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1.
Eur J Obstet Gynecol Reprod Biol ; 299: 248-252, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38905968

RESUMO

BACKGROUND: The global prevalence of caesarean section as a delivery method is increasing worldwide. However, there is notable divergence among countries in their national guidelines regarding the optimal technique for blunt expansion hysterotomy of the low transverse uterine incision during caesarean section (cephalad-caudad or transverse). AIM: To compare the risk of severe postpartum haemorrhage (PPH) between cephalad-caudad and transverse blunt expansion hysterotomy during caesarean section. METHODS: This prospective comparative observational study was conducted in a university maternity hospital. All women who gave birth to one infant by caesarean section after 30 weeks of gestation between November 2020 and November 2021 were included in this study. The exclusion criteria were a coagulation disorder, the presence of placenta previa, multiple pregnancies, or enlargement of the hysterotomy with scissors. The choice between cephalad-caudad or transverse blunt expansion of the low transverse hysterotomy was left to the surgeon's discretion. The primary outcome measure was severe PPH, defined as estimated blood loss ≥ 1000 ml. Univariate and multivariate analyses were employed to assess the risk of severe PPH associated with the two methods of enlarging the low transverse hysterotomy. RESULTS: The study included 850 women, of whom 404 underwent transverse blunt expansion and 446 underwent cephalad-caudad blunt expansion. The overall incidence of severe PPH was 13.3 %. Univariate analysis revealed no significant difference in the frequency of severe PPH between the cephalad-caudad and transverse blunt expansion groups (13.9 % vs 12.6 %; p = 0.61). However, the use of additional surgical sutures (mainly additional haemostatic stitches) was less common with cephalad-caudad blunt expansion (26.7 % vs 36.9 %; p < 0.05). Multivariate analysis showed no significant difference in risk between the two techniques (odds ratio 1.17, 95 % confidence interval 0.77-1.78). CONCLUSION: No significant difference in the risk of severe PPH was found between cephalad-caudad and transverse blunt expansion of the low transverse hysterotomy during caesarean section.

3.
Gynecol Obstet Fertil Senol ; 51(11-12): 493-510, 2023.
Artigo em Francês | MEDLINE | ID: mdl-37806861

RESUMO

OBJECTIVE: To identify strategies for reducing neonatal and maternal morbidity associated with intrahepatic cholestasis pregnancy (ICP). MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 14 questions (from 12 PICO questions and one definition question outside the PICO format), there was agreement between the working group and the external reviewers on 14 (100%). The level of evidence of the literature was insufficient to provide a recommendation on two questions. ICP is defined by the occurrence of suggestive pruritus (palmoplantar, nocturnal) associated with a total bile acid level>10µmol/L or an alanine transaminase level above 2N after ruling out differential diagnoses. In the absence of suggestive symptoms of a differential diagnosis, it is recommended not to carry out additional biological or ultrasound tests. In women with CIP, ursodeoxycholic acid is recommended to reduce the intensity of maternal pruritus (Strong recommendation. Quality of the evidence moderate) and to decrease the level of total bile acids and alanine transaminases. (Strong recommendation. Quality of the evidence moderate). S-adenosyl-methionine, dexamethasone, guar gum or activated charcoal should not be used to reduce the intensity of maternal pruritus (Strong recommendation. Quality of evidence low), and there is insufficient data to recommend the use of antihistamines (No recommendation. Quality of evidence low). Rifampicin (Weak recommendation. Very low quality of evidence) or plasma exchange (Strong recommendation. Very low quality of evidence) should not be used to reduce maternal pruritus and perinatal morbidity. Serum monitoring of bile acids is recommended to reduce perinatal morbidity and mortality (stillbirth, prematurity) (Low recommendation. Quality of the evidence low). The level of evidence is insufficient to determine whether fetal heart rate or fetal ultrasound monitoring are useful to reduce perinatal morbidity (No recommendation). Birth is recommended when bile acid level is above 99µmol/L from 36 weeks gestation to reduce perinatal morbidity, in particular stillbirth. When bile acid level is above 99µmol/L is below 100µmol/L, women should be informed that induction of labor could be considered 37 and 39 weeks gestation to reduce perinatal morbidity. (Strong recommendation. Quality of evidence low). In postpartum, total bile acids and alanine transaminases level should be checked and normalized before prescribing estrogen-progestin contraception, ideally with a low estrogen dose (risk of recurrence of pruritus and cytolysis) (Low recommendation. Quality of evidence very low). CONCLUSION: Although the quality of evidence regarding ICP gestational cholestasis remains low, there is a strong consensus in France, as shown by our Delphi study, on how to manage women with ICP. The reference first-line treatment is ursodeoxycholic acid.


