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Biomedical subjects

F Audibert

Publications and source records attributed to F Audibert.

136 records · Page 8Linked to original sources

[Alternatives to amniocentesis for maternal age].

Screening strategies of Down's syndrome should be re-evaluated. Amniocentesis for advanced maternal age has been proposed in the 70's because no other screening test was available. Maternal serum screening and first trimester nuchal translucency are now well validated, including in women over 38. The sequential and independent use of different screening tests leads to a dramatic increase of the false positive rate and thus of iatrogenic fetal losses. Maternal age remains the major risk factor for chromosomal anomalies, but it should be included in risk calculation strategies (ideally combining serum screening and nuchal translucency), and not taken as an isolated information. These screening strategies require strict quality control and audit, which is currently better achieved with serum screening than ultrasound screening. A complete information about Down's syndrome screening strategies should be given to women, regardless of their age, and their personal choice should be respected. For women of advanced maternal age, a policy of selective rather than routine amniocentesis is likely to reduce the risk of iatrogenic fetal loss and yet to allow for a reasonable sensitivity.

Adult↗

Efficiency of ultrasound and biochemical markers for Down's syndrome risk screening. A prospective study.

OBJECTIVE: To evaluate the sequential combination of ultrasound screening for fetal aneuploidy at 11-14 weeks with maternal biochemistry at 12-14 and 15-18 weeks of gestation. METHODS: A prospective study including 1,656 women, with a singleton pregnancy booked before 13 weeks of gestation. Nuchal translucency (NT) thickness was measured by transabdominal ultrasound examination. alpha-Fetoprotein, free betahCG and hCG were measured by immunoradiometric (12-14 weeks) or immunometric (15-18 weeks) assays. Derived risks were then calculated. Cutoff risks were chosen first arbitrarily at 1/250 and then adjusted for a 5% false-positive rate. RESULTS: Seven fetal aneuploidies were diagnosed, including 5 Down's syndromes, 1 trisomy 18 and 1 triploidy. Three Down's syndromes had concordant high risk with the 3 screenings. One was at low risk with NT, and another was at low risk by maternal serum screening, but sequential combination of screenings led to a 100% detection rate with cutoffs of 1/240, 1/160 and 1/250 for NT, first- and second-trimester biochemistry, respectively (i.e. for a cutoff adjusted for a 5% false-positive rate). CONCLUSION: This preliminary study suggests a benefit in combining maternal age-related risk together with NT and biochemical markers in the first or the second trimester. The algorithm combining these risks needs to be established in a wide population.

Adolescent↗

Is routine amniocentesis for advanced maternal age still indicated?

OBJECTIVE: To evaluate a policy of selective rather than routine use of amniocentesis for advanced maternal age. METHOD: A consecutive series of 359 pregnant women aged 38-47 underwent nuchal translucency measurement (NTM) at 10-14 weeks, maternal serum screening (MSS) by alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) at 15-17 weeks, and second trimester ultrasound at 21-23 weeks. Women with NTM <3 mm, MSS-derived risk <1/250, and a normal second trimester sonography were considered at low risk and were suggested not to have an amniocentesis. RESULTS: Either the NTM or MSS test was positive in 130 women; 105 (81%) of them elected to have an amniocentesis, versus 122 (53%) of 229 in whom both tests were negative (p < 0.001). Nineteen (5%) of 359 patients had NTM > or =3 mm; all 7 cases of Down's syndrome were in this group; 122 (34%) of 359 patients had a MSS-derived risk > or =1/250; 6 of the 7 cases of Down's syndrome were in this group: Ten patients had an abnormal second trimester ultrasound, 1 of which had trisomy 18. Of the 219 patients with MSS-derived risk <1/250, a NTM <3 mm, and a normal second trimester ultrasound, none had a baby with a chromosomal abnormality (95% confidence interval: 0-1.4%). CONCLUSION: Amniocentesis may be offered on a selective rather than routine basis in women over 38, based upon the results of noninvasive screening tests.

Adult↗

Role of the proline residues on the immunogenic properties of a P. falciparum circumsporozoite peptide linked to a carrier protein.

