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Biomedical subjects

G Prosperini

Publications and source records attributed to G Prosperini.

30 records · Page 2Linked to original sources

Relative potencies and time course of changes in adenosine 5'-monophosphate airway responsiveness with inhaled furosemide and bumetanide in asthma.

A randomized, double-blind, placebo-controlled study was conducted to compare the effects of two chemically unrelated "loop" diuretics, furosemide (40 mg) and bumetanide (2 mg) on the bronchoconstrictor response to inhaled adenosine 5'-monophosphate (AMP) in 12 subjects with asthma. In eight additional volunteers with asthma, we also carried out a separate randomized, double-blind study to examine in more detail the time course of change in bronchial reactivity to inhaled AMP after administration of nebulized furosemide and bumetanide. Inhaled loop diuretics significantly increased the provocative concentration of AMP causing a 20% fall in forced expiratory volume in 1 second (FEV1) from the value of 21.2 mg/ml (range, 2.5 to 96.9 mg/ml) after placebo administration to 83.4 mg/ml (range, 11.3 to 345.0 mg/ml) (p < 0.01) and 33.8 mg/ml (range, 4.7 to 120.9 mg/ml) (p < 0.05) after administration of furosemide and bumetanide, respectively. After placebo administration, the provocative concentration of AMP causing a 20% fall in FEV1 (PC20 AMP) at 10, 30, and 120 minutes did not differ significantly; their geometric mean (range) values were 57.8 mg/ml (10.9 to 341.0 mg/ml), 55.0 mg/ml (13.2 to 304.1 mg/ml), and 52.8 mg/ml (14.4 to 252.2 mg/ml), respectively. When compared with placebo, inhaled furosemide significantly reduced the airway responsiveness to AMP at all time points; the PC20 AMP values at 10, 30, and 120 minutes were 154.6 mg/ml (29.4 to 658.7 mg/ml) (p < 0.01), 142.6 mg/ml (25.5 to 639.9 mg/ml) (p < 0.01), and 103.9 mg/ml (12.5 to 605.5 mg/ml) (p < 0.05), respectively. The PC20 values for AMP after pretreatment with bumetanide were significantly increased up to 110.2 mg/ml (25.9 to 639.0 mg/ml) (p < 0.01) and to 92.0 mg/ml (21.6 to 531.7 mg/ml) (p < 0.05) at 10 and 30 minutes, respectively. At 120 minutes, inhaled bumetanide failed to affect AMP airway responsiveness; the PC20 AMP was not significantly different from that of placebo, with a value of 71.5 mg/ml (22.6 to 318.0 mg/ml). We conclude that comparable equidiuretic doses of furosemide and bumetanide are effective in attenuating the airway response to AMP, with furosemide being approximately 2.5 times more potent than bumetanide (p < 0.01). The time course of change in bronchial reactivity to AMP is similar for both drugs with a peak effect at 10 minutes. It is possible that the mechanism(s) underlying the protective effects of inhaled loop diuretics in asthma may be distinct from those responsible for their diuretic properties.

Adenosine Monophosphate↗

Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects.

Neurokinin A (NKA) elicits a potent contractile effect in asthmatic airways. Its mechanism of action in bronchial asthma is still unknown. Recent work supports the view that NKA may stimulate mediator release from mast cells. To investigate the relative contribution of mast cell degranulation to the action of NKA, a randomized, double-blind study has been undertaken, to evaluate the effect of a potent and selective histamine H1-receptor antagonist, terfenadine (180 mg q.d., for three days), on bronchoconstriction provoked by inhaled NKA in six asthmatic subjects. Bronchial provocation tests with histamine were included in this study as control challenge. In the subjects studied, oral terfenadine, when compared to placebo, significantly increased the geometric mean (range) provocation dose of inhaled histamine required to reduce forced expiratory volume in one second (FEV1) by 20% of baseline (PD20) from 0.05 (0.03-0.08) mg (0.16 (0.10-0.26) mumol) to 1.19 (0.63-2.04) mg (3.88 (2.05-6.64) mumol). However, terfenadine failed to increase the airway responsiveness to NKA in all of the subjects studied, the geometric mean (range) PD15 NKA value being 0.94 (0.47-2.49) micrograms (8.36 (4.14-21.9 nmol) and 0.75 (0.48-1.59) micrograms (6.62 (4.23-14.0) nmol) after placebo and terfenadine, respectively. We conclude that NKA is a potent bronchoconstrictor agonist in asthma, being approximately 19 times more potent than histamine in molar terms. In this study on a small number of subjects, pharmacological intervention with oral terfenadine failed to achieve significant protection of the airways against the constrictor effect of NKA.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Cross-tachyphylactic airway response to inhaled bradykinin, kallidin and [desArg9]-bradykinin in asthmatic subjects.

Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[Whole body irradiation in conditioning for bone marrow transplantation. Experiences with 35 cases of leukemia].

Total body irradiation, carried out in two different regimens (10 Gy single dose; 200 cGy X 5 fractions) has been used in 35 patients with acute leukaemia or chronic leukaemia in chronic or accelerated phase, in preparation for bone marrow transplantation. The dose rate was in the range of 2-4 cGy . min-1. No lung shielding was adopted. The role of total body irradiation in the development of interstitial pneumonitis is considered. Rather than to the regimen of total body irradiation--single dose or five fractions--the incidence of interstitial pneumonitis seems to be related to other factors; mainly to the presence of Graft-versus-Host-Disease: Five patients out of six with III or IV grade GvHD, developed interstitial pneumonitis; only one patient out of twenty without GvHD or with a low grade GvHD developed interstitial pneumonitis.

