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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 55 records · Page 3Linked to original sources
PubMed1987

Treatment of menorrhagia with meclofenamate sodium.

A double-blind, placebo-controlled crossover trial was undertaken to determine the efficacy of meclofenamate sodium in the treatment of menorrhagia. Twenty-nine patients who had a baseline menstrual blood loss greater than 60 ml received 2 months' each of meclofenamate sodium, 100 mg by mouth, three times a day, or a placebo. The mean menstrual blood loss was reduced from 141.6 +/- 15.9 ml at baseline to 69.0 +/- 6.3 ml during treatment cycles but remained increased during placebo cycles (135.6 +/- 11.3 ml). The symptoms of dysmenorrhea, backache, and headache were significantly reduced only during active drug periods. The number of days of flow and pads or tampons used was also reduced during drug cycles but not during placebo cycles. Overall, 26 of the 29 patients evaluated had a reduction in menstrual blood loss with the use of meclofenamate sodium. It appears that many women with unexplained menorrhagia may benefit from this treatment.

Adolescent↗
PubMed1987

Effects of the antiprogesterone RU 486 in normal women. I. Single-dose administration in the midluteal phase.

The response to a single oral dose of the antiprogesterone RU 486 was studied in the midluteal phase in 26 normal women. Each subject received a dose between 50 and 800 mg RU 486 on days 6 to 8 after the luteinizing hormone surge and blood samples were taken over the following 48 hours. Another group of five patients received a single oral dose of 200 mg RU 486 and blood sampling was extended for 14 days. Menses were induced in all women but one within 3 days after RU 486 administration. Two distinct patient populations emerged. In nine of the subjects, there was a single bleeding episode and the treatment cycle was significantly shorter (p less than 0.05) than the following cycle. In 16 of these 25 patients a second bleeding episode occurred 19.0 +/- 0.8 days after the luteinizing hormone surge. The total treatment cycle was significantly prolonged (p less than 0.05) when compared with the following cycle. In the group with a single bleeding episode, there was a significant decline in follicle-stimulating hormone, estradiol, and progesterone over the 48-hour sampling period, but there was no change in these values in the group with two bleeding episodes. These two groups could not be separated on the basis of RU 486 dose or serum levels. After the four higher doses, there was a dose-dependent rise in serum prolactin. There were no alterations in mean cortisol values with the three lower doses, but there was a significant increase at 24 and 48 hours after the higher doses. Serum levels of RU 486 were maximal between 1 and 4 hours and the half-life of serum RU 486 was determined to be 24 hours.

Administration, Oral↗
PubMed1987

Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase.

RU 486, a synthetic steroid with antiprogesterone receptor activity, was used to investigate the importance of progesterone on gonadotropin secretory dynamics in the midcycle of the normal menstrual cycle. Six normally cycling women were followed for three consecutive cycles. During each cycle, blood samples were obtained beginning on day 10 and continued until menses. After a control cycle, 100 mg RU 486 was given orally between days 10 and 17. The patients were followed for a posttreatment cycle with no medication. When RU 486 was given before the midcycle, the luteinizing hormone surge was delayed by 15.0 +/- 2.1 days after ingestion of the last pill, resulting in cycles of 40.6 +/- 2.6 compared with 28.0 +/- 2.3 days (p less than 0.01). During RU 486 administration and at the time a normal luteinizing hormone surge was anticipated, an attenuated luteinizing hormone/follicle-stimulating hormone surge was noted that was not followed by a rise in progesterone. After the attenuated surge a normal luteinizing hormone/follicle-stimulating hormone level occurred, with a normal rise in progesterone. Estradiol levels during RU 486 administration decreased during treatment, indicating a possible direct action of RU 486 on the ovary.

Administration, Oral↗
PubMed1987

Resumption of ovulation after ectopic pregnancy.

Forty-four patients with ectopic pregnancies were followed with serial serum progesterone determinations for up to 40 days after surgery. Seven patients (16%) failed to show luteal function during the study. Thirty-seven (84%) demonstrated luteal activity (serum progesterone at least 3 ng/mL): in six patients by days 17-19, in 50% by day 24, and in 72% by day 30. Because hormonal contraception delayed until the first postoperative office visit would miss the onset of folliculogenesis in approximately three-quarters of ectopic pregnancies, contraception should be begun immediately after surgery.

