Search PubMed⌕ Search

Biomedical subjects

R L Barbieri

Publications and source records attributed to R L Barbieri.

At least 109 records · Page 6Linked to original sources
PubMed1989

A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata.

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Adult↗
PubMed1989

Galactose-1-phosphate uridyl transferase activity associated with age at menopause and reproductive history.

Reproductive history was obtained and the activity and electrophoretic pattern of the blood enzyme galactose-1-phosphate uridyl transferase (transferase) was measured in 104 adult Caucasian women, less than 70 years of age, sampled from the general population. Fifteen women were identified as carriers for the Duarte (GtD) or galactosemia (gt) variants of transferase--genes associated with reduced transferase activity compared with normal (Gt+). The mean age at menopause for 8 women with a natural menopause who were GtD/Gt+ or gt/Gt+ was 44.8, significantly younger (P = 0.007) than the mean age of 49.2 reported by 31 naturally postmenopausal subjects with Gt+/Gt+ genotypes and normal transferase activity. Compared with the latter group, women who were Duarte or galactosemia carriers were 13.7 times more likely to have a menopause before age 48 (with 95% confidence limits of 2.0 to 95.5). Six of 13 (46%) married women who were GtD/Gt+ or gt/Gt+ reported more than 2 years' trying to achieve a pregnancy, compared with 11 of 74 (15%) with normal genotypes and activity (P = 0.02). The authors conclude that genetic deficiency of transferase may be associated with infertility and early menopause.

Adult↗
PubMed1989

The effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation in an in vitro fertilization program.

The purpose of this study was to examine the effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation (COH) in an in vitro fertilization (IVF) program. Patients were divided into two groups: group 1 (n = 21) had cysts with mean diameters between 10 and 45 mm on their baseline ultrasound before COH, and group 2 (n = 76) had no ovarian cysts on their baseline ultrasound. There was no statistically significant difference between the groups in maximum serum estradiol, the number of follicles greater than or equal to 10 mm on the day of human chorionic gonadotropin (hCG) injection, the number of follicles greater than or equal to 15 mm on the day of hCG injection, the number of oocytes retrieved, and the number of embryos transferred. There was no difference between the groups in the cycle cancellation rate, in the pregnancy rate per cycle, or in the pregnancy rate per embryo transfer. This study suggests that small baseline ovarian cysts do not negatively impact on ovulation induction parameters or pregnancy rates in an IVF program.

Adult↗
PubMed1989

Estrogen 2-hydroxylase oxidation and menstrual function among elite oarswomen.

We monitored the estrogen metabolism and menstrual function of two groups of elite oarswomen as they progressed from a phase of low intensity training (phase I), to high intensity training (phase II), and back to low intensity training (phase III). Each phase lasted 3 months. The two groups of oarswomen included five oarswomen (group A) who experienced no menstrual dysfunction during the training year, even during the phase of high intensity training, and five oarswomen (group B) who experienced normal menses during phases of low intensity training but disrupted menses during the phase of high intensity training. Four nonathletic controls were also studied. Menstrual function was monitored throughout the training year by assay for pregnanediol glucuronide in overnight 12-h urine samples collected twice weekly. Repeated measures of the extent of estradiol metabolized by 2-hydroxylase oxidation, total body water, and nutrient intake of group A and B oarswomen were made at the three phases of the training year; the extent of estradiol metabolized by 2-hydroxylase oxidation was evaluated by radiometric analysis; total body water was measured by deuterium oxide dilution and bioimpedance analysis; and nutrient intake was evaluated by food frequency questionnaire. The group B oarswomen were found to metabolize a significantly greater fraction of administered [2-3H]estradiol by 2-hydroxylase oxidation than group A oarswomen (chi 2(1) = 6.57; P = 0.01). The extent of estradiol metabolized by 2-hydroxylase oxidation among group A oarswomen did not differ from that among nonathletic controls. The extent of 2-hydroxylase activity did not change significantly with the intensity of training among either group A or group B oarswomen. Oarswomen in groups A and B lost body weight and became leaner during the phase of high intensity training (phase II). Group A and B oarswomen did not differ in the degree of weight loss or in relative fatness during phase II. Over all subjects, the extent of estradiol metabolized by 2-hydroxylase oxidation was positively correlated with the extent of leanness. These data suggest that elevated estradiol 2-hydroxylase oxidation among elite oarswomen is associated with the occurrence of menstrual disturbances during phases of high intensity training and increased relative leanness.

