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Biomedical subjects

F Palermo

Publications and source records attributed to F Palermo.

At least 19 recordsLinked to original sources

Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients.

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 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.

Adolescent

Effect of topical application with capsaicin on skin responses to bradykinin and histamine in man.

Pre-treatment with topical capsaicin is known to induce neuropeptide depletion from sensory nerve endings and it is a useful pharmacological tool to evaluate the contribution of these nerves to skin injury and inflammation. To investigate the relative contribution of sensory neural stimulation to the action of bradykinin and histamine, a randomized, double-blind study has been undertaken evaluating the effect of topical capsaicin pre-treatment on the responses to intradermal injections of both agonists in 12 healthy volunteers. Capsaicin pre-treatment caused significant inhibition of the immediate mean flare responses (95% CI) to both bradykinin (from 51.5 [39.7-63.3] mm2 to 16.2 [8.0-24.5] mm2) (P < 0.01) and histamine (from 108.4 [80.4-136.4] mm2 to 52.3 [37.1-67.1] mm2) (P < 0.01). Topical capsaicin elicited a significant inhibition of the weal response induced by histamine, the mean weal area being reduced from 14.8 (12.6-17.0) mm2 to 12.1 (10.1-14.1) mm2 (P < 0.05). In addition, the effect of topical capsaicin was to completely inhibit the bradykinin induced weal response compared to control, the mean weal area (95% CI) being reduced from 13.4 (11.4-15.4) mm2 to 8.2 (5.3-11.0) mm2 (P < 0.01). Our findings show that repeated topical application with capsaicin led to a significant reduction of the skin responses to intradermal injections with both agonists, and particularly with bradykinin. The weal responsiveness to bradykinin may entirely follow neuropeptide release from sensory nerves within the skin and the same applies to the flare response, although this is not completely inhibited by topical application with capsaicin.

Administration, Cutaneous

Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma.

Although adenosine-induced bronchoconstriction is mainly due to mast cell mediator release, vagal reflexes have also been implicated in this response. We have investigated the effect of a specific muscarinic-receptor antagonist, ipratropium bromide, on methacholine- and adenosine-induced bronchoconstriction in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Airway response was evaluated as forced expiratory volume in one second (FEV1). Inhaled ipratropium bromide (40 micrograms), administered 20 min prior to bronchoprovocation, increased the provocation dose of inhaled methacholine and adenosine required to reduce FEV1 by 20% from baseline (PD20) from 0.11 to 0.79 mg (p less than 0.01) and from 0.57 to 1.27 mg (p less than 0.01), respectively. The mean baseline FEV1 values after administration of ipratropium bromide were significantly higher than after placebo administration (p less than 0.05). However, there was no correlation between the degree of bronchodilatation and dose-ratios for methacholine and adenosine. The findings of the present study implicate vagal reflexes in the bronchospastic response induced by inhaled adenosine in asthma.

Adenosine

[A splenic autograft in omental pockets following splenectomy for trauma. The authors' personal experience of 10 cases].

Personal experience on 10 patients splenectomised for trauma and subjected to splenic autotransplantation on omental pockets is reported. After describing autotransplant candidate selection criteria and the surgical technique followed, the flattering results are reported. Particularly interesting was the fact that no local suppuration was encountered and the transplant took in all patients, as demonstrated by scans carried out with labelled red globules and radiocolloid.

Adult

Influence of antihistamine (astemizole) and anticholinergic drugs (ipratropium bromide) on bronchoconstriction induced by substance P.

Several studies have demonstrated that neuropeptides are present in bronchial tissue. The aim of this study was to evaluate in vivo the influence of antihistamine in comparison to an anticholinergic drug on bronchospasm induced by inhalation of substance P (SP). Seven moderate asthmatic patients (mean age = 34.4 +/- 8.9), five being female, were studied. The acetate salt of SP was prepared in 0.9% saline to produce a dose range of 23 to 184 x 10(-6) mol. Patients were studied on three separate days with an interval of 3 weeks between challenges. On the first day the dose of SP producing a 20% change in FEV1 was calculated from the individual semilogarithmic dose-response curve. On subsequent days, in a randomized double-blind manner, the patients were treated either with astemizole (20 mg BID for three days) and placebo ipratropium bromide or with placebo of astemizole (twice a day for three days) and with pressurized aerosol of ipratropium bromide (IB) (40 micrograms 20 minutes before the challenge). Two way analysis of variance was used for statistical analysis. Our results demonstrated that inhaled SP is able to produce a dose-response curve of bronchoconstriction with a geometric mean of PD20 of 50.51 x 10(-6) moles (37.38 to 68.19 x 10(-6) mol). Treatment with astemizole induced a geometric mean PD20 of 65.51 x 10(-6) mol (33.02 to 130.21 x 10(-6) mol) and the premedication with the IB induced a significant (P less than .05) shift of dose-response curve to SP (geometric mean PD20 = 109.1 x 10(-6) mol; 58.67 to 204.05 x 10(-6) mol). Our results demonstrated that bronchoconstriction induced by SP could be attributed to a weak cholinergic activation and not to histamine release.

Administration, Inhalation

Tachyphylaxis to repeated challenges with inhaled adenosine in asthmatic subjects.

