Search PubMed⌕ Search

Biomedical subjects

F Audibert

Publications and source records attributed to F Audibert.

At least 73 records · Page 4Linked to original sources

Protection of ruminants by Pasteurella haemolytica A1 capsular polysaccharide vaccines containing muramyl dipeptide analogs.

The capsular polysaccharide (CP) of Pasteurella haemolytica serotype A1 is a poor immunogen for the prevention of pneumonic pasteurellosis of ruminants. To improve CP immunogenicity, vaccines were prepared with 1.0 mg CP dose-1 with and without the synthetic adjuvant, muramyl dipeptide (MDP; range 0.2-1.0 mg) or a lipophilic derivative, MDP-sn-glyceryl-dipalmitoyl (MDP-GDP; range 0.1-1.0 mg). The optimum effective concentration of adjuvant was first determined in lambs and calves and then the efficacy of CP +0.5 mg MDP and CP +1.0 mg MDP-GDP was compared with that of two commercial vaccines in calves. After immunization with CP, antibody titers in lambs and calves were typical of that seen with polysaccharide immunogens and characterized by an early IgM response followed by later IgG1 and IgG2 responses. CP + MDP or MDP-GDP vaccines induced significantly higher IgM, IgG1, and IgG2 titers. After transtracheal challenge of immunity with P. haemolytica serotype A1, extensive pulmonary consolidation containing P. haemolytica (10(6)-10(8) c.f.u. g-1) was seen in all lambs and calves vaccinated with CP alone and was not significantly different (P < 0.05) from the consolidation and concentrations of organisms in nonvaccinated challenge controls. In lambs, vaccines containing 1.0 mg CP +0.05 mg MDP or MDP-GDP significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. In calves, vaccines containing 0.2 mg MDP, 0.5 mg MDP, or 1.0 mg MDP-GDP also significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. Vaccines containing CP +0.5 mg MDP and CP +1.0 mg MDP-GDP induced high titer bactericidal antibodies by 7 days and were more efficacious than two commercial vaccines. Potentiation of CP with MDP or MDP-GDP has great promise in furthering the potential of CP as a vaccine immunogen for the prevention of pneumonic pasteurellosis.

Acetylmuramyl-Alanyl-Isoglutamine↗

Vaccination of patas monkeys experimentally infected with Schistosoma haematobium using a recombinant glutathione S-transferase cloned from S. mansoni.

The capacity of a recombinant glutathione S-transferase from Schistosoma mansoni (rSm28GST) to vaccinate primates (Erythrocebus patas) against a heterologous infection with Schistosoma haematobium has been tested. Two injections of the purified molecule with Muramyl-Di-Peptide (MDP) as adjuvant resulted in a high level antibody response in the five immunized animals and in a significant reduction in worm fecundity compared to the controls which received adjuvant alone. Mean levels of daily egg excretion in urine an faeces were reduced by respectively 55% and 74% although perfusion revealed that worm burdens were similar in both groups. The protective effect was long lasting since it was maintained up to the end of the experiment, 42 weeks after infection. Hatching rates and the numbers of intra-uterine eggs were also significantly affected by the vaccination. Tissue eggs were also drastically diminished in the urogenital system (-80%) but the reduction was not statistically significant. One animal was not protected by the immunization. There was a good correlation between parasitological data and the intensity of bladder lesions assessed by microscopic examination. Polypoid formations together with an intense exudation of the lamina propria were frequently seen in the controls but rarely in the vaccinated group where formation of scar tissue was predominant. These results underline the vaccine potential of the recombinant Sm28GST as a possible valuable prophylactic tool for the control of egg-induced pathology and transmission of African schistosomes.

Animals↗

[Preliminary study of the use of fetal pulse oximetry during labor].

OBJECTIVE: To assess continuous monitoring of fetal blood oxygen staturation (SpO2) during labour using a fetal pulse oxymeter. STUDY DESIGN: Preliminary results obtained with the Nellcor N-400 fetal pulse oxymeter at the Maternité Port-Royal-Baudelocque between November 1992 and November 1993 in cases of abnormal fetal heart rate are presented. We analyzed: the correlation between SpO2 during labour and cord vein pH as well as Apgar score, the correlation between changes in SpO2, expressed as a desaturation index, and cord vein pH as well as Apgar score. The negative predictive value of oxymetry was assessed. RESULTS: We found a significant positive correlation between the last SpO2 measurement during labour and umbilical vein pH as well as 1 minute Apgar score. We observed a highly significant correlation between the index of desaturation and cord vein pH as well as 1 minute Apgar score. No neonatal pH below 7.20 was observed when SpO2 was > or = 40% during labour. The negative predictive value of oxymetry was 100% in this short series of patients. CONCLUSION: If these results were confirmed in a larger series of patients, a normal SpO2 value during labour could be reassuring in case of abnormal fetal heart rate.

