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Laurent Mandelbrot

Publications and source records attributed to Laurent Mandelbrot.

17 recordsLinked to original sources
PubMed2006

Placental transfer of lopinavir/ritonavir in the ex vivo human cotyledon perfusion model.

OBJECTIVE: This study was done to determine the placental transfer of the human immunodeficiency virus protease inhibitor lopinavir with ritonavir. STUDY DESIGN: Twenty-five human cotyledons that were obtained after uneventful pregnancies and deliveries were perfused in an open double circuit with lopinavir (1099-10,606 microg/L) and ritonavir (254-1147 microg/L) at various albumin concentrations (2, 10, and 40 g/L). RESULTS: The fetal transfer rate of lopinavir, when combined with ritonavir, was 23.6% +/- 6.9% at an albumin concentration of 2 g/L. The fetal transfer rate decreased to 20.7% +/- 10% at an albumin concentration of 10 g/L and to 3.3% +/- 0.5% at an albumin concentration of 40 g/L. CONCLUSION: The placental transfer of lopinavir, a highly protein-bound molecule, was compatible with passive diffusion of the unbound fraction. Even at physiologic maternal albumin concentrations, the amount of drug transferred into the fetal compartment was well above the 50% inhibitory concentration.

Albumins↗
PubMed2006

Latzko operation for vault vesicovaginal fistula.

BACKGROUND: Various surgical procedures are currently performed for the treatment of posthysterectomy vesicovaginal fistula. Most of them are carried out via an abdominal incision. OBJECTIVE: Report of our experience with Latzko's operation, a simple purely transvaginal procedure. METHODS: Retrospective study of vesicovaginal fistulas treated by a Latzko procedure between June 1991 and June 2005. RESULTS: Eleven patients were operated on. Two (18%) had a prior failed attempt of vesicovaginal fistula repair. Mean size of the fistulas was 12+/-11 mm (range: 2-40 mm). Mean operative duration was 62+/-33 min (range: 20-110 min). All fistulas healed. No intraoperative complications were observed. There was only one postoperative complication, a lower urinary tract infection in one patient. Mean hospital stay was 6+/-4 days (range: 2-12 days). CONCLUSIONS: The Latzko procedure is an efficient, safe, and simple technique for the management of vault vesicovaginal fistulas, and can therefore be proposed as the first-line surgical treatment.

Adult↗
PubMed2006

Pregnancy-related effects on nelfinavir-M8 pharmacokinetics: a population study with 133 women.

A relationship between nelfinavir antiretroviral efficacy and plasma concentrations has been previously established. As physiological changes associated with pregnancy have a large impact on the pharmacokinetics of many drugs, a nelfinavir population study with women was developed, and the large intersubject variability was analyzed in order to optimize individual treatment schedules for this drug during pregnancy. A population pharmacokinetic model was developed in order to describe the concentration time course of nelfinavir and its metabolite M8 in pregnant and nonpregnant women. Individual characteristics, such as age, body weight, and weeks of gestation or delivery, which may influence nelfinavir-M8 pharmacokinetics were investigated. Data from therapeutic drug monitoring in 133 women treated with nelfinavir were retrospectively analyzed with NONMEM. Nelfinavir pharmacokinetics was described by a one-compartment model with linear absorption and elimination and M8 produced from the nelfinavir central compartment. Mean pharmacokinetic estimates and the corresponding intersubject percent variabilities for a nonpregnant woman were the following: absorption rate, 0.83 h(-1); absorption lag time, 0.85 h; apparent nelfinavir elimination clearance (CL(10)/F), 35.5 liters/h (50%); apparent volume of distribution (V/F), 596 liters (118%); apparent formation clearance to M8 (CL(1M)/F), 0.65 liters/h (69%); and M8 elimination rate constant (k(M0)), 3.3 h(-1) (59%). During pregnancy, we observed significant increases in nelfinavir (44.4 liters/h) and M8 (5 h(-1)) elimination but unchanged nelfinavir transformation clearance to M8, suggesting an induction of CYP3A4 but no effect on CYP2C19. Apparent nelfinavir clearance and volume showed a twofold increase on the day of delivery, suggesting a decrease in bioavailability on this day. The M8 elimination rate was increased by concomitant administration of nonnucleoside reverse transcriptase inhibitors. A trough nelfinavir plasma concentration above 1 mg/liter was previously shown to improve the antiretroviral response. The Bayesian individual pharmacokinetic estimates suggested that the dosage should not be changed in pregnant women but may be doubled on the day of delivery.

Adult↗
PubMed2004

[Syphilis and pregnancy].

