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In this paper, we give a survey of the known results concerning the tensor rank of multiplication in finite extensions of finite fields, enriched with some unpublished recent results, and we analyze these to enhance the qualitative understanding of the research area. In particular, we identify and clarify certain partially proved results and emphasise links with open problems in number theory, algebraic geometry, and coding theory. Bibliography: 92 titles.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

This paper considers the situation of older workers in developed economies generally, and the specific cases of Australia and Japan. It examines trends in the employment of older people, the development of public policies, and identifies measures for promoting longer employment, re-employment, and gradual retirement.

We generalize the multiplication algorithm of D.V. and G.V. Chudnovsky. Using the new algorithm, we improve the upper bounds of the bilinear complexity of multiplication in all extensions of a finite field of characteristic 2. On the other hand, we also improve in characteristic 2 the asymptotic upper bounds of this complexity.

In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 micrograms gestodene and 20 micrograms ethinylestradiol were assessed.Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15-21 in cycle 6 for 13 subjects (Group A) and during days 15-21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B).All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Pre-decidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6.With monophasic gestodene/ethinylestradiol 75 micrograms/20 micrograms, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.

Flow cytometry was used to: (1) determine residual leucocyte numbers in red cell suspensions following the range of leucocyte depletion procedures used in our organisation, and (2) to characterize phenotypically the leucocytes using direct immunofluorescence with monoclonal antibodies to cell surface receptors. Under the conditions used, a lower limit of detection of 2.5 leucocytes per microliter (equivalent to 3.43 log10 or 99.96% removal) could be achieved. Filtration through polyester filters was found to remove up to > 99.96% of the initial leucocytes; however, a significant differential efficacy was observed between filters from different manufacturers even when filters with similar costs were compared. The order of filter brands with respect to leucocyte removal found was Pall BPF4 = Erypur Optima G-O > Sepacell R500 > Pall RC50. Phenotyping revealed that increasing filtration efficacy was associated with a preferential removal of lymphocytes; conversely, a second filtration over one brand of filter allowed proportionately more lymphocytes to pass through compared with the first filtration. A saline wash following filtration removed a further 0.5% of the initial leucocyte content, and was associated with a preferential loss of granulocytes. Freeze-thawing the red cell suspension removed fewer leucocytes (96.3%) than did filtration (98.74% to > 99.6%) or filtration followed by washing (99.22%), and also led to preferential loss of granulocytes. Flow cytometry provides a reliable tool for the quality control of leuco-depleted red cells, and allows a qualitative assessment of the residual leucocytes. This information is of value in choosing procedures aimed at decreasing the risk of alloimmunisation and post-transfusion reactions.

Background . In a prospective study the effect of the behavioral risk factors of both partners on fecundability was studied. Methods . Information was collected on smoking habits, alcohol consumption, and caffeine intake (e.g. coffee, tea, and cola consumption) by interviewing 259 female nonmedical hospital workers, i.e., clerical staff, cleaners, kitchen and restaurant workers, and their partners, who were planning a pregnancy. The occurrence of pregnancy was tested prospectively during the 12 months after enrollment. Results . Among the participants as well as among their partners, smoking a moderate number of cigarettes (1-10/day) was associated with higher fecundability (i.e., the probability of becoming pregnant each month) than among those not smoking (participant: OR = 1.4 (95% CI, 0.9-2.2); partner: OR = 2.1 (95% CI, 1.2-3.5)). The level of alcohol consumption in the female partner was not related to fecundability. However, in the male partner, there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 (OR = 1.6; 95% CI, 1.0-2.4). Participants with a moderate caffeine intake (400-700 mg/day) showed a higher fecundability than those with a lower intake level (OR adjusted = 2.1 (95% CI, 1.2-3.7)). Heavy caffeine intake (>700 mg/day) among partners was negatively related to fecundability when compared with the lowest intake level (OR adjusted = 0.6 (95% CI, 0.3-0.97)). Conclusions . This study does not support the hypothesis that moderate cigarette smoking, caffeine intake, and alcohol consumption have an adverse influence on fecundability.

