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Biomedical subjects

E Fournier

Publications and source records attributed to E Fournier.

At least 73 records · Page 4Linked to original sources

Effects of physical exercise and anti-G suit inflation on atrial natriuretic factor plasma level.

The purpose of this study was to measure the effect of enhanced venous return on atrial natriuretic factor (ANF) secretion during exercise and upright posture and the consequences on renin angiotensin aldosterone system (RAAS) activity. Six healthy male subjects were submitted to four different procedures. All procedures were performed in the same position, i.e. riding on a support with legs hanging. Two procedures were performed at rest: the subjects were studied after a 25-min rest in this position, with and without the lower limb fitted with an anti-G suit inflated to 60 mmHg. Two procedures were carried out with physical exercise; arm-cranking was performed in the same position with and without the anti-G suit inflated to 60 mmHg. Venous blood was collected before and after each procedure in order to measure plasma ANF, plasma aldosterone concentration (PAC), plasma renin activity (PRA), corticotrophin (ACTH) and catecholamine level. The data mean +/- SEM showed that the ANF plasma level decreased significantly (p less than 0.05) from 32.5 +/- 4 to 28 +/- 6 pg.ml-1 after a 20-min rest in the upright posture, whereas this effect was absolished with anti-G suit inflation. Physical exercise with and without the anti-G suit increased the ANF level above control values (60 +/- 13.6 pg.ml-1 and 53 +/- 13 pg.ml-1): anti-G suit inflation had no significant effect. PRA increased after rest in an upright posture and during physical exercise; anti-G suit inflation abolished this increase in both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vivo micronucleus test using mouse hepatocytes.

The bone-marrow micronucleus (BMM) test is highly specific for clastogenic effects but its sensitivity is determined to a great extent by the substances tested, particularly by their metabolism. Some compounds, such as unstable mutagens or those which generate short-lived metabolites, are not detected in this test because the metabolites produced in the liver do not reach the bone marrow. In an attempt to provide qualitative and quantitative assessments of chromosomal mutations produced in vivo by genotoxic agents not detected in the mouse BMM test, a mouse-liver micronucleus test, adapted from Tates model, was developed. The animals were treated twice, with an interval of 24 h between treatments, and then subjected to partial hepatectomy (PH) 24 h after the second treatment in order to induce mitotic stimulation. The incidence of micronucleated hepatocytes was determined 96 h after PH. The test was evaluated with 5 procarcinogens, each with a complex metabolic pattern: dimethylnitrosamine (DMN), diethylnitrosamine (DEN), 1,1-dimethylhydrazine (1,1-DMH), 4-aminophenol (4-APOL), 4-aminobiphenyl (4-ABPYL) and one direct unstable mutagen, beta-propiolactone (BPL). All these compounds are negative in the mouse BMM test but caused a major increase in the incidence of micronuclei in mouse hepatocytes. This test is simple and can be readily compared with the BMM test. Furthermore, it offers a better assessment of the impact of a compound at the chromosomal level in a metabolically competent cell and can therefore be used for the evaluation of the genotoxic activity of compounds with complex metabolic pathways.

Aminobiphenyl Compounds↗

Lateral visually-guided saccades in progressive supranuclear palsy.

Lateral visually-guided saccades were studied electro-oculographically in 40 patients with progressive supranuclear palsy (PSP) in order to increase understanding of the pathophysiology of the oculomotor syndrome and the suprareticular control of saccades. In the two main paradigms used, the central fixation point was removed just before the appearance of a lateral target, the subject being told either to look at the target (gap task) or, particularly to test frontal lobe influence, in the direction opposite to the target (antisaccade task). Saccade latency distribution in the gap task was significantly more scattered in patients as compared with 40 normal control subjects, although mean latencies did not differ greatly. In particular, many patients had latencies shorter or longer than those of control subjects. In the PSP group, the percentage of errors in the antisaccade task (misdirected saccades made towards the target) was strongly correlated with latency in the gap task, high percentages of errors corresponding to short latencies. There was also a correlation between latency and the frontal dysfunction evaluated by neuropsychological tests. These correlations suggest that short latencies could result from a severe impairment of the frontal inhibitory system involved in saccade initiation. Long latencies would result from damage to diverse excitatory suprareticular pathways (such as the superior colliculus) or to circuits responsible for shifts in visual attention. Lastly, 20 patients were followed longitudinally (for 3-12 months). The initially great intersubject variability of saccade latency in the gap task significantly decreased over a period of several months. This finding could result from a secondary balance between the impairment of the frontal inhibitory system and that of the diverse excitatory pathways.

