Biomedical subjects

R Riccardi

Publications and source records attributed to R Riccardi.

At least 37 records · Page 2Linked to original sources

PubMed2001

Different patterns of atrial activation in idiopathic atrial fibrillation: simultaneous multisite atrial mapping in patients with paroxysmal and chronic atrial fibrillation.

OBJECTIVES: We aimed to evaluate: 1) the behavior of electrical activity simultaneously in different atrial regions during atrial fibrillation (AF); 2) the difference of atrial activation between paroxysmal and chronic AF; 3) the atrial refractoriness dispersion; and 4) the correlation between the effective refractory periods (ERPs) and the FF intervals. BACKGROUND: Little data exist on the electrophysiologic characteristics of the different atrial regions in patients with AF. A more detailed knowledge of the electrical activity during AF may provide further insights to improve treatment of AF. METHODS: Right and left atria were extensively mapped in 30 patients with idiopathic AF (18 paroxysmal and 12 chronic). In different atrial locations, we analyzed 1) the FF interval duration; and 2) the grade of organization and, in case of organized electrical activity, the direction of atrial activation. Furthermore, in patients with paroxysmal AF, we determined the atrial ERP, evaluated the ERP dispersion and assessed the presence of a correlation between the ERPs and the FF intervals. RESULTS: In patients with chronic AF, we observed a shortening of the FF intervals and a greater prevalence of disorganized activity in all the atrial sites examined. In patients with paroxysmal AF, a significant dispersion of refractoriness was observed. The right lateral wall showed longer FF intervals and more organized atrial activity and, unexpectedly, the shortest mean ERPs. In contrast, the septal area showed shorter FF intervals, greater disorganization and the longest mean ERPs. CONCLUSIONS: Electrical activity during AF showed a significant spatial inhomogeneity, which was more evident in patients with paroxysmal AF. The mean FF intervals did not correlate with the mean ERPs.

Adult↗

PubMed2001

The novel trinuclear platinum complex BBR3464 induces a cellular response different from cisplatin.

BBR3464 is a new platinum-based drug non cross-resistant with cisplatin. To characterise the cellular basis of BBR3464 cytotoxicity as opposed to cisplatin, we performed a comparative study of the two drugs in cisplatin-resistant neuroblastoma and astrocytoma cells. In both model systems, BBR3464 proved to be more potent than cisplatin and was able to overcome cisplatin resistance. The higher potency exhibited by BBR3464 correlated with an increased cellular platinum accumulation and DNA-adduct formation. At equitoxic doses, BBR3464 induced apoptosis to a lesser extent than cisplatin and failed to overcome the decreased susceptibility to cisplatin-induced apoptosis in cisplatin-resistant cells. Cell cycle analysis showed a dose-dependent G2/M arrest by BBR3464. In astrocytoma cells, cisplatin treatment resulted in the upregulation of p53, p21 and bax, while only p21 induction was observed after BBR3464 treatment. In cisplatin-resistant cells, the reduced sensitivity to cisplatin paralleled a resistance to the induction of p53/p21 pathway by cisplatin, while the same doses of BBR3464 induced p21 to a similar extent in the resistant cells as in the parental cells. In conclusion, BBR3464 induces a cellular response that is different from cisplatin, supporting the view that the two drugs act through different mechanisms. Our data indicate that BBR3464 may be a promising agent in the treatment of tumours unresponsive to cisplatin and with a non-functional p53.

Antineoplastic Agents↗

PubMed2001

Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice?

