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This article reports the observed rate of infection with severe acute respiratory syndrome coronavirus-2 in healthcare workers (HCWs) who worked on wards dedicated to care of patients with coronavirus disease 2019 (COVID-19) compared with HCWs who worked on non-COVID-19 wards. The infection rate was significantly higher among HCWs who worked on non-COVID-19 wards (odds ratio 2.3, P=0.005), illustrating the need to strengthen social distancing measures and training.

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Introduction Le cancer du poumon (CBP) est aujourd’hui la premiere cause de deces par cancer en France. Meme si le tabac est de loin le premier facteur de risque de ce cancer, 10 a 20 % des CBP auraient une origine professionnelle. Une sous declaration du CBP en maladie professionnelle est actuellement observee en France, ce qui entraine un defaut de reparation des patients au titre de la maladie professionnelle indemnisable (MPI). La plupart des CBP reconnues en maladie professionnelle, sont associes a une exposition professionnelle a l’amiante, alors que, 10 autres agents cancerigenes du poumon sont identifies dans les tableaux de maladies professionnelles du regime general. L’objectif de cette etude, est de faciliter chez des patients presentant un CBP, le reperage des expositions professionnelles anterieures potentielles a des agents cancerigenes du poumon (ACP) inscrits dans les tableaux de MPI, en creant et en validant un auto-questionnaire, simple et rapide d’utilisation. Methodes Un auto-questionnaire court (30 questions), reprenant les situations d’expositions aux ACP inscrits dans les tableaux de MP, a ete elabore par des medecins oncologues, pneumologues et des medecins du travail. Une phase pre-test d’evaluation de la comprehension et de l’acceptabilite de l’auto-questionnaire a ete realisee aupres de 10 patients presentant un CBP. Pour la phase test, 70 patients salaries ou anciens salaries, hospitalises pour un CBP primitif au CHU de Saint-Etienne ou a l’institut de cancerologie Lucien Neuwirth ont ete inclus. Chacun de ces patients completait l’auto-questionnaire. Un medecin du travail interrogeait ensuite le patient en utilisant comme guide d’entretien directif, le questionnaire de reperage des CBP d’origine professionnelle valide par la societe de pneumologie de langue francaise (SPLF) et la societe francaise de medecine du travail (SFMT). La sensibilite et la specificite de l’auto-questionnaire ont ete evaluees en comparant les reponses aux items de l’auto-questionnaire avec celles du questionnaire de la SPLF et de la SFMT, considere comme « gold standard ». La fiabilite a ete evaluee par l’analyse de concordance des items entre les deux questionnaires a l’aide du coefficient kappa. Resultats Le temps moyen de remplissage de l’auto-questionnaire est de 3,1 minutes (versus 8,12 minutes pour le questionnaire gold standard). La concordance entre les reponses aux deux questionnaires est de 85,7 % avec un coefficient kappa de 0,695 [0,52–0,87]. La sensibilite de l’auto-questionnaire est de 0,85 et la specificite de 0,875. Une exposition potentielle professionnelle a un ACP (amiante, arsenic, derives du chrome, hydrocarbures aromatiques polycycliques, cobalt) a ete identifiee chez 54 % ( n = 38) des patients inclus. Suite a la prise en compte des caracteristiques de l’exposition aux ACP, une demarche de reconnaissance du CBP en MPI a ete conseillee a 29 de ces patients. Conclusion Cet outil devrait contribuer a favoriser les demandes de reconnaissance du CBP en MPI et ainsi reduire la sous declaration de cette pathologie en MPI notamment pour les ACP autres que l’amiante. Les modalites de passation de cet auto-questionnaire integre au parcours de soin du patient, font l’objet d’une etude qualitative en cours de realisation.

International audience; In this paper we clarify for the first time the correlation between endurance, window margin and retention of Resistive RAM. To this aim, various classes of RRAM (OXRAM and CBRAM) are investigated, showing high window margin up to 10 10 cycles or high 300°C retention. From first principle calculations, we analyze the conducting filament composition for the various RRAM technologies, and extract the key filament features. We then propose an analytical model to calculate the dependence between endurance, window margin and retention, linking material parameters to memory characteristics.

