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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 19 recordsLinked to original sources
PubMed1992

Cochlear blood flow in response to dilating agents.

Reduced cochlear blood flow (CBF) has been implicated in various pathologies of the inner ear, including sudden deafness, noise-induced hearing loss and Meniere's disease. Thus the aim of some current therapeutic regimens to treat these conditions is to increase CBF and thereby improve oxygenation of the inner ear tissues. Most of the vasodilating agents in clinical use, however, do not have specific experimental evidence to support their effects on CBF. The hypotension which can follow systemic administration may limit their local effectiveness and general utility, just as it complicates the interpretation of the data in animal experiments. In the current study we investigated the effect of six agents, known for their systemic cardiovascular actions, on CBF: hydralazine, sodium nitroprusside, papaverine, nicotinic acid, verapamil and histamine. The effect of these drugs was studied after topical applications on the round window membrane (RWM) and systemic intravenous administrations. CBF was monitored with a laser Doppler flowmeter (LDF). Topical administration of sodium nitroprusside was the most effective in increasing CBF, followed, in order, by hydralazine and histamine. No change in CBF was observed for papaverine, verapamil or nicotinic acid. Systemic administrations of all the agents caused a marked decrease in blood pressure and variable effects on CBF. We discuss the CBF changes in relation to the different pharmacological mechanisms of action of each drug. The study demonstrates the effectiveness of topical application of vasodilating agents in increasing CBF.

Administration, Topical↗
PubMed1992

Expression of P-glycoprotein on normal lymphocytes: enhancement of the doxorubicin-sensitivity of concanavalin A-responding mouse spleen cells by P-glycoprotein blockers.

The in vitro proliferative response of mouse spleen cells (SC) to the T-cell mitogen, concanavalin A (ConA), displays a doxorubicin (DOX)-resistant component. This T-cell proliferative response displays a much higher DOX sensitivity in the presence of novel potent inhibitors of P-glycoprotein (Pgp)-mediated multidrug resistance (MDR), the cyclosporin (Cs) derivative, SDZ PSC 833, and the semi-synthetic cyclopeptolide, SDZ 280-446. Another resistance modulator, verapamil, might share this property, but its detection was impaired by the intrinsic toxicity of this calcium channel blocker for T-cell proliferation. A CD8+ cell-depleted SC suspension displayed a higher sensitivity to DOX alone, as well as a different sensitivity profile to SDZ 280-446. The CD8+ cells that are sensitized to DOX by the resistance modulating agents (RMA) might correspond to a formerly described T-cell subpopulation with the MDR phenotype, which seems to be essentially constituted of CD8+ (cytotoxic) T cells. Our results may open the way to a novel form of immunomodulation combining classical antineoplastic agents with Pgp-blocking Cs analogs (even non-immunosuppressive ones), which may be particularly useful when treating acute graft rejection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[A unilateral hyperlucent lung...].

The occurrence in a young patient of a chronic cough with dyspnoea and restrictive ventilatory failure as shown by respiratory function tests suggested the possibility of a Mac Leod syndrome. However, other aetiologies could be considered such as vascular malformations, bronchial malformations and also tumours. If the chest X-ray sometimes enables an aetiological slant, bronchoscopy remains a first line investigation.

Adolescent↗
PubMed1992

[Plasma extravasation in the tracheo-bronchial airways. Mechanisms and physiopathological consequences in asthma].

Plasma extravasation (EP) is an important phenomenon during the course of inflammation. In asthmatic subjects, EP is produced not only in the walls of the airways, but also in the lumen. This has consequences for the bronchial calibre and the qualitative and quantitative characteristics of the secretions. Numerous experimental methods have been developed in animals in order to study EP induced in the airways by different stimuli. For the most part these are inapplicable in man where EP is generally validated in an indirect fashion by measuring the quantity of certain plasma proteins, such as albumin in the secretions or the bronchoalveolar lavage. EP is linked to an increase in the permeability of the vessels, notably this is situated in the subepithelial zone. It is influenced by the appearance of disruption between the endothelial cells and possibly amplified by an increased blood flow linked to vasodilatation. It is the association of these phenomena of epithelial hyperpermeability which favours the appearance of EP in the lumen. In experimental systems the greater part of the mediators implicated in the pathophysiology of asthma are capable of inducing EP in the airways. The perfecting of reliable and non-invasive methods of study is, however, necessary to achieve a perfect understanding of the role of EP in the pathophysiology of asthma or other inflammatory diseases of the bronchi and to assess the efficacy of this parameter of different therapeutic techniques.

