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Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 19 recordsLinked to original sources
PubMed2005

Occurrence of Pneumocystis jiroveci pneumonia after allogeneic stem cell transplantation: a 6-year retrospective study.

Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.

CD4 Lymphocyte Count↗
PubMed2004

Polymorphisms and intronic structures in the 18S subunit ribosomal RNA gene of the fungi Scytalidium dimidiatum and Scytalidium hyalinum. Evidence of an IC1 intron with an His-Cys endonuclease gene.

The fungi Scytalidium dimidiatum (Nattrassia mangiferae synanamorph) and Scytalidium hyalinum are mainly encountered in (sub)tropical areas as plant pathogens and agents of human dermatomycosis. Because the classification and differentiation of these two species is unclear, we studied 22 S. dimidiatum and 15 S. hyalinum isolates in order to identify potential species-specific insertions and polymorphisms in the 18S subunit ribosomal gene. The presence of an IE intron in S. dimidiatum, together with a single polymorphism (A in S. dimidiatum, G in S. hyalinum) in the coding region, allowed us to differentiate these two species in most cases. Moreover, in one S. dimidiatum isolate we found a group IC1 intron containing a putative truncated His-Cys endonuclease gene. This enzyme shows strong similarity to the intronic homing endonuclease of Physarum polycephalum. Based on these results and our previous findings, we propose an evolutionary pathway for 18S rDNA S. dimidiatum insertions, implying independent events.

Ascomycota↗
PubMed2004

Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp.

The synthesis of four new computer-designed fluoroquinolones which have been predicted by QSAR analysis to be active against the protozoa Toxoplasma gondii is described. These compounds are inhibitory in vitro for T. gondii. One of these compounds has a remarkably high activity comparable to that of trovafloxacin. It combines the basic cyclopropyl-quinoline structure of gatifloxacin or moxifloxacin with the C-7 6-amino-3-azabicyclo[3.1.0]hexyl side chain of trovafloxacin. The four compounds are also inhibitory for blood stages of Plasmodium falciparum though at high concentration. These results confirm the potential of quinolones as anti-T. gondii and antimalarial drugs but also show that the QSAR models for T. gondii cannot be reliably extended for screening antimalarial activity.

Animals↗
PubMed2004

[New methodologic approaches in antimalarial molecular research].

The estimated worldwide incidence of Plasmodium falciparum malaria is about 500 million cases a year. In tropical areas, the dramatic increase of resistance to most antimalarial drugs is directly responsible for persistent widespread high endemicity and related morbidity. The search to identify new drug targets and agents is a high priority. However the value of standard pharmacological research methods is greatly diminished by technical problems involving in vitro and in vivo modeling of malaria infection. In recent decades new mathematical tools have been developed to predict drug properties and to estimate biological activity in silico. Various approaches have been proposed based on 2D or 3D descriptions of the chemical structure of the drug and target followed by mathematical and statistical characterization of their interaction. These techniques are now widely used in medicinal chemistry and have proven their efficacy for screening the anti-malarial activity of numerous molecules in large databases and for virtual synthesis. Incorporating new knowledge from the genomic studies of Plasmodium has markedly increased the performance and range of application of these tools for identifying new drug targets against malaria.

Antimalarials↗
PubMed2002

Detection of Microsporidia, cryptosporidia and Giardia in swimming pools: a one-year prospective study.

In order to estimate the rate of microsporidia, cryptosporidia and giardia contamination of swimming pools, sequential samples of water were collected during a one-year period in six different swimming pools in Paris, France. Fourty-eight samples were submitted to filtrations. Eluates were examined for microsporidia using polymerase chain reaction (PCR) and for cryptosporidia and giardia using immunofluorescence staining. One of 48 specimens was positive for microsporidia. Using DNA sequence analysis, unknown microsporidia species were identified, which were close to an insect microsporidia Endoreticulatus schubergi. One sample was positive for cryptosporidia and none were positive for giardia. This study shows a low level of swimming pool water contamination by microsporidia, cryptosporidia or giardia, demonstrating the efficacy of cleaning filtration and disinfection procedures used in French swimming pools.

