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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 91 records · Page 5Linked to original sources

Stellate ganglion drives sympathetic regulation of cochlear blood flow.

The functional properties of the sympathetic fibers innervating the cochlea are not well understood. Adrenergic fibers supplying lateral wall structures of the cochlea have been observed terminating on radiating arterioles and collecting venules. Adrenergic fibers also terminate as 'free' endings in the spiral osseous lamina. Stimulation or transection of sympathetic fibers originating from superior cervical chain and supplying the cochlea have yielded mixed results concerning many aspects of cochlea physiology. In order to clarify the origin of sympathetic fibers and their role in control of cochlear blood flow (CBF), we examined the effect of electrical stimulation of the stellate ganglion (ESS) and transection of postganglionic fibers from the stellate on CBF measured by laser Doppler flowmetry and on systemic blood pressure (BP) in the guinea pig. ESS produced a 20-35% increase in BP and 10-15% decrease in CBF. The decrease in CBF presumably reflects the net result of increased perfusion pressure, local autoregulatory mechanisms, and a direct sympathetic-induced vasoconstriction. Section of the immediate postganglionic sympathetic trunk had little or no effect on the ESS-related change in BP; however, it eliminated the CBF reduction. Intravenously infused beta 1-blocker diminished the BP increase due to ESS, while the electrically-evoked reduction in CBF remained. Local application of an alpha-blocker on the round window blocked ESS evoked CBF reductions without altering the BP increase. These data confirm the functional role of sympathetic projections from the stellate ganglion in CBF regulation in guinea pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

The vascular component of sodium salicylate ototoxicity in the guinea pig.

Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (> or = 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosecretory function a decreased blood flow contributes to the ototoxicity of salicylates.

Action Potentials↗

Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray. A multicenter, double-blind, double-dummy, parallel-group study.

Fluticasone propionate aqueous spray, a new intranasal corticosteroid preparation, and disodium cromoglycate 2% aqueous nasal spray, an established preventive treatment for seasonal allergic rhinitis, were compared in a double-blind, double-dummy, parallel-group, multicentric study in France. A total of 218 patients with seasonal allergic rhinitis caused by grass pollen (verified by positive skin prick test) were preventively treated before the onset of the grass pollen season with either fluticasone propionate 200 micrograms once daily or disodium cromoglycate 5.2 mg four times daily. Half of these doses was given in each nostril. Treatment started before the onset of the pollen season in most patients (178/218). Diary cards, including symptoms of rhinitis and usage of nasal sprays, were filled in twice daily for 6 weeks. Terfenadine in 60-mg tablets and eye-drops could be used as rescue medications. We treated 110 patients with fluticasone propionate and 108 patients with disodium cromoglycate. Patients treated with fluticasone propionate had significantly more days free of primary efficacy symptoms of sneezing (P < 0.001) and nasal discharge during the day (P = 0.002), as well as free of all the other nasal symptoms (P < 0.01), and significantly lower median scores (P < 0.05) for all nasal symptoms except nasal discharge than patients treated with disodium cromoglycate. There was no difference in eye symptoms or in rescue medication use between the two groups. Compliance with the treatment was assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Self-expandable prostheses in the tracheobronchial tree.

Under endoscopic and radiologic control, two types of self-expandable metal prostheses were implanted in tracheobronchial lesions to help reestablish airway caliber. Thirty-nine metal stent prostheses (6-20 mm in diameter) and 35 Gianturco stents (30 mm in diameter) were used in 55 adult patients with 62 lesions of the trachea (n = 33) or bronchi (n = 29). All lesions except one were endoscopically confirmed to be noninflammatory. Immediately after implantation, radiologic and endoscopic studies verified reestablishment of a satisfactory airway diameter in all patients. At a mean follow-up of 10.35 (range, 3-27) months, improvement in the respiratory status of 49 of the 55 patients (89%) was maintained and tolerance of the device was excellent. For the Wallstent endoprosthesis, the six complications observed at endoscopy were successfully treated. The Gianturco stent, however, led to a high rate of complications: 30% of cases had migration and/or rupture of the metallic mesh, potentially leading to obstruction or wall perforation; one case of respiratory distress was fatal. This procedure offers rapid epithelialization and incorporation of the device into the tracheobronchial wall.

Adult↗

[Invasive pulmonary aspergillosis in 4 patients with acute decompensation of chronic respiratory insufficiency].

Invasive pulmonary aspergillosis (API) is a necrotising pneumonia generally occurring in profoundly immunodepressed subjects. These observations were based on four patients in the intensive care unit, suffering from chronic respiratory failure (IRC), without profound immunodepression. After a pathophysiological and clinical review, a focus on the diagnostic methods permits one to stress on the reliability, in this type of patient, of the evidence from direct examination of aspergillus filaments in the bronchoalveolar lavage (LBA) or protected bronchial brushings, taking account of the weak value of routine culture of spit or bronchial aspiration in IRC in whom patients are frequently colonised. These four cases permit one to discuss the factors which predispose to the development of API outside the usual immune suppression: IRC itself, by the disorder of mucociliary function, which it leads to; repeated antibiotic therapy which destabilises the saprophytic flora; viral infections which would be responsible for transitory immunodepression. But it is above all steroid therapy which seems to be the major factor favouring the development of API without producing profound immunodepression but probably because it inhibits phagocytosis of aspergillus spores. In these circumstances it is necessary to make an early diagnosis and to use fibre optic bronchoscopy with protected sampling and bronchoalveolar lavage with a complete microbiological. Only early treatment allows one to contemplate a cure.

Acute Disease↗

[Diagnostic perspectives in rhinology].

The physical evaluation of the nasal cavity and paranasal sinuses has been improved by recent advances in diagnostic endoscopic systems and computerized tomography. Today, nasal endoscopy is considered to be the only comprehensive diagnostic rhinoscopic examination and computerized tomography has replaced the standard plain film roentgenograms in the initial evaluation of the paranasal sinuses. Advances have also been made in the evaluation of nasal functions, particularly in the assessment of obstruction. Rhinomanometry is the only method of objective assessment of the patency of the nasal cavities and makes it possible to perform nasal provocation tests. Today, this method of exploration should not be overlooked. Secretory function may be assessed by various methods: nasal cytology, quantification of inflammatory mediators in nasal cavity washing, and biochemical analysis of nasal secretions (albumin/protein ratio). Mucociliary function can be evaluated by measuring the nasal mucociliary clearance, by determining the frequency of cilia strokes (after brushing of the nasal mucosa and microscopic examination under stroboscopic light) and by election microscopic ultra-structure studies. Other methods of exploration which do not yet have a practical application are currently being investigated: rheologic studies of the mucus, immunologic evaluation of nasal secretions and acoustic rhinometry.

Endoscopy↗

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↗

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↗

[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↗

[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↗

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↗

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↗

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↗

[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↗

[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↗