As an estuary being restored, the Scheldt (Belgium/The Netherlands) offers an interesting setting to study the response of organisms and ecosystems to changing conditions. This study specifically deals with this with regard to the spatio-temporal distribution and possible genetic differentiation among the species complex Eurytemora affinis (copepoda, calanoida). Until the 1990s, E. affinis typically occurred downstream the Scheldt estuary (Belgium/The Netherlands). In parallel to water quality improvement, E.affinis has recently also occurred upstream the estuary and in some of the tributaries. This paper aims to assess the origin of the copepod sibling species complex E. affinis occurring upstream the Scheldt estuary through genetic characterization. Using the Inter Simple Sequence Repeat (ISSR) technique, we explored genetic pools of the E. affinis complex in three Scheldt localities (downstream, middle-estuary and upstream) and two of its tributaries. Four ISSR primers produced 75 polymorphic loci. Bayesian and hierarchical analysis revealed different but close genetic entities in both down and upstream localities. The middle-estuary individuals were genetically a composite mix of downstream and upstream populations (84% from downstream and 16% from upstream). A distinctive separation of the tributaries and the main Scheldt stream populations suggests that two fully independent genetic pools are present. It is of note that the tributaries showed a lack of genetic subdivision, that upstream and downstream E. affinis populations are closely related, and that the downstream population is most likely at the origin of the upstream one, which implies the necessity to guarantee sufficient oxygen concentration levels throughout the estuarine continuum to guarantee the presence of this species upstream. The results of the ISSR technique are discussed in comparison with genetic studies on E. affinis using COI barcoding. (C) 2014 Elsevier Ltd. All rights reserved.

The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other oral contraceptives. Both preparations were well accepted by the volunteers. The data obtained demonstrate clinically acceptable cycle control, good tolerance, and a high standard of contraceptive reliability for both drugs. Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible. In case of persistent cycle control problems, a switch to the 30 micrograms EE2 drug should be considered.

A case of false-negative discrepancy between results of chorionic villi (direct preparation) and those of fetal tissue with an isochromosome 18q [i(18q)] in amniotic cells and fetal blood is reported. Fluorescence in situ hybridization (FISH) confirmed this uncommon chromosomal rearrangement. The fetus showed cyclopia and multiple congenital anomalies which have never been reported in cases of i(18q).

Matairesinol is a central precursor in planta in the biosynthesis of numerous lignans, including that of the important antiviral and anticancer agent, podophyllotoxin. In this study, the approximately 32-kDa NAD-dependent secoisolariciresinol dehydrogenase, which catalyzes the enantiospecific conversion of (-)-secoisolariciresinol into (-)-matairesinol in Forsythia intermedia, was purified6,000-fold to apparent homogeneity. The 831-base pair cDNA clone encoding this 277-amino acid protein was next obtained from a library constructed from F. intermedia stem tissue, whose fully functional recombinant protein, produced by expression of this cDNA in Escherichia coli, catalyzed the same enantiospecific conversion via the corresponding lactol intermediate. A homologous secoisolariciresinol dehydrogenase gene was also isolated from a Podophyllum peltatum rhizome cDNA library, whose 834-base pair cDNA clone encoded a 278-amino acid protein with a calculated molecular mass of approximately 32 kDa. Expression of this protein in E. coli produced a fully functional recombinant protein that also catalyzed the enantiospecific conversion of (-)-secoisolariciresinol into (-)-matairesinol via the intermediary lactol. Various kinetic parameters were defined and established conversion of the intermediary lactol as being rate-limiting. With this overall enzymatic conversion now unambiguously defined, the entire biochemical pathway to the lignans, secoisolariciresinol and matairesinol, has been elucidated. Last, both secoisolariciresinol and matairesinol are metabolized in the gut of mammals, following digestion of high fiber dietary grains, seeds, and berries, into the so-called "mammalian" lignans, enterodiol and enterolactone, respectively; these in turn confer significant protection against the onset of breast and prostate cancers.