Aged↗

Evidence for mutual inhibition of opposite Ia interneurones in the human upper limb.

The H-reflex technique was used to collect indirect evidence for changes in excitability of the interneurones mediating reciprocal Ia inhibition between wrist extensors and flexors. Stimulating the radial nerve results in an inhibition of the flexor carpi radialis (FCR) H-reflex and evidence has previously been presented that the early phase of inhibition is mediated by extensor-coupled Ia interneurones (Ext Ia INs), i.e. by inhibitory interneurones fed by muscle spindle Ia afferents from wrist extensors. Variations in the level of this inhibition were used to assess changes in excitability of Ext Ia INs. Stimulation of group I fibres from flexors was shown to depress the "reference" Ia inhibition, i.e. to inhibit the Ext Ia INs. The central latency of this interneuronal inhibition was compatible with a disynaptic linkage between flexor Ia afferents and Ext Ia INs. Its threshold and time course profile could almost exactly be superimposed on those of reciprocal Ia inhibition from flexors to extensor carpi radialis (ECR) motoneurones (MNs). This suggests that the Ia inhibitions to extensor MNs and extensor Ia INs are collateral effects mediated by the same flexor-coupled Ia interneurones. In two subjects, in whom it was possible to elicit an H-reflex in the ECR, inhibition of flexor-coupled Ia interneurones by activation of extensor Ia interneurones could similarly be demonstrated.

Adult↗

[Determination of the neurotoxic esterase in neurologic pathology of toxic origin. Measurement in human lymphocytes in poisoning by organophosphates, ciguatera and ethyl alcohol].

Lymphocytic NTE activity was measured after intoxication by organo phosphorus compounds and in chronic alcoholics at the beginning of alcohol withdrawal. The results showed a rapid fall in lymphocytic NTE activity; neuropathy developed when the inhibition was 75 p. 100 or more. In chronic alcoholics, the fall in NTE activity is a new concept which must be taken into account when considering the causal factors of neurotoxicity in exposed professions and in patients taking potentially neurotoxic drugs. The NTE may be a useful parameter to demonstrate the toxic origin of chronic neuropathies, especially those caused by drugs. The capacity for lymphocytic NTE activity to return to normal seems to be different in acute, compared with chronic, intoxications.

Acute Disease↗

Evidence for interneuronally mediated Ia excitatory effects to human quadriceps motoneurones.

The possibility was investigated that interneuronal pathways contribute to Ia excitation of quadriceps motoneurones in normal man. Two techniques were used: the indirect spatial facilitation technique for investigating summation of Ia excitatory effects in interneurones which may be interposed in pathways to quadriceps motoneurones; the post-stimulus time histogram method for time course measurement of the firing probability of voluntarily activated motor units following femoral nerve stimulation. The spatial facilitation technique was applied while using the quadriceps H reflex to assess the excitability of the whole motoneurone pool: the comparison was made between the excitatory effects of two conditioning stimuli applied either separately or together. Summation of effects at a premotoneuronal level is suggested if facilitation of the reflex evoked on combined conditioning stimulation is larger than the algebraic sum of facilitations evoked by separate stimuli. Quadriceps tendon tap and electrical stimulations applied to either the femoral nerve or to two of its branches, the nerves to the vastus lateralis and vastus medialis muscles, were used as conditioning stimuli. Since these stimuli were very weak (their strength being about at the threshold for facilitation of the test reflex), it can be assumed that they activated predominantly Ia fibres. The facilitation of the quadriceps H reflex evoked on combined stimulation was significantly larger than the algebraic sum of facilitations evoked by separate stimuli. In many experiments, although conditioning stimuli did not evoke any reflex facilitation when applied alone, a significant facilitation appeared on combined stimulation. This 'extra' facilitation of the reflex on combined stimulation appeared with a central latency of 4-5 ms. It is argued that the only mechanism compatible with such a latency is summation at a premotoneuronal level. Post-stimulus time histograms (p.s.t.h.s) of voluntarily activated quadriceps motor units were made following femoral nerve stimulation. Stimulation was triggered at a fixed delay time after the activation of the motor unit. A special attempt was made to set this delay so that the motoneuronal after-hyperpolarization following the spike would partially prevent the discharge evoked by a monosynaptic excitatory post-synaptic potential (e.p.s.p.). At stimulus strengths near motor threshold, femoral nerve stimulation regularly evoked an early increase in firing probability of motor units with the same latency as the H reflex.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