To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital.Randomised controlled trial.Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway.A total of 1111 women assessed to be at low risk at onset of spontaneous labour.Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit.Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score7 at 5 minutes, metabolic acidosis and transfer to neonatal intensive care unit.There were no significant differences in total operative deliveries between the three units: 16.3% in the midwife-led unit; 18.0% in the normal unit; and 18.8% in the special unit. There were no significant differences in postpartum haemorrhage, sphincter injuries or in neonatal outcomes. There were statistically significant differences in augmentation (midwife-led unit versus normal unit RR 0.73, 95% CI 0.59-0.89; midwife-led unit versus special unit RR 0.69, 95% CI 0.56-0.86), in epidural analgesia (midwife-led unit versus normal unit RR 0.68, 95% CI 0.52-0.90; midwife-led unit versus special unit RR 0.64, 95% CI 0.47-0.86) and in acupuncture (midwife-led unit versus normal unit RR 1.45, 95% CI 1.25-1.69; midwife-led unit versus special unit RR 1.45, 95% CI 1.22-1.73).The level of birth care does not significantly affect the rate of operative deliveries in low-risk women without any expressed preference for level of birth care.

This paper presents a new approach based on converter networks using elementary cells (ec). It deals with the beginning of research and development carried out on the design of the "ec", the random command and the magnetic coupling among the elementary cells. This paper introduces at first the recent works carried out on interleaved "ec" and power electronics converters (cvs) into networks: from basic interleaving approaches, trying to minimize filter sizes up to highly coupled solutions trying to optimize sizes but also current and voltage levels. In the next sections of the paper, the modular approach will be presented. The paper presents a study showing how a random mode control is used to simplify the implementation of a generic "ec" into any network. Evaluating the output voltage filtering criteria, we compare classical synchronous interleaved and random mode controls. Then, the paper focuses on the design and the characterization of the elementary cell and especially on its active part. The last part of the paper focuses on magnetic coupling for converter coupling and filtering. Experimental results underline the importance of coupling among elementary cells and inside the corresponding "cvs" and an analytical study of magnetic coupling is presented. An 2n-windings transformer formed of n identical three-winding transformers is used to connect the "ec" among them. The aims of these studies are to improve electrical management of modular "cvs" network without any constraints on the modularity and the genericity of the approach.

Objective To study human sperm motility in a coculture system for in vitro fertilization (IVF). Design We studied the viability and motility (percentage and curvilinear velocity) of human spermatozoa after incubation in: (1) medium 199 supplemented with fetal calf serum (M199/FCS) together with Vero cells; (2) Vero cell conditioned M199/FCS; (3) M199/FCS supplemented with Vero cell extract; and (4) some control media. In a second experiment, FCS was substituted by sera from different IVF patients. Setting Semen samples were obtained from the fertility laboratory of the St. Radboud Hospital, Nijmegen, The Netherlands. Patients Twelve men of couples with fertility problems. Interventions None. Main Outcome Measure The motility parameters were determined with a computerized motility-analyzing system, after 24 hours' incubation at 37°C and 5% CO 2 . Viability was determined after eosi'n Y staining. Results Sperm viability was the same in all media. In the coincubation system, the Vero cell-conditioned medium, and the experiment with human sera, the sperm motility parameters were higher ( P Conclusions Coincubation has a positive effect on sperm motility and may be beneficial to IVF, intrauterine insemination, and artificial insemination.

Forty-two black and white male dairy calves were used to determine the effect of iron concentration in concentrate diets on growth performance and meat color. The experimental period began after weaning at 6 wk of age. Calves, averaging 67.2 kg, were randomly divided into three groups. Each group received, ad libitum, concentrates with different iron concentrations: low iron concentration, 100 mg kg−1 of dry matter (LI, n = 15), intermediate iron concentration, 150 mg kg−1 (II, n = 14) and a high iron concentration, 200 mg kg−1 (HI, n = 13). Calves were slaughtered at 190 kg body weight. Total iron intake averaged 30.0, 56.1 and 74.7 g for groups LI, II, HI, respectively. Iron concentration in the diet did not affect (P > 0.10) average daily gain or total dry matter intake, which averaged 1.23 kg d−1 and 334.5 kg, respectively. Blood samples were collected from the jugular vein on days 1, 29, 57 and on the day of slaughter. Hemoglobin concentration and hematocrit averaged, respectively, 11.9 g 100 mL−1 and 37% on slaughter day and were not affected (P > 0.10) by treatments. Carcass weight and classification, color of the pectoralis major, and composition of the liver and of the longissimus dorsi at the 12th rib level were not affected (P > 0.10) by treatments. Unexpectedly, color score of the longissimus dorsi was linearly (P −1 of iron, exceed the iron concentration required to produce light meat color or affect hemoglobin concentration of grain-fed calves. Therefore, concentrates made using commercial ingredients would need the addition of an agent-chelating iron to produce light meat color. Key words: Iron, calves, growth, meat, liver, color, hemoglobin

