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Biomedical subjects

F Peyron

Publications and source records attributed to F Peyron.

At least 73 records · Page 4Linked to original sources

Effects of 2',3'-dideoxyinosine on Toxoplasma gondii cysts in mice.

The activity against Toxoplasma gondii of 2',3' dideoxyinosine (ddI), an anti-human immunodeficiency virus drug, was examined in an in vitro and in vivo study. Cell cultures infected with a strain known to cause chronic infections were used to show the dose-dependent effect of this drug compared with spiramycin and sulfadiazine. When a dose of 4 microg/ml was used, no infected THP-1 cells or parasites were found after 60 h of incubation. An electron-microscopic study confirmed that after 12 h at 1 microg/ml, the few parasites observed were severely altered. The treatment of chronically infected mice 3 months postinfection showed that a 30-day treatment with 2 mg of ddI/ml induced a significant reduction in the number of T. gondii cysts in the cerebral tissue. These cysts were not viable, as confirmed by immunofluorescence and reinfection experiments. These experiments suggest a possible role for ddI in the treatment of toxoplasmosis, and this possibility deserves further investigation.

Animals↗

Evaluation of a flow cytofluorometric method for rapid determination of amphotericin B susceptibility of yeast isolates.

A rapid-flow cytofluorometric susceptibility test for in vitro amphotericin B testing of yeasts was evaluated and compared to the National Committee for Clinical Laboratory Standards (NCCLS) M27-T reference broth macrodilution method. The flow cytofluorometric method is based on the detection of decreased green fluorescence intensity of cells stained with DiOC5(3), a membrane potential-sensitive cationic dye, after drug treatment. Testing was performed on 134 clinical isolates (Candida spp. and Torulopsis glabrata). From the dose-response curve obtained for each isolate, three endpoints were calculated by computer analysis (the concentrations at which the fluorescence intensity was reduced by 50, 80, and 90%, i.e., 50% inhibitory concentration [IC50], IC80, and IC90, respectively). A regression analysis correlating these endpoints with the M27-T MICs showed that the best agreement was obtained with IC80. The flow cytofluorometric method showed good reproducibility with control strains. These initial results suggest that the flow cytofluorometric method is a valid alternative to the NCCLS reference method.

Amphotericin B↗

[Immunocompromised travelers].

More and more immunocompromised people travel abroad especially in tropical countries where infectious risks are high. Before leaving, these subjects must consult their general practitioner who will determine their fitness in function of type of immunodeficiency, travel destination, availability of medical care at the destination, and possibility of medical evacuation. Counseling should also be provided concerning the precautions necessary to avoid the hazards of exposure to fecal material, venereal disease, insect bites, and sun. Antimalarial drug prophylaxis is the same as for uncompromised subjects. Advising immunocompromised subjects about vaccinations is difficult since there is no consensus on the subject. Administration of inert vaccines is usually recommended but their effectiveness is often diminished and harmful effects have been observed in HIV-infected subjects. Administration of live vaccines is always contraindicated in severely immunocompromised subjects but some live vaccines can be used in moderately immunocompromised subjects. The guidelines for vaccination differ depending on the underlying cause of immunodeficiency: congenital defects, cancer, hemopathy, treatment with immunosuppressors or corticosteroids (transplant patients and patients with systemic disease), HIV-infection, or spleen dysfunction. If there is a high risk of contracting a disease for which vaccination is contraindicated, drug prophylaxis or administration of immunoglobulins can be an alternative. If not, travel should either be postponed or the destination should be changed.

Counseling↗

Analysis of the antibody response in humans with a new inactivated hepatitis A vaccine.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

Adolescent↗

Identification of human IgG autoantibodies specific for IL-10.

Since autoantibodies to IL-1alpha, interferon-alpha (IFN-alpha) and IL-6 have been described, this study concentrated on the search for autoantibodies to hIL-10 using an assay based on the precipitation of 125I-hIL-10 autoantibody complexes using Protein G-Sepharose. Among 1860 tested sera, only seven were found to specifically precipitate IL-10, thus indicating the rare occurrence of such autoantibodies. Four of those seven anti-IL-10 autoantibody sera were specific for hIL-10, two recognized both human and viral IL-10, while the last one recognized human, viral and murine IL-10, thus suggesting the existence of at least three different epitopic specificities. The purification of anti-IL-10 autoantibody from one serum demonstrated the existence of a single (IgG1, lambda) autoantibody that neutralized IL-10 biological activity. Thus, autoantibodies to IL-10 may represent natural antagonists to IL-10.