Apgar Score↗

Therapeutic strategy in tubal infertility.

The foregoing description of various methodologies reveals how rich and evolutive the possibilities are for treating tubal disease with a rational approach. Different solutions are possible.

Catheterization↗

Fetal pulse oximetry: correlation between changes in oxygen saturation and neonatal outcome. Preliminary report on 39 cases.

Arterial oxygen saturation of the fetus during labour (SPO2) measured with a fetal pulse oximeter was compared to the neonatal condition measured by umbilical vein pH and Apgar score. Changes in oxygen saturation (index of desaturation) during the second stage of labour were also compared to neonatal outcome. Fifty-five patients with abnormal fetal heart rate pattern during labour had a continuous monitoring of fetal oxygen saturation using the Nellcor N-400 pulse oximeter. SPO2 measurement during the last 10 min of labour was significantly correlated to umbilical vein pH and to 1-min Apgar score (P = 0.022 and P = 0.025, respectively). A much higher correlation was found between the index of desaturation and umbilical vein pH at birth and with 1-min Apgar score (P = 0.002 and P < 0.001, respectively). When considering the lower value of umbilical vein pH at birth to be 7.20, and the normal value of SPO2 during labour to be > or = 40% (negative test), we observed a 100% negative predictive value of oximetry. If these results are confirmed in a larger series of patients, analysis of the changes in fetal arterial oxygen saturation during labour (index of desaturation) could be a good indicator of the condition of the newborn. A normal SPO2 value during labour could be reassuring in case of abnormal fetal heart rate.

Apgar Score↗

Evidence for a hyperexcitability state of staggerer mutant mice macrophages.

We recently reported an abnormal production of interleukin-1 (IL-1) in peripheral macrophages of several neurological mutant mice that exhibit patterns of neuronal degeneration, especially in the cerebellum. After in vitro activation by lipopolysaccharide acid (LPS), these macrophages hyperexpress IL-1 beta mRNA and hyperproduce IL-1 protein in comparison with +/+ controls. In the present study, focused on the staggerer mutant mice, we investigate if this genetic dysregulation is specific for IL-1 beta or if it reflects a generalized hyperexcitability of these macrophages. The hyperexpression of IL-1 beta mRNA in sg/sg macrophages is present whatever the duration of LPS stimulation, even for periods as short as 15 min, although it reaches a maximum after 4 h of stimulation. The hyperinducibility of sg/sg macrophages is observed even when very low doses of LPS are used (0.01 microgram/ml) and reaches its maximum for 5 micrograms/ml LPS. Synthetic molecules (muramyl dipeptides), such as N-acetylmuramyl-L-alanyl-D-isoglutamine or murabutide, known as macrophage activators, are also efficient in revealing the cytokine hyperexpression in sg/sg macrophages. In addition, hyperexpression of two other cytokines, i.e., tumor necrosis factor-alpha and IL-1 alpha mRNAs, is also detected in LPS-stimulated macrophages of mutant mice. Finally, the effect of an inhibitor of protein synthesis, cycloheximide, is similar in +/+ and sg/sg macrophages. As a whole, these data lead us to conclude that the sg/sg macrophages are in a state of general hyperexcitability when compared with +/+ ones.

Acetylmuramyl-Alanyl-Isoglutamine↗

[The use of LHRH analogs in ovulation induction].

The use of LH-RH agonists is appropriate for the stimulation of ovulation. In contrast, in the case of induction of ovulation in a patient with deficient ovulation, suppression of influences of the hypothalamo-pituitary axis does not modify the pathological condition responsible for the ovulatory anomaly.

Clinical Protocols↗

Therapeutic strategies in tubal infertility with distal pathology.