We have studied the concentrations of intact human choriogonadotropin (hCG) and the free hCG beta-subunit in blood samples from singleton pregnancies at risk for habitual or threatened abortion. The samples were obtained weekly between the 6th and 12th weeks and in the 14th and 16th weeks of gestational age. The concentrations of intact hCG, of the free hCG beta-subunit, and of "total" hCG (i.e., intact hCG and the free hCG beta-subunit: hCG + beta) were measured in serum by specific immunoassays. The distributional statistics (the 5th, 50th, and 95th percentiles) of "total" hCG + beta and of intact hCG showed very similar patterns, whereas the response curves for the free hCG beta-subunit showed very much lower serum concentrations. From these data we also estimated distributional statistics of the percent molar ratios of free hCG beta-subunit to intact hCG. We conclude that (a) the relatively small proportion of free hCG beta-subunit in serum during the first half of singleton pregnancy is far too low to interfere with the applied "total" hCG assay, as compared with the serum values obtained for intact hCG, and (b) the percent molar ratios of free hCG beta-subunit to intact hCG, or to "total" hCG + beta, never exceeded 1.0% throughout the period of pregnancy studied.

Objective: To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital. Design: Randomised controlled trial. Setting: Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway. Population: A total of 1111 women assessed to be at low risk at onset of spontaneous labour. Methods: Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit. Main outcome measures: Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score

Large quantities and reduced costs: in the field of telecommunications, the terminal market is going to pull up the semiconductor market. The development in the direction of silicon-based systems is clear. The equipment manufacturer has to improve his expertise.

This study was designed to compare the efficacy and safety of two sizes of Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50, a reservoir system. Three hundred and ninety-four (394) hysterectomised postmenopausal women between 30 and 65 years of age participated in this open-label, randomised, multicentre clinical trial. The main efficacy criterion was the reduction in the mean number of hot flushes per day at six months. Secondary efficacy end points included other climacteric symptoms as well as various psychofunctional and genitourinary disorders. A significant decrease from baseline in the mean number of hot flushes/day was observed in all three groups from the end of cycle 1, reaching 90% at the end of cycle 7. there was no statistically significant difference between Lyrelle 50 and Estraderm at any time point for any parameter; however, between-group differences between Lyrelle 80 and Estraderm for various parameters were seen in the first three cycles in favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all three groups, without significant between-group differences. We conclude that the new Lyrelle patch is a highly effective system for transdermal oestrogen replacement therapy that may enhance long-term patient compliance.

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.Health researchers randomly assigned 100 healthy women aged 18-38 from the Netherlands and Saudi Arabia to one of four various oral contraceptive (OC) groups to undergo six cycles of OC therapy so they could evaluate changes in plasma concentrations of sex hormone binding globulin (SHBG), corticosteroid-binding globulin (CBG), albumin (Alb), testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A), dehydro-epiandrosterone-sulphate (DHEA-S), and 17 alpha-hydroxyprogesterone (17OHP). The four monophasic OCs were Cilest (35 mcg ethinyl estradiol [E2] and 250 mcg norgestimate), Femodeen (30 mcg E2 and 75 mcg gestodene), Marvelon (30 mcg E2 and 150 mcg desogestrel), and Mercilon (20 mcg E2 and 150 mcg desogestrel). There were 12 dropouts. Neither body weight nor blood pressure changed significantly during the study. All steroidal serum parameters (T, FT, DHT, A, DHEA-S, 17OHP, Alb) fell significantly during the six cycles of OC treatment (ratio of decrease, 1.3-3), regardless of OC type. These changes had appeared after cycle 4. The only significant difference between the OC groups was that the mean decrease of DHEA-S for Mercilon was lower than that for the other OC groups (21% vs. 43% for Cilest, 44% for Marvelon, and 34% for Femodeen; p 0.05). SHBG and CBG rose greatly during OC use in all four OC groups (mean increase = 263% and 94%, respectively; p 0.05). The increase in CBG was significantly less in the Mercilon group than in the other OC groups (74% vs. 96% for Cilest, 101% for Femodeen, and 102% for Marvelon; p 0.05). These findings show that OC use changed the endogenous androgen environment in the direction of hypoandrogenism. Thus, all four OCs can equally treat androgen-related syndromes (e.g., acne and hirsutism).

