[Decision-making in termination of pregnancy: a French perspective]. / Décision d'interruption médicale de grossesse : le point de vue des soignants français.

OBJECTIVE: To evaluate the caregivers' opinions regarding decision-making in termination of pregnancy (TOP) for fetal anomaly. MATERIAL AND METHODS: Questionnaire survey using a semi-structured survey based on visual analogue scales, sent to all multidisciplinary centres for prenatal diagnosis in France. Answers were received from 26 centres nation-wide. RESULTS: Response rate was 39% (213 responses received over 550 questionnaires sent). Fifty-five percent of respondents were women, 90% physicians, 7,5% midwives. A vast majority (69.8%) believes that their own convictions play a bigger role in decision in real practice than in their ideal. The major decisional factors in decision-making for TOP are: the long-term prognosis of the anomaly, a specialized opinion on its curability, the quality of the information given to the future parents, their expressed opinion, the existence of a multidisciplinary decision, the ability of the future parents to understand the medical data, the obtention of a medical consensus, the proof level of the medical information. For only 55% of the respondents, the current legal framework is adequate to manage the situations that result from prenatal diagnostic practices today. The question of late third-trimester TOP raises ethical debate: over a third (37%) see no ethical difference between TOP and withdrawal of care during the neonatal period; the majority (48% versus 43%) feel that ethically speaking a neonate and a foetus at 39 weeks gestational age (GA) should not be treated differently; 37% of the respondents feel that current practice is likely to lead to eugenism. DISCUSSION AND CONCLUSION: As far as TOP is concerned, the huge discrepancies in responses from the professionals highlight the ongoing ethical debate, especially concerning the concept of informed choice in TOP, which we believe should be entirely revisited.

[Study of treatment adherence by patients living with HIV in 2009 at the outpatient care and treatment center of Brazzaville, Congo]. / Observance thérapeutique des personnes vivant avec le VIH en 2009 au centre de traitement ambulatoire de Brazzaville, Congo.

OBJECTIVES: The purpose of this study was to evaluate treatment adherence and its determinants in patients living with HIV followed up at the outpatient care and treatment center in Brazzaville, Congo. METHODS: This cross-sectional study included patients who attended the center from July to October 2009. Adherence was evaluated using a self-administered questionnaire, 5 distinct measurement tools, and global adherence index. Correlations between patient characteristics and adherence data were analyzed. RESULTS: A total of 214 patients were enrolled in the study. Mean patient age was 42 years. The female-to-male ratio was 2. There were 6 children. Most patients (92.5%) were receiving a first-line antiretroviral regimen; it consisted of a combination of zidovudine, lamivudine and nevirapine in 53.3% of cases. Adherence was estimated at 55.4-86.9% depending on the measurement tool. The global adherence index was significantly higher in patients who achieved their pre-defined life project (OR 4.33, p = 0.04) and in those who spoke lingala (OR 3.99, p = 0.01). After 6 months of antiretroviral therapy, mean weight gain was 4.8 kg; mean increase in CD4 was 104/mm3 (262 versus 158); and viral load was undetectable in 89.4% of patients. CONCLUSION: This study in Brazzaville (Congo) confirms that antiretroviral treatment adherence is satisfactory in sub-Saharan Africa. Adherence was mainly correlated with structural factors, e.g. language and life project, and with the patient friendliness of the regime. Most patients had favourable responses based on clinical, immunological, and virological criteria.

[Ten years of commitment to persons living with HIV-AIDS: evaluation of the management in three ambulatory treatment centers of the French Red Cross in Africa]. / Dix ans d'engagement auprès des personnes vivant avec le VIH-sida : évaluation de la prise en charge dans trois centres de traitement ambulatoire de la Croix-Rouge française en Afrique.

The French Red Cross (FRC) has developed a strategy for the follow-up of people living with HIV-AIDS in Africa by setting-up and managing healthcare centers specialized in the management of HIV infection. Nearly one hundred and seventy thousand patients have had access to care in fifteen Ambulatory Treatment Centers (ATCs). For the ten years anniversary of the FRC's AIDS programs, we present the results of the evaluation of three ATCs in Africa. These results which show a low mortality rate in the patients on antiretroviral therapy and a very low rate of second line patients (1.5%) confirm the efficiency of the management of people living with HIV in the ATCs and generally of the AIDS programs of the FRC. However, the mortality remains high in patients who have a CD4+ cell count of less than 50/mm3 when antiretrovirals (ARVs) initiation. Services and care dispensed in the ATCs and particularly the antiretroviral therapy have demonstrated their feasibility and efficiency. In ten years, the challenge of the management of HIV has changed. Today, there is a need to integrate additional actions in the area of the supply of primary healthcare, of training and of motivation of the care providers. In addition, the follow-up/evaluation of the patient management programs remains useful to determine the impact and long-term efficacy of ARVs in resource-limited countries.