The difficulties in the diagnosis of Pallister-Killian syndrome are illustrated in this study of nineteen fetuses and children. Diagnosis based on clinical appearance alone is often difficult due to the broad spectrum of clinical anomalies not specific to this syndrome. Due to mosaicism, it is altogether necessary to examine several tissues for the presence of tetrasomy 12p, including circulating lymphocytes in which mosaicism can be as low as 1-3%, amniocytes, chorionic cells and skin fibro-blasts in which mosaicism ranges from 6-100%. When highly suspected on ultrasound examination, the diagnosis recommends prenatal cytogenetic studies because survivors are severely mentally retarded. All the cases are sporadic with only a single preliminary report of recurrence. The cytogenetic diagnosis is therefore helpful in order to reassure family members in regard to genetic counseling.

The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p=0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

Gonadotropin releasing hormone (GnRH) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions. However, their use could be limited by the bone loss they induce. To evaluate the use of nasal salmon calcitonin (sCT) in preventing this bone loss, 40 patients with endometriosis were treated for 6 months with triptoreline (3.75 mg monthly) and calcium (1 g daily), and randomized in three groups-placebo, sCT 100 IU daily and sCT 200 IU daily-in a prospective double-masked study. Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment. At baseline, there were no statistically significant differences between the groups. After 6 months, estradiol and biochemical markers of bone metabolism were at postmenopausal levels, with no difference between the groups. There was no difference in bone loss in the three groups, at all sites. Mean lumbar bone loss was 4.01 +/- 2.59% (mean +/- SD) in this population. In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment.

The purpose of this study is to theoretically evaluate the performance of a vertical receiving array in a fluctuating medium by means of arrival time-angle diagrams.

We propose a new model for the prediction of sound propagation in a three-dimensional oceanic environment. It is based on a paraxial approximation of the Helmholtz equation. This model can take into account the range and azimuth dependence of sediment layers and thermal fronts.

The general aerothermodynamics environment of hypersonic vehicles is usually performed considering a smooth simplified geometry. However, in the case of the intermediate experimental vehicle (IXV), the thermal protection system includes a mono-block ceramic matrix composite nose and an assembly of shingles between which steps and gaps are generated. From an aerothermodynamic point of view, such a distributed roughness layout cannot be ignored in terms of modification of the interaction between the flow and the body and possible induced transition along the windward side. To assess these effects, dedicated wind tunnel tests and numerical simulations have been performed. This paper presents the general logic of the work, with emphasis on the wind tunnel model design, tests involving infrared thermal measurements as well as the computational fluid dynamics (CFD) rebuilding of the flow in the wind tunnel and the extrapolation from ground to flight.

We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.

The antiovulatory action of chlormadinone acetate was studied in six healthy volunteers who were given two daily doses of 5 mg each from the seventh to the twenty-fifth cycle day. Chlormadinone acetate is of potential interest as a contraceptive method for the small group of women with contraindications to synthetic estrogens and norsteroid progestins for whom no other methods are acceptable. The observation period included four cycles: a control cycle before treatment during which ovulation was confirmed, two treatment cycles, and an observation cycle after treatment. Antiovulatory action was assessed by daily determination of plasma FSH, LH, estradiol, and progesterone levels. The results confirmed the antiovulatory action of chlormadinone acetate and revealed no clinical signs of functional ovarian cysts or premenstrual syndrome. In all cases, the LH surge observed in the control cycle was blunted by chlormadinone acetate, while the base gonadotropin levels were not modified. Hormonal profiles in the second treatment cycle showed no preovulatory gonadotropin surge and no significant progesterone secretion. Estradiol production was variable through midcycle and then low normal in all subjects. In the last cycle week, the estradiol level was below 50 pg/ml in two cases and between 50 and 100 pg/ml in the others. In five cases out of six, the level of progesterone was 1 ng/ml or lower. In the sixth case, the data were incompatible with ovulation. Cycle tolerance was good and ovarian function returned during the first posttreatment cycle. No significant variation in weight or blood pressure was observed at the end of the second treatment cycle.

