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Biomedical subjects

V D Castracane

Publications and source records attributed to V D Castracane.

At least 55 records · Page 3Linked to original sources

Immediate postpartum insertion of the norplant contraceptive device.

OBJECTIVE: To determine the safety and efficacy of Norplant (Wyeth-Ayerst Laboratories, Philadelphia, PA) insertion immediately postpartum. DESIGN: Prospective study of 14 women receiving Norplant immediately postpartum compared with controls (n = 6) having a bilateral tubal ligation. Subjects were followed for 3 months postpartum, and data were analyzed by analysis of variance and chi2. SETTING: Academic Health Sciences Center. PATIENTS: Female subjects 18 to 35 years old who had an uncomplicated term pregnancy, normal spontaneous vaginal delivery, and did not breast-feed. INTERVENTION: A brief interview, physical exam, and blood and urine samples were evaluated during a 12-week postpartum period. MAIN OUTCOME MEASURES: Major complaints, serum chemistry panels, hematologic and coagulative measures, serum E2, P, levonorgestrel, PRL, LH, FSH, and urinary estrone-3 conjugates and pregnanediol-3-glucuronide concentrations. RESULTS: Serum levonorgestrel peaked at approximately 2,000 pg/mL (6,400 pmol/L) during the 1st week after Norplant insertion, declining to approximately 250 pg/mL (800 pmol/L) by the 8th week. Significant differences between Norplant and control groups included bleeding irregularities, headaches, alopecia, and abdominal discomfort. Serum electrolytes, metabolic markers, and blood components were within normal limits. Serum E2, P, and urinary steriod biomarkers indicated that steroid secretion was suppressed severely in the Norplant group compared with controls who exhibited normal postpartum ovarian activity. CONCLUSION: Norplant inserted immediately postpartum appears to be a safe and effective method of contraception. However, the long-term hypoestrogenic state and contraceptive efficacy beyond the 3-month postpartum period as observed in this study are concerns that need further clinical evaluation.

Adolescent↗

Postimplantation increase in plasma fibrinogen concentration with increase in relaxin concentration in pregnant dogs.

OBJECTIVE: To determine time courses of pregnancy-related changes in plasma fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity (CRP-LI) concentrations in pregnant and nonpregnant dogs. ANIMALS: 16 pregnant and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant dogs of other breeds. PROCEDURE: Fibrinogen was measured by nephelometric centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10 nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7 nonpregnant dogs. RESULTS: During pregnancy, fibrinogen concentration increased between days 21 and 30 after the luteinizing hormone surge, and was > 280 mg/dl between days 29 and 50 in 84 of 86 samples, with peak values 539 +/- 29 mg/ dl higher (P < 0.01) than those in nonpregnant dogs (188 +/- 8 mg/dl), higher values from days 21 to 50 (P < 0.01) than those in nonpregnant dogs, and values similar to those in nonpregnant dogs after day 50. Relaxin concentration was increased from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI concentration was higher in pregnant dogs at days 26 to 50, but values were inconsistent within and among dogs, and near the limit of sensitivity of the assay. CONCLUSIONS: Concentration of the acute-phase reactant protein fibrinogen increases after day 20 following implantation in dogs, at or just before the pregnancy-specific increase in relaxin concentration from days 26 to 30, and persists until day 50. CLINICAL RELEVANCE: Fibrinogen assay may be useful for pregnancy diagnosis in dogs.

Acute-Phase Proteins↗

When is it safe to switch from oral contraceptives to hormonal replacement therapy?

