Women and academic careers in obstetrics and gynaecology: aspirations and obstacles among postgraduate trainees - a mixed-methods study.

OBJECTIVE: To examine the relationship between gender and a career in academic medicine. DESIGN: Mixed-methods study. SETTING: Obstetrics-gynaecology postgraduate training programme in Paris, France. SAMPLE: Postgraduate trainees in obstetrics-gynaecology (n = 204). METHODS: Statistical analysis of quantitative survey data, thematic analysis of qualitative interview data and integrative analysis. MAIN OUTCOME MEASURES: Women's aspirations and obstacles related to their decision about a career in academic medicine. RESULTS: A career in academic medicine was envisaged by 13% of the women residents and 27% of the men (P = 0.01). Women reported receiving advice from a mentor less often than men (38.8% versus 52.9%, P = 0.002). Overall, 40.6% of women and 2.9% of men reported experiencing gender discrimination (P < 0.001). In response to the question 'Do you have doubts about your ability to pursue or succeed at an academic career?', 62.4% of the women and only 17.7% of the men answered yes (P < 0.001). The global analysis identified the following obstacles: persistent gender stereotypes that produce everyday sexism, lack of identification with male role models, lack of mentors, perceived discrimination, an ideal of professional excellence that is difficult to attain, constraining professional organisational norms, inequality between men and women in the domestic and family spheres, and finally self-censorship and important doubts about their ability to combine a demanding career and a fulfilling personal life. CONCLUSIONS: Women reported the desire to follow a career in academic medicine half as often as men. Improving the presence and visibility of role models for residents and combating workplace discrimination will address some of the barriers to women choosing a career in academic medicine. TWEETABLE ABSTRACT: Women obstetric trainees in France are only half as likely as men to envisage following an academic path.

Does a three-hour delayed pushing benefit the mode of delivery?

OBJECTIVE: The objective of this study was to compare two strategies for passive second stage management: three-hour vs two-hour delayed pushing after the diagnosis of full cervical dilation on mode of delivery and perinatal outcomes. STUDY DESIGN: This retrospective observational study included low-risk nulliparous women who reatched full cervical dilation under epidural analgesia with a single term fetus in cephalic presentation and normal fetal heart rate, between September and December 2016. Mode of delivery (spontaneous vaginal delivery versus operative delivery including cesarean section and instrumental vaginal delivery) and perinatal outcomes (post-partum hemorrhage, perineal lacerations, 5-min Apgar score, umbilical cord pH and transfer to neonatal intensive care unit) were compared between two maternity units: maternity unit A, where women could have up to a three-hour delayed pushing period after full cervical dilation diagnosis, and maternity unit B, where the delayed pushing period was a maximum of 2 h. Outcomes were compared using univariate and multivariable analyses. Adjusted odds ratios (aOR) were estimated using a logistic regression multivariable model that included potential cofounders. RESULTS: During the study period, 614 women were included, 305 in maternity unit A and 309 in maternity unit B. Women's pre-existing characteristics were comparable between the two maternity units. Women delivering in the maternity unit A had significantly lower risks of having an operative delivery compared to women delivering in the maternity unit B (respectively 18.4 vs 26.9%; aOR = 0.64; 95%CI [0.43 - 0.96]). Perinatal outcomes were comparable in the two maternity units, particularly in terms of post-partum hemorrhage rates (7.4 vs 7.8%; aOR = 1,19 [0.65 - 2.19]). CONCLUSION: Increasing the possible length of the delayed pushing period from 2 to 3 h after the diagnosis of full cervical dilation in low-risk nulliparous women appears to reduce operative deliveries without adverse effects on maternal or neonatal morbidity.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.

Benefits of the «en caul¼ technique for extremely preterm breech vaginal delivery.

