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Biomedical subjects

P Faure

Publications and source records attributed to P Faure.

At least 55 records · Page 3Linked to original sources

[History of Saint-Louis' hospital through his building's history].

After a few epidemics of pestis in the XVth century, the authority decided to erect a new hospital far from the heart of the city of Paris with an adapted architecture to isolation of contagious patients. All the buildings of the hospital were built in the same time and the result is homogeneous. The architecture is characterized by a central quadrilateral, four buildings in square, a chapel and few others pavilions. To maintain isolation, many galleries communicate to the squares and the stores. We can also find a cistern, a pavilion for the baths and one consecrated to the treatment of the leprosy and erected by the Order of Knighthood of Malta. All these edifices are scheduled as an ancient monument and actually don't receive patients but are hallowed to research, formation or meeting. A new hospital has been erected at the back of the old one.

France↗

A nonrandom dynamic component in the synaptic noise of a central neuron.

Continuous segments of synaptic noise were recorded in vivo from teleost Mauthner cells and were studied with the methods of nonlinear analysis. As in many central neurons, this ongoing activity is dominated by consecutive inhibitory postsynaptic potentials. Recurrence plots and first or third order Poincaré maps combined with surrogate shuffling revealed nonrandom patterns consistent with the notion that synaptic noise is a continuously varying mixture of periodic and chaotic phases. Chaos was further demonstrated by the occurrence of unstable periodic orbits. The nonrandom component of the noise is reproducibly and persistently reduced when the level of background sound, a natural stimulus for networks afferent to the Mauthner cell, is briefly elevated. These data are consistent with a model involving a reciprocally connected inhibitory network, presynaptic to the Mauthner cell and its intrinsic properties. The presence of chaos in the inhibitory synaptic noise that regulates the excitability of the Mauthner cell and its sensitivity to external stimuli suggests that it modulates this neuron's function, namely to trigger a fast escape motor reaction following unexpected sensory information.

Acoustic Stimulation↗

The sizes of the exchangeable pools of selenium in elderly women and their relation to institutionalization.

Exchangeable pools of Se after an intravenous injection of 74Se-enriched isotope as sodium selenite were measured in two groups (n 9) of elderly women (free-living aged 64-82 years and institutionalized aged 68-82 years), and a comparison group (n 9) of young women aged 31-40 years to evaluate the effect of age and institutionalization on Se reserves. Dietary Se intake was not different among the three groups. Plasma Se and glutathione peroxidase (EC 1.11.1.9) levels were significantly lower in the institutionalized elderly women (P < 0.05). In each of the three groups, two pools were determined from our model. The size of the first pool and the sum of the two pools were lower in the group of institutionalized elderly women than in the other two groups. The significant correlation between plasma Se level and total Se pool size (r 0.66, P < 0.01) indicated that this last variable could serve as a new marker of Se status. Finally, these data suggest that the Se status of elderly women is more related to lifestyle, in terms of institutionalization or not, than to age per se.

Adult↗

Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets.

The purpose of this study was to investigate the effects of vitamin E in rats fed a high fructose diet which leads to insulin resistance, on some components of the free radical defense system and on insulin sensitivity. The rats (postweaning, 50 g) were divided into three groups: the control group (C, n = 16), which received a purified diet containing 60 g/100 g carbohydrates, the high fructose-fed group (FT, n = 16),fed a diet in which 56.8% of the carbohydrate as fructose, and a high fructose and vitamin E-fed group (FVE, n = 16), fed the FT diet supplemented with 3.4 g vitamin E/kg diet (vs. 0.17 g/kg in C and FT groups). The duration of the treatment was 6 wk. Insulin sensitivity was determined in half of the rats in each group using the euglycemic hyperinsulinic glucose clamp technique. The remaining rats were investigated for plasma glucose, insulin, triglyceride and fructosamine concentrations and for components of the free radical defense system. The FT group had a significantly lower insulin sensitivity than the C group. Basal glycemia was not different among the groups. In comparison with the C group, the FT group had a greater lipid peroxidation, as indicated by the higher concentrations of plasma thiobarbituric acid reactive substances (TBARS) and blood disulfide glutathione (GSSG) and the lower Cu-Zn superoxide dismutase (Cu-Zn SOD) activity. These markers approached the values of the controls after addition of vitamin E. Moreover, the FVE group had a higher insulin sensitivity than the FT group, but it remained lower than in the C group. These results show that a high fructose diet in rats leads to insulin resistance and a defect in the free radical defense system. Vitamin E supplementation improves insulin sensitivity in fructose-fed rats.

