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Biomedical subjects

P Ambroise-Thomas

Publications and source records attributed to P Ambroise-Thomas.

At least 19 recordsLinked to original sources

[Congenital toxoplasmosis: prevention in the pregnant woman and management of the neonate].

The management of a pregnant women or a child infected by Toxoplasma gondii rests on the screening of pregnant women at risk of infection. Treatment is prescribed if an infection occurs. A prenatal diagnosis (detection of T. gondii in amniotic fluid) may be performed, a positive result leading to a reinforcement of the treatment. After birth, the follow-up of the child is needed in order to prevent and detect the sequellae, mainly ocular. For all these steps, the biological methods used to diagnose T. gondii infection are of paramount importance.

Adult↗

Eight-year surveillance of environmental fungal contamination in hospital operating rooms and haematological units.

An eight-year fungal environmental surveillance was carried out in 15 operating theatres and two haematological units. Sampling was performed twice a year in each room, using contact plates for plane surfaces and sterile swabs for grids. From 1992 to 1999, individual rooms in the 17 units were sampled on 1094 occasions and 3822 samples were collected. The percentage of rooms without fungus increased regularly between 1992 and 1999 (41.1% and 74.8%, respectively). The units were classified according to the fungal contamination during the eight years: the operating theatres which required the highest protection (cardiological, thoracic, vascular, hand, orthopaedic and neurosurgery) and the adult haematological unit showed least contamination (71.8% rooms were negative). The most frequent species isolated were Penicillium spp. (28.4%), Cladosporium spp. (15.6%) and Aspergillus spp. (7.6%). Aspergillus fumigatus was rarely isolated (3.7%), and was mainly isolated at the beginning of the study. This study demonstrates that environmental control programmes are effective in reducing environmental mould contamination and could be useful in establishing exposure guidelines, especially by defining an acceptable level of biocontamination in zones at risk.

Aspergillus↗

Tumour necrosis factor alpha receptors: role in the physiopathology of protozoan parasite infections.

Tumour necrosis factor alpha (TNF alpha) is an important cytokine in immune regulation and resistance to various micro-organisms. It provides signals to the target cells through two different receptors: TNFR1 and TNFR2. The present report reviews the role of TNF receptors (TNFRs) in the immune response against protozoan parasite infections of medical interest (Toxoplasma gondii, Leishmania major, Trypanosoma cruzi, Plasmodium spp.). TNF alpha has been regarded as a modulator cytokine in host defence against protozoans infections and recent findings on experimental gene-deficient mice have showed that TNF alpha/TNFRs pathway may be beneficial for host protection during these infections.

Animals↗

Chemokines in host-protozoan-parasite interactions.

Here, we review the interactions between parasites and chemokines and chemokine receptors in toxoplasmosis, trypanosomiasis, leishmaniasis, malaria and other diseases caused by protozoan parasites. The potential roles of chemokines after infection by these intracellular pathogens include host defence functions such as leukocyte recruitment, participation in cell-mediated immunity and antiprotozoal activity. However, these interactions can also help the parasite in, for example, the penetration of host cells.

Amebiasis↗

Parasitic diseases and immunodeficiencies.

In the last two decades, major immunodeficiency syndromes have strongly influenced medical parasitology. Some animal parasitoses, once unknown in human medicine, have become zoonotic and sometimes anthroponotic. In other cases, the clinical evolution of human parasitoses has been severely aggravated and/or modified in immunodeficient patients especially in toxoplasmosis, cryptosporidiosis, leishmaniasis, strongyloidiasis and scabies. The parasites implicated are varied (protozoa, helminths and even Acaridae) but have in common the capacity to reproduce in or on the human host. These immunodeficiency syndromes are often related to AIDS but other major immunodepressions, such as post-therapeutically in organ transplantation, may also be responsible and raise difficult problems for prevention. The munological mechanisms involved are not always well understood. In addition, genetic predisposition factors, gradually becoming better-understood in parasites and man, complete and complicate our understanding of the immunological mechanisms.

AIDS-Related Opportunistic Infections↗

Evaluation of Candida ID, a new chromogenic medium for fungal isolation and preliminary identification of some yeast species.

Candida ID, a new chromogenic medium, allows identification of Candida albicans (blue colonies) and preliminary identification into a group of four species (pink colonies). In comparison with Albicans ID2 and Sabouraud gentamicin chloramphenicol on 446 fungal strains, Candida ID allowed the isolation of more species than Albicans ID 2 (95.5% versus 91.2%).

Chromogenic Compounds↗

Hydrocortisone, prednisolone and dexamethasone act on Aspergillus fumigatus in vitro susceptibility to itraconazole.