AIMS: The 6-min walk test has been incorporated into studies on the efficacy of new therapies and into prognostic stratification for chronic heart failure patients. Firm conclusions on the usefulness of the test in clinical practice are still lacking. The aim of this study was to investigate (1) the correlation between walk test performance and standard indices of cardiac function and exercise capacity, and (2) the prognostic value of the walk test with respect to peak VO2 and NYHA class. METHODS AND RESULTS: Three hundred and fifteen chronic heart failure patients (age: 53+/-9 years, NYHA class: II (182), III (133)) underwent a functional evaluation and a 6-min walk test. Of these, 270 were followed-up for a minimum of 6 months (mean 387+/-177 days). Walked distance was 396+/-92 m. There was no significant correlation between distance walked and central haemodynamic data. Functional capacity, as measured by ergometry, correlated moderately with distance walked (duration: r=0.48, peak VO2: r=0.59, anaerobic threshold: r=0.54; all P<0.001). During follow-up, 46 patients died from cardiovascular causes and 12 were urgently transplanted. Either of these events were considered end points of the study. Survival analysis was performed from a continuous walk test and peak VO2 measurements or after categorization of (a) quartile segmentation, (b) cut-off points from the literature and (c) thresholds from receiver operating characteristic curves. At univariate survival analysis (Cox regression), the association of the walk test with survival was of significance (P=0.03, continuous variable), or borderline significance (0.05< or =P< or =0.1, after categorization). Peak VO2 was always significant, independent of the scale used (0.005< or =P< or =0.03). The strongest association was found for NYHA class (P<0.001), which showed the highest sensitivity and specificity for the prediction of the event (0.64 and 0.65, respectively). When walk test performance, continuous or categorized, was entered into a multivariate model with NYHA class or peak VO2, it lost any significant association with survival (P>0.76 in all models with NYHA class and P>0.27 in all models with peak VO2). CONCLUSION: In moderate-to-severe chronic heart failure patients, the 6-min walk test is not related to cardiac function and only moderately related to exercise capacity. Walking performance does not provide prognostic information which can complement or substitute for that provided by peak VO2 or NYHA class. Hence the test is of limited usefulness as a decisional indicator in clinical practice.

Adult↗

PubMed2001

Intrathecal chemotherapy with antineoplastic agents in children.

Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.

Adrenal Cortex Hormones↗

PubMed2001

Accessory pathway potential recording in a case of permanent junctional reciprocating tachycardia with decremental conduction localized on the atrial site.

Permanent junctional reciprocating tachycardia (PJRT) is an uncommon form of atrioventricular reentrant tachycardia due to the presence of an accessory pathway characterized by slow and decremental retrograde conduction. We report a case of PJRT where we demonstrated the possibility of recording a distinct accessory pathway potential. Decremental retrograde conduction was evident using ventricular extrastimuli and it was also adenosine-sensitive. Delivering ventricular extrastimuli a prolongation of the accessory pathway potential-atrium interval was seen demonstrating that decremental conduction was located at the atrial insertion of the pathway. The accessory pathway was successfully ablated using the potential as the target of radiofrequency delivery. These electrophysiological findings seem to support the hypothesis that a nodal-like structure may be responsible for this arrhythmia.

Catheter Ablation↗

PubMed2001

Atrial mapping by basket catheter in patients with atrial fibrillation submitted to linear ablation.

Recently non-pharmacological therapies for atrial fibrillation (AF) have been developed. The electrophysiological mechanisms of AF is thought to be the development of multiple reentrant wavelets circulating around anatomic barriers and variable regions of functional conduction block responsible of the perpetuation of the arrhythmia. Also the role of the triggering foci has been highlighted. To cure AF by means of non pharmacological therapy we may eliminate and/or modify the substrate. To better understand the mechanism underlying the AF and to choose the best ablation strategy is of fundamental importance to map the right and the left atrium during AF. Our experience shows that in chronic idiopathic AF disorganized atrial activity is observed at all atrial regions while in paroxysmal idiopathic AF the left septum and the right atrial posterior areas are highly disorganized while the lateral region shows more organized atrial electrical activity. Multipolar basket catheters are extremely useful in mapping right and left atrium in order to guide the best ablation strategy.

Atrial Fibrillation↗

PubMed2000

Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population.

Diamond-Blackfan anemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation and physical malformations. Most cases are sporadic, but dominant or, more rarely, recessive inheritance is observed in 10% of patients. Mutations in the gene encoding ribosomal protein (RP) S19 have recently been found in 25% of patients with either the dominant or the sporadic form. DBA is the first human disease due to mutations in a ribosomal structural protein. Families unlinked to this locus have also been reported. In an investigation of 23 individuals, we identified eight different mutations in 9 patients. These include five missense, one frameshift, one splice site defect, and one 4-bp insertion in the regulatory sequence. Seven mutations are new; one has so far been found in 8 patients and is a relatively common de novo event. Two mutations are predicted to generate a truncated protein. We also report the prevalence of RPS 19 mutations in the Italian DBA population, as shown by an analysis of 56 patients. No genotype-phenotype correlation was found between patients with the same mutation. The main clinical applications for molecular analysis are clinical diagnosis of patients with an incomplete form of DBA and testing of siblings of a patient with a severe form so as to avoid using those who carry a mutation and a silent phenotype as allogeneic stem cell donors.

Adult↗

PubMed2000

Limited posterior left atrial cryoablation in patients with chronic atrial fibrillation undergoing valvular heart sugery.