Adolescent↗
PubMed1986

Biochemical and histologic effects of sequential estrogen/progestin therapy on the endometrium of postmenopausal women.

Medroxyprogesterone acetate in doses of 10, 5, and 2.5 mg was administered sequentially to three groups of postmenopausal women receiving 0.3 mg, 0.625 mg, and 1.25 mg of conjugated equine estrogens, respectively. Serial endometrial biopsies were performed on these women before therapy, during estrogen therapy alone, and during sequential estrogen-progestin therapy. Endometrial histology and estrogen receptor concentrations were assessed. A linear increase of cytosolic estrogen receptor concentration occurred over the dosage range of conjugated equine estrogen. When medroxyprogesterone acetate was added to the estrogen therapy, the concentrations of estrogen receptors fell. Within the groups of women receiving 0.3 mg and 0.625 mg of conjugated equine estrogen, all doses of medroxyprogesterone acetate were equally effective in reducing the levels of cytosolic receptor to pretreatment levels. However, at the conjugated equine estrogen dose of 1.25 mg, only 5 mg and 10 mg doses were effective in reducing the cytosolic receptor concentration to pretreatment levels. Histologically, little effect was observed from the lowest doses of either drug. However, even though 5 and 10 mg of medroxyprogesterone acetate were identical biochemically, the 10 mg dose was the only one producing a homogeneous, secretory pattern within the endometrium.

Biopsy↗
PubMed1986

Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device.

Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly.

Adult↗
PubMed1986

Pregnancy termination with a high and medium dosage regimen of RU 486.

Sixty healthy pregnant women who wished to terminate their pregnancy and who were no more than 49 days pregnant were treated with one of three different dose regimens of a synthetic progesterone receptor blocker, RU 486. Serum cortisol was measured to determine the antiglucocorticoid effects of this compound. The high dose but shorter treatment regimen (400 mg/day RU 486 X 4 days or 200 mg/day X 4 days) was associated with a high (greater than 80%) rate of side effects, especially nausea, vomiting, weakness and heavy bleeding and a low rate of success (10%). A group of 50 subjects received the medium dose but longer treatment regimen (100 mg/day X 7 days). This group had less side effects (40-60%) and a 72.3% success rate of complete abortion. The AM cortisol values were significantly elevated in all treatment groups but higher in those receiving the high dose. These values returned to normal one week following cessation of treatment. Medium dose but longer duration (100 mg/day X 7 days) of RU 486 treatment is associated with a higher success rate and less side effects than higher dose therapy administered over a shorter period. There were no predictive indices to determine which subjects would respond successfully. The reason for the failure of the drug in 30% of the subjects on the medium dose is not known at this time.

Abortifacient Agents↗
PubMed1986

Altered fetal growth and development in a patient with Turner's syndrome.

Fertility in cases of Turner's syndrome is rare. In cases where conception does occur, spontaneous abortion and structural and chromosomal defects commonly are discovered. A review of the literature and a case report are presented in which pregnancy was complicated by severe intrauterine growth retardation and musculoskeletal deformities of the fetus.

Abnormalities, Multiple↗
PubMed1986

Size and weight determinations of nongravid enlarged uteri.

Uterine size was estimated in 66 women before hysterectomy by bimanual examination, uterine sounding, and pelvic ultrasound. The results were compared with weight and dimensions recorded after removal. There was greater error in estimation of uterine size using bimanual examination (standard error of the estimate [SEE] = 2.6 weeks) or uterine sounding (SEE = 2.2 weeks) than with ultrasound (SEE = 1.06 weeks). A close correlation existed between uterine size and weight (r = 0.95).

Female↗
PubMed1985

Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol.

