We report here the observations of positive maternal serum screening tests for Down syndrome, cytogenetic and molecular analysis, and dysmorphic fetal features in a pregnancy with 18q-syndrome. A 33-year-old primigravida was referred for genetic counselling because of multiple-marker screen positive results. At 14 weeks' gestation, the woman had a Down syndrome risk of 1:107 calculated from a maternal serum alpha-fetoprotein (MSAFP) level of 1.49 multiples of the median (MOM), a total human chorionic gonadotrophin (hCG) level of 2.42 MOM, and a serum unconjugated oestriol (uE3) level of 0.55 MOM. At 17 weeks' gestation, a repeat test showed a Down syndrome risk of 1:10 calculated from an MSAFP level of 1.09 MOM and a free beta-hCG level of 12.3 MOM. Genetic amniocentesis revealed a de novo deletion of 18q22.2-qter. Intrauterine fetal death occurred at 21 weeks' gestation. At birth, the fetus manifested clinical findings of the 18q-syndrome. The phenotype was correlated with the extent of the deletion. Linkage analysis of the family confirmed the extent and paternal origin of the deletion.

Pregnancy in a diabetic woman carries with it a risk of intra-uterine death for the foetus. In this paper the authors report on 9 cases of pregnancy in diabetic women and the results obtained when a systematic management of the condition involving delivery before term, always by caesarean section, is carried out. It is absolutely vital to have perfect stabilisation of the diabetic state during the pregnancy, in order to do this the patient must be seen very often and brought into hospital early, soon after the 28th week. It would appear to us that caesarean delivery is the delivery of choice because it allows the extraction of a foetus in good condition, at a chosen time when a trained team is ready. It is essential to end the pregnancy somewhere between the 36th and 37th week of the pregnancy and sometimes even earlier if there is associated pathology such as toxaemia. This systematic method implies a constant check on the fetal well-being by oestriol estimations, although we realise that the levels are still low between the 7th and 8th month and that watching a graph that is steadily climbing allows the team to wait until the calculated date for bringing the pregnancy to its conclusion. In two cases the pregnancy was interrupted early because of variations in the graph; in one early delivery was justified by the development of toxaemia and in the other a moderate drop in the oestriol levels led us to intervene early. When there is a drop in the levels is it very important to ensure that is is due to fetal distress and not to daily physiological changes because the risk is of excessive prematurity if induction is carried out too soon.

Ninety-seven postmature pregnancies were monitored by amnioscopy or amniocentesis (to determine presence or absence of meconium), oxytocin challenge tests (OCT), 24-hour urinary oestriol estimations and fetal movement counts. The colour of the amniotic fluid and the result of the OCT predicted almost all cases of fetal distress in labour and infants with low Apgar scores. Oestriol estimations and fetal movement counts predicted fetal distress only when combined with other positive tests. Of 50 patients with no abnormal test results, 49 had uneventful labours. The Caesarean section rate was not above average and all babies were liveborn.

In 92 pregnant women with low urinary oestriol excretion after 30 weeks' gestation, there was a higher incidence of fetal distress, premature delivery and induced labour, while resuscitation of the infant at birth was required more often than in controls. The birth weights, head circumference, and body lengths of the infants were significantly lower than those of the controls. In the 26 cases where maternal oestriol levels were persistently low, three were associated with placental sulphatase deficiency, and three infants died postnatally. Four infants had evidence of neurological defects on follow up, as did four infants in the control group. The low head circumferences, weight, and length were still present at two years of age. It is concluded that, although low oestriol excretion during pregnancy is associated with increased risk to the fetus, it is not associated per se with permanent neurological damage, provided the infant is born alive, and is congenitally normal. However, many infants remain smaller than average, at least for the first years of life.

Twenty post-menopausal women were treated using oestriol vaginal suppositories (Ortho-Gynest). Subjective disturbances such as dyspareunia, pruritus, and kraurosis vulvae showed a good response to the therapy, while the anaplastic activity of the vaginal epithelium to the suppositories was shown by an increase in the vaginal superficial cells which followed the course of treatment. Side-effects were minimal and disappeared following cessation of treatment.