Long-acting Propranolol (160 mg/day) and Amiodarone (200 mg/day after impregnation) were compared in chronic stable angina pectoris. Forty-three patients with stable angina of effort were included in a randomised double blind trial (19 in the amiodarone and 24 in the propranolol group). The duration of the study was 8 weeks; the placebo phase (2 weeks) was followed by 6 weeks of active treatment. An exercise stress test was performed before and after the treatment period. The number of episodes of angina and the consumption of glyceryl trinitrate decreased significantly (p less than 0.001) in the same proportion with both drugs with respect to the placebo period. The time to the appearance of criteria of positivity of the exercise stress test increased from 6.82 +/- 0.50 mn to 8.35 +/- 0.50 mn with amiodarone, and from 7.15 +/- 0.47 mn to 9.50 +/- 0.52 with the propranolol preparation. This improvement was very significant compared with the placebo phase (p less than 0.001) but the difference between the two drugs was not statistically significant (p = 0.39). The other parameters which were studied (time to onset of angina, total duration of exercise, maximum heart rate, double product, maximum ST depression) changed in a parallel fashion significantly versus placebo. There were no differences between the two treatment groups with the exception of the resting heart rate which decreased more in patients on propranolol (80.94 +/- 3.92 to 62.47 +/- 1.97) than in patients on amiodarone (84.87 +/- 2.63 to 73.41 +/- 2.01; p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

The choice of an optimal contraceptive method (OC) therapy is a significant problem in female SLE patients. In view of the influence of sex hormones on the evolution of SLE, oral contraceptive (OC) therapy has to be efficient, reversible and safe, without aggravating disease activity and causing metabolic and vascular side effects. Ethinyl estradiol-containing preparations, even at 30 micrograms/day, have been shown to trigger a crisis or unmask SLE, and they exert adverse metabolic and vascular effects. Therefore, combination estrogen-progestogen compounds must be avoided in women with SLE. Pure progestogen OC preparations do not stimulate SLE activity, but norsteroids have harmful metabolic effects and microprogestogens are not sufficiently reliable. In light of the decreased level of plasma androgens in female SLE patients, an attempt to modulate the hormonal milieu by lowering the estrogen to androgen ratio, while ensuring contraception was attempted using cyproterone acetate. This agent markedly lowered plasma estrogens and was effective and well tolerated, but its long-term effect on bone mineralization remains to be evaluated. Chlormadinone acetate, a 17-OH progesterone derivative, was proven effective and devoid of any metabolic or vascular side effects, and should be recommended as the safest routine OC therapy in women with SLE.

Recombinant protein translation in Escherichia coli may be limited by stable (i.e. low free energy) secondary structures in the mRNA translation initiation region. To circumvent this issue, we have set-up a computer tool called ‘ExEnSo’ (Expression Enhancer Software) that generates a random library of 8192 sequences, calculates the free energy of secondary structures of each sequence in the −70/+96 region (base 1 is the translation initiation codon), and then selects the sequence having the highest free energy. The software uses this ‘optimized’ sequence to create a 5′ primer that can be used in PCR experiments to amplify the coding sequence of interest prior to sub-cloning into a prokaryotic expression vector. In this article, we report how ExEnSo was set-up and the results obtained with nine coding sequences with low expression levels in E. coli. The free energy of the −70/+96 region of all these coding sequences was increased compared to the non-optimized sequences. Moreover, the protein expression of eight out of nine of these coding sequences was increased in E. coli, indicating a good correlation between in silico and in vivo results. ExEnSo is available as a free online tool.

Herpes virus infection is an extremely common disease that affects between 90 to 100% of the population above the age of 15. The authors propose studying successively the clinical and virological diagnosis of this infection, it's treatment, and finally it's prevention in the dental clinic where there is a large possibility of transmitting the infective diseases.

