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Biomedical subjects

A Cartier

Publications and source records attributed to A Cartier.

At least 163 records · Page 9Linked to original sources

Heterogeneity of hepatic microsomal UDP-glucuronosyltransferase activities. Conjugations of phenolic and monoterpenoid aglycones in control and induced rats and guinea pigs.

In this report we present evidence that the heterogeneity of hepatic microsomal UDP-glucuronosyltransferase(s) (UDPGT) activities depends on the chemical structures of the aglycones as well as their biophysical constants. Three animal models were used: Wistar rats, which have active UDPGTs; Gunn rats, in which some of the UDPGT activities are reduced, but which can be induced by phenobarbital; and guinea pigs. In Wistar rats, we found that some coumarins were poor substrates of UDPGT (GT1) and that twenty monoterpenoid alcohol activities showed typical phenobarbital-inducible behavior. In Gunn rats, we showed that substitution of the phenolic aglycone by bulky (alkyl- or methoxy-) groups in the 2-position of the phenolic ring decreased UDPGT (GT1) activity, whereas substitution in the 4-position resulted in an increase in this activity. We also showed that, in this particular strain, activities toward terpenes were less affected than activities toward flat (aromatic) aglycones. Induction by phenobarbital in Gunn rats increased the activity and limited the deficiency for monoterpenoid alcohols. In guinea pigs, we confirmed that phenobarbital selectively increased the activities of UDPGT towards twenty monoterpenoid alcohols without affecting other typical phenobarbital-induced activities such as those for conjugation of morphine. Finally, we showed that orientation of the aglycone molecule in the active site was apparently related to its dipole moment and that the distance between "acceptor-oxygen" (hydroxyl) and the carbons out of the general plane of the molecule was an important factor. These studies clearly suggest that rat and guinea pig contain a UDPGT(monoterpenoid alcohols) with restricted specificities and also that UDPGT(GT1) comprises at least two or three different isoenzymes, each with a slightly different restricted specificity towards flat aromatic aglycones.

Animals↗

Follow-up of occupational asthma caused by crab and various agents.

Sixty-three subjects with occupational asthma caused by crab (n = 31) and various other agents (n = 32) were studied after cessation of exposure at work for mean +/- SD intervals of 12.3 +/- 5.5 and 24.5 +/- 18.7 months (greater than 6 months in every subject), respectively. Nineteen of the subjects with asthma caused by crab and 30 of the subjects with asthma caused by various agents were still symptomatic of asthma, nine subjects of the latter group requiring bronchodilators (with inhaled beclomethasone in five) regularly. No significant changes in baseline spirometry were observed at the time of follow-up as compared with initial assessment, nine subjects (all in the asthma group caused by various agents) demonstrating significant bronchial obstruction. Improvement in bronchial responsiveness to histamine was significant (p less than 0.01) in the group with asthma caused by crab but not in the other group. Forty-eight of 52 subjects still had significant airway hyperexcitability. Subjects with asthma caused by crab who were asymptomatic and those subjects with asthma caused by various agents who used bronchodilators only if they were needed had worked for shorter intervals after onset of symptoms (p less than 0.01 and p less than 0.05, respectively). It is concluded that subjects with occupational asthma caused by various agents can remain symptomatic of asthma and demonstrate a persistence of bronchial obstruction and hyperexcitability for prolonged intervals after cessation of exposure.

Adult↗

Isolated late asthmatic reaction due to nickel sulphate without antibodies to nickel.

A worker with occupational exposure to nickel developed asthma a few months after starting work. Skin prick tests to nickel sulphate were negative. Inhalation challenge with nickel sulphate, at a concentration of 10 mg/ml for 30 min induced a late asthmatic reaction, starting 3 hr after the end of exposure leading to severe nocturnal attack. Tests for antibodies with nickel reactivity were negative.

Adult↗

Occupational asthma due to azobisformamide.