Women may continue to use oral contraceptives (OCs) into their 40's and 50's, but to date no method has been evaluated to ascertain their ovarian status, i.e., whether fertility and estrogen production have diminished sufficiently so they could be safely switched to hormonal replacement therapy. A group of 12 postmenopausal women who had been, for long periods of time, on a regimen of 3 back-to-back packages (i.e., 63 days on, 7 days off) of low-dose oral contraceptives have been studied. Secondly, a group of 9 perimenopausal women aged 36 to 47 were examined in the same manner. The third group consisted of early reproductive age women (arbitrarily divided into subsets aged 17-25 and 26-35 using low-dose OCs in the customary regimen) as normal controls. Blood samples were obtained on the last day of a pill cycle and at 7 days off the pill. In some menopausal women, blood samples were obtained at both 7 and 14 days off OCs. Serum was assayed by RIA for estradiol, FSH and LH. As expected in the young reproductive age women, estradiol levels increase at one week off the pill, together with a rebound in FSH and LH to follicular phase levels. In the perimenopausal group, there was a sharp distinction based on age. The women over 40 showed a more marked rise in FSH while those aged 36-40 showed a distinctly lesser response. Estradiol levels were variable, but tended to show some age grouping. Little diagnostic separation was observed for LH. In postmenopausal women, FSH levels were not always elevated at one week post-pill, and even in a second trial with sampling at one and two weeks off the OC, not all postmenopausal women showed a "menopausal" increase in FSH. The more uniform feature was that estradiol levels never increased above basal values. The study found that serum estradiol levels increase after a week off the pill in controls, but are unchanged at one and two weeks in the menopausal group. FSH levels rebound normally in reproductive age women and usually, but not always, increase substantially in postmenopausal women. After two weeks off OCs, an increased FSH and/or no change in basal estradiol levels is strong evidence that it is now safe (contraceptively speaking) to switch from OCs to standard hormone replacement regimens.

Adolescent↗

Physiopathology of premature progesterone elevation.

OBJECTIVE: To determine the effects of the last hMG administration on plasma P and androgen profiles during controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Controlled clinical study. SETTING: The IVF-ET program of a tertiary outpatient care center, Hôpital A. Béclère, Clamart, France. PATIENTS: Nine IVF-ET candidates aged 25 to 36 years having presented normal responses to COH in previous IVF-ET cycles. INTERVENTIONS: Controlled ovarian hyperstimulation was induced for IVF-ET using hMG after endogenous gonadotropins were suppressed with a time-release GnRH agonist. Just before the last hMG administration (225 IU), the participants were hospitalized for 24 hours for serial blood sampling. These occurred before (baseline) and after hMG administration, every 30 minutes for 1 hour, hourly for 4 hours, and every 3 hours for the remaining part of a 24-hour post-hMG observation period. MAIN OUTCOME MEASURE: Measurement of P, T, androstenedione (A), E2, FSH, and LH. RESULTS: Plasma P and androgens (T and A) increased significantly, reaching peak values 12 to 15 hours after hMG administration and decreased progressively thereafter, to reach values not significantly different from baseline 24 hours after hMG administration. Plasma E2 levels increased progressively and steadily during the 24-hour observation period. Plasma FSH levels remained constant after hMG administration while LH stayed undetectable. CONCLUSION: In COH cycles induced for IVF-ET, the hormonal profile after the last hMG injection suggests that hMG triggers an increase in plasma P and androgens that culminates 12 to 15 hours after hMG administration. This elevation in plasma P and androgens observed after hMG administration is likely to reflect a direct action of the LH and/or FSH components of hMG on granulosa cells. In some women these hormonal consequences of hMG treatment may impair endometrial receptivity in IVF-ET cycles.

Adult↗

Testosterone and androstenedione in premature ovarian failure pregnancies: evidence for an ovarian source of androgens in early pregnancy.