Consequences of syphilis for mother, pregnancy, fetus and child are considerable, but preventable. Serological screening must be offered at the first prenatal visit, using both a treponemal (eg. TPHA) and a non treponemal (eg. VDRL or RPR) test. When the results are compatible with any type of active syphilis, treatment is required. The treatment of choice is penicillin: benzathine penicillin G, 2.4 million units intramuscular, repeated one week later, and most authors recommend a third dose if a late latent syphilis is suspected, or in case of coinfection with HIV. Women with a proven penicillin allergy can be desensitized. Alternative therapies, such as macrolids, are less well evaluated. Follow-up during and after therapy must not be neglected. In case of Jarisch-Herxheimer reaction, the mother should be managed on an inpatient basis, and the fetus carefully monitored. The VDRL should be repeated (usually every trimester), and therapy be renewed if there is not a significant decrease in titer. The fetus should be followed by serial ultrasound examinations. Finally, the child must be followed up clinically and biologically, and treated in case of congenital syphilis. The residual risk of adverse outcome is increased in case of reinfection, lack of maternal therapy or incomplete treatment, or when diagnosis and therapy are performed late in pregnancy.

Adult↗
PubMed2004

Maternal-fetal transfer and amniotic fluid accumulation of protease inhibitors in pregnant women who are infected with human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to investigate placental transfer and amniotic fluid concentrations of protease inhibitors when they are given to pregnant women who are infected with human immunodeficiency virus. STUDY DESIGN: Fifty-eight mothers who received antiretroviral therapy that included > or =1 protease inhibitors for clinical indications at the time of delivery were enrolled in the study. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean delivery, and paired cord blood samples were obtained by venipuncture immediately after the delivery. Drug concentrations were measured with high performance liquid chromatography. RESULTS: Most maternal protease inhibitor plasma concentrations (38/66 concentrations) were below the trough concentrations that are recommended for therapeutic drug monitoring. Cord blood concentrations were below the assay limit of detection in 10 of 40 samples for nelfinavir and 25 of 40 samples for its metabolite M8, 9 of 11 samples for ritonavir, 4 of 6 samples for indinavir, 5 of 6 samples for saquinavir but were detectable in 3 of 3 samples for amprenavir. Among the 24 amniotic fluid samples that were available, the concentrations below the detection limit were 10 of 16 samples for nelfinavir, 11 of 16 samples for M8, 1 of 3 samples for indinavir, 4 of 4 samples for ritonavir, and 0 of 1 samples for amprenavir. There were significant correlations between cord blood and maternal concentrations of nelfinavir and its metabolite M8. CONCLUSION: Placental transfer of the human immunodeficiency virus protease inhibitors is generally low; however, it may differ greatly according to the molecule.

Adult↗
PubMed2004

Thoracoamniotic shunting for fetal pleural effusions with hydrops.

OBJECTIVE: The purpose of this study was to evaluate perinatal outcome after thoracoamniotic shunting for fetal pleural effusions with hydrops. STUDY DESIGN: This was a retrospective study. RESULTS: Shunting was performed immediately after diagnosis and was successful in all 54 of the cases that were attempted. There were 7 pregnancy terminations, 9 in utero deaths, and 38 live births, of which 7 children died in the neonatal period and 31 children survived. Among the liveborn infants, 27 infants were delivered preterm (71%), of whom 7 infants (15%) had preterm premature rupture of membranes and 4 infants (8.5%) had chorioamnionitis. Perinatal death (23/54 infants; 43%) was related to underlying anomalies (7 cases), pulmonary hypoplasia (5 cases), chorioamnionitis (2 cases), or treatment failure for unknown reasons (9 cases). All 31 survivors had chylothorax; for 28 of the survivors, the chylothorax was primary, and for 3 survivors, the chylothorax was the result of right congenital diaphragmatic hernia, pulmonary sequestration, or Noonan syndrome. CONCLUSION: After the shunting, pleural effusion with hydrops has a 57% survival rate; premature delivery is the leading source of morbidity.

Amniotic Fluid↗
PubMed2004

Maternal-fetal transfer and amniotic fluid accumulation of nucleoside analogue reverse transcriptase inhibitors in human immunodeficiency virus-infected pregnant women.

