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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 145 records · Page 8Linked to original sources
PubMed1981

The effect of a contraceptive vaginal ring and oral contraceptives on the vaginal flora.

Premenopausal women seeking a steroid contraceptive method were allowed to choose between a contraceptive vaginal ring (CVR) containing levonorgestrel and estradiol used in a 3-week in, 1-week out regimen (n=20) and an oral contraceptive (OC) containing levonorgestrel and ethinyl estradiol in a 28-day regimen (n = 10). Cultures from the posterior vaginal fornix were obtained before therapy in both groups and monthly for 6 months for the CVR group and after 1, 3, and 6 months for the OC group. These cultures were streaked on specific media to provide quantitative aerobic and anaerobic, lactobacillus, Candida sp., Gardnerella vaginalis and Neisseria gonorrhoeae counts in micro-organisms per milliliter. A comparison of the number and types of organisms isolated from vaginal cultures obtained initially and at 6 months demonstrated no statistically significant differences in colony counts between CVR and OC users. The results of this study suggest that the use of the CVR is not associated with a greater growth of pathogens than is oral administration of a progestin and estrogen combination.

Adult↗
PubMed1981

Termination of early gestation with (15S)-15-methyl prostaglandin F2 alpha methyl ester vaginal suppositories.

Vaginal suppositories containing (15S)-15-methyl prostaglandin F2 alpha methyl ester were administered to 40 subjects, in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects received a 3-mg suppository followed in 3 hours by a 1 mg suppository, ten subjects received the 1-mg suppository followed in 3 hours by a 3-mg suppository, and twenty subjects received the 3-mg suppository followed in 1 hour by the 1-mg suppository. Twenty-four subjects (60%) had a successful termination of their pregnancy using the two vaginal prostaglandin suppository regimen. All subjects who aborted had 10 percent or less of their pretreatment levels of beta-hCG 7 to 22 days after therapy. Sixteen subjects (40%) did not abort. One of the subjects who failed treatment refused the second suppository due to gastrointestinal side effects and uterine cramping following the insertion of the 1-mg suppository. A second subject had an incomplete abortion and developed mild endometritis. Sixteen subjects reported side effects which included nausea, emesis, diarrhea, uterine cramping requiring analgesia, restlessness, shakiness, and dizziness. The addition of the second vaginal suppository containing this particular prostaglandin analogue did not significantly increase the overall abortifacient activity of this method.

Abortion, Induced↗
PubMed1981

Correlation of Ovutron readings and the basal body temperature (BBT) with serum sex-hormone and luteinizing hormone levels.

Prior studies have produced conflicting results about whether a change in electric potential occurs at the time of ovulation. This study was undertaken to determine whether the Ovutron, a digital voltmeter which displays the sign and magnitude of voltage measured when the index fingers are applied to the electrodes, would produce a mix in polarity, some positive and some negative voltages, with 5 consecutive measurements preceding ovulation. This device was used daily in 10 normally ovulating women to determine whether such a mix in polarity occurred during the menstrual cycle and its relationship to the corresponding daily measurements of luteinizing hormone, total immunoreactive estrogen (IRE) and progesterone heralding and confirming ovulation. In addition, the Ovutron readings were compared to the basal body temperature (BBT) measurements. In 8 of 10 women studied with the Ovutron device, a mix in polarity was observed in 2 of 3 consecutive days preceding ovulation and was associated in all but 2 subjects with a 50 pg/ml/day incremental increase in IRE. By comparison, only 4 of the 10 subjects had a "classic" biphasic BBT curve. This novel device should be evaluated in a large group of women employing these and other additional parameters (e.g., ultrasonography) in order to determine its efficacy and whether it has a role in the treatment of infertility as well as contraception.

Adolescent↗
PubMed1981

Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with PCO.