INTRODUCTION: The "en caul" technique, i.e. delivery with intact membranes, may reduce the risk of obstetric trauma in vaginal breech delivery of extreme preterm infants. We aimed at comparing perinatal mortality and morbidity among extremely preterm breech vaginal deliveries between infants delivered "en caul" and those with "ruptured membranes". MATERIAL AND METHODS: We performed a fourteen-year retrospective study in a tertiary university center. All vaginal deliveries of singleton breech live infants with an antenatal decision of active resuscitation between 24 weeks and 27+6 weeks were included. Perinatal outcomes were compared between the "en caul" group, with intact membranes at the onset of pushing efforts and the "ruptured membranes" group, with ruptured membranes at the onset of pushing efforts. The primary outcome was perinatal mortality defined by intrapartum or neonatal death. The secondary outcomes were fetal extraction difficulties, arterial pH and 5 min Apgar score. RESULTS: We included 52 infants in the "en caul" group and 71 in the "ruptured membranes" group. The perinatal mortality rate did not differ between the two groups (19.2% in the "en caul" group versus 28.2% in the "ruptured membranes" group, p = 0.25). The mean arterial pH at birth was higher in the « en caul ¼ group (7.32 ± 0.1 vs 7.24 ± 0.1, p = 0.001). There were no differences between the groups for fetal extraction difficulties, especially fetal head entrapment (9.6% versus 9.9%). CONCLUSION: Even though the "en caul" technique does not seem to decrease the perinatal mortality rate, it remains a simple technique, which could improve neonatal morbidity.

[Term Prelabor Rupture of Membranes: CNGOF Guidelines for Clinical Practice - Methods for Inducing Labor]. / Rupture des membranes à terme avant travail. Recommandations pour la pratique clinique du CNGOF ­ Méthodes de déclenchement.

OBJECTIVES: To assess the studies comparing induction methods in women with term prelabor rupture of the membranes and establish if one is superior to the others. METHODS: The MedLine database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: The included studies compared medical induction methods: oxytocin (intravenous), dinoprostone (vaginal gel, pessary or intracervical gel), and misoprostol (oral or vaginal route); and a mechanical induction method: the Foley catheter. The primary outcome measures were: labor induction to delivery interval, number of women delivered within 12 or 24hours of initiation of induction and cesarean delivery rate. The small sample size of the included studies as well as the limited number of reported complications does not provide a reasonable basis for concluding on the secondary outcome measures: pyrexia, chorioamnionitis, uterine tachysystole, Apgar scores of<7 at 5minutes. Induction of labor with misoprostol (oral and vaginal) reduced the labor induction to delivery interval compared with dinoprostone (LE2). This interval was unchanged when comparing induction with oxytocin and Foley catheter (LE2). The data comparing this interval in women induced with dinoprostone versus oxytocin and misoprostol versus oxytocin is limited or inconsistent. The cesarean delivery rate was comparable in women induced with dinoprostone (vaginal gel) versus oxytocin (LE2), misoprostol (oral and vaginal route) versus oxytocin (LE2), Foley catheter versus oxytocin (LE2), misoprostol versus dinoprostone (LE2) and misoprostol versus Foley catheter (LE2). The number of women delivered within 24hours of initiation of induction was comparable when induced with oral misoprostol versus oxytocin (LE2) and Foley catheter versus oxytocin (LE2). There is a lack of data for this outcome when comparing dinoprostone versus oxytocin, vaginal misoprotsol versus oxytocin, and misoprostol (oral and vaginal) versus dinoprostone. No induction method is superior to another for nulliparous women or women with unfavorable cervix (LE2). CONCLUSION: The superiority of an induction method, in terms of effectiveness or safety, could not be established with the current available data for women with term prelabor rupture of the membranes. An increased risk of chorioamnionitis due to induction using Foley catheter could not be ruled out by the available data. All medical methods are suitable for inducing women with term prelabor rupture of the membranes (Grade B).

Evaluation of the 4 diagnosis criteria proposed by the SMFM and the AFE foundation for amniotic fluid embolism in a monocentric population.