Adolescent↗

[Basal blood glucose oscillations in diabetics treated with microinfused insulin. Comparison between hormonal distributions by the square wave-form at various frequencies].

Basal glycemic oscillations in 3 type I-diabetics treated with continuous subcutaneous insulin infusion (CSII) and without endogenous insulin secretion have been studied. Insulin infusion with different frequencies of square wave-form basal insulin delivery (1 min and 10 min) have been utilized. Aim of the present investigation was to observe whether basal blood glucose oscillations could be affected by the frequency of basal square wave-form insulin delivery. Blood glucose has been measured at 3 min intervals for 90 min for each frequency. The glycemic patterns obtained did not show any periodism in relationship with the two frequencies engaged, hence the glycemic fluctuation, similar between the two experiments, cannot be considered as dependent on the different frequency of insulin pulses.

Blood Glucose↗

Present status of treatment for invasive cervical carcinoma.

The results are presented of a retrospective clinical study carried out on 341 patients affected with cancer of the uterine cervix, with lymphography in the pretreatment diagnostic work-up, treated in our Institute from January 1961 to December 1976. The clinical classification of the patients studied was: 157 cases in Stage I (46.0%), 95 cases in Stage II (27.9%), and 89 cases in Stages III and IV (26.1%). During the period considered, the therapeutic approach for carcinoma of the cervix was practically constant and in line with the therapeutic policy most frequently followed for these neoplasms. For the early stages (9/341 patients or 27.6%) preference was given to a radical surgery and postoperative radiotherapy combination; for borderline cases and "bulky" and "barrel-shaped" lesions, radiotherapy usually preceded surgical treatment to enlarge its indications and improve its results (36/341 patients or 10.5%). The cases that were more developed locally or that presented contraindications to surgery received radiological treatment alone (211/341 patients or 61.9%). Radiotherapy treatment consisted of radium therapy performed with a single application of 226Ra conventional sources, followed by percutaneous irradiation with 60Co-teletherapy in the more developed cases and/or in the presence of lymph node metastases. All the patients were submitted to diagnostic lymphography at the onset of the treatment and 92 (26.9%) had lymph node metastases. In the framework of this clinical review, the 5-year disease-free survival from onset of the treatment varied from 88.2% for the cases at Stage Ib occult, 72.5% for the cases at Stage Ib, 63.8% for the Stage II cases, to 40.5% for the cases at Stage III and IV. The presence of a pathologic report at lymphography makes a considerable difference in terms of disease-free, long-term survival after treatment

Adenocarcinoma↗

[The modulator effect of bradykinin with respect to tracheobronchial clearance in healthy subjects].

Bradykinin (Bk), a vasoactive nonapeptide which has been proposed as mediator in the pathogenesis of bronchial asthma, is a potent secretagogue in canine airways and in human nasal mucosa in vivo. A study was carried out in order to evaluate the effect of inhaled Bk on tracheobronchial clearance (TBC), measured by a radioaerosol technique in 10 healthy volunteers. Subjects inhaled Bk (8 mg/mL) or vehicle placebo on two occasions, at least 2 weeks apart, in a double blind and randomized fashion 30 min after radioaerosol inhalation. TBC, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 hours (AUC 0-6h), was enhanced in 9 of 10 subjects following inhaled Bk when compared to placebo. The mean values for AUC 0-6h were significantly reduced from 132%.h to 92%.h (p < 0.001) with placebo and Bk respectively. We conclude that Bk has a marked effect on tracheobronchial clearance in normal human airways.

Adult↗

[Mast cell mediator release after endobronchial challenge with adenosine 5'-monophosphate in asthmatic subjects].

Mediator release from activated mast cells is also likely to take place in the asthmatic airways in vivo during adenosine-induced bronchoconstriction. To test this hypothesis, we evaluated mast cell mediator release directly into the airways of 9 asthmatic subjects after endobronchial challenge with adenosine by bronchoalveolar lavage (BAL). The mediators measured were histamine, tryptase, and PGD2. When compared to the saline-challenged segment, the response to AMP instillation was characterized by a prompt reduction in airway calibre paralleled by a significant 4.2-fold increase in PGD2 levels in the BAL fluid (p = 0.004). There were also increases in median histamine (from 200.1 to 433.6 pg/mL) and tryptase levels (from 0.31 to 0.46 ng/mL) recovered after AMP challenge, although they were not significant. These findings support the view that acute bronchospastic response to AMP in asthmatic airways is paralleled by the local release of mast cells derived products, particularly PGD2.

Adenosine Monophosphate↗

Anaphylactic reaction to oral prednisone: a case report and review of the literature.

Reports of corticosteroid anaphylactic reactions are rare in the medical literature. We describe the case of a nonatopic 17-year-old girl with bronchial asthma and aspirin intolerance who developed a dramatic anaphylactic reaction to oral prednisone. She recovered with shock therapy and intravenous administration of diphenhydramine and hydrocortisone. Intradermal testing with a wide range of steroid preparations gave positive results to prednisone. No reactions occurred to methylprednisolone and hydrocortisone. This case and the brief review of the literature which follows emphasize the danger of prednisone administration in patients who have asthma and a history of drug intolerance.

Administration, Oral↗