Effect of a new synbiotic supplement on symptoms, stool consistency, intestinal transit time and gut microbiota in patients with severe functional constipation: a pilot randomized double-blind, controlled trial.

BACKGROUND: Data on the benefits of synbiotics in functional constipation are conflicting. The aim of this study was to assess whether the administration of the synbiotic supplement Psyllogel Megafermenti(®) normalized stool consistency and decreased intestinal transit time (ITT) in patients with severe functional constipation, based on its ability to impact on the gut microbiota. METHODS: We conducted a pilot randomized, double-blind, controlled trial. After a 2-week run-in period, patients from a tertiary care setting with severe functional constipation fulfilling the Rome III Diagnostic Criteria in the past year were randomly assigned to receive by mouth 2 bags/day of Psyllogel Megafermenti(®) (Group A) or 2.8 g of maltodextrin twice daily (Group B) for 8 weeks. Primary endpoints were increase of bowel evacuations with normal stool consistency and volume, and ITT reduction. Secondary endpoints included symptom improvement according to the Rome III Diagnostic Criteria, reduction of the Agachan-Wexner score and changes in gut microbiota composition. RESULTS: Twenty-nine patients completed the study: 17 were allocated to Group A and 12 to Group B. A statistically significant increase in stools with normal consistency was observed only in Group A (p = 0.001), even when considering patients with normal stools ≤50 % of time at baseline. In Group A, a significant reduction in ITT was also found (p = 0.022). According to polymerase chain reaction-denaturing gradient gel electrophoresis profiling of stool samples, 50 % of the patients treated with synbiotics harbored all the probiotic species of the study product. CONCLUSIONS: An 8-week treatment with Psyllogel Megafermenti(®) improved the main clinical parameters of functional constipation in patients extremely homogeneous for disorder severity and underlying pathophysiology ( Eudract.ema.europa.eu , No. 2008-000913-30).

Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation.

This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.

Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families.

BACKGROUND: The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. METHODS AND RESULTS: Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). CONCLUSIONS: At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Gaining and losing health insurance: strengthening the evidence for effects on access to care and health outcomes.

This study uses longitudinal data to examine the consequences of losing and gaining health insurance coverage for access to care and health. For both Medicaid and privately insured persons, compared with those who remained insured, persons losing coverage over a 2-year period were more likely to lack a usual source of care, encounter difficulty in obtaining medical care, be very dissatisfied with ability to obtain needed care, and report no physician visits in the previous 12 months. Uninsured people who gained coverage showed improvement across all indicators of access, in contrast to those who remained without insurance. The effects of changes in coverage on health were in the same direction as those for access, but did not reach statistical significance. This study strengthens the evidence that health insurance coverage has a substantial impact on ability to gain access to medical care and may affect health status.

RFLP- and RAPD-based genetic relationships of seven diploid species of Avena with the A genome.

Relatively few molecular analyses are available for diploid oat species, which constitute the majority of the wild species of Avena and, therefore, the principal natural reservoir of variability. The present work reports an RAPD-(random amplified polymorphic DNA) and RFLP-(restriction fragment length polymorphism) based study of the intra- and interspecific variability of seven diploid A-genome oat species. Both types of markers resulted in valid tools for identifying polymorphisms both within and between species. The two statistical analyses, UPGMA (unweighted pair group method, arithmetic mean) and PCoA (principal coordinate analysis), computed on the basis of genetic similarities estimated from RAPDs and RFLPs, showed that the different accessions grouped according to species, but the similarity coefficients were consistently higher in the RFLP analysis. Furthermore, slight differences were observed in the intra- and interspecific relationships found with the two types of markers. This may support the hypothesis that the polymorphisms revealed by the two types of markers may associate with regions of the genome having different evolutionary rates. The relationships among species are not identical to those deduced from previous karyotypic and morphological studies, thus suggesting a partially different evolutionary pathway in oat speciation.

[Changes in myocardial Tc-99m-sestamibi uptake in asynergic territories during low-dose echo-dobutamine test]. / Modificazioni della captazione miocardica di Tc-99m-sestamibi in territori asinergici durante test eco-dobutamina a bassa dose.