Assuntos
Colestase Intra-Hepática , Complicações na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Natimorto/epidemiologia , Ácido Ursodesoxicólico/uso terapêutico , Obstetra , Ginecologista , Complicações na Gravidez/terapia , Complicações na Gravidez/tratamento farmacológico , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/terapia , Colestase Intra-Hepática/complicações , Ácidos e Sais Biliares , Estrogênios/uso terapêutico , Prurido/diagnóstico , Prurido/etiologia , Prurido/terapia , Transaminases/uso terapêutico , Alanina/uso terapêutico
4.
Ultrasound Obstet Gynecol ; 56(4): 557-565, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32212388

RESUMO

OBJECTIVE: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. METHODS: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. RESULTS: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9). CONCLUSION: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/epidemiologia , Ultrassonografia Doppler/estatística & dados numéricos , Ultrassonografia Pré-Natal/estatística & dados numéricos , Adulto , Pressão Sanguínea , Pré-Escolar , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , França/epidemiologia , Idade Gestacional , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico por imagem , Incidência , Recém-Nascido , Modelos Logísticos , Transtornos do Neurodesenvolvimento/etiologia , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Fluxo Pulsátil , Fatores de Risco , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/embriologia , Artérias Umbilicais/fisiopatologia
7.
BJOG ; 126(1): 73-82, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30216654

RESUMO

OBJECTIVE: To assess whether planned route of delivery is associated with perinatal and 2-year outcomes for preterm breech singletons. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: France, 2011. SAMPLE: Three hundred and ninety women with breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes. METHODS: Propensity-score analysis. MAIN OUTCOME MEASURES: Survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment. RESULTS: Vaginal and caesarean deliveries were planned in 143 and 247 women, respectively. Neonates with planned vaginal delivery and planned caesarean delivery did not differ in survival (93.0 versus 95.7%, P = 0.14), survival at discharge without severe morbidity (90.4 versus 89.9%, P = 0.85), or survival at 2 years without neurosensory impairment (86.6 versus 91.6%, P = 0.11). After applying propensity scores and assigning inverse probability of treatment weighting, as compared with planned vaginal delivery, planned caesarean delivery was not associated with improved survival (odds ratio, OR 1.31; 95% confidence interval, 95% CI 0.67-2.59), survival without severe morbidity (OR 0.75, 95% CI 0.45-1.27), or survival at 2 years without neurosensory impairment (OR 1.04, 95% CI 0.60-1.80). Results were similar after matching on propensity score. CONCLUSIONS: No association between planned caesarean delivery and improved outcomes for preterm breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes was found. The route of delivery should be discussed with women, balancing neonatal outcomes with the higher risks of maternal morbidity associated with caesarean section performed at low gestational age.