In a previous in vitro investigation from the same laboratory a therapeutic level of hydrocortisone enhanced the itraconazole susceptibility of a single strain of Aspergillus fumigatus. In the present work, the influence of therapeutic levels of hydrocortisone (1 microM), prednisolone (0.125 microM 0.25 microM and 0.5 microM) and dexamethasone (0.25 microM and 0.5 microM) on the itraconazole susceptibility of four A. fumigatus strains, was determined. A. fumigatus conidia were germinated either in the absence or in the presence of a glucocorticoid. The germinated conidia were then spread onto plates and grown either in the presence or in the absence of a glucocorticoid, together with increasing concentrations of itraconazole. The mean colony forming units (CFU) were measured. Two factor analyses of variance showed that hydrocortisone significantly (p <0.001) potentiated the action of itraconazole. The cytotoxic effect of prednisolone on the fungal strains added significantly to the effect of itraconazole (p <0.001). Dexamethasone was also cytotoxic to the fungus but, when used in conjunction with itraconazole, it effectively increased (p <0.01) the number of CFU. This study showed a direct effect of glucocorticoids, currently in use for patient therapy, on in vitro A. fumigatus susceptibility to itraconazole.

Antifungal Agents↗

Evidence for tumor necrosis factor receptors (TNFRs) in human MRC5 fibroblast cells.

Previous reports have shown that tumor necrosis factor alpha (TNF-alpha) controls the functions of fibroblasts cells, such as proliferation, cell migration and secretion of factors. The signaling for the biological effects of this and other cytokines is usually exerted through cell surface receptors. In this study, we demonstrated the presence of a surface and soluble TNF receptor in MRC5 fibroblasts. The presence of TNFRI and TNFRII mRNA was demonstrated by reverse-transcriptase-PCR (RT-PCR). Both surface TNFRI and TNFRII are expressed and the number of both membrane receptors is 9,251 sites per cell. Using TNF receptor specific antibodies and flow cytometry, we showed that MRC5 cells express mainly TNFRI.

Base Sequence↗

[Malaria, genetics and molecular biology: myths, hopes and realities].

In the last two decades, progress in molecular biology has revealed a considerable genetic diversity among several parasitic species and especially in Plasmodium falciparum. This variability is of course facilitated by the haploid state of all plasmodial stages present in the human organism. Demonstrating this has lead to great progress in understanding some of the great epidemiological, pathophysiological, or therapeutic problems raised by malaria. The therapeutic aspects, especially those concerning resistance to antimalarials, will be presented elsewhere. We will deal only the following questions Several studies, some of which are very recent, partially answer these questions and our expertise should considerably increase with the future full sequencing of the Plasmodium falciparum genome. These observations are of considerable interest but should not be over estimated. Indeed, the structure of a genome does not reflect all the aspects of biological reality and it will be long and difficult to establish a correspondence between plasmodial genotypes and the features of a parasitic disease for which there is no true experimental model. Furthermore, the host-parasite relationships are of course not unifactorial and do not limit themselves to the parasite's features. Ecological and ethiological parameters, as well as the anophele's vector capacity, the human genetic predisposition for receptivity or sensitivity to malaria, and specific or non-specific immune phenomena all play a role. Possible interactions with co-infecting micro-organisms, whether viruses (CMV, HIV), or other parasites of the same genus (Plasmodiumvivax), or even other strains of the same parasitic species (Plasmodium falciparum) may also be of crucial importance

AIDS-Related Opportunistic Infections↗

[Prevention of congenital toxoplasmosis in France. Risk assessment. Results and perspectives of prenatal screening and newborn follow up].

In France, a national program for the prevention of congenital toxoplasmosis has been set up 25 years ago. This program is here presented and discussed in details. It is based on a decision tree well defined, with pre and/or per gravidic serological screening with several different tests, completed, if necessary, by ultrasounds examinations of the fetus, biomolecular tests (PCR) on amniotic fluid, and by clinical, biological, and radiological surveillance of neo-nates. The purpose of this prevention program is to: 1/identify nonimmune young women and limit their contamination risk during pregnancy by appropriate counseling on hygiene and diet; 2/screen and treat per gravidic toxoplasmosis as early as possible so as to prevent or limit transmission to the fetus and its consequences. 3/in utero diagnose and treat infestation of the fetus; 4/diagnose and treat asymptomatic congenital toxoplasmosis in neonates, to prevent risks of reactivation and late complications, especially ocular. Such a prevention program has a cost validated by the prevalence of acquired toxoplasmosis in adults in France (over 50% of the population) and by the yearly incidence of congenital toxoplasmosis (at least 0.1% of births according to the best hypothesis). These 6 to 700 congenital toxoplasmosis cases per year may be compared to the 6 to 7,000 per gravidic seroconversions which could lead to fetal contamination if no preventive measures are taken. Nevertheless, as it is often the case in the field of prevention, it is very difficult to statistically assess the efficacy of this program even though several arguments show that it allows to eliminate the most serious toxoplasmosis, sources of serious handicaps at birth, and to limit the frequency of late complications (especially retino-choroiditis) of asymptomatic infections in neonates. The position of European countries varies as to prevention of congenital toxoplasmosis. Some countries (Austria, Belgium) have national prevention programs similar to the French one, whereas others have set up only limited programs or set up no systematic prevention. These differences may be accounted for by the different frequencies of toxoplasmic risk. It seems mandatory to forget all dogmatism and not to stick to a strictly statistical approach for a disease with not only medical but also social and human consequences.