Numerous anecdotal reports but few scientific approaches have suggested an increase in androgens in early pregnancy. In this study we have compared the concentration of serum androgens, testosterone and androstenedione in early pregnancy, starting within the cycle of conception. We have taken the opportunity to study women with premature ovarian failure where pregnancy develops in the virtual absence of ovarian functions. This study demonstrates that the concentration of testosterone (0.29 +/- 0.04 ng/ml) and androstenedione (1.770 +/- 0.136 ng/ml) in these subjects is as low as, if not lower than, non-pregnant women (0.39 +/- 0.02 and 2.170 +/- 0.025 ng/ml), significantly increased in normal pregnancies (1.190 +/- 0.118 and 3.920 +/- 0.297 ng/ml; P < 0.05) and even further increased in human menopausal gonadotrophin-treated cycles (1.990 +/- 0.230 and 8.19 +/- 0.72 ng/ml; P < 0.05). These studies demonstrate that the ovary is a contributor to the circulating concentrations of testosterone and androstenedione starting within the cycle of conception.

Androstenedione↗

Genetic variation in plasma androgens and ovarian aromatase activity during mouse pregnancy.

Genetic variation in fetal survival, maternal plasma androgen levels, and ovarian aromatase activity was examined mid (Day 9) and late gestation (Day 16) in strains of mice that differ in reproductive performance (A/J, C57BL/6J, C8/JIs, C17/JIs, and S15/JIs). At both gestational stages, females selected for large litter size (S15/JIs) carried more fetuses than any of the other strains examined. Particularly at midpregnancy, S15/JIs females also maintained higher plasma levels of androstenedione and testosterone relative to both control strains, C8/JIs and C17/JIs. Consistent with previously reported changes in peripheral estrogen levels during mouse pregnancy, aromatase activity was higher on Day 16 than on Day 9. This study demonstrates genetic variation in fetal survival that is correlated with increased maternal androgen levels. A stage-specific gestational increase in aromatase activity occurs in several strains of mice and is associated with elevated plasma estrogen during the second half of pregnancy.

Androgens↗

Follicular and luteal phase hormonal responses to low-volume resistive exercise.

The purpose of the study was to 1) determine the effects of a low-volume resistive exercise protocol on serum concentrations of estradiol (E2), progesterone (P4), growth hormone (GH), testosterone (T), and androstenedione (AN) and 2) ascertain whether the endocrine responses are affected by the phase of the menstrual cycle. Eleven untrained, healthy women were assigned to either an early follicular or luteal testing group. The subjects completed three sets of bench press, lat-pull, leg extension, and leg curl exercises at a 10 repetition maximum load on fixed machines with 2-min of rest between sets. Blood samples were collected through an indwelling cannula before, during, and after the exercise. Area-under-the-response-curve (AUC) data demonstrated that E2 concentrations were significantly elevated in both follicular and luteal phases with a greater response in the luteal phase. Moreover, data suggest there is a luteal phase-induced increase in GH and AN in response to the low-volume resistive exercise; however, P4 and T concentrations in untrained women are not increased by low-volume resistive exercise with 2-min rest periods, nor does the altered hormonal milieu produced by the phase of the menstrual cycle affect these hormonal responses.

Adult↗

Recurrent ovarian sex cord tumor with annular tubules: tumor marker and chemotherapy experience.

Recurrent sex cord tumor with annular tubules is an unusual ovarian cancer. The authors report a patient with recurrent disease that was ultimately followed with multiple tumor markers. During this period the patient was treated only with chemotherapy. Her regimen consisted of a combination of etoposide, bleomycin, and cisplatin. The tumor markers that were followed were CA-125, CEA, inhibin, and Müllerian-inhibiting substance (MIS). There was no elevation of the CA-125 or CEA, but inhibin and MIS proved to be effective markers. Serum inhibin and MIS correlated perfectly with her documented disease status and was brought into the normal range when the patient was disease-free. This disease-free status was proven by surgical reexploration. This report is the first documented complete response in this rare malignancy treated by chemotherapy alone with distant metastatic spread. It also gives strong linkage of inhibin and MIS as good markers in this particularly rare malignancy.

Adult↗

Danazol: prolonged suppression of gonadotropins after subcutaneous administration in the castrate male rat.