To study the contribution of smoking and alcohol consumption to semen quality.Retrospective analysis.University-based fertility clinic.Smoking and alcohol consumption were investigated in a control group (68) and in a group of 47 subjects with defined poor semen quality (PSQ). The control group was composed of subjects whose semen showed a greater than 60% morphological normality, a greater than 60% motility with a linear progression, and a density of greater than 20 million spermatozoa/mL. The group with PSQ was composed of subjects whose semen showed a less than 30% morphological normality, less than 60% motility, characterized by slow, weak motility, and a density of less than 20 million spermatozoa/mL. Medical dossiers were studied regarding the life style of the subjects.The distribution of heavy smokers and light smokers did not differ statistically between the groups. There appeared to be a higher, but statistically insignificant, proportion of heavy smokers in the PSQ group (50%) compared to the control group (32.3%; P.1); nor were significant differences found between cases and controls with respect to alcohol consumption pattern. In the PSQ group, a comparison of the semen characteristics of the daily drinkers with those of all the other subfertile patients showed no statistical difference concerning semen volume (4.1 +/- 1.9 vs. 3.3 +/- 1.3 mL; P.1), sperm density (10.6 +/- 7.8 vs. 8.9 +/- 5.8 million spermatozoa/mL; Por = .1), and percentage of motile spermatozoa (27.0 +/- 15.1 vs. 25.5 +/- 16.1%; P.1). However, a lower percentage of normal sperm morphology was observed in the daily-drinker group (17.6 +/- 7.2% vs. 23.0 +/- 6.5% for the other subfertile patients; P.05).Factors such as smoking and alcohol consumption do not seem to play a pivotal role in the etiology of poor semen quality, but a pattern of excessive alcohol consumption may decrease further an already low percentage of sperm with normal morphology.

Changes in endogenous androgen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives (OCs). One hundred women were randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4) 30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded, and plasma levels of the following variables were recorded: sex-hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and hydroxyprogesterone. The free androgen index was also calculated. These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles. There were no statistically significant differences in androgenic variables among the four OCs. The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations (20% vs. 45%). Concentrations of SHBG and CBG increased significantly in all four groups (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations (about 100%). The four modern, low-dose OCs tested had similar impacts on endogenous androgen metabolism, yielding significant decreases in testosterone, dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be beneficial in women with androgen-related syndromes such as acne and hirsutism. Large studies are under way to establish which of the third-generation OCs is the least androgenic. In vitro studies suggest that norgestimate has the least androgenic profile.

Oral combination contraceptives (OCs) can exert a beneficial effect on the hypo-estrogenic condition of the lactating mother postpartum as well as on flushes and dyspareunia resulting from genital atrophy. During the 1st week after delivery there is an increased risk of thromboembolic episodes, especially for women who breast-feed. A 1989 meta analysis indicated that OC use considerably increases the risk of suspension of breast-feeding within 3 months postpartum (odds ratio 7.3). Although hormones reach the child via the mother's milk, negative consequences have not been reported. The minipills contain progestins alone, but they have been hardly used in the Netherlands because of irregular bleeding. The IUD is reliable and does not adversely affect breast-feeding, but after delivery there is an increased chance of perforation, expulsion, and infection associated with its use, especially when it is inserted in the weeks after delivery. Insertion 4-6 weeks postpartum reduces this risk. Echoscopic controls are necessary to preclude expulsion. Condoms are suitable when short-term contraception is desired before another pregnancy. They can also protect against ascending infections, but they are less reliable than OCs or the IUD. The diaphragm cannot be used in the first months because of changes in the genital tract that can occur until 3-6 months postpartum. During this time an alternative is needed, possibly the female condom. Sterilization in general should be avoided after childbirth because of the emotionally unstable period, and subsequent regret. Also postpartum sterilization is more difficult because of thickened tubes. The Bellagio consensus in 1988 recommended exclusive breast-feeding also for contraception because during the first 6 months postpartum the risk of getting pregnant is less than 2%. In the Netherlands in 1991, only 26% of women were still fully breast-feeding after 3 months. Contraceptive counseling should consider individual factors such as contraceptive experience, breast-feeding or bottle feeding, and whether the risk of pregnancy is acceptable.

