Search

Standard electrophoretic methods for the diagnosis of hemoglobinopathies are confounded in individuals chronically transfused. We present the accurate diagnosis of sickle cell disease in two such transfused patients by the application of polymerase chain reaction technology to analyze patient's hemoglobin beta-chain genes directly.

Summary Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 × 10−9 mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects. However, further studies are necessary to investigate the exact role and the mode of action of tachykinins in human airways.

Mutants of Drosophila melanogaster that are sensitive to chemical mutagens were analyzed for sensitivity to X-rays and for the capacity to repair single-strand DNA breaks induced by X-rays. Analysis of X-ray sensitivity demonstrated that 74% of the mutants assayed display some X-ray sensitivity, with 75% of the sensitive lines being extremely sensitive. Repair of single-strand breaks was assayed after both high and low doses of irradiation in order to permit detection of repair over a wide range of damage. The results of this investigation fail to show a correlation between X-ray sensitivity and this particular repair process. Repair of single-strand breaks is therefore mediated by repair processes unrelated to those that are disrupted in the current mutant collection.

The endogenous tachykinins exhibit a range of properties which may be relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, and a histamine PD20 mean value of 0.024 mg, were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phosphoramidon sodium salt (10(-5) M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV1 values (3.29 +/- 0.90 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.

This study was performed in a randomized double-blind manner on 6 separate days in 10 asthmatic patients to investigate the effect of a sustained theophylline on baseline bronchial hyperreactivity to histamine in relation to the theophylline serum levels and the degree of bronchodilatation produced. No significant bronchodilatation was seen after theophylline administration at every time of evaluation. An improvement of PD20 values of histamine was observed after 4 h (p less than 0.05), 8 h (p less than 0.01) and 12 h (p less than 0.05) from theophylline administration versus respective PD20 values obtained with placebo at the same times. No significant correlation was found between serum theophylline levels and percentage change of PD20 values after drug administration (r = 0.250). We observed an improvement of PD20 mean values in relation to the maximal serum theophylline concentration but our study failed to correlate the degree of protection with serum concentration.

There is now considerable evidence in favor of vasoactive intestinal peptide (VIP) as a neurotransmitter of nonadrenergic noncholinergic nerves in the airways. The purpose of our study was to evaluate the influence of inhaled VIP on bronchomotor tone after a beta-adrenergic- and cholinergic-receptor blockage. The study was performed in six patients with asthma in 4 days. On the first day, a propranolol provocative dose producing a 20% change in FEV1 (PD20) was determined from the individual semilogarithmic dose-response curve. On the other days, the propranolol challenge was performed after inhalation of ipratropium bromide (40 micrograms), VIP (70 micrograms), and both drugs in randomized double-blind order. Statistical analysis was performed by two-way analysis of variance. The results demonstrated that mean propranolol PD20 was 0.14 mg (geometric mean + SD = 1.22). Ipratropium bromide administration, like VIP administration, significantly raised the PD20 value. The administration of both drugs elicited a further remarkable increase of mean propranolol PD20. The results demonstrated that inhaled VIP influences bronchomotor tone and that this effect is independent of the cholinergic blockage.

