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Biomedical subjects

D Tulchinsky

Publications and source records attributed to D Tulchinsky.

At least 19 recordsLinked to original sources

Effects of estrogens on sleep and psychological state of hypogonadal women.

A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile.

Adult

Estriol determinations in diabetic pregnancies complicated by nephropathy.

In order to study the effect of renal disease on urinary estriol clearance rate, we have measured the concentrations of plasma and urinary estriol (E3) in pregnancies of 69 diabetic patients, 25 of whom had nephropathy. No correlation was found between endogenous creatinine clearance (CCr) and estriol clearance (CE3) rates (r = 0.07), and mean CE3 of diabetic patients with diminished CCr (less than 100 ml/min) was not significantly different from that of patients with normal CCr (greater than or equal to 100 ml/min). The ratios between total, unconjugated estriol and urinary estriol concentrations in patients with diminished CCr were not different from those patients with normal CCr. Cases where high plasma estriol and low urinary estriol concentrations coexisted were not found. It is concluded that in this group of diabetic patients, diminished CCr had no discernible effect on urinary CE3 possibly because renal tubular function remained intact. In patients with diabetic nephropathy either urinary or plasma E3 could be used to assess fetoplacental function.

Creatinine

Endocrine studies of normal and polycystic ovarian tissues in vitro.

The purpose of this study was to compare the steroidogenic potential of the granulosa, theca, and medullary tissues from polycystic and normal ovaries. These ovarian endocrine compartments were isolated from appropriate ovaries and were cultured in vitro for three days in the absence (control) and presence of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) (1 lU/ml), N6,O2-dibutyryladenosine-3':5''-cyclic monophosphoric acid (Bu2cAMP) (10(-2)M), and adrenocorticotropic hormone (ACTH) (1.3 U/ml). After the incubation, steroids in the media were measured by radioimmunoassay. Granulosa cells (10(5) cells per dish) from 4 to 7 mm follicles of normal and polycystic ovaries secreted progesterone spontaneously during the culture period and the production of progesterone was markedly stimulated (between tenfold and thirtyfold) by gonadotropins and Bu2cAMP but not by ACTH. Little, if any, androgen (androstenedione, dehydroepiandrosterone, and testosterone) or estrogen (estrone and estradiol) accumulated in the media of any granulosa cell culture. The control cultures of theca tissue from normal and polycystic ovaries secreted large amounts of androstenedione and progesterone and the production of these steroids by normal and polycystic ovary theca was stimulated in most cases by LH/FSH and Bu2cAMP but not by ACTH. Both normal and polycystic ovary theca secreted some testosterone and dehydroepiandrosterone but little, if any, estrone or estradiol accumulated in any theca culture. The medullary tissue of normal and polycystic ovaries produced only trace amounts of steroids in vitro except for the results from one polycystic ovary with hyperthecosis in which case significant quantities of C19 and C18 steroids were secreted. These experiments have demonstrated that isolated granulosa and theca cells from midantral follicles of normal and polycystic ovaries have a similar capacity to secrete C21 and C19 steroids in the absence and presence of trophic agents. Therefore, it seems probable that chronic anovulation in patients with polycystic ovaries is not caused by an obvious deficiency in the de novo steroidogenic potential of the multiple midantral follicles of the polycystic ovaries or by the absence of gonadotropin receptors on the polycystic ovary follicular cells.

Adrenocorticotropic Hormone

Prenatal diagnosis of congenital adrenal hyperplasia.

The accurate prenatal diagnosis of 21-beta-hydroxylase deficiency, based on amniotic fluid levels of 17-hydroxyprogesterone, is documented for a fetus 14 1/2 weeks old. In addition, family HLA genotyping data are consistent with the purported linkage between the HLA locus and the locus for 21-beta-hydroxylase.

Adrenal Hyperplasia, Congenital

Testicular testosterone concentration following testicular vein ligation.

UNLABELLED: A rat model to study the local effects of testicular vein ligation is described. One hour after unilateral testicular vein ligation, the testicular concentration of testosterone was significantly greater (P less than 0.01) on the side that was ligated than in the contralateral testis (177.1 +/- 19.7 [SEM] ng/gm of tissue as compared with 108.8 +/- 11.8 ng/gm of tissue, respectively). This effect was not seen 1 week after the testicular vein ligation. The testosterone concentration in the ligated testis was also higher than that in sham-operated animals. These differences in testicular testosterone concentration were not associated with changes in peripheral serum testosterone levels. CONCLUSION: ligation of the testicular vein causes an acute rise in the testicular concentration of testosterone and may thus mediate changes in testicular function.