Azobisformamide is a low molecular weight agent used in the plastic industry as a foaming product. Two subjects with a history of work-related asthma in association with exposure to azobisformamide underwent specific inhalation tests. One subject developed an isolated late asthmatic response, whereas in the other a dual reaction was observed.

Adult↗

Allergic bronchopulmonary aspergillosis and sensitization to Aspergillus fumigatus in chronic bronchiectasis in adults.

Fifty adult subjects for whom a diagnosis of idiopathic bronchiectasis (excluding those secondary to tuberculosis or hypogammaglobulinaemia) had been confirmed previously were investigated by: questionnaire; blood eosinophil count; sputum culture for Aspergillus fumigatus and eosinophil count; chest radiography; skin-prick tests with several aeroallergens and four preparations of A. fumigatus, including a reference extract; measurement of specific IgE antibodies; precipitin testing and self-crossed immunoelectrophoresis with A. fumigatus. Five subjects were possible cases of allergic bronchopulmonary aspergillosis in whom the condition had been previously misdiagnosed or in whom sensitization to A. fumigatus had occurred after the onset of bronchiectasis. These five subjects had positive immediate skin reactions to A. fumigatus and a history of recurrent pneumonias. Four had a previous history of asthma and the others showed increased bronchial responsiveness to inhaled methacholine. At the time of the survey, A. fumigatus grew in the sputum of one out of five subjects. These subjects had increased levels of specific IgE. Two had precipitins by double diffusion and three subjects were positive on self-crossed immunoelectrophoresis. It is concluded that allergic bronchopulmonary aspergillosis or evidence of sensitization to A. fumigatus can be identified in a significant proportion of adult subjects with so-called idiopathic bronchiectasis.

Adult↗

Slope of the dose-response curve to inhaled histamine and methacholine and PC20 in subjects with symptoms of airway hyperexcitability and in normal subjects.

Slopes of the dose-response curves to inhaled histamine or methacholine and PC20 were compared in 14 subjects with symptoms of bronchial hyperexcitability and in 10 normal subjects. Slopes were obtained by analyzing curves with 3 to 6 points by the least squares method. Only curves with satisfactory correlation coefficients corresponding to p values less than 0.05 were kept for analysis. Twelve of the 14 subjects with symptoms of bronchial hyperexcitability and 1 of the 10 normal subjects had slopes greater than 20 (percent change in FEV1/log histamine or methacholine concentration) (chi-square = 13.5, p less than 0.001). Eleven of the 14 subjects with symptoms of bronchial hyperexcitability and 1 of the 10 normal subjects had PC20 results less than or equal to 16 mg/ml (chi-square = 11.0, p less than 0.001). It is concluded that, using the method described in our study, slopes of the dose-response curve to inhaled histamine or methacholine are different in subjects with and without symptoms of bronchial hyperexcitability.

Adult↗

Kinetics of the recovery of airway response caused by inhaled histamine.

The time course of recovery from airway response induced by the inhalation of progressively doubling doses of histamine phosphate (3 to 4 depending on the subject) was studied in 8 asthmatic subjects by serial measurements of lung resistance (RL). For every subject, the time required for functional recovery became longer with increasing histamine doses and/or degrees of airway response. The slopes of the curves obtained from a single exponential fit relating time on the abscissa and functional recovery on the ordinate were significantly (F = 4.9 to 50.0, p less than 0.01) and progressively lower in 7 of 8 instances. This suggested a multiple compartment model, which was confirmed (r2 greater than or equal to 0.95) in 5 subjects by applying a double exponential regression that provided the most satisfactory fit. We conclude that the recovery from airway response caused by inhaled histamine is longer with increasing doses of histamine and/or degrees of airway response. A double-compartment model, a fast one followed by a slow one, fit this pattern of recovery in 5 of the 8 subjects.

Adult↗

Occupational asthma in snow crab-processing workers.

