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Biomedical subjects

B Little

Publications and source records attributed to B Little.

At least 19 recordsLinked to original sources

Reduced serum inhibin concentrations during ovulatory cycles of estrogen-treated rhesus monkeys: an indicator of FSH bioactivity.

Female rhesus monkeys treated with exogenous estrone initially were anovulatory. Although estrone and estradiol concentrations were maintained 1.5- to 2.5-fold elevated, i.e. in the midfollicular range, ovulatory cycles resumed in three of four animals after 6-15 months of anovulation. During the ovulatory cycles the serum bio LH concentrations were the same in estrone-treated animals as during ovulatory cycles of control monkeys, but the daily basal serum FSH concentrations detectable by RIA were significantly reduced during the ovulatory cycles of the estrone-treated animals compared to the cycles of the controls. In the present study serum inhibin concentrations were measured to determine whether or not they were increased and the cause of the selective decrease in FSH concentrations in the estrogen-treated monkeys. Serum LH, FSH, progesterone, and inhibin concentrations were measured by RIA in blood samples collected during the third year of continuous estrogen treatment. The lack of an effect of elevated estrogen on LH concentrations and a significant estrogen-induced decrease in serum FSH concentrations during ovulatory cycles was confirmed (FSH, control: 5.6 +/- 0.68 ng/ml; estrogen-treated: 2.5 +/- 0.09 ng/ml; P = 0.01). There was also a significant decrease in the serum inhibin concentrations detectable by RIA during the follicular phase of the estrone-treated monkeys compared to the follicular phase of the control animals (119 +/- 17 vs. 462 +/- 105 microliter eq/ml; P = 0.04). These results indicate that the lower serum concentrations of FSH in the estrogen-treated monkeys were not a result of an increase in ovarian secretion of inhibin. The lower inhibin concentrations suggest that FSH bioactivity, as well as immunoreactive FSH, is significantly reduced during the ovulatory cycles of the estrone-treated monkeys. Even though the estrogen treatment decreased the FSH bioactivity, sufficient FSH secretion occurs in the presence of the elevated estrone and estradiol concentrations to induce and support apparently normal ovulatory cycles.

Animals

The failed appointment.

OBJECTIVE: To determine reasons for failed internal medicine clinic appointments. DESIGN: A retrospective telephone survey of patients within one month of a failed appointment. SETTING: An ambulatory teaching clinic for indigent patients staffed by 30 internal medicine residents where patients have scheduled visits every 30 minutes. PATIENTS/PARTICIPANTS: From the 1,622 scheduled patient visits, the names of 405 patients who failed their appointments were selected for further contact. Successful contact was established with 100 patients. MEASUREMENTS AND MAIN RESULTS: The patients completed a telephone survey administered by residents and students regarding demographics, general health, reasons for failed appointment, and satisfaction with the clinic. Transportation problems accounted for 13% of missed visits, forgetfulness accounted for 11%, personal or family illness and rescheduling problems accounted for 8% each. Miscellaneous reasons accounted for the remainder. Seventeen percent of patients who missed their appointments feared the encounter, but none volunteered this as a reason for their no-show. Fifty-one percent of patients felt that the failed appointments could not have been prevented. Ninety percent of those surveyed were satisfied with their clinic physician, and 82% were seen on-time when appointments were kept. CONCLUSIONS: Lack of transportation appeared to be the most prohibitive factor in continuity of care among this indigent population. Patients are generally seen on-time and are satisfied with their care. Financial pressure does not appear to keep people away. Fear of the physician encounter and forgetfulness may be areas for improved patient education.

Adult

Escape from chronic estrogenic suppression of ovarian function in the adult rhesus monkey: evidence for changing sensitivity of gonadotropin secretion to estrogen inhibition.

Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing packed with estrone. The implants were replaced every 6-8 months to maintain the serum estrone and estradiol concentrations constantly elevated 1.5-2.5-fold, i.e. in the midfollicular phase range, for 4 yr. Increasing the estrone and estradiol concentrations initially led to anovulation which persisted for 6 to 15 months after which three of four of the estrogen-treated animals resumed ovulatory cycles. These animals then waxed and waned between anovulation and ovulatory cycles for the remainder of the study period. The resumption of ovulatory cycles were attributed to an escape of the central nervous system-pituitary axis from the suppressive effect of the elevated estrogen concentrations, since serum estradiol concentrations did not change. During anovulatory and ovulatory months the basal LH concentration was not significantly increased in the estrogen-treated monkeys compared to the control animals, but it was significantly reduced during anovulatory months compared to ovulatory months. Furthermore, LH secretion in response to a bolus of GnRH was attenuated in the monkeys chronically exposed to the acyclic elevation of blood estrogen levels. As the sensitivity to estrogen decreased, sufficient basal concentrations of FSH and LH were achieved to support ovulatory cycles with associated midcycle surges of LH and FSH secretion and apparently normal luteal patterns of progesterone secretion. Since the daily FSH concentrations of these ovulatory cycles of the estrone-treated animals were significantly lower than that of ovulatory cycles of the control monkeys, the ovulatory cycles of the estrogen animals may not have been normal, but this was not directly documented. These studies suggest that elevated basal estrogen levels do not lead to elevated basal LH secretion in the female primate; and also in the intact adult primate the central nervous system-pituitary axis has the potential to change its sensitivity to the negative feedback effects of estrogen on gonadotropin secretion.

Animals

Proximal chronic inflammatory polyneuropathy with multifocal conduction block.

The pathological findings in proximal and distal nerve biopsy specimens are described in a patient with the clinical and electrophysiological features of chronic inflammatory polyneuropathy with multifocal conduction block. Proximal onion bulb hypertrophic changes in the brachial plexus were associated with inflammatory cell infiltrates. In contrast, the sural nerve biopsy specimen showed a mild picture of mixed axonal degeneration and demyelination-remyelination without inflammatory infiltration.

Action Potentials

An in vitro study of the effects of androgens on the cytoskeleton of ovarian granulosa cells with special reference to actin.

Ovarian granulosa cells from small antral follicles from immature rats were cultured in a serum-free medium for 1-6 days with or without the presence of 10(-5) M dehydroepiandrosterone (DHEA) or 10(-5) M-androstenedione (delta 4-A). Control cultures reveal that the cells are flattened and contain many filamentous bundles organized as stress fibers, numerous scattered cytoplasmic actin filaments, microtubules and vimentin. Alpha actinin and myosin were shown by immunocytochemistry to have a punctate pattern along the stress fibers. For the most part, cells exposed to androgens did not flatten; however, they assumed a varied shape and contained fewer stress fibers and actin filaments. Many of these cells did not develop stress fibers and those that did develop were fewer in number and displayed--actinin and myosin in a punctate pattern. Microtubules and vimentin filaments remained unaltered when compared to controls. It is believed that the deficiency of actin filaments, coupled with certain other degenerative changes which express themselves in other cellular compartments, leads to an early atresia of the granulosa cell cultured in high concentrations of androgens.

Actinin

Androgen-induced changes in rat ovarian granulosa cells in vitro.

Ovarian granulosa cells collected from small antral follicles from immature rats were cultured in McCoy's 5A medium, for 1-6 days in the presence of delta 4-androstenedione, testosterone, dihydrotestosterone, and dehydroepiandrosterone (10(-5) M and 10(-7) M). Granulosa cells examined by electron microscopy demonstrated many lipid droplets, mitochondria with tubular cristae and profiles of smooth endoplasmic reticulum, all suggestive of active metabolism in the cell. Cells cultured in androstenedione, testosterone, dihydrotestosterone and dehydroepiandrosterone produced estrogen and progesterone as measured by radioimmunoassay. By day 4, cells cultured in androgen had almost completely degenerated. The control cells acquired none of the aforementioned characteristics and survived up to beyond 6 days, at which time the experiments were terminated. This study supports the hypothesis that high concentrations of androgens in cultured granulosa cells contribute to their degeneration through altered structure, which is associated with functional change.

Androgens

Effect of chronically elevated androgen or estrogen on the glucose tolerance test and insulin response in female rhesus monkeys.

