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Biomedical subjects

L Speroff

Publications and source records attributed to L Speroff.

At least 73 records · Page 4Linked to original sources

The endocrinology of the menstrual cycle: the interaction of folliculogenesis and neuroendocrine mechanisms.

(1) The gonadotropins are secreted in a pulsatile fashion in response to the similar pulsatile release of GnRH from neurosecretory neurons centered in the arcuate nucleus of the medial basal hypothalamus. (2) The gonadal steroids appear to exert their feedback effects both directly on the pituitary and through modulation of the pulsatile pattern of GnRH secretion. They may also influence the degree of sialylation and subsequent biologic activity of the gonadotropins. (3) GnRH release is under the control of catecholaminergic neurotransmitters. Norepinephrine appears to act as an excitatory agent, whereas dopamine inhibits GnRH secretion. (4) Dopamine also directly inhibits PRL release and may be the prolactin-inhibiting factor. (5) The endorphins are endogeneous opiate peptides and are derived from a common ACTH/ beta-lipotropin precursor. Through modulation of neurotransmitter mechanisms, the endorphins may affect both PRL and gonadotropin secretion. (6) The catecholestrogens, by virtue of their structural similarity to the neurotransmitters, may mediate the central feedback actions of the gonadal steroids.

Animals↗

Terbutaline and maternal cardiac function.

The effect of terbutaline sulfate on left ventricular size and performance was studied by M-mode echocardiography in pregnant women with premature labor. Patients with uterine activity initiated during either oxytocin challenge testing or induction of labor served as a comparison group. During terbutaline therapy, heart rate, ejection fraction, and cardiac output increased significantly. End-diastolic volume and systolic blood pressure (BP) were unchanged, and diastolic BP and end-systolic volume fell. No changes in echocardiographic or hemodynamic parameters were present during oxytocin-induced uterine activity. Terbutaline, as currently used to prevent premature labor, is a potent inotropic and chronotropic agent. Pulmonary edema accompanying terbutaline treatment is probably not due to cardiac failure.

Adolescent↗

A practical approach for the evaluation of women with abnormal polytomography or elevated prolactin levels.

Based upon the experience gained in the evaluation of 60 patients with abnormal polytomography and/or elevated prolactin levels, the following observations can be made: Patients with amenorrhea, amenorrhea and galactorrhea, galactorrhea alone, or anovulatory cycles and infertility may or may not have pituitary tumors. Clinical symptoms do not always correlate with the prolactin level, and patients with normal prolactins may have pituitary tumors. The incidence of empty sella is significant (15.8% in this series). Visual field examination is not a useful screening procedure, but evaluation of thyroid function is important to detect the occasional patient with hypothyroidism (3.5% in this series). The insulin tolerance test is not helpful in detecting the presence of pituitary tumors or in guiding management decisions, and the CT scan contributes little and should be omitted from the evaluation process. A straightforward, economical, and efficient approach to this clinical problem is presented.

Adenoma↗

Plasma estradiol window and urinary estriol glucuronide determinations for monitoring menotropin induction of ovulation.

The plasma estradiol response is maximal 8--10 hours following mentropin injection. To obtain closer control, a menotropin protocol using 5 PM--8 PM injections and 8 AM blood sampling with a plasma estradiol window of 1000--2000 pg/ml was evaluated with simultaneous calibration of a urinary estriol glucuronide radioimmunoassay. One hundred twenty-eight paired urine and plasma samples were assayed in 48 cycles. In 26 cycles with paired samples on the day of human chorionic gonadotropin (hCG) injection, there were no cases of severe hyperstimulation, 2 cases of moderate hyperstimulation, and 11 pregnancies (42% of cycles given hCG). A window of between 40 and 100 micrograms/day of urinary estriol glucuronide corresponded to the 1000--2000 pg/ml plasma estradiol window by regression analysis. The pregnancy and hyperstimulation rates were compared with those observed in protocols previously published. Radioimmunoassay of urinary estriol glucuronide is faster and simpler than radioimmunoassay of plasma estradiol.