The pronounced hepatic impact of oral ethinyl estradiol has been attributed by some to its so-called first-pass effect through the liver as only some 40% of ingested ethinyl estradiol reaches the systemic circulation. Others believe that ethinyl estradiol exerts its hepatic effects because of its chemical composition, specifically its 17 alpha-ethinyl group. In an attempt to resolve this controversy, a study was undertaken to determine whether vaginal administration of ethinyl estradiol can selectively reduce the hepatic effects of oral ethinyl estradiol. To compare the effects of oral and vaginal ethinyl estradiol, a group of postmenopausal subjects received either 5 micrograms of oral and 20 micrograms of vaginal ethinyl estradiol or 10 micrograms of oral and 50 micrograms of vaginal ethinyl estradiol in either sequence, respectively. Oral ethinyl estradiol was four to five times more potent than vaginal ethinyl estradiol. The potency ratios of the oral-vaginal ethinyl estradiol doses required to suppress follicle-stimulating hormone and luteinizing hormone were 4.4 and 3.2 and those to raise sex hormone-binding globulin binding capacity, corticosteroid-binding globulin binding capacity, and high-density lipoprotein cholesterol as well as lower low-density lipoprotein cholesterol were 3.5, 5.0, 4.2, and 4.2, respectively. These essentially equal oral-vaginal route potency ratios for both central nervous system and hepatic effects indicate that vaginal administration of ethinyl estradiol does not selectively reduce its hepatic impact in relation to its central nervous system effects. The pronounced hepatic effects of ethinyl estradiol are therefore attributed to its chemical composition.

Administration, Oral↗
PubMed1985

Dynamics of human chorionic gonadotropin, prolactin, and growth hormone in serum and amniotic fluid throughout normal human pregnancy.

This study was performed to establish the dynamics of human chorionic gonadotropin, prolactin, and growth hormone throughout pregnancy in serum and amniotic fluid. Two hundred fifty healthy women at 8 to 42 weeks' gestation were studied. The highest serum human chorionic gonadotropin level was measured between weeks 8 to 12 (53,715 +/- 3574 mIU/ml, mean +/- SEM), with a decline to a mean plateau of 11,806 +/- 1250 mIU/ml from week 18. Amniotic fluid human chorionic gonadotropin had a similar pattern with a mean of 68,100 +/- 8422 mIU/ml at weeks 8 to 10, declining from week 18 to a plateau of 2005 +/- 260 mIU/ml. Human chorionic gonadotropin showed a significant correlation (r = 0.85, p less than 0.001) between levels of both compartments demonstrating an even distribution. Prolactin levels showed a dichotomy of patterns and levels. Serum prolactin showed a continuous rise from 45.3 +/- 14 ng/ml at week 8 to 224 +/- 20 ng/ml at week 36. In contrast, amniotic fluid prolactin remained low until week 14 (33.1 +/- 0.8 ng/ml), followed by a sharp and significant (p less than 0.001) increase to a plateau of 3750 +/- 200 ng/ml between weeks 18 to 26, declining to a second plateau of 500 +/- 50 ng/ml at week 36. Serum growth hormone increased from a mean of 3.5 +/- 1.4 ng/ml seen at weeks 8 to 10 to a mean of 14 +/- 2.0 ng/ml at weeks 28 to 30, followed by a plateau of similar levels. The pattern of growth hormone secretion in amniotic fluid demonstrated a sharp increase during the 14-16 interval with a maximum mean level of 15.5 +/- 1.5 ng/ml and a slow steady decline thereafter. In conclusion, the similar pattern and concentration of human chorionic gonadotropin throughout pregnancy in both maternal and amniotic fluid are probably the result of direct human chorionic gonadotropin diffusion from the placenta. The dissimilar pattern and concentration of prolactin are the result of two different sources of prolactin secretion during pregnancy. Serum prolactin originates from the pituitary and amniotic fluid prolactin from the decidua. Since the pattern of growth hormone secretion resembles that of prolactin, it is possible that growth hormone, like prolactin, is secreted by the same sources.

Amniotic Fluid↗
PubMed1985

Contraception with long-acting subdermal implants. A five-year clinical trial with Silastic covered rod implants containing levonorgestrel. The International Committee for Contraception Research (ICCR) of the Population Council.

A total of 189 women volunteered to accept subdermal implants for contraception. The implants were "covered rods", consisting of a core rod containing equal parts by weight of levonorgestrel and polydimethylsiloxane and sealed inside a thin-walled tube of Silastic tubing with medical adhesive. In one study 78 women used 4 3cm rods (study 07) and in the other 111 women used 6 3cm rods. In 5 years of use there were no pregnancies in either group. Terminations because of menstrual problems were twice as frequent among the 4-rod users than among users of the 6 rods. Menstrual pattern analysis is presented for the two rod regimens and compared with the previously reported patterns for the 6-capsule regimen (NORPLANT). Long--term in vivo release rates are also presented.

