Biomedical subjects

Giuseppe Reina

Publications and source records attributed to Giuseppe Reina.

12 recordsLinked to original sources

PubMed2006

Exercise metaboreflex activation and endothelial function impairment in atrial fibrillation.

Exercising muscle hypoperfusion stimulates afferents (metaboreceptors) involved in the regulation of ventilation. Atrial fibrillation (AF), particularly when combined with diseases causing endothelial (ED) impairment, such as hypertension (HP) and diabetes mellitus (DM), depresses the ED activity and enhances exercise hyperventilation. The relationship between these two functions and the underlying mechanisms have not been explored previously. In lone AF or AF associated with HP or DM (12 subjects in each cohort), we investigated the brachial artery flow-mediated dilatation (ED function) and ventilation during the recovery phase of handgrip (metaboreflex) exercise for subjects receiving placebo or oral vitamin C (double-blind crossover), both before and after cardioversion (CV) to sinus rhythm. Baseline ED impairment was increasingly more severe and the ergoreflex activity more pronounced in AF + HP and AF + DM compared with lone AF. Vitamin C and CV significantly improved both flow-mediated dilatation and metaboreflex activity in lone AF and AF + HP, and vitamin C did not produce any additive effect when administered after CV. In AF + DM, neither vitamin C nor CV was effective. This study provides the following information: AF generates oxidative injury, which is less when the arrhythmia is lone AF and greater when the arrhythmia is associated with HP. In DM, the oxidative injury generated by AF is refractory to a rather weak antioxidant, like vitamin C, or the baseline damage is such as to prevent any additive influence of AF. In AF, a cause-effect link exists between ED dysfunction and metaboreflex activity. Ventilatory advantages of CV seem to be inversely related with the extension of the underlying ED oxidative impairment.

Aged↗

PubMed2006

Bivariate statistical approach to evaluate laboratory performance by analysis of standard curves in an External Quality Assurance program for quantitative assays based on real-time PCR with Taq-Man probes.

Recently a revolutionary technique for quantitative PCR determination was introduced in diagnostic laboratories. To determine the influence of technical variability on the reliability of the quantitative assay, it is crucial to use External Quality Assurance (EQA) programs. An EQA program was developed in Italy to check the analytical performance of real-time PCR procedures based on Taq-Mantrade mark probes. This article suggests a new statistical approach to discriminate, using a bivariate technique, laboratory performance that appears to be questionable, by separately considering the two main features of the standard curve: analytical sensitivity and efficiency. Furthermore, specific indexes to evaluate the impact of these two features on the determination of the initial number of molecules are given to help to improve the assay procedure.

Chemistry, Clinical↗

PubMed2006

[Statistical notes. Which risks do the patient incur if his own cardiologist accepts to be involved in a clinical trial without deep consideration of the a priori available evidence?].

The aim of this statistical note is to describe the results of the randomized controlled clinical trial TARGET, which compared the effect of tirofiban (new treatment) and abciximab (standard treatment) in patients who were expected to undergo coronary stenting. Primary aim of TARGET was to evaluate the non-inferiority of tirofiban with respect to abciximab, but it concluded in favor of superiority of the standard treatment. The authors of this study point out that a deep consideration regarding a priori available evidence could have avoided to expose 2398 patients randomized to tirofiban to the risk of death or non-fatal myocardial infarction.

Abciximab↗

PubMed2005

Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients.

BACKGROUND: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. METHODS: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). RESULTS: Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). CONCLUSIONS: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.

Aged↗

PubMed2005

[Statistical notes. Hazard curves of sudden death: their role in the cardiologist's clinical decision].

In long-term studies researchers are mainly concerned with occurrence of death during the follow-up period. This statistical note is focused on survival analysis which is the main tool to process this kind of data. Survival curve, cumulative mortality curve and hazard curve are here introduced together with an appropriate effect indicator: hazard ratio. In particular, the use of the latter is shown by resorting to the randomized controlled clinical trial TARGET.

Cardiology↗

PubMed2005

[An alarming problem in the therapy of infective endocarditis: the development of antibiotic-resistant strains].

