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Biomedical subjects

M Santini

Publications and source records attributed to M Santini.

At least 37 records · Page 2Linked to original sources
PubMed2002

Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival.

BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001). CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.

Antigens, Viral↗
PubMed2002

The value of permanent follow-up of implantable pacemakers--first results of an European trial.

A clinical study investigates the use of Home Monitoring (HM) in pacemaker therapy. For 3 months patients are supervised by daily automatic HM messages. Endpoints are the technical feasibility and the clinical benefit of HM. Ninety three patients have currently been included and followed for 72 +/- 30 days. Three patients were excluded due to insufficient mobile net coverage at their living sites. For the other patients, 5311 of 5911 messages were successfully registered. Interrupts in the sequence of messages occurred 331 times. Two hundred ten of these (63%) lasted just 1 day, 14 interrupts (4%) lasted 5 or more days. Two patients did not show any interrupts, 34 patients (38%) had interrupts of 3 and more days. The clinical benefit of Home Monitoring was found in the remote detection of arrhythmia and lead dislocation.

Adult↗
PubMed2001

Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial.

BACKGROUND: This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope. METHODS AND RESULTS: Patients from 14 centers were randomized to receive either a DDD pacemaker provided with rate-drop response function or the beta-blocker atenolol at the dosage of 100 mg once a day. Inclusion criteria were age >35 years, >/=3 syncopal spells in the preceding 2 years, and positive response to tilt table testing with syncope occurring in association with relative bradycardia. The primary outcome was the first recurrence of syncope after randomization. Enrollment was started in December 1997, and the first formal interim analysis was performed on July 30, 2000. By that time, 93 patients (38 men and 55 women; mean age, 58.1+/-14.3 years) had been enrolled and randomized, although follow-up data were available for all patients (46 patients in the pacemaker arm, 47 patients in the pharmacological arm). The interim analysis showed a significant effect in favor of permanent cardiac pacing (recurrence of syncope in 2 patients [4.3%] after a median of 390 days) compared with medical treatment (recurrence of syncope in 12 patients [25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to 0.632; P=0.004). Consequently, enrollment and follow-up were terminated. CONCLUSIONS: DDD pacing with rate-drop response function is more effective than beta-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope.

Anti-Arrhythmia Agents↗
PubMed2001

Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay.

BACKGROUND: One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay, which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony. We assessed the clinical efficacy and safety of this new therapy. METHODS: Sixty-seven patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msec, received transvenous atriobiventricular pacemakers (with leads in one atrium and each ventricle). This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing. The primary end point was the distance walked in six minutes; the secondary end points were the quality of life as measured by questionnaire, peak oxygen consumption, hospitalizations related to heart failure, the patients' treatment preference (active vs. inactive pacing), and the mortality rate. RESULTS: Nine patients were withdrawn from the study before randomization, and 10 failed to complete both study periods. Thus, 48 patients completed both phases of the study. The mean distance walked in six minutes was 22 percent greater with active pacing (399+/-100 m vs. 326+/-134 m, P<0.001), the quality-of-life score improved by 32 percent (P<0.001), peak oxygen uptake increased by 8 percent (P<0.03), hospitalizations were decreased by two thirds (P<0.05), and active pacing was preferred by 85 percent of the patients (P<0.001). CONCLUSIONS: Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Impact of consistent atrial pacing algorithm on premature atrial complexe number and paroxysmal atrial fibrillation recurrences in brady-tachy syndrome: a randomized prospective cross over study.

AIM OF THE STUDY: The Consistent Atrial Pacing (CAP) algorithm has been designed to achieve a high percentage of atrial pacing to suppress paroxysmal atrial fibrillation. The aim of our study was to compare the impact of DDDR+CAP versus DDDR pacing on paroxysmal atrial fibrillation recurrences and triggers in patients with Brady-Tachy Syndrome. METHODS: 61 patients, 23 M and 38 F, mean age 75+/-9 y, affected by Brady-Tachy Syndrome, implanted with a DDDR pacemaker, were randomized to DDDR or DDDR+CAP pacing with cross over of pacing modality after 1 month. RESULTS: 78 % of patients in DDDR pacing and 73 % in DDDR + CAP pacing (p=n.s.) were free from symptomatic paroxysmal atrial fibrillation recurrences. During DDDR+CAP pacing, the atrial pacing percentage increased from 77+/-29 % to 96+/-7 % (p<0.0001). Automatic mode switch episodes/day were 0.73+/-1.09 in DDDR and 0.79+/-1.14 (p=n.s.) in DDDR+CAP. In patients with less than 50 % of atrial pacing during DDDR, automaticmode switch episodes/day decreased during DDDR+CAP from 1.13+/-1.59 to 0.23+/-0.32 (p<0.05) and in patients with less than 90 % from 1.23+/-1.27 to 0.75+/-1.10 (p<0.001). The number of premature atrial complexes per day decreased during DDDR + CAP from 2665+/-4468 to 556+/-704 (p<0.02). CONCLUSION: CAP algorithm allowed continuous overdrive atrial pacing without major side effects. Triggers of paroxysmal atrial fibrillation induction, such as premature atrial complexes, were critically decreased. Paroxysmal atrial fibrillation episodes were reduced in patients with atrial pacing percentage lower than 90 % during DDDR pacing.