A clinical study was undertaken, in twenty-four patients with atrophic vaginal changes, to assess the efficacy and the acceptability of treatment with Ortho-Gynesi vaginal suppositories, which have as their active constituent the naturally occurring substance oestriol. A regenerative effect on the vaginal epithelium could be objectively demonstrated by an increase in the proportion of superficial cells following treatment. Changes in the vaginal epithelium were accompanied by a diminution in the incidence of infection and inflammation. Subjective complaints such as dyspareunia, pruritus and kraurosis vulvae, which could also be ascribed to a relative oestrogen deficiency, responded well to treatment.

BUF/Mna rats develop spontaneous thymomas with nearly 100% incidence in both sexes. While the thymomas in males develop from around 9 months of age, those in females start from 13-15 months of age. To clarify the mechanism of the delay of thymomagenesis in females, the effect of sex hormones on the development of thymomas was examined after either gonadectomy or oestrogen treatment. Prepubertal ovariectomy accelerated the thymoma development in females, whereas orchiectomy did not affect it. An intraperitoneal injection of oestriol (20 mg) into males at 2 months of age remarkably diminished the thymic weight to about one-tenth of age-matched controls at 16 months of age. These results suggest that oestrogen can actually retard the onset of thymoma in spite of genetic control of its incidence. However, oestrogen did not cause thymic involution when it was injected into rats over 9 months of age. Immunohistochemically, there seemed to be no distinct difference in distribution of oestrogen-receptor-bearing epithelial cells between thymomas and 2- to 3-month-old thymuses. The oestrogen sensitivity of the thymus might be destined to be lost, as the thymic epithelial cells start neoplastic changes with the impairment of oestrogen-receptor function.

Hormone replacement therapy is a personal not a theoretical question for women. This article reviews the literature on the use of oestrogen assessed from the personal female perspective which emerges when the hormones are to be taken by myself. I should probably choose oestrogens for myself if I suffered very troublesome oestrogen-related climacteric vasomotor or atrophic symptoms. The increased risk of breast cancer would make me delay such treatment as long as possible. -Until reliable and valid methods for individual risk assessment are available I should prefer physiological and less risky ways of preventing my own osteoporosis than years of hormone treatment. If, in old age, I may need oestriols to prevent urogenital troubles I am glad to know that they are efficient and involve little risk. Nevertheless, I should not want to take hormones "to be on the safe side".

Although there is no doubt that increasing numbers of women are presenting with carcinoma of the endometrium, this could be due only to the fact that many more women live to an age when they are liable to get this cancer. Even when age specific incidence rates are considered, the apparent increase could be due to risk factors other than oestrogens. Recent developments in hormone replacement therapy have placed increasing emphasis on the natural oestrogens, oestradiol and oestrone, but they present problems of their own. Nor has the induction of periodic bleeding by cyclical administration of oestrogens, with or without a progestogen, proved an unqualified success. A special case might yet be made for the weaker physiological oestrogen, oestriol.

Urinary oestrogen excretion was measured in 20 healthy middle-aged men (controls), in 30 patients with benign prostatic hyperplasia (BPH) and in 32 prostatic cancer (PC) patients. The mean oestradiol (E2) excretion was significantly lower in the PC patients than in the controls and BPH patients. No other significant differences were found in oestrone (E1), oestriol (E3) and total oestrogen (E1 + E2 + E3) excretion between the 3 groups. The decreased E2 excretion in the PC patients is in accordance with our previous finding concerning significantly lower E2 plasma levels in PC patients. It seems possible that elderly men with lower endogenous oestrogen levels are at higher risk of developing cancer. On the other hand, the age-dependent increased oestrogen levels may play an aetiological role in BPH.