OBJECTIVE: Our purpose was to compare oral versus subcutaneous administration of danazol for its effect on elevated serum luteinizing hormone and follicle-stimulating hormone levels in castrated male rats. STUDY DESIGN: A single dose of danazol, either 100 or 400 mg/kg, was administered by gastric intubation or injected subcutaneously. Jugular venipuncture blood samples were taken at 0, 3, 24, and 48 hours and at 7, 10, 15, and 25 days, and serum levels of luteinizing hormone and follicle-stimulating hormone were determined by radioimmunoassay. RESULTS: Gonadotropin levels returned to control values 96 hours after oral administration, whereas 400 mg/kg of danazol administered subcutaneously resulted in suppression of gonadotropins for 25 days. CONCLUSIONS: Subcutaneous administration of danazol results in an unexpectedly prolonged suppression of serum gonadotropins compared with the same dose administered orally. A change from oral administration to a prolonged-release subcutaneous preparation of danazol may enhance the use of this drug in clinical situations and may lessen undesirable side effects.

Administration, Oral↗

Running-induced alterations in growth hormone, prolactin, triiodothyronine, and thyroxine concentrations in trained and untrained men and women.

This study examined whether gender and/or training were related to the exercise-induced changes in plasma concentrations of growth hormone (GH), prolactin (PRL), triiodothyronine (T3), and thyroxine (T4). Twenty subjects (male and female 10-km runners; untrained males and females) ran on a treadmill for 30 min at 80% of previously determined maximum heart rate. Blood samples were taken through an indwelling catheter from an antecubital vein at -30, 0, +15, +30 min of the test and 30 min of recovery. Rectal temperature rose significantly (p < .01) at +15 and +30 min with concomitant rise in GH concentration, but PRL, T3, and T4 were not affected by the exercise. We concluded that a 30-min run at 80% of maximum heart rate is associated with higher concentrations of GH but not of PRL, T3, and T4. Neither training state nor gender affected the aforementioned results.

Adult↗

Growth hormone, IGF-I, and testosterone responses to resistive exercise.

It has been suggested that growth hormone (GH), testosterone (T), and insulin-like growth factor I (IGF-I) play large roles in muscle tissue growth; however, in only two investigations IGF-I responses to resistive exercise have been examined. Eight young males who had not weight trained for a minimum of 5 months participated in the study. Three sets of bench press (BP), lat-pull (LP), leg extension (LE), and leg curl (LC) exercises were performed at a 10-RM load for 10 repetitions or until failure. Blood samples were collected from an IV catheter before exercise (-30 min and -10 min), after each individual exercise (BP, LP, LE, LC), and after the exercise session (+5, +15, +25, +35, +95 min; +5:35, +22:30, and +23:30 h). GH, IGF-I, and T determinations were corrected for plasma volume change. GH significantly increased (P < 0.05), but IGF-I did not change. Correction for plasma volume accounted for significant increases in T, but did not account for GH and IGF-I results. These data suggest that moderate resistive exercise may increase GH concentrations, whereas elevated T levels can be accounted for by exercise-induced alteration of plasma volume.

Adult↗

The relationship of conceptus number and fetal sex to maternal serum testosterone concentration in the rat.

On Day 8 of pregnancy, the number of implantation sites in pregnant rats was adjusted to 1, 2, 4, 6, or greater than 10. Blood was collected on Days 11, 12, 15, 18, and 20 for the determination of serum testosterone, progesterone, and androstenedione. Serum testosterone levels exhibited a direct linear relationship with implantation number, increasing from 1 through greater than 10 implants. This linear relationship was particularly evident at Days 12, 15, and 18 of pregnancy. Serum progesterone levels increased from one to four conceptuses and plateaued above this number. There was no apparent relationship between the number of conceptuses and serum androstenedione levels, which may reflect the multiple origins of this steroid in the pregnant rat. In a separate group of rats in which the number of conceptuses was adjusted to three on Day 8 of pregnancy, blood was collected on Days 11, 12, 15, 18, and 20. Fetal sex was determined between the last bleeding and the day of parturition. Serum testosterone was determined and results were examined with regard to the number of male/female fetuses in the litter of three. There was no relationship between maternal serum testosterone levels and the number of male fetuses, indicating that the fetal testis does not make a significant contribution to circulating maternal testosterone levels.