We shall focus on infective endocarditis due to Enterococcus spp and Staphylococcus aureus, both able to develop resistance to antibiotics with different mechanisms. Vancomycin-resistant strains produce some of the most challenging nososocomial infections. Enterococci develop resistance practically to all classes of antibiotics. Vancomycin-resistant strains, in the '90s, passed from 2% to more than 25%. Five types of vancomycin-resistance were reported (from van A to van E), linked to the presence of certain classes of genes regulating the production of abnormal precursors of peptidoglycan which inhibit the action of vancomycin. Staphylococcus aureus is a fearful organism whose infections can reach a mortality rate of 80%. In 1943, as soon as penicillin G was introduced into therapy, Staphylococcus strains producers of beta-lactamase were identified. After beta-lactamase-resistant penicillins were introduced into therapy, methicillin-resistant Staphylococcus strains appeared in the '60s. In 1996 the first strain of methicillin-resistant and vancomycin-resistant Staphylococcus aureus was isolated. In 2001, in Japan, the first case of infective endocarditis due to Staphylococcus aureus resistant to methicillin and non-responsive to vancomycin was described. The resistance is connected to an increased synthesis of the cell wall, which thickens reducing the activity of vancomycin.

Drug Resistance, Bacterial↗

PubMed2005

[Statistical notes. Randomized controlled clinical trials of both superiority and non-inferiority: critical considerations].

The aim of this statistical note, the fourth in the series, is to describe and critically appraise the randomized controlled clinical trial (RCCT) GUSTO V, which combined in a single RCCT both the superiority and non-inferiority hypotheses. In this note we present the logical path that the authors have presumably followed in planning a RCCT of such a kind. The results are reported and possible critical aspects are highlighted and debated upon. Finally the cardiologist reader is stimulated to give his own opinion on this kind of approach.

Algorithms↗

PubMed2004

Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure.

AIMS: In chronic heart failure (CHF) patients, the ventilation (Ve) needed to eliminate metabolically produced CO(2) during exercise (i.e. the Ve/Vco(2) slope) is a strong prognosticator. Ve/Vco(2) slope determinants are the dead space-tidal volume (Vd/Vt) ratio and the arterial CO(2) partial pressure (Paco(2)). We aimed at defining the respective prognostic role of these two variables. METHODS AND RESULTS: One hundred and twenty-eight stable CHF patients (average left ventricular ejection fraction 34+/-10%) underwent cardiopulmonary exercise testing and blood gas analysis. The prognostic relevance of the Ve/Vco(2) slope, Vd/Vt, and Paco(2) at peak exercise was evaluated by the Kaplan-Meier approach with log-rank testing and by multivariate Cox regression analysis. During a mean period of 31.3+/-20 months, 24 patients died from cardiac causes. In univariate analysis, predictors of death included the use of anti-aldosterone drugs, low peak Vo(2), peak Ve/Vo(2), peak Paco(2) and high Ve/Vco(2) slope, and peak Vd/Vt. Multivariate analysis identified a low peak Paco(2) (<35 mmHg) as the strongest independent prognostic indicator [hazard ratio 4.65, 95% confidence interval (CI) (1.695-12.751), P=0.003] that primarily accounts for the Ve/Vco(2) slope prognostic power. CONCLUSION: These findings imply that regulatory mechanisms involved in the tight control of ventilatory command and blood gas tension, rather than lung function abnormalities, play a critical pathophysiological role in the exercise ventilation inefficiency of CHF patients.

Blood Gas Analysis↗

PubMed2004

Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure.

Chronic heart failure (CHF) may impair lung gas diffusion, an effect that contributes to exercise limitation. We investigated whether diffusion improvement is a mechanism whereby physical training increases aerobic efficiency in CHF. Patients with CHF (n = 16) were trained (40 min of stationary cycling, 4 times/wk) for 8 wk; similar sedentary patients (n = 15) were used as controls. Training increased lung diffusion (DlCO, +25%), alveolar-capillary conductance (DM, +15%), pulmonary capillary blood volume (VC, +10%), peak exercise O2 uptake (peak VO2, +13%), and VO2 at anaerobic threshold (AT, +20%) and decreased the slope of exercise ventilation to CO2 output (VE/VCO2, -14%). It also improved the flow-mediated brachial artery dilation (BAD, from 4.8 +/- 0.4 to 8.2 +/- 0.4%). These changes were significant compared with baseline and controls. Hemodynamics were obtained in the last 10 patients in each group. Training did not affect hemodynamics at rest and enhanced the increase of cardiac output (+226 vs. +187%) and stroke volume (+59 vs. +49%) and the decrease of pulmonary arteriolar resistance (-28 vs. -13%) at peak exercise. Hemodynamics were unchanged in controls after 8 wk. Increases in DlCO and DM correlated with increases in peak VO2 (r = 0.58, P = 0.019 and r = 0.51, P = 0.04, respectively) and in BAD (r = 0.57, P < 0.021 and r = 0.50, P = 0.04, respectively). After detraining (8 wk), DlCO, DM, VC, peak VO2, VO2 at AT, VE/VCO2 slope, cardiac output, stroke volume, pulmonary arteriolar resistance at peak exercise, and BAD reverted to levels similar to baseline and to levels similar to controls. Results document, for the first time, that training improves DlCO in CHF, and this effect may contribute to enhancement of exercise performance.