OBJECTIVES: We sought to evaluate whether a limited surgical cryoablation of the posterior region of the left atrium was safe and effective in the cure of atrial fibrillation (AF) in patients with associated valvular heart disease. BACKGROUND: Extensive surgical ablation of AF is a complex and risky procedure. The posterior region of the left atrium seems to be important in the initiation and maintenance of AF. METHODS: In 32 patients with chronic AF who underwent heart valve surgery, linear cryolesions connecting the four pulmonary veins and the posterior mitral annulus were performed. Eighteen patients with AF who underwent valvular surgery but refused cryoablation were considered as the control group. RESULTS: Sinus rhythm (SR) was restored in 25 (78%) of 32 patients immediately after the operation. The cryoablation procedure required 20 +/- 4 min. There were no intraoperative and perioperative complications. During the hospital period, one patient died of septicemia. Thirty-one patients reached a minimum of nine months of follow-up. Two deaths occurred but were unrelated to the procedure. Twenty (69%) of 29 patients remained in SR with cryoablation alone, and 26 (90%) of 29 patients with cryoablation, drugs and radiofrequency ablation. Three (10%) of 29 patients remained in chronic AF. Right and left atrial contractility was evident in 24 (92%) of 26 patients in SR. In control group, two deaths occurred, and SR was present in only four (25%) of 16 patients. CONCLUSIONS: Linear cryoablation with lesions connecting the four pulmonary veins and the mitral annulus is effective in restoration and maintenance of SR in patients with heart valve disease and chronic AF. Limited left atrial cryoablation may represent a valid alternative to the maze procedure, reducing myocardial ischemic time and risk of bleeding.

Aged↗

PubMed2000

Typical atrial flutter ablation: conduction across the posterior region of the inferior vena cava orifice may mimic unidirectional isthmus block.

INTRODUCTION: The aim of this study was to map the low right atrium before and after radiofrequency ablation of the inferior vena cava-tricuspid annulus (IVC-TA) isthmus in patients with typical atrial flutter (AFI) to better understand the electrophysiologic meaning of incomplete or unidirectional block following the ablation procedure and its relationship with AFI recurrence. METHODS AND RESULTS: We performed atrial mapping in 12 patients using a "basket" catheter in the IVC orifice, Halo catheter in the right atrium, and multipolar catheters in the coronary sinus (CS) and His region. In patients in sinus rhythm, atrial activation was analyzed during pacing from the CS and low lateral right atrium (LLRA) before and after ablation. Atrial activation propagated across the isthmus and posterior region of the IVC orifice simultaneously before ablation. Mapping during AF1 in four patients showed that the crista terminalis was a site of functional block. After ablation, evaluation of Halo catheter recordings in three patients showed apparent unidirectional counterclockwise block, whereas analysis of basket catheter recordings demonstrated complete bidirectional block. The apparent conduction over the isthmus during pacing from proximal CS was due to conduction along the posterior part of the IVC orifice, which activated the LLRA despite complete isthmus block. CONCLUSION: Our results demonstrate that limited endocardial mapping may yield a pattern compatible with unidirectional block in the IVC-TA isthmus, although bidirectional block is present at this anatomic level.

Atrial Flutter↗

PubMed2000

Electrophysiology of atrial fibrillation: evolving insights.

In the last few years many studies have been performed to better understand the pathophysiological nature of atrial fibrillation (AF). These recent observations provide new insights into the initiation and perpetuation of AF, underlying the importance of the pulmonary veins as major sources of atrial triggers and introducing new concepts such as atrial electrical remodeling and spatial heterogeneity of the electrophysiologic characteristics of this arrhythmia. The purpose of this review was to provide current knowledge about AF electrophysiology in an effort to unite old models and new concepts.

Animals↗

PubMed2000

Immune tolerance by intermittent factor VIII boluses in two high responder hemophilia A patients.

Immune tolerance (IT) in hemophilia A patients with anti-factor VIII antibodies is generally based on daily factor VIII administrations. Here we report the preliminary results of an immune tolerance regimen based on recombinant high-dose (400 U/kg) factor VIII boluses administered at 48-hour intervals. Two high responder hemophilia A patients aged 2 and 3 years received this treatment without the need of permanent venous access. In both cases the IT regimen caused an anamnestic response of less than three weeks' duration and an antibody reduction to less than 5 Bethesda units was achieved in about 8-10 weeks. In the child with a more prolonged follow-up the inhibitor became undetectable after four months and factor VIII recovery at 6 months was > 85%. This intermittent high-dose regimen seems to be effective in rapidly inducing immune tolerance and seems particularly suitable for very young children in whom it may be useful to avoid the risks and to reduce the psychological burden of permanent venous access.