Adult↗
PubMed1989

Cotinine and nicotine inhibit human fetal adrenal 11 beta-hydroxylase.

The effects of nicotine and cotinine on fetal adrenal 11 beta- and 21-hydroxylase were examined using enzymatic and spectral techniques. The addition of nicotine or cotinine to preparations of adrenal mitochondria yielded a type II cytochrome P-450 binding spectrum. The apparent spectral dissociation constants (Ks) for nicotine and cotinine binding to mitochondrial cytochrome P-450 were 20 and 19 microM, respectively. The addition of nicotine to preparations of adrenal microsomes yielded a type II cytochrome P-450 binding spectrum, with an apparent Ks of 70 microM. Adrenal mitochondrial 11 beta-hydroxylase was assayed by measuring the conversion of deoxycorticosterone to corticosterone. Nicotine and cotinine competitively inhibited 11 beta-hydroxylase, with apparent Michaelis-Menten inhibition constants (Ki) of 9.9 and 9.0 microM, respectively. Nicotine competitively inhibited microsomal 21-hydroxylase, with an apparent Ki of 110 microM. Cotinine, in concentrations as high as 1 mM, did not inhibit 21-hydroxylase. These results suggest that nicotine and cotinine inhibit 11 beta-hydroxylase by binding to the heme iron of the cytochrome P-450 component of this enzyme system. Inhibition of 11 beta-hydroxylase could contribute to the altered pattern of steroidogenesis observed in smokers.

Adrenal Glands↗
PubMed1989

Effects of previous ovarian surgery on the follicular response to ovulation induction in an in vitro fertilization program.

This study examined the effects of previous ovarian surgery on the clinical response to ovulation induction with clomiphene citrate-human menopausal gonadotropin in an in vitro fertilization program. Patients were divided into five clinical groups: group A (n = 63), no previous ovarian surgery; B (n = 9), unilateral cystectomy; C (n = 6), unilateral oophorectomy with no contralateral ovarian surgery; D (n = 7), bilateral ovarian surgery with both ovaries present; and E (n = 4), unilateral oophorectomy and contralateral cystectomy. Patients in group E demonstrated significantly lower serum estradiol on cycle days 9-11 (P less than or equal to .05) and fewer follicles on cycle days 11-12 (P less than or equal to .05) than did patients in groups A-D. The percentage of cancelled cycles increased with increasing amounts of ovarian surgery (P less than or equal to .03). The study suggests that one cause of a poor response to ovulation induction for in vitro fertilization may be prior extensive ovarian surgery.

Adult↗
PubMed1989

Effect of transport conditions on the stability of biochemical markers in blood.

We examined the stability of lipids, carotenoids, alpha-tocopherol, and endogenous hormones in plasma prepared from whole blood that had been mailed to a central location for processing. Initially, to simulate transport conditions, whole-blood samples were stored in the laboratory, either at room temperature or cooled, for up to 72 h before processing. In the latter samples, lipid concentrations changed up to 1.4% per day, carotenoids up to -5.5%, and hormones up to 9.5%. In a second study, analyte concentrations in plasma from cooled whole blood mailed via overnight courier were compared with those from plasma that had been immediately separated, frozen, and mailed via overnight courier. Concentrations of cholesterol, high-density lipoprotein subfraction 3, apolipoprotein B, and retinol were stable. Overall, for each marker except estradiol, the between-person variation was at least twice the within-person variation. In a third study, at least 340 micrograms of DNA was recovered from 30 mL of cool-shipped whole blood. Our results indicate that shipping whole-blood samples by overnight courier is feasible for assay of several biochemical markers of interest in epidemiological research.

Adult↗
PubMed1988

Rat Leydig cell and granulosa cell 17-ketosteroid reductase activity: subcellular localization and substrate specificity.