Androstenedione↗

Mood alteration from treadmill running and its relationship to beta-endorphin, corticotropin, and growth hormone.

We examined the effects of running on mood alteration in males and females and its relationship to changes in beta-endorphin (B-EN), corticotropin (ACTH), and growth hormone (GH). Thirteen males and ten females ran on a treadmill for 30 min at 80% of previously determined maximum heart rate. Five plasma samples were obtained through an indwelling catheter before exercise (-30 and 0 min), during exercise (15 min), at exercise completion (+30 min), and after 30 min of recovery (R30); the Profile of Mood States (POMS) inventory was administered at -30 and +30. Composite mood improved after the run for both males and females withput concomitant rise in B-EN. For males but not females, an increase in mood was associated with lower B-EN (r = 0.65) and ACTH (r = 0.65) and this relationship was also significant prior to exercise for B-EN (r = 0.74) and ACTH (r = 0.81). It appears that an increase in peripheral beta-endorphin concentration may not be a major contributor to improved mood in response to exercise, but is an indicator of negative mood in males.

Adrenocorticotropic Hormone↗

Effects of treadmill running on plasma beta-endorphin, corticotropin, and cortisol levels in male and female 10K runners.

Reports of plasma beta-endorphin (B-EN) levels in response to submaximal exercise have been highly disparate. Variations in experimental design have complicated interpretation of previous research. The present study was designed to determine whether a sequential change in plasma beta-endorphin (B-EN), corticotropin (ACTH), and cortisol levels occurs in response to a 30-min submaximal run. Twenty-three subjects were divided into four groups: male runners, female runners, sedentary males and sedentary females. Subjects ran on a treadmill at 80% of previously determined maximum heart rate. Five plasma samples were obtained through an indwelling catheter before exercise (-30 and 0 min), at 15 and 30 min of exercise, and after 30 minutes of recovery. The run resulted in no rise in B-EN, ACTH, and cortisol despite an elevated rectal temperature. B-EN values were significantly higher in males than in females (p less than 0.01). No sex or training differences were seen with respect to change of hormone concentrations over the course of the run. Three male runners developed symptoms of vasovagal syncope after the catheter placement and had high initial B-EN, ACTH, and cortisol concentrations which decreased throughout the run. These data indicate that gender and training do not affect ACTH and cortisol concentrations before, during, and after 30 min of treadmill running at 80% of maximum heart rate, whereas B-EN concentrations are higher in males under these conditions.

Adrenocorticotropic Hormone↗

Diethylstilbestrol-induced cervical and vaginal adenosis using the neonatal mouse model.

The relevance of diethylstilbestrol (DES) administration to neonatal mice as a model for human pathology attributed to the use of DES in high-risk pregnancies has been investigated, particularly with respect to cervical and vaginal changes in female offspring. Neonatal DES treatment of mice results in tonic pituitary gonadotropin release and continuous estrogen secretion by the ovary. Studies were designed to determine the effect of this altered ovarian endocrine activity on cervical and vaginal histopathology. Ovariectomy of DES-treated mice, with or without estradiol replacement, did not eliminate the lesions, nor did estrogen and progesterone administered in a regimen intended to mimic estrous cycle changes. Induction of the constant estrus state by neonatal estradiol benzoate or testosterone propionate administration or by exposure to constant light did not produce the type of vaginal or cervical changes seen in DES mice. Thus, altered ovarian function is apparently not required for the vaginal and cervical changes appearing in later life. A role for endogenous (or exogenous) ovarian hormones in the developmental progression toward normality is suggested.