A multidisciplinary study was conducted on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. It was possible to analyse whether the MRKH syndrome can be considered as a single clinical entity or whether two or more syndromes lie behind the title 'the MRKH syndrome'. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data: a typical and an atypical form of the MRKH syndrome. We performed various diagnostic investigations to establish whether there were any associated congenital anomalies. These tests included general physical examination, radiographs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryngological and ossicular chain examinations. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an isolated form of congenital agenesis of the vagina and uterus and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic. The term MRKH syndrome should no longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome.

In the western world the median age of the menopause is close to 51 years of age [1,2]. At this age nearly all follicles have reached atresia and the remaining number is insufficient to sustain the cyclic hormonal process, necessary for menstruation. In modern statistic terms it would be natural to define precocious menopause as the cessation of menstruation before the age of two times the standard deviation of the mean age of menopause. However, precocious menopause is typically defined as occurring before the age of 40 [3]. Originally it has been assumed that precocious menopause is similar to the natural menopause with permanent loss of follicles and fertility. We do now know, that if we widen the definition, several reports in the literature demonstrate recurrent ovarian activity in women with well-documented premature ovarian failure. Since an increasing number of women are delaying pregnancy until an older age, and since we better understand that hormonal replacement therapy (HRT) is necessary in premature hypergonadotropic hypogonadism, early cessation of menses becomes a diagnostic challenge. Before discussing the several different pathophysiologic mechanisms underlying premature hypergonadotropic hypogonadism a short review will be given of normal ovarian development and of menopause.

To test non-hysteroscopic thermodestruction of the endometrium for safety and efficiency.Prospective pilot study from February 1991 to July 1992.University Hospital Nijmegen.There were 68 patients aged 30-55 years with menorrhagia, who did not want children but wished to retain the uterus. There were two patients with a subserous myoma but with a normal uterine cavity. Patients with hypergonadotropism, a markedly enlarged uterus, abnormalities at cytological examination of the cervix, adnexal lesions, prolapse, intrauterine lesions and coagulation disorders were excluded. By way of preparation, danazol was administered for 4 weeks before the intervention (36 patients). Three patients with side effects were given lynestrenol. From January 1992, an LH-RH analogue was administered (29 patients) for 6 weeks prior to the intervention or in the patients with a subserous myoma for 12 weeks. Thermodestruction of the endometrium by means of radio waves was carried out according to a standard protocol under general or epidural spinal anaesthesia. The intracavitary temperature measured was 62-65 degrees C, mean duration of the treatment 20 minutes.The patients were discharged 10-24 hours after the intervention. A non-disturbing watery discharge of 3-6 weeks' duration was reported. Normal activities were resumed after one week. Success (duration of follow-up 3-21 months) was defined as amenorrhoea (6 patients; 9%) or a markedly reduced menstruation or duration of menstruation (48 patients; 70%). Six patients (9%) reported no improvement and of eight patients (12%) with slight, unsatisfactory improvement three were treated again, with success (4%). During the trial period the method was further adjusted and perfected. There were no complications.This preliminary experience shows that thermodestruction with radio waves is simple, safe and efficient.

The purpose of this study was to discriminate typical (type A) from atypical (type B) Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (congenital absence of vagina and uterus) and determine their association with renal anomalies and ovarian disease.The excretory urographic, sonographic, and laparoscopic findings in 91 patients with MRKH syndrome were compared retrospectively. Symmetric muscular buds and fallopian tubes were diagnostic of type A, and asymmetric muscular buds or abnormally developed fallopian tubes were diagnostic of type B.On the basis of laparoscopic findings, type A was diagnosed in 40 patients (44%) and type B was diagnosed in 51 patients (56%). Renal anomalies were found in 34 (37%) of the 91 patients, all of whom had type B syndrome. Renal agenesis and a pelvic kidney were the most common findings in the upper part of the urinary tract. Ovarian abnormalities were seen in 14 patients (15%), all of whom had type B syndrome. Sonography did not allow discrimination between types A and B in patients with normal kidneys (17/51 = 33%), but it provided important information in patients with associated cyclic abdominal pain, in cases of diagnostic dilemma, and in patients with associated renal anomalies.Discrimination between type A and type B of MRKH syndrome is important because associated renal and ovarian abnormalities occur only in type B. Laparoscopy is still needed to discriminate between these two forms. Sonography is useful for diagnosing cyclic abdominal pain and associated renal anomalies.

