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OBJECTIVE: The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). METHODS: Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ-) group. RESULTS: 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ- group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group (p = 0.001), particularly in terms of preterm delivery, 15.8% versus 44.2% (p = 0.006), and IUGR, 10.5% versus 28.6% (p = 0.03). No adverse outcomes were reported in the HCQ+ group. CONCLUSION: HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction.
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Antirreumáticos/efeitos adversos , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/diagnóstico , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/tratamento farmacológico , Nascimento Prematuro/induzido quimicamente , Adulto , Antirreumáticos/administração & dosagem , Estudos de Coortes , Feminino , Idade Gestacional , Glucocorticoides/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Recém-Nascido Prematuro , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Gravidez , Complicações na Gravidez/prevenção & controle , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We report exciton-polariton condensation in a new family of fully hybrid ZnO-based microcavity demonstrating the best-quality ZnO material available (a bulk substrate), a large quality factor (~4000) and large Rabi splittings (~240 meV). Condensation is achieved between 4 and 300 K and for excitonic fractions ranging between 17% and 96%, which corresponds to a tuning of the exciton-polariton mass, lifetime, and interaction constant by 1 order of magnitude. We demonstrate mode switching between polariton branches allowing, just by controlling the pumping power, to tune the photonic fraction by a factor of 4.
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BACKGROUND: Syphilis has been making a comeback over the last 10 years. Neurosyphilis can occur at any stage of the infection but is difficult to diagnose because of the existence of misleading forms, of which we describe an example below. PATIENTS AND METHODS: A 56-year-old woman presented symptoms evoking polymyalgia rheumatica and giant-cell arteritis in a context of ibuprofen treatment for a few weeks. She also had myodesospsia, syphilids and syphilitic roseola, together with laboratory indicators of inflammation. A lumbar puncture revealed lymphocytic meningitis and a positive Treponema Pallidum Haemagglutination Assay (TPHA) for cerebrospinal fluid, thus confirming the diagnosis of neurosyphilis. Moreover, the ophthalmologic examination showed optic neuritis with papilla lesions of syphilitic origin. This was successfully treated with a 3-week course of penicillin G infusions. CONCLUSION: Symptoms evocative of Horton's disease and polymyalgia rheumatica can reveal syphilis, a disease dubbed "the great simulator" on account of the variety of clinical forms it can take.
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Arterite de Células Gigantes/diagnóstico , Neurossífilis/diagnóstico , Polimialgia Reumática/diagnóstico , Astenia/etiologia , Biópsia , Diagnóstico Diferencial , Feminino , Testes de Hemaglutinação , Humanos , Pessoa de Meia-Idade , Morbidade/tendências , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/complicações , Neurossífilis/tratamento farmacológico , Neurossífilis/microbiologia , Neurite Óptica/etiologia , Penicilina G/uso terapêutico , Sífilis/diagnóstico , Sífilis/epidemiologia , Artérias Temporais/patologia , Treponema pallidum/isolamento & purificaçãoRESUMO
The recent expansion of Aedes albopictus across continents in both tropical and temperate regions and the exponential growth of dengue cases over the past 50 years represent a significant risk to human health. Although climate change is not the only factor responsible for the increase and spread of dengue cases worldwide, it might increase the risk of disease transmission at global and regional scale. Here we show that regional and local variations in climate can induce differential impacts on the abundance of Ae. albopictus. We use the instructive example of Réunion Island with its varied climatic and environmental conditions and benefiting from the availability of meteorological, climatic, entomological and epidemiological data. Temperature and precipitation data based on regional climate model simulations (3 km × 3 km) are used as inputs to a mosquito population model for three different climate emission scenarios. Our objective is to study the impact of climate change on the life cycle dynamics of Ae. albopictus in the 2070-2100 time horizon. Our results show the joint influence of temperature and precipitation on Ae. albopictus abundance as a function of elevation and geographical subregion. At low-elevations areas, decreasing precipitation is expected to have a negative impact on environmental carrying capacity and, consequently, on Ae. albopictus abundance. At mid- and high-elevations, decreasing precipitation is expected to be counterbalanced by a significant warming, leading to faster development rates at all life stages, and consequently increasing the abundance of this important dengue vector in 2070-2100.