Twenty-three women considered to have polycystic ovarian disease (PCO) were studied in an effort to better understand the mechanism of inappropriate secretion (IGS) which is so characteristic of these women. Criteria for PCO included oligomenorrhea, infertility, an obesity index (ponderal index, PI) < 12, and an LH:FSH ratio > 3. The mean +/- SE weight and PI for this group were 175 +/- 7.5 lbs. and 11.2 +/- 0.2 respectively. Weight was not correlated with steroid levels in PCO or control women. The mean (+/- SE) of serum androgen concentrations (DHEA-S: 2.9 +/- 0.5 micrograms/ml; androstenedione: 2.6 +/- 0.3 ng/ml; and testosterone: 47 +/- 5 ng%) were all significantly higher than those in control women (p < .05). Total serum estradiol (E2) was comparable to those of controls in the follicular phase, while estrone (E1): E2 ratios averaged 2:1. Serum sex hormone binding globulin-binding capacity (SHBG-BC) averaged 56.8 +/- 4.2 nM which was significantly lower than that of controls (p < .05). The percent unbound E2 was significantly elevated in PCO (62% vs 37%). The mass of unbound E2 was also significantly higher in PCO women (40 +/- 3 pg/ml) than in controls (17 +/- 2 pg/ml) (p < .005). Serum LH:FSH ratios had a positive correlation with the relative and absolute concentration of unbound E2. In control women, unbound E2 correlated significantly with LH levels. This suggests that IGS characteristically found in PCO patients and exemplified by elevated LH;FSH ratios, is the result of the feedback response to elevated levels of unbound (i.e., biologically active) E2.

Adolescent↗
PubMed1981

A separate mechanism of gonadotropin recovery after pregnancy termination.

To further elucidate the mechanism of return of pituitary secretory function after gestation, eight women were studied for up to 55 days after pregnancy termination. As long as serum estradiol (E2) and progesterone (P) levels were elevated, serum FSH remained low. Four to 6 days after abortion, serum E2 and P decreased to levels seen in the early follicular phase, and thereafter the initial increase in FSH occurred while serum beta-LH remained undetectable. After the initiation of FSH secretion, the levels fluctuated within the normal follicular phase range, resulting in a steady increase of E2 to a mean preovulatory peak of 257 +/- 37 pg/ml at a mean time of 21 +/- 1.3 days after pregnancy termination. This E2 peak was followed by FSH and LH peaks and subsequent ovulation. In contrast to FSH, serum beta-LH levels increased only after PRL-concentrations diminished to 30 ng/ml or less. This initiation of beta-LH secretion followed the advent of FSH secretion in six of eight patients. Therefore, a temporally separate mechanism of FSH and LH secretion after pregnancy termination is theorized. The theory of FSH occurs soon after the E2 and P levels decline while PRL levels are still elevated. However, the secretion of beta-LH increases only after levels have risen from the postabortion decline.

Abortion, Induced↗
PubMed1981

Clinical and laboratory evaluation of patients with primary amenorrhea.

Sixty-two patients with primary amenorrhea were retrospectively categorized into 4 groups: 1) breast development absent and uterus present (29 patients), 2) breast development present and uterus absent (9 patients), 3) both breast development and uterus absent (2 patients), and 4) both breast development and uterus present (22 patients). Patients in category 1 were diagnosed as having hypogonadotropic hypogonadism (low or normal follicle-stimulating hormone [FSH]) or gonadal dysgenesis (elevated FSH). Patients in category 2 were diagnosed as having congenital absence of the uterus (female range testosterone [T] or testicular feminization [male range T]). In the 2 patients in category 3, a 46,XY karyotype occurred with an enzyme defect (17,20 desmolase) in 1 and the other had agonadism. In category 4, 5 patients with elevated prolactin and a pituitary adenoma were identified. The remaining 17 patients were divided into 2 groups based on progesterone withdrawal bleeding. Patients who had withdrawal bleeding and had elevated luteinizing hormone level were diagnosed as having polycystic ovaries and patients with normal gonadotropins as having hypothalamic dysfunction. Patients who did not bleed were diagnosed as having hypothalamic failure (normal or low FSH) or primary ovarian failure (elevated FSH). This study demonstrates that it is possible to classify patients with primary amenorrhea into 4 useful diagnostic categories based on physical examination and a minimal laboratory investigation.

