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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 127 records · Page 7Linked to original sources
PubMed1996

Evidence for modulation of dopamine-neuronal function by tachykinin NK3 receptor stimulation in gerbil mesencephalic cell cultures.

Primary cultures of gerbil mesencephalon were used for studying the modulation exerted by tachykinin NK(3) receptor activation on the activity of dopamine (DA) neurons. Dopamine neurons were identified by their ability to take up [(3)H]DA in a nomifensine-dependent manner. Moreover, tyrosine hydroxylase immunohistochemistry revealed that these neurons accounted for 5-7% of the total cell population. The NK(3) receptor agonists, senktide (EC(50) = 0.58 nM) and [MePhe(7)]neurokinin B (EC(50) = 3 nM), increased spontaneous [(3)H]DA release in a concentration-dependent manner. In contrast, tested at a supramaximal concentration (IC(50) = 0.89 nM), neither septide nor substance P were found to affect [(3)H]DA release. The senktide-evoked [(3)H]DA release was not observed when extracellular Ca(2+) was chelated, but was unaffected by nomifensine. This indicates that this increase in [(3)H]DA outflow resulted more from an exocytotic process than from reversal of carrier-mediated DA uptake. Moreover, the senktide effect was unaffected by the Na+ channel blocker tetrodotoxin, a result suggesting a direct action of senktide on DA neurons. The non-peptide NK(3) receptor antagonist, SR 142801, shifted or blocked (IC(50) = 0.89 nM) the senktide-evoked [(3)H]DA release, while its (-)-antipode, SR 142806, was 80-fold less potent, in agreement with binding data. Selective antagonists for Nk1 (SR 140333) or Nk2 (SR 48968) receptors failed to reduce the senktide effect. Light scanning microscopic analysis of mesencephalic cells loaded with the Ca(2+) sensitive dye, fluo-3, showed that senktide induced a rise in cytosolic Ca(2+) in 8-10% of the cell population. The senktide-induced elevation in intracellular Ca(2+) was rapid in onset and transient (at 10-8 M) or more sustained with no further increase in fluorescence intensity (at 10(-7) M). The proportion of senktide-responsive cells was not significantly modified when extracellular Ca(2+) was chelated, but was reduced by 87% in the presence of SR 142801 and by 75% in cultures that were pre-treated with the DA neurotoxin 1-methyl-4-phenylpyridinium. The present study shows that enhancement of spontaneous [(3)H]DA release and intracellular Ca(2+) mobilization may be observed after NK(3) receptor stimulation and that both biochemical events are likely to occur in DA neurons.

Animals↗
PubMed1996

Myosin phenotype and SDH enzyme variability among motor unit fibers.

Motor units in cat diaphragm and tibialis posterior muscles were classified physiologically as slow-twitch, fast-twitch, fatigue-resistant, fast-twitch fatigue-intermediate, or fast-twitch fatigable. Motor unit fibers were then identified by glycogen depletion and classified as type I, IIa, IIb, or IIx on the basis of myofibrillar adenosinetriphosphatase-staining profiles and immunoreactivity for myosin heavy-chain (MHC) isoforms. In both muscles, slow-twitch and fast-twitch fatigue-resistant units comprised type I and IIa fibers expressing MHC-slow and MHC-2A isoforms, respectively. Fast-twitch fatigue-intermediate and fast-twitch fatigable units comprised type IIx fibers expressing the MHC-2X isoform. Some fast-twitch fatigue-intermediate units had a mixed composition with a few fibers (approximately 10%) expressing the MHC-2A isoform. Motor unit fiber succinate dehydrogenase (SDH) activity was quantified, and variability was estimated by the interquartile range, which was lower among motor unit fibers than in adjacent fibers of the same histochemical type but comparable to that along the length of individual fibers. We conclude that, despite the mixed-MHC phenotype of some diaphragm and tibialis posterior motor units, SDH activity is relatively uniform. This supports the hypothesis that motoneurons exert a predominant influence on muscle fiber SDH activity.

Animals↗
PubMed1996

Functional role and structure of the scalene: an accessory inspiratory muscle in hamster.