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Aedes , Dengue , Animais , Humanos , Mosquitos Vetores , Reunião/epidemiologia , Mudança Climática , Dengue/epidemiologiaRESUMO
The conserved Shugoshin (SGO) protein family is essential for mediating proper chromosome segregation from yeast to humans but has also been implicated in diverse roles outside of the nucleus. SGO's roles include inhibiting incorrect spindle attachment in the kinetochore, regulating the spindle assembly checkpoint (SAC), and ensuring centriole cohesion in the centrosome, all functions that involve different microtubule scaffolding structures in the cell. In Caenorhabditis elegans, a species with holocentric chromosomes, SGO-1 is not required for cohesin protection or spindle attachment but appears important for licensing meiotic recombination. Here we provide the first functional evidence that in C. elegans, Shugoshin functions in another extranuclear, microtubule-based structure, the primary cilium. We identify the centrosomal and microtubule-regulating transforming acidic coiled-coil protein, TACC/TAC-1, which also localizes to the basal body, as an SGO-1 binding protein. Genetic analyses indicate that TAC-1 activity must be maintained below a threshold at the ciliary base for correct cilia function, and that SGO-1 likely participates in constraining TAC-1 to the basal body by influencing the function of the transition zone 'ciliary gate'. This research expands our understanding of cellular functions of Shugoshin proteins and contributes to the growing examples of overlap between kinetochore, centrosome and cilia proteomes.
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Caenorhabditis elegans , Cílios , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Microtúbulos/metabolismo , Cinetocoros , Centrossomo/metabolismo , Fuso Acromático/metabolismoRESUMO
Multilayered cuprates possess not only the highest superconducting temperature transition but also offer a unique platform to study disorder-free CuO2 planes and the interplay between competing orders with superconductivity. Here, we study the underdoped trilayer cuprate HgBa2Ca2Cu3O8+δ and we report quantum oscillation and Hall effect measurements in magnetic field up to 88 T. A careful analysis of the complex spectra of quantum oscillations strongly supports the coexistence of an antiferromagnetic order in the inner plane and a charge order in the outer planes. The presence of an ordered antiferromagnetic metallic state that extends deep in the superconducting phase is a key ingredient that supports magnetically mediated pairing interaction in cuprates.
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We compare the quality factor values of the whispering gallery modes of microdisks (µ-disks) incorporating GaN quantum dots (QDs) grown on AlN and AlGaN barriers by performing room temperature photoluminescence (PL) spectroscopy. The PL measurements show a large number of high Q factor resonant modes on the whole spectrum, which allows us to identify the different radial mode families and to compare them with simulations. We report a considerable improvement of the Q factor, which reflects the etching quality and the relatively low cavity loss by inserting QDs into the cavity. GaN/AlN QDs-based µ-disks show very high Q values (Q>7000) whereas the Q factor is only up to 2000 in µ-disks embedding QDs grown on the AlGaN barrier layer. We attribute this difference to the lower absorption below bandgap for AlN barrier layers at the energies of our experimental investigation.
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Fascination with glassy states has persisted since Fisher introduced the vortex-glass as a new thermodynamic phase that is a true superconductor that lacks conventional long-range order. Though Fisher's original model considered point disorder, it was later predicted that columnar defects (CDs) could also induce glassiness - specifically, a Bose-glass phase. In YBa2Cu3O7-x (YBCO), glassy states can cause distinct behavior in the temperature (T ) dependent rate of thermally activated vortex motion (S). The vortex-glass state produces a plateau in S(T ) whereas a Bose-glass can transition into a state hosting vortex excitations called double-kinks that can expand, creating a large peak in S(T ). Although glass phases have been well-studied in YBCO, few studies exist of other materials containing CDs that could contribute to distinguishing universal behavior. Here, we report on the effectiveness of CDs tilted ~30° from the c-axis in reducing S in a NbSe2 crystal. The magnetization is 5 times higher and S is minimized when the field is parallel to the defects versus aligned with the c-axis. We see signatures of glassiness in both field orientations, but do not observe a peak in S(T ) nor a plateau at values observed in YBCO. Finally, we discuss the possibility that competing disorder induces a field-orientation-driven transition from a Bose-glass to an anisotropic glass involving both point and columnar disorder.
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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We demonstrate edge-emitting exciton-polariton (polariton) laser operation from 5 to 300 K and polariton amplifiers based on polariton modes within ZnO waveguides. The guided mode dispersion below and above the lasing threshold is directly measured using gratings placed on top of the sample, fully demonstrating the polaritonic nature of the lasing modes. The threshold is found to be smaller than that expected for radiative polaritons in planar ZnO microcavities below 150 K and comparable above. These results open up broad perspectives for guided polaritonics by enabling easier and more straightforward implementation of polariton integrated circuits that exploit fast propagating polaritons, and, possibly, topological protection.
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Efficient de novo folding of actins and tubulins requires two molecular chaperones, the chaperonin TRiC (or CCT) and its novel cofactor GimC (or prefoldin). Recent studies indicate that TRiC is exquisitely adapted for this task, yet has the ability to interact with and assist the folding of numerous other cellular proteins.