Adolescent↗
PubMed1985

Ovulation inhibition with nafarelin acetate nasal administration for six months.

A group of 24 women with normal menstrual cycles were treated with nafarelin acetate administered in doses of either 125 micrograms or 250 micrograms daily intranasally for 6 months. Each subject was studied for one ovulatory control cycle, six treatment cycles, and post-treatment until the return of ovulation was documented. Once a week progesterone, estradiol, follicle stimulating hormone, and luteinizing hormone were measured in the serum. Acute hormone responses to nafarelin acetate were determined on day 1, day 98 and day 186 of treatment. Two subjects failed to complete the treatment phase. One subject using the 250 micrograms daily dose of nafarelin acetate discontinued treatment on the sixth day because of heavy uterine bleeding. One subject using the 125 micrograms daily dose of the study drug terminated treatment on day 126 because of a 21-pound weight gain. There were significantly less presumed ovulatory cycles at the higher dose (2 out of 60 cycles) than at the lower dose (10 out of 54 cycles) (p less than 0.01). On the average menstrual cycles were reestablished 28.5 +/- 8.3 (S.D.) days after discontinuing the 125 micrograms daily dose and 33.7 +/- 17.9 (S.D.) days after terminating the 250 micrograms daily dose. With the higher dose of nafarelin acetate there were significantly fewer bleeding episodes, less number of days of bleeding, and longer cycles. During the treatment phase the area under the LH curve was significantly less and the acute response of LH in the last week of treatment was significantly less with the higher dose of drug. With both doses of nafarelin acetate the acute responses of LH, FSH and estradiol were significantly greater on day 1 than on either day 98 or day 186. Side effects observed during this study included galactorrhea (2 subjects) and vasomotor symptoms (7 subjects).

Administration, Intranasal↗
PubMed1985

Reliability of urinary pregnancy tests in the diagnosis of ectopic pregnancy.

Recently a new generation of urinary pregnancy tests with increased sensitivity and specificity for beta-human chorionic gonadotropin (beta-HCG) was introduced. The clinical sensitivity of seven of these tests was evaluated in patients with surgically proven ectopic pregnancy. Two enzyme-linked immunosorbent assays (Tandem Visual, Hybritech; Mod C1, Monoclonal Antibodies), with a sensitivity of 50 mIU of beta-HCG, were positive in 90% of ectopic pregnancies. The three-tube tests (Sensitex, Roche; UCG Beta Stat, Wampole; beta-Neocept, Organon), with a sensitivity of 150-250 mIU of beta-HCG, were positive in 81-85% of ectopic pregnancies. Two slide tests (UCG Beta Slide, Wampole, and Sensislide, Roche), with a sensitivity of 500-800 mIU of beta-HCG, were positive in 51-61% of ectopic pregnancies. Both the immunosorbent assays and the tube tests were statistically more sensitive than the slide tests (P less than .001). There was no statistically significant increase in sensitivity between the tube tests and the immunosorbent assays. The sensitivities of these tube tests in ectopic pregnancy are similar to those of tube tests from other manufacturers previously reported on.

Adolescent↗
PubMed1985

Effect of suckling on serum prolactin, luteinizing hormone, follicle-stimulating hormone, and estradiol during prolonged lactation.

Eight nursing subjects had serum prolactin (PRL), luteinizing hormone, follicle-stimulating hormone, and estradiol levels studied during the first six months postpartum. Each subject had serum samples obtained just before the initiation of suckling and during the next 120 minutes. Baseline PRL levels were high at ten days postpartum (90.1 ng/mL), then slowly declined but remained elevated at 180 days postpartum (44.3 ng/mL), with the stimulus of suckling being able to double the baseline PRL value throughout the study period. Mean estradiol levels were low at ten days postpartum (7.2 pg/mL), then gradually rose to a mean level of 47.3 pg/mL at 180 days postpartum; however, in four subjects who were amenorrheic during the study period, the mean estradiol levels remained low (4.25 pg/mL), while baseline PRL levels remained high (63.6 ng/mL).

Amenorrhea↗