Adenoma↗
PubMed1981

Feedback effects of estradiol and progesterone upon gonadotropin and prolactin release.

The relationship between estradiol- and progesterone-mediated gonadotropin release and steroid-induced changes in prolactin levels was investigated in an improved human experimental model. Three women who had undergone bilateral ovariectomy were studied after they had received a subcutaneous implant of one 25-mg estradiol (E2) pellet. Serum E2 levels remained between 60 and 125 pg/ml, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were within the normal or slightly elevated range. Serum prolactin (PRL) levels were normal. Each woman received intramuscular injections of gradually increasing doses of estradiol benzoate (E2B) alone and in combination with progesterone (P) in 7 different experiments. An E2B-induced rise in E2 levels comparable to that observed at midcycle elicited a clearly defined LH surge but no change in FSH and PRL. Rising E2 concentrations followed by increasing P levels caused LH and FSH release but no change in PRL. When only P was administered or when serum P levels rose concomitantly with E2 levels, PRL and gonadotropin levels remained unchanged. These data indicate that a surge of E2 similar to that observed at midcycle triggers an acute release of LH only. Moreover, P levels commensurate with those found at mid-cycle facilitate an E2-mediated LH release and induce a concomitant peak in FSH. The lack of a significant increase in PRL levels suggests that different mechanisms are responsible for the pituitary release of PRL and gonadotropins.

Adult↗
PubMed1980

Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes.

Subderman estradiol (E2) pellets (25 mg) were inserted immediately after hysterectomy and oophorectomy in 22 menstruating women, ages 29 to 50 years. Serum samples were obtained daily for 7 days, weekly for 4 weeks, and at monthly intervals for 6 months. Although there was significant variation between patients, E2 levels remained within the follicular phase range, averaging 50 to 70 pg/ml for 3 months, and then slowly declining to a mean of 37 pg/ml at 6 months, when new pellets were inserted. Over the entire study period, the E2:estrone (E1) ratio was greater than unity. Subdermal E2 pellets limited the rise in luteinzing hormone (LH) and follicle-stimulating hormone (FSH) after gonadectomy and the levels of LH and FSH 6 months after the insertion of E2 pellets were significantly lower (p < 0.01) than in 20 postmenopausal women who had undergone oophorectomy and whose serum E2 levels were less than 20 pg/ml. Serum corticosteroid binding globulin-binding capacity (CBG-BC) and serum testosterone-estradiol binding globulin-binding capacity (TeBG-BC) remained unchanged with E2 pellets. Although high-density lipoprotein-cholesterol increased significantly (p < 0.05), low-density lipoprotein-cholesterol, total cholesterol, and triglycerides were unaffected, except for a rise in triglycerides in three older women with diabetes mellitus and hypertension. There were no complaints of severe hot flushes. Women who had vasomotor symptaoms had mild or moderate flushes that occurred at 5 or 6 months after replacements of the pellets. Thus, E2 pellets are an effective form of parenteral estrogen replacement therapy and offer both practical and theorteical advantages over other forms of estrogen.

Adult↗
PubMed1980

Comparison of metabolic and clinical effects of four oral contraceptive formulations and a contraceptive vaginal ring.