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Chaperoninas/metabolismo , Citosol/metabolismo , Chaperonas Moleculares/metabolismo , Dobramento de Proteína , Chaperonina com TCP-1 , Chaperoninas/classificação , Modelos TeóricosRESUMO
Because maximum expiratory flow-volume rates in normal subjects are dependent on gas density, the resistance between alveoli and the point at which dynamic compression begins (R(us)) is mostly due to convective acceleration and turbulence. We measured maximum expiratory flow-volume (MEFV) curves in asthmatics and chronic bronchitics breathing air and He-O(2). In the latter and in some asthmatics, MEFV curves did not change, indicating that R(us) is mostly due to laminar flow. Therefore, the point at which dynamic compression begins must be further upstream than in normal subjects and the site of obstruction must be in small airways. In other asthmatics, flow increased normally indicating obstruction in larger airways. The response to He-O(2) did not correlate with initial values of pulmonary resistance, the initial MEFV curves or the response to bronchodilators. We conclude that the site of airway obstruction varies among asthmatics and that the site of obstruction is not detectable by measurement of the usual parameters of lung mechanics.
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Obstrução das Vias Respiratórias/fisiopatologia , Asma/fisiopatologia , Sistema Respiratório/fisiopatologia , Adolescente , Adulto , Idoso , Ar , Resistência das Vias Respiratórias , Bronquite/fisiopatologia , Feminino , Hélio , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio , EspirometriaRESUMO
Systemic scleroderma is an autoimmune disease, due to a connective tissue alteration characterized by extracellular matrix increase in the skin and internal organs. It is already known that the Raynaud's phenomenon and the microcapillary obliteration lead to ischemia and peripheral tissue injury. The ischemia-reperfusion phenomenon releases free radicals, that react with red blood cells (RBCs) membrane components originating lipid peroxidation and impairment of the ATP-Ca(++) pump, two possible mechanisms responsible of disease pathogenesis. Nifedipine is a Ca(++)-channel antagonist that has been used for a long time in Raynaud's phenomenon treatment. In the present study we were able to demonstrate that erythrocyte deformability and two other related variables such as membrane fluidity and osmotic fragility improve significantly with nifedipine therapy. It is likely that nifedipine inhibiting cytoplasmic calcium accumulation could restore some red blood cell membrane properties.
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Viscosidade Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Deformação Eritrocítica/efeitos dos fármacos , Nifedipino/farmacologia , Fragilidade Osmótica/efeitos dos fármacos , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Feminino , Hemorreologia/efeitos dos fármacos , HumanosRESUMO
Since 2004, in France, pertussis booster is recommended in parents of young infants and adults likely to become parents. This recommendation adds to others such as rubella vaccination in unvaccinated or seronegative women and decennial dT-IPV booster. The objective of this study is to evaluate the impact of these recommendations in parents of young infants. Pediatricians had to include parents of infants at the first well-baby visit after birth. Vaccination data were secondary recorded from parent's health record or called upon their memory. Between June and October 2006, 41 pediatricians included parents of 400 infants (median age: 36 days). dT-IPV booster was recorded or recalled in 37.4% within the 10 previous years and 17.7% within the 3 previous years. Among this last group, only 11.8% had received a combination including pertussis. Rubella serology was declared as positive by 94% of the mothers, but the physicians obtained the information of a previous rubella vaccination in only 71.7% of the mothers. Among the 9 seronegative mothers during pregnancy, only 3 were vaccinated in postpartum. Adults' immunization guidelines are not well known and poorly applied in France. The unavailability of monovalent pertussis vaccine reduces the eligible population. Two years after the launch of the pertussis cocoon strategy, the coverage of eligible young parents remains low and many opportunities are too frequently missed on the opportunity of decenial dTPolio booster. Rubella catch up strategy should be improved. Adults' vaccination strategies and guidelines need to be better broadcasted to health care professionals and also families.