We have estimated the binding characteristics of an oestrogen binding protein in the human vagina and in the human myometrium. The specificities of these binding proteins were analyzed in binding studies using competitors and ligands with different structural features representing the various elements considered to be of importance for binding. The specificity of an oestrogen binding protein in human myometrium was found to be similar to those of oestrogen binding proteins in human breast tumour tissue and in human MCF-7 cells. This specificity was also similar to those of oestrogen receptors in myometrium, endometrium and vagina of the rat. However, the specificity of an oestrogen binding protein in the vagina of postmenopausal patients was different. The vaginal oestrogen-binding protein displayed similar high affinities for 17 beta-oestradiol, 17 alpha-oestradiol and oestriol but low affinity for diethylstilbestrol. The equilibrium dissociation constants for [3H]oestriol and [3H]17 beta-oestradiol were 4.3 X 10(-10) M and 4.0 X 10(-10) M respectively and the concentration of this protein varied between 30 and 170 fmol/mg vaginal cytosol protein. We conclude that the human vagina contains an oestrogen binding protein with characteristics different from those of oestrogen receptors present in myometrium and breast tumour tissue.

The relation between maternal plasma unconjugated oestriol (E3) concentrations and uterine activity was investigated by very frequent, carefully timed determinations of E3 during synchronously recorded uterine contractions in six normal subjects. There was an initial rise (10 to 50 per cent above the mean) in E3 levels reaching a peak coincident with the contraction peak (range 20 seconds before to 15 seconds after) followed by a fall of similar magnitude below the mean reaching a nadir about 80 seconds (range 60 to 105 seconds) after the contraction peak. Although the pattern of E3 fluctuation was most marked in labour the overall degree of variation was no greater than at other times. Cystine aminopeptidase (CAP) concentrations in the same serum samples showed no significant correlation with uterine contractions. The reasons for, and practical applications of, the E3 results are discussed.

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were studied prospectively in 29 pregnancies complicated by intrauterine growth retardation. The newborn growth-retarded infants were examined by neurological and behavioural techniques. Growth variables and neurological and developmental findings were compared with those in 18 healthy controls at 5, 10 and 18 months of age. The growth-retarded infants caught up with regard to body size from 5 months of age, although the severely retarded infants (birth weight less than or equal to -2 SD) differed from the controls with regard to weight and head circumference at 18 months of age. Abnormal maternal oestriol excretions were negatively correlated to weight and length during the follow-up period. Infants who had been severely growth-retarded at birth were neurologically below optimal level at 10 months of age, compared to the controls. There were no significant differences between the growth-retarded infants and the controls with regard to psychomotor development, as assessed by a screening test and by Griffiths' method. Significant correlations were found between abnormal biochemical placental tests (especially urinary oestriol and S-CAP) and psychomotor development. Significant correlations also appeared between neonatal orientation and motor behaviour and some Griffiths' scales at 18 months of age. No relationship was found between the neurological condition in the neonatal period and the neurological findings and development at follow-up.

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.

Radioimmunoassay of sex steroids and prostaglandins was performed on plasma obtained from 10 uncomplicated primigravid subjects at a stated time of the day at varying stages of gestation. Prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), oestrone and oestriol concentrations reached a peak a few weeks before term and then declined. Progesterine, 17-hydroxyprogesterone and oestradiol increased during pregnancy particularly after 32 weeks. In two normal patients repeated blood samples were taken throughout the day at weekly intervals in late pregnancy for sex steroid assays to evaluate the variation of concentrations with the time of sampling and the significance of changes in mean concentrations of different steroids with approaching parturition. Marked variability was found in the levels of different steroids during the day. Plasma oestriol values were lowest at 8.00 a.m. in one patient sampled frequently. A marked decrease in oestriol, oestrone, oestradiol and 17-hydroxyprogesterone was found in one patient prior to the onset of spontaneous labour. In another subject there was no decrease in concentrations of oestrogens or progestogens prior to induction of labour at term.