A group of 100 women desiring OC received one of the following four formulations on a randomized basis: (1) mestranol 50 micrograms and norethindrone 1 mg, , (2) ethinyl estradiol 50 micrograms and norethindrone 1 mg, (3) ethinyl estradiol 35 micrograms and norethindrone 1 mg, and (4) ethinyl estradiol 30 micrograms and levonorgestrel 150 mg. An additional 10 women received a CVR containing levonorgestrel and estradiol. Measurement of a large number of serum chemistries, lipids, proteins, clotting factors, and liver enzymes was obtained before and 3 and 6 months after starting medication. Clinical factors such as weight, blood pressure, bleeding or spotting, or any adverse side effects were also recorded. There was no significant difference in the metabolic parameters measured among the four oral contraceptives except the increase in angiotensinogen was slightly less in the groups receiving the compounds with 30 or 35 micrograms estrogen and the groups receiving the norgestrel compound had no increase in triglycerides and a slight decrease in cholesterol levels. When the CVR was compared with all oral contraceptives it was found to produce no change in angiotensinogen levels and a decrease in triglycerides. Some of each group of OC users had a lowering of antithrombin III to abnormal levels but none of the CVR users had his amount of decrease. As oral steroids with 30 or 35 micrograms of estrogen do not produce significantly less metabolic alteration than do compounds with 50 micrograms of estrogen, it is unlikely that their use will reduce the incidence of the uncommon serious adverse effects associated with OC use. However, since the CVR's did not increase angiotensinogen, their use as contraceptives will most likely not produce hypertension and possibly the other serious circulatory problems which are increased in some OC users.

Adolescent↗
PubMed1980

Ectopic pregnancy. A study of 300 consecutive surgically treated cases.

Three hundred consecutive women with the surgical and histological diagnosis of ectopic pregnancy were studied to evaluate the etiological factors associated with this problem. Seventy-seven women had a history of surgical evidence of pelvic inflammatory disease (PID); 46 had a history of abdominal pelvic surgery; 32 had a history of both PID and surgery. Forty-three women had used an intrauterine device (IUD), and 32 had a device in utero at the time of the ectopic pregnancy. However, no definite relationship between use of the IUD and ectopic pregnancy could be established. A pregnancy test was positive in 207 of the 251 women on whom it was performed. Culdocentesis, performed on all patients, yielded nonclotting blood in 285 patients. Hematocrit value, measured on the culdocentesis specimen, was greater than 15% in 278 of the 285 women.

Adolescent↗
PubMed1980

Prolactin synthesis and release during pregnancy and puerperium.

Prolactin (PRL) synthesis and its release following thyrotropin-releasing hormone (TRH) administration during pregnancy and puerperium was studied in 45 women. Mean baseline E2 increased from 1,900 +/- 384 (SEM) pg/ml in the first trimester to 3,520 +/- 849 in the second trimester (P less than 0.05) and 43,057 +/- 5,765 pg/ml in the third trimester (P less than 0.001) of pregnancy. Mean baseline progesterone increased from 27.6 +/- 3.2 ng/ml in the first trimester to 41.9 +/- 6.6 in the second trimester (P less than 0.01) and 109.3 +/- 11.2 ng/ml in the third trimester (P less than 0.001) of pregnancy. Ten days after delivery, mean E2 dropped to 13 +/- 2.9 pg/ml and progesterone dropped to 0.56 +/- 0.07 ng/ml in the lactating women; in the nonlactating women, mean E2 level was 100 +/- 44 pg/ml and mean progesterone was 0.63 +/- 0.09 ng/ml. Baseline PRL increased from 27 +/- 15 ng/ml in the third trimester (P less than 0.002). The increased synthesis of PRL with increasing gestation was thought to be due to the stimulatory effects of E2 and progesterone, resulting in hyperplasia of the lactotrophs. In response to TRH, PRL demonstrated a significant increase from the first trimester to the second, with no further increase in the third. Therefore, it appears that the PRL reserve increases only during the first and second trimesters of pregnancy. Ten days after delivery, baseline PRL in response to TRH decreased to levels found in the first and second trimesters. However, the lactating women released less PRL than the nonlactating subjects (P less than 0.01), since PRL is released with each lactating episode which in turn probably reduces the PRL reserve.

Estradiol↗
PubMed1980

Clinical and endocrinologic study of continuous levonorgestrel administration from subcutaneous solid polydimethylsiloxane rods.