The prevalence of occupational asthma was studied in two snow crab-processing industries in operation since 1980. Before the 1982 season, all except 10 of the 313 employees were investigated by a questionnaire, prick skin tests with common allergens, crab n and crab-boiling water extracts, and spirometry. The diagnosis was confirmed in 46 (15.6%) workers (including 33 of 64 subjects with a history highly suggestive of occupational asthma in the previous seasons) by (1) specific inhalation challenges in 33 subjects (one immediate, nine dual, and 23 late asthmatic responses) and/or (2) a combination of monitoring of peak expiratory flow rates (n = 12) and significant changes in bronchial responsiveness to histamine (n = 16) as well as in spirometry (n = 18) after reappearance of symptoms on return to work. Positive skin tests to crab (p less than 0.001) and, to a lesser degree, smoking history (p = 0.03) but not atopy (p greater than 0.05) were related to the presence of occupational asthma. A high prevalence of rhinoconjunctivitis (35 of 46) and urticaria (16 of 46) was also documented in the affected individuals.

Asthma↗

Occupational asthma due to pepsin.

A 30-year-old atopic worker exposed to pepsin powder, herb, and pollen extracts at work developed an increase in asthmatic symptoms. Monitoring of peak expiratory flow rate revealed more important fluctuations at work. Skin prick tests yielded a large immediate reaction to pepsin. Specific inhalation challenges confirmed the diagnosis; an intense early response was documented after exposure to pepsin. The pepsin IgE RAST was positive and selectively inhibited by pepsin.

Adult↗

Effect of sodium cromoglycate on histamine inhalation tests.

Sixteen adult asthmatic subjects in a clinical steady state were included in the study. On day 1, after baseline assessment of spirometry (FEV1, FEV1/FVC, FEF25-75), they underwent three to four consecutive inhalation tests using twofold increasing doses of histamine to measure the provocative concentration causing a fall in FEV1 of 20% (PC20). Baseline FEV1 was back to +/- 5% of the initial assessment before each histamine inhalation test (HIT). On days 2, 3, and 4, after baseline spirometry which confirmed that FEV1 was within 10% of initial day 1 assessment, placebo-lactose (P) or 40 mg of sodium cromoglycate (SCG) were nebulized in a double-blind randomized 4.3.1. two-treatment crossover study design. Ten minutes later, spirometry was repeated and followed by an HIT. Baseline spirometry was not significantly different on each day or after P and SCG. There was no statistical difference between the geometric means of the three or four PC20's done on day 1, indicating that there is no tachyphylaxis induced by repeated HIT. There was no statistical difference between mean PC20 after P (0.52 +/- 3.3 (SD) mg/ml), after SCG (0.50 +/- 3.2), and of the three to four HIT done on day 1 (0.40 +/- 3.6). We conclude that in asthmatic subjects SCG has no acute bronchodilator effect and does not alter the response to inhaled histamine.

Adult↗

Monitoring of maximum expiratory peak flow rates and histamine inhalation tests in the investigation of occupational asthma.

A 49 year old carpenter developed asthma after he was employed in a new workshop. Specific inhalation tests carried out in a laboratory with presswood sawdust and the different glues used at work were negative. Monitoring peak expiratory flow rates (PEFR) at work revealed a progressive fall on consecutive days with recovery after periods off-work. Histamine inhalation tests showed a definite increase in bronchial hyperexcitability after working periods. Monitoring of PEFR in conjunction with histamine inhalation tests can thus help in confirming occupational asthma.

Asthma↗

Histamine phosphate has a cumulative effect when inhaled at five minute intervals.