Since 1980, various treatments have been proposed for patients suffering from distal tubal infertility. Difficult choices between surgical (microsurgery/laparoscopy) treatments and in-vitro fertilization (IVF) still confront many workers. In this study, we evaluated the cumulative results of both therapeutic methods for this group of patients. From 1979 to 1990, 266 patients with distal tubal infertility were operated in our programme (group M: microsurgery, n = 211; group L: laparoscopy, n = 55). In group M, pathological findings were hydrosalpinges (n = 135) and incomplete distal tubal occlusion, (n = 76) and in group L hydrosalpinges (n = 31) and incomplete distal tubal occlusion (n = 24). After differing time intervals, IVF was proposed for these patients when no pregnancy occurred. The results were as follows: in group M, 35.5% intra-uterine pregnancy (IUP) and 6.6% ectopic pregnancy (EP) after fimbrioplasties versus 28.1% IUP and 11.9% EP after salpingostomy; in group L, 16.6% IUP and 4.2% EP after fimbrioplasty versus 12.9% IUP and 6.5% EP after salpingostomy. Following IVF, 55.7% of patients in group M and 14.5% in group L became pregnant. The cumulative results including both treatment techniques (surgery and IVF) show an average of 70% and 65% pregnancy rates in groups M and L respectively. The best results after surgery and throughout IVF were obtained during the first year. It is concluded that a short delay after surgery, averaging 6 months to 1 year, before involving patients in IVF, is very important.

Adult↗

[Intra-conjugal immunotherapy and the pathology of reproduction. Experiences at the Center for the Treatment of Sterility, Montpellier-Nîmes].

81 patients who had consulted for infertility, of whom 26 had recurrent spontaneous abortions (RSA), 28 unexplained infertility (UI), and 27 with difficulties for implantation following in vitro fertilization (IVF) were tested by a cross-match for the presence of the partner's lymphocyte antibodies. When the result was negative, leucocyte transfusions were carried out (200 million of the partner's lymphocytes in 3 successive injections at intervals of one month). Positive antipaternal cytotoxic antibodies were found in 81% of cases. There was, however, no benefit in groups of unexplained infertility or implantation difficulties. In the RSA group there was a 50% recurrence of spontaneous abortions.

Abortion, Habitual↗

Polyvalent synthetic vaccines: relationship between T epitopes and immunogenicity.

Three different synthetic polyvalent vaccines have been constructed by conjugating four synthetic peptides without any carrier protein. The peptides were copy fragments of two bacterial antigens (Streptococcus pyogenes M protein and diphtheria toxin), two parasitic antigens (circumsporozoite protein of Plasmodium falciparum and Plasmodium knowlesi), and one viral antigen (hepatitis B surface antigen). Outbred guinea-pigs immunized with polyvalent vaccine containing streptococcal, diphtheric, P. knowlesi and hepatitis peptides raised high specific antibody response against the four specificities. Individual T cell analysis demonstrated that hepatitis peptide bears T dominant epitope. A similar immune response was obtained with a second polyvalent vaccine where the P. knowlesi peptide had been replaced by the P. falciparum peptide. In both experiments the malarial peptides behave like pure B epitopes. Prediction of immunodominant helper T-cell antigenic sites were performed with the five peptides using computer algorithm. Hepatitis and diphtheric peptides were selected whereas the streptococcal peptide was rejected although it can experimentally contain a T epitope. To confirm this result animals were immunized with a third polyvalent vaccine which does not contain the hepatitis peptide. No T cell proliferation or antipeptide antibodies were detected. These results demonstrate that the cooperative immune response requires a certain degree of antigenic complexity for the induction of antibody response.

Amino Acid Sequence↗

Obstetrical results after embryonic reductions performed on 34 multiple pregnancies.

Thirty-four women with multiple pregnancies (three or more fetuses) underwent embryonic reduction in order to reduce abortions, premature births or fetal growth-retardation by obtention of twins. Four early abortions occurred. Thirty pregnancies reached term and out of 60 fetuses, 58 infants were born alive. Fetal death in utero of one twin occurred in two pregnancies. The mean term until delivery was 36 +/- 2.8 weeks gestation and the prematurity rate was 51.7%. Of 55 neonates, 25 were underweight within the 10th percentile and 10 out of 55 neonates were underweight below the 3rd percentile. There were three deaths in the early neonatal period. The rate of perinatal mortality was 8.3%. Fifty-four children are currently healthy and one child has a mild axial hypotonia. A reduction in prematurity was observed with a gain of 2 weeks on reported data concerning triplet pregnancies. The rate of low-birth-weight infants was high, 63.5% being underweight at birth.