Aged↗
PubMed2001

Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.

The aim of this work was to investigate the distribution of 5-methoxypsoralen in the skin after oral administration of the drug and to examine the correlation between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was measured in both healthy and psoriatic sites of 10 psoriatic patients after single and multiple oral doses. The results obtained show that 5-methoxypsoralen accumulates at higher levels in the more external layers of the skin after oral administration. The high affinity of drug for the stratum corneum was confirmed by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in the skin was similar in both psoriatic and healthy sites, indicating that the pathology does not influence drug distribution in the skin. After single dose administration, a linear correlation was found between skin and plasma drug concentration. After multiple dose administration, drug concentration in the skin was fairly constant despite the variable plasma concentrations in different subjects.

5-Methoxypsoralen↗
PubMed2001

The World Survey of Cardiac Pacing and Implantable Cardioverter Defibrillators: calendar year 1997--Europe.

The registry of the European Working Group on Cardiac Pacing (EWGCP) is based on the European Pacemaker Identification Card originally designed in July 1978. National registration centers collect the local data and send aggregated annual data to the EWGCP. For 1997, data were obtained from 2,887 hospitals in 20 European countries representing a population of 568 million. Across all participating countries, the median value for all implanted pacemakers was 378 per million population. For initial pacemaker implants, the median value was 290 per million population. Single chamber atrial pacing was important in Denmark, the Netherlands, Poland, Slovak Republic, Spain, and Sweden for the treatment of sick sinus syndrome. Dual chamber pacing accounted for < 50% of initial implants in only 5 of 14 countries for atrioventricular block, and in only 3 of 15 countries for sick sinus syndrome. In 7 of 15 countries, unipolar ventricular leads were used in > or = 50% of cases. In 6 of 14 countries, there was > 15% use of unipolar atrial leads. Nine of 13 countries frequently used atrial active-fixation leads. For the 1997 survey, ICD data were obtained from 16 countries. The total number of ICDs per million population was a median value of 14. Initial ICD implants per million population was 11. Only 3 of 16 countries implanted a total of 30 or more ICDs per million population. Pacing and ICD practices were dependent on the availability of medical and technical resources and influenced by economic constraints inherent in health care administration and insurance coverage patterns.

Aged↗
PubMed2001

Radiofrequency catheter ablation of idiopathic left ventricular outflow tract tachycardia: utility of intracardiac echocardiography.

INTRODUCTION: The site of origin of idiopathic ventricular tachycardia (VT) arising from the left ventricular outflow tract (LVOT) may be closely related to the aortic valve leaflets, and radiofrequency (RF) delivery potentially can damage them. Intracardiac echocardiography (ICE) can identify accurately the ablation electrode and anatomic landmarks, and contact with the endocardium can be easily assessed. The aim of this study was to define the utility and the accuracy of ICE in guiding RF ablation of idiopathic VT of the LVOT. METHODS AND RESULTS: Five consecutive patients (all men; mean age 20.4 years, range 16 to 25) symptomatic for idiopathic VT underwent RF ablation. A 9-French, in-sheath catheter with a 9-MHz ultrasound transducer was inserted through the femoral vein and positioned in the His-bundle region or right ventricular outflow tract to provide a clear view of the aortic root. Local earliest ventricular activation during tachycardia and pace mapping were used to identify the ablation site. Idiopathic VT was ablated successfully in all patients using a median of two RF pulses, delivered during tachycardia. High-resolution images of the aortic valve and ablation electrode were achievable in all cases. Direct vision of ablation electrode-endocardial contact in the outflow tract was assessed easily in all patients. CONCLUSION: Idiopathic VT of the LVOT can be treated successfully with RF ablation. ICE can accurately guide catheter ablation and identify anatomic landmarks, endocardial contact, and ablation electrode movement.

Adolescent↗
PubMed2001

Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart.

