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Background: With advances in neonatal care, management of prolonged pain in newborns is a daily concern. In addition to ethical considerations, pain in early life would have long-term effects and consequences. However, its treatment remains inadequate. It was therefore important to develop an experimental model of long-lasting analgesia for neonatal research. Materials and Methods: Experiments were performed in six groups of rats with transdermal fentanyl 0, 3, 12, 50, 100, or 200 µg/kg/h from second postnatal day (P2) until weaning. Assessment of analgesia was carried out at P21, with behavioral scores (ranging from 0 to 3) using a 4% formalin test. Plasma levels of fentanyl were determined by UPLC/TQD at P22. Growth rate was investigated. Results: Fentanyl 100 and 200 µg/kg/h reduced scores of formalin-evoked behavioral pain. They increased time spent in pain score 0 (8 min 55 s and 6 min 34 s versus 23 s in controls) as in low pain scores 1 and 2, and decreased time in the most severe pain score 3 (19 min 56 s and 17 min 39 s versus 44 min 15 s). Fentanylemia increased in a dose-dependent manner from 50 µg/kg/h (2.36 ± 0.64 ng/ml) to 200 µg/kg/h (8.66 ± 1.80 ng/ml). Concerning growth, no difference was observed except weaker growth from P17 to P22 with 200 µg/kg/h. Clinically, we noticed no visible side effect from 3 to 100 µg/kg/h. Concomitantly, 200 µg/kg/h was responsible for ophthalmological side effects with appearance of corneal bilateral clouding in 90% pups. No difference was observed between male and female rats. Conclusion: Altogether, results indicate that transdermal fentanyl 100 µg/kg/h is an efficient therapeutic for long-lasting analgesia in lactating pups. This new model provides a useful tool for protection and welfare, and future opportunity for studying long-term health consequences of sustainable neonatal analgesia.
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UNLABELLED: Introduction: In this prospective multicenter study, we aimed to describe (1) the outcome of pregnancy in the case of previous chronic histiocytic intervillositis (CHI), (2) the immunological findings and associated diseases, (3) the treatments, and (4) the factors associated with pregnancy loss. METHODS: We prospectively included all patients with a prior CHI with ongoing pregnancy between 2011 and 2013. RESULTS: Twenty-four women (age 34±5 years) were included in this study. An autoimmune disease was present in seven (29%) cases. Twenty-one prospective pregnancies were treated. The number of live births was more frequent comparatively to the previous obstetrical issues (16/24 versus 24/76; p=0.003). Most of the pregnancies were treated (88%), whereas only 13% of previous pregnancies were treated (p<0.05). No difference was found with respect to the pregnancy outcome in the different treatment regimens. In univariate analyses, a prior history of intrauterine death and intrauterine growth restriction and the presence of CHI in prospective placentas were associated with failure to have a live birth. DISCUSSION: In this multicenter study, we show the frequency of the associated autoimmune diseases in CHI, as well as the presence of autoantibodies without characterized autoimmune disease. The number of live births increased from 32% to 67% in the treated pregnancies. Despite the treatment intervention, the risk of preterm delivery remained at 30%. Last, we show that the recurrence rate of an adverse pregnancy outcome persisted at 30% despite treatment intervention. CONCLUSION: CHI is associated with high recurrence rate and the combined regimen seems to be necessary, in particular, in the presence of previous intrauterine death.
Assuntos
Aborto Habitual/imunologia , Doenças Autoimunes/complicações , Vilosidades Coriônicas/imunologia , Histiócitos/imunologia , Trabalho de Parto Prematuro/imunologia , Aborto Habitual/tratamento farmacológico , Aborto Habitual/patologia , Adulto , Aspirina/uso terapêutico , Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Movimento Celular , Vilosidades Coriônicas/patologia , Feminino , Morte Fetal/prevenção & controle , Heparina de Baixo Peso Molecular/uso terapêutico , Histiócitos/patologia , Humanos , Hidroxicloroquina/uso terapêutico , Recém-Nascido , Nascido Vivo , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/patologia , Prednisona/uso terapêutico , Gravidez , Estudos Prospectivos , RecidivaRESUMO
INTRODUCTION: On March 30, 2010, Afssaps issued a health alert concerning breast implants brand PIP, after identifying a rupture rate higher than for other manufacturers. This alert asking the recall of all concerned patients with, according to the clinical examination, ultrasound and the desire of the patient, the possibility of explantation. We focus on PIP implanted in Oscar-Lambret center in Lille. MATERIALS AND PATIENTS: A retrospective study on all patients carrying breast prosthesis PIP implanted in the Oscar-Lambret center. We are interested in the rate of patients who chose clinical and ultrasound monotoring, explantation rates, and prosthetic rupture. RESULTS: Thirty-three PIP (in 31 patients) have been implanted in the center between May 2, 2006 and March 9, 2010. The mean age of implants was 15.35 months. We realized eight explants, and found three intracapsular rupture. Two of three rupture were symptomatic. CONCLUSION: The majority of patients chose surveillance. Our short series does not give precise information about their risk of prosthetic failure, a national register should be established. The literature illustrates the low sensitivity of ultrasonography in the diagnosis of intracapsular rupture and the superiority of MRI. In the context of a health alert, could we propose a monitoring tool implant breast MRI in order to minimize the rate of patients carrying a ruptured implant (false negative).