The potent gonadal steroids testosterone and estradiol are synthesized from the biologically weak precursors, androstenedione and estrone, by enzymatic reduction of the ketone group at carbon-17 of the steroid nucleus (17-ketosteroid reductase). To test the hypothesis that Leydig and granulosa cells may contain a distinct 17-ketosteroid reductase enzyme, the subcellular localization and the substrate specificity of the enzyme was examined in each cell type. In Leydig cells, the 17-ketosteroid reductase activity was concentrated in the microsomal fraction of the cell. In granulosa cells, the 17-ketosteroid reductase activity was concentrated in the cytosolic fraction of the cell. In Leydig cell microsomes, the apparent Michaelis-Menten constant for the conversion of androstenedione to testosterone was 0.41 mumol/L and for the conversion of estrone to estradiol it was 12 mumol/L. In granulosa cell cytosol, the apparent Michaelis-Menten constant for the conversion of estrone to estradiol was 1.1 mumol/L and for the conversion of androstenedione to testosterone it was 15 mumol/L. These results demonstrate that rat Leydig and granulosa cells each contain a 17-ketosteroid reductase enzyme with unique subcellular localization and substrate specificity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri.

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

Adult↗
PubMed1988

The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism.

The evidence that supports the hypothesis that insulin and LH both regulate ovarian androgen production was presented. The most dramatic clinical example of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. Our hypothesis is that, in the HAIR-AN syndrome, the severe insulin resistance causes a compensatory hyperinsulinemia, which stimulates ovarian androgen production if adequate LH is present. The acanthosis nigricans is an epiphenomenon of the syndrome. Acanthosis nigricans is a dermatologic manifestation of severe insulin resistance. In vitro evidence suggests that insulin and IGF-I stimulate androgen production in incubations of human stroma and theca. The stromatropic effects of insulin may sensitize the stroma to the stimulatory effects of LH. In some hyperandrogenic-insulin-resistant women, a glucose load appears to produce an acute rise in circulating androgens. The magnitude of the rise in circulating androgens is proportional to the magnitude of the insulin response to the glucose load. These data suggest that hyperinsulinemia may play a central role in the development of ovarian hyperandrogenism.

Acanthosis Nigricans↗
PubMed1988

Hyperinsulinemia and ovarian hyperandrogenism. Cause and effect.

The evidence that supports the hypothesis that hyperinsulinemia causes ovarian hyperandrogenism was reviewed. The most dramatic clinical expression of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. In the HAIR-AN syndrome, severe insulin resistance results in a compensatory hyperinsulinemia that stimulates ovarian androgen production. Acanthosis nigricans, a dermatologic manifestation of severe insulin resistance, is an epiphenomenon of the disease. Hyperandrogenic (HA) women can be divided into two major groups: insulin-resistant (HA-IR) and non-insulin-resistant (HA-nIR). HA-nIR women have markedly elevated LH, often have minimally elevated serum prolactin, and have polycystic ovaries. HA-IR women have minimally elevated LH, markedly elevated plasma insulin, and stromal hyperthecosis. Women with HA-nIR probably have a primary hypothalamic-pituitary abnormality as the cause of their hyperandrogenism. Women with HA-IR probably have a primary metabolic abnormality as the cause of their hyperandrogenism. The relationship between hyperinsulinemia and hyperandrogenism is one example of the complex interrelationships that exist between central metabolism and reproduction.

Acanthosis Nigricans↗
PubMed1987

The effects of nicotine, cotinine and anabasine on rat adrenal 11 beta-hydroxylase and 21-hydroxylase.

The effects of nicotine, cotinine and anabasine on rat adrenal steroidogenesis were examined by spectral and enzymatic techniques. The addition of nicotine, cotinine or anabasine to preparations of rat adrenal mitochondria produced type II cytochrome P-450 difference spectra. The addition of nicotine or anabasine, but not cotinine, to rat adrenal microsomes yielded type II cytochrome P-450 difference spectra. Nicotine and anabasine competitively inhibited rat adrenal mitochondrial 11 beta-hydroxylase and microsomal 21-hydroxylase. Cotinine competitively inhibited mitochondrial 11 beta-hydroxylase, but did not inhibit microsomal 21-hydroxylase. The apparent enzymatic inhibition constants for cotinine, nicotine, anabasine and metyrapone inhibition of the mitochondrial 11 beta-hydroxylase were 32, 96, 120 and 74 microM respectively. These studies suggest that components of cigarette smoke may alter patterns of adrenal steroidogenesis.

