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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 73 records · Page 4Linked to original sources

Effects of Ginkgo biloba extract (EGb 761) on cochlear vasculature in the guinea pig: morphometric measurements and laser Doppler flowmetry.

Ginkgo biloba extract (EGb 761) was administered orally for 4 or 6 weeks to healthy adult guinea pigs. Animals were then decapitated under deep ketamine anesthesia. Post-mortem morphometric measurements of cochlear vessels in the spiral lamina revealed a vasodilating effect of the extract in four of ten animals following 6 weeks of treatment. In vivo testing of the effect of 4 or 6 weeks of treatment with EGb 761 was monitored with laser Doppler flowmetry of the cochlear blood flow under pathological conditions. Results demonstrated that EGb 761 partly counteracted sodium salicylate-induced decreases in cochlear blood flow (CBF) and enhanced CBF increases induced by hypoxia. These findings indicate that EGb 761 may help to improve oxygenation in cochleas with compromised blood flow.

Administration, Oral↗

Detection of P-glycoprotein expression by tumoral cells with NBDL-CsA, a fluorescent derivative of cyclosporin A.

The P-glycoprotein (P-gp) molecules which are expressed on multidrug-resistant (MDR) tumor cells efflux a variety of anti-cancer drugs, such as doxorubicin. Though first described as an inhibitor of P-gp function, cyclosporin A (CsA) was more recently shown to behave as a substrate of the P-gp pump. The retention of [3H]CsA was reduced in MDR cells of the human leukemic CEM cell subline, in comparison with the drug-sensitive parental (Par) subline. MDR-CEM cell treatment by the P-gp blockers restored the [3H]CsA retention to the control Par-CEM cell levels. Using a novel fluorescent CsA derivative, [N-epsilon-(4-nitrobenzofurazan-7-yL)-D-Lys8] cyclosporin (NBDL-CsA), we now show that MDR cells can be distinguished from Par cells both at the cell population level (in microculture) and at the single cell level (by use of flow cytometry).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The abamectin derivative ivermectin is a potent P-glycoprotein inhibitor.

Among the compounds endowed with the capacity to reverse the P-glycoprotein (Pgp)-mediated multidrug resistance of cancer cells, a powerful agent was found to be the cyclosporin D derivative SDZ PSC 833. After in vivo treatment with SDZ PSC 833, mice showed a decreased tolerability to cyclosporin A (CsA), but also to ivermectin, a widely used polycyclic lactone pesticide of Streptomyces avermitilis origin. The sequels were suggestive of CsA- or ivermectin-induced central nervous system dysfunction; they were interpreted as caused by the neutralization of the Pgp at the blood-brain barrier level, implying that CsA and ivermectin were Pgp substrates. CsA was already known to display both Pgp substrate and Pgp inhibitor properties. It now appears that ivermectin may also inhibit Pgp function. When compared in short-term assays for Pgp function inhibition, which measure the restoration of the retention of two Pgp probes in multidrug-resistant (MDR) cells to their parental (Par) cell levels, ivermectin appeared only a few fold weaker that SDZ PSC 833 in the case of murine monocytic leukemia MDR-P388 cells and nearly as active as SDZ PSC 833 in the case of human lymphocytic leukemia MDR-CEM cells. Therefore, like CsA or FK-506, ivermectin may also be a substrate and an inhibitor of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Mineralogical analysis of the respiratory tract in aluminium oxide-exposed workers.

A retrospective study was conducted in order to characterize the retention of fibrous and nonfibrous mineral particles in the respiratory tract in subjects with previous occupational exposure in the aluminium industry. Bronchoalveolar lavage (BAL) fluid (three samples) or lung parenchyma (two samples) were studied using analytical transmission electron microscopy in five patients. A high concentration of aluminium fibres (> 10(7) fibres.g-1 dry lung) was identified in two lung tissue samples, and aluminium fibres were also identified in BAL fluid in three patients. All fibres were short (mean length: 1-2 microns), with no fibre longer than 5 microns. Some biopersistence of these fibres in the respiratory tract is suggested from these observations, since fibres were identified in biological samples collected more than 4 yrs after cessation of exposure in four out of five patients. Occupational physicians should be aware of possible exposure to short, thin aluminium fibres during primary aluminium production. Further studies are needed to assess the potential health effects of these fibres. Industrial hygiene measurements should also be performed to document the potential sources of exposure to aluminium fibres in this industry.

Adult↗

[Specific respiratory manifestations associated with hemorrhagic rectocolitis. Analysis of a case and review of the literature].