In an open prospective study, we have tested clinical efficacy and tolerance of two antigonadotropic drugs, that is danazol (D) and cyproterone-acetate (CA). This study was performed in 11 female patients ranging in age from 19 to 47 years, who suffered from midly-active SLE, during 12 therapeutic periods on the whole (that is 6 for each drug), the minimum period of which was one year. Because of side-effects, D had to be early withdrawn in 2 patients, whereas (the) AC appeared to be well-tolerated in all of them. On the whole, 16 clinical exacerbations of DLE were observed during the 12 months pre-treatment period, versus 9 exacerbations during the 12 months treatment period (p less than 0.05, Wilcoxon test), whereas the average dose of prednisone was reduced from 9.6 to 3.5 mg/day. A dramatic improvement was then observed in 3 patients suffering from mucous ulcerations. Increased plasma testosterone level without any change in estradiol level was observed in patients treated with D. Conversely, plasma estradiol decreased without any change in testosterone level in patients treated with CA. Both drugs induced reduction in plasma sex-hormone binding protein. These preliminary results suggest that D and CA may both reduce lupus disease activity, in parallel with an hormonal environment modification, towards a lower estrogen-androgen balance, along with a better tolerance as for CA.

Contraception in women affected by renal insufficiency aims at preserving their fertility potential while waiting for a kidney transplant which may make childbearing possible. In older women contraception aims at avoiding a pregnancy which may worsen their condition. Women with renal insufficiency and aged 40-50 must avoid combined oral contraceptives. An IUD would be the best choice as well as progestational agents in regular doses 21 days a month, from the 5th to the 25th day of the cycle. Given the different metabolic impact of each progestational agent the choice remains with the gynecologist after a careful consideration of the patient's condition. Contraception by low-dose progestational agents may be advisable in some patients. Women undergoing periodic hemodialysis usually have normally ovulating cycles. An IUD would not be advisable since it may cause anemia, the same for low-dose progestational agents. The continued administration of high-dose progestational agents would be better suited for this group of patients, alternated with combined sequential pills in women with normal lipid and cholesterol levels. Women who have had a kidney transplant must wait at least 2 years before becoming pregnant. During this period mechanical contraception and the IUD are not indicated, and neither are combined contraceptives because of the risk of vascular side effects; continued or discontinued administration of low-dose progestin would be the method of choice. Alternating the different contraceptive methods is a possibility at every stage of the disease. Patients must be carefully checked at regular intervals.

The exposition of the Tilapia guineensis to concentrations used in the field to destroy the simulium larvae in their aquatic biotopes is 0,05 mg/l/10 minutes. The authors have previously remarked a significant lowering of acetylcholinesterasic brain activity in this fish. In the case of a much prolonged contact (24h corresponding 144 times the theoretic time of contact), it is noticed that, if this immediate effect is not more pronounced, on the other hand it is noticeable for a much longer acetylcholinesterasic activity extends beyond forty days. In the same conditions, three successive weekly treatments lead the acetylcholinesterasic activity to the level of vital activity.

Contraceptive use of normal dosed progestins continues to be useful for many women who cannot use other contraceptive methods, but appropriate use depends on perfect knowledge of their modes of action, advantages, disadvantages, dosages, and duration of action. Each progestin has its own indications, and contraindications, and not all progestins have contraceptive properties. Most progestins used for contraception are derived from 19 nor-testosterone. Structural modifications of progesterone and testosterone have produced synthetic progestins resistent to hepatic degradation and bioavailable through the oral route. 2 main groups of progestins may be distinguished: androgenic progestins, including the estrone derivatives ethynodiol diacetate and lynestrenol, which have stong antigonadotropic activity and a braking effect on endogenous estrogen secretion, and "pure" progestins derived from 17 OH progesterone, or norpregnanes, such as chlormadinone and promegestone, which have strong luteomimetic activity, no androgenic activity, and weak antiandrogenic activity. Norsteroids administered at normal doses for 21 days/month or in some cases 17 days have a Pearl index of around 1%. This type of contraception requires counting days and taking 1 or 2 pills, and should only be used for women with certain types of problems or hormonal imbalances requiring treatment. Indications may include some cases of uterine polyps, endometrial mucus hyperplasia, uterine fibromas, endometriosis, mastodynies, benign mastopathies, existence of several risk factors for breast cancer, age over 40 years, premenopausal luteal insufficiency, and smoking. Secondary effects, especially metabolic disturbances, may occur and vary according to the formulation, route of administration, and duration of treatment. The 19 nortestosterone progestins commonly used because of their antigonadotropic and antiestrogenic activity have measurable effects on lipid metabolism, apparently in relation to apoproteins A and B, and on glucose metabolism. Some have an effect on the renin substrate, but their role in provoking arterial hypertension appears to be modest. Androgenic effects such as seborrhea and acne may be produced at some dose levels. Medroxyprogesterone acetate, derived from 17 OH progesterone, causes significant metabolic changes including androgenic and hypertensive effects, undesirable effects on glucoregulation, and coagulation effects.