BACKGROUND: Recent data suggest that contractile reserve in dysfunctional but viable myocardium during low-dose dobutamine infusion might be elicited not only by a direct inotropic stimulation but also by an increase in coronary blood flow. Aim of the study was to evaluate the effects of low-dose dobutamine on myocardial perfusion and function in asynergic but viable myocardium. METHODS: Nineteen patients with coronary artery disease and severe regional dysfunction were studied. Both regional ventricular function and myocardial perfusion were assessed at rest (PRE), during low-dose dobutamine (DOB) and, in twelve patients, after revascularization (POST). Regional ventricular function was evaluated with two-dimensional echocardiography using a score index ranging from 1 to 4. Myocardial perfusion was studied using Tc-99m-sestamibi Single Photon Emission Tomography (SPET); uptake defects were graded from 0 (normal) to 4 (absent uptake). For both evaluations the left ventricle was divided in 16 segments and two vascular territories were considered. RESULTS: Low-dose dobutamine elicited contractile reserve in 12 of 24 asynergic vascular territories (DOB+). Compared with PRE scintigraphy, DOB SPET showed perfusion improvement in 10/12 DOB+ and in 3/12 DOB- asynergic territories (p = 0.006). Mean uptake score decrease significantly in DOB+ (from PRE SPET 21.0 +/- 7.2 to DOB SPET 17.6 +/- 7.1; p = 0.0005) but not in DOB- (from SPET PRE 19.0 +/- 5.3 to SPET DOB 19.5 +/- 6.8, p = NS) abnormal territories. Fourteen asynergic territories underwent revascularization. Among them, 9 showed functional recovery after intervention (viable myocardium) and 5 showed no changes (fibrotic myocardium). A functional improvement under dobutamine was observed in 7 viable and in 1 fibrotic territories. Conversely, perfusion improved under dobutamine in 8 viable and in one fibrotic territory. After revascularization the perfusion defect score decreased significantly in viable territories (from PRE SPET 22.1 +/- 7.9 to POST SPET 13.3 +/- 6.6; p = 0.00001) but not in fibrotic regions (from PRE SPET 17.8 +/- 6.0 to POST SPET 15.6 +/- 4.9). CONCLUSIONS: In asynergic myocardium contractile reserve elicited by low-dose dobutamine is associated in most cases with an improvement in Tc-99m-sestamibi uptake. This suggests a possible link between increased blood flow and functional improvement during dobutamine in viable myocardium.

Wavelength index at three atrial sites in patients with paroxysmal atrial fibrillation.

The purpose of this study was to evaluate the wavelength index (WLI) at three atrial sites in a group of 23 patients with recurrent episodes of lone paroxysmal atrial fibrillation (LPAF) and a control group (n = 20). All patients underwent programmed atrial stimulation (paced cycle length = 600 ms) at high, medium, and low lateral right atrial wall. P wave duration, sinus cycle length, and corrected sinus node recovery time were not significantly different between the two study groups. WLI was calculated according to the following formulas: atrial effective refractory period (AERP)/duration of atrial extrastimulus electrogram (A2) or AERP/A2 + atrial latency; and atrial functional refractory period (AFRP)/A2. WLI was significantly shorter in LPAF than in the control group at each of the paced atrial sites independently of the formula used. Duration of premature atrial electrogram appeared to play the major role in determining the difference in WLI between patients with paroxysmal atrial fibrillation and the control group.

Effect of right atrial stimulation on both atrial pressure and atrial natriuretic peptide release in essential hypertension.

UNLABELLED: Several reports indicated a direct relationship between atrial pacing and atrial natriuretic peptide (ANP) blood levels, but few controlled hemodynamic studies have been reported. In particular, the relationship between increase in heart rate, release of ANP and increase in right atrial pressure (RAP) are still uncertain. Moreover, the effect of accelerated heart rate on ANP secretion in patients with essential hypertension has not yet been fully elucidated. For this, we studied 12 untreated essential hypertensive (EH; WHO stage I-II) and 10 age-matched normotensive subjects (NO) as control by right atrial stimulation (parasinusal site) in consecutive steps of 110, 130 and 150 b.p.m., each step lasting for 5 min. Both before and during stimulation at each pacing rate (after 5 min) RAP and systolic blood pressure (SBP) were measured and blood was drawn from the right atrium for ANP measurements (radioimmunoassay method). During stimulation we observed significant differences in the ANP release in comparison to the initial values: at 130 (p less than 0.05) and at 150 b.p.m. (p less than 0.01) in EH; at 150 b.p.m. (p less than 0.005) in NO. RAP and SBP did not differ significantly at each pacing rate from initial values both in EH and NO. No significant differences in ANP and RAP were found between EH and NO. IN CONCLUSION: (a) ANP release increases in both EH and NO, even if beginning at 130 in EH and at 150 b.p.m. in NO; (b) in both EH and NO, there is no relationship between RAP or SBP values and ANP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of training on the electrophysiologic properties of atrium and accessory pathway in athletes with Wolff-Parkinson-White syndrome.