Antibody Specificity↗

Transcription of myelin basic protein promoted by regulatory elements in the proximal 5' sequence requires myelinogenesis.

Myelination in the central nervous system requires synthesis by oligodendrocytes of enormous amounts of lipids and proteins for incorporation in the developing myelin membranes. To approach the regulatory events coordinating the transcriptional activation of the genes that encode myelin proteins, we examined control of the myelin basic protein (MBP) locus. MBP plays a major role in myelin compaction. During development, MBP is already expressed in mature non-myelinating oligodendrocytes. Here we show that, in transgenic animals in which the E. coli lacZ reporter gene is under the control of increasingly large portions (256, 1900 and 3200 bp) of the MBP promoter, 5' of the initiation of transcription site, reporter gene expression was initiated after myelin formation had started. This delayed expression of the transgene compared to MBP, strongly suggests that premyelinating expression is dependent on regulatory elements located outside of the 3200 bp sequence studied, while expression occurring at the time of myelin formation is dependent on the proximal promoter sequence.

Animals↗

[Decision analysis of congenital toxoplasmosis in the absence of exact knowledge of the treatment benefits and secondary effects].

Decision analysis seemed the appropriate method to bring out the interest of toxoplasmosis serology in children born from mothers who seroconverted during pregnancy. In particular it provides the possibility to choose between IgA serology, recently introduced in hospital practice, and IgM serology that is the reference test. We study a series of 96 children suspected of having congenital toxoplasmosis who were followed up until the age of one. A decision analysis is thereafter conducted by synthesizing data about clinical efficacy with the RBNCN ratio that is the net benefit of treating an affected person divided by the net cost of treating an unaffected person; these costs and benefits are clinical. The effectiveness of the treatment (sulphonamides in most cases) was not quantified. Therefore, we used the fact that the RBNCN ratio is equal to the number of healthy children likely to be treated unnecessarily in order not to leave untreated a contaminated child. Although data available in the literature and data from our study still remain insufficient to draw a final conclusion, IgA antibodies are significantly more sensitive than IgM antibodies (p < 0.01). Conversely, IgA antibodies are significantly less specific than IgM antibodies (p < 0.001). The sensitivity analysis shows that the IgA test is preferred to the IgM test if the mother is contaminated during the third trimester. On the other hand, for low prevalences, as observed in the first trimester, the IgM serology is more useful.

Anti-Infective Agents↗

[Halofantrine: for new rules of prescription].

Halofantrine is an antimalarial drug widely prescribed for chloroquine-resistant strains of Plasmodium falciparum. It has been recognized to cause serious deleterious effects which have dampened early enthusiasm for this compound. Basically, the adverse effects involve lengthening of the QTc interval, torsade de pointes and induction of late ventricular potentials. These side effects are related to the quinidine-like effect of the drug which has a chemical structure similar to quinine and quinidinic drugs. More recently, severe haemolytic accidents have been reported suggesting an autoimmunization mechanism. These side effects imply new rules for prescription and more prudent use of halofantrine, especially for prophylaxic therapy against malarial attacks in travellers.

Antimalarials↗

Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression.

Products of the PLP gene, proteolipid protein and its isoform DM-20, are the most abundant proteins in CNS myelin, and are markers of the oligodendrocyte, the myelin-forming cell in the CNS. The DM-20 transcript has previously been reported to be expressed in newborn oligodendrocyte progenitor cells and during embryonic development. We have therefore used a DM-20 cRNA probe to follow, by in situ hybridization, the oligodendrocyte lineage during embryonic development. DM-20-expressing cells were first detected at E9.5 in the ventricular germinal layer of the laterobasal plate of the diencephalon. At E14.5, DM-20+ cells had largely disappeared from the diencephalic ventricular germinal layer and had colonized the ventral mantle layer at the posterior part of the basal diencephalon. Between E17.5 and P1, the number of DM-20+ cells increased and progressively invaded the major white matter tracts. In the hindbrain, DM-20+ cells appeared at E12.5 in the caudal part of the rhombencephalon, and at E14.5 all along the ventral spinal cord. Between E14.5 and P1, DM-20+ cells progressively colonized, first ventrally then dorsally, all the spinal cord and more extensively the white matter tracts. At E14.5, a large gap separated, rostrally, the medullary columns from the mantle layer cells in the prosencephalon, suggesting that oligodendrocytes in the mid- and forebrain originate from a different pool of precursors than in the rhombencephalon and the spinal cord. Together, these observations suggest that expression of the DM-20 transcript is an early marker of commitment to the oligodendrocyte lineage, and that oligodendrocyte precursors originate in a ventrally restricted region.