Animals↗
PubMed1991

The effect of CO2- and O2-gas mixtures on laser Doppler measured cochlear and skin blood flow in guinea pigs.

The effects of carbogen (5% CO2: 95% O2) 10% CO2-in-air and 100% O2 on cochlear blood flow (CBF), skin blood flow (SBP), blood pressure (BP) and arterial blood gases were investigated in the anesthetized, respired or self-respiring guinea pig. In respired animals, CBF and SBF were increased with carbogen and 10% CO2-in-air and decreased with O2. BP was elevated with each gas. In freely breathing animals, only 10% CO2-in-air caused a small increase in CBF; both carbogen and O2 caused CBF to decrease. SPF changes were similar in form, but larger than those seen in respirated subjects. No consistent change in BP was seen during breathing of these mixtures. Arterial PO2 was increased by carbogen and 10% CO2-in-air for both groups. PCO2 increased for both CO2 gas mixtures during forced respiration; but in free-breathing animals PCO2 only increased for 10% CO2-in-air (normal PCO2 values were maintained with carbogen thorough increased breathing rate). The observed changes in CBF were consistent with a balance between a combined vasoconstrictive effect of PO2 and vasodilation effect of PCO2 on cochlear vessels. Analysis of cochlear vascular conductivity (CBF/BP) indicated that vasodilation was significant only with 10% CO2-in-air in respirated animals. In all other conditions the increased CBF apparently reflects the increase profusion pressure associated with respiration of each gas. For clinical purposes, while carbogen does not appear to directly cause vasodilation of cochlear vessels it does lead to an increased oxygenation of the cochlea blood and would appear to avoid the cochlear vasoconstriction caused by 100% O2.

Animals↗
PubMed1991

Possible implication of arachidonic acid metabolism in the decrease of chemiluminescence production after exposure of murine peritoneal macrophages to diethylnitrosamine and tumour promoter, 12-O-tetradecanoylphorbol-13-acetate.

The effect of the carcinogen diethylnitrosamine (DEN) on prostaglandins (PGs), leukotrienes (LTs) and reactive oxygen intermediates production by murine peritoneal macrophages was assessed. In vitro exposure to DEN (0.8, 1.6 and 8 mM) resulted in a dose-dependent stimulation of the PGs and LTs generation by macrophages. DEN-exposed peritoneal macrophages demonstrated enhanced production of arachidonic acid (AA) metabolites following stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) as compared to macrophages stimulated with TPA alone. Studies of [3H]AA release from glycerolipids of prelabelled macrophages and of the distribution of AA metabolites between intra and extracellular compartments indicated that DEN induced de novo synthesis of AA metabolites. The stimulation of AA metabolism by DEN was decreased by H-7 and staurosporine, protein kinase C (PKC) inhibitors, and so could be dependent on PKC activation. The generation of PGs by macrophages after DEN exposure was also inhibited by indomethacin (cyclo-oxygenase inhibitor). DEN at high concentrations (1.6-16 mM) inhibited chemiluminescence production by peritoneal macrophages in a dose-dependent manner, triggered by tumour promoter TPA; lower concentrations (0.8 and 1.2 mM) increased this reactive oxygen intermediates dependent chemiluminescence production induced by TPA. The role of AA metabolism in the alteration of chemiluminescence production by murine peritoneal macrophages treated in vitro with DEN and triggered by TPA has been evaluated by using AA metabolism inhibitors. The stimulation of chemiluminescence by TPA was inhibited by the addition of phospholipase A2 (PLA2) inhibitor, 4-p-BPB; this metabolic inhibitor did not affect the decrease of chemiluminescence production induced by DEN. The cyclo-oxygenase (CO) inhibitor, indomethacin, reversed the inhibition of TPA-induced chemiluminescence caused by DEN. These results suggest that AA and/or a lipoxygenase product can potentiate the reactive oxygen intermediates production by macrophages stimulated by TPA. The CO pathway could be involved in the inhibition by DEN of the reactive oxygen intermediates generating enzyme system. It is suggested that this inhibition could be related to AA metabolites issued from the CO pathway or to DEN oxygenated metabolites issued from the co-oxidation of the DEN by the PGs endoperoxide synthase. These results also raise the problem of macrophage dysfunction by chemical carcinogens and the implication of the CO pathway in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Measurement of human cochlear blood flow.

