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Biomedical subjects

A De Simone

Publications and source records attributed to A De Simone.

At least 19 recordsLinked to original sources

Structure and expression of a novel gene family showing male germline specific expression in Drosophila melanogaster.

We report the characterization of two novel genes of Drosophila melanogaster, named mst36Fa and mst36Fb. They define a novel gene family, showing identical time and tissue-specificity limited to male germ cells where their transcription starts during meiotic prophase. These two genes encode for two slightly basic proteins highly homologous to each other and fairly rich in leucine and glutamic acid. Although strictly clustered, these genes utilize different promoter regions as revealed by examination of transgenic flies bearing mst36F-promoter-lacZ reporter constructs and by reverse transcription-polymerase chain reaction assays. Our data suggest that at least one gene (mst36Fa) of the cluster is under translational repression until spermiogenesis suggesting a putative role in the spermatides differentiation. The present study is aimed at the structural analysis of these genes.

Amino Acid Sequence↗

Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation.

OBJECTIVES: We tested the hypothesis that the response to flecainide infusion can identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic and ablation therapy reduces the recurrences of AF. BACKGROUND: Infusion of class IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter. Catheter ablation of atrial flutter has been demonstrated to be highly effective in preventing recurrences of atrial flutter. METHODS: Seventy-one consecutive patients with paroxysmal or chronic AF, in whom flecainide infusion (2 mg/kg body weight, intravenously) determined the transformation of AF into common atrial flutter (positive response), were randomized to receive one of the following treatments: oral pharmacologic treatment with flecainide (group A, n = 23); the hybrid treatment (catheter ablation of the inferior vena cava-tricuspid annulus isthmus, plus oral flecainide) (group B, n = 24); or catheter ablation of the isthmus only (group C, n = 24). Thirty-seven patients with a negative response to flecainide, who chose to be submitted to the hybrid treatment, were selected as the control group (group D). RESULTS: During a mean follow-up period of 24 +/- 7.2 months, the recurrences of AF and atrial flutter in group B (42%) were significantly lower than those in group A (78%, p < 0.001), group C (92%, p < 0.001) and group D (92%, p < 0.001). CONCLUSIONS: The creation of a complete bi-directional conduction block at the inferior vena cava-tricuspid annulus isthmus, plus flecainide administration, reduces the recurrences of both AF and atrial flutter in patients with class IC atrial flutter. Moreover, the early response to flecainide is safe and reliable in identifying patients who may benefit from this therapy.

Administration, Oral↗

Resistance of human leukemic cell lines to 1-beta-D-arabinofuranosylcytosine: characterization of an experimental model.

1-beta-D-arabinofuranosylcytosine (ara-C) is an antimetabolite used for the treatment of acute myelogenous leukemia. The ability of ara-C to kill neoplastic cells has been correlated to the induction of apoptosis. The clinical use of ara-C is limited by the development of drug resistance. Alterations in drug-induced apoptosis play a critical role in ara-C resistance. In particular, the proto-oncogene bcl-2 has been implicated in this phenomenon. To better understand the molecular basis of the role of bcl-2 in ara-C resistance, we investigated the relationship between the cytotoxic effect of ara-C, the expression levels and the subcellular localization of bcl-2 in three human leukemic cell lines (HL-60, KG1, J111). We have also evaluated the effects of ara-C on the J111 leukemic cell line (showing the lowest levels of Bcl-2 and the highest sensitivity to ara-C) overexpressing the bcl-2 oncogene. The model we developed here will allow further studies on the role of post-translational events involving bcl-2 (such as translocation and/or phosphorylation) in the cellular response to ara-C treatment.

Antimetabolites, Antineoplastic↗

Pretreatment with verapamil in patients with persistent or chronic atrial fibrillation who underwent electrical cardioversion.

OBJECTIVES: To evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion (C). BACKGROUND: The increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload. METHODS: One hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C. RESULTS: During the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04). CONCLUSIONS: Six days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone.

Aged↗

Determinants of efficacy of atrial pacing in preventing atrial fibrillation recurrences.

