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Malerba M Bossoni S Radaeli A Mori E Romanelli G Tantucci C Giustina A Grassi V 《BONE》2006,38(1):119-124
BACKGROUND: Quantitative ultrasound bone densitometry (QUBD) is a new method to assess bone mineral density and bone microarchitecture. Corticosteroid (CS) therapy may diminish bone mass, alter bone quality and may influence growth hormone (GH) secretion and bone metabolism markers. Therefore, the aim of this study was to evaluate the effects of long-term therapy with inhaled CSs (ICSs) on structural bone characteristics and their correlations with GH secretion and bone markers in asthmatic patients. METHODS: In a cross-sectional study, we enrolled 60 adult patients with mild to moderate persistent asthma: 22 on chronic (>1 year) ICS therapy, 10 naive to ICSs treatment and 28 healthy control subjects. The groups were matched for age and BMI. Each subject underwent to QUBD at the phalanxes to assess bone microarchitecture by ultrasound bone profile index (UBPI), bone density by amplitude-dependent speed of sound (AdSos); test with GH-releasing hormone (GHRH) injection with calculation of peak GH and the Delta GH (peak GH-basal GH); and hormonal and bone markers measurements. RESULTS: Asthmatics treated with long-term ICS therapy showed a lower UBPI (P < 0.01) compared to controls (49.8 +/- 19.3 vs. 77.0 +/- 10.1, respectively) and to asthmatics never taking ICSs (73.2 +/- 9.6). In ICS-treated asthmatics, DeltaGH and GH-peak showed a significant correlation with UBPI. A significant difference was observed comparing asthmatics treated with ICSs to controls and asthmatics naive to ICSs in GH response to GHRH iv bolus. Serum osteocalcin was significantly reduced in asthmatic patients treated with ICSs. CONCLUSIONS: In asthmatic patients, long-term ICSs treatment produces negative effects on bone quality assessed by QUBD, and such effects are associated to an impaired GH secretion. 相似文献
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Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma 总被引:17,自引:2,他引:15
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Background: Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma. Methods: The effect of treatment with inhaled fluticasone propionate (1000 µg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients. Results: There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v –5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC20 (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (–1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters. Conclusions: Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke. 相似文献
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Growth hormone (GH) releasing activity of pyroglutamyl-seryl-glycinamide (PSG) and of thyrotropin-releasing hormone (TRH) was assayed on rat pituitaries in vitro, by radioimmunoassay of the GH released into the incubation media. TRH was found to be a partial agonist, producing maximal effects (at ca. 600 ng/ml) that were below the maximum response of the system to hypothalamic extract. The responses to a higher TRH concentration (1500 ng/ml) were smaller than that obtained at 600 ng/ml. PSG also behaved as a partial agonist producing maximum response at 150 ng/ml. The results are discussed in relation to possible structural similarities between the physiological GHRF and the tripeptides TRH, PSG and MIF (MSH release inhibiting hormone). 相似文献
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Twelve patients with chronic asthma received either high dose beclomethasone once a day or standard doses of beclomethasone three times a day in a double blind crossover trial to determine whether inhalation once a day would be sufficient. With the once a day regimen peak expiratory flow rates fell significantly, symptoms of nocturnal asthma increased, and two patients withdrew from the study because of worsening asthma. Whether control can be achieved with steroids inhaled once a day by simply increasing the total daily dose remains to be seen. 相似文献
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BACKGROUND: There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS: Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS: There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving =500 microg/day BDP (mean 366 (IQR 153-608) versus 494 (IQR 391-583), p = 0.08; 95% CI for the difference -31 to 288). Similarly, there was an increase in the percentage of lamina propria occupied by vessels in asthmatic patients not on ICS compared with controls (mean 15.6% (IQR 13.1-18.0) versus 10.1% (IQR 8.4-13.3), p<0.01; 95% CI for the difference 2.4 to 9.3) but a significant decrease in the percentage of lamina propria occupied by vessels was detected in asthmatic patients on ICS (mean 11.4% (IQR 9.1-14.9), p<0.01; 95% CI for the difference 0.7 to 7.7) compared with those not on ICS. The density of vessels correlated significantly with both airway hyperresponsiveness and percentage change in forced expiratory volume in one second (FEV1) after bronchodilator (r = -0. 38 for PD20 methacholine and r = 0.49 for change in percentage FEV1 after bronchodilator versus number of vessels/mm2, p<0.05). CONCLUSION: These findings suggest that ICS, especially at higher doses, may reduce airway wall vascularity in asthmatic subjects but further longitudinal intervention studies are required to confirm this suggestion. 相似文献
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24 hour and fractionated profiles of adrenocortical activity in
asthmatic patients receiving inhaled and intranasal corticosteroids 总被引:7,自引:2,他引:5
BACKGROUND: As both rhinitis and asthma are allergic conditions, they frequently occur together. The objective of this study was to assess the diurnal adrenocortical activity in asthmatics receiving inhaled (inh) and intranasal (n) formulations of two different corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TAA), both given at clinically recommended doses. METHODS: Twelve stable moderately severe asthmatic subjects of mean age 23.9 years and mean forced expiratory volume in one second (FEV1) 84% predicted were recruited into a randomised placebo (PL) controlled two-way crossover study comparing nPL + inhPL, nPL + inhFP (880 micrograms bid), and nFP (200 micrograms once daily) + inhFP (880 micrograms bid) with nPL + inhPL, nPL + inhTAA (800 micrograms bid) and nTAA (220 micrograms once daily) + inhTAA (800 micrograms bid), each given for five days with a 10 day washout period. Twenty four hour integrated and fractionated (overnight, 08.00 hours, daytime) serum cortisol levels and urinary cortisol/creatinine excretion were measured. RESULTS: For 24 hour and fractionated serum cortisol levels and corrected urinary cortisol/creatinine excretion there were significant (p < 0.05) differences