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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 109 records · Page 6Linked to original sources

[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↗

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↗

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↗

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↗

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↗

[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↗

[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↗

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↗

Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig.

Previous studies have demonstrated the existence of acoustic responses from the saccule in guinea pigs for stimulus intensities above 75 dB SPL. It is well known that the saccule receives a double afferent innervation: a bundle of the superior branch of the eighth nerve reaches its anterior part and another bundle of the inferior branch innervates its posterior part. These two bundles join just at the exit of the internal auditory meatus. An electrophysiological experiment was performed to investigate whether saccular acoustic responses could be similarly recorded from both bundles. Recordings from an electrode tip of 0.2 mm diameter were obtained in normal animals and also in animals with a complete and selective destruction of the cochlear sensory epithelium induced by treatment with an ototoxic antibiotic combined with a loop diuretic. In both normal and treated animals acoustic responses with the peculiar very short latency were specifically recorded in the area of the junction of the two bundles, they were of maximal amplitude on the bundle of the inferior branch. These data confirm in a more direct way the saccular origin of the short latency acoustic responses and indicate that they are probably conveyed in both saccular nerve bundles but mostly in that of the inferior branch of the eighth nerve. Finally these data show unequivocally that saccular acoustic responses exist in normal guinea pig ears.

Animals↗

Neurogenic inflammation in the airways. I. Neurogenic stimulation induces plasma protein extravasation into the rat airway lumen.

Activation of sensory nerves in rodent airways results in microvascular permeability and edema formation, presumably due to release of vasoactive neuropeptides from the nerve endings. We examined the possibility that neurogenic stimulation may also induce movement of plasma proteins into the airway lumen. Neurogenic plasma protein extravasation (PPE) was induced in Sprague-Dawley rats by electrical stimulation of both vagal nerves (EVS) at 10 V, 5 ms, 20 Hz. After 90 s of EVS, histologic examination showed Monastral blue B, a macromolecular tracer, extravasated within the endothelium of vessels in the subepithelial layer of the tracheobronchial mucosa. In animals given 125I-labeled albumin intravenously, PPE was quantitated as microliters of plasma deposited into the airways, lung, and tracheobronchial (TB) and bronchoalveolar (BA) lavages. One minute of EVS induced an immediate increase in PPE in the tracheal (+117%) and bronchial wall (+125%) but not in the peripheral lung. There was a concomitant increase in the 125I-labeled albumin recovered from both TB fluid (net increase, 1.29 microliter of plasma = +259%) and BA fluid (net increase, 2.79 microliters of plasma = +107%). In addition, both total protein and endogenous albumin concentrations in TB fluid also increased after EVS. The albumin/total protein ratio (the albumin percentage) in TB lavages was also significantly increased (1.4 x, 1.7 x, and 2.5 x in three separate experiments, respectively), indicating the vascular origin of the increased luminal proteins. Neither cholinergic (atropine) nor adrenergic blockade (phentolamine + propranolol) influenced EVS-induced PPE into the airway walls or movement of radiolabeled albumin into the airway lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Goodpasture's syndrome with normal renal function.

Two cases of Goodpasture's syndrome with severe pulmonary haemorrhage and normal renal function are described. In spite of minor (patient 2) or even no (patient 1) biological or light microscopic signs of glomerulonephritis, immunofluorescence of immunoglobulin G (IgG) was strongly positive in a linear fashion along the glomerular basement membranes in both patients. We suggest that renal biopsy in patients with apparently idiopathic pulmonary haemorrhage may lead to an early diagnosis of Goodpasture's syndrome. It is not possible in this disease to recognize on presentation those patients who will remit spontaneously and those who will undergo severe disease. The deadly evolution for patient 1 and some cases in the literature lend support to the notion that cytostatics and plasma exchange must be added to corticosteroids, even if pulmonary haemorrhage is not active and renal function is normal at the time.

Adult↗

Acute effects of noradrenalin related vasoactive agents on the ototoxicity of aspirin: an experimental study in the guinea pig.

Aspirin is known to be ototoxic when administered at high doses. Its mode of action is unknown but an alteration of the vascular function has been suspected. To further document this hypothesis, acute effects of some vasoactive agents on the ototoxicity of aspirin were tested in experiments on the guinea pig using sensori-neural electrophysiological responses and morphometry of the vessels of the stria and the spiral lamina. Electrophysiological measures showed no modification of sensory responses but neural responses revealed clear changes after administration of noradrenalin related agents, limited modifications after a drug acting partly as a serotonin antagonist, and no change after a dopaminergic agent. Morphometric studies showed no modification of the strial but some effect on the spiral vessels. The results are compatible with the hypothesis of a vascular involvement in the ototoxicity of aspirin and they point toward an interaction with the noradrenergic sympathetic cochlear system in the spiral lamina.

