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Biomedical subjects

A Courtois

Publications and source records attributed to A Courtois.

34 records · Page 2Linked to original sources

Psychological impact of the announcement of a fetal abnormality on pregnant women and on professionals.

The psychological impact of the announcement of a fetal abnormality after ultrasound examinations is examined in relation to the building up of the mother-child attachment. It represents the "psychological cost" of such techniques. Understanding the subjective experience of the patients could increase the effectiveness of clinical practice. We have assumed that the relationship between parents and professionals is a critical element that contributes to the establishment of an emotional link between the mother and her child. Pregnant women, mothers, and professionals were approached for interviews and by questionnaires including anamnestic data, opinions, and projective methods. The results showed that the women with fetopathy were less centered on themselves during the pregnancy. Long-term effects were found to be important. In pregnant women, ultrasound examination was experienced with satisfaction even if some ambivalence remained. In mothers with an impaired child, ultrasound examination was viewed as a technique with low reliability. Professionals reported not having preparation in making such an announcement. We concluded that a need exists for better management of the modalities of ultrasound examinations. Many parents have expressed their need for psychological support.

Adult↗

Induction of multidrug resistance gene expression in rat liver cells in response to acute treatment by the DNA-damaging agent methyl methanesulfonate.

Expression of multidrug resistance (mdr) genes encoding the P-glycoprotein (P-gp) drug efflux pump was analysed in cultured rat liver epithelial cells acutely treated by the DNA-damaging agent methyl methanesulfonate (MMS). Exposure to this alkylating agent used at 30 microg/ml for 12 or 24 h was shown to enhance mdr mRNA levels in rat liver cells without alteration of cell viability. Induction of mdr transcripts occurred through increased expression of the mdr1b gene as indicated by reverse transcriptase-polymerase chain reaction analysis using rat mdr gene-specific primers and was not associated with up-regulation of cytochrome P-450 1A1, thereby suggesting that this detoxifying enzyme and P-gp were not coordinately regulated by MMS. In addition, the DNA-damaging agent was found to enhance in a dose-dependent manner cellular efflux of the P-gp substrate rhodamine 123, which was inhibited by the P-gp inhibitor verapamil, thus providing evidence that exposure to MMS led to increased P-gp-related drug transport in rat liver cells. The up-regulation of functional P-gp expression occurring in MMS-treated liver cells may be interpreted as a part of the cellular response to DNA damage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prophylactic use of itraconazole for the prevention of invasive pulmonary aspergillosis in high risk neutropenic patients.

Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbidity and mortality in patients with hematologic malignancies. A major program of construction work close to our unit prompted us to evaluate the efficacy of itraconazole prophylaxis in preventing IPA in these patients. During September 1994 to December 1995, 77 patients undergoing 96 neutropenic episodes (mean duration, 19.3 days +/- 9.1) received itraconazole as antifungal prophylaxis. All patients were treated in laminar air flow rooms. Itraconazole was administered at a loading dose of 600mg/d, (day 1 to day 3) and 400mg/d on the following days, in 87 instances. In the remaining episodes, the daily dose was 200 or 400mg. Oral doses were adjusted to reach a plasma itraconazole level (PIL) above 1000ng/l. In cases of inadequate PIL or poor oral intake, IV AmphoB was started at a 20 mg daily dose. Five cases of IPA (proven n = 2, probable n = 3) were observed. This represents an incidence of 5.2% of the total number of episodes. One out of 67 (2%) treatment episodes with adequate PIL were associated with IPA as compared to 4 of 29 (14%) episodes with inadequate PIL, (p < 0.02). AmphoB was added in 28 cases because of low PIL (n = 25), and/or antibiotic-resistant fever persistent pulmonary infiltrate (n = 8). These results need to be interpreted with caution, because of the absence of randomization or a control group. The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.

Adult↗

Differential expression and activity of P-glycoprotein and multidrug resistance-associated protein in CD34-positive KG1a leukemic cells.

