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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 19 recordsLinked to original sources
PubMed1992

Oral contraception: past, present, and future perspectives.

Oral contraceptives (OCs) were initially approved for unrestricted use in 1960 in the United States and have been used and studied extensively for 30 years. The initial formulations contained a fixed dose of estrogen and progestogen ingested for 21 days, with a seven-day pill-free interval. Subsequent formulations contained a sequential estrogen dose, a progestogen alone given daily, and variable doses of both progestogen and estrogen. Although the estrogen and progestogen doses employed in currently marketed OCs are markedly lower than those used in the OCs of the 1960s and 1970s, the excellent contraceptive efficacy of these compounds has not been compromised. The estrogen component produces a dose-related increase in serum globulin concentrations, triglycerides, and high-density lipoprotein (HDL) cholesterol, along with a decrease in low-density lipoprotein (LDL) cholesterol, while the progestogen component causes peripheral insulin resistance, a decrease in HDL cholesterol, an increase in LDL cholesterol, and various androgenic effects. The effect of nicotine on thromboxane release acts synergistically with the elevated serum clotting factors to increase the incidence of both arterial and venous thrombotic events, particularly in women smokers over 35 years of age. However, there is no evidence of increased risk of myocardial infarction or stroke in healthy, nonsmoking women of any age who use OCs containing less than 50 micrograms estrogen. Likewise, the lower-dose estrogen/progestogen formulations do not have a clinically significant effect on glucose metabolism and have a neutral effect on lipoprotein metabolism. In addition, the many noncontraceptive health benefits associated with OCs are maintained with the lower-dose formulations. Thus, the low-dose formulations should improve the overall health of healthy, nonsmoking women as well as effectively prevent unwanted pregnancy.

Cardiovascular Diseases↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test.

Systematic pituitary evaluation was performed in four patients suspected of having Sheehan's syndrome. A sequential pituitary stimulation test, consisting of insulin-induced hypoglycemia followed by stimulation of gonadotropin-(GnRH) and thyroid-releasing hormone (TRH), a metyrapone test, and adrenocorticotropic hormone (ACTH) stimulation test, was performed. All four patients failed to develop a normal increase in serum growth hormone, cortisol, and prolactin (PRL) following insulin-induced hypoglycemia. All patients demonstrated a blunted PRL, follicle-stimulating hormone, and luteinizing hormone response to the combination of GnRH and TRH. Although thyroid stimulating hormone (TSH) response was impaired in all patients, two patients had normal T3 resin uptake and thyroxine, demonstrating minimal TSH reserve maintaining normal baseline free thyroxine index. Metyrapone administration was followed by no increase in 11-deoxycortisol or 17-ketogenic steroids, thereby adding no additional information to the hypoglycemia stimulation. ACTH infusion revealed normal adrenal cortisol response. In conclusion, in patients with suspected postpartum hypopituitarism, a complete pituitary function investigation can be done in a short time by using the described pituitary sequential stimulation test.

Adrenocorticotropic Hormone↗
PubMed1978

The significance of galactorrhea in patients with normal menses, oligomenorrhea, and secondary amenorrhea.

Thyroid-stimulating hormone and prolactin (PRL) were measured in a group of 149 women with galactorrhea. Three of these patients were found to have primary hypothyroidism. In the remaining 146 patients, the PRL assay was correlated with the menstrual history and the results of hypocycloidal polytomography. Sixty-two per cent of these patients had hyperprolactinemia and 35 per cent had abnormal tomograms. Nine patients with abnormal x-rays had normal prolactin levels. None of the patients with normal menses and normal PRL was found to have an abnormal x-ray. Fourteen of the 15 patients with PRL levels greater than 200 ng. per milliliter had abnormal tomograms. Almost 70 per cent of patients with secondary amenorrhea and low estrogen status had abnormal x-rays. In patients with oligomenorrhea and secondary amenorrhea with normal estrogen status, it was not possible to differentiate between patients with normal or abnormal tomograms based on the level of serum PRL. Polytomography remains the single most important diagnostic test in establishing the presence of a pituitary tumor.

Adolescent↗
PubMed1978

Factors affecting pituitary gonadotropin function in users of oral contraceptive steroids.

In order to determine whether certain factors influence the direct pituitary suppressive effect of contraceptive steroid, 50 subjects who had used various formulations of oral contraceptive steroids for periods of time ranging from one to nine years were stimulated with 50 microgram of gonadotropin-releasing hormone (GnRH) during the last week of oral contraceptive ingestion. The response of lutinizing hormone (LH) and follicle-stimulating hormone (FSH) was compared to the results obtained in nine control subjects with regard to: (1) age of subject. (2) type of contraceptive formulation used, and (3) length of use. Prestimulation levels of LH and FSH, respectively, were significantly decreased in 37 (74 per cent) and 42 (84 per cent) of the subjects. Following GnRH stimulation, peak responses of serum LH and FSH, respectively, were also significantly lower than those in the control subjects in 40 (80 per cent) and 45 (90 per cent of the subjects. The degree of suppression of pituitary gonadotropins, both before and after GnRH administration was significantly correlated with the type of steroid formulation used, being greatest with a combination of d-norgestrel and ethinyl estradiol. No correlation was found with length of use of oral contraceptives or age of the subjects.

Adult↗
PubMed1978

An in vivo system in man for quantitation of estrogenicity. I. Physiologic changes in binding capacity of serum corticosteroid-binding globulin.

A modified method of measuring the binding capacity of corticosteroid-binding globulin (CBG-BC) in serum using 3H-cortisol saturation-charcoal adsorption is described. Forty serum samples per day can be assayed in duplicate, each sample with a heated nonspecific binding blank (60 degrees C.). The interassay coefficient of variation is less than 6 per cent. All age groups of men and women had similar levels of CBG-BC, except postmenopausal women, whose levels were higher (15.9 +/- 0.2 vs. 18.7 +/- 0.8 microgram per 100 ml., mean +/- standard error of the mean, respectively; z = -3.51, p less than 0.001). The variance of serum levels of CBG-BC throughout the menstrual cycle in five women was small (coefficient of variation = 13 per cent) and showed no relationship to the marked and cyclic changes in estradiol levels (coefficient of variation = 73 per cent). In pregnancy the levels of CBG-BC increased linearly after estradiol levels exceeded 1,300 pg. per milliliter and after estrone levels exceeded 500 pg. per milliliter (r = 0.88, p less than 0.001; and r = 0.85, p less than 0.001, logarithmic regression analysis). The findings of this study indicate that serum levels of CBG-BC are relatively constant in men and menstruating women. In pregnancy after a high threshold of endogenous estrogen is reached, CBG-BC increases in a direct dose-response manner as levels of estradiol increase further.

Adult↗
PubMed1978

Contraception.

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Adolescent↗