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C Imbert

Publications and source records attributed to C Imbert.

At least 19 recordsLinked to original sources

Influence of sub-inhibitory concentrations of conventional antifungals on metabolism of Candida albicans and on its adherence to polystyrene and extracellular matrix proteins.

Five antifungal agents with different mechanisms of action were compared for their ability to affect mitochondrial dehydrogenase activity and adherence capacity of Candida albicans to polystyrene and extracellular matrix proteins. Only amphotericin B inhibited mitochondrial dehydrogenase activity when the culture medium was supplemented with galactose. 5-Fluorocytosine and terbinafine did not affect this activity, whereas itraconazole and fluconazole improved it. Furthermore, in these experimental conditions, the effect of sub-inhibitory concentrations of antifungals on adherence was dependent on the tested antifungal and the adherence surface: amphotericin B inhibited adherence to polystyrene and fibrinogen, but improved adherence to extracellular matrix. For all surfaces tested, when culture medium was supplemented with galactose, fluorocytosine did not affect adherence, and itraconazole, fluconazole and terbinafine inhibited adherence. Our results also confirmed the influence of the carbohydrates: sub-minimum inhibitory concentrations (MIC) of itraconazole increased or did not modify the mitochondrial metabolism of yeasts when the culture medium was supplemented with galactose, but this antifungal always decreased mitochondrial metabolism when the culture medium was supplemented with glucose. These data indicate that antifungals used below their MIC values can have various effects. It is important to distinguish the effects of antifungals on the metabolism of C. albicans from effects on its adherence capacity. The former effects are linked to the viability of the yeast and the latter depends on the colonization of cellular as opposed to inert surfaces.

Amphotericin B↗

Effect of matrix metalloprotease inhibitors on the 95 kDa metallopeptidase of Candida albicans.

A 95 kDa metallopeptidase of Candida albicans could be involved in the process of dissemination of the yeast. Matrix metalloproteases (MMPs) are also responsible for collagen breakdown in inflammatory and malignant processes. We tested six compounds on the C. albicans enzyme. Doxycycline, gentamicin, cefalothin, galardin, and elaidic and oleic acids are known for their capacity to inhibit some MMPs. Amongst these agents, only oleic acid was able to markedly inhibit the purified metallopeptidase at very low concentrations. Moreover, this fatty acid inhibited the secretion of the enzyme in the culture medium without altering the yeast viability.

Candida albicans↗

Spontaneous long-term compensatory dopaminergic sprouting in MPTP-treated mice.

The present study sought to determine whether severe 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication elicits spontaneous long-term compensatory sprouting in mice. Animals, once treated, were kept without further treatment for 0.5, 1, 5, or 7 months. The stability of the nigral degeneration was checked by evaluation of the number of tyrosine hydroxylase immunoreactive (TH-IR) neurons, whereas sprouting was assessed using both [(3)H]-dopamine (DA) uptake by striatal synaptosomes and optical density of TH-immunolabeled fibers in the striatum as markers. At 0.5 month after MPTP intoxication (80 mg/kg, i.p.), we observed comparable decreases of 83% in DA uptake, 83.3% in TH fiber density, and 74% in the number of TH-IR neurons compared to age-matched saline-treated animals. From 5 months onwards, both DA uptake and striatal TH fiber density increased significantly (50% and 34.9% at 5 months, 65% and 67.4% at 7 months, respectively) in comparison with age-matched saline-treated animals, although the number of TH-IR neurons remained stable (73% of degeneration at 7 months). These results indicate clearly that spontaneous long-term compensatory dopaminergic sprouting is a phenomenon that is not restricted to situations of partial nigral degeneration but can, on the contrary, constitute a response even to severe stable MPTP-induced nigral degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Comparison of eight clinical rating scales used for the assessment of MPTP-induced parkinsonism in the Macaque monkey.