Insulin concentrations, in response to an intravenous glucose bolus after a 24-hour fast, have been studied in female rhesus monkeys in which the circulating levels of androstenedione and testosterone or estrone and estradiol have been increased for as long as 4 1/2 years. No significant differences were observed in the basal insulin or C-peptide concentrations in the androgen or estrogen-treated animals compared with each other or with normal cycling, nontreated control animals. The insulin and C-peptide responses to intravenous glucose were similar in control and androgen-treated monkeys. Compared with both the control and androgen-treated monkeys, the responses of the estrogen-treated monkeys tended to be lower but were not significantly different. The glucose disappearance rate after the intravenous glucose bolus was not significantly different in androgen and control monkeys but was significantly slower during the initial 30 minutes in the estrogen-treated monkeys compared with both the control and androgen-treated monkeys. These studies suggest that chronically elevated androgen levels in the mature female subhuman primate do not lead to insulin resistance or overt glucose intolerance.

Androstenedione

Fatal immune hemolytic anemia and hepatic failure associated with a warm-reacting IgM autoantibody.

Autoimmune hemolytic anemia (AIHA) caused by warm-reacting IgM autoantibodies is rare. We report a fatal case of primary AIHA with a warm-reacting IgM autoantibody. Recurrent episodes of intravascular hemolysis, unresponsive to all therapy and progressive hepatic dysfunction characterized the patient's clinical course. Despite corticosteroid therapy, splenectomy and multiple blood transfusions, the patient died from liver failure. The IgM autoantibody caused autoagglutination of the patient's red cells at 37 degrees C. Eluates prepared from the patient's red cells agglutinated saline-suspended test cells without the addition of antiglobulin reagent. We propose that warm-reacting IgM antibodies may lead to in vivo autoagglutination and may be associated with hepatic failure.

Adult

Malignant gonadal stromal tumor of the testis arising with a malignant teratoma.

We report a case of a rare malignant gonadal stromal tumor arising with a malignant teratoma of the testis. The malignant gonadal stromal element of the tumor or the nongerminal cell component was resistant to chemotherapy and ultimately metastasized to the lymph nodes, lung, bones and liver. Nongerminal cell tumors arising with germinal cell neoplasms may become more common because the chemosensitive germ cell tumor may be destroyed and the chemoresistant nongerminal tumor remains. The nongerminal cell tumor is the most important prognostic factor and also dictates possible later changes in therapy.

Adult

The effect of chronic and acyclic elevation of circulating androstenedione or estrone concentrations on ovarian function in the rhesus monkey.

The concept that chronically elevated blood androstenedione concentrations increase the incidence of anovulation in the primate and that acyclic elevated basal blood androgen and/or estrogen concentrations cause abnormal gonadotropin secretion was studied. Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing filled with androstenedione or estrone and compared with controls. Androstenedione implants increased the serum androstenedione concentrations from 1.6 +/- 0.1 (SE) ng/ml to 6.30 +/- 0.27 ng/ml. By peripheral conversion the testosterone concentration increased from control values of 279 +/- 10 (SE) pg/ml to 1280 +/- 41 pg/ml. The testosterone concentration in the estrone-treated monkeys was 247 +/- 9.7 pg/ml. The estrone concentrations were: controls, 63.2 +/- 3.1 (SE) pg/ml; androstenedione-treated monkeys, 63.2 +/- 3.1 pg/ml; and estrone-treated animals, 150 +/- 5.3 pg/ml. The corresponding estradiol concentrations were: control animals, 35.1 +/- 2.1 (SE) pg/ml; androstenedione animals, 30.9 +/- 1.8 pg/ml; and estrone-treated monkeys, 65.7 +/- 3.9 pg/ml. There was no difference in the morning serum cortisol concentrations between any of the three groups or between ovulatory or anovulatory months. The chronic elevation of either androstenedione or estrone caused an increased incidence of anovulation compared with the controls. Increased estrogen concentrations caused increased anovulation during both summer and winter months; however, increased androgen concentrations caused increased anovulation only during the summer months. However, LH concentrations were unaffected in either group but were lower during anovulation months in all three groups. An LH or FSH surge followed an estradiol bolus in three of four control animals and four of six androstenedione-treated but none of the estrone-treated monkeys. Histological examination of ovarian biopsies demonstrated thickening of the tunica albuginea ovarii in androgen-treated ovaries and an apparent increased number of atretic follicles. Corpora lutea were absent in the ovaries of the estrogen-treated monkeys, but otherwise these ovaries were similar to those of controls. It is concluded that chronic acyclic elevation of blood androstenedione (and resultant testosterone) increases seasonal anovulation in the rhesus monkey. Increased blood estrone (and resultant estradiol) leads to almost complete anovulation throughout the year and renders the central nervous system-pituitary axis insensitive to positive feedback effect of estradiol. Neither treatment caused an increase in basal LH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex

Autoradiographic localization of estradiol- and progesterone-concentrating neurons in the isolated rhesus monkey hypothalamus.