Respiratory impairments occurring as systemic manifestations of ulcerative colitis are often misinterpreted. We report a case of chronic productive bronchitis associated with ulcerative colitis; symptoms appeared after colectomy. Clinical features distinguished it from common chronic bronchitis: it occurred in a woman without respiratory disease or smoking history, a chronic productive cough without bronchiectasis, negative infectious investigations, severe endoscopic and histologic lesions, and above all remarkable steroid efficacy. Systematic research and early treatment of these manifestations avoids aggravating pulmonary disease, especially secondary bronchiectasis. Though less frequent, other respiratory manifestations of ulcerative colitis have been described, such as asphyxiating tracheal stenosis, pneumonia or interstitial pulmonary diseases, pleurisy or pleuro-pericarditis.

Bronchitis↗

[Nocardia respiratory infection in patients with chronic obstructive lung disease].

Pulmonary nocardiosis is a respiratory infection which is usually described in the immunocompromised. We report three cases in patients suffering from chronic airflow obstruction. In two cases there was a parenchymal disorder and in one case bronchial suppuration without involvement of the alveolar region. The diagnosis was made in all cases by bacteriological examination from specimens obtained at fiberoptic bronchoscopy. The outcome was favourable in all three cases after appropriate treatment. These observations underline the diversity of the clinical forms of respiratory nocardiosis. Furthermore, it demonstrates their possible occurrence in non-immunocompromised patients and the need to look for this germ specifically in long drawn infections. A bacteriological diagnosis is vital to start early and appropriate antibiotic therapy which should be prolonged because of the risk of recurrence and disseminated infection.

Aged↗

[Transesophageal cardiac echography and paracardiac tumor masses. Apropos of a case].

Computed tomography is currently the reference examination in the investigation of mediastinal tumours. We report a case of pericardial tumour revealed by transoesophageal echocardiography. This investigation immediately defined the limits of this mass and its relations with cardiac cavities and large vessels and suggested the main features of its tissue structure. However, the aetiological diagnosis is still based on CT-guided needle biopsy or investigation by mediastinoscopy or thoracotomy. Our case consisted of a non-Hodgkin lymphoma. Transoesophageal echocardiography is a non-irradiating technique, which can be performed at the patient's bed and which allows a precise assessment of the pericardial regions, especially the right pericardial regions.

Adult↗

[Diagnostic percutaneous thoracic punctures. Assessment through a critical study of a compliation of 2406 cases].

The aim of this retrospective study of 2,406 diagnostic percutaneous thoracic needle aspirations under computer tomographic control was to assess the diagnostic value of this method, the technical problems and the complications and finally, to refine the indications. Percutaneous needle aspiration had been carried out after negative fibreoptic bronchoscopy. The authors review their technique and show the value of biopsy material which is only slightly traumatised. Computerised tomography and fine needle aspiration reduce the risk of pneumothorax and haemorrhage in a significant fashion. Personalized collaboration between the radiologist, physician and cytologist is a vital pre-requisite. The indications are discussed notably in cases of solitary pulmonary nodules and of mediastinal masses.

Adolescent↗

Lymphotoxicity and myelotoxicity of doxorubicin and SDZ PSC 833 combined chemotherapies for normal mice.

In the mouse, the P-glycoprotein-directed chemosensitizer SDZ PSC 833 could both restore a therapeutic window for doxorubicin against multidrug-resistant tumors, by inhibiting P-glycoprotein function, and increase the anti-cancer drug efficacy against drug-sensitive tumors, by increasing doxorubicin bioavailability. Since the success of such combined chemotherapy treatments might have been limited by the myelotoxicity of doxorubicin and the P-glycoprotein expression on some blood cells, their lymphotoxicity and myelotoxicity was studied on normal B6D2F1 mice, and whenever possible, the persistence of blood cell alterations was also searched for in scid recipients of lymphohaematopoietic grafts from the donor mice. Analyzed parameters were blood, lymphoid and myeloid cell numbers, proliferative responses to T- and B-cell mitogens, and serum immunoglobulin levels. Cell alterations caused by doxorubicin alone were potentiated by SDZ PSC 833, but did not persist in scid recipients. Chemotherapy regimens combining SDZ PSC 833 and doxorubicin, and known for their therapeutic benefit for multidrug-resistant tumor-bearing mice, only caused a rather mild toxicity for the lympho-myeloid system of normal mice.

Animals↗

Decreased uptake of cyclosporin A by P-glycoprotein (Pgp) expressing CEM leukemic cells and restoration of normal retention by Pgp blockers.