Animals

Cytoplasmic and nuclear progestin receptors in human myometrium during the menstrual cycle and in pregnancy at term.

Exchange assays have been developed for the determination of the total progestin in receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium using radiolabeled R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. These assays have been applied to the measurement of cytosol and nuclear progestin receptor sites in the myometrium during the menstrual cycle and in pregnancy at term. Both the cytosol receptor levels as well as the sum of cytosol and nuclear receptor levels were highest during the proliferative phase of the cycle, dropped moderately but significantly in the secretory phase, and decreased markedly in pregnancy at term. Despite the marked drop in cytosol receptor levels, nuclear receptor levels in pregnancy at term were similar to those observed in the proliferative or secretory phase. In addition, the fraction of the total cellular receptor that was associated with the nucleus increased from 5.5% in the proliferative phase to 60% in pregnancy at term. The decrease in cytosol progestin receptor concentration as well as the relative increase in nuclear localization of the receptor in human myometrium in pregnancy at term may be related to the high circulating progesterone levels.

Cell Nucleus

Plasma prostaglandin metabolites in human labor.

To elucidate the role of prostaglandins in initiating uterine contractions we studied the concentrations of 13,14-dihydro-15-keto-PGE2 (PGE2-M) and 13,14-dihydro-15-keto-PGF2alpha (PGF2alpha-M) in peripheral plasma of pregnant patients. The concentrations of PGE2-M and PGF2alpha-M in pregnant patients at term not in labor were not significantly different from those at midpregnancy. Induction of labor at term pregnancy caused a significant rise of both PGE2-M and PGF2alpha-M. During spontaneous labor there were no significant minute-to-minute fluctuations of plasma PGE2-M and PGF2alpha-M and their concentrations were not different from those at oxytocin-induced labor. Initiation of uterine contractions and abortion at midpregnancy by the intra-amniotic infusion of hypertonic saline was not associated with any change in PGE2-M concentration and a rise in PGF2alpha-M was noted in only one of five patients. The vaginal administration of PGE2 and the intra-amniotic infusion of PGF2alpha were associated in each case with a significant rise of both prostaglandin metabolites. It is concluded that the rise of prostaglandin metabolites in peripheral plasma is secondary to the initiation of uterine contractions at term pregnancy. Such a rise is not usually observed after the initiation of uterine contractions by hypertonic saline at midpregnancy.

Abortion, Induced

Amniotic fluid reverse triiodothyronine in complicated pregnancy.

The concentrations of reverse triiodothyronine (3,3',5'-T3 or rT3) in amniotic fluid (AF) were measured by radioimmunoassay in 81 patients with various complications of pregnancy and in 39 normal pregnant patients at equivalent gestational age. In normal pregnancy, AFrT3 concentrations decreased with advancing gestational age. At 21-25, 26-30, 31-35, and 36-40 weeks of normal pregnancy, AFrT3 concentrations (mean +/- SE) were 353 +/- 62 (n = 6), 131 +/- 49 (n = 7), 94 +/- 25 (n = 14), and 93 +/- 5 (n = 20) ng/dl, respectively (ranges: 200-600, 57-350, 66-135, and 50-135). Both normal and supranormal values of AFrT3 were found in patients with complicated pregnancy. In patients with RH isoimmune disease, higher than normal AFrT3 concentrations were associated with seriously affected or gravely ill fetuses wheras normal AFrT3 concentrations predicted a more favorable outcome. There was a good correlation between AFrT3 and AF pigment (deltaOD450) levels (r = 0.70, P less than 0.001). In complicated pregnancy other than erythroblastosis fetalis, AFrT3 concentrations were not of any prognostic significance, and there was no correlation between AFrT3 and lecithin/spingomyelin ratio. The data suggest that AFrT3 determination may help in the assessment of the fetal condition in erythroblastosis fetalis.

Amniotic Fluid

Effects of dexamethasone on fetal and maternal thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels.