Animals↗

Cellular pharmacology of lipophilic anthracyclines in human tumor cells in culture selected for resistance to doxorubicin.

We have studied the cytotoxicity and intracellular accumulation of two lipophilic anthracyclines, pirarubicin and idarubicin, as compared to doxorubicin, in two human tumor cell lines, MCF7 and K562, and in their doxorubicin-resistant counterparts, presenting the multidrug-resistant (MDR) phenotype. The new lipophilic anthracyclines were found to present a higher cytotoxicity and accumulation than the reference anthracycline, doxorubicin, and there was a significant inverse correlation between drug accumulation and IC50 in both cell types. With the aim of identifying the reasons for the higher cytotoxicity and accumulation of lipophilic anthracyclines, we used and compared the efficiency of three MDR modulators, verapamil, quinine and S-9788. We showed that all three were able to sensitize the resistant cells to the three anthracyclines, but with different efficiencies, S-9788 being the most active reverter and quinine the least active at equimolar doses. We also observed that there was no correlation between the abilities of a modulator to reverse resistance and to restore drug accumulation. In view of the sustained activity of the modulators to increase pirarubicin and idarubicin cytotoxicity and accumulation, as they do for doxorubicin, we conclude that the better efficiency of lipophilic anthracyclines is likely to be due to their high uptake rate rather than to a decreased activity of P-glycoprotein on these drug substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular rigid-body displacements in a tetragonal lysozyme crystal confirmed by X-ray diffuse scattering.

X-ray diffuse scattering from protein crystals is, at the moment, the only available experimental process to be directly sensitive to long-range correlations between protein-atom displacements. It is shown here that calculations based on independent rigid-body displacements of individual molecules yield a description in good agreement with the experimental diffuse-scattering pattern displayed by tetragonal crystals of hen egg-white lysozyme (HEWL) In particular, it appears that molecular rigid-body translations and rigid- body rotations appear roughly in the same proportion as the average atomic mean-square positional fluctuations. The crystallographic temperature-factor analysis by TLS (translation/libration/screw) refinement, performed by Sternberg, Grace & Phillips [Sternberg, Grace, & Phillips (1979). J. Mol. Biol. 130, 231-253], is then confirmed and completed by a quantitative estimation of the molecular rigid-body translation contributions. The major contribution of molecular rigid- body displacements to the average atomic mean-square positional fluctuations, contradicts a previous analysis of the tetragonal HEWL diffuse-scattering data by Clarage, Clarage, Phillips, Sweet & Caspar [Clarage, Clarage, Phillips, Sweet & Caspar (1992). Proteins Struct. Funct. Genet. 12, 145-157] which concluded that short-range correlations dominate. The origin of these opposite conclusions mostly lies in the different hypotheses made to model diffuse scattering, underlying the limits of the 'homogeneous disorder' model.

Journal Article↗

[Topoisomerases: therapeutic value].

Anticancer pharmacology offers rich prospects for future therapeutic design. Knowledge of antitumoral agents pharmacology have widely advanced: understanding of the molecular cytotoxic mechanism of available agents, discovery of new compounds with a different and no-interfering mechanism of action. Since ten years, the identification of a couple of nuclear enzyme, DNA-topoisomerases, has answered to this goal. These enzymes catalyse the topological changes of the double strand DNA, participating to vital processes of cell metabolism. These enzymes are now know to be the intracellular target of widely used cytotoxic agents (such as anthracycline, Etoposide, Teniposide for DNA topoisomerase II) and for two new compounds in clinical trials (irinotecan and topotecan, both analogues of camptothecin, for DNA-topoisomerase I). This two last molecules, currently in phase II development, are promising. They seem to be synergistic in combination with available anticancer agents, but this remains to be demonstrated. Other drugs, inhibiting both DNA-topoisomerases I and II, are yet investigating. Would they provide new answers for the future?

Antineoplastic Agents↗

[Current therapeutic methods in onco-hematology].

