulting in increased susceptibility to sepsis. Although studies indicate beneficial effects of calcium channel blockers on cell and organ functions after low-flow conditions, it remains unknown whether such agents have any effects on different immune responses after hemorrhage. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg and were maintained for 60 minutes, followed by resuscitation with their own shed blood and adequate fluid. The mice received either the water-soluble calcium channel blocker diltiazem (400 or 2400 micrograms/kg body weight) or saline solution (vehicle). Peritoneal macrophages were obtained by lavage 24 hours later. Antigen presentation was measured by coculturing peritoneal macrophages with the D10.G4.1 helper T-lymphocyte clone. Immune associated antigen (Ia) expression was determined by direct immunofluorescence. Interleukin (IL)-1, 6, and tumor necrosis factor-alpha (TNF) levels in peritoneal macrophage supernatants were measured by use of cytokine-specific cellular assays. Hemorrhage caused a significant decrease in peritoneal macrophage antigen presentation function, Ia expression, and IL-1 and IL-6 synthesis in the vehicle-treated group, whereas TNF levels were increased. However, both doses of diltiazem significantly improved peritoneal macrophage antigen presentation, Ia expression, and IL-1 synthesis. IL-6 synthesis was only increased with high doses of diltiazem, whereas both diltiazem doses decreased TNF production. These results indicate that the calcium channel blocker diltiazem can markedly improve macrophage functions after hemorrhage. The use of diltiazem might offer a new therapeutic modality in the treatment of immunosuppression and in decreasing the susceptibility to sepsis after hemorrhagic shock.

Animals↗
PubMed1989

Normal fertilization in men with high antibody sperm binding by the addition of sufficient unbound sperm in vitro.

A high incidence of fertilization failure has been reported in men with over 70% of their sperm bound with isoantibodies. In three men with greater than 80% antisperm antibody binding with IgG and IgA immunoglobulins, a normal rate of fertilization (29/46 oocytes; 63%) was achieved by adding a sufficient number of motile sperm to provide at least 50,000 unbound sperm per oocyte. This method appears to be simpler and more effective than attempting to separate unbound sperm in vitro.

Adult↗
PubMed1989

Routine pituitary suppression with leuprolide before ovarian stimulation for oocyte retrieval.

Pituitary suppression with leuprolide acetate (LA) was used before and during ovarian stimulation with human menopausal gonadotropins in 45 consecutive women having their first cycle of in vitro fertilization embryo transfer (IVF-ET). As anticipated, a low rate of cycle cancellation (6.7%) was necessary for poor responses. Follicles were allowed to develop to a larger diameter than with our prior protocol without LA. On the day of human chorionic gonadotropin (hCG), 11.5 + 0.7 follicles of at least 1.0 cm were visualized; 11.7 + 0.9 oocytes were retrieved; 67.5% fertilized and 6.7 + 0.6 normal embryos were available for transfer. Of the 3.4 + 0.1 embryos transferred per patient, 24.6% implanted. The rates of clinical pregnancy per retrieval and per stimulation were 54% and 47%, respectively, of which 23.8% aborted. Routine use of LA resulted in a highly efficient level of ongoing pregnancy per initiated cycle, and therefore may produce a superior first cycle for IVF-ET.

Adult↗
PubMed1989

Recovery of hormone secretion after chronic gonadotropin-releasing hormone agonist administration in women with polycystic ovarian disease.

Persistent suppression of gonadotropin and ovarian steroid production can be achieved in women with polycystic ovarian disease (PCO) by daily administration of a long-acting GnRH agonist (GnRHa). This study was designed to determine the patterns of recovery of clinical responses and hormonal secretion after chronic GnRHa administration in women with PCO. Six women with PCO were treated with daily sc injections of [D-His6(imBzl),Pro9-NEt]GnRHa (100 micrograms) for 6 months. Blood samples were obtained at the time of and three times weakly for 90 days after discontinuation of agonist therapy. In five women who did not ovulate, the suppressed serum FSH levels rose to pretreatment values within 10 days. In contrast, a gradual and progressive increase in serum LH (as measured by bioassay and immunoassay) was apparent by day 18. The LH increase coincided with progressive increases in serum estrone (E1), androstenedione, and testosterone. Serum estradiol (E2) began to rise on day 28. All hormones returned to their pretreatment baseline values within the 90-day recovery interval, with the exception of E2. Trend analysis of the slopes of recovery revealed that the incremental secretion patterns of E1, E2, androstenedione, and testosterone differed significantly from that of FSH, but not from those of bioactive or immunoactive LH. Serum progesterone, dehydroepiandrosterone sulfate, and cortisol did not change after withdrawal of GnRHa. One woman ovulated spontaneously on day 52 before which her hormone secretion patterns were indistinguishable from those of the other women. In summary, 1) during recovery after discontinuation of chronic GnRH agonist therapy the patterns of FSH and LH release suggested resumption of endogenous GnRH action on the pituitary with greater release of FSH than LH, a pattern that would be expected in the absence of ovarian steroid influence; 2) the lack of early estrogen production despite the increase in serum FSH concentrations suggests inadequate FSH secretion, abnormal ovarian responsiveness to FSH, or impaired FSH bioactivity; 3) androgen secretion was provoked by the increase in LH secretion; 4) per unit LH measured by bioassay, greater ovarian androgen secretion was stimulated in PCO than ovulatory women; and 5) the likelihood of spontaneous ovulation during recovery was minimal.