Bicycling↗

PubMed2004

[Statistical notes. Absolute and relative effect measures].

The aim of these statistical notes was to give the cardiologist the suitable tools for the understanding of the statistical aspects in the reading of papers presenting the results of randomized controlled clinical trials, in the most simple and intuitive way, without any previous knowledge of basic statistics. The fundamentals of the most common tools for the comparison of two experimental treatments, are developed by getting cue from classical cardiological examples and by guiding the reader, step by step, toward the understanding and critical discussion of the proposed examples. In particular, this note focuses the attention on the main "indicators" of absolute and relative effect measures by evidencing their most important differences.

Cardiology↗

PubMed2004

[Statistical notes. From superiority to non-inferiority clinical trials: a leap in the dark?].

In these "statistical notes", equivalence and non-inferiority randomized controlled clinical trials (RCCT) are considered. Equivalence trials are designed to confirm the absence of a meaningful difference between the effect of two treatments. Non-inferiority trials are designed to prove that the new treatment is no less effective than an existing one: it may be more effective or it may have a similar effect. In this note the attention is addressed to suitable criteria for the choice of the tolerance margin epsilon, i.e. the largest difference which is clinically acceptable, so that a difference bigger than that would matter in practice. In particular, the procedures for the determination of the margin epsilon, used by the authors of the non-inferiority RCCT COBALT and INJECT, are presented and discussed in detail. The ethical implications of equivalence and non-inferiority RCCT are here considered and the reader is repeatedly invited to consider the appropriateness of the basic arguments asserted by the supporters of this kind of studies.

Algorithms↗

PubMed2003

Aspirin-angiotensin-converting enzyme inhibitor coadministration and mortality in patients with heart failure: a dose-related adverse effect of aspirin.

BACKGROUND: It is debated whether in patients with chronic heart failure (CHF), aspirin may contrast the clinical benefits of angiotensin-converting enzyme inhibitors (ACEIs). Two major unresolved issues in patients with CHF are whether these agents together can affect mortality and whether the interaction is related with the dose of aspirin. We aimed at exploring these possibilities. METHODS: We evaluated more than 4000 hospitalizations with a principal discharge diagnosis of CHF from January 10, 1990, to December 31, 1999. The final analysis was restricted to 344 patients taking ACEIs who satisfied the selection criteria, in whom reliable information was available concerning drug therapy during follow-up. In these patients, treatment included no aspirin in 235 (group 1), a low dose (< or =160 mg) in 45 (group 2), and a high dose (> or = 325 mg) in 64 (group 3). RESULTS: During a mean follow-up of 37.6 months, there were 84 (36%) deaths in group 1, 15 (33%) in group 2, and 35 (55%) in group 3. By the Kaplan-Meier approach, survival was similar in groups 1 and 2, and significantly (P =.009) worse in group 3 compared with groups 1 and 2. After adjusting for potential confounding factors (including treatment, cause of heart disease, age, smoking, and diabetes mellitus), a time-dependent multivariate Cox proportional hazards regression analysis showed that the combination of high-dose aspirin with an ACEI was independently associated with the risk of death (hazard ratio, 1.03; P =.01) and that the combination of low-dose aspirin with an ACEI was not (hazard ratio, 1.02; P =.18). CONCLUSION: These results support the possibility that in some patients with CHF who are taking an ACEI, a dose-related effect of aspirin may adversely affect survival.

Angiotensin-Converting Enzyme Inhibitors↗