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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1984

Long-term reversible contraception with levonorgestrel-releasing Silastic rods.

Subcutaneously placed Silastic capsules containing levonorgestrel are effective for 5 years and have a higher continuation rate than other methods of reversible contraception. Six 3 cm capsules are required to achieve satisfactory circulating levels of levonorgestrel. Two 4 cm covered Silastic rods containing levonorgestrel, which are easier to manufacture, insert, and remove than the capsules, produce similar in vitro release rates. This study compared clinical and metabolic effects as well as bleeding patterns in 23 women using either six capsules (n = 11) or two covered rods (n = 12). Serum levels of levonorgestrel, lipids, and lipoproteins as well as frequency of elevated progesterone levels were compared in serum samples obtained before treatment and 1, 6, 12, 18, and 24 months after insertion with the two systems. While bleeding patterns were similar for users of the two systems, rod users had slightly higher serum levels of levonorgestrel and a lower incidence of cycles with elevated progesterone levels. Therefore, rods could replace capsules as a long-term, reversible contraceptive method.

Adolescent↗
PubMed1984

The relation of physiological changes to subjective symptoms in postmenopausal women with and without hot flushes.

This study was designed to fully correlate the temporal relationship between augmented digital perfusion, (vasodilatation) and hot flushes, peripheral temperature, plasma luteinizing hormone, (LH) epinephrine and norepinephrine. Plasma samples were measured every 3 min for 2-4 h, in 5 symptomatic women before and after estrogen replacement and in 3 asymptomatic post-menopausal women. In all 5 symptomatic women the augmented digital perfusion occurred at a mean (+/- SEM) of 1.5 +/- 0.2 min before the initiation of the flush, at least 3 min before the initial rise in temperature and 9 min before the LH rise. There was a significant (P less than 0.05) rise in epinephrine but not norepinephrine at 3 and 6 min after the initiation of augmented digital perfusion. Although subjective improvement occurred in all 3 women receiving estrogen, all measured parameters disappeared in only 1 subject and the 2 others continued having augmented digital perfusion, flushes, and temperature vasomotor changes although the related LH increase was absent. Surprisingly, asymptomatic women who never received estrogens also demonstrated similar augmented digital perfusion and temperature changes, but failed to show the LH related rise, as observed in women with short-term estrogen treatment. In conclusion, these results demonstrate that augmented digital perfusion consistently precedes the hot flush, the rise in temperature and plasma LH in symptomatic post-menopausal women. The increase in epinephrine may be a homeostatic mechanism to compensate for the peripheral vasodilatation. The finding that augmented digital perfusion and temperature changes also occur in asymptomatic post-menopausal women indicates that objective changes are more specific and reliable indicators of vasomotor instability than the subjective sensation of hot flushes.

Adult↗
PubMed1984

Effect of variable concentration of serum on mouse embryo development.

This study was undertaken to determine the optimal concentration of serum necessary for maximal embryo development. Mouse embryos were cultured in vitro with 0% to 30% concentrations of serum of 96 hours. After 72 and 96 hours of culture, embryo growth was improved with 5%, 10%, 20%, and 30% serum supplement when compared with Ham's F-10 medium alone. Embryos were then cultured with the same concentrations of serum for 29 hours, following which blastomere number, sister chromatid exchange (SCE), number of micronuclei, and chromosomal aberrations were observed. There was no difference in blastomere number with any concentration of serum supplement studied. All concentrations of serum decreased the number of SCE when compared with Ham's F-10 medium alone. The rate of SCE in embryos cultured with 10%, 20%, or 30% serum was also smaller than that of the embryos cultured with 5% serum. The results of these studies indicate that serum should be employed for culturing embryos, and at least 10% serum concentration is necessary to obtain optimal conditions for embryo development.

Animals↗
PubMed1984

Hyperprolactinemia: comparison of thyrotropic-releasing hormone and tomography.