Although the scalene muscle (Sca) is a primary inspiratory muscle in humans, its respiratory function in other species is less clear. The electromyographic (EMG) activity of the Sca was studied during resting ventilation (eupnea) in both the awake and anesthetized hamster and after a variety of respiratory challenges in the anesthetized animal. The EMG activities of the medial Sca and the costal diaphragm were compared. The medial Sca, the major component of the Sca, originates from cervical transverse processes 2 to 5 and inserts primarily onto rib 4, with a small segment onto rib 3. In both the anesthetized and awake animal, the Sca was always silent during quiet breathing. With CO2-stimulated hyperpnea, the Sca was always recruited during inspiration in phase with the diaphragm. Active recruitment of the Sca was also observed after resistive loading and total airway occlusion. After ipsilateral phrenicotomy, the Sca was persistently recruited during eupnea. The specificity of the EMG signals was tested both by excluding cross contamination from other rib cage muscles and by selective denervation studies. Muscle spindles were identified in the medial Sca histochemically, suggesting that the respiratory activity of the Sca can also be modulated by changes in muscle length and/or load. These results indicate that the Sca functions as an accessory inspiratory muscle in the hamster and may play an important role in conditions of chronic load.

Animals↗
PubMed1996

Refractory hypoxemia during liver cirrhosis. Hepatopulmonary syndrome or "primary" pulmonary hypertension?

We report an uncommon mechanism of severe hypoxemia in two cirrhotic patients under long-term beta-blocker therapy. Our patients presented with profound hypoxemia refractory to oxygen therapy, normal lung radiography and pulmonary function tests, and evidence of right-to-left anatomic shunt. Although these features are highly suggestive of hepatopulmonary syndrome, pulmonary hypertension was present, and a right-to-left shunt through a patent foramen ovale was demonstrated by contrast-enhanced echocardiography. No cause of pulmonary hypertension other than portal hypertension was identified. Pulmonary hypertension and intracardiac right-to-left shunt eventually regressed after discontinuation of beta-blocker therapy. We conclude that "primary" pulmonary hypertension associated with portal hypertension may because of severe hypoxemia during liver cirrhosis. Differential diagnosis of hepatopulmonary syndrome relies upon contrast-enhanced echocardiography and may be of critical importance because of possible therapeutic implications.

Adrenergic beta-Antagonists↗
PubMed1996

Proinflammatory effect of Pediococcus pentosaceus, a bacterium used as hay preservative.

Bacterial cultures, such as Pediococcus pentosaceus, are used to treat hay with the objective of preventing hay heating and moulding, and thus, the development of the microbial growth which causes farmer's lung. The aim of this study was to investigate whether such bacterial cultures have the potential to induce a pulmonary inflammatory response. Mice were instilled 3 days week-1 for 3 weeks with either saline or nonviable preparations of P. pentosaceus, Saccharopolyspora rectivirgula, Lactococcus lactis (control bacteria) or with the combinations of S. rectivirgula and P. pentosaceus. P. pentosaceus induced a significant inflammatory response in the lung which was similar to that produced by S. rectivirgula. L. lactis produced a response of a lower intensity. The total number of cells in bronchoalveolar lavage were: S. rectivirgula: 6.4 x 10(5) cells.mL-1; P. pentosaceus: 4.3 x 10(5) cells.mL-1; S. rectivirgula + P. pentosaceus: 5.4 x 10(5) cells.mL-1, L. lactis: 6.8 x 10(5) cells.mL-1 and saline group 3.7 x 10(4) cells.mL-1. The lung index was higher in S. rectivirgula+P. pentosaceus and P. pentosaceus groups than in S. rectivirgula, L. lactis and saline groups. The quantity of specific immunoglobulin G and A (IgG and IgA) to P. pentosaceus and L. lactis levels (in the blood and/or lavage fluid) were similar to those against S. rectivirgula. In mice, P. pentosaceus has the potential to induce a similar inflammatory response in the lung as S. rectivirgula, which is the most common antigen responsible for farmer's lung disease in Quebec. Further studies are needed to verify whether farmers can develop farmer's lung or other lung responses to this new potential antigen.

Animals↗
PubMed1996

Lung volume reduction in patients with severe diffuse emphysema. A retrospective study.