The most valuable model of Parkinson's disease available at present is the primate model treated with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), frequently used to study response to new drugs or surgical treatments. The evaluation of such therapies requires clinical rating scales which measure precisely motor behaviour in both normal and parkinsonian monkeys. It is obvious that such evaluation can only be valid if parallel studies are carried out under similar experimental conditions with well-defined objective criteria. Hence the need to compare and assess the different rating scales in use if we want to be able to compare the results of clinical studies. In order to give rise to some fresh thinking on the necessity of a certain uniformity of assessment, this study compares eight clinical rating scales and considers their capacity to express in quantitative terms both the severity of MPTP intoxication in five cynomolgus monkeys and the alleviation afforded by levodopa. None of the eight scales reaches all the criteria despite the Kurlan scale would appear as an interesting working basis for a further consensual definition of a worldwide used parkinsonian monkey clinical rating scale

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Riluzole delayed appearance of parkinsonian motor abnormalities in a chronic MPTP monkey model.

Preliminary studies have shown that riluzole, a Na+ channel blocker with antiglutamatergic activity, has neuroprotective efficacy in several models of acute dopaminergic neurodegeneration. A chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model which comes closer to the slow evolution of Parkinson's disease has recently been developed in order to allow dynamic studies. The present results show that riluzole delayed the appearance of parkinsonian motor abnormalities in this dynamic model, using from 10.2 +/- 1.6 daily injections for the MPTP-treated monkeys (n = 4) to 16.5 +/- 2.0 daily injections for the MPTP + riluzole-treated monkeys (n = 4). These results strongly suggest that riluzole may be beneficial to slow down the rate of progression of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Experimental models of Parkinson's disease: from the static to the dynamic.

The experimental models of Parkinson's disease (PD) available today can be divided into two categories according to the mode of action of the compound used: transient pharmacological impairment of dopaminergic transmission along the nigrostriatal pathway or selective destruction by a neurotoxic agent of the dopaminergic neurons of the substantia nigra pars compacta. The present article looks at the relative merits of each model, the clinical symptoms and neuronal impairment it induces, and the contribution it could make to the development of a truly dynamic model. It is becoming more and more clear that there is an urgent need for a chronic model integrating all the clinical features of PD including resting tremor, and reproducing the gradual but continuous nigral degeneration observed in the human pathology. Discrepancies have been reported several times between results obtained in classic animal models and those described in PD, and it would seem probable that such contradictions can be ascribed to the fact that animal models do not, as yet, reproduce the continuous evolution of the human disease. Dynamic experimental models which come closer to the progressive neurodegeneration and gradual intensification of motor disability so characteristic of human PD will enable us to investigate crucial aspects of the disease, such as compensatory mechanisms and dyskinesia.

Animals↗

A chronic MPTP model reproducing the slow evolution of Parkinson's disease: evolution of motor symptoms in the monkey.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism both in man and non-human primates. Several models have now been developed, but acute MPTP administration does not consistently reproduce all the clinical features of the disease. To mirror the slow evolution observed in human pathology, a chronic model of intoxication is necessary. The present study describes a chronic MPTP protocol in the monkey. Six monkeys received daily injections of MPTP (0.2 mg/kg i.v.) until they reached a score over 8 on the clinical rating scale (15.5 days +/- 1.1). Full parkinsonism was first obtained on the 22nd day. Levodopa testing (20 mg/kg per os) alleviated motor abnormalities (51%), proving the parkinsonian nature of these disturbances. Histological lesions reproduced those observed in Parkinson's disease with a decrease in tyrosine hydroxylase immunoreactivity of 90%. This model so could be of great interest for the study of the dynamic physiopathological changes which occur in Parkinson's disease and consequently for research on new neuroprotective therapies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Visual localization within single geometric planes of a space habitat.