OBJECTIVE: The Society of Maternal Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation have recently proposed four diagnostic criteria for amniotic fluid embolism (AFE): presence of (1) sudden cardiac arrest or both respiratory and hemodynamic collapse, and (2) biological disseminated intravascular coagulopathy (DIC), and (3) absence of fever, and (4) clinical onset during labor or within 30 min of delivery. The objectives of our study were to describe the clinical presentation of women with a strong suspicion of AFE and to assess the validity of the four criteria proposed for AFE definition. MATERIAL AND METHODS: We performed a retrospective study including all patients with a strong suspicion of AFE who delivered between 2006 and 2018 at the Port Royal maternity unit, Paris. Strong suspicion of AFE was defined by a clinical presentation in favor of AFE associated with a biological pattern and/or autopsy result supporting AFE. The mention of AFE in files was essential to include the patients in our study. We estimated the incidence and mortality rate of AFE. Then, the presence of each of the four diagnosis criteria of the SMFM score was described, as well as the clinical and biological patterns. RESULTS: Among the 54 140 women who delivered during the study period, 14 had a strong suspicion of AFE (0.03 %), accounting for 25.9/100 000 deliveries (95 %CI (12.3-39.5/100,000)). All women had biological tests or autopsy supporting the diagnosis of AFE. Six of 14 patients (43 %) presented with all the four diagnostic criteria of the SMFM definition. All 14 women presented a hemodynamic collapse, but respiratory symptoms were lacking in 8 patients (57 %); 71 % fulfilled the criterion of biological DIC, and all patients had a clinical coagulopathy and a massive postpartum hemorrhage. Absence of fever was lacking in three women. In addition, all patients presented premonitory symptoms such as neurological disorders or irreversible and inaugural fetal bradycardia. CONCLUSION: The four SMFM diagnostic criteria were present in less than half of the women with a strong suspicion of AFE. We propose an alternative clinical and pragmatic definition to diagnose AFE, which has to be validated in the future. Early diagnosis of AFE based solely on clinical criteria can help clinicians anticipate the severity of the situation and optimize care.

[Term Prelabor Rupture of Membranes: CNGOF Guidelines for Clinical Practice - Short Text]. / Rupture des membranes à terme avant travail. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVE: To determine the management of patients with term prelabor rupture of membranes. METHODS: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges. RESULTS: Term prelabor rupture of membranes is considered a physiological process up to 12hours of rupture (Professional consensus). In case of expectant management and with a low rate of antibiotic prophylaxis, home care compared to hospitalization could be associated with an increase in neonatal infections (LE3), especially in case of group B streptococcus colonization (LE3). Home care is therefore not recommended (Grade C). In the absence of spontaneous labor within 12hours of rupture, antibiotic prophylaxis could reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12hours of rupture in term prelabor rupture of the membranes is therefore recommended (Grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (Grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1) or misoprostol (LE1), is associated with shorter rupture of membranes to delivery intervals when compared to expectant management. Compared with expectant management, immediate induction of labor is not associated with lower rates of neonatal infection (LE1), even among women with a positive streptococcus B vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (Grade B). Induction of labor is not associated with an increase or decrease in the cesarean delivery rate (LE2), whatever parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (Grade B). No induction method (oxytocin, dinoprostone, misoprostol or Foley® catheter) has demonstrated superiority over another, whether to reduce rate of intrauterine or neonatal infection, rate of cesarean delivery or to shorten rupture of membranes to delivery intervals regardless of Bishop's score and parity. CONCLUSION: Term prelabor rupture of membranes is a frequent event. A 12-hour delay without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation justifying an antibiotic prophylaxis. Expectant management or induction of labor can both be proposed, even in case of positive screening for streptococcus B, depending on the patient's wishes and maternity units' organization (Professional consensus).

Update: Focus in-hospital maternal cardiac arrest.

The incidence of maternal cardiac arrest ranges from 1/55,000 to 1/12,000 births. It is due most frequently to cardiovascular, hemorrhagic, and anesthesia-related causes, as well as to amniotic fluid embolism. The basic principles of resuscitation remain applicable in this situation, but the physiological modifications of pregnancy must be taken into account, in particular, the aortocaval compression syndrome. After 24 weeks of gestation, a salvage cesarean delivery must be performed immediately, without transfer to the operating room, if resuscitation maneuvers have failed 4 min after arrest, because this interval conditions the mother's neurological prognosis and improves neonatal survival.

[Diversity of hepatitis B virus and its consequences]. / Impact clinique, thérapeutique et diagnostique de la diversité génétique du virus de l'hépatite B.