Summary To study the effects of sperm density on the results of computer-assisted semen analysis (CASA), 10 washed semen samples were diluted and measured with the CellTrak/S CASA system in a concentration range of 10–180×106 spermatozoa/ ml. All sperm motility parameters were influenced to some extent by sperm density. The motility percentage was influenced significantly in 5 samples (P

To study the reaction pattern of acrosome reaction in human semen and correlate it to the results of in vitro fertilization (IVF).The percentage of acrosome-reacted spermatozoa of 41 IVF semen samples was determined after 0, 2, 4, and 24 hours of incubation in human tubal fluid medium supplemented with 10% human pool serum.St. Radboud Hospital, Catholic University of Nijmegen, The Netherlands.Forty-one IVF couples.None.Acrosome reaction was determined using fluorescein isothiocyanate conjugated concanavalin A lectin. To avoid false-positive signals from dead spermatozoa, the sperm viability was determined.Three kinetic patterns of acrosome reaction could be distinguished: (1) normal reacting pattern (percentage of acrosome-reacted spermatozoa less than 10% at 2 hours and greater than 5% at 4 hours; 75% fertilization in IVF); (2) a quickly reacting pattern (percentage of acrosome-reacted spermatozoa greater than 10% at 2 hours; 22% fertilization in IVF); and (3) a nonreacting pattern (percentage of acrosome-reacted spermatozoa less than 5% at all time intervals studied; 15% fertilization in IVF).The timing of acrosome reaction and the percentage of acrosome-reacted spermatozoa are very important parameters in IVF.

We report the third patient with a successful pregnancy following operative correction of congenital cervical atresia. The pregnancy was achieved through zygote intrafallopian transfer (ZIFT). Although stenosis of the newly formed cervical canal causes considerable morbidity, therapy should be aimed at the creation of a conduit for menstrual blood and for possible future pregnancy. New techniques in assisted reproduction such as in vitro fertilization-embryo transfer, gamete intrafallopian transfer, and ZIFT increase the chances of pregnancy in patients with congenital cervical atresia. A hysterectomy, as advocated until very recently, should not, in our opinion, be the first treatment of choice.

We have studied the concentrations of intact human choriogonadotropin (hCG) and the free hCG beta-subunit in blood samples from singleton pregnancies at risk for habitual or threatened abortion. The samples were obtained weekly between the 6th and 12th weeks and in the 14th and 16th weeks of gestational age. The concentrations of intact hCG, of the free hCG beta-subunit, and of "total" hCG (i.e., intact hCG and the free hCG beta-subunit: hCG + beta) were measured in serum by specific immunoassays. The distributional statistics (the 5th, 50th, and 95th percentiles) of "total" hCG + beta and of intact hCG showed very similar patterns, whereas the response curves for the free hCG beta-subunit showed very much lower serum concentrations. From these data we also estimated distributional statistics of the percent molar ratios of free hCG beta-subunit to intact hCG. We conclude that (a) the relatively small proportion of free hCG beta-subunit in serum during the first half of singleton pregnancy is far too low to interfere with the applied "total" hCG assay, as compared with the serum values obtained for intact hCG, and (b) the percent molar ratios of free hCG beta-subunit to intact hCG, or to "total" hCG + beta, never exceeded 1.0% throughout the period of pregnancy studied.

We report the third patient with a successful pregnancy following operative correction of congenital cervical atresia. The pregnancy was achieved through zygote intrafallopian transfer (ZIFT). Although stenosis of the newly formed cervical canal causes considerable morbidity, therapy should be aimed at the creation of a conduit for menstrual blood and for possible future pregnancy. New techniques in assisted reproduction such as in vitro fertilization-embryo transfer, gamete intrafallopian transfer, and ZIFT increase the chances of pregnancy in patients with congenital cervical atresia. A hysterectomy, as advocated until very recently, should not, in our opinion, be the first treatment of choice.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

A multidisciplinary study was conducted on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. It was possible to analyse whether the MRKH syndrome can be considered as a single clinical entity or whether two or more syndromes lie behind the title 'the MRKH syndrome'. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data: a typical and an atypical form of the MRKH syndrome. We performed various diagnostic investigations to establish whether there were any associated congenital anomalies. These tests included general physical examination, radiographs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryngological and ossicular chain examinations. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an isolated form of congenital agenesis of the vagina and uterus and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic. The term MRKH syndrome should no longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome.