[Drug supply for HIV patients in day care centre in Republic of Congo: the French Red Cross experience]. / Problématique du médicament dans les centres de traitement ambulatoire de la Croix-Rouge Française au Congo.

The commitment of the French Red Cross Society to fight against HIV-AIDS in Africa is based on day care centres (DCC) set up and operated within public hospitals, for instance in Brazzaville and Pointe-Noire in Republic of Congo. These outpatient facilities offer global care including supply of medicines and antiretroviral therapies. The regular supply of medicines, laboratory and medicals materials necessary for the follow-up of the patient is the key of the quality of these structures and their durability. The French Red Cross guarantees this supply chain in countries where no secure pharmaceutical purchasing centre exists, as for exemple in Republic of Congo.

Outcome of a school screening programme for carriers of haemoglobin disease.

OBJECTIVES: To assess the impact of a screening programme for haemoglobinopathies which was organised from 1978 to 1985 in high secondary schools of the Marseille region. METHODS: Several variables that reflected the influence of this preventive programme on the uptake of prenatal diagnosis were investigated. To evaluate the partner's uptake for the testing, a letter was sent, together with an anonymous questionnaire, to all the haemoglobin carriers detected in this programme. To evaluate the number of prenatal diagnoses, the charts of all couples from the Marseille area who underwent genetic counselling for haemoglobinopathies were compiled. The number of affected children born between 1980 to 2000 was recorded, and the cases in which one of the parents had previously been screened at school were noted. RESULTS: Half of the carriers replied to the questionnaire: 86% knew that they have to test their partner. Six carrier couples were identified, four asked for genetic counselling and requested eight prenatal diagnoses, two couples did not request genetic counselling and have had two affected children. CONCLUSIONS: Despite the time lapse between screening, informing, and pregnancy (mean 15 years), the information was well conserved and resulted in testing of the partner. The screening programme was effective in motivating requests for prenatal diagnosis.

[Glucose-6-phosphate dehydrogenase et neonatal jaundice]. / Déficit en glucose-6-phosphate déshydrogénase et ictère néonatal.

OBJECTIVE: Since 1986, quantification of G6PD activity has been a routine test for all babies born at the public maternity hospitals of Marseilles. The objective of our study was to determine the prevalence of G6PD deficiency in the population tested and to evaluate the relative risk of neonatal jaundice in newborns with G6PD deficiency. METHODS: Neonatal screening is performed on cord blood by spectrophotometric measurements of G6PD activity. A group of 7779 newborns was studied retrospectively. The occurrence of neonatal jaundice was evaluated in 85 children with G6PD deficiency and compared to 85 children with normal G6PD activity. RESULTS: The incidence of G6PD deficiency in male newborns was found to be 2.1%. The relative risk for neonatal jaundice in the G6PD deficient population compared to the non-deficient population is estimated to be 2.6. CONCLUSION: Neonatal jaundice with pathological hyperbilirubinemia develops more frequently in cases of G6PD deficiency. The early characterization of G6PD activity provides an etiological diagnosis for neonatal jaundice, as well as the opportunity to give the newborn's family information concerning hemolytic crisis prevention.

A first molecular approach towards CGG repeat expansion in FMR1 gene in systemic lupus erythematosus and in Sjögren's syndrome: a preliminary report.

Co-occurrent autoimmune disease and fragile X syndrome has been reported in the literature and we have therefore studied the expansion of Cytosine-Guanine-Guanine (CGG) repeat in FMR1 gene in a series of females with autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome, with PCR and Southern blot methods. The average length of trinucleotide repeat was not increased in these female patients as compared with controls. These preliminary data on a short series of patients suggest a possible absence of trinucleotide repeat expansion abnormality associated with autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome.