The P-glycoprotein (Pgp) molecules which are expressed on multidrug resistant (MDR) tumor cells can efflux a variety of cytostatics. In both normal and tumoral epitheliums, Pgp molecules are selectively expressed on the apical surface of the epithelial cells. Such a distribution seems to be responsible for the transcellular transport of Pgp substrates, including cyclosporin A (CsA), from the basal to the apical side. Some normal lymphoid cells also express small amounts of Pgp molecules, for as yet unknown functions. Nevertheless, the sensitivity of their mitogen-induced proliferation to cytostatics, including doxorubicin and CsA, could be increased by the Pgp blockers. Using isotopically-labeled CsA and tumoral lymphoid cell lines, we now show a higher CsA retention in Pgp-lacking parental ('Par') cells than in Pgp-expressing MDR cells. The Pgp blockers can restore the CsA retention in the MDR cells to its level in the Par cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Substance P and alveolar macrophages: effects on oxidative metabolism and eicosanoid production.

The tachykinin substance P (SP) is present in lung sensory nerve endings and may be released after neurogenic stimulation. Its role in the pathogenesis of asthma is still unclear. Nevertheless, it may play a major role in airway neurogenic inflammation. Alveolar macrophages are the predominant cells of the airway space and are involved in various types of airway inflammation. We studied guinea pig alveolar macrophage response to SP and other related peptide (C- and N-terminal sequences, NK1-receptor agonist) stimulation. Alveolar guinea pig macrophages were recovered by bronchoalveolar lavage (BAL). Macrophage reactive oxygen intermediate (ROI) production was studied by luminol-dependent chemiluminescence with several concentrations of SP and related peptides. Eicosanoid synthesis after stimulation was evaluated by thin-layer chromatography (TLC) and enzyme-linked immunosorbent assay (ELISA). SP, C-terminal sequence, and NK1-receptor agonist significantly increased ROI production by alveolar macrophages (P < 0.01). NK1-agonist and C-terminal sequence modified arachidonic acid metabolism and induced a significant increase in prostaglandin (PG)D2 synthesis (211% and 66%, respectively). We concluded that SP and related peptides directly affect guinea pig alveolar macrophages by inducing the production of inflammatory metabolites.

Animals↗

Differential subcellular distribution of glutamate and taurine in primary olfactory neurones.

Taurine and glutamate are widely distributed amino acids in the mammalian brain, including the olfactory bulb where their functions have not been fully elucidated. This study investigated the precise cellular distribution of taurine and glutamate in the nerve layer and the glomeruli of the olfactory bulb, using semiquantitative immunocytochemistry at the electron microscopic level. The results show that both amino acids are present at higher concentrations in primary olfactory neurones than in the postsynaptic dendrites. Glutamate is also enriched in terminals vs axons of the primary olfactory neurones. This suggests that glutamate acts as a neurotransmitter at the primary synapse in the olfactory system. An opposite concentration gradient is found for taurine, with a higher level of taurine-like immunoreactivity in axons than in terminals of primary olfactory neurones. Further studies are required before conclusions can be drawn about the function of taurine in these neurones.

Animals↗

Balloon dilatation and self-expanding metal Wallstent insertion. For management of bronchostenosis following lung transplantation. The Toulouse Lung Transplantation Group.

Here we report our experience on the use of balloon dilatation or self-expandable metal Wallstent implantation, or both, for the management of twelve bronchial stenoses in ten lung transplant recipients during the past two years. Both techniques were carried out endoscopically, under fluoroscopic guidance and without general anesthesia. Both methods were straightforward, well tolerated, and resulted in immediate symptomatic and functional improvement. The first-line treatment relied on Wallstent insertion (n = 4) or on balloon dilatation (n = 8). Early restenosis occurred in four of eight dilated stenoses and subsequently led to Wallstent insertion. Following Wallstent implantation, growth of granulation tissue occurred in one case and necessitated repeated balloon dilatations inside the stent during the following months. On two occasions, the stenosis was located such that the lower end of the Wallstent overlapped the upper lobe bronchus orifice. This necessitated laser therapy to eliminate the filaments of the stent crossing the lobar orifice, preventing subsequent obstruction. Laser therapy was followed, in one case, by a fibroinflammatory stenosis which was successfully treated by balloon dilatation inside the prosthesis. At the time of writing, the mean +/- SE of the follow-up after Wallstent implantation is 15.3 +/- 2.7 (range: 6 to 32) months. Most Wallstent prostheses are overgrown with bronchial epithelium. We conclude (1) that self-expanding metal Wallstent implantation is a safe procedure and good alternative to silicone stent insertion for the treatment of bronchostenosis following lung transplantation, provided granulomas are not present and (2) that balloon dilatation, although possibly leading to recurrences, can be used to allow inflammatory tissue to mature or to dilate restenoses inside the Wallstent.

Adult↗