Assuntos
Apresentação Pélvica/epidemiologia , Cesárea , Resultado da Gravidez/epidemiologia , Adulto , Apresentação Pélvica/terapia , Cesárea/efeitos adversos , Cesárea/estatística & dados numéricos , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Feminino , França/epidemiologia , Humanos , Lactente , Lactente Extremamente Prematuro , Vigilância da População , Gravidez , Pontuação de Propensão , Fatores de Risco , Adulto Jovem
8.
Gynecol Obstet Fertil Senol ; 46(12): 1068-1075, 2018 12.
Artigo em Francês | MEDLINE | ID: mdl-30389541

RESUMO

OBJECTIVE: To identify the ideal gestational age at delivery for preterm premature rupture of membranes and modalities of birth. METHOD: To identify studies, research was conducted using Pub-Med, Embase and Cochrane databases. RESULTS: Prolonged latency duration after pPROM does not worsen neonatal prognosis (NP3). Therefore, it is recommended not to deliver before 34 weeks of gestation for patient with uncomplicated preterm rupture of membranes (pPROM) (Grade C). After 34 weeks of gestation, expectant management for pPROM is not associated with neonatal sepsis (NP1) but is associated to intra-uterine infection (NP2). Early delivery is associated with higher risk of respiratory distress syndrome (NP2), higher risk of cesarean section (NP2) and longer duration of NICU hospitalization (NP2). Before 37 weeks of gestation, expectant management is recommended for uncomplicated pPROM (Grade A), even if vaginal group B streptococcus is positive, as long as antibiotics are used at the time of membranes rupture (Professional consensus). Elective cesarean section is reserved for usual obstetrical indications. Oxytocin and prostaglandins are reasonable options for inducing labor (Professional consensus). Data are too scarce to establish recommendation regarding intra-cervical balloons in case of pPROM (Professional consensus). CONCLUSION: Expectant management is recommended for uncomplicated pPROM before 37 weeks of gestation.


Assuntos
Parto Obstétrico/métodos , Ruptura Prematura de Membranas Fetais/terapia , Antibacterianos/administração & dosagem , Cesárea , Feminino , França , Idade Gestacional , Humanos , Recém-Nascido , Infecções/microbiologia , Trabalho de Parto Induzido/métodos , Ocitocina/administração & dosagem , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Nascimento Prematuro , Prognóstico , Prostaglandinas/administração & dosagem , Doenças Uterinas/microbiologia
9.
Gynecol Obstet Fertil Senol ; 46(12): 998-1003, 2018 12.
Artigo em Francês | MEDLINE | ID: mdl-30392986

RESUMO

OBJECTIVE: To determine management of women with preterm premature rupture of membranes (PPROM). METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus). CONCLUSION: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A).


Assuntos
Ruptura Prematura de Membranas Fetais/terapia , Feminino , Morte Fetal , Ruptura Prematura de Membranas Fetais/epidemiologia , França/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Infecções , MEDLINE , Gravidez , Complicações na Gravidez , Resultado da Gravidez , Nascimento Prematuro , Prognóstico , Fatores de Risco
10.
Phys Rev E ; 98(1-1): 012907, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30110837

RESUMO

Using laboratory experiments, we investigate the influence of water and sediment discharges on the morphology of an alluvial fan. In our flume, a single-thread laminar river deposits corundum sand into a conical fan. We record the fan progradation with top-view images and measure its shape using the deformation of a Moiré pattern. The fan remains virtually self-affine as it grows, with a nearly constant slope. We find that, when the sediment discharge is small, the longitudinal slope of the fan remains close to that of a river at the threshold for sediment transport. Consequently the slope depends on the water discharge only. A higher sediment discharge causes the fan's slope to depart from the threshold value. Due to the downstream decrease of the sediment load, this slope gets shallower towards the fan's toe. This mechanism generates a concave fan profile. This suggests that we could infer the sediment flux that feeds a fan based on its proximal slope.

