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Biomedical subjects

A Arnaud

Publications and source records attributed to A Arnaud.

At least 127 records · Page 7Linked to original sources

Asthma without airway hyperresponsiveness to carbachol.

Generally, asthma is closely associated with hyperresponsiveness to bronchoconstrictor agents. However, we have observed three patients who initially had symptoms of asthma but no hyperresponsiveness. Responsiveness to carbachol was assessed by specific airway resistance (SRaw) measurement after bronchodilatators had been discontinued. The carbachol challenge was repeated 6-18 months later. Initially, no change in SRaw was observed after inhalation of 3 mg carbachol (cumulated dose). On the second occasion, carbachol responsiveness increased into the asthmatic range while the baseline values of SRaw were not different. Since we have used the SRaw measurement, the bronchodilatator effect of maximal inspiration is not the explanation for the failure to demonstrate hyperresponsiveness. These observations suggest that airway hyperresponsiveness is not a necessary condition for induction of asthma and symptoms of asthma may precede the appearance of airway hyperresponsiveness.

Adolescent↗

Biosynthesis regulation of the beta-glucosidase produced by a yeast strain transformed by genetic engineering.

The biosynthesis of the beta-glucosidase enzyme was studied in a transformed yeast obtained by cloning in Saccharomyces cerevisiae the structural gene coding for beta-glucosidase in Kluyveromyces fragilis. The enzyme biosynthesis was found to be non-adaptative, and repressed by glucose. These features are similar to those observed in K. fragilis. beta-Glucosidase activity in the transformed yeast was much higher than in K. fragilis. We attempted to ferment cellobiose with the transformed yeast: practically no cellobiose was consumed, growth and ethanol production were negligible. Warburg experiments showed that cellobiose fermentation did not occur when the respiratory chain was not functioning.

Cellobiose↗

Regulation of nitrile-hydratase synthesis in a Brevibacterium species.

The regulation of nitrile-hydratase biosynthese was studied in Brevibacterium sp R 312. Enzyme biosynthesis was not influenced by any carbon and nitrogen source used in the growth medium. It was, however, repressed by amide and amide analogues. Acetamide repressed nitrile-hydratase biosynthesis and induced the wide-spectrum amidase. Therefore, it appeared reasonable to hypothesize a single repressor gene for the nitrile-hydratase/wide-spectrum amidase system.

Acetamides↗

Comparative study of the respiratory effects of two beta 1-selective blocking agents atenolol and bevantolol in asthmatic patients.

Seven asthmatic patients were given a single placebo tablet in a first test session and then in two subsequent double blind sessions they randomly received 400 mg bevantolol or 100 mg atenolol, with at least 2 days between each of the sessions. Neither beta-blocker had any significant effect on FVC as compared to the placebo. FEV 1, however, was significantly lower 2 and 3 h after atenolol or bevantolol; there was no significant difference between the effects of the two drugs on FEV 1. Peak expiratory flow rate was reduced by bevantolol but not by atenolol, the difference reaching significance after 3 h. Fenoterol inhalation at the end of each test session always enhanced pulmonary performance, but to a lesser extent after bevantolol than after placebo or atenolol. A slower heart rate was recorded 2, 3, and 4 h after bevantolol and 3 and 4 h after atenolol; the mean 2-h value was significantly lower with atenolol than with bevantolol. No patient suffered any adverse effect. Bevantolol may be slightly less selective than atenolol.

Adrenergic beta-Antagonists↗

[Nifedipine in the treatment of chronic cor pulmonale].