These next years, many anticancer drugs will be available with new mechanism of action. The taxoïd compounds: Taxol and Taxotere have been judged efficous in the treatment of advanced ovary and breast cancers. Also, DNA-Topoisomerase I inhibitors, a new enzyme molecular target, will expand solid tumors therapeutic strategies. The adenosine analogs represent the xnewest advances in hematology: fludarabine becomes the second line treatment for chronic lymphoïd leukemia, cladribine the reference treatment for hairy cell leukemia. At least, all-trans retinoïc acid has changed acute promyelocytic leukemia pronostic by differentiating tumor cells, and open a very new way of cancer treatment. All these agents are the first compounds available, others are still in development. They, all, are benefit of a productive research.

Antineoplastic Agents↗

Multiple psoas abscesses after posterior spinal fusion.

STUDY DESIGN: A case of multiple psoas abscesses after Dove lumbar spine fixation is reported. OBJECTIVES: To review the diagnosis and treatment of deep infection after internal spinal fixation. METHODS: The possibility of septic complications after spinal surgery that may present with a degenerative pattern is examined. The clinical and computed tomographic findings of a psoas abscess are recalled. RESULTS: Surgical drainage of the purulent collection was performed along with prolonged parenteral antibiotic treatment. CONCLUSION: Infection should be considered as a cause of recurrence of pain after internal fixation of the lumbar spine.

Female↗

Influence of a long-term zinc-deficient diet on rat platelet function and fatty acid composition.

A reduced zinc intake is associated with numerous abnormalities and, in particular, with hemostasis dysfunction. In this report, we studied the effects of a long-term dietary zinc restriction on platelet function. Three groups of rats were analyzed: a zinc-deficient group (ZD) and two zinc-adequate fed groups, one pair-fed (PF) and one ad libitum fed (AL). We found that ZD diet (0.2 p.p.m.) impaired ADP-induced aggregation of washed platelet after 4 and 8 weeks of diet. Thrombin-induced aggregation was impaired in ZD rats and PF rats after 8 weeks. The thrombin-induced mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids was followed as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products. Stimulated platelets of ZD rats exhibited a decreased production of cyclooxygenase and lipoxygenase products, particularly after 8 weeks of diet. Moreover, platelet thromboxane generation was decreased in the ZD group as studied using a radioimmunoassay after thrombin stimulation. In addition, we measured the total fatty acid compositions of platelet and plasma. As a whole, 20:5 (n - 3) and 22:5 (n - 3) fatty acids content were significantly increased in platelet lipids after 8 weeks. On the other hand, it is known that enrichment of these fatty acids through dietary studies, both in animal and human as well as in vitro incorporation in platelets, resulted in an inhibition of platelet function. Consequently, these changes in platelet membrane fatty acid composition may contribute to the impaired platelet aggregation observed in ZD rats.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Protective immunity against malaria: cellular changes in the liver vary according to the method of immunization.

Characterization of cells present in the extravascular compartment of murine liver was performed after different immunization procedures against the malaria parasite Plasmodium yoelii. Mice were immunized with live or irradiated sporozoites or with parasitized erythrocytes. Whatever the immunization protocol used, the mice were protected against a sporozoite challenge but each immunization procedure induced a specific profile of cell types. Immunization with irradiated sporozoite induce a significant increase in CD8+ lymphocytes, parasitized erythrocytes stimulates production of monocytes/macrophages and CD8+ lymphocytes while, after live sporozoites immunization, polymorphonuclear cells, macrophages/monocytes, B cells and a range of T cell subsets were increased in number.

Animals↗

The French experience of treatment of chronic type D hepatitis with a 12-month course of interferon alpha-2B. Results of a randomized controlled trial.

Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon-a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon-a2b subcutaneously three times weekly for 12 months (5 MU/m2 for 4 months and then 3 MU/m2 for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV-RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/or virological relapse over the 6-month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon-a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric side effects.

Adult↗

Effect of lenograstim on the cost of autologous bone marrow transplantation. A preliminary communication.