Animals↗
PubMed2002

[Mycologic surveillance of the environment for preventive invasive aspergillosis. Proposals for standardization of the methodologies and implementation].

A MAJOR RISK: The infection of immunodepressed patients by Aspergillus-type fungi increases morbidity and mortality, particularly in hematology units or during solid organ transplantation. Although present diagnostic means benefit from the progress over the last years, they remain limited and chemoprophylaxis protocols have still not demonstrated significant efficacy. THE NEED FOR RECOMMENDATIONS: Today, the handling of environmental risks is the only strategy that has proved its efficacy and usefulness. On the basis of administrative recommendations and data from the literature, a multicentric and pluri-disciplinary task force, grouping clinicians, microbiologists and hygienists, has assessed different methods and has proposed recommendations for the standardization and optimization of fungal surveillance of the environment.

Air Microbiology↗
PubMed2002

Tinea pedis in European marathon runners.

BACKGROUND: Epidemiological studies suggest that 15% of the population in industrial countries suffer from tinea pedis (athlete's foot) and that persons who do sports are a high-risk population. OBJECTIVE: To investigate the responsibility of dermatophytes in interdigital lesions of the feet in European marathon runners and to identify associated risk factors. SUBJECTS AND METHODS: Runners of the 14th Médoc Marathon (n = 147) were interviewed on risk factors for tinea pedis and underwent physical and mycological examinations. RESULTS: Interdigital lesions of the feet were found in 66 runners (45%). A dermatophyte was isolated in 45 runners (31%), 12 of whom were asymptomatic. Trichophyton interdigitale and T. rubrum accounted for 49% and 35.5%, respectively, of the cases of tinea pedis. Thirty-three (22%) of the 102 runners free of dermatophyte infection had lesions resembling those of tinea pedis. Increasing age and use of communal bathing facilities were predictive of T. rubrum culture. CONCLUSIONS: Marathon runners are at high risk for tinea pedis, but dermatophytes are responsible for only half of the foot lesions found in runners. The existence of asymptomatic carriers calls for prophylactic measures.

Adult↗
PubMed2002

Microplate method for obtaining Leishmania clonal populations.

The various clinical expressions observed in human leishmaniases result from complex host-parasite relationships in which the biodiversity of the parasite is a determining factor. Because Leishmania strains isolated from humans are composed of heterogeneous populations, it is crucial to use clonal lineages for studies on the characterization of these parasites. Presently, techniques used for cloning Leishmania spp. parasites are time-consuming and show poor efficiency. Here, a method developed in 96-well microplates is described, which allows one to rapidly obtain numerous clones of Leishmania in the most versatile and efficient way. The technique may be useful for cloning various protozoa as well as Leishmania spp.

Animals↗
PubMed2002

Application of topological descriptors in QSAR and drug design: history and new trends.

Powerful methodologies for drug design and drug database screening and selection are presently available. Studies relating the structure of molecules to a property or a biological activity by means of statistical tools (QSPR and QSAR studies, respectively) are particularly relevant. An important point for this methodology is the use of good structural descriptors that are representative of the molecular features responsible for the relevant activity. Topological indices (TIs) are two-dimensional descriptors which take into account the internal atomic arrangement of compounds, and which encode in numerical form information about molecular size, shape, branching, presence of heteroatoms and multiple bonds. The usefulness of TIs in QSPR and QSAR studies has been extensively demonstrated, and they have also been used as a measure of structural similarity or diversity by their application to databases virtually generated by computer. In this article we will briefly review the history of TIs, their advantages and limitations with respect to other descriptors, and their possibilities in drug design and database selection. These applications rely on new computational techniques such as virtual combinatorial synthesis, virtual computational screening or inverse QSAR.

Algorithms↗
PubMed2001

Immune recovery under highly active antiretroviral therapy is associated with restoration of lymphocyte proliferation and interferon-gamma production in the presence of Toxoplasma gondii antigens.