Taking Solid-Phase Extraction (SPE) as pre-treatment process, a laboratory experiment was conducted by adopting the technology of High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MSMS) to develop a method to determine the concentrations of 13 steroids in feedlot wastewater. Atmospheric Press Chemical ionization (APCI) source was applied and operated in negative ion model, with the parameters of Chromatography and Spectrometry being optimized. Quasi-molecular ion peak [M + H]+ appeared in the full scan of the first quadrupole of mass spectrometer (Q1) of Testosterone propionate and other 6 steroid compounds, while quasi-molecular ion peak [M + H-H2O]+ appeared in the full scan of Q1 of rest 6 steroid compounds. The linear range of the 9 points calibration curve for the 13 target compounds was determined to be from 1 to 1000 ng x ml(-1), and the calibration curve regression correlation coefficients (R) were always above 0.9990 for all sample batches. The average recovery rate of all target compounds was 83.75%-111.50%, and the methodological stability was determined to be acceptable, with the relative standard deviations between 2.02%-14.21% (n=6). Except that the limit of detection (LOD) of Mestradiol and Oestriol was higher than 15 ng x ml(-1), all the other target compounds had a LOD lower than 5 ng x ml(-1). In the determination of real samples from feedlot wastewater, the developed method represented a good profile to all target compounds at different concentrations in each stage of treatment.

A limited numbers of published studies evaluate the referral reasons for genetic counseling services in the literature. These studies are focused on prenatal genetic counseling services, in particular, prenatal diagnosis. In order to provide the most effective and helpful genetic counseling services, genetics professionals need adequate knowledge about the profile of individuals referred for these services. In addition, physicians need increased awareness of the nature of genetic issues in order to make appropriate referrals. This study was intended to provide a descriptive analysis of the referral reasons of patients that received genetic counseling at a genetics center in Izmir, Turkey during an 11-year period. A total of 8965 records generated between 1998 and 2008 from one genetic center (which consists of The Department of Medical Genetics and Division of Pediatric Genetics) were evaluated retrospectively. Of these, 6,258 involved referrals for prenatal reasons, and 2,707 involved referrals for postnatal reasons. Both prenatal and postnatal records were further classified into more specific categories of referral reasons. The most common reason for genetic counseling among the prenatal patients was advanced maternal age (42.0%), followed by high risk results on prenatal biochemical screening tests such as second trimester double test [(serum concentration of alphafetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG)], triple test (serum concentration of AFP, beta-HCG, oestriol) and integrated test (26.5%). The most common indications for postnatal patients were recurrent miscarriages (28.2%) and infertility (19.7%). A significant increase in number of specific categories of referrals for genetic counseling was observed for the last 3 years after the establishment of the Medical Genetics Department. These data provide useful information about the frequency of referrals to the genetics department, and the feasibility of genetic services. Organization of genetic services and systematic procedures for genetic counseling and genetic testing may improve the public's awareness of genetics and ensure a high standard of patient care.

Previously in world literature there have been reports of 40 pregnancies in women with untreated Cushing's syndrome. The perinatal mortality in these series has been 12.9%. This paper reports on a case in which low serum oestriol excretion was the first abnormal laboratory value in a patient with only a few signs of Cushing's syndrome habitus and adrenal adenoma.

This prospective study investigates the relationship between insulin-dependent diabetes and maternal serum levels of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). It also examines the potential impact on screening for Down syndrome. The population-based cohort included 20,321 pregnant women in Maine who underwent routine serum screening for Down syndrome in the second trimester. The cohort included 52 women with insulin-dependent diabetes. Maternal serum AFP levels are now routinely adjusted for insulin-dependent diabetes. These adjustments, therefore, were made routinely in the diabetic women, but no equivalent adjustments were made for uE3 and hCG values. The initial false-positive rate (using all three markers) among the women with diabetes was not significantly different from that in the non-diabetic population (7.7 and 5.4 per cent, respectively). Prior to adjustment for insulin-dependent diabetes, the median AFP level in the 52 women was 0.73 multiples of the median (MOM); the median levels of uE3 and hCG were 0.93 and 0.98 MOM, respectively. When the uE3 and hCG levels were adjusted, the initial false-positive rate was unchanged. Median serum levels of uE3 were significantly higher in the 33 women whose onset of diabetes was prior to 19 years of age (0.99 MOM) than in the 19 women whose onset of diabetes was at age 19 or older (0.84 MOM). This is the first population-based study to investigate the relationship between diabetes and serum levels of AFP, uE3, and hCG, and confirms earlier observations from a case-control study that found only slightly lower uE3 and hCG levels.