The effects of a single dose of nifedipine (20 mg sublingual) on the haemodynamics and parameters of tissue oxygenation were assessed by right heart catheterisation and oximetry of mixed arterial and venous blood in 24 patients with pulmonary hypertension secondary to severe chronic obstructive airways disease. The haemodynamic effects of 15 days' oral therapy (30 mg/day) were studied in 10 other patients. Significant improvement in right ventricular pump function (25 p. 100 increase in cardiac index. average reduction of 3 mmHg of right ventricular end diastolic pressure), and lowering of pulmonary hypertension (mean pulmonary artery pressures reduced by an average of 10 p. 100 and total pulmonary resistance by 25 p. 100) were observed after the single dose of nifedipine. This improvement was maintained after oral therapy for 15 days. The significant improvement of tissue oxygenation was reflected by an increase in oxygen transport (+ 24 p. 100), in the coefficient of delivered oxygen (+ 19 p. 100), in the oxygen partial pressure (+ 4 p. 100) and saturation (+ 3 p. 100) in the mixed venous blood. Arterial lactate concentrations fell by about 28 p. 100. In addition, a moderate fall in ppO2 and arterial saturation was observed due to a weak shunt effect which was more than compensated by the increase in cardiac output, and especially by the increase in the coefficient of relieved oxygen. These results show that nifedipine may be a valuable addition in the treatment of cor pulmonale secondary to chronic obstructive airways disease by improving right ventricular haemodynamics and pulmonary circulation and by increasing the quantity of oxygen delivered.

Adult↗

[Comparative study of anticholinergic and betamimetic agents in the treatment of asthma attacks].

Four regimens of bronchodilatation therapy administered on 2 consecutive days were tested in 4 randomly selected groups of 6 asthmatic patients: 1) intravenous atropine + inhaled oxitropium bromide; 2) intravenous atropine alone; 3) intravenous salbutamol + inhaled salbutamol; 4) intravenous salbutamol alone. On the second day the treatments were crossed over, i.e. the groups which had received the intravenous + inhaled treatment on the first day received the same drug in i.v. form alone and vice versa. The intravenous doses of atropine and salbutamol were 0.5 mg each administered over 1 hour, and those of oxitropium and salbutamol aerosol were 100 mcg hourly for 6 hours. In addition, all patients received methylprednisolone 20 mg i.v. on each day of the study. Peak expiratory flow rate (PEFR), heart rate (HR) and arterial pressure were recorded before treatment, then hourly for 6 hours. All 4 regimes produced significant improvement in PEFR (P less than 0.01). Bronchodilatation was not significantly different in the 4 groups, but improvement was markedly better when intravenous injections were associated with inhalations. No side-effects were recorded with the anticholinergic drugs, whereas a slight but significant increase in HR (P less than 0.05) was observed with the adrenergic drug. This study suggests that anticholinergic agents provide a therapeutic alternative for severe acute asthma when beta 2-adrenergic stimulants cannot be used.

Administration, Inhalation↗

[Comparative study of plasma levels of 2 delayed-action theophyllines: Theostat 200 and Theodur 200, after a single evening dose].

Plasma levels of two slow-release theophylline preparations, Theostat 200 and Theodur 200, administered in one single evening dose during steady state were compared in a double-blind cross-over study involving 10 male volunteers (mean age: 52.3 +/- 7.5 years) with chronic obstructive lung disease and free from pathology or treatment that might have interfered with theophylline kinetics. Mean areas under the drug plasma concentration curves were 222 +/- 101 mg.h/l with Theostat 200 and 264 +/- 114 mg.h/l with Theodur 200. Mean percentages of fluctuation were 72 +/- 13 and 71 +/- 17 respectively (N.S.). The free fractions measured at peak level were higher with Theodur (9 +/- 2.9 mg/l) than with Theostat (7.1 +/- 2.4 mg/l) (P less than 0.05). While mean values were approximately the same with the two products, interindividual variations were pronounced, with several plasma levels of Theostat 200 in areas regarded as ineffective and several plasma levels of Theodur 200 in areas regarded as toxic. This type of preparation therefore is mostly useful to patients who would benefit from high plasma levels of theophylline in the early morning.

Adult↗

[Results of specific desensitization in allergic asthma].