[Value of x-ray computed tomography in assessing the extent of invasive lympho-epithelial thymoma in the adult. Therapeutic implications].

This study concerns 12 patients who were in hospital for the work-up and treatment of an invasive lympho-epithelial thymoma. The extent of the disease was studied by systemic computed tomographic (CT) scanning of the thorax and abdomen. Three patients out of nine examined presented initially with asymptomatic renal metastasis. Three patients were treated straight away by poly-chemotherapy; the nine others benefitted either from radiotherapy alone (four cases) or from radiotherapy associated with surgery (4 cases) or an isolated surgical exploration (1 case). CT examination was carried out in 11 patients 3 months after the beginning of treatment and 7 times clinically latent metastasis were rediscovered (renal, adrenal, hepatic, thyroid, cerebral and osseous). These 11 patients benefitted secondarily from polychemotherapy. The results confirm the gravity of the condition: only three patients are living and in complete remission with a follow up of 24 to 48 months. The frequency of latent metastasis, detected by CT scanning, during the course of a malignant thymoma justifies the systematic performance of this examination in the work up of the disease extent and therapeutic surveillance in these patients, and leads one to reconsider the place of chemotherapy in the therapeutic strategy of these tumours.

Adrenal Cortex Neoplasms↗

[Mutagenicity of urine after ingestion of saccharin in man].

In vitro tests of mutagenicity help detect carcinogenic substances. A variation of the Ames test may be used to study the mutagenicity of urine after exposition of the organism in vivo. Saccharin is a widely used artificial sweetener excreted in the urine which can induce dose-dependent tumours of the bladder in the animal. We studied the mutagenicity of the urine of healthy volunteers after the ingestion of a single dose of saccharin. The results show a mutagenic effect related to the dose ingested in two types of Salmonella typhimurium (TA 98 and TA 38). These results are difficult to interpret as saccharin is not mutagenic in vitro alone or in the presence of control urine which eliminates a direct carcinogenic or cocarcinogenic effect; we were unable to detect impurities or metabolites. This study underlines the difficulty of prophylactic detection of chemical carcinogens.

Administration, Oral↗

Cutaneous facilitation of transmission in Ib reflex pathways in the human upper limb.

Group I effects from wrist extensors to flexors, i.e. an early inhibition followed by a relative facilitation which are thought to be Ia and Ib in origin respectively, were compared in control conditions and when preceded by a weak cutaneous stimulation. Stimulating the skin of the dorsal side of fingers II-III, which did not modify the test reflex size when applied alone, increased Ib facilitation. By contrast this Ib effect was not changed by stimulation of the skin of the palmar side. It has previously been shown that heteronymous Ib inhibition in the lower limb during voluntary contraction is facilitated by cutaneous stimulation from restricted receptive fields. Thus, present results lend support to the idea that cutaneous facilitation of transmission in Ib reflex pathways might be functional in curtailing exploratory movements.

Adult↗

[Dermatopolymyositis and pulmonary fibrosis associated with Gougerot-Sjogren syndrome. Study of 3 cases].

3 new cases of dermatomyositis associated with diffuse interstitial pulmonary fibrosis and, more exceptionally, with Sjögren's syndrome are reported. The pulmonary fibrosis observed in patients with dermatomyositis differs from that found in other connective tissue diseases in that it follows a more acute course and may respond to corticosteroids. Thus, in 2 of these patients treated with corticosteroids (combined in 1 case with cyclophosphamide) the high percentage of lymphocytes and polymorphonuclears in the broncho-alveolar lavage fluid, which reflects alveolitis activity, was reduced and the pulmonary fibrosis was cured in one patient and stabilized in the other.