INTRODUCTION: Several studies have shown that single or dual site atrial pacing is effective in reducing the frequency of recurrent atrial fibrillation (AF) in selected patients. However, it is still unclear what the best predictors are of long-term efficacy of atrial pacing. METHODS AND RESULTS: Forty-seven patients with paroxysmal AF requiring demand pacing underwent electrophysiologic study and dual chamber pacemaker implant. After 4 months of follow-up, patients were divided into two groups according to the presence (group 1) or absence (group 2) of symptomatic AF recurrences. Atrial pacing markedly reduced AF recurrences in all patients. Twenty-four patients were free of arrhythmia. The basal state conduction times (CTs) and the incremental conduction times (ICTs), during programmed electric stimulation between the high right atrium (HRA) and the coronary sinus ostium (CSos), but not between the HRA and the His-bundle region, were significantly longer in group 1. There was no statistical difference in the effective refractory period (ERP) recorded at the HRA, the low right atrium (LRA), and the CSos between the two groups, whereas the differences between the greatest and least recorded ERPs measured from the HRA, LRA, and CSos (deltaERP) were significantly greater in group 1 patients. Two parameters were selected by discriminant multivariate analysis, namely deltaCTos (ICT-CT between HRA and CSos) and deltaERP. The first had a greater relative importance in predicting AF recurrence (r2 = 0.33 and r2 = 0.1, respectively). CONCLUSION: Single site atrial pacing is effective in reducing AF recurrences, with decreasing efficacy in patients with greater right atrial conduction delay and wider refractoriness dispersion.

Aged↗

[The predictive value of junctional beats during the radiofrequency transcatheter ablation of the slow pathway of the nodal reentry circuit].

BACKGROUND: Junctional beats (JB) are often recorded during slow pathway (SP) radiofrequency (RF) ablation in patients with atrioventricular nodal reentrant tachycardia (AVNRT). Neither the correlation between JBs and SP potentials nor the role of mechanically-evoked JBs has been clarified yet. METHODS: Two hundred-eleven consecutive patients, with common AVNRT, underwent RF transcatheter ablation guided by Jackman SP potential searching. If we were unable to record an SP potential or if 4 RF pulses delivered on ideal ablation sites were ineffective, the ablation was carried out on anatomical landmarks. Light pressure was applied with the ablation catheter to each ablation site before RF delivery in order to evaluate the inducibility of JBs. RESULTS: Transcatheter ablation was performed successfully in 209/211 (99%) patients. In 17 (8.1%) patients, no SP potential was recorded. JBs were observed more often delivering RF in the mid-septal region, whereas SP potentials were more often recorded at the base of the Koch triangle. The success rate (successful pulses/overall pulses) was higher in the mid-septal (58.6% in M1, 77.8% in M2) than in the postero-septal region (4% in PSC, 16.8% in P1). JBs showed a higher specificity (73.2 vs 5.3%), positive (55.5 vs 24.6%) and negative predictive value (97.3 vs 63.8%) than SP potential in identifying the successful ablation site. Mechanical JBs were evoked in 23 patients on 29 ablation sites, and 18/29 (62.1%) of them were successful ablation sites. CONCLUSIONS: The recording of JBs during or before RF ablation is a useful parameter to guide SP ablation in patients with AVNRT. Although the underlying mechanism has not been clarified yet, their preferential occurrence in the mid-septal region suggests that they might be due to thermal stimulation of compact atrioventricular node.

Cardiac Pacing, Artificial↗

Familial idiopathic intracranial hypertension with spinal and radicular pain.

OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic intracranial hypertension (IIH), associated in the sons with root irritation symptom. Unlike the other 4 families reported previously, obesity was not present in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years) and her 2 sons (aged 14 and 9 years) developed IIH at different times. Neuroimaging showed an empty sella in the mother, while IIH was associated with spinal and radicular pain in her 2 sons. The mother and the younger son developed permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients indicates that IIH is a chronic disease. Surgical treatment should be considered an option.

Adolescent↗

Feasibility and safety of two French electrode catheters in the performance of electrophysiological studies.