Twenty-two subjects with Wolff-Parkinson-White (WPW) electrocardiographic pattern performing agonistic physical activity were referred to our laboratory to assess arrhythmogenic risk (group 1). This allowed us to evaluate a less known aspect, namely that of effects of training on the electrophysiologic properties of the atrium and accessory pathway. This was done utilizing a control group of 10 WPW patients who did not perform agonistic physical activity (group 2). All subjects were symptom free, and without signs of associated cardiopathy if we exclude 1 patient of group 1, who presented moderate mitral valve prolapse. Group 1 patients showed significantly higher mean values for basic cycle length (p less than 0.001), atrial effective (p less than 0.04) and functional (p less than 0.02) refractory period, and anterograde effective refractory period of the accessory pathway (p less than 0.02). The different behavior observed in group 1 patients could be explained considering the known influence of training on the equilibrium of the autonomic nervous system. Moreover, it is noteworthy that the two groups did not differ for inducibility of atrial fibrillation (AF). This should be taken into account considering the importance of AF in WPW. In conclusion, our study does not demonstrate any negative electrophysiologic effects of training in patients with WPW.

[Atrial electrophysiologic properties in paroxysmal atrial fibrillation. Study conducted with the stimulation of 5 atrial sites]. / Proprietà elettrofisiologiche atriali nella fibrillazione atriale parossistica. Studio effettuato stimolando cinque sedi atriali.

Programmed atrial stimulation at five atrial sites was performed to evaluate electrophysiologic atrial properties in 17 control patients (14 M, 3F, mean age 61 +/- 9 years) (Group A) and in 18 patients with paroxysmal atrial fibrillation (13 M, 5 F, mean age 61 +/- 5 years) (Group B) with normal sinus node function. The mean value of the P wave duration was similar in both groups. Programmed atrial stimulation was performed at five atrial sites: high, medium and low lateral wall, and high and low medial wall. We evaluated the following parameters: A) local conduction delay measured at the functional refractory period as the difference between A1-A2 and S1-S2 intervals; B) widening of local electrogram measured at the functional refractory period as the difference between A1-A2 interval measured at the end of each local electrogram and A1-A2 interval measured at the beginning of each local electrogram. We evaluated the mean and the maximum value of the two above-mentioned parameters; C) dispersion of effective refractory period and functional refractory period, determined as the longest minus the shortest refractory period from the range of refractory periods measured in each patient; D) the mean of effective refractory periods and functional refractory periods observed at five atrial sites. Mean and maximum local conduction delay, mean effective and functional refractory periods did not present significant differences in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between age and anterograde refractoriness of the accessory pathway in Wolff-Parkinson-White patients.

In 22 patients (age range 13-40 years) with Wolff-Parkinson-White ECG pattern without evidence of associated cardiomyopathy we measured the anterograde effective refractory period of the accessory pathway (ERP-AP) by extrastimulus method (at twice diastolic threshold) during atrial pacing (100/min). The ERP-AP range was 220-480 ms. There was a significant direct correlation between age and ERP-AP (r = 0.50, p less than 0.01). An ERP-AP less than or equal to 250 ms was found in 4 patients (age less than or equal to 23 years). This is noteworthy in the light of reports that, over the years: (1) typical Wolff-Parkinson-White ECG signs can disappear and (2) the frequency of tachycardic episodes decreases. Our data suggest a lower risk of high ventricular rates during atrial fibrillation with increasing age.

Effects of propafenone on directly measured sinoatrial conduction time.

Electrophysiologic investigation of the effects of antiarrhythmic drugs on sinoatrial conduction time (SACT) is conditioned by the inadequacies of indirect methods employing premature or asynchronous atrial stimulation. Direct recording of sinus node electrogram (SNE) is unaffected by the limitations of the indirect methods and is particularly useful when the effect of a drug on SACT is to be studied. In the present study the effect of propafenone on SACT directly (D) measured from SNE in 12 patients (7 male and 5 female subjects, 61 +/- 10 years) with normal sinus node function (NSNF) was investigated. DSACT, sinus node cycle length (SCL) and corrected sinus node recovery time (CSNRT) were evaluated before and 20 min after i.v. administration of 1 mg/kg propafenone. The following results (mean +/- SD) were obtained: in control condition SCL was 854 +/- 143 ms; CSNRT 316 +/- 82 ms; DSACT 88 +/- 20 ms. After propafenone SCL was 849 +/- 119 ms; CSNRT 340 +/- 93 ms; DSACT 97 +/- 15 ms (p less than 0.05). DSACT ranged from 60 to 105 ms and from 60 to 120 ms, respectively, before and after propafenone. In conclusion, in patients with NSNF propafenone 1. does not affect sinus node automatism and 2. prolongs significantly DSACT, which, however, remains within the upper normal limit.