Adult↗
PubMed1988

Timing of initiation and dose schedule of leuprolide influence the time course of ovarian suppression.

The time course of suppression of ovarian estrogen production and follicular development with leuprolide was examined in 40 normal women before ovarian stimulation for in vitro fertilization (IVF). Initiation of leuprolide during the midluteal phase caused a significantly more prompt suppression than when treatment was started during the early follicular phase (day 1). Injection of the same total amount of leuprolide in two divided doses also caused a significantly more prompt suppression. These two methods were consistent enough to make routine use of leuprolide practical before ovarian stimulation for IVF.

Estradiol↗
PubMed1988

Blood coagulation in postmenopausal women given estrogen treatment: comparison of transdermal and oral administration.

The responses of the blood coagulation and related systems were studied in 23 postmenopausal women, all of whom received, in randomized order, therapy with conjugated oral estrogens (0.625 and 1.25 mg daily) and transdermally administered estradiol in doses of 25, 50, 100, and 200 micrograms/24 hr. Neither plasma fibrinopeptide A determinations nor plasma fibrinogen chromatographic findings were altered; thus there is no evidence of accelerated fibrinogen turnover with either form of therapy. However, alpha 1-antitrypsin and plasminogen concentrations were significantly increased with the higher dosage of oral but not with transdermally administered estrogen. Similarly, ceruloplasmin concentration was significantly elevated with both oral doses but was unchanged by transdermal therapy.

Administration, Cutaneous↗
PubMed1987

Evolution of a highly successful in vitro fertilization-embryo transfer program.

During the first 2 1/2 years of operation of the University of California at Los Angeles in vitro fertilization-embryo transfer program, 47 clinical pregnancies were achieved in 154 laparoscopies for oocyte aspiration (31%). Two of these pregnancies were achieved through transfer of cryopreserved embryos when ongoing pregnancy did not result from embryo transfer in the stimulated cycle. An increase in clinical implantation was noted with a reduction of transfer volume and proportion of air, with 34% of laparoscopies being followed by clinical pregnancy over the last 18 months. No difference in the rate of clinical pregnancy was noted relative to uterine depth or position. The high rate of multiple implantation (47%) suggested a high level of embryo quality. The success rate was attributed to a strong ovarian, human menopausal gonadotropin stimulation, accurate timing of human chorionic gonadotropin, a high oocyte retrieval rate, meticulous laboratory technique, atraumatic, high-fundal transfer of embryos, and initiation of embryo cryopreservation.

Embryo Transfer↗
PubMed1987

Suppression of the ovary using a gonadotropin releasing-hormone agonist prior to stimulation for oocyte retrieval.

Five women with prior suboptimal ovarian stimulation for in vitro fertilization and embryo transfer (IVF-ET) were pretreated with a long-acting gonadotropin-releasing hormone (GnRH) agonist beginning in the midluteal phase of the preceding menstrual cycle. The four women with normal luteal function had castrate estrogen levels following regression of the corpus luteum, whereas one woman with an abnormal luteal phase and perimenopausal levels of gonadotropins had an agonistic response. In the three women with adequate stimulation, 20 oocytes were obtained and one women became pregnant. Initiation of GnRH agonist therapy during the luteal phase of a normal menstrual cycle may be an efficient way of obtaining ovarian suppression without an agonistic response.

Embryo Transfer↗
PubMed1987

Factors influencing maintenance of sperm motility during in vitro processing.

Addition of serum to culture medium during washing of sperm was shown to significantly improve sperm motility upon subsequent 24-hour incubation, distinct from the beneficial effects of adding serum after washing. Commercial sources of human and bovine albumen tested did not preserve motility as well as serum, but addition to serum showed that the lesser effect was probably due to toxic contaminants. One of the most commonly available disposable plastic syringes was found to be markedly toxic to sperm. The materials found to have sperm toxicity also manifested toxicity to mouse embryos. These findings show that a similar degree of caution is advisable in testing of materials contacting sperm in vitro to that which has become standard practice for culture of human embryos.

Blood↗
PubMed1987

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.

Androgens↗
PubMed1987

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist.

Sixteen women with endometriosis were treated with daily subcutaneous injections of a potent agonist of gonadotropin-releasing hormone (GnRH) for six months. Ovarian estrogen secretion was reduced to castrate levels during most of the course of treatment. Blinded evaluation of laparoscopic photographs confirmed marked suppression of visually apparent disease, but biopsy specimens showed occult, inactive endometriosis in most cases. Marked pain relief was noted by all patients. As a result of this "medical oophorectomy," the women experienced severe hot flashes, and many had insomnia and emotional disturbances. Vaginal cytology showed menopausal changes but related symptoms were generally mild. Calcium excretion rose to menopausal levels. High-density lipoprotein and total cholesterol remained unchanged. These results indicate that GnRH agonist administration has impressive effects on endometriotic implants, and these actions may be enhanced with longer therapy. Further development of this new form of therapy should involve either use of lesser degrees of ovarian suppression or adjunctive therapy to counter the side effects of "medical oophorectomy."

Adult↗
PubMed1986

Biologic effects of transdermal estradiol.

We conducted a dose-response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 micrograms of transdermal estradiol per 24 hours, and 0.625 and 1.25 mg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 micrograms of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins.

Administration, Oral↗