Prenatal detection of a 17p11.2 duplication resulting from a rare recombination event and novel PCR-based strategy for molecular identification of Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease, type 1A (CMT1A) is caused in most cases by a 1.5 Mb duplication on chromosome 17p11.2 arising after unequal crossing-over between repeated sequences called CMT1A-REPs, flanking the 1.5 Mb unit. A 3.2 kb recombination hot spot has been defined, resulting in a junction fragment between EcoRI (distal CMT1A-REP) and SacI (proximal CMT1A-REP). This was further reduced to a 1.7kb EcoRI-NsiI fragment, and recently to a 731 bp hot spot region within this fragment. We describe the CMT1A-REPs-based PCR method used to identify CMT1A duplications and report on a family case in which a 29-year-old pregnant woman requested prenatal diagnosis for two successive pregnancies because her husband was affected with CMT1A. Our method enabled us to characterise the duplication in both foetuses and demonstrate that it arose from a rare recombination event taking place outside the 1.7 kb region. Since our approach is simple and enables the entire set of duplications occurring after recombination in the enlarged 3.2kb region including the hot spot to be detected, we suggest it might be considered for use in primary screening for pre- and postnatal diagnosis of CMT1A.

[The ethical question of the embryo]. / La question éthique de l'embryon.

The possible use of embryonic stem cells for therapeutic purposes raises once more the ethical question concerning the position of the embryo in relation to medical needs. Since this technology treats the embryo as a raw material, the debate must incorporate a semantic clarification, in order to identify the conceptual ambiguities that exist between popular thought, science, anthropology and the religious and philosophical convictions of the individual. The problem is knowing whether the end always justifies the means and whether the future may be sacrificed to the present.

Molecular basis of haemoglobinopathies and G6PD deficiency in the Comorian population.

INTRODUCTION: The Comoro archipelago is characterised by a high prevalence of red cell genetic disorders such as G6PD deficiency and haemoglobinopathies, being a region endemic for malaria. Over the last 15 years, the city of Marseilles in France has become the main destination for Comorian immigrants. This Comorian community includes patients with sickle cell disease, sickle cell/beta-thalassaemia trait, thalassaemias and G6PD deficiency. MATERIALS AND METHODS: Allele frequencies for haemoglobin S, beta-thalassaemia and G6PD deficiency were determined from neonatal and prenatal screenings of the Comorian community. Haemoglobin fractions were detected by isoelectrofocalisation, and the quantitation of HbS, HbA, HbA(2) and HbF was performed by cation exchange high performance liquid chromatography. The molecular study involved 31 alleles carrying the betaS mutation (Cd 6 [A-->T]), six beta-thalassaemic alleles and 17 G6PD-deficient alleles, selected from a group of carriers or affected subjects. RESULTS: Allele frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait and 9.5% for G6PD deficiency. Molecular analysis had revealed that the African alleles are predominant, being present in almost all the subjects studied. Mediterranean alleles were found for all the beta-thalassaemia mutations and for three G6PD chromosomes out of 17. CONCLUSION: These data are consistent with the mixed Arab and African origin of the population of the Comoro Islands, and are of clinical interest in prenatal and newborn screening plans.

Characterization of a new polymorphism, IVS-I-108 (T-->C), and a new beta-thalassemia mutation, -27 (A-->T), discovered in the course of a prenatal diagnosis.

We report two new substitutions, IVS-I-108 (T-->C) and -27 (A-->T), identified in a couple at risk for beta-thalassemia. One is of Iranian origin and presents with two mutations: a new substitution of T-->C at nucleotide IVS-I-108, which is a silent polymorphism, and a previously described beta-thalassemia mutation at nucleotide -28 (A-->C). The other is from the island of Corsica, the only place in France where beta-thalassemia is endemic. He presents a new substitution of A-->T at nucleotide -27 in the TATA box, which was also found in several members of his family with the beta-thalassemia trait. The fetus was found to have inherited both these novel mutations.

Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling.

Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling.

Phenotype-genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patients.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the absence of a maternal contribution to chromosome 15q11-q13. There are four classes of AS according to molecular or cytogenetic status: maternal microdeletion of 15q11-q13 (approximately 70% of AS patients); uniparental disomy (UPD); defects in a putative imprinting centre (IM); the fourth includes 20-30% of AS individuals with biparental inheritance and a normal pattern of allelic methylation in 15q11-q13. Mutations of UBE3A have recently been identified as causing AS in the latter group. Few studies have investigated the phenotypic differences between these classes. We compared 20 non-deletion to 20 age-matched deletion patients and found significant phenotypic differences between the two groups. The more severe phenotype in the deletion group may suggest a contiguous gene syndrome.