The in vitro lymphocyte proliferative response (LPR) and interferon (IFN)-gamma production in the presence of Toxoplasma antigen were evaluated in 97 human immunodeficiency virus (HIV)-1-infected patients with CD4 cell counts of <100 cells/microL (group 1), currently >300 cells/microL but previously <100 cells/microL (group 2), or always >300 cells/microL (group 3) and in 28 non-HIV-infected blood donors (group 4), all seropositive to Toxoplasma. In group 2, 81% of patients had a positive LPR, versus 20% in group 1 (P<10(-3)). IFN-gamma production was greater in group 2 than in group 1 (922 vs. 0 Deltapg/mL; P=10(-4)). Multivariate analysis found a significant association between a positive LPR to Toxoplasma antigen and a CD4 count >300 cells/microL (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.3-50.2) and anti-Toxoplasma IgG titer >150 IU/mL (OR, 5; 95% CI, 1.6-15.2). Immune reconstitution under highly active antiretroviral therapy was associated with a restoration of immune responses against Toxoplasma.

Adult↗
PubMed2001

[Microsporidiosis].

OPPORTUNISTIC PARASITES: Microsporidia are primitive eukaryotic parasites widespread in a large range of animal species. These opportunistic parasites can cause infections in humans, mainly in immunocompromised patients. PATHOGENIC SPECIES: Four microsporidian species are important in human pathology, Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon cuniculi and Encephalitozoon hellem. LABORATORY DIAGNOSIS: A difficult task, laboratory diagnosis is based on direct microscope visualization of the parasite. Special stains not used in routine practice are required for identifying spores. TREATMENT: Species differentiation, achieved with the polymerase chain reaction technique, is necessary to select the appropriate treatment. Treatment of the most common microsporidiosis (caused by Enterocytozoon bieneusi) with fumagillin is currently under assessment in an ANRS clinical trial.

Humans↗
PubMed2001

Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study.

BACKGROUND: Invasive aspergillosis (IA) is a well recognized, life-threatening infection in neutropenic patients and stem cell transplantation recipients. Early diagnosis is important to achieve the best outcome for these patients; however, definite proof often is difficult to obtain due to counterindicated invasive procedures. METHODS: This study evaluated the specificity and sensitivity of the detection of galactomannan (GM) for the diagnostic and prediction of IA in 347 children from the Pediatric Hematology Service and 450 patients from the Bone Marrow Transplantation Unit at the Hôpital Saint-Louis in Paris. Serial screening of Aspergillus GM circulating antigen was evaluated using a double sandwich ELISA assay (Platelia Aspergillus) on 6209 sera. Among the patients studied, 53 presented with confirmed IA (n = 27 patients) or probable IA (n = 26 patients). RESULTS: Antigen was detected on at least two sequential sera in 48 of 53 patients, with a sensitivity of 90.6%. GM antigenemia was detected before the onset of radiologic signs in 31 of 48 patients (64.6%), with a mean of -8.4 days, and before clinical symptoms in 18 of 48 patients (39.6%), with a mean of -6.9 days. In patients without IA, 44 of 744 had positive antigenemia, resulting in a specificity of 94%. False positive results could not be related to the presence of a concurrent mucositis. CONCLUSIONS: This large, prospective study allowed the authors to define better the conditions for the use of GM immunocapture ELISA in surveying patients who are at high risk for IA. The presence of antigen has a good diagnostic value mainly when there is an increase in the titer on two consecutive sera samples. A repeated negative result is a strong argument against the diagnosis of IA; however, an awareness of the possibility of unexplained false negative results is important.

Adolescent↗
PubMed2001

Assessment of Leishmania promastigote growth in vitro by means of nucleoside hydrolase activity determination.