11.
Gynecol Obstet Fertil ; 44(12): 679-684, 2016 Dec.
Artigo em Francês | MEDLINE | ID: mdl-27836521

RESUMO

OBJECTIVE: To evaluate whether the position of preventive cerclage determined by immediate postoperative transvaginal cervical ultrasound is predictive of preterm birth. METHODS: A single-center retrospective study conducted between 1 August 2007 and 31 December 2015 in a maternity type III who included women carrying out for a single pregnancy and who receive a McDonald preventive cerclage. Measurements of internal os-stitch, stitch-external os and the total length of the cervix were performed during immediate postoperative transvaginal cervical ultrasound. The position of the cerclage has been defined by the internal os-stitch/cervical length and stitch-external os/cervical length ratios. Measures were compared according to gestational age at delivery (before and after 32weeks and before and after 37weeks). RESULTS: During the study period, 379 single pregnancies that received a McDonald preventive cerclage were included. The mean gestational age at delivery was 37.6±3.6 SA. The rate of preterm birth before 32weeks was 6.5% (n=25) and before 37weeks was 16.6% (n=63). There was no significant difference in the internal ost-stitch/cervical length ratios and the stitch-external ost/cervical length ratio between women who delivered before and after 32weeks or for those who delivered before and after 37weeks. The areas under the ROC curves for the various parameters studied were all less than or equal to 0.6. CONCLUSIONS: The position of cerclage determined by transvaginal cervical ultrasound in immediate post operative does not seem predictive of the risk of premature birth.


Assuntos
Cerclagem Cervical/métodos , Colo do Útero/diagnóstico por imagem , Idade Gestacional , Nascimento Prematuro/diagnóstico por imagem , Nascimento Prematuro/prevenção & controle , Ultrassonografia Pré-Natal/métodos , Adulto , Colo do Útero/cirurgia , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Incompetência do Colo do Útero/cirurgia
12.
J Gynecol Obstet Biol Reprod (Paris) ; 44(10): 1234-47, 2015 Dec.
Artigo em Francês | MEDLINE | ID: mdl-26527012

RESUMO

OBJECTIVES: To synthetize the available evidence regarding the incidence and risk factors of shoulder dystocia (SD). METHODS: Consultation of the Medline database, and of national guidelines. RESULTS: Shoulder dystocia is defined as a vaginal delivery that requires additional obstetric manoeuvres to deliver the foetus after the head has delivered and gentle traction has failed. With this definition, the incidence of SD in population-based studies is about 0.5-1% of vaginal deliveries. Many risk factors have been described but most associations are not independent, or have not been constantly found. The 2 characteristics consistently found as independent risk factors for SD in the literature are previous SD (incidence of SD of about 10% in parturients with previous SD) and foetal macrosomia. Maternal diabetes and obesity also are associated with a higher risk of SD (2 to 4 folds) but these associations may be completely explained by foetal macrosomia. However, even factors independently and constantly associated with SD do not allow a valid prediction of SD because they are not discriminant; 50 to 70% of SD cases occur in their absence, and the great majority of deliveries when they are present is not associated with SD. CONCLUSION: Shoulder dystocia is defined by the need for additional obstetric manoeuvres to deliver the foetus after the head has delivered and gentle traction has failed, and complicates 0.5-1% of vaginal deliveries. Its main risk factors are previous SD and macrosomia, but they are poorly predictive. SD remains a non-predictable obstetrics emergency. Knowledge of SD risk factors should increase the vigilance of clinicians in at-risk contexts.


Assuntos
Traumatismos do Nascimento/epidemiologia , Parto Obstétrico/estatística & dados numéricos , Distocia/epidemiologia , Ombro , Parto Obstétrico/efeitos adversos , Distocia/terapia , Feminino , Macrossomia Fetal/complicações , Macrossomia Fetal/epidemiologia , Humanos , Incidência , Recém-Nascido , Gravidez , Fatores de Risco
13.
J Gynecol Obstet Biol Reprod (Paris) ; 44(4): 324-40, 2015 Apr.
Artigo em Francês | MEDLINE | ID: mdl-25728782