This study was performed to investigate placental transfer of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A total of 100 HIV type 1-infected mothers receiving antiretroviral therapy, including one or more NRTIs, for clinical indications at the time of delivery were enrolled. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean section, and paired cord blood samples were obtained by venipuncture immediately after delivery. Drug concentrations were measured by using high-performance liquid chromatography. A significant relationship between concentrations in maternal and cord plasma samples was found for zidovudine, lamivudine, stavudine, and didanosine. The ratio between the concentrations in cord and maternal plasma samples (R) was high for zidovudine (R = 1.22), its glucuronide metabolite (3'-azido-3'-deoxythymidine-beta-d-glucuronide) (R = 1.01), stavudine (R = 1.32), lamivudine (R = 0.93), and abacavir (R = 1.03) and was low for didanosine (R = 0.38). The ratio between the concentrations in amniotic fluid and cord plasma samples was high for zidovudine (R = 2.24), its glucuronide metabolite (R = 2.83), stavudine (R = 4.87), and lamivudine (R = 3.99) and was lower for didanosine (R = 1.14). These findings indicate that most NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic fluid, probably through fetal urinary excretion. The efficacy or toxicity of NRTIs may vary according to placental transfer.

Adult↗
PubMed2002

Assisted reproduction in HIV-1-serodifferent couples: the need for viral validation of processed semen.

BACKGROUND: Many HIV-infected men and women have a strong desire for a child. Assisted reproductive technologies (ART) are an option for HIV-serodifferent couples to reduce the risk of HIV transmission from an infected man to the woman. Potential HIV contamination of selected spermatozoa after semen processing is an important issue in this context. METHODS: HIV in processed semen obtained in our laboratory since 1995 were analysed. HIV RNA and DNA detection was performed in the selected spermatozoa of 125 men. HIV RNA was analysed in blood and semen plasma as well as HIV DNA in non-sperm cells. RESULTS: HIV RNA and DNA were detected in the selected spermatozoa of eight and two men (6.4% and 1.6%), respectively. HIV RNA was detected with a median load of 5 copies/10(6) spermatozoa. Six of the eight men were untreated, one was taking nucleoside analogue therapy and one was on highly active antiretroviral treatment (HAART). HIV RNA detection was more likely to be positive in selected spermatozoa of men with high seminal plasma viral load. HIV RNA was detected in 26% and 11% of selected spermatozoa fractions when the seminal plasma load was > 10,000 copies/ml and 20-10,000 copies/ml, respectively, but in none when the seminal plasma tested negative. CONCLUSION: Selected spermatozoa may be positive for HIV RNA detection even in treated patients. Viral validation of processed semen is necessary in ART programmes for serodifferent couples, particularly in men with only partially or poorly controlled HIV infection.

Anti-HIV Agents↗
PubMed2002

Field acceptability and effectiveness of the routine utilization of zidovudine to reduce mother-to-child transmission of HIV-1 in West Africa.

OBJECTIVE: To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission (MTCT) of HIV in breastfed children after a randomized clinical trial demonstrated its efficacy in Côte d'Ivoire and Burkina Faso. METHODS: Pregnant women aged 18 years or older, who had confirmed HIV-1 infection, haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36-38 weeks' gestation to receive an oral short course of zidovudine. Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction, or if aged 15 months or older, a positive HIV serology. RESULTS: The acceptability of HIV pretest counselling was significantly higher in the cohort (90.3%) than in the trial (83.7%) (P < 0.001), but the return rate for HIV test results and for inclusion was low. A similar proportion of women accepted starting zidovudine in the cohort, 30.4% compared with 27.3% in the trial (P = 0.13). The proportions of women who took more than 80% of the expected zidovudine regimen were 81.8% before labour, 86.7% during labour, and 88.1% during the postpartum period, compared with those observed during the trial, 78.1, 81.1, and 85%, respectively. The MTCT probability at age 15 months was 19.6% in the cohort (n = 185) versus 21.2% in the trial (P = 0.52). CONCLUSION: The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures. For women who consent, zidovudine is well accepted and efficacious under routine circumstances.

Adolescent↗
PubMed2002

Differences in postpartum morbidity in women who are infected with the human immunodeficiency virus after elective cesarean delivery, emergency cesarean delivery, or vaginal delivery.

OBJECTIVE: The aim of this study was to assess the impact of elective cesarean delivery on postpartum morbidity in women who are infected with the human immunodeficiency virus (HIV). STUDY DESIGN: We performed a retrospective study of 401 women who were infected with HIV who were delivered in a single reference center from 1989 through 1999. Women who had cesarean deliveries (n = 201), of which 109 were elective and 92 were emergency, were compared with a group of women who were delivered vaginally (n = 200), composed of the women who were infected with HIV preceding each cesarean delivery. RESULTS: One or more serious complications occurred after 12% of emergency cesarean deliveries, after 6.4% of elective cesarean deliveries, and after 4% of vaginal deliveries (P =.04). In a multivariate analysis, which was adjusted for maternal CD4 lymphocyte count and antepartum hemorrhage, the relative risk of any postpartum complication (serious or minor) was increased by 1.85 (range, 1.00-3.39) after elective cesarean delivery and 4.17 (range, 2.32-7.49) after emergency cesarean delivery, compared with vaginal deliveries (P =.0001). CONCLUSION: Postpartum morbidity in women who are infected with HIV was highest after emergency, rather than elective, cesarean deliveries.