Animals↗

[Diagnosis of malaria in Africa using the Parasight F test].

The purpose of this study which was carried out in the Central African Republic between January and February 1994 was to evaluate the effectiveness of the Parasight F test in diagnosing malaria in the indigenous population. Comparison of test results in a series of 62 malaria suspects who had been residing in the country for more than 10 years and 67 malaria suspects who had been living abroad showed significant differences but the overall value of the test was satisfactory. The test was specific for Plasmodium falciparum. In-field trials showed that the test could be used effectively by paramedics and community health care workers. Basing the decision to perform antimalarial treatment in semi-immune subjects with suspected malarial solely on the results of the Parasight F test would have led to unwarranted non-treatment in 10% of cases. Presumptive treatment of malaria is justified. The Parasight F test allows identification of Plasmodium falciparum and adaptation of therapy if required by the spread of chemoresistance.

Blood Proteins↗

[A medical evaluation mission to the mountain tribes on the high plateaus of central Vietnam].

The Vietnamity Association and Association for Aid to Ethnic Minorities in Vietnam is sponsoring a health plan for the mountain tribes living on the high plateaux of central Vietnam in the Kontum region. Within this framework a team of doctors undertook a medical evaluation mission in several villages in the region. The purpose of this report is to describe observation made in the subjects who consulted on a voluntary basis without active screening. A total of 618 subjects including 400 children were examined. Fifty Blood smears and 12 direct stool examinations were performed. Otorhinolaryngologic, respiratory, parasitic, and digestive disorders due mainly to poor hygiene of the skin and teeth were the most frequent reasons for consultation. Management of malaria and tuberculosis are urgent problems. Several realistic proposals are made based on the diseases observed, the populations involved, and the facilities at the disposal of the commissioning associations.

Adult↗

ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection.

The ParaSight(R)-F test is a qualitative diagnostic test of Plasmodium falciparum, which is based on the detection by a monoclonal antibody of a species-specific soluble antigen (histidine-rich protein (HRP-II)) in whole blood and which can be performed without special equipment. A visual reading is given by a polyclonal antibody coupled with dye-loaded liposomes; when positive, a pink line appears. The test has been compared with microscopic examination of thin blood smears and with Quantitative Buffy Coat malaria test (QBC(R) in a single-blind study. A total of 358 patients who had returned to France from malarial areas and consulted their doctor with symptoms or for a routine examination were enrolled in the study; 33 of them were found to have a falciparum malaria infection by the diagnostic test. On the day of consultation, the specificity of the ParaSight(R)-F test was 99% and its sensitivity 94%. The follow-up of infected patients after treatment showed that the test became negative later than the other reference tests. There was no correlation between antigen persistence and the intensity of the ParaSight(R)-F signal or circulating parasitaemia. No cross-reaction was noted for seven malaria cases due to other Plasmodium species. The test was performed quickly (10 tests in 20 minutes), was easy to read, and required minimal space. For cases of imported malaria, the test's specificity and low threshold for detection could make it a valuable adjunct test. However, in its present form, it cannot replace microscopic techniques which are species-specific and quantitative. In endemic areas, the test seems to be very promising by its results and ease of use according to published field studies.

Adolescent↗

[Congenital toxoplasmosis, evaluation of the prevention policy].

OBJECTIVES: This study was performed to assess the effect of a prevention programme against congenital toxoplasmosis conducted as part of the French health policy developed in the Rhône department. METHODS: A descriptive epidemiological survey was conducted in 1991 including 806 post-partum women who were hospitalized in 22 maternities in the Rhône department. RESULTS: Forty-nine percent of the women had negative serology tests. French legislation requiring detecting non-immunized women at diagnosis of pregnancy was applied satisfactorily by the attending physicians. Inversely, women at risk were insufficiently informed: only 17% of the women at risk were aware of the three main routes of contamination; 63% believed vaccination is possible and 11% though they had been vaccinated. Deficient information was probably the cause of poor compliance to preventive measures as observed in this sample: only 17% of the serologically negative women stated they had applied anti-toxoplasmosis prophylaxy measures. CONCLUSION: Women at risk must be informed to convince them to modify their behaviour during pregnancy. The role of the attending physician and biologist is of major importance.

Adult↗