AIMS: To present and discuss a comprehensive and ready to use prediction model of risk of death after myocardial infarction based on the very recently concluded follow-up of the large GISSI-Prevenzione cohort and on the integrated evaluation of different categories of risk factors: those that are non-modifiable, and those related to lifestyles, co-morbidity, background, and other conventional clinical complications produced by the index myocardial infarction. METHODS: The 11-324 men and women recruited in the study within 3 months from their index myocardial infarction have been followed-up to 4 years. The following risk factors have been used in a Cox proportional hazards model: non-modifiable risk factors: age and sex; complications after myocardial infarction: indicators of left ventricular dysfunction (signs or symptoms of acute left ventricular failure during hospitalization, ejection fraction, NYHA class and extent of ventricular asynergy at echocardiography), indicators of electrical instability (number of premature ventricular beats per hour, sustained or repetitive arrhythmias during 24-h Holter monitoring), indicators of residual ischaemia (spontaneous angina pectoris after myocardial infarction, Canadian Angina Classification class, and exercise testing results); cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, systolic and diastolic blood pressure, blood total and HDL cholesterol, triglycerides, fibrinogen, leukocytes count, intermittent claudication, and heart rate. Multiple regression modelling was assessed by receiver operating characteristic (ROC) analysis. Generalizability of the models was assessed through cross validation and bootstrapping techniques. POPULATION AND RESULTS: During the 4 years of follow-up, a total of 1071 patients died. Age and left ventricular dysfunction were the most relevant predictors of death. Because of pharmacological treatments, total blood cholesterol, triglycerides, and blood pressure values were not significantly associated with prognosis. Sex-specific prediction equations were formulated to predict risk of death according to age, simple indicators of left ventricular dysfunction, electrical instability, and residual ischaemia along with the following cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, blood HDL cholesterol, fibrinogen, leukocyte count, intermittent claudication, and heart rate. The predictive models produced on the basis of information available in the routine conditions of clinical care after myocardial infarction provide ready to use and highly discriminant criteria to guide secondary prevention strategies. CONCLUSIONS AND IMPLICATIONS: Besides documenting what should be the preferred and practicable focus of clinical attention for today's patients, the experience of GISSI-Prevenzione suggests that periodically and prospectively collected databases on naturalistic' cohorts could be an important option for updating and verifying the impact of guidelines, which should incorporate the different components of the complex profile of cardiovascular risk. The GISSI Prevenzione risk function is a simple tool to predict risk of death and to improve clinical management of subjects with recent myocardial infarction. The use of predictive risk algorithms can favour the shift from medical logic, based on the treatment of single risk factors, to one centred on the patient as a whole as well as the tailoring of medical interventions according to patients' overall risk.

Adult↗
PubMed2001

Immediate and long-term atrial sensing stability in single-lead VDD pacing depends on right atrial dimensions.

AIMS: Single-pass VDD is a physiological stimulation mode which requires a single-lead with a floating dipole to detect the atrial signal. We investigated the impact of right heart dimensions on immediate and long-term atrial sensing stability in VDD systems to draw guidelines for optimal atrial sensitivity programming. METHODS: Forty-one patients (23 males, mean age 73 +/- 11 years) with II or III degree AV block and normal sinus node function received a Thera VDD Medtronic 8948 pulse generator with Medtronic 5032 lead. Atrial sensing was evaluated at pre-discharge and during 12-months follow-up in the supine and upright positions, during normal and forced breathing. Atrial sensing variability, quantified by a D value (mV), which represents the difference between the maximum and the minimum atrial electrogram amplitude obtained during the various activities, was analyzed and related to right heart dimensions measured at echocardiography. RESULTS: Long-term appropriate atrial sensing was obtained in 40/41 patients. P wave mean amplitude at pre-discharge, during every specific activity, was predictive of 12-month values. No atrial oversensing was observed. According to the right atrial dimension (RAD), patients with RAD > 38 mm had a sensing variability significantly higher than those with RAD < or = 34 mm (D=1 + 1 Vs D=0.4+/-0.5; P<0.05). A linear relationship between D and RAD dimensions was observed (r=0.47; P<0.005). According to the distance from the roof of the right atrium to the right ventricular apex (RAVD), patients with RAVD < 93 mm had D=1.1 +/- 1, while patients with RAVD > 93 mm had D=0.5 +/- 0.4; P<0.05); a inverse correlation between RAVD and D was highlighted (r=-0.43; P<0.01). Using a cluster analysis, the combination of RAD and RAVD identified a subgroup (RAD > 30 mm and RAVD < 80 mm) at high risk of loss of AV synchrony with 67% sensitivity and 80% specificity. Nevertheless, apart from heart dimensions, no patient showed an atrial signal amplitude lower than 0.3 mV. CONCLUSIONS: According to our data, in VDD single-lead systems the amplitude of the atrial signal is stable over time in every physical activity. High RAD and low RAVD values may select patients with poor atrial sensing stability. Anyway, taking into account that no atrial oversensing was observed, atrial sensitivity setting at the highest value should be recommended.

Aged↗
PubMed2001

Doppler myocardial imaging in patients with heart failure receiving biventricular pacing treatment.