BACKGROUND: For most authors, surgery of emphysema is restricted to resection of large bullae, whereas resection of small bullae or lung volume reduction is generally considered to have poor results. STUDY OBJECTIVE: To report our experience of lung volume reduction in patients with severe emphysema without large bullae. PATIENTS: Thirteen patients were operated on from 1982 to 1992. Before surgery, they all had severe diffuse emphysema with a dyspnea grade 4 or 5 and mean FEV1 values of 18 +/- 5% of predicted. Seven patients had a PaCO2 greater than 42 mm Hg. On radiologic evaluation, they had either small bullae or, most often, areas of destroyed lung. INTERVENTION: The surgical procedure was unilateral in 11 patients and bilateral in 2. MEASUREMENTS AND RESULTS: Postoperative assessment included dyspnea grading, FEV1 measurements, and blood gas analysis followed at 6- to 12-month intervals. There was no perioperative mortality and the morbidity was limited. At 6, 12, 18, 24, and 36 months postoperatively, a symptomatic improvement was observed in 92%, 85%, 54%, 31%, and 31% of the patients, respectively, with FEV1 increasing by at least 20% in 92%, 46%, 46%, 31%, and 24% of the patients, respectively. CONCLUSION: Our data show that lung volume reduction may result in symptomatic and spirometric improvement in patients with severe emphysema without large bullae.

Adult↗
PubMed1996

Hepatotoxicity of antitubercular treatments. Rationale for monitoring liver status.

The standard antitubercular regimen currently includes a combination of 3 antitubercular agents: isoniazid, rifampicin (rifampin) and pyrazinamide. Administration of a fourth agent, ethambutol, is recommended when isoniazid resistance is suspected. Two of these 4 agents (isoniazid and pyrazinamide) are major hepatotoxins. The remaining 2 agents (rifampicin and ethambutol) are rarely or not hepatotoxic. However, rifampicin, which is a powerful enzyme inducer, may enhance the hepatotoxicity of isoniazid. In patients receiving a combination of isoniazid, rifampicin and pyrazinamide, 2 patterns of fulminant liver injury can be observed. The first pattern is characterised by an increase in serum transaminase activity that occurs soon (usually within the first 15 days) after initiation of treatment. This pattern is likely to be caused by rifampicin-induced isoniazid hepatotoxicity. The prognosis is good in most cases. The second pattern is characterised by an increase in serum transaminase activity that occurs late (usually more than 1 month) after the initiation of treatment. It has been suggested that this pattern may be related to pyrazinamide hepatotoxicity. The prognosis of this type of hepatitis is generally poor. In order to reduce the risk of severe hepatic adverse effects during antitubercular treatment, several measures are proposed. First, patients with underlying liver test abnormalities should not be given pyrazinamide. Second, isoniazid and pyrazinamide should be administered at the lowest dosage within their respective therapeutic ranges. Third, serum transaminase levels should be determined twice weekly during the first 2 weeks of treatment, every 2 weeks during the rest of the first 2 months, and every month thereafter. When serum transaminase levels increase to greater than 3 times the upper limit of normal, therapy with isoniazid, rifampicin and pyrazinamide should be stopped. After serum transaminase levels have returned to normal, isoniazid can be re-introduced at a low daily dose, without rifampicin. Pyrazinamide may not be re-introduced because of the risk of recurrence and the poor prognosis of pyrazinamide-induced hepatitis. Although it is nephrotoxic, streptomycin is an alternative in patients with liver test abnormalities during antitubercular treatment.

Antitubercular Agents↗
PubMed1996

[Treatment of severe acute asthma].

Severe acute asthma remains associated with significant mortality. Medical treatment of acute severe episodes includes oxygentherapy, inhaled or intravenous beta-2-agonists, and high doses of systemic corticosteroids. The benefit of additional treatment with other agents such as nebulized ipratropium bromide, epinephrine and intravenous aminophylline is still not well defined. Mechanical ventilation, which remains necessary in case of life-threatening acute respiratory failure, addresses specific problems: PaCO2 may be allowed to remain elevated and ventilator settings should be chosen that avoid barotrauma under appropriate sedation. The use of inhalation anesthesics, helium or even extracorporeal life support necessitates further study to determine the optimal therapeutic strategy in those particular situations.

Acute Disease↗
PubMed1996

Antibody production and blastogenic response in pigs experimentally infected with porcine reproductive and respiratory syndrome virus.

Seven five-week piglets were infected intranasally with 10(5) TCID50 of porcine reproductive and respiratory syndrome (PRRS) virus strain IAF.exp91. All virus-exposed pigs developed fever, labored abdominal breathing, conjunctivitis, and lymph node enlargement within the first 96 h postexposure (PE), which continued to d 10 to 14 PE. Two pigs that were necropsied at d 7 and 10 PE had diffuse interstitial pneumonitis, cardiopathy and lymphadenopathy. All 5 remaining pigs produced serum IgM and IgG antibodies against PRRS virus by 7 or 14 days PE, as demonstrated by indirect immunofluorescence. This corresponded with the capability of isolating the virus from serum d 7 to d 49 or d 63 PE. Low serum neutralizing antibody titers were detected in 3 of the virus-exposed pigs by 35 days PE. A transient episode of diminished proliferative response of peripheral blood lymphocytes to mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was observed in the virus-exposed pigs at d 3 PE. However, in vitro spontaneous uptake of [3H]-thymidine was significantly increased in lymphocyte cultures of the same pigs at d 7 or d 14 PE. These results suggest polyclonal activation of peripheral blood lymphocytes.