Objective: To compare the efficacy and safety of nafarelin and danazol for endometriosis. Design: Randomized, double-blind, double-dummy. Setting: Multiple European institutions. Patients: In total, 307 patients with laparoscopically diagnosed endometriosis received nafarelin (n = 206) or danazol (n = 101); 263 (171 nafarelin, 92 danazol) were analyzed for efficacy. Interventions: Intranasal nafarelin 200-mu-g two times a day or oral danazol 200 mg three times a day were administered for 6 months. Main Outcome Measures: Efficacy assessments were based on preadmission and end-of-treatment laparoscopic scores and subjective symptom scores at admission, end of treatment, 1, 3, 6, and 12 months after treatment. Safety was evaluated by adverse events and clinical laboratory tests. Results: In each group, endometriosis growth and symptoms significantly improved during treatment (P < 0.001). After treatment, symptoms returned in each group, but severity was less than at admission at all time points (P less-than-or-equal-to 0.016). Mean body weight increased in the danazol-treated group (P < 0.001), serum glutamic oxaloacetic transaminase increased in both groups (P < 0.001 for both) but significantly more in danazol users (P < 0.002), and more nafarelin recipients had hot flushes (P < 0.001). Conclusions: Nafarelin and danazol were equally effective in reducing endometriosis growth and symptoms during treatment and in preventing the return of symptoms during 12-month followup.

The prolactin-lowering and lactation-inhibiting effects of lisuride and bromocriptine, two dopaminergic drugs, were compared in a double-blind study. Twenty-six women took lisuride, 0.2 mg b.i.d., and 24 women took bromocriptine, 2.5 mg b.i.d., during 14 days postpartum. Though both drugs gave satisfactory inhibition of puerperal milk production, in these dosages bromocriptine was a more effective lactation inhibitor and prolactin suppressor. After discontinuation of treatment rebound symptoms were more pronounced in the bromocriptine group than in the lisuride group.

This study deals with serum prolactin concentrations during various conditions in the early puerperium in an attempt to investigate some characteristics of the mechanisms responsible for the regulation of the lactotropes. In nursing, in non-nursing, non-medicated and in non-nursing, bromocriptine-treated women prolactin and 17 beta-oestradiol were measured during the early puerperium. In the first and the third group this was repeated during and after challenge with oestradiol-benzoate. The pituitary responsiveness to TRH was also determined in these two groups, challenged and unchallenged with oestradiol-benzoate. Nursing women had higher prolactin levels than the non-nursing groups, while bromocriptine decreased prolactin to very low levels. Non-nursing non-medicated women had prolactin values between those of nursing and those of bromocriptine-treated mothers. The already elevated prolactin levels in nursing women were not influenced by chronic oestradiol administration. In non-nursing puerperal women treated with bromocriptine, exogenous oestradiol caused a significant rise in plasma prolactin. The prolactin response to TRH in nursing women was clearly reduced in comparison with the normal menstrual cycle. In the bromocriptine-treated group the basal concentration of prolactin and its response to TRH stimulation was similar to normal non-pregnant women. In nursing and in non-nursing women treated with bromocriptine prolactin responses to TRH were increased after oestradiol challenge.

Subcellular fractions from porcine corpora lutea of the reproductive cycle and pregnancy were shown to have specific binding sites for ovine prolactin (oPRL). Aside from oPRL, only ovine and bovine growth hormone preparations competed with [125I]iodo-oPRL for its binding site. These cross reactions were at a level consistent with the prolactin contamination of these preparations. Rat growth hormone, FSH, LH, TSH, insulin, and ACTH exhibited negligible cross-reactivity. Both corpora hemorrhagica and albicantia had lower specific binding of [125I]iodoPRL than did active corpora lutea of the reproductive cycle, while corpora lutea of pregnancy demonstrated a nearly 5-fold increase in specific binding compared with that of the cycle. Corpora lutea from animals with larger fetuses (greater gestational age) bound the most prolactin. Analysis of data from cold competition studies employing weighted non-linear least-square fitting to a three-parameter model, showed high-affinity binding of oPRL with an association constant (Ka, 23 C) of 2.0 X 10(9)M-1 for the binding site of the corpus luteum of the cycle. The Ka shows no appreciable change with pregnancy. In contrast, the binding site concentration (N) increases markedly from less than 10 fmol/mg protein in corpora lutea from non-pregnant animals to approximately 40 fmol/mg protein for animals at a gestational stage of 40-46 days. The observed Ka's are similar to values obtained for the prolactin binding site in porcine granulosa cells harvested from unruptured follicles and to the prolactin-binding site in the mammary gland.

