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1.
Lancet ; 403(10433): 1235-1236, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555126
3.
Eur Respir J ; 40(5): 1164-72, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22523367

RESUMO

Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.


Assuntos
Depressores do Apetite/efeitos adversos , Fenfluramina/análogos & derivados , Hipertensão Pulmonar/induzido quimicamente , Adulto , Idoso , Hipertensão Pulmonar Primária Familiar , Feminino , Fenfluramina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
J Heart Valve Dis ; 20(3): 348-50, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21714428

RESUMO

Fenfluramine has been associated with an increased risk of pulmonary hypertension and valvular disease. Benfluorex is a fenfluramine derivative approved for the treatment of metabolic syndrome and type 2 diabetes mellitus. To date, only three isolated clinical cases of valvular disease and two recent case-control studies have been reported in patients exposed to benfluorex. Herein, the case is described of a patient with mitral and aortic valvular disease, with both echocardiographic and histopathological findings, who had been receiving benfluorex for several years, without any other etiology of valvular disease. The case is suggestive of toxic valvular lesions, similar to those observed previously during treatment with fenfluramine, pergolide, and cabergolide.


Assuntos
Valva Aórtica/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenfluramina/análogos & derivados , Doenças das Valvas Cardíacas/induzido quimicamente , Hipolipemiantes/efeitos adversos , Valva Mitral/efeitos dos fármacos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Evolução Fatal , Feminino , Fenfluramina/efeitos adversos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/patologia , Humanos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Ultrassonografia
5.
J Cyst Fibros ; 15(4): 452-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27013383

RESUMO

BACKGROUND: Cascade carrier testing within cystic fibrosis (CF) affected families offers relatives of CF patients the opportunity to know their status regarding the mutation that segregates within their family, and thus to make informed reproductive choices. As an Australian study has recently shown that this test seemed underused, we searched to assess uptake of this test in a European area where CF is common, and to report its public health implications. METHODS: This study relied on 40 CF-affected families from western Brittany, France. Investigations included drawing of family trees and registration of carrier tests performed in those families. RESULTS: Of the 459 relatives eligible for testing, 185 were tested, leading to an adjusted uptake rate of testing of 40.7% (95% CI: [34.1%; 47.3%]). The main predictors for having testing were being female (p=0.031) and having a high prior risk (p<0.001). Planning a pregnancy or expecting a child (reported in at least 38.4% of tested relatives) also appeared critical in choosing to be tested. Overall, carrier testing allowed to reassure more than 1/4 of the relatives and to detect five new 1-in-4 at-risk couples who then requested prenatal diagnosis. CONCLUSIONS: This observational study assesses, for first time in Europe, uptake of CF cascade carrier testing within CF families, which is a critical tool to reassure non-carriers and to detect early new at-risk couples.


Assuntos
Fibrose Cística , Aconselhamento Genético/psicologia , Adulto , Comportamento de Escolha , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Fibrose Cística/psicologia , Saúde da Família , Feminino , França/epidemiologia , Triagem de Portadores Genéticos/métodos , Triagem de Portadores Genéticos/estatística & dados numéricos , Humanos , Masculino , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/psicologia , Diagnóstico Pré-Natal/estatística & dados numéricos , Saúde Reprodutiva , Medição de Risco/métodos
6.
Mol Biotechnol ; 26(3): 193-206, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15004288

RESUMO

Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet. In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo. In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a F508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Fibrose Cística/terapia , Terapia Genética , Mucosa Nasal/citologia , Cátions , Células Cultivadas , Fibrose Cística/patologia , Células Epiteliais/citologia , Células Epiteliais/patologia , Expressão Gênica/genética , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Lipossomos , Mucosa Nasal/patologia , Pólipos Nasais/genética , Pólipos Nasais/patologia , Fosfolipídeos , Proteínas Recombinantes/genética , Transgenes/genética
7.
Trans R Soc Trop Med Hyg ; 97(2): 251-5, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14584386

RESUMO

During a prospective evaluation of malaria prophylaxis in pregnancy in a refugee population on the north-western border of Thailand from 1987 to 1990, an extremely high infant mortality rate (18%) was documented despite good access to health care. Infantile beri-beri was recognized as the main cause of death accounting for 40% of all infant mortality. Thereafter, severe vitamin B1 deficiency in infants was diagnosed and treated promptly. The impact of this was assessed prospectively from 1993 to 1996 in a second cohort study. The case fatality of infantile beri-beri fell from almost 100% to 7%. The overall infant mortality rates declined from 183 to 78 per 1000 live births. Post-neonatal deaths fell by 79% (95% CI 65-87%) while neonatal mortality remained unchanged. Mortality resulting from acute respiratory infections did not change (15 and 11 per 1000, respectively), whereas mortality attributable to beri-beri decreased from 73 to 5 per 1000 (P < 0.0001). Before its recognition approximately 7% of all infants in this population died from infantile beri-beri. This lethal but preventable syndrome may be more common than hitherto recognized, particularly in refugee populations, in this populous region.