A group of 95 women with unexplained hyperprolactinemia (over 20 ng/mL) underwent radiologic examination of the sella turcica with hypocycloidal polytomography (N = 58), computed axial tomography (N = 8), or both (N = 29). All patients also underwent a thyrotropin-releasing hormone (TRH) stimulation test, with serum prolactin (PRL) measurement before and 20 and 30 minutes after a 500-micrograms intravenous bolus of TRH. Their PRL responses were compared with those of two control groups, nine normal women in the follicular phase of the menstrual cycle, and 13 women in the first five months of gestation with pregnancy-related hyperprolactinemia. Both control groups exhibited PRL increases with 95% confidence limits at least 200% above baseline levels. In all, 12 patients from the study group also had a normal PRL response (more than a 200% increase) to TRH, and none of these women had tomographic findings consistent with a pituitary tumor. The remaining 83 women all had diminished or absent PRL increases after TRH administration; 46 (55%) of these patients had radiographic evidence of an adenoma, whereas 37 (45%) had no clear signs of a tumor on either polytomography or computed axial tomography. No patient with a baseline PRL level in excess of 60 ng/mL had a normal PRL response to TRH. The results of the study indicate that 1) in patients with PRL between 20 and 60 ng/mL, a normal TRH test can be relied upon to avoid the expense and radiation of tomography (computed axial tomography or polytomography), 2) there is no benefit to be obtained in performing a TRH test in patients with a baseline PRL level over 60 ng/mL, and 3) about 45% of patients with hyperprolactinemia and an abnormal TRH test have a normal computed tomography or polytomography. These patients may have a small adenoma, and thus warrant closer follow-up than patients with a normal TRH test.

Adenoma↗
PubMed1984

The effect of serum fractions on embryo growth.

In order to determine optimal culture conditions for embryos, human fetal cord serum (HCS) small- and large-molecular-weight fractions of HCS, and human serum albumin were employed as media supplements. In the first phase, embryos were cultured with the various protein supplements for 96 hours and observed morphologically every 24 hours. In the second phase, embryos were cultured with the various protein supplements and 5-bromo-2-deoxyuridine for 29 hours. Blastomere number, sister chromatid exchange (SCE), micronuclei, and chromosomal aberrations were observed. Morphologically, any protein supplement was better than no media supplement. Whole HCS and large-molecular-weight fraction provided the best conditions for embryo growth. Blastomere number was increased with whole serum when compared with no supplementation, small-molecular-weight fraction, or human serum albumin. In the analysis of SCE, all supplements had a lower SCE number than no serum supplement, and HCS supplement demonstrated a significantly lower SCE number than the other supplements. No difference in micronuclei or chromosomal aberration was observed in any of the supplements. In conclusion, whole HCS provides optimal conditions for culturing embryos, compared with the various serum fractions, and the beneficial components are primarily found in the large-molecular-weight fraction.

Animals↗
PubMed1983

A modified technique of human in vitro fertilization and embryo transfer.

Forty-seven ovulatory women were treated with a modified technique of human in vitro fertilization and embryo transfer. All patients received clomiphene citrate, 150 mg per day, and follicle development was monitored by real-time ovarian ultrasound and serum estradiol measurement. In the 45 patients who underwent laparoscopy, eight patients were found to have a poor response to clomiphene citrate and were dropped from the treatment cycle. Four additional patients had an endogenous luteinizing hormone increase and did not undergo laparoscopy. Nine patients were found to have inaccessible ovaries at the time of laparoscopy. In patients with accessible ovaries, oocytes were recovered in all cases. Embryo transfers were performed in 72% of patients, and 19% of these transfers resulted in pregnancy. This technique of ovulation monitoring appears to increase oocyte recovery and fertilization rate and subsequent implantation success.

Adult↗
PubMed1983

Clinical applications of techniques used in human in vitro fertilization research.

Human in vitro fertilization-embryo transfer not only provides an opportunity for pregnancy in women who were previously considered to be sterile, but also provides a unique method by means of which basic reproductive physiology can be investigated. From September, 1981, to September, 1982, 71 women with normal cycles who elected to attempt in vitro fertilization-embryo transfer underwent timed laparoscopy for recovery of oocytes. Oocytes were recovered in 60 patients, with embryo transfer resulting in 50 patients, and normal implantation occurred in nine patients. There was a significant correlation between ultrasound observation of follicle size and serum estradiol levels, thus making ultrasound monitoring of follicular growth during stimulation with clomiphene citrate or human menopausal gonadotropin in anovulatory women clinically useful. The technique of sperm washing employed for in vitro fertilization has now been used with good results for intrauterine insemination in patients with infertility due to a cervical factor or oligospermia. Therefore, the techniques used in human in vitro fertilization-embryo transfer are now clinically applicable for couples with infertility due to causes other than tubal disease.