Cochlear blood flow (CBF) was measured with a laser-Doppler (L-D) flowmeter (Periflux PR2-B) in four unanesthetized human subjects with chronic tympanic membrane perforations and nine anesthetized human subjects undergoing middle ear operations. The L-D recordings were made over the promontory and/or the round window membrane during carbogen breathing and direct electrical stimulation of the cochlea in both groups and with warm water irrigation of the external ear canal in the anesthetized subjects. Carbogen led to little or no change in CBF as monitored with either measurement approach in either subject group. Electrical stimulation yielded an increase (15% to 25%) in CBF as recorded from the promontory in seven of the nine subjects tested. Warm (44 degrees C to 49 degrees C) water irrigation produced changes of 20% to 60% in CBF that were partially recoverable in the 10 minutes available for study. This study demonstrated the feasibility of direct CBF measurement in humans with the L-D method. Moreover, the data indicate that carbogen has little influence on CBF and that electrical stimulation at relatively safe levels and warm water irrigation of the ear canal produce increases in human CBF.

Aged↗
PubMed1991

[Should arterial hypertension in sleep apnea syndrome be stressed?].

The frequent association of sleep apnea syndrome and essential hypertension led to think of sleep apnea as an etiology of hypertension, especially as a good correlation has been found between the severity of both diseases. Moreover, treating the apnea syndrome results in a decrease of blood pressure. The aim of our study is to depict the outlines of a severe hypertensive individual with sleep apnea by comparing 9 men primarily referred to the hypertension clinic with refractory hypertension and finally found to have sleep apnea (study group) to 23 men whose diagnosis of sleep apnea was made in the pulmonary unit (controls). Fifteen of these were hypertensives. Mean age of the study group was 47 +/- 7 years vs 60 +/- 11. Controls were less overweighted: BMI = 33 +/- 6 kg/m3 vs 39 +/- 5. Mean blood pressure was 171 +/- 16/107 +/- 4 mmHg in the study group vs 157 +/- 19/92 +/- 12 mmHg in controls. Prevalence of glucose metabolism disorders was significantly greater in the study group: 6 patients with maturity onset diabetes and 3 with proven glucose intolerance, vs respectively 4 and 6 controls. Triglycerides were elevated in both groups whereas mean cholesterol was slightly above normal values. Six patients of the study group could have an echocardiogram which showed left ventricular hypertrophy (mean left ventricular mass index = 206 +/- 31 g/m2 after the Penn convention).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Thrombo-embolic disease with antiphospholipid-type serum auto-antibodies].

We report a case of thrombo-embolic disease in which we were able to detect the presence of serum antiphospholipid auto-antibodies. The existence of antiphospholipid auto-antibodies has already been described in cases of recurrent thrombo-embolism. The thrombogenic role is only partially explained, but would for the greater part be linked to an action on the fibrolytic activity of the vascular parietal wall. Amongst these antibodies one can find amongst others VDRL, antiprothrombinase and anticardiolipin. The association of other stigmata of auto immunity is not rare, especially disseminated lupus erythematosus (LED). When phospholipids are found in an isolated fashion in cases of recurrent thrombo-embolism they produce the syndrome of antiphospholipids. The long term prognosis of this syndrome has not yet been established but the risk of a secondary systemic disease developing justifies a clinical follow up and regular blood checks.

Adult↗
PubMed1990

[Therapeutic modalities in pulmonary tuberculosis].

In 1990, specific antituberculous chemotherapy can cure almost 100 p. cent of patients with pulmonary tuberculosis in France, provided practitioners follow strict therapeutic rules and patients' compliance with treatment is perfect. A single standard treatment is proposed for those patients whose tuberculosis has never previously been treated; it consists of a six months' course of isoniazid (5 mg/kg/day) and rifampicin (10 mg/kg/day); combined with ethambutol (20 mg/kg/day) and pyrazinamide (30 mg/kg/day) during the first two months. This treatment must be administered under regular medical supervision, and it must be prolonged for some time after cure has been obtained. In case of relapse or in some special situations (e.g. pregnant women, HIV positive patients, serofibrinous pleurisy, complex anatomico-clinical forms of the disease) treatment is more difficult, but it should always give favourable results.

Adult↗
PubMed1990

GABA immunoreactivity of calyceal nerve endings in the vestibular system of the guinea pig.