Progesterone- and estradiol-concentrating neurons were autoradiographically localized in the in situ, vascularly isolated, rhesus monkey hypothalamus. Estradiol-concentrating neurons were dispersed throughout the hypothalamus, their density being greatest in the medial preoptic (MPOA) and medial basal hypothalamic nuclei (viz. dorsomedial, ventromedial (VMH) and infundibular nuclei). In contrast, progesterone-concentrating neurons were less densely localized in the medial preoptic, ventromedial (medial division) and infundibular nuclei. There was a virtual absence of progestin-concentrating cells in the anterior and posterior hypothalamic zones. This localization of cells was not attributed to the perfusion pattern of the isolated hypothalamus since a complete distribution of injected microspheres was found throughout the hypothalamus. The results of these studies indicate that a possible division between estradiol- and progesterone-concentrating neurons exists within the MPOA-medial basal hypothalamic nuclei of the rhesus monkey.

Animals

Tissue sites of aromatization in the female rhesus monkey.

Nine female rhesus monkeys (four in the follicular and five in the luteal phases of their cycles) had catheters implanted and were infused iv with [7-3H]androstenedione (A) and [4-14C]estrone (E1) for 4 h. Blood samples were drawn at intervals from the hepatic, renal, jugular, uterine, and brachial veins and the femoral artery. The samples were analyzed for radioactivity as A and E1. The mean +/- SE MCRs for A and E1 were 280 +/- 40 and 270 +/- 30 liters/day, respectively. The mean extractions across the liver measured in six of the monkeys were 0.83 +/- 0.03 for A and 0.71 +/- 0.06 for E1. The percentage of A entering each tissue, which was measured as E1 leaving the tissue (pA,E1AV), was 0.20 +/- 0.10 for splanchnic, 0.21 +/- 0.11 for renal, 0.46 +/- 0.21 for jugular, 2.36 +/- 1.27 for arm, and 0.35 +/- 0.10 for uterine veins. Because of the sampling technique, the value for the uterus may be a reflection of ovarian blood admixture with uterine blood. There were no apparent differences in tissue aromatization between values in the follicular and luteal phases of the cycle. The overall mean value for the percentage of A infused and measured as E1 in arterial blood (pA,E1BB) was 1.01 +/- 0.38%. Using previously reported tissue blood flow, we calculate that the contributions to the overall aromatization rate of tissues drained by the brachial, renal, jugular, hepatic, and uterine veins are 23%, 5%, 5%, 4%, and 0.2%, respectively. Thus, the splanchnic tissue is a minor site for extraglandular aromatization of androgens in the rhesus monkey. An important site appears to be the arm, which reflects aromatization in adipose tissue, muscle, skin, and supporting structures.

Androstenedione

Uterine metabolism of gonadal steroids during the menstrual cycle.

The metabolic clearance rate and uterine extraction of (3H)progesterone, (3H)estradiol, and (14C)estrone were studied at the time of hysterectomy in six women on or before day 12 of the menstrual cycle, in three women after day 12, and in one postmenopausal woman. The metabolic clearance rates of progesterone, estradiol, and estrone were in the same range as for normal women as previously reported by us. The uterine extraction for progesterone ranged between 12% and 37% on or before day 12 and 0% to 5% after day 12, and was 7.4% in the postmenopausal woman. The uterine extraction of estradiol was 0% to 25% on or before day 12, and 0%, 4%, and 22% after day 12 and was 18% in the postmenopausal woman. The uterine extraction of estrone was 7% to 24.5% on or before day 12 and 0% after day 12 and was 18% in the postmenopausal woman. The across-uterine interconversion of estradiol to estrone was 0% to 2.7% and of estrone to estradiol 0% to 2.6%. Both conversions appeared to be independent of the day of the menstrual cycle. The results suggest that the uterine metabolism of progesterone and estrone and perhaps estradiol is lower in the luteal phase of the cycle as compared to the follicular phase and that the conversion of estradiol to estrone may not be a major reaction of estradiol metabolism in the human uterus.

Adult