The genetic diversity of hepatitis B virus (HBV) was defined on the basis of the characterisation of the major determinants in the antigenic loop of HBs antigen (Ag). Historically, nine subtypes were defined. Recently, based on sequence analysis, HBV genomes have been classified into eight genotypes (A-H) which present distinct geographical distributions. Genetic mutants may have a selective advantage in patients treated with passive or active immunization (hepatitis B immune globulin or vaccine). Anti-viral treatment can be responsible for the emergence of escape mutants with resistant mutations in the polymerase gene. These substitutions can lead to changes on HBsAg structure. The lack of detection of several envelope mutant viruses by some commercial HBsAg assays has been demonstrated. Substitutions involving precore/core region have also been found to prevent HBeAg synthesis.

[Intrauterine blood transfusion: Status report of 4years of practice in France (2011-2014)]. / Transfusions fœtales érythrocytaires : état des lieux sur 4 ans en France (2011­2014).

OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's (IUT) performed in France, among the French prenatal diagnosis centers in order to study the etiology of severe anemia requiring IUT. METHODS: We conducted a national retrospective descriptive study between 2011 and 2014. The data were collected using a survey sent by email to all French prenatal diagnosis centers. RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during the study period. The geographical repartition of these centers was appropriate for the "Aquitaine Pyrénées" region. Five centers performed 68 % of the national activity and one center performed 40 % the national activity. Each year, a mean of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the etiologies) with anti-RhD being the most prevalent antibody. The second etiology was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The French IUT activity was stable in numbers and indications during the study period. A national register could be set up in order to better evaluate prospectively the number of pregnancies concerned by IUT and to study the prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.

Reactivity of HDL subfractions towards lecithin-cholesterol acyltransferase. Modulation by their content in free cholesterol.

(1) Human HDL2 (d 1.070-1.125) and HDL3 (d 1.125-1.21) labelled with unesterified [14C]cholesterol, were incubated with a source of lecithin-cholesterol acyltransferase. For optimal activity, the reaction required the addition of albumin in excess, at least 3-times greater than the concentration of HDL-free cholesterol. Under such conditions, the reaction appeared saturable. HDL3 was found the most efficient substrate and the Vmax values expressed for 1.5 IU LCAT/ml and with an albumin/free cholesterol ratio of 3, were 8.3 nmol free cholesterol esterified/ml per h and 4.1 nmol/ml per h for HDL3 and HDL2, respectively. (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis with a semipurified lipoprotein lipase from bovine milk. The newly formed HDL had gained free cholesterol and phospholipids, so that about 50% of these modified HDL, referred to as light-LIP-HDL3, were reisolated in the HDL2 density range. Light-LIP-HDL3 were enriched mostly in free cholesterol (+ 160%) and in phospholipid (+ 40%). Their reactivity towards LCAT was half-reduced compared to parent HDL3, which correlated well with a decrease in their phospholipid/free cholesterol molar ratio. Moreover, HDL3 artificially enriched in free cholesterol and exhibiting a comparable PL/FC behaved like lipolysis-modified HDL in their reactivity towards LCAT. (3) HDL3 were also modified by co-incubation with VLDL (post-VLDL-HDL3), or with VLDL and a source of lipid transfer protein (CET-HDL3). The latter treatment greatly affected the lipid composition of the core particle (-25% esterified cholesterol, +190% TG). In both cases, the moderate decreasing LCAT reactivity observed could be related to the phospholipid/free cholesterol ratio. Thus, like in artificial substrates, the lipid composition of the HDL surface may control the rate of LCAT-mediated cholesterol esterification.

[Epidemiological surveillance of blood donors and residual risk of blood-borne infections in France, 2001 to 2003]. / Surveillance épidémiologique des donneurs de sang homologues et risque résiduel en France entre 2001 et 2003.

The national surveillance of French blood donors is performed by the Institut de Veille Sanitaire and the National Reference Center for Hepatitis B and C in transfusion in collaboration with the Etablissement Français du Sang and the Army blood center. The main objectives of this surveillance are to evaluate trends in prevalence and incidence rates of blood-borne infections in the blood donor population, to identify routes of contamination and to assess residual risk. This exhaustive surveillance also contributes to evaluate the blood donor selection and the impact of measures taken to prevent infections in the general population. The analyse of the database of all blood donations obtained from 2001 to 2003 has shown that prevalence rates were stable in the study period (0.60 per 10(4) donors for HIV, 8.0 per 10(4) donors for HCV, 1.8 per 10(4) first-time donors for HBs Ag and 0.56 per 10(4) donors for HTLV), The incidence rate of HIV and HBV (1 per 10(5) person-years) was three-times higher than for HCV (0.35 per 10(5) person-years) and eleven times higher than for HTLV (0.09 per 10(5) person-years). At least, the residual risk of transfusion-transmitted viral infections is very low: 1/3,150,000 donations for HIV, 1/10,000,000 donations for HCV and 1/640,000 donations for HBV. The yield of Nucleic Acid Testing (NAT) is limited since only 2 donations for HIV and 3 for HCV which were negative for antibodies were discarded thank to the NAT.

