Effect of ergot alkaloids on serum prolactin in non-psychotic organic brain syndrome of the elderly.

A compound of ergot alkaloids (Hydergine-Sandoz) or placebo was given to sixty elderly nursing home patients with non-psychotic organic brain syndrome. Subsequent to 12 weeks of treatment, the mean serum prolactin of the drug was significantly lower than that of the placebo group. No correlation was found between changes in prolactin and changes in behavior using Sandoz Assessment of Clinical Status Rating Form-Geriatric [SCAG]. It may be that a higher dose of Hydergine with an accompanying greater drop in prolactin would be required to observe this effect.

Acute visual loss during pregnancy after bromocriptine-induced ovulation. The elusive tumor.

The evaluation of patients complaining of amenorrhea with or without galactorrhea has been greatly enhanced by the availability of serum prolactin determinations and advances in diagnostic radiology. Likewise, the treatment of these patients with ergot derivative has resulted in the return of normal menses, and many pregnancies have been reported. The present report is of a patient with hyperprolactinemic amenorrhea-galactorrhea successfully treated with bromocriptine. A pregnancy followed resumption of menses, and a suprasellar cromophobeadenoma became manifest by producing blindness of the patient. The case is presented with recommendations for diagnosis and treatment.

Alterations in steroid binding plasma proteins in Macaca nemestrina during pregnancy.

We measured the corticosterone and dihydrotestosterone steroid binding capacities of corticosteroid-binding globulin (CBG) and sex steroid plasma binding protein (SBP) throughout pregnancy in seven Macaca nemestrina. The nSBP binding capacity rises significantly by 28 days of pregnancy, remains elevated through 56 days, tends to fall through midpregnancy, and then decreases dramatically to very low values 130-153 days after conception. In contrast, nCBG rises slightly (1.2-fold) in early pregnancy, is elevated in midpregnancy, but is similar to nonpregnant values during the last trimester of pregnancy. Our data indicate that factors controlling the plasma concentration of nCBG and nSBP are not identical. The results are in sharp contrast to those observed in human pregnancies in which both hSBP and hCBG are increased severalfold during pregnancy, including at term. Because the changes of nCBG and nSBP during pregnancy do not paralle the changes observed in human beings even though their steroid binding characteristics are similar, the M. nemestrina may serve as a valuable model for defining the physiologic function of SBP and CBG and the mechanism(s) controlling their concentrations in blood.

Radioimmunoassay of alpha-fetoprotein, with special reference to iodination and purification techniques.

We report a relatively simple and convenient method for iodinating human alpha-fetoprotein and for purifying the 125I-labeled material. The label is incorporated into human alpha-fetoprotein enzymatically by use of lactoperoxidase. Before each assay the labeled material is purified over two successive short columns: Sepharcryl S-200 Superfine and cellulose. This procedure removes both free iodine and "damaged" fetoprotein. With the purified material we developed a sensitive and reliable radioimmunoassay for alpha-fetoprotein in serum and amniotic fluid.

Meconium staining of amniotic fluid at midtrimester amniocentesis.

Meconium-stained fluid was found in six of the first 234 amniocenteses performed at the University of Washington Prenatal Diagnosis Center. The taps were done between 16 and 20 weeks from the last menstrual period. Although in each case there was a factor that could have produced fetal distress, in no instance did intrauterine demise occur. All the pregnancies have terminated in the births of healthy children. Therefore, we believe that meconium staining of midtrimester amniotic fluid may in fact reflect a transient episode of fetal compromise but that the finding cannot be used to prognosticate either impending fetal death or the presence of congenital malformations in the newborn.

Sex hormones correlated with sex skin swelling and rectal temperature during the menstrual cycle of the pigtail macaque (Macaca nemestrina).

Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction.

A faster radioimmunoassay of progesterone in plasma, with use of polyethylene glycol as precipitant.

We report a reliable radioimmunoassay for plasma progesterone in which polyethylene glycol ("Carbowax 6000") is used to separate antibody-bound and free hormone. Initially, progesterone is concentrated by putting the sample through a column of LH-20 Sephadex. Procedural losses in each sample are not monitored. We compared the reliability and practicality of this method with that of another method in which procedural losses are monitored for each sample; accuracy and precision were similar. Our method saves technical assay time and scintillation counter space and time without sacrificing reliability.

A rapid specific radioimmunoassay for unconjugated estriol in plasma.