Cyclophosphamide↗

Aspirin-sensitive asthma: abnormal platelet response to drugs inducing asthmatic attacks. Diagnostic and physiopathological implications.

The pathogenesis of aspirin-sensitive asthma remains unknown. Using a new model of platelet activation, initially described as a response of platelets to IgE antibody-dependent stimuli, this study was designed to test the hypothesis of a possible involvement of platelets in aspirin-sensitive asthma. Washed platelets from 35 aspirin-sensitive asthmatics showed an abnormal in vitro response to cyclooxygenase inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs)--aspirin, indomethacin or flurbiprofen--characterized by the generation of a cytocidal supernatant and (14 patients explored) a burst of chemiluminescence; these drugs had no similar effect on platelets from 31 controls (p less than 0.0001). It was shown that the abnormal platelet response to NSAIDs was not mediated by IgE. In contrast to platelets, aspirin-sensitive asthmatic leukocytes generated neither cytocidal factors nor chemiluminescence in the presence of NSAIDs. Sodium salicylate and salicylamide, which, though structurally similar to aspirin, do not inhibit cyclooxygenase and are well tolerated by aspirin-sensitive asthmatics, did not activate their platelets to release cytocidal factors. Moreover, preincubation of platelets with sodium salicylate, salicylamide or prostaglandin endoperoxide PGH2, highly prevented their abnormal response to NSAIDs (greater than 80%; p less than 0.0001). Since several lipoxygenase inhibitors (NDGA, esculetin), including inhibitors of both cyclooxygenase and lipoxygenase (ETYA, BW755c), did not activate patient platelets and prevented the subsequent abnormal response to NSAIDs, it is suggested that the abnormal platelet activation by NSAIDs is not only the consequence of an inhibition of cyclooxygenase, but also involves generation of lipoxygenase metabolites of arachidonate. Besides, platelets from 4 aspirin-sensitive asthmatics undergoing aspirin desensitization were found to have completely lost their abnormal responsiveness to NSAIDs. These findings represent the first identification in aspirin-intolerant asthmatics of a specific abnormal cellular response to drugs inducing asthmatic attacks and open new perspectives into the pathogenesis, prevention and diagnosis of this disease. They also provide support to the concept of a role for platelets in asthma.

Adult↗

Early neutrophil alveolitis after antigen inhalation in hypersensitivity pneumonitis.

Bronchoalveolar lavage (BAL) was carried out before and after antigen inhalation in ten hypersensitivity pneumonitis (HP) and five control subjects. Control subjects did not show any significant variation in BAL cells after challenge with diluted pigeon serum. In HP patients, the total number of BAL cells increased from (41.5 +/- 16.8) X 10(4) cells/ml before challenge to (84.0 +/- 28.9) X 10(4) cells/ml after challenge. Of greater interest, the values of polymorphonuclear neutrophils in patients increased from 8.3 +/- 9.7 percent before challenge to 41.2 +/- 24.35 percent, 24 hours after antigen challenge (p - 0.0001). Another BAL, carried out a week later, recovered a persistently high number of cells, (74.67 +/- 33.36) X 10(4) cells/ml. However, the percentage of polymorphonuclear neutrophils and lymphocytes did not differ from the initial pre-challenge BAL. Our study demonstrates an immediate and transient neutrophil alveolitis after antigen inhalation in patients with acute hypersensitivity pneumonitis.

Adolescent↗

Acute effects of tobacco smoke on alveolar macrophages cultured in gas phase.

With a culture technique in gaseous phase which permits a direct contact between cells and the atmosphere, without any liquid interposition, we studied the short-term effects of tobacco smoke on guinea pig alveolar macrophages (AM). Tobacco smoke had a cytotoxic effect on AM as evaluated by the decrease in cell ATP content, total smoke appearing more toxic than the gas phase. Toxicity of smoke gas phase is also ascertained by morphologic cell changes in electron microscopy and by a decrease in cell bactericidal activity. The large variation in AM susceptibility is not related to cell content in superoxide dismutase but seems to be in good correlation with AM glutathione content, especially when cells are cultured with N-acetylcysteine. However, the protective glutathione action is not total and seems less important than the one observed with a low concentration of NO2 (0.2 ppm/24 hours).

Adenosine Triphosphate↗