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

Antibodies to hepatitis C virus by second generation test in hemodialyzed patients.

To assess the prevalence and the incidence of hepatitis C virus (HCV) in a dialysis unit, we prospectively tested for anti-HCV in chronic hemodialysis patients and staff members since January 1989, using a first generation assay. Incidence was nil in staff and low in patients (3.7% in 89, 1% in 90), and prevalence was 30% in patients. In January 1991 blood samples from 115 patients were tested by first (EL1) and second generation (EL2) ELISA (Ortho Diagnostic System). Positive subjects were tested by a RIBA-2 confirmation test. Fifty-three patients were negative by all tests. Positive tests were observed in 62 patients (54%) including 36 positive in EL1 and EL2, and 26 only by EL2. All positive patients were reactive by RIBA-2 but nine were classified undetermined (only one positive band). In five patients reactivity of antibodies to 5-1-1 and C-100-3 gradually declined during the study. Second generation tests gave a better correlation with time on dialysis and blood transfusion. We conclude that second generation tests for HCV are more accurate for estimating true prevalence of HCV infection in hemodialysis units.

1,25-Dihydroxyvitamin D3 regulates gamma 1 transpeptidase activity in rat brain.

gamma-Glutamyl transpeptidase (gamma-GT), primarily described as a kidney enzyme, is also expressed in several cell types of the central nervous system (CNS). It is involved in the glutathione cycle and in cysteine transport. Here we report that the specific activity of this enzyme is transiently increased in the rat brain, following a treatment with 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D. In vitro experiments showed that this positive regulatory effect does not affect endothelial cells of the brain microvessels, but does affect pericytes and parenchymal astrocytes. Changes in the specific activity of gamma-GT were not correlated with any important modification of brain amino acid concentrations. Since gamma-GT is though to participate in the scavenging of reactive oxygen species, these data suggest that 1,25-D3 could be an effector controlling detoxification processes in the brain.

Toxoplasma gondii: demonstration of intrinsic peroxidase activity during lacto-peroxidase mediated radioiodination of tachyzoites.

Tachyzoites of Toxoplasma gondii have been radioiodinated under various conditions with or without lactoperoxidase, with glucose oxidase being used to generate hydrogen peroxide. Erythrocytes were iodinated simultaneously as a control. In our conditions, tachyzoites were more intensely labelled in the absence of lactoperoxidase. This result can be explained by the existence of an intrinsic peroxidase activity which interfere with the exogenously added enzyme during surface radioiodination.

Effects of keto-analogues on phosphocalcic and aminoacid metabolism in dialysed patients: a crossover study.

It has been suggested that calcium salts of keto-analogues (KA) have beneficial effects on phosphocalcic and aminoacid (AA) metabolism. To confirm this, their short-term effects were evaluated on chronic dialyzed patients. In a prospective, randomised, crossover study, eight and seven patients were put on KA (200 mg/kg/d) and assigned either a low-protein diet (LP:0.4 g/kg/d) or a normal one (NP: 1 g/kg/d) for 15 days. The two treatments were interchanged after 15 days of washout. KA.LP was accompanied by: a) decreases in calorie intake (12%; p = 0.001) and in blood concentrations of albumin (5%, p = 0.004), urea (32%, p = 0.001), phosphate (29%, p = 0.001), parathormone (27%, p = 0.008), isoleucine (24%, p = 0.04), 1 and 3 methyl-histidine (71%, p = 0.03; 24%, p = 0.005), valine (19%, p = 0.004) and hydroxyproline (85%, p = 0.009); b) increases in calcemia (9%, p = 0.002), cystathionine (991%, p = 0.0001) and threonine (22%, p = 0.04). KA.NP was accompanied by: a) decreases in phosphatemia (15%, p = 0.03) and parathormone (18%, p = 0.06); b) increases in calcemia (9%, p = 0.002), cystathionine (427%, p = 0.0001), and phenylalanine (28%, p = 0.013). Calcium salts of keto-analogues together with a low or normal protein diet thus seem to reduce blood concentrations of phosphates and parathormone, and raise calcium; however their action on aminoacids needs further investigation.