High dose chemotherapy and autologous bone marrow transplantation (BMT) can produce prolonged remission in patients with malignant lymphoma or solid tumours. However, neutropenia is a serious complication of treatment in patients with these diseases. In this study, we investigated the costs and effects of using lenograstim, a recombinant human granulocyte colony-stimulating factor, to treat neutropenia in 16 patients with lymphoma or solid tumours. The cost of lenograstim was not included in the calculations. The duration of neutropenia and hospitalisation were both lower in patients who received lenograstim compared with no treatment. The mean cost of autologous BMT was FF142,000 in patients who received lenograstim, compared with FF166,000 in patients who did not. Savings were largely attributable to decreased expenditure on hospitalisation in the lenograstim-treated group. The cost of 14 days' treatment with lenograstim was estimated at FF10,500, based on a daily dosage of 150 micrograms/m2/day.

Adjuvants, Immunologic↗

G-CSF (Granulocyte Colony-Stimulating Factor): follow-up and use in a French University hospital.

Granulocyte Colony-Stimulating Factor or G-CSF (NEUPOGEN) was approved for use in France in November 1991 for prevention of chemotherapy-induced neutropenia. This retrospective study was conducted at Saint-Louis Hospital, Paris, France, from November 1991 to March 1993 with a more detailed analysis of patient profiles for courses ordered between November 1991 and December 1992. Data were collected on standardized G-CSF-treatment summary forms. The purpose of the study was to define, in clinical terms, the patients treated by G-CSF to determine the average cost per course of therapy and its impact on the hospital pharmacy budget. From November 1991 to December 1992 data from 307 patient profiles were collected and analyzed. The subcutaneous route was the preferred route and only 16.6% of courses were administered intravenously. 45.6% of patients received a single course, 24.3% received two courses, and 30.1% received more than two courses. Each patient completed an average of 2.3 courses at an average cost per course of $2,000.00 (Canadian dollars). During March 1993, 50% of vials dispensed were administered to outpatients. During the 14-month period, an average of 613.8 vials were dispensed per month corresponding to an average monthly expenditure of $104,000.00 (Canadian dollars). In the first 12 months following the commercial availability of G-CSF, G-CSF expenditures accounted for 8% of the pharmacy budget.

Adolescent↗

Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation.

DESIGN: Placebo for 3 months, followed by 30 mg/day zinc gluconate in identical capsules. SETTING: Diabetic out patients clinic at the University Hospital, Grenoble. SUBJECTS: Diabetic patients cared for type I diabetes mellitus. 22 patients began the study, 4 dropped out. 10 patients suffered of an early retinopathy, 8 patients had no retinopathy. INTERVENTIONS: In this order: T0 biological measurements, 3 months placebo treatment, T1 biological measurements, 3 months zinc gluconate treatment, T2 biological measurements. Plasma Zn, Cu, Se, thiobarbituric acid reactants and antioxidant enzymes were measured [plasma and red glutathione peroxidase (Se-GPx), red cell superoxide dismutase (Cu-Zn-SOD)]. RESULTS: Lower plasma zinc level in the two groups. An increase in zinc level was observed and was more important in diabetic patients with no retinopathy (P = 0.05). The thiobarbituric acid reactants were above the reference values in all the patients, and were decreased at T2 (P < 0.05). Increase of GPx activity after zinc supplementation in patients with retinopathy. CONCLUSIONS: Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation. Moreover this supplementation decreases lipid peroxidation. The effects of zinc are different in diabetic patients with or without retinopathy. The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself.

Adult↗

Zinc prevents the structural and functional properties of free radical treated-insulin.

We have previously reported that zinc deficiency could increase in vivo lipid peroxidation and decrease rat insulin sensitivity. In the present paper, we address the hypothesis of the role of zinc on insulin molecule in relation to free radical damage. From native recombinant human insulin, we prepared a zinc-depleted insulin. Both preparations were subjected to controlled free radical attack by incubation in the presence of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). To obtain minimally oxidized insulin, the oxidation process was monitored by measuring the intrinsic fluorescence of the insulin preparations. For 2.5 mM of AAPH, the autofluorescence of zinc-depleted insulin markedly decreased as compared to that of native insulin. These data are in favor of conformational changes of the insulin molecule which were further studied by quenching of fluorescence by means of potassium iodide. Using the euglycaemic hyperinsulinic glucose clamp technique in rats, the in vivo activities of the different insulin preparations, showed that oxidized zinc-depleted insulin had a marked reduced activity as compared to oxidized native insulin. From our results, we suggest that structural modification of the insulin molecule took place after zinc depletion and free radical treatment. Moreover, zinc depletion appeared to increase the susceptibility of insulin to free radicals.

Animals↗