A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%.

Nonchromatographic radioimmunoassay of unconjugated estriol in plasma, with polyethylene glycol as precipitant.

We describe a rapid, reliable radioimmunoassay for unconjugated estriol in plasma. Polyethylene glycol (Carbowax 6000) is used to separate antibody-bound and free steroid. The assay is sensitive (25 pg for standards), precise, and accurate. At high and low concentrations of estriol, intra-assay coefficients of variation were 7.1% and 7.6%, respectively, and inter-assay coefficients of variation were 7.2% and 10.0 %, respectively. Free [3H] estriol is not precipitated by polyethylene glycol. This radioimmunoassay of estriol, with a highly specific antiserum and with polyethylene glycol as the antibody precipitant, is a reliable one-day assay that is practical both for the clinical laboratory and the obstetrician.

Radioimmunoassay of plasma testosterone, with use of polyethylene glycol to separate antibody-bound and free hormone.

We have developed a reliable radioimmunoassay for testosterone in plasma, polyethylene glycol ("Carbowax 6000") being used to separate antibody-bound and free hormone. Testosteron is separated from interfering steroids, notably dihydrotestosterone, by liquid-liquid partition chromatography on infusorial earth (Celite). The assay is sensitive (9 pg for standards), precise, and accurate. The lowest measurable concentration fo testosterone is 350 ng/liter for plasma from men and 70 ng/liter for plasma from women. Intra- and inter-assay coefficients of variation were 6.9% and 9.7%, respectively, for plasma from men, and 9.6% and 11.8%, respectively, for plasma from women. Our method for separating antibody-bound and free hormone is practical and convenient and may be generally applicable to all radioimmunoassays of steroid hormones in plasma.

Nonchromatographic radioimmunoassay of plasma 11-deoxycortisol, for use in the metyrapone test, with polyethylene glycol as the precipant.

We have developed a simple, reliable radioimmunoassay for plasma 11-deoxycortisol. The method does not require chromatography but instead makes use of a simple extraction procedure which, in combination with the antibody characteristics, is highly specific for the metyrapone test. Polyethylene glycol was used to separate free and antibody-bound steroid. The smallest amount measurable is 15 pg (2.0 mug/liter of plasma). The method is shown to be precise and accurate. Intraassay precision of the method for two plasma pools was 26.7 plus or minus 2.5 mug/liter (CV equals 9.4%) and 61.2 plus or minus 3.7 mug/liter (CV equals 6.0%). The respective inter-assay precision was 27.0 plus or minus 1.7 mug/liter (CV equals 6.3%) and 59.9 plus or minus 2.3 mug/liter (CV equals 3.8%). The validity of the assay was further verified by evaluating the plasma 11-deoxycortisol response to metyrapone administration. The relative simplicity of the method and the commercial availability of all reagents, including antisera, makes this radioimmunoassay procedure practical for use in clinical laboratories.

Perturbations of the human menstrual cycle by oxymetholone.

The luteolytic activity of oxymetholone, and anabolic steroid, has been evaluated in 10 women. Administration early in the follicular phase of the cycle inhibited ovulation and prolonged the duration of the cycles in 2 of 3 subjects, but treatment beginning on Day 10 (3 subjects) did not prevent ovulation, although subsequent plasma progesterone concentrations were reduced. Treatment after ovulation (4 subjects) suppressed progesterone levels by 50 to 80 per cent and shortened cycle length by 6 to 8 days. Side effects were weight gain and bromosulfophthalein retention. The most likely mechanisms producing these perturbations are the inhibition of luteinizing hormone release early in the cycle and, later, inhibition of progesterone biosynthesis.

PIP: 10 ovulating women were treated with oxymetholone in 1 of 3 ways: 1) 50 mg twice daily every other day starting on the sixth day of the treatment cycle (early follicular phase), 2) 50 mg twice daily every other day starting in the late follicular phase (tenth day), or 3) 100 mg daily starting in early luteal phase. 2 women treated in early follicular phase had ovulation suppression and cycles prolonged 9 to 10 days, with progesterone suppressed by ovulated, and a third had a 71% suppression of progesterone. In the third group, cycle lengths were shortened due to a luteal phase shortening of 6 to 8 days, with progesterone values decreased 53 to 81%. Side effects noted were: weight gain (9 out of 10 patients) transient nausea, and increased bromsulphalein retention.