Adenosine, when administered as an aerosol to asthmatic subjects, provokes a prompt dose-dependent bronchoconstriction. The aim of this study was to establish whether tachyphylaxis in response to repeated inhalations with adenosine occurs in asthmatic subjects. Eight asthmatic patients were studied on three separate days (days A, B, and C) at the same time of day for each subject. Three inhalation tests were performed, separated by one hour, on each study day. The study was conducted in a double-blind fashion and performed in random order. On day A, three adenosine inhalation tests were performed to assess adenosine tachyphylaxis. On day B, a saline inhalation test was carried out between two adenosine challenges to assess the time course of the adenosine tachyphylaxis. On day C, three methacholine inhalation tests were performed to confirm that tachyphylaxis does not occur to methacholine. Repeated inhalation with adenosine, but not methacholine, produced a progressive loss of responsiveness to the nucleoside, which was particularly manifest with the third challenge.

Adenosine

Effect of indomethacin on adenosine-induced bronchoconstriction.

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)

Adenosine

Lung permeability in smokers after ambroxol treatment.

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.

Adult

Diagnostic efficacy of dynamic radiothallium uptake in thyroid nodules determined by computer-assisted scintigraphy. Reevaluation of a radioisotopic procedure.

Radiothallium (201Tl) has been proposed as a tracer in nuclear medicine for the diagnosis of cold thyroid nodules. Its potassium-mimetic characteristics, like those of 131Cs, can provide information on its turnover in the thyroid nodules; this serves as a basis for the distinction between benign and malignant thyroid tumours. The author presents a study on the diagnostic efficacy of 201Tl as a tracer for thyroid nodules with the aim of evaluating the dynamic uptake and the biodistribution of 201Tl after intravenous injection of 555-740 kBq/kg. A quantitative analysis was made by continuous scanning of 201Tl distribution during the first 20-30 min following thallium injection, with further surveys from 40 to 60 min or more when fixation in a nodule was demonstrated. The ratio between 201Tl uptakes in the nodule and in healthy tissue (density index) was calculated and a multiparametric analysis of the corresponding activity/time curves was performed. This study included 176 patients. Concordance between clinico-histological diagnosis and radio-isotopic findings was demonstrated in 102 out of 106 colloidocystic goitres, in 42 out of 48 benign nodules including thyroiditis, and in 21 out of 22 malignant tumours; a significant statistical difference in the density index between solid and cystic nodules, but no difference between benign and malignant nodules; and a different 201Tl dynamic behaviour in nodules of different nature, with a clear statistical difference in the thallium release between malignant nodular and healthy tissue (nodular disappearance index). This method can improve the diagnosis value of scintigraphy for thyroid nodules enhancing the sensitivity of the radioisotopic applications in comparison with other non-invasive techniques.

Adenocarcinoma

Effect of an aerosol delivery system on bronchodilator activity.

Metered dose inhalers (MDIs) are often used incorrectly by patients who find difficulty using MDI for drug inhalation. The study was performed in 11 asthmatic patients in four days in order to evaluate the efficiency of a new Drug Delivery System (DDS-InspirEase) for metered dose inhalers. Clenbuterol was administered via DDS and via conventional MDI in a randomized manner. On the first two days, DDS and MDI were used by patients without any physician's help. On the subsequent days, clenbuterol was administered via DDS and via conventional MDI directly by the physician. FEV1 and MEF75 values were measured 15', 30', one hour, and two hours post-drug inhalation. Statistical analysis (ANOVA) showed that clenbuterol delivered by DDS, administered by patients or by physician, produced a greater increase in FEV1 values (P less than .05) and MEF75 values (P less than .01) in comparison to the conventional MDI on each test day. No significant differences existed between physician or patient administration of clenbuterol with DDS and MDI. The results showed a greater bronchodilator effect obtained by clenbuterol delivered by DDS.

Adult

Effect of vasoactive intestinal peptide (VIP) on propranolol-induced bronchoconstriction.

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.

Adult

Comparative study of the effects of nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) on adenosine-induced bronchoconstriction in asthmatic subjects.

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).

Adenosine

Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects.

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 x 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.

Adolescent

Enhancing effect of dipyridamole inhalation on adenosine-induced bronchospasm in asthmatic patients.

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.

Adenosine

Effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction.

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)

Adenosine

Bronchospasm induced by inhalation of substance P: effect of sodium cromoglycate.

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.

Administration, Inhalation

Radioisotope evidence of varying transit of solid food in gastrectomized patients with and without dumping syndrome.

Of 29 Billroth II gastrojejunostomy patients studied by scintigraphy, 11 were dumpers and 18 were non-dumpers; of 20 controls, 11 were patients with different gastric complaints and 9 volunteers with no history of gastrointestinal pathology. The tracer used was human albumin microspheres labelled with 99mTc, mixed thoroughly with a fresh scrambled egg, cooked as an omelet and eaten as a sandwich with white toasted bread. The transit and emptying of the radiolabelled meal in the gastric and derivative loop areas were followed with gamma camera 90-120 min. In the dumpers half-emptying times were significantly shorter than in the controls; in the non-dumpers they were even shorter. Dynamic selective analysis of the radiolabelled food transit through derivative afferent and efferent loops showed, on the other hand, different patterns for the two groups of gastroresected patients: the progression of propulsive waves was very irregular and constantly hyperperistaltic only in the dumpers.

Administration, Oral