Animals↗

Neuroanatomical study of Galen's anastomosis (nervus laryngeus) in the dog.

To further knowledge of the laryngeal nerves, the nerve fibers of Galen's anastomosis were studied using two neuroanatomical methods, namely nerve degeneration and horseradish peroxidase labeling. It is demonstrated that the superior laryngeal nerve forms part of the tracheal and esophageal nervous system. The value of the results in relation to physiological laryngeal studies and to human laryngeal diseases is discussed.

Animals↗

[Sarcoidosis and autoimmunity. Apropos of 2 cases].

Several immunologic abnormalities exist in patients with active sarcoidosis. Impairment of in vivo and in vitro cellular immunity is well known. Humoral immunity disorders are characterized by increase in polyclonal serum immunoglobulin, existence of circulating immune complexes and auto-antibodies. In the serum, these abnormalities are nearly the same than disorders observed during auto-immune diseases. We report 2 cases of patients where active sarcoidosis was associated with auto-immune disease. Then we discuss the relationship which could exist between the 2 types of diseases. The first patient was a woman (aged 66 years). She presented an active sarcoidosis and clinical symptoms of sclerodermia. The second patient, a man (aged 24 years), presented active sarcoidosis diagnosed 4 years ago. He had never received any treatment. Thrombopenic purpura occurred suddenly and needed steroid therapy. Antibodies to platelets were found in the serum. These associations raise some questions: 1) are they only fortuitous? such cases are rare but their frequency is perhaps underestimated; 2) could any common abnormalities of the immune response explain the emergence of the 2 diseases? 3) could one of the diseases favour emergence of the other? This hypothesis seems possible only if sarcoidosis is the initial disease. Eventually these associations also raise difficult therapeutic problems and must incite to explore precisely the immunity of patients with active sarcoidosis.

Adult↗

[Current aspects of Goodpasture's syndrome].

Goodpasture's syndrome is an auto-immune disorder with antibodies directed against alveolar and glomerular basement membrane. These antibodies are usually present in the serum but their detection is difficult, requiring a radio-immunological technique which remains uncommon. The fixed antibodies are detected more easily and more constantly in the kidney tissue than in the lung; they appear on a kidney biopsy in the form of linear deposits of immunoglobulins on the basement membrane. Thus, the renal biopsy appears to be the essential requirement to establish a diagnosis of Goodpasture's syndrome, and one should not hesitate to perform a biopsy in the presence of diffuse alveolar haemorrhage without an evident aetiology and even in the absence of any biological evidence of renal disease. Alveolar lavage may be used to confirm a haemorrhage which has been purely alveolar. The treatment for respiratory and renal recovery, using immunological therapy includes corticosteroids, cytotoxic drugs and plasmapheresis. The exact methods are not yet fully defined during the course on certain clinical forms of the disease: for oliguric patients, dialysis is the single treatment; the isolated pulmonary forms have often been treated and improved by corticotherapy alone. The responsible antigen, probably unique, has been recently been identified as collagen type IV of the glomerular basement membrane. The pathogenesis of Goodpasture's syndrome remains unknown. The inhalation of hydrocarbons has been frequently noted. The dismal prognosis in the natural history of the disease and the therapeutic possibilities available make diagnosis an urgency. Currently, renal biopsy represents the most reliable and rapid mean of diagnosis.

Adult↗

[The value of Doppler echocardiography in the diagnosis of pulmonary artery hypertension in chronic obstructive bronchopneumopathies].

We report a study using Doppler echocardiography looking for pulmonary arterial hypertension (HTAP) in 36 patients presenting with chronic airflow obstruction (BPCO) who are in a stable state. 18 of these (group 1) had confirmed HTAP by right heart catheterisation which had been done the day before and was defined as a mean pulmonary arterial pressure (PAPm) of greater than 20 mm of mercury. The other 18 patients (group 2) did not have HTAP at rest. The systolic ejection flow and the duration of the peak (expressed in msec) was analysed at the time of each examination. The Doppler data was compared between the two groups of patients and also with the results obtained in ten healthy subjects. The Doppler examination was successfully performed in 35 patients in spite of a poor echographic window in 86% of cases. When there was HTAP, the systolic ejection flow had a triangular aspect which contrasted with the dome shaped appearance of the normals. In group 1 the peak time was significantly shortened (p less than 0.01) compared to group 2 and to the healthy subjects. On the other hand there was no linear correlation between the value of the peak time and the level of HTAP measured by the catheter. Thus the severity of HTAP could not be precisely measured using these parameters. In considering that the peak time is normally greater than 100 msec, the sensitivity and specificity of the Doppler examination for the detection of HTAP during the course of BPCO are 90 and 88% respectively, which appears to be superior to the values obtained using other non invasive methods in the diagnosis of HTAP.

Adult↗