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Pais , Vacinação/estatística & dados numéricos , Adulto , Vacina contra Varicela/uso terapêutico , Demografia , França , Inquéritos Epidemiológicos , Humanos , LactenteRESUMO
GOALS: Transcatheter aortic valve or leaflets thrombosis are mainly misapprehended. It negatively impacts the long-term efficiency of such prosthesis. Moreover, its incidence is presumably higher than previously described. EPIDEMIOLOGY: Recently reported subclinical leaflet thrombosis, occurring between first to third months after implantation, is about 10to 15%. All prosthesis are concerned by potential thrombosis. DIAGNOSIS: Transcatheter aortic valve thrombosis is usually detected on the basis of increased transvalvular pressure gradients or symptoms at routine follow-up. Main causes of post-TAVI thrombosis are: elderly patients, incomplete TAVI expansion, incomplete TAVI apposition to the aortic wall, areas of diminished blood flow and stagnation around the prosthesis. Main risk-factors of thrombosis are: large valves, patients with ejection fraction lower than 35%, valve-in-valve implantation, males, patients with large sinus of Valsalva, patients without anticoagulants. TREATMENT: Post-TAVI anti thrombotic regimen remains empirical. It is based on aspirin alone or dual antiplatelet therapy for 1-6months, followed by aspirin for life. Symptomatic patients with thrombus-based valve dysfunction are to be treated by oral anticoagulation (i.e., VKA or new oral anticoagulants NOAC). This treatment allows the restoration of normal leaflet motion in patients with a median time of 14 days.
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Anticoagulantes/uso terapêutico , Próteses Valvulares Cardíacas/efeitos adversos , Trombose/tratamento farmacológico , Trombose/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Valva Aórtica/cirurgia , França/epidemiologia , Humanos , Incidência , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Trombose/diagnóstico , Trombose/epidemiologia , Resultado do TratamentoRESUMO
Here we report a theoretical investigation of excitonic complexes in polar GaN/(Al,Ga)N quantum dots (QDs). A sum rule between the binding energies of charged excitons is used to calculate the biexciton binding energy. The binding energies of excitonic complexes in GaN/AlN are shown to be strongly correlated to the QD size. Due to the large hole localization, the positively charged exciton energy is found to be always blueshifted compared to the exciton one. The negatively charged exciton and the biexciton energy can be blueshifted or redshifted according to the QD size. Increasing the size of GaN/AlN QDs makes the identification of charged excitons difficult, and the use of an Al0.5Ga0.5N barrier can be advantageous for clear identification. Our theoretical results for the binding energy of exciton complexes are also confronted with values deduced experimentally for InAs/GaAs QDs, confirming our theoretical prediction for charged excitonic complexes in GaN/(Al,Ga)N QDs. Finally, we realize that the trends of excitonic complexes in QDs are significantly related to competition between the local charge separation (whatever its origin) and the correlation effect. Following our findings, entangled photons pairs can be produced in QDs with careful control of their size in order to obtain zero exciton-biexciton energy separation.
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Murine Bacillus Calmette-Guérin-activated macrophages mediate discrete cytotoxic effects in cocultured tumor target cells in vitro. These effects include: the loss of intracellular iron, in part associated with reversible inhibition of the Kreb's cycle enzyme, aconitase; cytostasis, associated with reversible lesions inflicted in the electron transport chain (ETC) of the mitochondria resulting in reversible loss of proliferative capacity; and cytolysis, manifested by eventual gross perturbation of the integrity of the plasma membrane. We demonstrate that these manifestations of cytotoxicity are the result of three independent mechanisms employing apparently distinct macromolecules for their commission. Analysis of target cells that are highly susceptible (L-929), highly resistant (L-1210), or have incomplete resistance (EMT-6) to the cytolytic effects of cocultured activated macrophages indicates that there is no consistent relationship between the release of intracellular 59Fe and 51Cr. Thus, perturbation of intracellular iron pools did not appear to be an obligatory step on the pathway to cytolysis. Further evidence for this dissociation was obtained by employing a specific heteroantiserum reactive with cytolytic molecule(s). This antiserum could block the cytolytic response (51Cr release of cocultured L-929 and EMT-6 targets) but had no effect on the extent of iron release from viable EMT-6 or L-1210 targets. Furthermore, the cytolytic factor itself was incapable of mediating effects on the ETC or in causing release of intracellular iron. Two lines of evidence suggested that effects on the ETC are not linked with loss of intracellular iron. First, the monokine respiration inhibitory factor was incapable of causing release of intracellular iron from target cells in which the mitochondria were strongly suppressed. Second, the kinetics of release of respiration inhibitory factor from endotoxin-triggered Bacillus Calmette-Guérin-activated macrophages indicate a retarded appearance compared to the time at which a factor mediating release of intracellular iron was detectable. Our results strongly suggest that these three distinct cytotoxic reactions are under differential control by the effector cell.
