Analysis of nonderivatized steroids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using C70 fullerene as matrix.

Neutral steroid hormones are currently analyzed by gas or liquid chromatography/mass spectrometry based methods. Most of the steroid compounds, however, lack volatility and do not contain polar groups, which results in inadequate chromatographic behavior and low ionization efficiency. Derivatization of the steroids to form more volatile, thermostable, and charged products solves this difficulty, but the derivatization of compounds with unknown chemical moieties is not an easy task. In this study, a rapid, high-throughput, sensitive matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method is described using C(70) fullerene as a matrix compound. The application of the method is demonstrated for five general sex steroids and for synthetic steroid compounds in both negative and positive ionization modes.

[Evaluation of the value of triple diagnosis in prenatal medicine]. / Anfragen an die Wertigkeit der Triple-Diagnostik in der pränatalen Medizin.

The evaluation for every new method of early diagnostics is the criterion of quality of previous methods. The Triple diagnostics in the prenatal medicine however does not fulfill the criterion of standard for example for early diagnostics in gynecological oncology. Particularly, the precision in laboratories cannot be safely assumed so that false positive as well as false negative results are possible. The consequences of this method of early diagnostics are uncertainty for patients and physicians and of high expenditure for both.

A randomized trial of induction at 42 weeks gestation versus expectant management for postdates pregnancies.

A randomized prospective clinical trial of induction of labor at 42 completed weeks gestation versus expectant management in postdates pregnancies was performed. The primary screening test was the 24-hr urinary estriol creatinine ratio. The cesarean section rate was high in both groups and did not differ statistically. Intervention by delivery at 42 weeks decreased the development of small for gestational age infants, but costs slightly more. Twenty-four-hour urinary estriol creatinine ratio determinations predicted fetal distress in labor, but could not predict postmaturity syndrome or infants who were small for gestational age. As expectant management did not differ from induction of labor at 42 weeks from the standpoint of maternal outcome, and as the cost difference was small, induction of labor at 42 weeks may be the preferred management as it improves infant outcome.

Variation in antenatal testing over time and between clinic settings.

Variation in the use of diagnostic procedures may be due to characteristics of patients, physicians, or their environment. Testing rates for 24-hour urinary estriol levels (EST), diagnostic ultrasound, and antepartum fetal heart rate testing (AFHRT) were examined in 8,527 deliveries from 1975 through 1978. Over the period, utilization of EST remained constant at about 7% of deliveries, while ultrasound increased from 20% to 35% and AFHRT, from 7% to 12%. This increase persisted after stratifying patients on a multivariate confounder score using 45 items of clinical information. Those receiving antenatal care in a hospital-based group practice or a resident-staffed community clinic were more likely to be tested than patients seen in private offices or a prepaid group practice.

Plasma estrogens in the assessment of fetoplacental function.

A retrospective study has been undertaken to assess the diagnostic value of plasma estriol (E3) determinations, as compared with determinations of other biochemical parameters, in predicting the outcome of pregnancy. The normal levels of plasma unconjugated and total E3 were determined on weekly samples obtained during the third trimester of 258 normal pregnancies. Weekly concurrent specimens of plasma and 24-hour urine collections were obtained from 17 high-risk pregnancies associated with hypertension, intrauterine growth retardation and diabetes. Determination of plasma unconjugated and total E3 were made along with human placental lactogen (HPL), urinary E3, and other biophysical parameters such as the oxytocin challenge test, non-stressed test, ultrasonography, etc. The results of plasma E3 were not reported nor used for the clinical management of the patient. The data suggests that weekly plasma determinations were of little value in the assessment of feto-placental status. Some observations on the extent of variability of plasma E3 are discussed.

Oxytocinase versus estriol for the assessment of fetal well-being.

In a group of 26 primiparae, 48 hours after cesarean section, we have examined the urinary estriol (E3) and serum cystine aminopeptidase (CAP). 13 patients received ampicillin treatment, and 13 patients did not. In the group of patients without antibiotic treatment the urinary estriol after 48 h reached an average value of 5.55 mg/24 h. in the group of treated patients the drastic decrease of E3 reached a mean value of 1.62 mg/24 h. This fact may be explained by the arrest of the feto-placental inflow after delivery, and the blocking effect of the antibiotic on the enterohepatic circulation, compartment which afford for 50% of the maternal circulating estrogen. From the present work it results that the determination of the serum CAP activity, which is not affected by antibiotic treatment, is an appropriate test for the assessment of the fetoplacental unit activity. It must be mentioned that all the biochemical tests complete one another and may have a decisive role in taking immediate obstetrical decisions, together with the additional fetal heart rate monitoring and oxytocin challenge test.

Socioeconomic status, urine estrogens, and breast cancer risk.

Urine estrogens were measured in 46 women students, ages 15-18, at a middle-class high school in Athens and in 40 women of the same age residing at one of three orphanages in the same city. The lower socioeconomic status (SES) of the latter group was documented by their lower mean height (by 5.2 cm) and weight (by 5.3 kg) relative to the high school students. Both in follicular and luteal phases of the menstrual cycle, the women with lower SES had 50% higher estriol ratios (ratio of the concentration of estriol to the sum of the concentrations of estrone and estradiol). In luteal specimens the concentration of all three major estrogens was higher in the group with low SES than in the women in the other group, but the concentration of estriol was most increased. There was also an indication of less frequent anovular cycles among the women with low SES. These findings are consistent with hypotheses linking either the estriol ratio or the frequency of anovular cycles to breast cancer risk.