Some recent works currently give some solid scientific basis to suppose that immunization with appropriate antigens might be beneficial for asthmatic patients. As numerous studies have now shown on the one hand that there was a relation between allergy, inflammation and bronchial hyper-reactivity and in the other that desensitization was able to modify the liberation of mediators to inflammation and the responses attributed to these mediators. The number of controlled studies performed up till now with the principal allergens are, for asthma, insufficient. However, no-one currently doubts the efficacy of specific desensitization to spasmodic pollen coryza. For pollen asthma, six studies conclude that there were superior results with desensitization than to placebo. Two studies showed no difference. Four controlled studies made for episodic house dust mite coryza ended with a favourable result. In allergic bronchial asthma to the dust mite, nine studies were favourable and five showed no benefit. It should be mentioned at this stage that all the studies on children have shown favourable results. There are few studies on the efficacy of desensitization to animal squamae (epithelial debris). Nevertheless, a very recently published study has shown, using cat squamae, clinical efficacy on bronchial, nasal and ocular symptoms. Desensitization with mould extracts cannot be judged at present, published controlled studies on the subject are almost nonexistent. On the other hand at the moment one can say that with microbial antigens non-standardised antigens, no clinical evidence has been shown to date. Incidents and accidents encountered during specific desensitization in respiratory allergy are extremely rare but may be serious.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Leukocyte histamine release to suxamethonium in patients with adverse reactions to muscle relaxants.

In an earlier study we confirmed the usefulness of intradermal skin tests and histamine release in diagnosis of patients reactive to muscle relaxants, and we suggested an IgE-mediated reaction rather than an idiosyncratic mechanism. In a later study, we studied the relationship between (Formula: see text) that is one of the muscle relaxants producing the most frequent adverse reactions under anesthesia. Histamine release was measured in five patients with increasing concentrations of suxamethonium in the presence or absence of human serum albumin in Tris buffer. Suxamethonium by itself without any carrier in the buffer could, in vitro, act as a true allergen on target leukocytes in the sensitized patients' group. Acetylcholine (20 and 200 micrograms/ml) did not induce significant histamine release in five patients with positive histamine release in the presence of suxamethonium. Preincubation of leukocytes from 11 patients for 30 min with 20 and 200 micrograms of acetylcholine in Tris albumin CA++ Mg++ buffer decreased the histamine release induced by suxamethonium (10 micrograms/ml); mean maximal histamine release of 46% +/- 4.2 was reduced to 31.4 +/- 5.8 and 7% +/- 4 (p less than 0.001), respectively. However, in eight control subjects similar concentrations of acetylcholine did not change the maximal histamine release induced by anti-IgE (0.2 micrograms/ml). In the same way acetylcholine did not modify histamine release induced by Dermatophagoides pteronyssinus extract (1/10,000 w/v) in six patients allergic to this allergen. This study suggests that suxamethonium acts as a true allergen and that acetylcholine or one of its metabolites may act as a hapten inhibitor in the model of histamine release induced by suxamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Anaphylactic reactions to suxamethonium prevention of mediator release by choline.

IgE antibodies cross-reacting with choline and suxamethonium were found in the sera of 15 of 22 patients with life-threatening sensitivity to suxamethonium, one of the most commonly used muscle relaxants. Furthermore, choline that is one of the metabolites of acetylcholine and a monovalent part of the suxamethonium molecule could act as a hapten inhibitor in vitro and in vivo, blocking specifically the basophil histamine release induced by suxamethonium and the positive skin tests to the drug in allergic patients. These results confirm the IgE dependency of allergic reactions to suxamethonium and suggest a possible way of preventing such reactions with choline.

Anaphylaxis↗

Two-week nifedipine treatment for pulmonary hypertension complicating chronic obstructive lung disease.

The effects of nifedipine on hemodynamics and blood gases were studied in 10 patients with pulmonary hypertension secondary to chronic obstructive lung disease. Two different sets of test data were recorded. The first set of readings was taken immediately before and during the initial hour after sublingual administration of 20 mg of nifedipine. The second set was taken after 2 weeks of therapy with 3 X 10 mg per day. After the acute sublingual dose, a significant decrease in pulmonary arterial pressure and pulmonary vascular resistance was recorded: 13% and 26% respectively. This decrease was accompanied by a 32% increase in cardiac output. Similar findings were recorded at the end of the 2-week therapy. Moreover, at this time, although blood gas tension had not been significantly altered, oxygen delivery was 35% higher. No adverse side effects were observed. This study suggests that nifedipine therapy can improve hemodynamics and tissue oxygenation in patients with pulmonary hypertension complicating chronic obstructive lung disease.

Administration, Oral↗