The exact mechanism of adenosine-induced bronchoconstriction in patients with asthma is unknown. Adenosine contraction of guinea pig trachea was antagonized by inhibitors of cyclooxygenase. The aim of this study was to investigate the effect of indomethacin (100 mg/day) on adenosine-induced bronchoconstriction in 14 asymptomatic patients with asthma. Airway response was evaluated as FEV1, and adenosine was administered as an aerosol diluted in 0.9% saline to produce a concentration range of 0.125 to 4 mg/ml. The dose of adenosine producing a 20% change in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curve; the results of PD20 were converted to log values for statistical analysis (Student's paired t test). The study was performed on 3 separate days. On the first day, the adenosine challenge was performed, and on subsequent days patients were pretreated with either placebo or indomethacin in a randomized, double-blind manner. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 0.71 mg (95% confidence limits, 0.44 to 1.16). After placebo, a geometric mean PD20 of 0.91 mg (95% confidence limits, 0.53 to 1.58) was obtained. Indomethacin pretreatment decreased adenosine hyperresponsiveness and shifted the dose-response curves of adenosine challenge to the right with a geometric mean PD20 of 1.28 mg (95% confidence limits, 0.64 to 2.56). The effect of indomethacin on adenosine bronchoconstriction (p less than 0.01 versus baseline; p less than 0.05 versus placebo) suggests an indirect mechanism of adenosine on inducing release of arachidonic acid derivatives. Inflammatory mediators inhibited by indomethacin may be involved in adenosine bronchoconstriction, even if this mechanism is not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Se estudio la respuesta hemodinamica al prazosin (PZ) en 12 pacientes con infarto agudo de miocardio (IAM) y falla de bomba definida por los datos clinicos (disnea o polipnea, ester-tores congestivos

Different therapies can be applied for the prevention of chronic bronchitis exacerbations: vaccinations, antibiotics, immunomodulating and mucoregulating drugs. Among the latter, ambroxol was tested i

The study was performed on 13 asthmatic patients to determine whether inhaled dipyridamole would act directly by inducing bronchoconstriction or indirectly by potentiating the adenosine-induced bronchoconstriction. The study was performed in 3 consecutive days. On the first day adenosine challenge was performed and the PD20 value calculated. On the other days the adenosine challenge was done 5 min after randomized inhalations of dipyridamole or a control solution. The mean percent change in FEV1 after dipyridamole (delta % = 2.0) and control solution (delta % = 1.0) was not significant. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 1.09 mg. After control solution inhalation, a mean PD20 value of 1.31 mg was observed. Dipyridamole inhalation increased adenosine hyperresponsiveness and in all subjects shifted the dose-response curves of adenosine challenge to the left with a mean PD20 value of 0.40 mg. This enhancing effect of dipyridamole was significant when compared with the baseline value (P less than 0.01) and control solution (P less than 0.01). The study demonstrated that dipyridamole inhalation increased airway responsiveness to adenosine in all subjects. This effect is due to indirect activity of dipyridamole on airways without changes in baseline airway caliber.

Classification of different types of preventive measures for ischemic heart disease (IHD) has been much debated. In the classical use of terms “primary prevention” (prevention of occurrence) includes removal of risk factors in otherwise healthy individuals, while the attempts to change diet and life style in the very early age, in order to avoid the acquisition of risk factors, has been called “preprimary prevention” or “early prevention.”

Inhaled adenosine causes bronchoconstriction in asthmatic patients. In 7 symptom-free asthmatics a study was performed to investigate the effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction. All patients were challenged with increasing doses (from 0.03 to 2 mg) of nebulized adenosine to assess airway reactivity. The same procedure was repeated on different days at the same time each morning after administration of placebo and drugs in a randomized double-blind study. Airway response was measured as the forced expiratory volume in 1 s (FEV1). The PD20 value and the fall of FEV1 at the provocative dose were calculated. The PD20 data were modified in log values and the statistical analysis was performed by two-way analysis of variance. Mean decrease of FEV1 after adenosine challenge was 26.02 and 28.87% with placebo sodium cromoglycate and placebo nifedipine, respectively. Sodium cromoglycate and nifedipine gave a mean decrease of FEV1 of 6.44% (p less than 0.05) and 22.22%, respectively. PD20 values (geometric mean) after adenosine inhalation were 0.72 and 0.74 mg for placebo sodium cromoglycate and placebo nifedipine and 0.86 mg for nifedipine. Sodium cromoglycate gave a significant protection against adenosine in all subjects and in no case did the maximum dose used (2 mg) result in a fall in FEV1 value greater than 20%. Adenosine antagonism could be considered as a possible factor contributing to the pharmacologic efficacy of sodium cromoglycate in asthmatic patients. No protective effect was noticed with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