Although the etiology of lupus is imperfectly understood, immune factors, heredity, viral infections, and hormonal status are known to play a role. Studies of the sex ratio of lupus patients indicate that before age 10, twice as many girls as boys are affected, but after 12 years, 9.6 females are affected for each male. The incidence of lupus is almost constant for males of all ages but is much higher for women of fertile age than for other women. The deleterious effect of synthetic estrogens was 1st reported in 1966, and various studies since then have confirmed the results. The etiologic role of pregnancy is debated, but pregnancies can be successfully carried to term in periods of remission. Certain lines of mice spontaneously develop an autoimmune disease resembling disseminated lupus erythematosus. Anti-DNA antibodies appear earlier in the female and death from renal insufficiency occurs earlier than in males. Prepubertal castration does not influence the survival of female mice but significantly reduces that of males. Treatment with estradiol diminishes survival of castrated males and females, while treatment with androgens increases survival time of castrated to control females and of castrated males to that of control males. The timing and dose of treatment modify the response. Progesterone administered alone does not influence survival time of females but somewhat increases that of castrated males. Cyproterone acetate, an antiandrogenous progestin, has no effect in 2-3 week old males. Danazol, a moderately active androgen, has no effect on female mice. Nafoxidine, an antiestrogen, increases survival times. These results support the opinion that estrogens aggravate lupus while androgens have a protective effect. Different hormonal treatments have been prescribed for human lupus. Some beneficial effect for female patients has been observed with danazol, but the drug entails significant hepatic, metabolic, and hypertensive risks and may produce androgenic side effects such as voice modifications and hirsutism. Cyproterone acetate, a derivative of 17-hydroxyprogesterone, is without vascular and metabolic side effects and can halt ovarian function at a dose of 50 mg/day. It behaves as a peripheral antiandrogen and may have androgen agonist activity in some tissues. The mechanism of interaction of sex hormones in lupus may be explained by their influence on cellular and humoral immunity. Estrogens appear to suppress cellular immunity and stimulate humoral immunity, while androgens appear to play a suppressive role at the 2 levels. Contraception for women with lupus must be effective. Combined oral contraceptives and low-dose norsteroid progestins are contraindicated because of their thromboembolic and vascular risks. Low-dose progestins may be used but cause hyperestrogenism in some women. Chlormadinone acetate at a daily dose of 10 mg has no significant vascular effect. IUDs may have reduced efficacy during corticotherapy and pose a risk of infection. Only mechanical vaginal methods ose no threats for lupus patients, but they must be understood and accepted by the patient.

The presence of a virilizing ovarian hilum cell tumours was suspected on account of a rise of plasma testosterone level above 3.5 ng/ml in one patient and a rise of plasma androstenedione level above 3.0 ng/ml in another. The diagnosis was made by selective catheterization of the ovarian and adrenal veins, which showed a high androgen concentration gradient in the vein of the ovary affected as compared with that observed in the adrenal and peripheral veins, and was confirmed by histological examination after ovariectomy. These two cases are contrasted with two other cases with high testosterone plasma levels but without gradient on selective catheterization. One of the patients had abnormal hepatic metabolism (porto-caval shunt) and the other had taken high doses of androgens.