Abortion, Spontaneous↗

Interrelationships between maternal and cord prolactin, progesterone, estradiol, 13,14-dihydro-15-keto-prostaglandin F2alpha, and cord cortisol at delivery with respect to initiation of parturition.

Estradiol, progesterone, prolactin, and 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) were measured in both maternal and cord venous blood obtained at the time of delivery in 24 maternal infant pairs evenly divided among six different physiologic groups. Progesterone and prolactin were significantly higher and estradiol was significantly lower in cord than in maternal blood. There were no significant differences between the groups for cortisol, estradiol, or progesterone in maternal or cord blood. A significant increase in prolactin was demonstrated in women receiving oxytocin for induction of labor. Both estradiol and PGFM were highly correlated between maternal and cord blood. PGFM was significantly higher in cesarean section patients in labor than in those not in labor in both the maternal and cord circulations. Among those delivered vaginally, PGFM tended to be higher in those in spontaneous labor than in those with induced labor. PGFM in induced labor was intermediate between spontaneous labor aptients delivered by cesarean section and those delivered vaginally. Duration of labor was negatively correlated with cord estradiol concentration. The physiologic significance of these findings is discussed.

Animals↗

Ovulation and pregnancy rates with clomiphene citrate.

A review of recent experience with clomiphene citrate at the Yale-New Haven Medical Center yields the following conclusions: 1) Clomiphene citrate administered at high doses (150 mg and 200 mg) is effective in inducing ovulation in women who would otherwise have failed to conceive if treatment were restricted to only lower dosage regimens. 2) Therapy with clomiphene citrate should be initiated with the 50-mg dose. The 100-mg dose should be reserved for those who fail with the lower dose. 3) Children resulting from clomiphene-induced ovulations appear to be developing normally both mentally and physically. Congenital malformations found in children from clomiphene-induced pregnancies are those seen commonly in general obstetric practice resulting in no significant problems for the children. 4) After 3 ovulations with clomiphene citrate approximately 50% of the patients can be expected to conceive. A 50% conception rate after 3 ovulations with clomiphene citrate does not represent a discrepancy between ovulation rates and pregnancy results, for it agrees statistically with the results obtained for the general population.

Abnormalities, Drug-Induced↗

Ultrastructure of the placental villi, chorion laeve, and decidua parietalis in normal and hypertensive pregnant women.

The fine structure of the placental villi, chorion laeve, and decidua parietalis from normal and hypertensive pregnant women is described. Placental villi from hypertensive women revealed an increase in syncytial degeneration and fibrinoid deposition. Also noted were greater numbers of cytotrophoblast cells. On the other hand, there were no morphologic differences detected in the cellular and noncellular elements of the chorion laeve and decidua parietalis between normal and hypertensive subjects. Secretory granules were observed in both the placental villi and the chorion laeve.

Chorion↗

A direct radioimmunoassay for estriol-16-glucuronide in urine for monitoring pregnancy and induction of ovulation.

Antibodies to estriol-16alpha-[beta-D-glucuronide] were raised in sheep with the use of keyhold limpet hemocyanin and bovine serum albumin conjugates of estriol-16alpha-[beta-D-glucuronide]. A simple, rapid method is presented for direct radioimmunoassay of estriol-16alpha-[beta-D-glucuronide] in urine with dextran-coated charcoal used for separation of free from bound and deionized water used for dilutions. The method is thrifty in its use of reagents. The assay has been evaluated in the pregnancy range, and the sensitivity has been extended into the range necessary for monitoring induction of ovulation with Pergonal.

Animals↗

A radioimmunoassay for 13, 14-dihydro-15-keto prostaglandin F2alpha with chromatography and internal recovery standard.