Adrenal Glands↗
PubMed1987

Serum steroid hormone profiles in postmenopausal smokers and nonsmokers.

Morning serum steroid levels were determined in postmenopausal chronic smokers and nonsmokers. Postmenopausal smokers (n = 9) had significantly elevated levels of cortisol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone compared with nonsmokers (n = 16). The increases were most significant for cortisol (P less than 0.001) and 17-OHP (P less than 0.0005). Estrone, estradiol, dihydrotestosterone, and dehydroepiandrosterone sulfate did not differ between the groups. P to estrogen ratios tended to be higher in the smoking population. The significantly elevated P levels observed in the group of postmenopausal smokers may explain, in part, the epidemiologic finding that women smokers have a decreased incidence of endometrial carcinoma. In addition, the hypercortisolism associated with smoking may increase the risk of osteoporosis.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin-releasing hormone agonist.

Fourteen premenopausal women with uterine leiomyomata were randomized to receive a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide, either by daily subcutaneous (SC) injection (500 micrograms/day) or by intranasal (IN) spray (1600 micrograms/day) for 24 weeks. In the SC group, a significant reduction in uterine volume occurred from a pretreatment volume of 368 +/- 60 (mean +/- standard error of the mean [SEM]) cm3 to 202 +/- 61 cm3 at 12 weeks of therapy (P less than 0.01) and to 172 +/- 49 cm3 at 24 weeks of therapy (P less than 0.005). In the IN group, no significant reduction in uterine volume occurred. In addition, there was a significant negative correlation between the serum estradiol concentration during treatment and the percent decrease in uterine volume (r = -0.55, P less than 0.05). Four months after completing therapy, uterine volume increased to 296 +/- 104 cm3 in the SC group, which was not significantly different from pretreatment volume. These findings suggest that reduction in uterine volume depends on the degree of hypoestrogenism induced and that uterine volume increases soon after cessation of GnRH-a therapy.

Administration, Intranasal↗
PubMed1987

Androgen and insulin response to an oral glucose challenge in hyperandrogenic women.

To further investigate the relationship between insulin and androgen secretion in hyperandrogenic women, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects. Significant positive correlations were demonstrated between fasting serum insulin concentration and both androstenedione (delta 4A) and testosterone (T) concentrations, which were independent of body mass index (kg/m2). A strong negative correlation was demonstrated between fasting insulin and dehydroepiandrosterone sulfate (DHEAS) levels within the HA group (r = -0.84, P = 0.003). Significant positive correlations were also demonstrated between the cumulative sum insulin response during OGTT and the percent change from fasting baseline to 3 hours in serum delta 4A (r = 0.65, P = 0.006), T (r = 0.51, P = 0.033), and dihydrotestosterone (DHT) concentrations (r = 0.75, P less than 0.001). Our data suggests that abnormalities in insulin secretion are common in HA women and that there is a strong correlation between changes in serum concentrations of insulin and androgens during an OGTT.

Androgens↗
PubMed1987

Detection of T8 (suppressor/cytotoxic) lymphocytes in human ovarian follicular fluid.

Clear ovarian follicular fluid and the follicular flush (bloody) of aspirated follicles from 18 women undergoing oocyte retrieval for in vitro fertilization were tested for the presence of T-lymphocyte subpopulations with the use of a panel of monoclonal antibodies in indirect immunofluorescence assay. A sample of peripheral venous blood from each patient was run as a control. There was no difference in the percentage of cells positive for the various markers between bloody follicular fluid (i.e., ovarian blood) and peripheral venous blood. T8-positive (suppressor/cytotoxic) lymphocytes were recovered from all clear follicular fluids; ten of the patients exhibited a dramatically decreased T4/T8 ratio (peripheral blood, 2:1; clear follicular fluid, 1:25; P less than 0.001). These lymphocytes may be involved in the suppression of autoimmune responses directed against ovarian antigens.

Adult↗