UNLABELLED: The aim of this study was to analyze prospectively the feasibility and safety of using 2 Fr versus 6 Fr standard electrode catheters for diagnostic electrophysiological study. METHODS: Two hundred and five consecutive patients were randomized to receive the 6 Fr approach (3 quadripolar, 6 Fr, electrode catheters inserted through the left or right femoral vein and placed in the high right atrium, right ventricular apex, and His bundle area) or the 2 Fr approach (3 quadripolar, 2 Fr, electrode catheters inserted through a single, 7 Fr, triple lumen, guiding catheter and positioned at the same sites as the 6 Fr approach). RESULTS: Introduction time was shorter in the 2 Fr group (133.3 +/- 65 s, range 87-669 s) than in the 6 Fr group (242.8 +/- 91.8 s, range 168-1024 s, P < 0.001). The overall fluoroscopy time was longer in the 2 Fr group (141.2 +/- 40.1 s, range 78-312 s) than in the 6 Fr group (126.4 +/- 39.7 s, range 58-341 s, P = 0.009). However in the last 100 patients there was no more difference between the two groups (137.6 +/- 28.2 s vs 128.4 +/- 23.2 s, P = 0.07). There was no significant difference between 2 Fr and 6 Fr groups in the mean atrial (5.9 +/- 2.2 mV, range 2.2-11.3 mV, vs 6.1 +/- 2.3 mV, range 2.4-12.4 mV, P = 0.57) and ventricular (5.6 +/- 2.1 mV, range 1.9-9.7 mV, vs 5.7 +/- 2.2 mV, range 2.3-10.5 mV, P = 0.66) activation potential amplitudes recorded during sinus rhythm, or in the rate of stable His bundle potential recording (P = 0.3), and catheter dislodgment (P = 0.54). The overall number of complications was significantly higher in the 6 Fr group than in the 2 Fr group (29 vs 5, P = 0.001), as well as the number of entry site related complications (3 vs 12, P = 0.02) and catheter manipulation related complications (2 vs 17, P < 0.001). CONCLUSIONS: The results of this study show that the use of 2 Fr electrode catheters reduces the rates of entry site and catheter manipulation related complications during EPS. Despite their small size, these catheters allow quick and precise positioning of the electrode.

Cardiac Catheterization↗

Radiofrequency modification of the atrioventricular node in patients with chronic atrial fibrillation: comparison between anterior and posterior approaches.

INTRODUCTION: We compared, in a prospective and randomized fashion with a cross-over design, the anterior and posterior approaches to radiofrequency (RF) modification of the AV node in patients with chronic atrial fibrillation. METHODS AND RESULTS: Thirty-three patients were randomized to receive first an anterior (group I) or posterior (group II) approach for RF modification of AV nodal conduction. Patients who did not fill the endpoint ventricular rate (< 90 beats/min) were crossed over to the alternative approach. After the anterior approach in group I patients, mean ventricular rate was significantly lower than in group II patients after the posterior approach (79.6 +/- 18.8 beats/min vs 110.8 +/- 16.2 beats/min, P < 0.001). In group I, 14 (82%) of 17 patients fulfilled the endpoint, 1 (6%) had complete AV block, and 2 (12%) were crossed over to the posterior approach fulfilling the endpoint. In group II, 4 (25%) of 16 patients fulfilled the endpoint. No transient or permanent high-degree AV block was observed. Among the 12 patients who were crossed over to the anterior approach, 8 fulfilled the endpoint, whereas 4 had permanent high-degree AV block. RF ablation carried out only in the anterior region was safer than a stepwise approach (6% vs 33% incidence of AV block), even though the difference did not reach statistical significance (P = 0.09). CONCLUSION: Posterior AV nodal modification is less effective but safer than anterior AV nodal modification. However, to reduce the incidence of AV block, the anterior approach is preferable to a stepwise approach from the posterior to the anterior zone.

Aged↗

Inappropriate sinus tachycardia after radiofrequency ablation of para-Hisian accessory pathways.

INTRODUCTION: Inappropriate sinus tachycardia (IST) has been observed following radiofrequency ablation (RFA) of the AV nodal fast pathway. This study was aimed to prospectively analyze the incidence and clinical significance of IST following RFA of para-Hisian accessory pathways (APs). METHODS AND RESULTS: Twenty-eight patients (pts) with para-Hisian APs underwent RFA. An AP was defined as para-Hisian whenever its atrial and ventricular insertions were associated with a His-bundle potential > or = 0.1 mV. RF current was always delivered at the atrial aspect of the tricuspid annulus, to a site where the His-bundle potential was < 0.15 mV. Time- and frequency-domain analysis of heart rate variability was performed in 22 patients, before and after RFA. Abolition of AP conduction was obtained in all pts, and no AV conduction alteration occurred. Six pts (21.4%) presented with IST 45 to 240 minutes after the ablation procedure. In 5 of them, IST disappeared spontaneously within 72 hours, whereas in 1 pt beta-blockers were required for 2 months. The atrial potential amplitude (1.217 +/- 0.264 mV vs 0.882 +/- 0.173 mV, P = 0.009) and A/V potential amplitude ratio (2.633 vs 1.686, P = 0.05) were significantly higher in pts who developed IST than in those who did not. A marked decrease in heart rate variability was observed only in pts who developed IST. CONCLUSION: IST is a relatively frequent complication after RFA of para-Hisian APs: it is generally short-lasting and usually does not require any treatment. IST after catheter ablation is likely to depend upon transient parasympathetic denervation of the sinus node.