Antibodies to the 13, 14-dihydro-15-keto metabolite of prostaglandin F2alpha(PGF2alphaM) were raised in sheep using a bovine thyroglobulin conjugate of PGF2alphaM. Labeled 13, 14-dihydro-15-keto prostaglandin A2(PGA2M), 13, 14-dihydro-15-keto prostaglandin E2 (PGE2M) and PGF2alphaM were prepared from their corresponding high specific activity parent prostaglandins with swine kidney homogenate and purified using reverse phase liquid-liquid partition chromatography. A rapid method of column chromatography for use prior to radioimmunnoassay was developed. Mathematical corrections for the effect of recovery tracer on the logit/log transformation are presented with a new approach to expression of radioimmunoassay cross reactions allowing continuous expression of the variation of these cross reactions with displacement. These mathematical approaches are widely applicable to other radioimmunoassay systems and transformations. The assay was used for measurement in groups of human volunteers: males, females, women at delivery and paired venous umbilical cord bloods. A correlation between venous cord and maternal peripheral PGF2alphaM levels is demonstrated with a gradient from the cord plasma to maternal plasma.

Antibody Formation↗

Cardiac prostaglandin release during myocardial ischemia induced by atrial pacing in patients with coronary artery disease.

The relation between myocardial release of prostaglandin and myocardial ischemia was studied in 12 selected patients with multivessel coronary artery disease. These 12 were chosen for analysis because they experienced angina pectoris, ischemic electrocardiographic changes and decreased myocardial lactate uptake during atrial pacing. Simultaneous aortic and coronary sinus blood samples were obtained at rest, during angina and after recovery and were assayed for prostaglandins F, E and A with radioimmunoassay. Cardiac release of prostaglandin F was observed during angina in 11 of 12 patients. Aortic prostaglandin levels remained constant throught each study. During angina, the mean aortovenous difference (+/- standard error) was -0.30 +/- 0.04 ng/ml (P less than 0.001) for prostaglandin F and -0.10 +/- 0.03 ng/ml (Pless than 0.001) for prostaglandin E. There was no significant release of prostaglandin A. Blood samples were also drawn at subanginal heart rates in two patients. Prostaglandin F was released only during angina. In three control patients with a chest pain syndrome and normal coronary arteries, comparable atrial pacing produced no release of prostaglandin F, E or A. These results, together with the known vascular and metabolic actions of prostaglandins, suggest that these pharmacologically active compounds may also play a physiologic role in the cardiac response to ischemia in man.

Adult↗

The effect of angiotensin II and indomethacin on uterine artery blood flow in pregnant monkeys.

In experiments performed in anesthetized monkeys in the third trimester of pregnancy, mean maternal arterial blood pressure was continuously monitored, the uterine artery blood flow was measured with an electromagnetic flow probe, and prostaglandin levels were assayed in the uterine venous effluent. After inhibition of prostaglandin systhesis with indomethacin, the mean arterial blood pressure in response to angiotensin II was greater than the response prior to indomethacin treatment, and an increase in uterine artery blood flow was prevented. These findings are consistent with the suggestion that prostaglandins mediate the uterine artery blood flow response to angiotensin II, as well as modifying the maternal systemic blood pressure response.

Angiotensin II↗

Estrogen-induced luteolysis in the rhesus monkey: reversal with indomethacin.

Normally cycling Rhesus monkeys were treated with diethylstilbestrol (25 mg/day) alone or in combination with indomethacin (25 mg/day) for five consecutive days beginning in the early luteal and mid-luteal phase of the menstrual cycle. Blood specimens were obtained daily to monitor corpus luteum function (progesterone), and the length of each menstrual cycle was recorded. Diethylstilbestrol alone cause premature luteolysis as indicated by decreasing plasma progesterone and shortened menstrual cycle, and indomethacin effectively blocked the luteolytic action of diethylstilbestrol. These results suggest that the probable mechanism of diethylstilbestrol action in causing luteolysis is mediated via the prostaglandins.

Animals↗

Pentobarbital anesthesia: lack of effect on venous prostaglandins in dogs.

Venous prostaglandins A, E, and F were determined by radioimmunoassay in 10 dogs before and one hour after administration of sodium pentobarbital (35 mg/Kg, iv). In the conscious state, PGA was 0.34 + 0.04 ng/ml (mean +/- SE), PGE 0.20 + 0.01 ng/ml, and PGF 0.25 + 0.03 ng/ml. During pentobarbital anesthesia, these levels were unchanged (p greater than 0.05). Thus, pentobarbital anesthesia had no effect on peripheral venous prostaglandin levels.

Anesthesia↗