RESUMO

Calcium channel blockers are widely used as first-line tocolytic, but prescribed off-label for this indication. The primary objective of this review is to evaluate the efficiency and safety of calcium channel blockers compared to placebo and to all tocolytic agents used. This review concerns the randomized trials, comparative studies and meta-analyzes of randomized trials on the subject. Nifedipine is superior to placebo in reducing the risk of delivery within 48 hours (RR=0.3; 95 % CI [0.21-0.43]), but induces more maternal side effects (RR=3.8; 95 % CI [1.02-16.92]). The effectiveness of nifedipine is greater than that of betamimetics to prolong pregnancy beyond 48 hours (OR=1.52; 95 % CI [1.03-2.24]), and up to 34 weeks (OR=1.87; 95 % CI [1.11-3.15]), with a lower incidence of adverse events requiring discontinuation of treatment in case of use of nifedipine (RR=0.22; 95 % CI [0.10-0.48]), but no significant difference in neonatal mortality. Efficacy of nifedipine is similar to that of oxytocin antagonists to prolong pregnancy beyond 48 hours (RR=0.92; 95 % CI [0.37-2.30]), but causes more mild maternal adverse events (RR=2.61, 95 % CI [1.43-4.74]). Nicardipine is not evaluated as nifedipine as a tocolytic treatment. It appears as effective as salbutamol and appears to have fewer maternal side effects than IV salbutamol.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocólise/métodos , Tocolíticos/farmacologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Gravidez , Tocolíticos/efeitos adversos
15.
J Immunol ; 167(11): 6374-81, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11714802

RESUMO

Previous studies based on the use of serum as a source of C have shown that fibrils of beta-amyloid peptides that accumulate in the brain of patients with Alzheimer's disease have the ability to bind C1q and activate the classical C pathway. The objective of the present work was to test the ability of fibrils of peptide Abeta1-42 to trigger direct activation of the C1 complex and to carry out further investigations on the site(s) of C1q involved in the interaction with Abeta1-42. Using C1 reconstituted from purified C1q, C1r, and C1s, it was shown that Abeta1-42 fibrils trigger direct C1 activation both in the absence of C1 inhibitor and at C1 inhibitor:C1 ratios up to 8:0, i.e., under conditions consistent with the physiological context in serum. The truncated peptide Abeta12-42 and the double mutant (D7N, E11Q) of Abeta1-42 did not yield C1 activation, providing further evidence that the C1 binding site of beta-amyloid fibrils is located in the acidic N-terminal 1-11 region of the Abeta1-42 peptide. Binding studies performed using a solid phase assay provided strong evidence that C1q interacts with Abeta1-42 fibrils through its C-terminal globular regions. In contrast to previous studies based on a different experimental design, no significant involvement of the C1q collagen-like domain was detected. These findings were confirmed by additional experiments based on C1 activation and C4 consumption assays. These observations provide direct evidence of the ability of beta-amyloid fibrils to trigger activation of the classical C pathway and further support the hypothesis that C activation may be a component of the pathogenesis of Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/fisiologia , Complemento C1/metabolismo , Via Clássica do Complemento/fisiologia , Fragmentos de Peptídeos/fisiologia , Sequência de Aminoácidos , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/metabolismo , Animais , Asparagina/fisiologia , Ácido Aspártico/fisiologia , Sítios de Ligação/imunologia , Complemento C1q/metabolismo , Ácido Glutâmico/fisiologia , Glutamina/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Estrutura Terciária de Proteína/fisiologia , Ratos
16.
J Immunol ; 162(7): 4088-93, 1999 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10201932

RESUMO

Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors.


Assuntos
Proteínas do Sistema Complemento/fisiologia , HIV-1/imunologia , Modelos Imunológicos , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Linhagem Celular , Complemento C2/deficiência , Complemento C2/fisiologia , Complemento C3/deficiência , Complemento C3/fisiologia , Complemento C4/isolamento & purificação , Complemento C4/fisiologia , Fator H do Complemento/isolamento & purificação , Fator H do Complemento/fisiologia , Fator I do Complemento/isolamento & purificação , Fator I do Complemento/fisiologia , Relação Dose-Resposta Imunológica , Sinergismo Farmacológico , Humanos , Receptores de Complemento 3d/química , Receptores de Complemento 3d/metabolismo
17.
Fundam Appl Toxicol ; 39(2): 120-30, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9344624