Neurotransmitters involved in the vestibular system are largely uncharacterized. On the basis of results of earlier electrophysiological and immunohistochemical experiments, glutamate and gamma-amino-butyric acid (GABA) have been proposed in both mammalian and non-mammalian species as afferent transmitters between the sensory cell and the afferent dendrite. GABA is also suspected to act as an efferent neurotransmitter in the cochlea. We describe in this study the immunocytochemical localization of GABA within the vestibular end organs in the guinea pig. GABA immunoreactivity was found in the calyceal nerve endings surrounding type I hair cells of the vestibular epithelia. The most significant labelings were obtained in the crista ampullaris. Labeling was more difficult to observe in the utricular and saccular macula. These results contribute to the recent proposal that the calyx has a secretory function, and suggest that GABA may have a modulatory influence upon the type I hair cells.

Animals↗
PubMed1990

Evidence for potassium-induced motility in type I vestibular hair cells in the guinea pig.

In higher vertebrates, vestibular epithelia contain two types of hair cells, type I and type II cells. Physiological properties of single nerve units have been correlated to the corresponding hair cell type and a better knowledge of the hair cell static and dynamic properties should help in understanding transduction and coding in the vestibular system. For the auditory system, isolated outer cochlear hair cells (OHCs) have provided a useful approach for electrophysiological studies and for observations of motile processes involved in the active control of cochlear micromechanics. The present study tests the hypothesis of motile properties in guinea-pig vestibular hair cells, using stimuli known to elicit motile events in OHCs. After exposure to a medium containing a high concentration in potassium (125 mM or 80 mM KCl), 19 of 26 type I hair cells showed an irreversible tilt of the neck region often accompanied by an obvious swelling of the cell body. In contrast, no shape changes were detected in type II cells. In response to extracellular electrical stimulation, no motility was observed in either type I or type II cells.

Animals↗
PubMed1990

Neurogenic inflammation, vascular permeability, and mast cells. Capsaicin desensitization fails to influence IgE-anti-DNP induced vascular permeability in rat airways.

Mast cells and neuropeptide-containing nerves occur in close proximity throughout the mucosa. The vasodilation that characteristically occurs after mast cell mediator release in skin is dependent upon sensory nerve activation with neuropeptide release. It was therefore of interest to examine the relationship between antigen-induced mast cell activation, vascular permeability, and the influence of capsaicin-sensitive sensory nerves in the airways. To examine this question, capsaicin was administered systemically and the "desensitization" of the animals to topical capsaicin confirmed. Thereafer, capsaicin-desensitized animals were studied to see if mast cell mediator-induced vascular permeability was affected. Plasma protein extravasation (PPE) was induced in Sprague-Dawley rats by intratracheal infusion of capsaicin or by intratracheal infusion of mouse serum albumin-dinitrophenol (MSA-DNP) after passive sensitization with IgE-anti-DNP. Leaking vessels in the airways were localized by using Monastral blue B, a macromolecular tracer. In the trachea, leaking vessels were predominantly located in the anterior wall after capsaicin challenge and in the posterior wall after antigen challenge. PPE was quantified by preinjecting animals with 125I-labeled BSA and expressed as microliter of plasma deposited in the trachea, bronchi, lungs, and tracheobronchial lavage (TBL). Within one minute after challenge, concentrations of capsaicin greater than 10(-7) M significantly increased PPE in trachea and bronchial wall (+ 160% and + 175% above control, respectively, with 10(-5) M). PPE was also observed in the trachea and bronchi after antigen challenge in animals passively sensitized with IgE-anti-DNP (+ 200% and + 153%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pulsed Doppler echocardiography in the diagnosis of pulmonary hypertension in COPD.

We used pulsed Doppler echocardiography to examine the systolic ejection flow from the right ventricle in 66 patients with chronic obstructive pulmonary disease. Adequate recordings were obtained in 60 patients, in conjunction with right heart catheterization. Patients without pulmonary artery hypertension at rest (mean pulmonary artery pressure less than 20 mm Hg) underwent an exercise test which identified a group with PAH during exercise (MPAP greater than 30 mm Hg). The patients were divided into four groups: group 1, or control group: 17 healthy nonsmokers without normal respiratory function data; group 2: COPD without PAH (n = 12); group 3: PAH during exercise (n = 26); group 4: PAH at rest (n = 22). Analysis of Doppler data included time to peak velocity, right ventricular pre-ejection period, and ejection period. Pulsed Doppler echocardiography was a simple and reliable method of detecting PAH. Latent PAH, revealed by the exercise test, was accompanied by significant changes in Doppler findings, confirming the sensitivity of the method.

Cardiac Catheterization↗
PubMed1990

[Sarcoidosis and heredity. 3 familial cases].