The circumsporozoite (CS) protein of P. falciparum contains an immunodominant epitope, NADP, that is repeated 37 times in the native molecule. The presence of proline in the coat proteins of the Plasmodium parasite at various developmental stages and strains is a frequent occurrence. In this study we evaluate the influence of substitution of proline residues by glycine on the immunogenic behavior of two tandemly repeated peptides linked via glutaraldehyde to a protein carrier: The (NANP)4 P. falciparum circumsporozoite peptide and its glycine-substitute analog, (NANG)4. The results obtained show that the (NANP)4 induces antibodies which recognize the peptide free in solution, bound on a solid phase, and linked to a carrier protein. It has been previously reported that such antibodies recognize the antigenic sites of the peptide in the native protein on the surface of the sporozoite. Antibodies raised against (NANG)4 in the same experimental conditions as (NANP)4, cannot recognize the peptide free in solution or bound to the solid phase. However, these antibodies can react with the peptide when it is linked to a protein carrier. The coupling of a glycine-containing analog to a carrier results in a significant shift in its conformation, allowing it to be recognized by the antibodies.

Animals↗

[Effects of mycobacterial hydrosoluble adjuvants on the induction and prevention of experimental autoimmune uveo-retinitis in guinea-pigs (author's transl)].

Experimental uveo-retinitis (EAU) was induced in guinea-pigs after one systemic injection of retinal extract mixed with the hydrosoluble adjuvants (WSA) or muramyl dipeptide (MDP). In this model, 50 micrograms of WSA in incomplete Freund's adjuvant had the same adjuvanticity as 50 micrograms mycobacteria. The MDP, tested at low doses (2 to 100 micrograms), was less effective. But MDP, even in aqueous solution without oil, stimulated the induction of a tolerance to the retinal antigen: with addition of MDP, only one injection of the antigenic preparation was sufficient to delay and clearly reduce the development of EAU induced by the antigen plus complete Freund's adjuvant two and a half months later.

Adjuvants, Immunologic↗

[Autoimmune aspermatogenetic orchiepididymitis in guinea pigs induced by water-soluble adjuvants].

Use was made of water-soluble adjuvant fractions with homologous sperm, sperm extract or sperm autoantigens to induce autoimmune aspermatogenic orchiepididymitis (AIAO) in guinea-pigs. Guinea-pigs were injected with soluble sperm extract or sperm purified autoantigen S emulsified in incomplete Freund adjvant (IFA) together with two synthetic watersoluble adjuvants, Mur-Nac-L-Ala-D-isoGlu et Mur-Nac-L-Ala-acide D-isoGlu. These animals developed lesions of AIAO, delayed hypersensitivity reactions and specific anti-spermatozoa antibodies. These lesions and reactions were comparable to the ones induced in a control group treated with the same spermatozoa extract or autoantigen S in complet Freund adjuvants. No lesion was observed in the absence of IFA, Other guinea-pigs received a mixture of spermatoza or purified sperm autoantigens, S, P, T. and of polyadenylicpolyuridylic complex either in saline or emulsified in IFA. The recipients of sperm or autoantigen T mixed with Poly A:U, with ou without IFA, displayed lsdions of AIAO; autoantigen S and Poly A:U in IFA, provoked AIAO but did not do it in the absenceof IFA.

Adjuvants, Immunologic↗

Relationship between chemical structure and adjuvant activity of some synthetic analogues of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP).

Synthetic N-acetyl-muramyl-L-alanyl-D-isoglutamine, hereafter referred to as muramyl dipeptide or MDP, represents the minimal structure which can replace mycobacterial cells in Freund's complete adjuvant. This synthetic adjuvant can also enhance the humoral antibody response when administered to mice with an antigen in water by various routes including the oral route. The present paper reports some new results concerning the relationship between the structure and the adjuvant activity of MDP. Synthetic analogues of MDP were tested either in a water-in-oil emulsion in guinea-pigs or in saline in mice. The chemical modifications concerned essentially the D-glutamyl residue. The results obtained confirm the importance of maintaining the intact structure of the D-Glu residue and show that adjuvant activity can be abolished by certain modifications at the level of both carboxyl functions.

Adjuvants, Immunologic↗