Adult↗
PubMed1983

Effects of two low-dose oral contraceptives on serum lipids and lipoproteins: differential changes in high-density lipoprotein subclasses.

Oral contraceptives containing DL-norgestrel or norethindrone with ethinyl estradiol were administered by random assignment to 21 menstruating women, matched for anthropometric measurements, age, diet, alcohol consumption, smoking, and exercise habits. Pretreatment and 7-week treatment blood samples were obtained and assayed for serum cholesterol, triglyceride high-density lipoprotein cholesterol (HDL-C), and total high-density lipoprotein (HDL), HDL2a, HDL2b, and HDL3 subclasses by analytic ultracentrifugation. Subjects using the norethindrone oral contraceptive had a significant increase in HDL-C: baseline, 46 mg/dl; 7 weeks, 51 mg/dl. Values for the subjects using the norgestrel oral contraceptive were not significantly changed: 46 and 44 mg/dl, respectively. Users of the norethindrone oral contraceptive had significant elevations of total HDL and HDL3, while norgestrel oral contraceptive users demonstrated no significant changes. HDL2b increased with the norethindrone oral contraceptive and declined with the norgestrel oral contraceptive. The changes in HDL2b from baseline to treatment were not significant (p greater than 0.05), but the change with the norethindrone oral contraceptive did differ significantly from that with the norgestrel oral contraceptive (p less than 0.02). These changes may indicate oral contraceptive-induced alterations in HDL structure and metabolism that could be related to the risk of development of atherosclerosis.

Adult↗
PubMed1983

Psychological stress and increases in urinary norepinephrine metabolites, platelet serotonin, and adrenal androgens in women with polycystic ovary syndrome.

Twenty-three women with polycystic ovary syndrome, 10 women with hypothalamic-pituitary dysfunction, and 50 control subjects were studied in an attempt to investigate the prevalence of psychological stress and its possible relationship to various hormonal parameters. Norepinephrine (NE) excretion, as reflected by urinary 3-methoxy-4-hydroxyphenylglycol (MHPG), and urinary 3-methoxy-4-hydroxymandelic acid (VMA), platelet serotonin, plasma adrenocorticotrophic hormone (ACTH), urinary free cortisol, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione (Adione), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), delta 5-androstenediol (delta 5-Adiol), testosterone (T), and unbound estradiol (E2) were measured. In addition, psychological stress was assessed by means of questionnaires modified from the Schedule of Recent Experiences, in which a Life Events Inventory was scored between 1 and 100. Women with polycystic ovary syndrome had significantly elevated levels of serum LH, LH:FSH ratios, unbound E2, Adione, DHEA, delta 5-Adiol, T, and DHEA-S (p less than 0.01). The number of Major Life Events (events scored on the questionnaire above 60) was significantly higher in women with polycystic ovary syndrome than in control women and women with hypothalamic-pituitary dysfunction (p less than 0.05). Urinary MHPG and platelet serotonin levels were also significantly higher in women with polycystic ovary syndrome (p less than 0.05), whereas VMA was normal. Levels of plasma ACTH and urinary free cortisol were similar in all groups. There was a significant positive correlation between MHPG and DHEA-S, MHPG and LH, and LH and T levels in women with polycystic ovary syndrome and those with hypothalamic-pituitary dysfunction (p less than 0.01). VMA also correlated with DHEA-S (p less than 0.05). In conclusion, psychological stress may be more prevalent in women with polycystic ovary syndrome and may be associated with elevated levels of MHPG and platelet serotonin. Because we have found that MHPG, but not VMA, correlated with LH, and because both MHPG and VMA correlated with DHEA-S, we hypothesize here that psychological stress and neurotransmitter levels may be linked to some of the hormonal derangements, including inappropriate gonadotropin secretion and elevated adrenal androgen levels in women with polycystic ovary syndrome.

Adolescent↗