BACKGROUND: The present study investigated how human subjects capture and restore visual information within a line representation drawing the three-dimensional configuration of a space module. METHODS: Nine subjects were asked to perform a visual localization task within this geometric model. The task consisted of localizing a light point appearing during 3 s in 40 different spatial positions and for 8 tilt angles of the model in the following random order: 0 degree, 45 degrees, 180 degrees, 225 degrees, 90 degrees, 315 degrees, 135 degrees, and 270 degrees. RESULTS: Results showed symmetric variations of the point-localizing errors about 180 degrees of tilt angle (vertical orientation) and a decrease of the errors when the points occurred in the distal, then in the median and in the proximal planes (virtual depth). The performance also varied according to the virtual ceiling, floor, right, left and back planes. The results have been discussed using a three-dimensional space representation based on a conservative mode of spatial information up to 90 degrees of tilt (horizontal orientation), and on a transformation mode beyond 90 degrees of tilt. CONCLUSION: We conclude that the visual localization in single geometric planes is orientation-dependent.

Computer Graphics↗

[The new patient].

Explore the source record for details and available documents.

Attitude to Death↗

Percutaneous embolectomy: in vitro investigations of the self-expanding tulip sheath.

A self-expanding sheath with a tulip-shaped distal end was designed for performance of percutaneous embolectomy. Its ability to retrieve clots was tested in an in vitro flow model; results were compared with those obtained with a conventional 10-F sheath. Simulated embolectomy of clots weighing 0.1-1.5 g was performed with a 0.75-mL Fogarty balloon on a 4-F catheter. The clot material that embolized distally during the procedure was sampled and quantified. No effective embolectomy was performed via a conventional sheath. With the tulip sheath, however, complete clot removal was achieved unless the clot size exceeded the tulip volume. On the basis of results of in vitro testing, the tulip design is promising for use in several applications during percutaneous interventions.

Catheterization↗

Emergency stenting for acute occlusion after coronary balloon angioplasty.

Acute coronary artery occlusion complicates 2-12% of the balloon angioplasty procedures, and despite repeat angioplasty, emergency surgical revascularization is often necessary. We report our initial experience with the emergency implantation of endoluminal stents for acute vessel closure after coronary balloon angioplasty. Nine patients received one stent, and two patients received two stents during the study period. Implantation was technically successful in all patients; there were no deaths, no myocardial infarctions as evidenced by Q wave on the electrocardiogram, and no need for emergency surgery. One additional patient, not satisfying the study inclusion criteria, died 16 hours after stent implantation from left ventricular failure and intractable arrythmias. Two patients in the study group had a moderate creatinine phosphokinase rise during the first 48 hours after implantation. During a median follow-up period of 3 months (range, 1-20 months), there have been no deaths and no need for elective coronary bypass surgery. One patient required emergency recanalization 3 months after implantation because of acute occlusion of the stented segment with limited myocardial infarction. Six patients have undergone control angiography, and none has developed chronic restenosis within the stented segment. For selected patients, coronary artery stenting appears to be a promising alternative to emergency bypass surgery after acute vessel occlusion during balloon angioplasty.

Adult↗

Self-expanding endovascular prosthesis: an experimental study.

A new type of endovascular prosthesis was inserted in 28 animals and evaluated for several factors, including thrombogenicity, tendency to migrate, critical implant zones, and incorporation into the vascular wall. The new prosthesis is a woven, multifilament structure of stainless steel alloy; its inherent elastic, self-expanding characteristics hold it against the vessel walls. Forty-seven endoprostheses (3-5 mm in diameter, 15-50 mm long) were percutaneously implanted with either a 6-F introducer sheath, a coaxial 9-F catheter, or a 0.014-inch (0.036-cm) guide wire into the femoropopliteal, coronary, carotid, and renal arteries and iliac veins. Anticoagulant or platelet antiaggregating agents were not used before or after implantation. Angiographic and histologic analyses showed that the prosthesis had a very low thrombogenicity when it was well adapted to the native vessel diameter and that it was incorporated into the vessel wall by a new intima by the 3d week after implantation. No migration occurred, and branch vessel flow was preserved even in those vessels in which ostia were traversed by the prosthesis. This prosthesis has potential for clinical application in the treatment of postangioplasty restenoses, particularly in the coronary arteries.

Animals↗

Intravenous immunoglobulins: can the blood pressure response in laboratory animals be considered a predictive criterion for good clinical tolerance?