BACKGROUND: In patients with heart failure, biventricular pacing (BIV) improves left ventricular (LV) performance by counteracting LV unsynchronized contraction caused by the presence of left bundle branch block (LBBB). However, no data are yet available on regional long-axis function in patients with LBBB or on BIV effectiveness in improving such a function in patients with heart failure and LBBB. METHODS AND RESULTS: We studied with standard 2D echocardiography and tissue Doppler imaging (TDI) 21 nonischemic patients in New York Heart Association (NYHA) class III-IV, with LBBB and QRS >/=120 ms, receiving BIV. To assess long-axis function, TDI qualitative analysis at the basal level of each LV wall was performed in M-mode color and pulsed wave Doppler modalities before and after BIV. By analysis of the interventricular septum, the inferior, posterior, lateral, and anterior walls, of 105 basal segments, the following electromechanical patterns were identified: normal (pattern I), mildly unsynchronized (pattern IIA), severely unsynchronized (pattern IIB), reversed early in systole (pattern IIIA), reversed late in systole (pattern IIIB), and reversed throughout all the systole (pattern IV). After BIV, (1) 49 (46.7%) of 105 segments showed unsynchronized contraction of the same degree as before; (2) 36 (34.3%) of 105 and 20 (19%) of 105 showed unsynchronized contraction of lesser and greater degree, respectively, than before; and (3) a preexcitation pattern was found in 11 (10.5%) of 105, but no segment with pattern IV was observed. According to TDI analysis, patients were divided into group 1 (10 of 21), with less severe LV asynchrony than before BIV, and group 2 (11 of 21), with no change or more severe LV asynchrony than before BIV. In group 1, (1) the LV ejection fraction increased significantly (P =.01); (2) the exercise tolerance, expressed as time and work capacity on the bicycle stress testing, increased significantly (P =.01, P =.003, respectively); (3) the 6-minute walked distance increased significantly (P =.01); and (4) the NYHA class decreased significantly (P =.003). In group 2, no significant differences were found either in LV ejection fraction, in NYHA class, or in exercise tolerance data (P = not significant for all). Conversely, the QRS narrowing was significant in both groups (P =.003 in group 1 and P =.01 in group 2). CONCLUSIONS: TDI is useful in assessing the severity of LV asynchrony in patients with LBBB with heart failure as well as in evaluating the pacing effects on long-axis function in these patients. BIV reduced unsynchronized and/or dyskinetic contraction in at least one third of the LV basal segments, whereas it induced preexcitation in approximately 10%. Such changes were responsible for better LV synchrony in approximately one half of patients. After BIV, LV performance improved significantly in patients with better LV synchrony evaluated by TDI, whereas the QRS narrowing was not predictive of this functional improvement.

Bundle-Branch Block↗
PubMed2001

Randomized crossover comparison of right atrial appendage pacing versus interatrial septum pacing for prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia.

BACKGROUND: New atrial pacing techniques and overdrive pacing algorithms have been introduced to prevent atrial fibrillation. This study was designed to test the hypotheses that (1) interatrial septum pacing (IASP) at the triangle of Koch would be more effective than right atrial appendage pacing (RAAP) in preventing paroxysmal atrial fibrillation (PAF) in patients with sinus bradycardia and (2) an algorithm (CAP) designed to achieve constant atrial capture would increase the efficacy of rate-responsive atrial pacing. METHODS: We studied 46 patients with PAF and sinus bradycardia implanted with a DDD(R) (Medtronic Thera) pacemaker. Twenty-four patients (6.0 +/- 10.1 PAF episodes/month within 3 months before study) were randomized to RAAP and 22 patients (5.4 +/- 7.1, not significant) to IASP. Within each arm 2 randomized crossover periods of CAP-OFF and CAP-ON function were programed. RESULTS: The PAF episodes per month significantly decreased in the RAAP (CAP-OFF: 2.1 +/- 4.2, P <.05; CAP-ON: 1.9 +/- 3.8, P <.05) and in the IASP group (CAP-OFF: 0.2 +/- 0.5, P <.05; CAP-ON: 0.2 +/- 0.5, P <.05). Values were significantly lower in the IASP group than in the RAAP group in both CAP-OFF (0.2 +/- 0.5 vs 2.1 +/- 4.2, P <.05) and CAP-ON (0.2 +/- 0.5 vs 1.9 +/- 3.8, P <.05) conditions. PAF burden was significantly lower in the IASP than in the RAAP group in CAP-OFF (47 +/- 84 min/d vs 140 +/- 217, P <.05) and in CAP-ON (41 +/- 72 vs 193 +/- 266, P <.05) conditions. No differences were observed within each arm in PAF burden between the 2 crossover CAP programing periods. CONCLUSIONS: Rate-adaptive IASP at the triangle of Koch is more effective than RAAP in preventing PAF in patients with sinus bradycardia. In our sample of patients no additional clinical benefit is furnished by the CAP algorithm.

Aged↗