Three solid polydimethylsiloxane (Silastic) rods containing levonorgestrel were inserted into the subcutaneous tissue of the volar aspect of the forearm of 8 women. Serum samples were drawn three times a week for 2 months and weekly thereafter for 2 years in 3 of the subjects. The other subjects had serum drawn during the twelfth and last treatment months. Levonorgestrel, estradiol and progesterone were measured in all samples. The subject kept a bleeding record. In comparison to an earlier clinical trial in which 6 hollow capsules of Silastic filled with levonorgestrel were used, the 3 solid levonorgestrel-containing rods provided higher serum levels of levonorgestrel, fewer serum estradiol peaks, only a single episode of ovulation and better bleeding performance.

Adult↗
PubMed1980

Termination of early gestation with a single vaginal suppository of (15S)-15-methyl-prostaglandin F2alpha methyl ester.

Abortion was induced in 20 women who were less than 49 days pregnant with a vaginal suppository containing 3.0 mg (15S)-15-methyl-prostaglandin F2alpha methyl ester. Peripheral serum levels of (15S)-15-methyl F2alpha free acid, beta hCG and progesterone were measured before, during the 10 hours after treatment and over the next 14 days. Eighteen of the subjects had a complete follow-up: ten were aborted (53%), three had incomplete abortions and five were failures. There was a correlation between serum levels of F2alpha (15S)-15-methyl-prostaglandin F2alpha free acid, and the incidence of success. Progesterone was significantly reduced in all three groups of subjects and, therefore, could not be utilized to judge the success of the procedure. A small but insignificant reduction of betahCG occurred in all subjects regardless of outcome during the ten-hour observation period. Since minor side effects of diarrhea and vomiting occurred in less than half of the aborted and only a few of the not aborted subjects, a larger amount of drug might improve the success rate.

Abortion, Induced↗
PubMed1980

Serum levels of ethinylestradiol following its ingestion alone or in oral contraceptive formulations.

The pharmacodynamics of ethinylestradiol (EE2) were studied utilizing a specific radioimmunoassay to measure serum levels in subjects ingesting EE2 alone or in combination with various gestagens. Following the administration of a single oral dose of 20 micrograms of EE2 to three postmenopausal women, peak serum levels ranging from 29 to 58 pg/ml were reached within one hour. Levels fell below the sensitivity of the assay (20 pg/ml) 2, 5 and 8 hours after ingestion. In normal menstruating women, peak serum EE2 concentrations averaged 84 +/- 27 pg/ml after the ingestion of 35 micrograms EE2 and 0.5 mg norethindrone, 152 +/- 57 pg/ml after the ingestion of 50 micrograms mestranol and 1.0 norethindrone and 201 +/- 11 pg/ml after the ingestion of 50 micrograms EE2 and 0.5 mg norgestrel. After the ingestion of mestranol, peak serum levels of EE2 were less than and occurred later than peak levels obtained after the ingestion of the same dose of EE2.

Adult↗
PubMed1980

A comparison of clinical and laboratory methods in monitoring human menopausal gonadotropin therapy.

Twenty infertile, anovulatory women were treated with human menopausal gonadotropin (hMG) for a total of 61 treatment cycles. Cervical scores (all cycles) and vaginal maturation indices (23 cycles) were compared with serum concentrations of total immunoreactive estrogens to determine their clinical efficacy in monitoring hMG treatment. All courses of therapy were judged to have induced ovulation. Singleton pregnancies occurred in nine patients, and one patient conceived twice. All pregnancies were uncomplicated. There was good clinical correlation between cervical score and increasing estrogen levels in approximately one-third of the cycles. Most of these good correlations occurred in patients with low estrogen status. Very poor correlation was found with vaginal cytologic changes. Therefore, in conjunction with serum estrogen determinations, the cervical score is a safe and less expensive means of monitoring hMG therapy in selected patients.

Adult↗