Nucleoside hydrolases (NH) are involved in the purine salvage pathway of protozoan cells for the biosynthesis of nucleic acids. We developed a simple and reliable microassay based on N-ribohydrolase dosage using 4-nitrophenyl-beta-D-ribofuranoside (NPR) substrate for the quantification of Leishmania infantum. The free promastigote stage of L. infantum contains high amounts of NH capable of cleaving NPR, but the parasitic amastigote does not. The method allows reliable quantification of viable parasites over a wide range of concentrations (5 x 10(4) 2 x 10(8) parasites ml(-1)) in a single assay. No difference in NH activity was observed between various strains at equivalent concentrations and growth curves determined with NH dosage were similar to optical counts. Samples can be stored at -20 degrees C for weeks before use in this unique assay without significant loss of NH activity. The method is particularly simple and versatile and proves well adapted for the determination of growth characteristics and drug screening studies of L. infantum promastigotes in vitro.

Animals↗
PubMed2001

Comparative performance of impactor air samplers for quantification of fungal contamination.

The aim of this study was to assess the performance of different impactor air samplers for fungal spore collection in the hospital environment. Four recent impactor air samplers were selected: Samplair (AES, Combourg, France); Air Test Omega (LCB, France); Air Samplair Mas-100 (Merck, France); and BioImpactor 100-08 (AES). They were compared with one another at three different hospital sites with varying levels of contaminated air. No significant difference in the efficiency of spore recovery was found between Air Test Omega, Mas-100 and BioImpactor, whereas Samplair was significantly less efficient. BioImpactor was then selected to represent the three superior impactors and was compared with the single-stage Andersen disposable sampler and the Collectron MD8 air sampler (Sartorius, France) and the High Flow Air Sample (BioTest, France), which are based on filtration and centrifugation methods, respectively. No significant difference was observed in terms of spore recovery. On the basis of their performance, unit sampling cost, autonomy and simplicity of use, we conclude that Air Test Omega, Air Samplair Mas-100 and BioImpactor 100-08 are suitable for routine indoor evaluation of fungal contamination of air in hospitals.

Air Microbiology↗
PubMed2001

Relationship between environmental fungal contamination and the incidence of invasive aspergillosis in haematology patients.

Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Spore inhalation is the usual route of Aspergillus infection, suggesting a determining role of environmental contamination by spores in the epidemiology of IA. We prospectively examined the relationship between environmental contamination by Aspergillus and other fungal species and the incidence of invasive nosocomial aspergillosis (INA) in a bone marrow transplantation unit and two haematology wards. During a four-year period, levels of air and surface fungal contamination were determined bi-monthly in patients' rooms (some equipped with HEPA filters and LAF systems), and various common sites in each ward (corridors, nursing stations, etc.). Results were compared to the incidence of INA. A total of 3100 air and 9800 surface samples were collected, and 79 cases of IA were diagnosed, of which 64 were probably or possibly INA. Patterns of fungal contamination were comparable in the three wards, with a gradient ranging from high levels in common sites to a virtual absence in rooms equipped with HEPA filters and LAF systems. Using a regression model, a significant relationship was found between the incidence of INA and the degree of fungal contamination of air and surfaces in conventional patient rooms (not equipped with HEPA) and common sites. This study shows that in a non-epidemic setting, there is a significant relationship between environmental fungal contamination in haematology wards and the incidence of INA. Our findings underline the importance of environmental surveillance and strict application of preventive measures.

Aspergillosis↗
PubMed2001

Immunoblot profile as predictor of toxoplasmic encephalitis in patients infected with human immunodeficiency virus.

In order to define more accurately human immunodeficiency virus-infected patients at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot profile, in addition to AIDS stage, a CD4(+) cell count <50/mm(3), and an antibody titer > or =150 IU/ml, in patients with CD4 cell counts <200/mm(3) and seropositive for T. gondii. Baseline serum samples from 152 patients included in the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo) were used. The IgG immunoblot profile was determined using a Toxoplasma lysate and read using the Kodak Digital Science 1D image analysis software. Mean follow-up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative probability of TE varied according to the type and number of anti-T. gondii IgG bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa. In a Cox model adjusted for age, gender, Centers for Disease Control and Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG 25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001) was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T. gondii antibody titer and CD4 cell count were not predictive of TE. Thus, detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when primary prophylaxis for TE should be started or discontinued, especially in the era of highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