There is evidence suggesting the involvement of the surfactant system in the development of lung diseases in cigarette smokers. The aim of the present study was to evaluate the effect of Ambroxol on lung epithelial permeability (LEP) in healthy smokers. Ambroxol is known to stimulate surfactant production. Twenty male patients aged between 20 and 60 years participated in the study. They all smoked at least 15 cigarettes daily for 10 years. We carried out a random double-blind study versus placebo: the drug (Ambroxol 75 mg) or the placebo were given once a day after breakfast for 30 days. Lung permeability was evaluated through scanning pulmonary scintigraphy by inhalation of the polydispersed liquid aerosol diethylenetriaminepentaacetic acid (DTPA), labelled with 99Tc, and delivered by a 'Venticis' system. LEP was expressed as the half-time clearance from the lung of 99Tc-DTPA (T50). The significance of the differences between the two treatments was determined by the Student's test for unpaired data. LEP was not different from the baseline value (T50 = 18.49 min) after placebo administration (T50 = 19.57 min). The patients receiving Ambroxol showed an increased LEP mean value (T50 = 18.36 min) in comparison with the baseline mean value (T50 = 16.41 min). Our results demonstrate that the treatment with Ambroxol was able to decrease LEP in 6 subjects, though not significantly.

The effect of nedocromil sodium (4 mg; 7.8 X 10(-6) M) on adenosine-induced bronchoconstriction was compared with that of a higher dose of sodium cromoglycate (10 mg; 24.1 X 10(-6) M). Eleven allergic asthmatic patients (mean age 26.28 +/- 12.21 years) were studied. Adenosine (0.03-4.00 mg) was administered as nebulized aerosol. The dose of adenosine producing a 20% change in FEV1(PD20) was calculated from the individual semi-logarithmic dose-response curves. Patients were studied on 4 separate days. On the first day the adenosine challenge was performed; on subsequent days patients were pretreated (20 min before challenge) with either placebo or test drug (nedocromil sodium 2 x 2 mg or sodium cromoglycate 2 x 5 mg) administered by pressurized aerosol in a randomized, double-blind manner. Statistical analysis was performed by two-way analysis of variance. Neither sodium cromoglycate nor nedocromil sodium showed a significant bronchodilator effect. In patients treated with placebo, inhalation of adenosine produced a dose-related bronchoconstriction with a geometric mean PD20 of 0.42 mg. After drug administration the mean PD20 values were 1.29 mg with sodium cromoglycate and 2.30 mg with nedocromil sodium. Both drugs produced a significant increase in mean PD20 value in comparison with placebo and baseline (P less than 0.01). These results demonstrate that nedocromil sodium (4 mg) is significantly more potent than a larger dose of sodium cromoglycate (10 mg) in inhibiting adenosine-induced bronchoconstriction (P less than 0.05).

Summary Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 × 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23–736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.

The aim of this study was to evaluate in vivo the effect of inhaled substance P (SP) and to determine the effect of sodium cromoglycate (SCG) on bronchospasm induced by its inhalation in 6 asthmatic patients. At the beginning of the study, all patients were asymptomatic, with an FEV1 value not less than 20%. SP was administered as aerosol, prepared in 0.9% saline to produce a dose range of 0.03-1 mg. Airway response was measured as FEV1 using a pulmonary system 47120A Hewlett-Packard instrument. The dose of SP producing a 20% change in FEV1 was calculated from the individual semi-logarithmic dose-response curve (PD20). After administration of the placebo, SP produced a dose-related bronchoconstriction with a geometric mean PD20 of 0.15 mg. After SCG, the mean PD20 value was of 0.64 mg (p less than 0.01). These results confirmed the bronchospasm induced by inhalation of SP and demonstrated that SCG is able to prevent this effect although it is impossible to define the exact mechanism of the drug.