PIP: Urine estrogen levels were measured in 46 women students, ages 15-18, at a middle-class high school in Athens, Greece and in 40 women of the same age residing at 1 of 3 orphanages in the same city. The lower (SES) socioeconomic status of the latter group was documented by their lower mean height (by 5.2 cm) and weight (by 5.3 kg) relative to the high school students. Both in follicular and luteal phases of the menstrual cycle, the women with lower SES had 50% higher estriol ratios (ratio of the concentration of estriol to the sum of the concentrations of estrogens and estradiol). In luteal specimens, the concentration of all 3 major estrogens was higher in the group with low SES than in the women in the other group, but the concentration of estriol was most increased. There was also an indication of less frequent anovulan cycles among the women with low SES. These findings are consistent with hypotheses linking either the estriol ratio or the frequency of anovular cycles to breast cancer risk.

Assessment of foetal welfare.

While the reduction in maternal and perinatal mortality remains a constant goal, the emphasis in modern obstetrics has shifted towards the assessment of foetal welfare in utero. However, if the clinician is to avoid ultimate confusion, he must temper the information which may be obtained from the numerous tests and techniques available with shrewd clinical judgement. In addition, in the current climate of economic audit, he must consider the cost of the investigations in pure monetary terms.

Fetal movements in utero: nature, assessment, prognostic value, timing of delivery.

Fetal movements in utero are an expression of fetal well-being. However, a sudden increase of fetal movements is a sign of acute fetal distress, such as in cases of cord complications or abruptio placentae. Decreased fetal movements are seen in cases of chronic fetal distress such as preeclampsia, hypertension in pregnancy, etc. It was shown that in these cases a pronounced decrease up to cessation of fetal movements occurred before fetal death in utero while fetal heart beats were still audible for at least 12 hours. This situation was called "movements alarm signal" (MAS). This sign points to a severely disturbed fetus and indicates impending intrauterine fetal death. Such a development is an indication for immediate delivery of the fetus, provided it is viable. High-risk pregnant women are instructed to assess and record fetal movements daily as a monitor of fetal condition. A special device which records fetal movements is used to confirm the women's assessment of fetal movement. It was shown that fetal movement monitoring was found to be more reliable than the urinary estriol determination in predicting impending fetal death in utero. It was also shown that in cases of MAS, fetal heart rate (FHR) changes will appear 1 to 4 days after the MAS has appeared. Meconium was found in only 50% of these cases. Increased fetal movements are manifested as a response to various stimuli such as sound, light, touch, and ultrasound. Classification of high-risk pregnancies into 3 groups according to the hormone assays, enzyme assays, ultrasonic cephalometry, fetal movements, and FHR is suggested.

Diagnostic studies and fetal assessment in advanced extrauterine pregnancy.

Advanced extrauterine pregnancy occurs rarely and may present diagnostic difficulty. Failure to induce uterine contractions during oxytocin infusion is a well-established diagnostic technic. The present case suggests that additional newer technics for fetal assessment, including sonography, unstressed monitoring of the fetal heart rate, uterine contractions, fetal movements, and serial urinary estriol determinations may also be useful in diagnosing and managing such complex cas-s.

Urinary estriol for assessment of fetoplacental function.

A total of 1,607 urinary estriol determinations were performed in 447 patients with normal and complicated pregnancies. In general, the test provided reliable information concerning fetal status, particularly in pregnancies complicated by toxemia, diabetes, and postmaturity. When measured consecutively, a drop of 50% or more in estriol level usually should be considered a significant index of fetal distress. Limitations of the test and several compensatory measures aimed at minimizing inaccuracy are discussed.

Toxemia of pregnancy: assessment of fetal distress by urinary estriol and circulating human placental lactogen and alpha-fetoprotein levels.

The efficacy of three biochemical methods for the detection of fetal distress was assessed in a prospective study of 224 singleton pregnancies complicated by toxemia. Fetal distress was diagnosed in 65 cases (29 per cent). Abnormally low urinary estriol (E3) excretion pointed out 63 per cent, low serum levels of human placental lactogen (HPL) 27 per cent, and elevated maternal serum alpha fetoprotein (AFP) 10 per cent of distressed fetuses. The efficacy of each test increased with the severity of maternal disease. The frequencies of false pathologic levels were: E3 19 per cent, HPL 0 per cent, and AFP 1 per cent of the cases with a normal fetal outcome. Although E3 was by far the most effective marker, abnormal levels of HPL and AFP provided supportive evidence for fetal distress by pointing out those cases in which E3 reading was not a false positive.

Assessment of placental function in normal and pathological pregnancies by estimation of plasma oestradiol levels after injection of dehydroepiandrosterone sulphate.

A test of placental function was assessed by measurement of plasma oestradiol levels in 32 patients after intravenous injection of 50 mg dehydroepiandrosterone sulphate (DHAS). Every pregnant patient showed a rise in plasma oestradiol after DHAS; two puerperal patients showed no rise. It was not possible to distinguish the variable response in normal pregnancy from that in patients with severe hypertension and proteinuria or with retarded intrauterine fetal growth. The test was of no value in one hypertensive patient as a predictor of fetal death eight days later or, in another, to confirm fetal death of two days duration. Our results do not suggest that this test is a useful addition to currently available tests of placental endocrine function.