CD34+ acute myeloid leukemias generally respond poorly to chemotherapy when compared to CD34- myeloid leukemias. In order to contribute to the analysis of the mechanisms involved in this drug resistance, expression and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), two drug efflux pumps conferring multidrug resistance, have been investigated in the CD34+ KG1a leukemic myeloid cell line and in two CD34- K562 and HL60 leukemic myeloid cell lines. Reverse transcription-polymerase chain reaction and dye efflux assays revealed that KG1a cells express P-gp but not MRP whereas neither P-gp nor MRP were detected in K562 and HL60 cells. In addition, KG1a cells were demonstrated to display resistance to anticancer drug substrates for P-gp such as vincristine and daunorubicin and to poorly accumulate vincristine. These results indicated that P-gp, in contrast to MRP, is expressed and functional in the drug-resistant CD34+ KG1a cell line, that may constitute a useful cellular model to analyze the constitutive chemoresistance of CD34+ acute myeloid leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Traumatic perilymphatic fistula and sports].

In the past ten years four sportsmen with a traumatic perilymphatic fistula were treated. Three of these four patients were surgically treated: two of them underwent a labyrinthectomy and with one of them, the oval window was grafted. After the analysis of these cases, we have made a study of the literature. Careful attention to the patient history and accurate review of the recurrent vestibulocochlear symptomatology isolate a clinical "audiovestibular syndrome of perilymphatic fistule". There is lack of precise preoperatoire diagnostic test. Nevertheless, entire positionnal audiometric test is a reliable and easy to perform test. The medical management is based on bed rest during a reasonable period. Only patients with significant suggestive symptomatology are surgically explored . They sometimes need destruction of vestibular function without preservation of hearing.

Adult↗

[Pituitary abscess. A rare complication of sinusitis].

This report is of a pituitary abscess arising from chronic sinusitis. The MRI suggested a pituitary tumor with suprasellar extension and diagnosis was made operatively. Pituitary abscesses are rare entities. Despite the advent of MRI, diagnosis is often only made operatively.

Abscess↗

Inhibition of P-glycoprotein activity in human leukemic cells by mifepristone.

The antiprogestatin drug mifepristone has previously been shown to potentiate anti-cancer drug activity in rodent multidrug-resistant cell lines through inhibition of P-glycoprotein (P-gp) function. In order to characterize P-gp-mifepristone interactions in human tumoral cells, we have studied the effect of the antiprogestatin agent on P-gp activity in human CD34+ leukemic cells known to display high levels of P-gp-related drug efflux. P-gp-mediated transport of the fluorescent dye rhodamine 123 occurring in the CD34+ KG1a myeloid leukemia cell line was found to be strongly inhibited by mifepristone in a dose-dependent manner. Similarly to verapamil, a well-known chemosensitizer agent, the antiprogestatin drug increased doxorubicin cytotoxicity in KG1a cells. Mifepristone, when used at a 10 microM concentration thought to be achievable in vivo without major toxicity, was also able to markedly decrease cellular rhodamine 123 efflux occurring in CD34+ blast cells isolated from six patients suffering from myeloid acute leukemias. These results thus indicate that mifepristone can strongly inhibit P-gp activity in human cells, including tumoral cells freshly isolated from patients, therefore suggesting that the clinical use of this compound may contribute to down-modulate P-gp-mediated drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel approach for investigating reaction mechanisms in cells. Mechanism of deoxy-trehalose synthesis in Saccharomyces cerevisiae studied by 1H-NMR spectroscopy.