RESUMO

It has generally been assumed that the skin contributes only minor amounts to the total uptake of solvent vapors, relative to the respiratory tract. Contrary to this assumption, the widely used glycol ether solvent, 2-butoxyethanol (BE), has been reported to be more effectively absorbed through the skin (75% of the total uptake) than through the lungs of humans (Johanson and Boman, 1991, Br. J. Ind. Med. 48, 788). The possibility that the finger prick blood sampling technique used in the Johanson and Boman study was confounded by locally high concentrations of BE at the site of absorption was suggested using a previously developed PBPK model (Corley et al., 1994, Toxicol. Appl. Pharmacol. 129, 61). The current study was conducted to verify the PBPK analysis and to determine whether or not the skin was the major site for absorption of BE vapor by exposing one arm from each of six human volunteers to 50 ppm 13C2-BE vapor for 2 hr. To evaluate the potential consequences of blood sampling techniques, samples were taken from both the unexposed arm (catheter; during and after exposure) and the exposed arm (finger prick; end of the exposure only) for analysis of both BE and its major metabolite, butoxyacetic acid (BAA). Butoxyacetic acid is responsible for the hemolysis observed in toxicity studies with laboratory animals. Humans, however, are significantly less sensitive to this effect. The concentration of BE in the finger prick blood samples averaged 1500 times higher than the corresponding concentration in venous blood sampled from a catheter installed in the unexposed arm at the end of the exposure. Blood BAA levels were generally within a factor of 4 of each other for the two techniques and, therefore, was considered a better indicator of systemic absorption. Urine was collected for 24 hr and analyzed for the following metabolites found in rat metabolism studies: free and conjugated BE, BAA, ethylene glycol (EG), and glycolic acid (GA), with only BAA detected in the human urine. More importantly, urinary BAA was found to be extensively conjugated ( approximately 67%) with glutamine, confirming recent reports. These results, coupled with PBPK modeling of worst-case exposure scenarios (no clothing, 100% of the body was exposed), demonstrated that no more than 15-27% (low-to-high relative temperatures and humidities), not 75%, of the total uptake of BE could be attributed to the skin of humans during simulated 8-hr exposures to the ACGIH TLV concentration of 25 ppm. Even less of the total uptake was attributed to the skin during simulations of exercise with whole-body exposures (5-9%) or by more realistic exposures of only the arms and head (1-8%). As a result, humans are unlikely to reach hemolytic concentrations of the metabolite BAA in blood following vapor exposures to BE.


Assuntos
Etilenoglicóis/farmacocinética , Glicolatos/metabolismo , Absorção Cutânea , Solventes/farmacocinética , Adulto , Isótopos de Carbono , Etilenoglicóis/química , Etilenoglicóis/metabolismo , Glutamina/urina , Glicolatos/sangue , Glicolatos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Volatilização
18.
Acad Med ; 72(8): 698-701, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9282145

RESUMO

Many medical schools are shifting to a problem-based learning (PBL) curriculum, some without any transition period, others using periods of parallel-track curricula. The authors report on and discuss a third strategy for implementing PBL: using a pilot course as a model to facilitate the transition. After the Université de Montréal Faculty of Medicine chose to switch PBL, one course in the third year of the traditional curriculum was changed to PBL format 11 months before the new curriculum was to start in September 1993. This was done to develop local expertise, to gain confidence, to test the feasibility of the method, to produce a showcase, to assess more accurately the resources required, and to provide a practice ground for the curriculum planners and managers and the faculty-development training team. The authors discuss the planning of the pilot course, the training of the faculty in various aspects of PBL (writing problems, tutoring methods, etc.), the course implementation, and the course evaluation. Overall, the pilot course was well received by both the faculty and the students and provided much beneficial information that assisted the university in its transition to a new PBL curriculum.