Animals↗

Timing of the luteal-placental shift in the baboon (Papio cynocephalus).

Normally cycling female baboons (Papio cynocephalus) were mated with males of proven fertility during the periovulatory period. After pregnancy was confirmed, the corpus luteum-bearing ovary was removed (CL-OVX) at day 18 (n = 1), day 20 (n = 4), day 25 (n = 3), or day 30 (n = 4) of gestation. Upon CL-OVX at day 18 or 20, there was an immediate decline in plasma progesterone to basal levels, and pregnancy was not maintained. After CL-OVX on days 25 or 30, there was a transient, small decline in plasma progesterone levels which recovered rapidly to levels found in pregnant controls, and pregnancy was maintained. Only one baboon failed to maintain pregnancy after CL-OVX on day 30, but progesterone levels remained elevated for 3 days before the termination of pregnancy suggesting that causes other than CL-OVX were responsible. In another group of three baboons, depot medroxyprogesterone acetate was administered before CL-OVX at day 20 of gestation and again at days 23 and 26. Progesterone declined sharply after CL-OVX to near basal levels but increased between days 22 and 24, and pregnancy was maintained in all cases. Estradiol levels did not decline as sharply as those of progesterone in any group, which indicates an exclusively luteal source for progesterone while estradiol comes from both the luteal and nonluteal ovaries. There is a placental increase in estradiol production which occurs much later than does the production of progesterone. The luteal-placental shift occurs between day 20 and 25 of gestation in the baboon, earlier than in women but later than in rhesus monkeys.

Animals↗

The relationship of estrogen to placental steroidogenesis in the baboon.

In previous studies in pregnant baboons, estrogen deprivation produced by the administration of the estrogen antagonist MER-25 resulted in a decline in plasma progesterone. In the present study, pregnant baboons in whom the corpus luteum-bearing ovary was removed early in pregnancy were used to distinguish between a luteal or placental effect of this estrogen deprivation. MER-25, administered from days 35 through 48 of pregnancy, resulted in a significant decline in plasma progesterone, indicating a direct placental action of estrogen deprivation on progesterone production. In a second experiment using intact pregnant baboons, concomitant administration of the nonsteroidal estrogen diethylstilbestrol (DES) prevented the inhibitory effect of MER-25 on placental progesterone, indicating that the effect was due to antiestrogenic action of MER-25 and not to some other pharmacological effect of the antagonist. Since DES administration alone had no effect on plasma progesterone levels, the role of estrogen may be a permissive action. The administration of MER-25 did not inhibit estradiol production in intact pregnant baboons with or without corpora lutea. When DES was administered to intact pregnant baboons, alone or together with MER-25, there was a significant decrease in plasma estradiol concentrations, which was only reversed after the cessation of treatment. These studies indicate that estrogen, perhaps by different mechanisms, may be important in the regulation of placental estradiol and progesterone production in the primate.

Animals↗

Glucocorticoid/antiinflammatory activities of nonsteroidal phenylpyrazoles in the rat.

Six nonsteroidal phenylpyrazoles are described that have significant glucocorticoid and antiinflammatory activities. These agents competed with dexamethasone for the glucocorticoid receptor from the rat thymus, suppressed adrenal weight when administered orally to intact female rats, produced liver glycogen deposition and thymolysis when administered orally to adrenalectomized male rats, and reduced cotton granuloma formation when administered in the cotton pellet. In addition, in the latter model, no systemic activity (thymolysis or reduced body weight gain) was seen with doses up to 500 to 5000 times the dose which reduced granuloma formation. At least one compound was more potent than methylprednisolone in three of the four rat assay systems used. The compounds described are structurally different from conventional steroidal glucocorticoids but possessed potent glucocorticoid activities. However, they exhibited antiinflammatory activity without evidence of systemic activity when administered locally.

Administration, Oral↗