A new approach is proposed for investigating the mechanism of metabolite synthesis in cells. This method, based on the competition between various substrates, allows the flux along a pathway, which is normally independent of the concentration of the corresponding precursor in the external medium, to be divided into partial fluxes. In particular, the mechanism deoxy-trehalose synthesis in glucose-grown repressed Saccharomyces cerevisiae was studied, by 1H-NMR spectroscopy, using the competition between 2-deoxy-D-glucose (dGlc) and 2-fluoro-deoxy-D-glucose (FdGlc) with respect to hexokinase. S. cerevisiae cells, suspended in a standard pyrophosphate medium containing about 5 x 10(7) cells/ml, were incubated with 30 mM glucose and various concentrations of dGlc and FdGlc. Apart from dGlc6P and FdGlc6P, trehalose and the dissacharides relative to dGlc, i.e. dideoxy-trehalose (dGlc-dGlc) and deoxytrehalose (dGlc-Glc), are observed while their analogues relative to FdGlc (FdGlc-FdGlc, FdGlc-Glc) are surprisingly absent. For the same external concentration of dGlc and FdGlc, the internal concentration of FdGlc6P is about three times larger than that of dGlc6P. The ratio of the FdGlc6P and dGlc6P concentrations is independent of the incubation times and proportional to the FdGlc and dGlc concentrations in the suspension. The dGlc6P concentration can thus be reduced at will by increasing the [FdGlc]/[dGlc] ratio. Under these conditions, the dGlc-Glc concentration was found to vary linearly with that of dGlc6P. The present data clearly show that deoxy-trehalose is not synthesized from UDP-dGlc and Glc6P but from UDP-Glc and dGlc6P. This conclusion was also confirmed by an experiment in which S. cerevisiae cells were previously charged with dGlc6P and then incubated with glucose.

Binding, Competitive↗

Reciprocal effects of 2-fluoro-2-deoxy-D-glucose and glucose on their metabolism in Saccharomyces cerevisiae studied by multi-nuclear NMR spectroscopy.

The effects of various concentrations of 2-fluoro-2-deoxy-D-glucose (FDG) on the aerobic metabolism of glucose and the reciprocal effect of glucose on the metabolism of FDG in glucose-grown repressed Saccharomyces cerevisiae cells were studied at 30 degrees C in a standard pyrophosphate medium containing 5 x 10(7) cells/ml by 1H-, 19F-, 31P-NMR and biochemical techniques. The glucose consumption rate is reduced by about 57% and 71% in the presence of 5 mM FDG and 10 mM FDG respectively. Under the same conditions, the ethanol production rate also decreases about 54% and 68%, respectively. When FDG is the unique carbon source, the alpha- and beta-anomers of 2-fluoro-2-deoxy-D-glucose-6-phosphate (FDG6P) and a much smaller quantity of 2-fluoro-2-deoxy-gluconic acid (FDGA) were observed. The quantities of alpha- and beta-FDG6P reach their maximum values within 1 h of incubation and then decrease continuously. In contrast, Glc favors the consumption of FDG and the synthesis of FDG6P and uridine-5'-diphosphate fluorodeoxy-glucose (UDP-FDG). In the presence of Glc, FDG6P reaches a plateau after 1 h or 2 h of incubation while UDP-FDG increases regularly with time. Apart from trehalose, no other disaccharide such as fluoro-dideoxy-trehalose (FDG-FDG) or fluoro-deoxy-trehalose (FDG-Glc) were observed. Thus, in contrast to UDP-Glc, UDP-DG, Glc6P and DG6P, UDP-FDG and FDG6P are not good substrates for trehalose-6-P synthetase.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

[Study by radiolabelling of the residual time of a therapeutic gel in the nasal fossae].

The residence times in the nose of the liquid and gel forms of the same therapeutic preparation were compared in 7 healthy subjects. A 50 microliters drop of the preparation, labelled with Tc99m, was placed down the head of the inferior turbinate, and the kinetics of its clearance from the site of deposition was monotired using a gamma camera, during 60 minutes for the liquid and 120 minutes for the gel. The average times for removal of 50% of the labelled material from the site of deposition were 10.3 minutes and 28.6 minutes for the liquid and gel forms respectively. The slower removal of the gel form is probably due to a mechanical effect, and seems to affect the whole nasal passage. The contact time between the preparation and the mucosa is increased in this galenic form and this should improve the efficiency of the preparation.

Adult↗

[Atypical cylindroma of the ethmoid].

The authors relate an ethmoidal cylindroma, whose extension includes the orbital apex, without any ocular symptomatology. They wonder about the possibility of an early diagnosis of such tumors.

Adult↗