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Vacina BCG/farmacologia , Citotoxicidade Imunológica , Ferro/metabolismo , Ativação de Macrófagos , Macrófagos/imunologia , Mitocôndrias/metabolismo , Neoplasias Experimentais/imunologia , Consumo de Oxigênio , Animais , Cromo/metabolismo , Endotoxinas/farmacologia , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
Screening of myocardial ischemia refers to the use of one or more diagnostic tests for coronary heart disease with a dual objective of appropriateness and promptness. In women, as compared to men, the accuracy of the different tests is worse. Thus, to overcome this sex-related penalty, we must define a diagnosis strategy based on risk stratification, enabling the identification of patients requiring invasive investigations. This review discusses various non-invasive diagnostic tests focusing on a female-specific approach and defines the use of numerous diagnostic tests with respect to both risk stratification and symptoms.
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Doença das Coronárias/diagnóstico , Programas de Rastreamento , Isquemia Miocárdica/diagnóstico , Doença das Coronárias/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Isquemia Miocárdica/epidemiologia , Valor Preditivo dos Testes , Fatores SexuaisRESUMO
The mechanism(s) with which tumor target cells actively resist the lethal lesion induced by murine macrophage cytolytic factory (CF) has been probed by drug-induced sensitization of these cells. We have examined whether drug-induced sensitization is attributable to the action of these drugs on cellular DNA, RNA, or protein synthetic rates. The murine mammary adenocarcinoma cell line EMT-6 pretreated with a dose range of actinomycin-D (.03-3.0 micrograms/ml) for 4 hr was inhibited from 66 to 98% in DNA synthesis rate, from 81 to 93% in RNA synthesis rate, and from 38 to 52% in protein synthesis rate. The maximum sensitization toward lysis by CF was achieved with a drug dose of 1.0 micrograms/ml. The lack of correlation between the drug-induced effects on sensitization and effects on these metabolic rates was evident from the correlation coefficients for the percentage of maximum sensitization of the target toward CF-induced lysis, and the percent of inhibition of DNA, RNA, and protein synthesis. These were 0.11, -0.11, -0.44, respectively. Similarly, target cells treated with a dose range of cycloheximide (0.3-30 micrograms/ml) were inhibited from 81 to 95% in DNA synthesis rate, 68 to 81% in RNA synthesis rate, and 82 to 93% in protein synthesis rate. However, at none of the drug levels employed was significant sensitization of the target cell to CF-induced lysis observed. This was reflected in the correlation coefficients of -0.55, -0.28, and -0.34 for DNA, RNA, and protein synthetic rates, respectively. The essential role of cellular microtubule-dependent events early in the lytic mechanism was demonstrated by exposing colchicone-treated targets to CF. While colchicone could markedly inhibit lysis if introduced before CF, this inhibitory effect was not detected if the drug were withheld for 4 hr after CF exposure. The importance of the repair mechanism(s) early in the cellular response to lesion formation was demonstrated by altering the schedule for CF and actinomycin D administration to the target. If actinomycin D treatment was withheld from the targets for as little as 3 hr following introduction of CF, the lytic mechanism had already bypassed the drug-sensitive steps, manifest in markedly decreased susceptibility to lysis. Collectively, the data show that the ability of the EMT-6 target cells to resist CF-induced lysis does not depend solely on the ability of the cells to synthesize DNA, RNA, or protein.
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Citotoxinas/toxicidade , Macrófagos/fisiologia , Proteínas/toxicidade , Animais , Células Cultivadas , Colchicina/farmacologia , Cicloeximida/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Dactinomicina/farmacologia , Técnicas In Vitro , Ativação de Macrófagos , Camundongos , Monocinas , Ácidos Nucleicos/biossíntese , Biossíntese de ProteínasRESUMO
OBJECTIVES: To describe emergency contraception provision, including the efficacy of the method, in family planning centers in suburban Paris two years after the method became available without a prescription. PATIENTS AND METHODS: A prospective study involving two questionnaires was conducted between September 2001 and July 2002 in 27 family planning centers in the Val-de-Marne region. The first questionnaire was completed at the time emergency contraception was dispensed and the second one upon a follow-up visit. Efficacy was calculated for both perfect use (only one act of unprotected intercourse in the current menstrual cycle, emergency contraception treatment initiated within 72 hours) and typical use (including multiple acts of unprotected intercourse in the cycle and/or treatment initiated after 72 hours). RESULTS: A total of 519 requests for emergency contraception was recorded, resulting in the provision of 518 treatments. The women requesting emergency contraception were young (96% under the age of 25) and cited unprotected intercourse and problems with condom use as the main reasons for the request. Information regarding the outcome of emergency contraception treatment was available in 77% of the cases, and a failure rate of 1.9% was observed with perfect use and 2.7% with typical use. DISCUSSION AND CONCLUSIONS: This prospective study of emergency contraception prescription in family planning centers confirms data on the efficacy and safety of the method observed in similar environments. The failure rate associated with typical use is higher than that observed with perfect use.