Assuntos
Aprendizagem Baseada em Problemas , Desenvolvimento de Programas/métodos , Docentes de Medicina , Modelos Educacionais , Projetos Piloto , Quebeque , Faculdades de Medicina
19.
Anat Rec ; 248(1): 129-36, 1997 05.
Artigo em Inglês | MEDLINE | ID: mdl-9143676

RESUMO

BACKGROUND: The ultrastructure of the vagal and spinal accessory nerves was studied 1) in normal sheep and 2) in sheep in which an experimental crossed-nerve anastomosis had been made by sectioning the supranodose vagal and spinal accessory nerves, then suturing the distal end of the vagal nerve to the distal end of the spinal accessory nerve, and allowing time for regeneration to occur. This study was carried out in order to analyze the modifications liable to occur when this technique is used and to specify the origin and the nature of the fibers that colonize the spinal accessory nerve. METHODS: The study was performed in 4- to 5-month-old-sheep. After the surgical procedure, the animals were housed indoors during 1 year until their sacrifice by fixative perfusion. Then, nerve samples were dissected out, processed for electron microscopy, examined, and systematically photographed. After printing, the diameters of the nerve fibers were determined. RESULTS: In sheep, the ratios of nonmyelinated to myelinated fibers (NF/MF) in the infranodose and supranodose vagal nerve and accessory spinal nerve were 1.21, 1.67, and 3.21, respectively. In both parts of the vagal nerve, the myelinated fibers had a unimodal diameter distribution around a peak of 4 microns; whereas, in the spinal accessory nerve, they were distributed bimodally, and 53% had values of 15-18 microns. After making the above anastomosis, the centrifugal vagal fibers degenerated, and the NF/MF ratios increased in the centripetal infranodose vagal nerve, in the reinnervating supranodose vagal nerve, and in the reinnervated spinal accessory nerve (approximately 1.87, 1.72, and 6.04, respectively). In all of these nerves, the myelinated fibers had a unimodal distribution with a peak at 4 microns, as in the vagal nerve of normal sheep. CONCLUSIONS: These results reveal the large part taken by the nonmyelinated fibers in the nerve fiber population of the vagal nerve and support the vagal origin of the fibers reinnervating the spinal accessory nerve.


Assuntos
Nervo Acessório/cirurgia , Nervo Acessório/ultraestrutura , Ovinos/anatomia & histologia , Nervo Vago/cirurgia , Nervo Vago/ultraestrutura , Nervo Acessório/fisiologia , Anastomose Cirúrgica , Animais , Microscopia Eletrônica , Fibras Nervosas/ultraestrutura , Fibras Nervosas Mielinizadas/ultraestrutura , Regeneração Nervosa , Gânglio Nodoso/fisiologia , Gânglio Nodoso/cirurgia , Gânglio Nodoso/ultraestrutura , Nervo Vago/fisiologia
20.
C R Acad Sci III ; 320(3): 233-44, 1997 Mar.
Artigo em Francês | MEDLINE | ID: mdl-9183442

RESUMO

The crossed nerve anastomosis between the peripheral end of the vagus nerve, cut above the nodose ganglion, and the peripheral end of the accessory nerve has demonstrated the capacity of some vagal afferents to reinnervate, via the accessory nerve stump, certain sternocephalicus muscle fibers in the rabbit. These results add to our understanding of the capacity of these afferents to counter the past-denervational atrophying process that occurs in the reinnervated muscles and to evaluate the changes induced in these muscles during reinnervation. Our work shows that within 3 months, the vagal sensory reinnervation of previously denervated sternocephalicus muscles induces their total weight recovery. This recovery is concomitant on the one hand with the hypertrophy of the four muscle fiber types (I, IIBD, IIC and IIA) identified histochemically in the normal muscles and, on the other, with the appearance of small newly formed myofibers, which are often underlined by characteristic central nuclei. The vagal sensory neurones induce important changes in the percentages and the muscle cross-sectional distribution of the fibers in reinnervated muscles. In these muscles we see also the disappearance of the fast myosin heavy chains MHCIIB and MHCIID, the upholding of the fast MHCIIA percentage and an increase in the slow MHCI isoform.


Assuntos
Músculo Esquelético/inervação , Nervo Vago/cirurgia , Animais , Feminino , Histocitoquímica , Fibras Musculares Esqueléticas/citologia , Músculo Esquelético/química , Miosinas/análise , Miosinas/química , Regeneração Nervosa , Coelhos , Suturas
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