It is very uncommon to find several cases of sarcoidosis in the same family. In the majority of published reports, only 2 persons are involved in each family. Genetic predisposition is probably, but its true importance as compared with environmental conditions is uncertain owing to the lack of epidemiology studies. We report 3 cases of sarcoidosis in the same family. In 2 of these cases (2 black sisters) the clinical set up was similar, consisting of multivisceral sarcoidosis involving the lung and mediastinum, the skin and the peripheral lymph nodes and muscles, with poor general condition and dependence on, or resistance to corticosteroids. Although the two sisters lived in different countries for several years and despite the 4-year age difference between them, the disease began in both cases at the age of 40 years. The history of this family is exemplarily in favour of a genetic predisposition and suggests than the penetrance of genetic transmission is underevaluated. Systematic pulmonary clinical and radiological examinations performed in the relatives of patients with sarcoidosis might provide information on the true incidence of familial cases. Studies of the genetic equipment of these familial cases would perhaps constitute a line of research aimed at determining the pathogenesis of the disease.

Adult↗
PubMed1990

[Effects of cotrimoxazole on some macrophage functions: microbicide, tumoricide, production of free oxygen radicals, prostaglandins and leukotrienes].

In order to demonstrate an immunomodulating effect of cotrimoxazole, we investigated its influence on some macrophage (M phi) functions in culture: P815 tumor cells killing, Toxoplasma gondii killing, production of free oxygen radicals by luminol-dependent chemiluminescence, prostaglandins and leukotrienes secretion evaluated after incorporation of tritiated arachidonic acid. In vitro, cotrimoxazole inhibited in a dose-dependent fashion the chemiluminescence of murine resident peritoneal or guinea pig alveolar M phi. Production of prostaglandin (PG) 6-keto-F1 alpha, PGF2 alpha, and 5-hydroxyeicosatetraenoic acid by resident peritoneal M phi was also inhibited. However, PGD2 synthesis by alveolar M phi was enhanced. A second study was performed on peritoneal M phi, resident or elicited in vivo by one intra-peritoneal injection of an extract from Mycobacterium Tuberculosis membranes and obtained from mice pretreated or not by cotrimoxazole per os. Resident M phi from cotrimoxale-treated animals showed increased production of leucotriene B4 compared to M phi from controls. 6-keto-PGF1 alpha and free oxygen radicals production by elicited M phi was greatly enhanced by cotrimoxazole whereas thromboxane B2 was reduced. Finally cotrimoxazole enhanced intracellular killing of Toxoplasma gondii and cytotoxicity for tumor cells P815 by resident but not by elicited M phi. It is concluded that cotrimoxazole can modulate MO activation and some M phi functions involved in immune homeostasis. This data could help to understand why an antibiotic such as cotrimoxazole, which is known to be frequently used in immunocompromised hosts, is also efficient in Wegener's granulomatosis.

Animals↗
PubMed1989

Lipid peroxidation in rat liver microsomes: influence of carcinogenic N-nitrosocarbaryl.

The reactivities of carbaryl, N-methyl 1-naphthylcarbamate insecticide and its N-nitrosated derivative carcinogenic, N-nitrosocarbaryl, were investigated on the microsomal hepatic lipid peroxidation and NADPH-dependent reductase activities. The in vivo treatment by N-nitrosocarbaryl produced a reduction in lipoperoxidative degradation induced in vitro by NADPH with regard to the formation of malonaldehyde and conjugated dienes. Carbaryl, its precursor did not affect lipid peroxidation under the same in vivo conditions. Moreover, following administration of the 2 compounds, the activities of NADPH-cytochrome c reductase as well as NADPH-neotetrazolium reductase were significantly decreased by N-nitrosocarbaryl but not influenced by carbaryl. Correspondingly, in vitro studies were performed; different action patterns of the 2 tested xenobiotics were also noted after treatment of rat liver microsomes in vitro by carbaryl and N-nitrosocarbaryl especially in their ability to cope with microsomal oxygen activation. N-Nitrosocarbaryl proved to have a potent inhibitor concentration effect on NADPH-dependent chemiluminescence response in vitro; carbaryl was virtually ineffective on this parameter. No significant difference appeared in the affinity of N-nitrosocarbaryl and carbaryl for the microsomal phospholipids. From the in vitro explorations, it was suggested that carcinogenic N-nitrosocarbaryl may be involved in the inhibition mechanism of microsomal lipid peroxidation through decreases in both NADPH-dependent reductase activities and superoxide generation.

Alkylating Agents↗