Assuntos
Beriberi/mortalidade , Causas de Morte , Estudos de Coortes , Seguimentos , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos , Refugiados , Tailândia/epidemiologia
8.
J Immunother ; 37(3): 170-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24598452

RESUMO

We report herein the results we obtained and the limitations we experienced during the production and use of a bank of Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion EBV-CTLs from each of the 13 selected donors. Subsequently, in a multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1-3 doses of 5 million EBV-CTLs/kg with 1-3 and 0-4 compatibilities for human leukocyte antigen (HLA)-I and HLA-II, respectively. Except for one event of fever after injection, no immediate or delayed toxicity, no graft versus host disease, and no graft rejection attributable to CTL infusion were observed. Three patients presented complete remission and 1 partial remission after treatment. Considering the clinical options currently available, and the constrains associated with CTL preparation and implementation, we conclude that CTL banks should consist of a reasonably small number of cell lines with documented specificities. This objective could be more easily achieved if the few homozygous donors for the most frequent HLA alleles of the targeted population could be made available for such a project.


Assuntos
Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4/imunologia , Imunoterapia Adotiva , Linfoma/terapia , Linfócitos T Citotóxicos/imunologia , Adolescente , Adulto , Idoso , Linhagem Celular , Criança , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Estudos de Viabilidade , Feminino , Humanos , Linfoma/imunologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
9.
Presse Med ; 42(4 Pt 1): 411-8, 2013 Apr.
Artigo em Francês | MEDLINE | ID: mdl-23490638

RESUMO

Since September 1st 2011, the National Bureau for Compensation of Medical Accidents represents a unique portal for out-of-court settlement of litigations concerning the harm caused by benfluorex. In December 2012, its official record is as follows: 7627 patients files have been received, 1378 have been studied, 797 led to a recommendation, and compensation by the drug company Servier has been recommended for 46 cases. The large number of rejections raises a problem which needs to be examined in the light of the available evidence on benfluorex associated heart valve disease. This evidence concerns both the morphological characteristics of the disease and the epidemiology of its association with benfluorex. More than 90% of emergent double valve disease (aortic and mitral regurgitation), of emergent aortic valve regurgitation, and of prevalent grade 2 aortic valve regurgitation are attributable to benfluorex. The proportion of benfluorex-attributable disease is larger than 75% for prevalent double valve disease, or for prevalent aortic valve regurgitation of any grade. This probabilistic information, derived from the available epidemiological studies, needs to be considered as part of the evidence to establish or refute a causal link between benfluorex and valvular disease for a given patient, particularly if the patient has a low grade valvular insufficiency or no morphological anomaly.


Assuntos
Insuficiência da Valva Aórtica/induzido quimicamente , Depressores do Apetite/efeitos adversos , Compensação e Reparação/legislação & jurisprudência , Indústria Farmacêutica/legislação & jurisprudência , Medicamentos Genéricos/efeitos adversos , Prova Pericial/legislação & jurisprudência , Fenfluramina/análogos & derivados , Insuficiência da Valva Mitral/induzido quimicamente , Insuficiência da Valva Aórtica/epidemiologia , Depressores do Apetite/uso terapêutico , Causalidade , Estudos Transversais , Diagnóstico Diferencial , Medicamentos Genéricos/uso terapêutico , Definição da Elegibilidade , Fenfluramina/efeitos adversos , Fenfluramina/uso terapêutico , França , Humanos , Insuficiência da Valva Mitral/epidemiologia , Probabilidade , Fatores de Risco
10.
Presse Med ; 39 Suppl 1: 1S46-50, 2010 Jun.
Artigo em Francês | MEDLINE | ID: mdl-20732618

RESUMO

Despite therapeutic advances, maternal mortality is high in pulmonary arterial hypertension (PAH). PAH treatment may interfere with the proposed method of contraception. Moreover, some treatments (endothelin receptor antagonists, anti-vitamin K) are teratogenic. If pregnancy is strictly not recommended in PAH, few specific contraceptive guidelines are available. The contraceptive method must be discussed on a case by case basis with the patient, the reference team for PAH, and the gynecology department.The advantages of the intrauterine device (IUD) with progesterone (reliability, simplicity, compliance, few contraindications and interactions, possibility of use in the nulliparous patient, reimbursement by the healthcare system) make it a good contraceptive choice in these circumstances. Therapeutic abortion is a situation of contraceptive failure, it must always be performed in hospitals. It must lead to effective contraceptive advice.


Assuntos
Aborto Terapêutico , Anticoncepção , Hipertensão Pulmonar/prevenção & controle , Complicações na Gravidez/prevenção & controle , Aborto Terapêutico/métodos , Anticoncepção/métodos , Serviços de Planejamento Familiar , Feminino , Idade Gestacional , Humanos , Hipertensão Pulmonar/mortalidade , Mortalidade Materna , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Gravidez , Complicações na Gravidez/mortalidade , Esterilização Reprodutiva/métodos
11.
PLoS One ; 5(4): e10128, 2010 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-20405030

RESUMO

BACKGROUND: Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. METHODS: We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. RESULTS: Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. CONCLUSION: The use of benfluorex is associated with unexplained mitral regurgitation.


Assuntos
Fenfluramina/análogos & derivados , Doenças das Valvas Cardíacas/induzido quimicamente , Hipolipemiantes/efeitos adversos , Idoso , Estudos de Casos e Controles , Feminino , Fenfluramina/efeitos adversos , Doenças das Valvas Cardíacas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/induzido quimicamente , Insuficiência da Valva Mitral/etiologia , Razão de Chances , Estudos Retrospectivos , Método Simples-Cego
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