Adolescent↗

Role of catheter-induced mechanical trauma in localization of target sites of radiofrequency ablation in automatic atrial tachycardia.

OBJECTIVES: We compared the efficacy of two different mapping techniques in identifying the ablation site for atrial tachycardia. Moreover, we evaluated the additive positive predictive value of mechanical interruption of atrial tachycardia to reduce the number of ineffective radiofrequency applications. BACKGROUND: Radiofrequency catheter ablation has been suggested as a highly effective technique to treat drug-resistant atrial tachycardia. However, irrespective of the mapping technique utilized, success was most often achieved with a large number of radiofrequency applications. METHODS: Forty-five patients with atrial tachycardia underwent radiofrequency catheter ablation. Mapping techniques included identification of earliest atrial activation and pace-mapping concordant sequence. RESULTS: Atrial tachycardia was successfully treated in 42 (93.3%) of 45 patients with a mean of 3.9 radiofrequency pulses/patient. An interval between the onset of the intracavitary atrial deflection and the onset of the P wave during atrial tachycardia (AP interval) > or = 30 ms (p < 0.001) and pace-mapping concordant sequence (p = 0.01) were all significant predictors of outcome. An AP interval > or = 30 ms and a pace-mapping concordant sequence were highly sensitive (92.8%, 95% confidence interval [CI] 80.5% to 98.5%; 85.7%, 95% CI 71.5% to 94.6%, respectively) but less specific (47.8%, 95% CI 37.9% to 58.2%, 36.8%, 95% CI 27.6% to 47.2%, respectively) in identifying the site of ablation. By using atrial tachycardia mechanical interruption combined with the AP interval >30 ms or the pace-mapping concordant sequence, we obtained a specifically of 76.5% (95% CI 66.4% to 84.0%) and 73.5% (95% CI 63.2% to 81.4%), respectively, and a positive predictive value of 49.2% and 44.6%, respectively. CONCLUSIONS: An AP interval > or = 30 ms and a pace-mapping concordant sequence were reliable mapping features for predicting the outcome of the ablation procedure. Mechanical interruption of atrial tachycardia improved the specificity and positive predictive value of these two mapping techniques.

Adolescent↗

[Radiofrequency catheter ablation of atrial tachycardia: technique, results and follow-up].

BACKGROUND: Recently radiofrequency (RF) catheter ablation (CA) of atrial tachycardia (AT) showed to be highly effective with a low incidence of compliance. Aim of our study was to report the results and follow-up of RFCA of drug-refractory AT in 59 consecutive patients (pts). METHODS: Two mapping techniques were used to localize the ablation site of AT: the earliest atrial activation and the pace-mapping. Traumatic interruption of AT was used to verify the ablation site identified by the previous procedures. Moreover we evaluated the sensitivity, specificity and the positive predictive value of the three mapping techniques. RESULTS: AT was successfully treated in 55/59 (93.2%) pts with a mean of 4.0 +/- 3.8 (range 1-16) RF pulses for patient. The mean procedure time was 185.2 +/- 48.5 min with a mean rx-time of 41.5 +/- 21.3 min. An interval between the onset of the intracavitary atrial deflection and the onset of the P-wave, during atrial tachycardia, (AP interval) > or = 30 ms and pace-mapping concordant sequence were highly sensitive (90.9% and 89.1%) but less specific (49.2% and 33.9%) in identifying the site of ablation. By using atrial tachycardia traumatic interruption combined with the AP interval > 30 ms or the pace-mapping concordant sequence we obtained a specificity of 78.7% and 77.0% respectively and a positive predictive value of 48.0% and 46.8% respectively. Four recurrences (7.3%) were observed during a mean follow-up of 23.4 +/- 13.3 months. In the 22 (37.3%) pts with dilated cardiomyopathy, chest Xr and echocardiography showed a significant decrease of cardiothoracic index (0.56 +/- 0.08 pre ablation, 0.43 +/- 0.07 post ablation, p < 0.001) and end-diastolic diameter (64 +/- 8 mm pre ablation, 52 +/- 8 mm post ablation, p < 0.001) and a significant improvement of left ventricular ejection fraction (37 +/- 9% pre ablation, 48 +/- 11% post ablation, p < 0.05). CONCLUSION: The RFCA of AT was effective and safe. Moreover we observed a hemodynamic improvement in patients with reduced ejection fraction and increased cardiac volumes. An AP interval > or = 30 ms and the pace-mapping concordant sequence were reliable features to predict the outcome of the ablation procedure. Traumatic ablation of atrial tachycardia improved the specificity and the positive predictive value of these two mapping techniques and was able to predict the response to radiofrequency with a high specificity.