Resume 198 enfants atteints d'asthme vus pour la premiere fois aux Enfants-Malades entre 1969 et 1975 ont ete revus en 1981. 39 sont encore suivis dans le service et 159 ont repondu a un questionnaire detaille. Apres une etude de la population choisie concernant la gravite de l'asthme, l'âge de debut, le delai avant la premiere consultation et les traitements suivis, les auteurs etudient le devenir de ces enfants 6 a 12 ans apres le premier examen. Le traitement par le DSCG a ete continu dans 156 observations (3 mois a 12 ans dont 64 plus de 4 ans) et discontinus dans 42 observations. Les doses cumulees administrees ont varie de 500 a 8000 capsules (54 fois plus de 4000) sans problemes de tolerance. Une evolution favorable a ete constatee dans 53 p. cent des observations, 14 p. cent d'asthmes sont restes graves. La scolarite et le devenir socio-professionnel de ces enfants sont plutot meilleurs que dans une enquete precedente. Le DSCG ne modifie pas le pronostic d'ensemble de l'asthme infantile mais ameliore le mode de vie et reduit de facon importante les traitements symptomatiques necessaires en particulier bronchodilatateurs et corticoides ainsi que le nombre des hospitalisations. L'inefficacite (24 observations) ou la mauvaise tolerance relative (7 observations) sont generalement dues a une mauvaise utilisation du produit, a des doses insuffisantes et a une trop grande irregularite des prises.

Resume Ce travail apprecie le devenir de 124 enfants asthmatiques vus pour la premiere fois entre 1959 et 1964, donc avec quinze a vingt ans de recul, en fonction de la gravite de leur maladie et des traitements suivis. Pour 89 d'entre eux, l'evolution a ete favorable (71,77 p. cent) avec une guerison totale chez 68 (54,83 p. cent) et partielle chez 21 (16,93 p. cent) ; chez les 35 autres, la maladie persiste, peu grave chez 22 (17,74 p. cent) mais invalidante chez 13 (10,48 p. cent). Les elements essentiels du pronostic sont la gravite evolative de l'asthme, la precocite du traitement preventif de desensibilisation et l'efficacite inconstante de ce dernier. Les autres moyens therapeutiques habituels utilises a l'epoque conditionnent peu le pronostic a long terme. La plupart de ces enfants ont eu une scolarite moyenne et un devenir socio-culturel egalement moyen. La moitie d'entre eux ont pu faire du sport et continuent. La possibilite d'une immunotherapie, sa precocite et son efficacite paraissent les elements essentiels d'une evolution a long terme favorable. meme a l'epoque deja lointaine ou a debute leur traitement.

Puerperal lactation is regulated by a complex system of hormones, including in particular prolactin. Prevention of lactation is in a few instances necessary on medical grounds, although far more often inhibition of lactation is carried out because the mother does not want to nurse.

Summary A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2×3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recoovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival.

The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double-blind randomized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage. The patients were randomly allocated to receive either 17 alpha-hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation. Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman. Only four maternal serum variables (17 alpha-hydroxyprogesterone, prolactin, thyroxin and thyroxin binding globulin) rose significantly. The serum progesterone levels in the hormone supplemented group were on average 20% higher than in the placebo group but the difference was not statistically significant. However, the relation between the progesterone levels and the fetal outcome was not clear. Therefore it is not advisable to prescribe 17-OHP-C during early pregnancy to prevent a miscarriage.

In a double-blind group sequential trial the efficiency of an oxytocin nasal spray in enhancing lactation was studied during the first five days after delivery in women who had given birth prematurely. The cumulative volume of breast milk obtained between the second and fifth days after delivery was 3.5 times greater in primiparas given oxytocin than in primiparas given placebo. There was no significant difference in the composition of the milk between the untreated women and those given oxytocin. The results of this study show that oxytocin nasal spray is an effective and safe means of enhancing lactation in women using a breast pump.