Adult↗
PubMed2002

Contraceptive use, protected sexual intercourse and incidence of pregnancies among African HIV-infected women. DITRAME ANRS 049 Project, Abidjan 1995-2000.

The aim of this paper is to describe the adherence of African HIV+ women to the counselling provided after announcement of the result of the HIV test during pregnancy, focusing on early weaning to reduce post-natal transmission, protected sexual intercourse to avoid sexual transmission, and contraceptive use to avoid unexpected pregnancies. In 1999-2000, a questionnaire on sexual and reproductive behaviours was administered to 149 HIV+ women followed in post-partum, informed and counselled in the ANRS 049 DITRAME project in Abidjan. Côte d'Ivoire. Duration of breastfeeding, post-partum amenorrhea and abstinence, contraceptive use and condom use were measured. Incidence of pregnancies during the first 24 months post partum was estimated and modelled by a Cox regression model. Average duration of breastfeeding was 7.9 months, average duration of post partum abstinence was 12.0 months, and 39% of women used contraceptives at the time of the survey. Frequency of condom use was 13%. Incidence of pregnancies was 16.5 per 100 women-years at risk. Half of these pregnancies were not desired and a third were terminated by induced abortion. The significant determinants of the pregnancy occurrence were the death of the previous child, the cessation of breastfeeding, the cessation of the post partum abstinence, and higher education. In conclusion, if counselling on early weaning can be followed by the HIV+ women, it is not easily the case for condom and contraceptive use. Hence, pregnancy incidence in the post-partum follow-up was high. The main strategy of these HIV+ women to avoid unexpected pregnancies as well as sexual transmission of HIV seems to be an increase of the duration of post-partum abstinence. The most educated women who cannot easily adopt this strategy are particularly exposed to unwanted pregnancies.

Adolescent↗
PubMedDate not supplied

Progesterone induces BRCA1 mRNA decrease, cell cycle alterations and apoptosis in the MCF7 breast cancer cell line.

BACKGROUND: Inherited mutations of the BRCA1 gene are responsible for hereditary breast and ovarian cancer syndrome. However, little is known of how disruption of BRCA1 functions preferentially increases cancer risk in hormone-dependent organs. We aimed to study whether BRCA1 was regulated by progesterone in the MCF7 breast cancer cell line. MATERIALS AND METHODS: MCF7 breast cancer cells were incubated with 10(-4) or 10(-10) M progesterone for 24 or 48 hours. BRCA1 expression, proliferation and apoptosis were analysed. RESULTS: 10(-4) M progesterone decreased cell proliferation, cell cycle progression and induced apoptosis. In addition, BRCA1 and cyclin A mRNA decreased. In contrast, none of these effects were observed in MCF7 cells incubated with 10(-10) M progesterone. CONCLUSION: The down-regulation of BRCA1 in MCF7 cells incubated with 10(-4) M progesterone seems to be a consequence of cell cycle alterations rather than a direct effect of the hormone on BRCA1.

Apoptosis↗
PubMedDate not supplied

Expression of BRCA1, HER-1 (EGFR) and HER-2 in sporadic breast cancer and relationships to other clinicopathological prognostic features.

BACKGROUND: The BRCA1 caretaker gene is associated with poor prognostic features in hereditary breast cancer and may also play a role in sporadic breast cancer (SBC). HER-1 and HER-2 overexpression is associated with adverse prognosis in SBC. We studied whether BRCA1 expression was associated with HER1, HER2 and other prognostic features in SBC. PATIENTS AND METHODS: Fifty newly-diagnosed SBC patients were studied for prognostic features and immunohistochemical expressions of BRCA1, HER-1 and HER-2. RESULTS: Tumors were positive for BRCA1 in 26%, HER-1 in 32% and HER-2 in 20% of cases. Lack of BRCA1 expression was associated with node metastases and decreased estrogen receptor. HER-2 expression was associated with young age, HER-1, Ki67 and decreased hormone receptors. No correlation was observed between BRCA1 and HER-1 or HER-2. CONCLUSION: In SBC, the lack of BRCA1 expression was associated with poor prognostic features, but unrelated to HER-1 and HER-2. HER2 and HER-1 were, however, highly correlated.

Adult↗