Catheter Ablation↗

[Atrioventricular conduction before and after the radiofrequency catheter ablation of a nodal reentry tachycardia circuit].

Aim of our study was to retrospectively evaluate atrioventricular conduction 24 hours after selective radiofrequency catheter ablation of the fast pathway or after selective ablation of the slow pathway of the atrioventricular nodal reentrant tachycardia circuit. Electrophysiologic modifications were retrospectively analyzed in 47/48 patients successfully submitted to fast pathway ablation and in 90/93 patients successfully submitted to slow pathway ablation. The atrioventricular conduction intervals (P-Q and A-H), both anterograde and retrograde Wenckebach point, the effective refractory period of atrioventricular node and the atrioventricular node function curve were evaluated before and after selective radiofrequency catheter ablation of slow and fast pathway. We identified the fast pathway ablation potential as: A:V ratio > or = 2:1, His electrogram < or = 150 microV. The slow pathway potential was identified as the widest, sharpest and latest atrial electrogram recorded during sinus rhythm in the posteroseptal region of the atrioventricular junction or as the widest, sharpest and earliest observed during retrograde conduction. We observed a significant increase in the P-Q and A-H intervals in patients submitted to fast pathway ablation, while no significant modification of these parameters was appreciated in patients submitted to slow pathway ablation. No significant modification of anterograde Wenckebach point (NS) was observed in patients submitted to successfully ablation of fast pathway while a statistically significant increase in anterograde Wenckebach point (p = 0.03) was observed in patients submitted to slow pathway ablation. After selective fast pathway ablation, retrograde conduction was absent in 82.9% of patients submitted to ablation; in the remaining 17.1% a significant increase of retrograde Wenckebach point was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Ablation of paroxysmal tachycardia in Wolff-Parkinson-White syndrome].

Surgical or catheter ablation of accessory pathways by means of high energy shock has been substantial associated with morbidity and mortality. On the contrary radiofrequency current, an alternative energy source for ablation, has a low incidence of complications and a very high success rate. Aim of this study was to relate about the results using catheter ablation of accessory pathways by radiofrequency current in our Electrophysiologic laboratory. Radiofrequency current (20-40 W) was delivered between a large-tip catheter electrode positioned against the mitral or tricuspid anulus and a standard adhesive electrosurgical dispersive pad applied to the left chest wall. When possible radiofrequency delivery was guided by catheter recordings of accessory pathway activation. Ablation was attempted in 181 patients with 191 accessory pathways. We obtained successful ablation of 187/191 accessory pathways and accessory pathway conduction was eliminated in 177/181 patients. During a mean follow-up of 14 +/- 10 months preexcitation returned in 7 patients (3.9%). All underwent a second successful ablation. In 1 patient, during the procedure, we observed a transient ischemic attack, with no complications. In accordance to other reports we conclude that radiofrequency ablation is highly effective in ablating accessory pathways, with low morbidity and no mortality.

Adolescent↗

[A methodological approach to the transcatheter radiofrequency ablation of anomalous Kent-type pathways].

Aim of this study is to suggest our methodological approach for transcatheter ablation of Kent bundles by radiofrequency energy as to the potential ablation sites, the need in unipolar or bipolar recording mode, single catheter or multiple catheters mapping of anomalous pathways, the vascular approach for both left sited and right sited anomalous pathways, and finally the duration and power to supply. The recording of Kent potential and/or a Va-QRS interval > or = 0 ms have been considered significant predictors of success (respectively p < 0.001 and p < 0.05). The unipolar recording mode has been considered critical in the choice of ablation site in 47 (29.9%) patients. A 6-catheter approach for both diagnostic electrophysiologic studies and mapping allowed us to easily localize accessory pathways and to record either a probable or possible Kent potential in a high percentage of patients and to reduce the permanence of the ablation catheter in the left ventricle. By transaortic retrograde approach in ablating left sited anomalous pathways, we obtained a high success rate, while right sited accessory pathway were approached from the inferior vena cava. In right sited anomalous pathway we delivered radiofrequency energy for a longer time in order to avoid a relapse soon after the procedure. We performed ablation of 174/178 (97.7%) anomalous pathways in 165/169 (97.6%) patients. We observed a 3.8% relapse during a mean follow up of 13 +/- 9 months.

Adolescent↗