Child, Preschool↗

PubMed2000

Management of idiopathic thrombocytopenic purpura in children: a single institution experience.

Idiopathic thrombocytopenic purpura (ITP) is a relatively common hematologic disease in childhood. ITP is often self-limiting and is characterized by a good clinical outcome. About 10-20% of cases can have a chronic course. In our retrospective analysis we have evaluated 45 patients affected by ITP from January '92 to December '97. Thirty-seven patients (82%) met the criteria of acute ITP and 8 (18%) had chronic ITP. Patients were stratified into 3 categories based up on the type of treatment received: no treatment, steroids, steroids and IVIG. In our series children treated with oral prednisone showed a slightly faster recovery in the first days from treatment. We suggest the use of steroids in children with low platelet count and signs and symptoms of bleeding.

Child↗

PubMed1999

Antitumour activity of oxaliplatin in neuroblastoma cell lines.

Oxaliplatin appears non cross-resistant with cisplatin and has a comparable antitumour effect both in preclinical and clinical studies. We compared the antitumour effect of oxaliplatin with that of cisplatin in human neuroblastoma cell lines SK-N-DZ, LAN-1 and BE(2)M17 following 24 h exposure at concentrations ranging from 0.5 to 5 microM. Oxaliplatin was less potent with IC50 values 1.08-3.4-fold higher than cisplatin. Like cisplatin, oxaliplatin induced a cell cycle block in the G2/M phase although to a lesser extent than that caused by cisplatin. The concomitant increase of DNA fragmentation and decrease of G2/G1 ratio at 72 h indicated that a fraction of blocked cells underwent apoptosis. Morphological analysis confirmed these data, although oxaliplatin appeared to be 2-3 times less potent than cisplatin in inducing apoptosis. Our results indicate that oxaliplatin is active in neuroblastoma in vitro and this finding warrants in vivo preclinical studies.

Antineoplastic Agents↗

PubMed1999

Influence of cisplatin and doxorubicin on 125I-meta-iodobenzylguanidine uptake in human neuroblastoma cell lines.

The combination of 131I-meta-iodobenzylguanidine (MIBG) with chemotherapy has recently been employed in the treatment of advanced stage neuroblastoma with encouraging results. However, the mechanisms underlying the interaction between these two different modalities of treatment have not yet been explored. In this study, human neuroblastoma cell lines pretreatment with cisplatin and doxorubicin increased cellular 125I-MIBG accumulation in a dose-dependent manner. Cell cycle analysis showed that increased 125I-MIBG accumulation correlated with the drug-induced G2/M phase block. Northern blot analysis demonstrated an increase in gene expression of the noradrenaline transporter induced by doxorubicin, but not by cisplatin treatment. Increased 125I-MIBG accumulation was also observed in murine xenografts of the human neuroblastoma cell line SK-N-DZ or BE(2)M17 treated intraperitoneally (i.p.) with cisplatin or doxorubicin, respectively. These results suggest that the combination of 131I-MIBG and these drugs could selectively increase radiation doses delivered to neuroblastomas.

3-Iodobenzylguanidine↗

PubMed1999

Interruption of the inferior extension of the compact atrioventricular node underlies successful radio frequency ablation of atrioventricular nodal reentrant tachycardia.

A recent anatomic study has revived interest in the inferior extensions of the compact atrioventricular node in humans. The rightward extension is on the right atrial aspect, close to the septal attachment of the tricuspid valve leaflet and, hence, closely related to the anticipated slow pathway considered to play a role in atrioventricular nodal reentrant tachycardia (AVNRT). This report documents a patient, 65 years of age, with dilated cardiomyopathy and AVNRT. The tachycardia was successfully terminated using selective radiofrequency (RF) ablation, delivered at a site where a slow potential was recorded and validated by atrial pacing, located between the tricuspid valve and the os of the coronary sinus (CS), close to its superior rim. In subsequent years the patient developed progressive heart failure and eventually died. Histopathologic examination revealed extensive scar tissue at the site of the burn, extending onto the crest of the underlying ventricular septum. Serial sections revealed the compact AV node superiorly and an inferior extension surfacing from the scar which could be traced inferiorly beyond the os of the CS. This is the first documentation of RF ablation interrupting an inferior extension of the compact AV node in a patient successfully ablated for AVNRT. The observation suggests that the slow pathway in this patient found its anatomic substrate in the inferior extension of the compact AV node.

