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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 181 records · Page 10Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Disappearance of human chorionic gonadotropin and resumption of ovulation following abortion.

The disappearance of human chorionic gonadotropin (hCG) and resumption of pituitary ovarian function was investigated in 13 patients following first- and second-trimester abortions. First-trimester abortion patients (with suction curettage) had a mean time of 37.5 +/- 6.4 days for the clearance of hCG to a level of 2 mlU/ml. Second trimester abortions (with prostaglandin) had a mean time of 27.4 +/- 4.8 days. Patients undergoing second-trimester hysterectomy had a mean disappearance time of 39.7 +/- 5.3 days and only 12 days if the hysterectomy was initiated with ligation of the uterine and ovarian vessels. No significant difference in clearance time was found when it was compared on the basis of the baseline hCG levels. Based on a concomitant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peak, nine of 12 patients resumed normal pituitary function. These LH and FSH peaks were seen even though the serum hCG levels were as high as 35 mlU/ml. Based on serum progesterone levels of greater than 3 ng/ml, all these nine patients ovulated as early as 21 days after abortion. In view of these results, the clearance of hCG after pregnancy termination depends mainly upon the type of procedure used. Moreover, in view of the early time of ovulatory recovery, contraception should be instituted within the first 2 weeks following pregnancy termination.

Abortion, Induced↗

Comparison of serum prolactin, plain radiography, and hypocycloidal tomography of the sella turcica in patients with galactorrhea.

Hypocycloidal tomography of the sella turcica is being used with increasing frequency in patients with galactorrhea in order to establish the diagnosis of pituitary adenoma. In 201 patients with galactorrhea, serum prolactin (PRL) levels were correlated with anteroposterior (AP)--lateral plain radiographs and hypocycloidal tomography of the sella turcica. Plain films were normal in 167 and abnormal in 34 patients. Of the 167 patients with normal AP-lateral plain films, 80 had normal tomograms and normal serum prolactin levels while 80 patients had normal tomograms and elevated serum PRL levels (21 to 256 ng/ml). The remaining seven of the 167 patients had normal plain films with abnormal tomograms and elevated serum PRL levels (28 to 176 ng/ml). All patients with abnormal plain radiographs had abnormal tomograms and had either elevated or normal serum PRL levels. In view of these findings, sella tomography is only necessary in patients with normal plain radiographs and elevated serum PRL levels.

Adenoma↗

The intrauterine contraceptive device and acute salpingitis: a multifactor analysis.

From an indigent population hospitalized with acute salpingitis, 163 patients were compared with 222 control patients from the minor trauma section of the emergency room. Four factors were significantly different between cases and controls: race, type of contraception, number of sex partners, and previous history of salpingitis. A discriminate analysis based on a linear logistic equation demonstrated that each risk factor was independent rather than a reflection of another risk factor. Thus factors associated with race, IUD use, multiple sexual partners, and previous salpingitis increase the risk of salpingitis in the population studied.

Acute Disease↗

Comparison of three different models of the copper T intrauterine contraceptive device.

A random sequential comparative study of three models of the Copper T intrauterine contraceptive device (IUD) was undertaken in 1,792 women. For 7 months, the TCu 300 and TCu 220C were randomly inserted, and then the TCu 380A and 220C were randomly inserted for the next 12 months. The log-risk method of life-table analysis of event rates was performed at the end of each of the first 3 years of use of each device. The TCu 380A had the lowest pregnancy rate during each year of use, although the difference was not significant. At the end of each of the first 2 years, the TCu 300 was removed significantly less than the TCu 220C and TCu 380A for bleeding and pain. At the end of three years, the rates of removal for bleeding and pain for the TCu 380A and TCu 300 were similar and lower than that for the TCu 220C, but the overall difference was not significant. There were no differences among the devices for any other relevant use-related reasons. The TCu 380A was removed for other medical reasons significantly more frequently than the other devices at the end of 2 and 3 years. Adjusting for parity did not alter the results. The findings of this study suggest that the copper sleeves along the horizontal arms together with copper wire on the vertical arm in the TCu 380A model provide greater protection against intrauterine pregnancy, whereas the copper sleeves along the vertical arm as in the TCu 220C caused increased removals for bleeding and pain. The TCu 380A should be studied in a larger number of patients for a longer period of time to determine its clinical effectiveness. It may become the IUD of choice for all women irrespective of parity.

