Bridging the gap in the symptomatic heart failure patient journey: insights from the Italian scenario.

BACKGROUND: The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM). RESEARCH DESIGN AND METHODS: Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers. RESULTS: One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3-6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents. CONCLUSIONS: Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

Airway responsiveness to adenosine after a single dose of fluticasone propionate discriminates asthma from COPD.

BACKGROUND: Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5'-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP). AIM: To determine whether this rapid protective effect of a single dose of FP is also present in COPD. METHODS: 23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 µg FP or matched placebo. RESULTS: In subjects with asthma, 1000 µg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3-116.3) to 81.5 (9.6-1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3-183.9) and 76.3 (21.0-445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma. CONCLUSION: A single dose of 1000 µg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD.

Feasibility of using E-mail counseling as part of a smoking-cessation program.

BACKGROUND: The need for more effective smoking-cessation interventions is firmly established. However, access to these services can be problematic in real life. E-mail messages may be a convenient alternative to deliver smoking-cessation interventions. The aim of this pilot study was to assess the effectiveness of incorporating tailored e-mail consultation messages in a smoking-cessation program for smokers willing to quit. METHODS: This pilot study examined the feasibility of integrating e-mail consultation messages in a smoking-cessation program for smokers willing to quit and with Internet access. At baseline, demographic data, smoking history and expired carbon monoxide (CO) levels were collected at a clinic visit. The subjects were provided with the specialist's e-mail address and instructed to prepare e-mail messages containing simple and clear information about their quitting progress. The counselor offered e-mail counseling throughout the smoking-cessation program. A 6-month follow-up visit was arranged, at which abstinence was reviewed. RESULTS: Of the 30 participants initially enrolled in the study, 21 (70%) attended the follow-up 6-month visit. E-mail counseling was more frequently offered (4-8 times) to the participants who completed the study, compared to those lost to follow-up (1-4 times). Comparisons with baseline exhaled CO values showed a significant within-group reduction at 6 months after smoking-cessation (P < .001) in the quitters, compared to smoking-cessation failures. Sustained smoking abstinence at 6 months was 37%. CONCLUSIONS: The integration of e-mail consultation counseling in a smoking-cessation intervention is feasible and effective. E-mail counseling as part of a smoking-cessation program warrants further evaluation.

Adenosine receptors: promising targets for the development of novel therapeutics and diagnostics for asthma.

Interest in the role of adenosine in asthma has escalated considerably since the early observation of its powerful bronchoconstrictor effects in asthmatic but not normal airways. A growing body of evidence has emerged in support of a proinflammatory and immunomodulatory role for the purine nucleoside adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma. The fact that adenosine enhances mast cell allergen-dependent activation, that elevated levels of adenosine are present in chronically inflamed airways, and that adenosine given by inhalation cause dose-dependent bronchoconstriction in subjects with asthma emphasizes the importance of adenosine in the initiation, persistence and progression of these common inflammatory disorders of the airways. These distinctive features of adenosine have been recently exploited in the clinical and research setting to identify innovative diagnostic applications for asthma. In addition, because adenosine exerts its multiple biological activities by interacting with four adenosine receptor subtypes, selective activation or blockade of these receptors may lead to the development of novel therapies for asthma.

Beclomethasone dipropionate attenuates airways hyperresponsiveness to neurokinin A and histamine in asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents available for the treatment of asthma but they produce only modest effects on airway inflammation and non-specific bronchial hyperresponsiveness (BHR). However, little is known about the possibility that treatment with ICS might cause additional protection on BHR to inhaled tachykinins such as neurokinin A (NKA). OBJECTIVE: Therefore, we compared the effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled histamine and NKA in a double-blind, controlled, cross-over study of asthmatic patients. METHODS: Patients attended the laboratory before and after each 6 weeks treatment period to undertake concentration-response studies with histamine and NKA. Bronchial responsiveness to both funs was expressed as the provocative concentration producing a 20% decrease in FEV(1) from baseline (PC(20)). RESULTS: BDP therapy attenuated the constrictor response to both agonists to a similar degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21-1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment) and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01, post-salb vs. post-BDP treatment) for histamine and NKA, respectively. CONCLUSION: Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.

Normal expression of isoforms activating cyclic adenosine monophosphate responsive element modulator in patients with spermatid maturation arrest.

OBJECTIVE: To evaluate whether defective cyclic adenosine monophosphate responsive element modulator (CREM) expression is the causative factor of spermatid maturation arrest (SMA). DESIGN: Comparative evaluation of the testicular histology in patients with SMA or normal spermatogenesis. SETTING: University clinic of andrology. PATIENT(S): Azoospermic patients undergoing testicular biopsy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of CREMtau in quantitative immunohistochemistry analysis of testicular biopsy samples. RESULT(S): Regular CREM expression was observed in the tubules with round, but not elongated, spermatids of patients with SMA (n = 9). Quantitative analysis showed that round spermatids of patients with SMA had a staining intensity similar to that observed in controls (n = 7). CONCLUSION(S): Lack of spermatid elongation was not due to defective CREM expression. Therefore, CREM did not play a pathogenetic role in the onset of SMA in humans.

Morphologically normal spermatozoa of patients with secretory oligo-astheno-teratozoospermia have an increased aneuploidy rate.

BACKGROUND: Normal morphology is a major criterion for selecting spermatozoa to be injected. Given that teratozoospermia is one of the most critical parameters associated with sperm aneuploidy, the purpose of this study was to evaluate the aneuploidy rate of morphologically normal spermatozoa of patients with oligo-astheno-teratozoospermia (OAT). METHODS: Ten patients with secretory OAT and six age-matched normozoospermic men with a normal karyotype were enrolled. After assignment to normal or abnormal category, the location of each spermatozoon was recorded using an electronic microstage locator. Slides were then subjected to triple-colour fluorescence in situ hybridization for chromosomes X, Y and 12. RESULTS: OAT patients had a lower number of morphologically normal and abnormal spermatozoa carrying the X chromosome, compared with normozoospermic men. They also exhibited increased XY and XX disomy rates. Morphologically abnormal spermatozoa from normozoospermic men also had an increased XX disomy rate compared with normally shaped spermatozoa obtained from the same men. The total sperm aneuploidy rate of morphologically abnormal spermatozoa of normozoospermic men was 4.4-fold higher than that of spermatozoa with normal morphology. The total aneuploidy rates of spermatozoa with normal or abnormal head shape from OAT patients were similar to each other and to that of abnormally shaped spermatozoa from normozoospermic men, but they were higher than the rate found in normally shaped spermatozoa of normal men. CONCLUSIONS: Normally shaped spermatozoa of OAT patients have an increased aneuploidy rate.