Abortion, Incomplete↗

Production and enhanced anti-tumor activity of tumor necrosis factor in mice treated with cyclophosphamide.

We demonstrated recently that the production of tumor necrosis factor (TNF) is induced in normal mice and in the immunosuppressed nude mouse model by the administration of muramyl dipeptide (MDP) derivatives followed by endotoxin (lipopolysaccharide). In the present study, the ability of this treatment to induce the production of TNF in mice receiving cyclophosphamide (CY) was examined. Two days following treatment with high-dose CY (250 mg/kg), mice exhibited leukocytopenia and drastically reduced splenic weight. However, these animals remained capable of producing TNF, albeit at lower levels, when treated with MDP derivatives and lipopolysaccharide (LPS), particularly when the lipophilic analogue MDP-dipalmitoyl glycerol (GDP) was utilized. TNF was also induced by the administration of MDP-GDP and LPS to Meth A sarcoma-bearing mice treated with this dose of CY. Furthermore, in all animals receiving this combination therapy, sarcoma necrosis and complete regression were obtained without any sign of tumor regrowth. A dose of 100 mg/kg CY was not effective for inhibiting tumor regrowth under the same experimental conditions. These results demonstrated that the anti-tumor activity of endogenously induced TNF is potentiated by combined therapy with a high dose of CY.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Hormone therapy in the 40-year-old woman].

Hormone replacement therapy is frequently prescribed in 40-year old women because of the hormonal changes which start to occur at this age. A progestogen-only treatment is often prescribed to restore the oestrogen/progestogen balance. This treatment alone can be sufficient on the therapeutic level as well as on the contraceptive level. However, in order to minimize the risks of such a treatment, a non-androgenic derivative must be chosen. There are no contra-indications for oral contraceptives in women who are over 40 years old on condition that the risk factors are not cumulated. Here also, it is advisable to use the lowest possible dose of steroids which has an adequate contraceptive action and enables a good cycle control. As for oestrogens, the minimum ethinyloestradiol dose must be sought. For the progesterone dose, a non-androgenic derivative should be chosen. The GnRH agonists may have some indications, but their exact place is yet to be defined.

Adult↗

Results of IVF attempts in patients with unexplained infertility.

From January 1986 to July 1987, 143 patients with unexplained infertility (UI) following 217 IVF attempts were studied and randomly assigned for statistical analysis to be compared with 434 tubal infertility (TI) patients undergoing 748 IVF attempts. The age of patients, previous pregnancy history and stimulation protocols were identical in both groups. In comparison with tubal patients, IVF attempts on the UI group were characterized by the same rates of cycle failure, mean number of oocytes retrieved per cycle, a lower fertilization rate (45.7% UI/59.8% TI) (P less than 0.01) and no difference in cleavage and nidation rates. However, a decrease in the pregnancy rate/attempt (13.8% UI/19.5% TI) tended towards a significant value (P = 0.06). Although the semen parameters were found to be in the normal range during the previous fertility screening in both groups, the incidence of at least one abnormality (count less than 20 X 10(6)/ml, and/or total motility less than 30% and/or abnormal forms greater than 75%) on the day of insemination was found to be significantly higher in UI (20%) than in TI (11%) patients. Moreover, 25% of UI patients did not fertilize any oocytes inseminated, whatever the number of oocytes retrieved. This rate of failed fertilization was significantly lower (9%) in tubal patients. The oestrogen response profiles were similar in both groups, analyzed according to the stimulation protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Buserelin↗

Construction of immunogens for synthetic malaria vaccines.

The immunogenicity of a peptide consisting of eight repeats of the tetrapeptide sequence NANP (Asn-Ala-Asn-Pro) contained in the circumsporozoite protein of Plasmodium falciparum was investigated in mice under different modes of presentation. This peptide was able to produce biologically active antibodies when administered with adjuvant and linked to a protein carrier. However, a (NANP) peptide polymerized by carbodiimide was found to be immunogenic in the absence of protein carrier in H-2b mice. In contrast, the (NANP)8 peptide polymerized by glutaraldehyde was not immunogenic in the same strain. Furthermore, the efficacy of murabutide in saline, as an immunological adjuvant, was compared to the efficacy of Freund's complete adjuvant.

Amino Acid Sequence↗