between all active treatments and placebo. For 24 hour integrated serum cortisol levels the ratio between inhaled TAA and FP was 2.3 fold (95% CI 1.2 to 4.3), and for 24 hour urinary cortisol/creatinine excretion the ratio was two-fold (95% CI 1.2 to 3.4). For 24 hour urinary cortisol excretion, with all active treatments, individual abnormal low values of < 40 nmol (< 14.4 micrograms) occurred in 17/24 with FP compared with 4/24 with TAA (p < 0.0005). The 24 hour serum cortisol profile was flattened by FP but not with TAA. The addition of nasal corticosteroid did not produce further significant suppression of mean cortisol values, although with intranasal FP there were three more abnormal values for 24 hour urinary cortisol excretion than with inhaled FP alone. CONCLUSIONS: Both inhaled FP and TAA caused significant suppression of adrenocortical activity which was twice as great with FP, the latter being associated with significantly more individual abnormal values and loss of the normal diurnal circadian rhythm. Fractionated serum cortisol levels and urinary cortisol/creatinine excretion were as sensitive as the respective integrated 24 hour measurements. Although the addition of intranasal formulations did not produce further significant suppression of mean values, there were more individual abnormal cortisol values associated with the addition of intranasal FP. 相似文献
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Randomised trial of an inhaled β2 agonist, inhaled
corticosteroid and their combination in the treatment of asthma 总被引:3,自引:0,他引:3
BACKGROUND: Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken. METHODS: Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment. RESULTS: Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness. CONCLUSIONS: In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid. 相似文献
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Luteinizing hormone releasing hormone (LHRH) analogs have been shown to be an effective alternative endocrine treatment of metastatic prostatic carcinoma. After a transient stimulation of testosterone (T) and dihydrotestosterone (DHT) during the first week of therapy, continued administration of LHRH analogs has reliably suppressed serum androgens to castrate levels. About 10 per cent of previously untreated patients begun on LHRH therapy will experience transient worsening of disease symptoms corresponding to the initial rise in androgen levels. In an attempt to eliminate the early rise of T and DHT, 9 patients with metastatic prostatic carcinoma were pretreated with diethylstilbestrol (DES), 3 mg/day, for one week prior to the initiation of LHRH therapy. Following this, both DES and LHRH were given concomitantly for a week, after which DES was discontinued. LHRH was then continued as long as patients experienced clinical benefit. T and DHT levels were performed pre-study and on days 4, 8-11, 13, 15, and 29 of study. Results indicate that pretreatment with DES did not completely prevent the rise in T and DHT seen during the first week of LHRH therapy, although T and DHT levels rose to only slightly above baseline during the first four days. T and DHT levels then markedly decreased, and castrate levels were achieved by day 29 of treatment. 相似文献
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Cardiovascular side effects of inhaled salbutamol in hypoxic
asthmatic patients 总被引:1,自引:0,他引:1
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BACKGROUND: Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and beta2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation. METHODS: Eight men with mild asthma underwent the following treatments: normoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia + placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 microg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value. RESULTS: There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than for HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0.001). CONCLUSION: Patients with asthma who are hypoxic and inhale beta2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death. 相似文献
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S Kumar R E Mansel M F Scanlon L E Hughes C A Edwards J S Woodhead R G Newcombe 《The British journal of surgery》1984,71(11):870-873
A generalized abnormality of hypothalamopituitary function was found in 17 patients with cyclical pronounced mastalgia compared with 11 controls by using a combined thyrotrophin releasing hormone and gonadotrophin releasing hormone test. The release of prolactin, luteinizing hormone and follicle stimulating hormone was significantly greater in cyclical mastalgia patients than in controls. Basal thyrotrophin, T3 and T4 levels were within the normal range in both groups indicating normal thyroid status in benign breast disease. The single measurement of oestrogen and progesterone in the luteal phase was not abnormal. These data demonstrate an alteration in lactotroph and gonadotroph function in patients with cyclical mastalgia. It is unknown at present whether this represents an appropriate cellular response to altered central or peripheral signals. There is no evidence to suggest, however, that the anterior pituitary cell types are abnormal per se. 相似文献
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Effect of negative ionisation of inspired air on the response of asthmatic children to exercise and inhaled histamine 总被引:3,自引:2,他引:1
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To evaluate the effect of negative ionisation of inspired air on bronchial reactivity, 11 asthmatic children were challenged twice by exercise and 10 were challenged twice by histamine inhalation. The children breathed negatively ionised air (4 X 10(5) - 10 X 10(5) ions/cm3) or control room air in random order in a double-blind fashion. All challenges were matched in terms of basal lung function and the exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise-induced asthma was significantly attenuated by exposure to negatively ionised air, the mean postexercise fall in one-second forced expiratory volume (FEV1) being 29% (SE 5%) of the initial value after the control and 21% (3%) after the ionised air test (p less than 0.02). Ten of the 11 subjects developed less exercise-induced asthma while breathing ionised air. Although the median dose of histamine (cumulative breath units) which caused a constant fall in FEV1 for each individual was higher with the ionised air challenge than with the control challenge the difference was not significant. Five of the 10 subjects were less sensitive to histamine and the other five more sensitive when breathing ionised air. It is concluded that negative ionisation of inspired air can modulate the bronchial response to exercise but the effect on the response to histamine is much more variable. 相似文献