As the duration of bronchoconstriction induced by inhaled histamine phosphate is greater than five minutes, a study was carried out to determine whether this leads to a cumulative effect when histamine is inhaled at five minute intervals as in standardised procedures. Fourteen clinically stable adult asthmatic subjects were studied. In the first part of the study (the noncumulative stage) they inhaled doubling concentrations of histamine until appreciable bronchoconstriction occurred (changes close to 50% in lung resistance for seven subjects and 15% in forced expiratory volume in one second for seven others). After functional recovery the last concentration of histamine was nebulised on two more occasions, allowing for functional recovery after each nebulisation. In the second part of the study (the cumulative stage) subjects inhaled, depending on their responsiveness, three to eight consecutive doses of the histamine concentration last administered in the non-cumulative stage, these doses being administered at five minute intervals, without recovery. The cumulative effect was assessed by linear regression analysis of the changes in the specific functional indices, all the values obtained during the non-cumulative stage being given the score 0 and those obtained during the cumulative step scores of 1, 2, etc. In all but one instance significant (p less than 0.01) correlations were obtained and the slopes were positive, thus showing a cumulative effect. It is concluded that histamine has a cumulative bronchoconstrictor effect if inhaled at five minute intervals once appreciable bronchoconstriction has been reached.

Adult↗

Bronchial responsiveness to methacholine and effects of respiratory maneuvers.

Eight asthmatic and six normal subjects had methacholine chloride inhalation tests on two visits. On first assessment the provocative concentration causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) was measured. On the second visit the provocative concentration causing a 35% fall in specific lung conductance (PC35sGL) was obtained in addition to the PC20FEV1. Lung resistance was continuously monitored to evaluate the bronchomotor effect of FEV1 maneuver. Results of PC20FEV1 were within one single twofold concentration on the two visits. In all subjects but one PC35sGL was lower than PC20FEV1, and in 10 instances this difference was superior to a single twofold concentration. The bronchodilator effect of FEV1 maneuver was significantly although loosely related to base-line airway caliber and excitability. However, we were unable to show a significant relationship between the differences between PC20FEV1 and PC35sGL and this bronchodilator effect. This suggests that other factors may explain the greater sensitivity of PC35sGL compared with PC20FEV1.

Asthma↗

Nonallergic bronchial hyperexcitability in chronic bronchitis.

The aim of this study was to assess responsiveness to inhaled histamine and methacholine using PC20, the concentration causing a 20% fall in forced expiratory volume in one second (FEV1) in 28 subjects with chronic bronchitis excluding asthma. Eighteen subjects had airway hyperexcitability, as demonstrated by a PC20 less than 16 mg/ml. The response to histamine and methacholine was not significantly different and the correlation coefficient was 0.75. Baseline airway caliber was related to the level of hyperexcitability, as 14 of 14 subjects with a FEV1 to forced vital capacity ratio less than 95% pred and/or a forced expiratory flow during the middle half of the FVC less than 80% pred, and only 4 of 10 subjects with normal spirometry, had a PC20 less than 16 mg/ml (x2 = 15.6, p less than 0.001). There was no correlation between blood or sputum eosinophilia, total IgE levels, or atopy and the level of airway hyperexcitability. Spontaneous daily variations of peak expiratory flow rates were significantly (t = 2.43, p less than 0.05) more pronounced in subjects with PC20 less than 16 mg/ml. We conclude that airway hyperexcitability assessed with PC20 is often present in chronic bronchitis and more often so in the presence of airway obstruction.

Bronchi↗

Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure.

Serial measurements of symptoms, peak flow rates, methacholine bronchial responsiveness, and ragweed-specific IgE antibodies were made before and during the ragweed pollen season in 13 sensitized subjects. Allergen inhalation tests were carried out with aerosols of pollen extract out of season in nine subjects; isolated early asthmatic responses were provoked in four, and dual responses (early followed by late) were provoked in five. During the pollen season all subjects developed hay fever and eight had symptoms of asthma. There was a real increase in methacholine responsiveness during the ragweed season. This increase appeared before or after the occurrence of asthma symptoms and changes in flow rates and was greater in subjects with symptoms in the pollen season, dual responses after allergen inhalation tests, and higher levels of ragweed-specific IgE antibodies. The results confirm the occurrence of seasonal asthma and increases in nonallergic (nonspecific) bronchial responsiveness to methacholine from seasonal pollen exposure. They suggest that the occurrence of symptoms is closely linked to the allergic inflammatory reaction and the induction of increased nonallergic responsiveness.

Adolescent↗