Animals↗
PubMed1996

[Management of bronchial infectious episodes in general medicine].

BACKGROUND: Acute bronchitis and chronic obstructive pulmonary disease exacerbations are frequent reasons for consultation with a general practitioner (GP). Since no consensus exists about the use of antibiotics in such indications and little is known about the use of pulmonary function tests in general practice, our objective was to describe GP's attitudes and prescription habits when faced with patients suffering from acute bronchitis (AB) or chronic bronchitis (CB) exacerbation. METHODS: The GPs participating in public health surveillance through the "réseau Sentinelles" (French Communicable Diseases Network) in March 1993 answered a postal questionnaire. This questionnaire collected their clinical attitude and prescriptions for 7 clinical cases of varying severity. RESULTS: 430 (94.7%) of the GPs answered the questionnaire. Of these more than 95% prescribed antibiotics in all the clinical cases, including for common acute bronchitis. Wide spectrum penicillins and macrolides were prescribed significantly less often as the past history increased in severity, whereas tetracyclins and oral cephalosporins were prescribed significantly more often in severe cases. Fluoroquinolones were nearly exclusively reserved for the treatment of advanced CB. Smoking cessation was systematically advised by the GPs. Faced with AB and a smoking history, 44.2% of the GPs prescribed a chest x-ray. In the case of repeat episodes of winter bronchitis, more than 70% of them evoked the diagnosis of CB. 98.% of the GPs had easy access to pulmonary function tests (PFTs) which 69.2% of the GPs prescribed as soon as CB was suspected. CONCLUSION: In the absence of a therapeutical consensus regarding bronchitis, antibiotics were prescribed virtually systematically. PFTs were not yet a routine gesture in general practice even though they were widely available and prescribed.

Acute Disease↗
PubMed1996

[Graft dysfunction, acute rejection and bronchiolitis obliterans in lung and heart-lung transplantation].

Three complications which influence both survival and quality of life in transplanted patients will be the object of this chapter. Graft dysfunction: this is a severe re-implantation oedema leading to inefficiency of the graft as regards haemostasis whether or not associated with haemodynamic complications. The liberation of free radicals and/or cytokines induced by ischemia-reperfusion of the graft plays an important role in the pathogenesis of this syndrome. Acute rejection: the mechanism is complex leading to the intervention of an immune response stimulated by the detection of allo-antigens. The clinical picture is often non-specific. Treatment requires boluses of methyl prednisolone completed by decreasing dose of corticosteroid therapy orally. The syndrome of bronchiolitis obliterans: this is a progressive failure of the airways. This syndrome occurs in the long term in 50% of patients and presents with progressive dyspnoea associated with persistent or recurrent cough. The pathogenesis is brought about principally by a chronic rejection with a specific cytotoxic reaction of T lymphocytes against the airway epithelium which expresses Class II major histocompatibility antigens. Attempts at curative treatment can be extremely deceptive and leads to, at best, a slowing in decline of respiratory function.

Acute Disease↗
PubMed1995

DNA synthesis primed by mononucleotides (de novo synthesis) catalyzed by HIV-1 reverse transcriptase: tRNA(Lys,3) activation.

HIV-1 RT is able to catalyze DNA synthesis starting from mononucleotides used both as minimal primers and as nucleotide substrates (de novo synthesis) in the presence of a complementary template. The rate of this process is rather slow when compared to the polymerization primed by an oligonucleotide. The addition of tRNA(Lys,3) to this system increased the de novo synthesis rate by 2-fold. Addition of low concentrations of agents able to modify protein conformation, such as urea, dimethylsulfoxide and Triton X-100, can activate the de novo synthesis by a factor 2 to 5. A dramatic synergy is observed in the presence of the three compounds since the stimulating effect of tRNA increases 10-15 times. These results suggest that compounds activating RT are able to induce a conformational change of the enzyme which results in a higher specific activity. Primer tRNA seems to play an important role in HIV-1 RT modification(s) leading to a polymerase having a higher affinity for the primer or the dTTP, but not for the template. The specificity of RT for the template is not influenced by changes in the kinetics or in the thermodynamic parameters of the polymerization reaction.