The concentrations of T4, T3, rT3, and TSH were measured at term pregnancy in maternal and umbilical plasma and in amniotic fluid of 11 normal patients who received 8-16 mg dexamethasone 3-48 h before elective cesarean section and of 10 control patients who received no dexamethasone. The mean (+/- SE) concentrations of T4 (micrograms per dl) in maternal and umbilical plasma of dexamethasone-treated patients (12.5 +/- 0.9 and 13.0 +/- 0.9) were not significantly different (P less than 0.05) from those of the control patients (13.9 +/- 1.5 and 10.4 +/- 0.6, respectively). The mean (+/- SE) maternal plasma concentrations of T3 and rT3 (nanograms per dl) of dexamethasone-treated patients (204 +/- 6 and 82 +/- 11) were not significantly different (P less than 0.05) from those of the control patients (201 +/- 26 and 72 +/- 6, respectively). However, the mean (+/- SE) concentrations of T3 and rT3 (nanograms per dl) in umbilical plasma of dexamethasone-treated patients (106 +/- 13 and 360 +/- 35) were 3- and 2-fold and significantly higher (P less than 0.05) than those of the control group (39 +/- 6 and 195 +/- 19, respectively). No significant differences (P less than 0.05) were observed between the mean concentrations of TSH (microunits per ml) in maternal and umbilical plasma of dexamethasone-treated patients (2.5 +/- 0.5 and 3.0 +/- 1.0) and those of the control group (2.8 +/- 0.5 and 6.9 +/- 2.7, respectively). Under the conditions studied, no differences in the mean concentrations of amniotic fluid T4, T3, rT3, or TSH were observed between the two groups of patients (P less than 0.05). The increase of T3 and rT3 levels in umbilical plasma after dexamethasone administration indicates alteration in fetal thyroid economy.

Dexamethasone

Congenital X-linked adrenal hypoplasia.

Fetal adrenal hypoplasia should be considered in pregnant patients with family histories of the condition and/or following observation of drastically reduced maternal estriol excretion. Antepartum diagnosis is important in the clinical management of these infants since deteriorating adrenal function frequently follows an asymptomatic period during the early neonatal life. Antepartum and neonatal diagnostic studies can identify fetal adrenal hypoplasia.

Adrenal Insufficiency

Amniotic fluid testosterone and follicle-stimulating hormone in the determination of fetal sex.

To determine whether hormone analysis could be used for accurate determination of fetal sex, we measured testosterone (T) and follicle-stimulating hormone (FSH) in 130 amniotic fluid samples at midgestation. The mean unconjugated T in amniotic fluid of 73 patients carrying male fetuses was 202 pg. per milliliter (95 per cent confidence limits [CL]: 70 to 580) and all but three had levels higher than 90 pg. per milliliter. The mean amniotic fluid unconjugated T for 49 patients carrying female fetuses of 41 pg. per milliliter (95 per cent CL: 11 TO 125) was fivefold lower than that for the male fetuses and all but three patients carrying female fetuses had amniotic fluid T levels of 90 pg. per milliliter or lower. The mean amniotic fluid FSH of 0.7 ml. U. per milliliter (95 per cent CL: less than 0.5 to 3.4) for subjects with male fetuses was tenfold lower than that for patients with female fetuses. Amniotic fluid FSH levels less than 2.0 ml. U. per milliliter were found in 88 per cent of patients carrying male fetuses and in only one patient with a female fetus, and levels greater than 10 ml. U. per milliliter were found in those with female fetuses only. In eight patients (7 per cent of cases), neither amniotic fluid T nor FSH determinations were indicative of fetal sex. Measurement of unconjugated T and FSH in amniotic fluid may be an adjunct to other methods of determining fetal sex.

Amniotic Fluid

Dexamethasone levels in treated pregnant women and newborn infants.

Dexamethasone concentration was measured in plasma and amniotic fluid by radioimmunoassay using a rabbit antiserum raised against DX-hemisuccinate-albumin. Recoveries of added tracers averaged 70% after paper chromatography. The within- and between-assay coefficients of variation averaged 10%. The lower limit of detection was 0.2 mug/dl when 0.4 ml of plasma was assayed. Ten healthy pregnant women at term had cesarean sections 8 to 11 hours following administration of 8 mg of DX orally. DX levels in maternal vein, in umbilical vein and artery, and in amniotic fluid averaged 2.2, 2.9, 2.6, and 2.5 mug/dl, respectively. Although cortisol levels were markedly suppressed, the total relative glucocorticoid activity in blood of fetuses treated with DX far exceeded that of the untreated group.

Amniotic Fluid