Aged↗

PubMed1999

Catheter ablation in a patient with a congenital giant right atrial diverticulum presented as Wolff-Parkinson-White syndrome.

A young woman symptomatic for tachycardia showed right ventricular preexcitation on the surface ECG with a pattern during induced atrial fibrillation suggestive of multiple APs. Noninvasive imaging techniques performed prior to catheter ablation demonstrated the presence of a giant right atrial diverticulum confirmed by hemodynamic procedure. This structure functioned as an enormous accessory AP. We performed catheter ablation of this pathway using a special 4-mm multipolar catheter inside the diverticulum. This is the first case of such as anomaly being successfully treated with catheter ablation.

Adult↗

PubMed1999

Reproducibility of spontaneous initiations of atrial fibrillation.

INTRODUCTION: It has been suggested that some atrial regions may play a role in the maintenance of atrial fibrillation (AF), whereas little is known about the presence of critical areas for the initiation of AF. It is conceivable that the identification of such critical areas may lead to more localized and selective strategies of ablative therapy. METHODS AND RESULTS: A patient suffering from paroxysmal AF was extensively mapped in both the atria with a multielectrode basket catheter in right atrium and two decapolar catheters placed in the coronary sinus and along the left septum. During the mapping, seven identical patterns of initiation of AF were recorded. AF was initiated by an atrial premature beat (APB) arising from the superior right septum, followed by a reentrant beat originating from the same area that slowly propagated through the atria and resulted in late activation of the right lateral wall. During sinus rhythm, the majority of the electrograms were single potentials, whereas during the APB, and particularly during the first atrial reentrant beat, a high percentage of fragmented complexes was present, mainly located in the right superior septum. These fragmented complexes were present in the same sites in each initiating episode and remarkably, they showed an almost identical morphology. CONCLUSION: This case suggests that in some patients the initiation of AF could be caused by reentrant circuits localized in specific atrial regions and the reentrant circuits could be identical in the different episodes of AF. This highlights the importance of increasing our understanding of the mechanisms of the initiation of AF so that we can identify any critical area involved in the genesis of AF where selective RF lesions may be effective in curing this arrhythmia.

Aged↗

PubMed1999

Unusual induction of slow-fast atrioventricular nodal reentrant tachycardia. Report of two cases.

INTRODUCTION: Generally, the induction of typical atrioventricular nodal reentrant tachycardia (AVNRT) occurs with a premature atrial stimulus that blocks in the fast pathway and proceeds down the slow pathway slowly enough to allow the refractory fast pathway time to recover. We describe two cases in which a typical AVNRT was induced in an unusual fashion. RESULTS: The first case is a 41-year-old man with paroxysmal supraventricular tachycardia. During the electrophysiology study, the atrial extrastimulus inducing the typical AVNRT was conducted simultaneously over the fast (AH) and the slow pathway (AH'). A successful ablation of the slow pathway was performed. During the follow-up no recurrence was noted. The second case is a 52-year-old woman with a Wolff-Parkinson-White syndrome due to a left posterior accessory pathway. After 5 minutes of atrioventricular reentrant tachycardia (AVRT) induced by a ventricular extrastimulus, a variability of the antegrade conduction was noted in presence of the same VA conduction. In fact, a short AH interval (fast pathway) alternated with a more prolonged AH intervals (slow pathway) that progressively lengthened until a typical AVNRT was induced. The ablation of the accessory pathway eliminated both tachycardias. DISCUSSION: A rare manifestation of dual atrioventricular nodal pathways is a double ventricular response to an atrial impulse that may cause a tachycardia with an atrioventricular conduction of 1:2. In our first case, an atrial extrastimulus was simultaneously conducted over the fast and the slow pathway inducing an AVNRT. This nodal reentry implies two different mechanisms: 1) a retrograde block on the slow pathway impeding the activation of the slow pathway from the impulse coming down the fast pathway, and 2) a critical slowing of conduction in the slow pathway to allow the recovery of excitability of the fast pathway. Interestingly, in the second case, during an AVRT the atrial impulse suddenly proceeded alternately over the fast and the slow pathway. The progressive slowing of conduction over the slow pathway until a certain point which allows the recovery of excitability of the fast pathway determines the AVNRT. This is a case of "tachycardia-induced tachycardia" as confirmed by the fact that the ablation of the accessory pathway eliminated both tachycardias.

Adult↗