DNA↗
PubMed1995

[Asthma and its treatment during pregnancy].

Asthma occurs in 0.4 to 4.0% of pregnant women and is considered to be the most frequent respiratory disease during pregnancy. Physiological modifications during pregnancy, including hyperventilation due to increased progesterone levels and lower residual volume and functional capacity resulting from increased uterine volume can interfere with the asthmatic disease and require adapted management. Results of studies evaluating the interaction between asthma and pregnancy provide a wide variety of results. For some authors, manifestations of asthma may worsen during pregnancy requiring reinforced medical treatment in as many as 42% of the patients. For others bronchial hyperreactivity is significantly diminished during pregnancy. These findings should be examined in light of several individual factors including the spontaneous clinical course of asthma itself and more rigorous control during pregnancy. It is thus very difficult to predict the effect of pregnancy on clinical manifestations of asthma in any given patient or from one pregnancy to another. Certain authors have observed a correlation between IgE levels and the gravity of asthma in pregnant women: normally IgE levels tend to decline during pregnancy but may remain unchanged or increase if asthma manifestations worsen. Therapeutic options remain unchanged during pregnancy although only drugs proven safe for the fetus may be used. If carefully managed, pregnancy in the asthmatic patient usually reaches term with no major problem.

Adrenal Cortex Hormones↗
PubMed1995

[Treatment of COPD (excluding acute distress)].

There is no available drug which has been demonstrated to reverse the pathological lesions associated with chronic obstructive pulmonary disease, either at the bronchial or at the parenchymal level. Bronchodilators may improve dyspnea and exercise tolerance; in some patients, they may also decrease moderately airflow obstruction. Their benefit on the rate of decline of forced expiratory volume in one second has not been documented. In the same way, the regular use of inhaled steroids has not been shown to prevent or limit the degradation of pulmonary function. On the other hand, long term oxygen supply improves the life expectancy of patients with chronic hypoxemia. Antibiotic treatment of exacerbations is recommended; however, the rationale for its use is still a matter of debate.

Anti-Inflammatory Agents↗
PubMed1995

Immunotoxicity of aminocarb. III. Exposure route-dependent immunomodulation by aminocarb in mice.

Aminocarb, a phenylsubstituted methylcarbamate pesticide (4-dimethylamino-3-methyl-N-carbamate; matacil), previously suspected of a relatively low immunotoxic potential, was administered by four different exposure routes to C57BL/6 mice. A single sublethal exposure by oral and dermal routes stimulated humoral immune response at a relatively low dose; 1/256 LD50 of aminocarb. Intraperitoneal (i.p.) injection decreased the humoral PFC response, whereas inhalation of aminocarb had no marked effect on peripheral immune status in exposed animals. Thus, i.p. exposure resulted in higher immunotoxicity over oral administration of aminocarb. Similarly, marked route-related exposure differences in immunomodulatory effects of aminocarb were noted for mitogenic stimulation of spleen lymphocytes and mixed lymphocyte response. Other indices, such as delayed type hypersensitivity (DTH) and production of interleukin-2 (IL-2) were unchanged. Interestingly, expression of major histocompatibility complex (MHC) class II by purified, lipopolysaccharide (LPS)-stimulated B cells increased equally after i.p. and oral exposures to aminocarb. Overall, a weak immunosuppressive potential of aminocarb was concluded, which was possibly due to indirect interaction of the pesticide with the immune system. However, aminocarb may represent an autoimmunity-inducing toxic.

Administration, Cutaneous↗
PubMed1995

Interaction of primer tRNA(Lys3) with the p51 subunit of human immunodeficiency virus type 1 reverse transcriptase: a possible role in enzyme activation.

In the interaction between HIV-1 RT and tRNA(Lys3) each subunit of the heterodimer interacts with tRNA showing a different affinity: Kd (p66) = 23 nM, Kd (p51) = 140 nM. Preincubation of heterodimeric RT with tRNA, at concentrations similar to that of the Kd value for p51, leads to an increase of the catalytic activity on poly(A)-oligo(dT). These results were compared to those using different tRNA analogs: oxidized tRNA, tRNAs lacking one, two or three nucleotides from the 3'-end, or ribo- and deoxyribonucleotides mimicking the anticodon loop sequence. In all cases, tRNA analogs were weaker activators of HIV-1 RT than natural tRNA. A possible mechanism of RT p66/p51 activation by tRNA and its analogs, mediated through the p51 subunit, is discussed.

Anticodon↗