Female↗

Galactorrhea and pituitary tumors in postpill and non-postpill secondary amenorrhea.

One hundred sixty-seven women with secondary amenorrhea were observed from six months to four years. In 66 patients, the amenorrhea followed the discontinuation of oral contraceptives (postpill) while in the remaining 101 the amenorrhea was not temporally pill related (non-postpill). Galactorrhea was present in 43 (65%) of those with postpill amenorrhea and in 32 (32%) of those with non-postpill amenorrhea (p less than 0.001). Tomography of the sella turcica was performed in the 75 women with galactorrhea and in the 35 without galactorrhea who did not have withdrawal uterine bleeding following progesterone administration and who had low or normal serum follicle-stimulating hormone levels (hypothalamic-pituitary failure). Forty of the 75 patients with amenorrhea and galactorrhea had radiographic evidence of a pituitary tumor whereas only eight of 35 patients with hypothalamic-pituitary failure without galactorrhea had an abnormal sella turcica (p less than 0.01). The incidence of radiographic abnormalities in those with galactorrhea was similar in both the postpill and non-postpill groups.

Adolescent↗

Gonadotropin insufficiency in patients with thalassemia major.

To elucidate whether the cause of sexual maturational arrest in thalassemia major is of hypothalamic or pituitary etiology, three female and two male patients were extensively studied. After the iv administration of 150 micrograms gonadotropin-releasing hormone (GnRH) and 500 micrograms of TRH, all patients demonstrated a minimal LH and no FSH response, with variable PRL and TSH responses. The test was repeated after the patients received 100 micrograms GnRH im daily for 7 days. The LH, FSH, PRL, and TSH responses were similar to those obtained previously. The female patients were then retested twice, after priming with 17 beta-estradiol (2 mg daily for 7 days) and again after treatment with human menopausal gonadotropins. The male patients were treated with hCG and, after testosterone reached normal adult male values, the GnRH-TRH stimulation test was repeated. In both the female and male patients, the pituitary responses remained unchanged. These results demonstrate the presence of primary gonadotropin insufficiency as well as the lack of positive estrogen feedback mechanism in patients with thalassemia major. The site of this abnormality has been demonstrated to be the pituitary gland, since hemosiderosis of the pituitary without hypothalamic involvement has been found at autopsy in one patient.

Adult↗

Roles of estradiol and progesterone in eiliciting the midcycle luteinizing hormone and follicle-stimulating hormone surges.

The positive feedback effects of estradiol (E2) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterupted E2 replacement by subdermal implants. Basal serum E2 levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E2B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E2B injections. In all three subjects, increasing serum E2 levels mimicking the preovulatory E2 peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E2 concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E2 concentrations had risen or when P levels increased without a rise in serum E2, neither a serum LH nor FSH peak was observed. When administered concomitantly, E2B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E2 is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak.

Adult↗

Ovulation induction in amenorrheic women.

Seventy-six patients with primary or secondary amenorrhea who wished to conceive were treated with clomiphene citrate, 2-Br-alpha-ergocryptine, and/or human menopausal gonadotropins (hMG). Of these 71 patients who received clomiphene citrate, 39 (55%) ovulated. Of these 71 patients, 52 had withdrawal uterine bleeding following IM progesterone, and 38 (73%) ovulated; only 1 of the 19 who did not bleed ovulated (P less than 0.001). Ovulation occurred in the former group of patients whether or not they had galactorrhea. Of the 32 patients who failed to ovulate despite treatment with the maximal dose of clomiphene, 250 mg/day for 5 days, 26 received hMG-hCG. All 26 ovulated and 15 conceived. All 8 patients with amenorrhea-galactorrhea who were treated either primarily or secondarily with bromergocryptine ovulated, and 4 conceived. Therefore, the drug of choice for ovulation induction in amenorrheic patients depends on 1) the presence of withdrawal bleeding after progesterone and 2) the presence of galactorrhea. In all patients with progesterone withdrawal bleeding with or without galactorrhea, the initial treatment of choice is clomiphene citrate. In the absence of withdrawal bleeding, hMG should be administered if galactorrhea is absent, and bromergocryptine should be administered if galactorrhea is present.

Amenorrhea↗