Having noted that the only physico-chemical and biological test recommended cannot ensure good tolerance of i.v. IgG in man, we studied a physiological test consisting of evaluating blood pressure during infusion in conscious dogs (10 mg/kg/min) or after i.v. injection in rats (250 mg/kg in 12 sec.). The data were obtained on more than 100 dogs and 500 rats. For preparations known to be well tolerated in man or inducing a few clinical intolerances, the correlation with hypotension in rats and dogs seems good. Therefore, we think this test has its place in the battery of i.v. IgG qualification tests carried out before passage to man. Institut Mérieux has developed a new intact i.v. IgG equilibrated in sub-classes, without PKA, low in IgA and not hypotensive in these two species.

Animals↗

Serum beta 2 microglobulin in adult myeloid acute leukemias.

Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses.

Adolescent↗

Pharmacokinetics of tinidazole in chronic renal failure and in patients on haemodialysis.

The pharmacokinetics of tinidazole after infusion (800 mg in 15 min) were studied in 12 patients with chronic renal failure (RI) and in five patients undergoing regular dialysis treatment (RD). Tinidazole elimination plasma half-life was 15.09 +/- 0.68 h (mean +/- s.e. mean) (RI) and 12.9 +/- 1.0 h after dialysis (RD), but there was a significant decrease in half-life during dialysis (4.25 +/- 0.43 h) P less than 0.001). The apparent volume of distribution (0.64 +/- 0.03 l/kg) was equal to extra and intracellular water volume and tinidazole was little bound to plasma protein (8%). There was a slight sex difference in apparent volume of distribution between male patients (0.70 +/- 0.09 l/kg) and female patients (0.59 +/- 0.10 l/kg) (P = 0.07), but as body clearance decreases in the same order, there was no modification of plasma half-life. In renal failure, pharmacokinetics of tinidazole were not disturbed because no correlation between half-life, body clearance and creatinine clearance occurred; urine elimination was about 7% of administered dose. Plasma clearance during dialysis was 49.9 +/- 3.2 ml/min and about 43% of the available drug was eliminated during the 6 h dialysis procedure. These results suggest that an additional half-dose infusion should be given after the end of dialysis in patients undergoing regular dialysis treatment.

Adult↗

[Prolonged survival in adults with acute myeloid leukemia treated with BCG immunotherapy].

Between november, 1974 and june, 1977, 64 adult patients with acute myeloid leukaemia in remission were divided at random into two treatment groups: chemotherapy alone (n = 32) or chemotherapy plus B.C.G. (n = 32). Fresh B.C.G. from the Pasteur Institute, Paris, was administered once a week, two or three times per month, in the intervals between chemotherapy cycles, using the Heaf-gun method. The duration of the first remission was significantly increased in the group receiving B.C.G. (median duration 685 days versus 390 days: p = 0.03 on log rank test) as was the overall survival (median duration of survival 1.471 days versus 554 days: p = 0.01). Second remissions were more frequent in the B.C.G. group (79% versus 42%; p = 0.014). In addition, prolonged survival was more frequent in the B.C.G. group, where 12/32 patients remained in first remission between 3 and 6 years, as against 5/32 in the chemotherapy group.

Adult↗

[An empirical combination of antibiotics used in aplasias during chemotherapy for acute malignant hemopathies (author's transl)].

Continuous infusion of amikacin, cotrimoxazole and carbenicillin was the second empirically established combination of antibiotics used when fever occurred during the induction phase of chemotherapy in sixty-five patients (58 acute myeloid leukemias, 5 acute lymphoid leukemias, 2 non Hodgkin lymphomas). Clinical evidence of infection was available in 25 cases and the infection was bacteriologically documented in 19 cases. Therapy was successful in 57 patients (89%). When infection was clinically or bacteriologically documented tha success rates were 92 and 82% respectively. The average length of treatment was ten days. In 25 patients receiving 2 g of amikacin in continuous infusion, the mean serum concentration was 15,9 micrograms/ml; in 17 patients receiving 3 g, the mean serum concentration was 19,4 micrograms/ml.

Adult↗