After having exposed during 10 minutes the Tilapia guineensis to a concentration of 0,05 mg/l of temephos (concentration of a larvicide used for the field test), the authors note a lowering of the acetylcholinesterastic activity of the brain to an order of 25%. The return to a normal activity is achieved within 20 to 25 days. A new exposure, happening one week after the first, provokes a further lowering before the return to a normal value. The authors question themselves on the consequences of these chemical attacks repeated on a weekly basis during antilarval treatments in the struggle against the onchocercose.

The aim of this study was to compare the metabolic effects of two presentations of 17 beta-oestradiol (E2) which are of recognized effectiveness in the prevention of post-menopausal bone loss, one being administered via the oral and the other via the percutaneous route. During this prospective, randomized study, 32 patients were treated for 2 mth with either 2 mg/day of oral micronized E2 (n = 16) or 1.5-3 mg/day of percutaneous E2 (n = 16). Both regimens proved efficacious, since significant increases in oestrone (E1) and E2 concentrations ranging up to mid-follicular values were observed. In the percutaneous-treatment group we noted a significant decrease in triglycerides (TG), without any significant changes in high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). In the oral-treatment group, we saw no significant increase in HDL-C, although significant increases were observed in body weight, TG, plasma renin substrate (PRS) and sex-hormone-binding globulin (SHBG) as well as significant decreases in antithrombin III (AT III) activity and antigen. All of these metabolic variations led us to the conclusion that oral E2 at the dose established as effective in preventing post-menopausal osteoporosis may, even when micronized, alter certain metabolic and haemostatic parameters in a population characterized by increases in cardiovascular risk factors and morbidity. Oral oestrogen replacement therapy should therefore continue to be used only in carefully selected patients and be strictly followed up by systematic checks on a series of metabolic criteria.

20 women with metabolic, vascular, or gynecoendocrinological contraindications to use of combined oral contraceptives (OCs) or norsteroid progestins participated in a 6-month study of chlormadinone acetate, a progestin derived from 17-OH progesterone known for its weak androgenic activity. 5 mg doses of chlormadinone acetate were administered on the morning and evening of the 6th to the 26th cycle day for 3 woman and on the 8th to the 26th cycle day for 17 others. Blood tests were conducted during the luteal phase after fasting. The average age of the study subjects was 29.9, the average weight was 57.8 kg, and the average height was 161 cm. There were no significant variations over the course of the study in weight, blood pressure, renin substrate, high density lipoprotein (HDL) cholesterol, triglycerides, plasma apo-B, or antithrombin III. There was a significant reduction in apoprotein A1, the principle protein fraction of high density lipoproteins, from the 3rd to the 6th cycles, and a nonsignificant reduction of the apoprotein B. The ratio of A1/B apoproteins was not significantly modified. There were no signs of hyperestrogenism, hyperandrogenic effects, or digestive intolerance. In most cases there was no significant change in cycle duration or intensity of menstrual bleeding. 3 patients were recurrently amenorrheic. The amount of bleeding was considered normal by 14 patients and diminished by 3. There were no cases of menorrhagia and 5 of minor metrorrhagia in the first 3 months of use. No pregnancies occurred. After voluntary termination of contraception, 2 patients rapidly became pregnant. Measurement of ovarian hormone levels and gonadotropins indicated that chlormadinone acetate at the prescribed dose completely inhibited progesterone secretion in all patients and considerably reduced the production of estradiol in the luteal phase. Chlormadinone acetate has the dual advantages of avoiding the estrogen-induced side effects of combined OCs and avoiding hyperestrogenism. The use of a progestin derived from 17-OH progesterone may offer a contraceptive method suitable for women with metabolic or vascular contraindications to combined OCs or gynecoendocrinological contraindications to low dose progestins, who are unable or unwilling to use mechanical or local contraceptives. Chlormadinone acetate should however remain a method for use under exceptional circumstances.