[Dissociation of hypotensive and renal hemodynamic effects of an angiotensin converting enzyme inhibitor in insulin-dependent diabetic patients with incipient nephropathy]. / Dissociation des effets hypotenseurs et hémodynamiques rénaux d'un inhibiteur de l'enzyme de conversion chez des diabétiques insulinodépendants avec néphropathie débutante.

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetics is controversial. In order to dissociate the hypotensive and intrarenal effects, 16 insulin-dependant diabetics with permanent microalbuminuria (30-300 mg/24 h) without hypertension were given Ramipril, a long acting ACE inhibitor, at hypotensive (treatment A 5 mg/day; N = 8) and at sub-hypotensive doses (treatment B, 1.25 mg/day; N = 8) over a 6 week period in parallel double-blind study. Blood pressure, UAE, glomerular filtration renal blood flow (continuous 125I-Iodothalamate + 131I-Hippurate infusion) and converting enzyme activity (Liebermann's method), before and after treatment. In treatment group A, the blood pressure fell from 133 +/- 5/79 +/- 4 (mean +/- SE) to 125 +/- 4/77 +/- 2 mmHg (p less than 0.05 for systolic blood pressure) whereas it remained stable in treatment group B (132 +/- 7/79 +/- 4 to 128 +/- 5/80 +/- 4 mmHg). The UAE decreased in both groups: group A from an average of 74 (40-198) to 47 (5-202) mg/24 h (p = 0.07; group B, from an average of 77 (50-136) to 19 (15-120) mg/24 h (p less than 0.005), as did ACE activity: group A from 332 +/- 44 to 163 +/- 33 iu/l (p less than 0.004), group B from 423 +/- 39 to 191 +/- 28 iu/l (p less than 10-4).(ABSTRACT TRUNCATED AT 250 WORDS)

[Increase of activity of angiotensin-converting enzyme in insulin-dependent diabetic patients with permanent microalbuminuria]. / Elévation de l'activité de l'enzyme de conversion chez des diabétiques insulino-dépendants présentant une microalbuminurie permanente.

Angiotensin I Converting Enzyme (ACE), which is synthesized by vascular endothelial cells, can be elevated in some diabetic subjects. To study if serum ACE can be elevated in subjects with high risk for malignant microangiopathy, 34 normotensive type I, insulin-dependent diabetic subjects with persistent microalbuminuria (30-300 mg/24 h) were compared for serum ACE activity (Liebermann's method) with 30 normotensive, normoalbuminuric type I, insulin-dependent diabetic subjects of same age (33 +/- 15 (M +/- SD) vs 39 +/- 14 years), sex (13 F/21 M vs 15 F/15 M), stage of retinopathy (14 vs 16 nil/11 vs 7 background/6 vs 4 preproliferative/3 vs 3 proliferative), HbA1c (7.7 +/- .9 vs 8.2 +/- 1.0%). Serum ACE activity of diabetic subjects were also compared with 120 age and sex related healthy controls. Serum ACE activity was higher in type I, insulin-dependent diabetic subjects with microalbuminuria than in those with normoalbuminuria (406 +/- 114 vs 359 +/- 97 IU/l; p = 0.05), or in controls (307 +/- 95 IU/l; p = 0.0001). Normoalbuminuric subjects also had higher ACE activity than controls (p = 0.02). In diabetic subjects, serum ACE activity was not related to diabetes duration (r = 0.1; ns), stage of retinopathy (r = 0.06; ns), HbA1c (r = 0.02; ns), or to blood pressure (r = 0.03; ns), but was related to urinary albumin excretion (r = 0.28; p = 0.03) in diabetic subjects. However, stage of retinopathy was related to diabetes duration (r = 0.74; p = 0.0004) and to age (r = 0.42; p = 0.003) in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)