Female↗

Emerging parasite zoonoses: the role of host-parasite relationship.

Human-parasite relationships have played an essential role in the emergence or re-emergence of some parasitic diseases. These interactions are due to numerous causes. Some are linked to humans (immunodeficiencies due to AIDS among other causes, treatments, nosocomial contaminations, genetic predisposition), others concern the parasite (particular genotypes having modified their parasitic specificity). Several of these causes were predominant in the emergence of parasitoses such as cryptosporidiasis, microsporidioses or, to a certain point, pneumocystosis, the transmission of which has become zoonotic or even anthroponotic, inter-human. Re-emergent diseases (toxoplasmosis, leishmaniasis, giardiasis, strongyloidiasis, scabies) had already been described in human pathology, but their frequency or symptomatology have been drastically modified. In this case also, the unbalanced host-parasite relationship is largely responsible but it can not be dissociated from other causes, especially environmental and nutritional.

Animals↗

Toxoplasma gondii induces the secretion of monocyte chemotactic protein-1 in human fibroblasts, in vitro.

Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion was observed 24 h after infection by live tachyzoites. Analysis of chemokine mRNA transcripts by RNase protection assay revealed that this MCP-1 secretion seems associated with increased MCP-1 mRNA expression. However, these increased levels of MCP-1 secretion and expression were not obtained after stimulation by heat-killed tachyzoites or parasites pre-treated by a specific inhibitor of phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite multiplication by pyrimethamine did not modify MCP-1 secretion. Thus, it appeared that the active penetration of T. gondii in cells was of major importance in the induction of MCP-1 secretion. None of the other chemokines studied by RNase protection assay (lymphotactin, RANTES, IP-10, MIP-1alpha, MIP-1beta, IL-8, and I-309) were expressed after infection by live tachyzoites. We also found that MCP-1 secretion induced by live T. gondii is blocked by inhibitors of nuclear factor (NF)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the control of T. gondii infection and in its pathogenesis.

Animals↗

Emerging pathogens.

The ever increasing numbers of immunosuppressed individuals has led to a significant increase in the incidence of opportunistic infections, particularly those caused by fungi. The epidemiology of infections caused by the common fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus has been well documented. However, in addition to these, a number of species which have previously been unrecognized (e.g., C. dubliniensis) or have previously been assumed to be non-pathogenic (e.g., Saccharomyces cerevisiae, Scedosporium spp. and Fusarium spp.) have emerged as agents of human disease. Since these species have only been identified recently as human pathogens, their role in disease is poorly understood. In most cases, identification of these species is problematic and therefore their epidemiology has yet to be elucidated adequately. In addition, several of these species fail to respond to conventional antifungal therapies. In this article, we describe the emergence of two separate yeast species (C. dubliniensis and S. cerevisiae) and two separate groups of moulds (Scedosporium prolificans and Fusarium spp.), as human pathogens. It is apparent from what we already know, that much work has yet to be performed before we have a clear understanding of how these species cause disease and most importantly how they can be controlled.

Candida↗

Aspergillus Fumigatus antigen detection in sera from patients at risk for invasive aspergillosis.

We have developed an inhibition enzyme immunoassay (inhibition-EIA) to monitor for the occurrence of invasive aspergillosis (IA) in sera from 45 immunocompromised (IC) patients. The test uses rabbit polyclonal antibodies and a mixture of components from Aspergillus fumigatus, containing three predominant antigens with molecular weights of 18,000, 33,000, and 56,000. Circulating antigens were found in five of seven proven cases of IA due to A. fumigatus. In two of the five positive cases, antigenemia was detected with inhibition-EIA earlier than with X ray or other biological methods. No antigens were detected in the sera from two patients with proven IA due to Aspergillus flavus and Aspergillus terreus nor in the sera from four patients with probable IA. Circulating antigens were not detected in the control group, composed of 30 healthy adult blood donors. Four of the 32 at-risk patients examined, though they displayed no definite evidence of IA, gave a positive result in this test. The sensitivity, specificity, and positive predictive value of inhibition-EIA were 71.4, 94.4, and 71.2%, respectively. The data were compared with those obtained by a latex agglutination assay of galactomannan (GM) that was positive in only one patient with probable IA. The higher sensitivity obtained by inhibition-EIA may well be due to its ability to detect circulating antigens other than GM in the sera of IC patients with IA. Detecting these antigens may improve the diagnosis of IA, as they may serve as markers of this infection.

Antigens, Fungal↗