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M Gasparini

Publications and source records attributed to M Gasparini.

At least 37 records · Page 2Linked to original sources
PubMed2000

A curve-free method for phase I clinical trials.

Consider the problem of finding the dose that is as high as possible subject to having a controlled rate of toxicity. The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity. The continual reassessment method (CRM) is an improvement over traditional up-and-down schemes for estimating the MTD. It is based on a Bayesian approach and on the assumption that the dose-toxicity relationship follows a specific response curve, e.g., the logistic or power curve. The purpose of this paper is to illustrate how the assumption of a specific curve used in the CRM is not necessary and can actually hinder the efficient use of prior inputs. An alternative curve-free method in which the probabilities of toxicity are modeled directly as an unknown multidimensional parameter is presented. To that purpose, a product-of-beta prior (PBP) is introduced and shown to bring about logical improvements. Practical improvements are illustrated by simulation results.

Bayes Theorem↗
PubMed2000

Inferior vena cava loop of the implantable cardioverter defibrillator endocardial lead: a possible solution of the growth problem in pediatric implantation.

The ICD is an important treatment option in adults and children with life-threatening tachyarrhythmias. The possibility of lead displacement caused by growth and the lack of dedicated leads and devices poses special problems in pediatric ICD implantation. We describe our experience in three children in whom we left a redundant lead loop within the inferior vena cava (IVC) is allow for further growth. Since February 1998, three children underwent ICD implantation at our institution. A lead (screw-in) was advanced into the right ventricular apex, and a loop was created in the IVC by progressively withdrawing the stylet and pushing in the lead. Satisfactory sensing and pacing threshold values were obtained and a successful single 16-J defibrillation test was performed. No complications were encountered. After a mean follow-up of 16 months, with a mean increase in body weight and height of 4.1 +/- 0.5 Kg and 6.3 +/- 0.4 cm, respectively, chest X ray showed some release of additional lead length, in the absence of dislodgments, while significant changes in pacing/sensing parameters were not found. In conclusion, the creation of a loop within the IVC allows the lead to adjust for growth in children receiving an ICD. This approach is feasible and safe.

Child↗
PubMed2000

Noncontact system-guided simplified right atrial linear lesions using radiofrequency transcatheter ablation for treatment of refractory atrial fibrillation.

This article describes our experience with a staged "hybrid" approach to the treatment of drug resistant AF, in which the completeness of a single linear lesion in the RA was verified with a noncontact mapping system. Inferior vena cava-tricuspid annulus ablation was performed and followed by the creation of a single intercaval lesion. The study population consisted of 24 patients with a 3.4 +/- 1.6-year history of drug resistant, severely symptomatic, lone paroxysmal (n = 19), or persistent (n = 5) AF. During a follow-up of 8 +/- 2.6 months, 12 (50%) patients remained asymptomatic and 6 (25%) had a significant decrease in AF episodes, while the arrhythmia was unchanged in 5 (21%) patients and aggravated in 1 (4%) patient. Overall, a favorable clinical result was achieved in 18 (75%) patients.

Anti-Arrhythmia Agents↗
PubMed2000

Long-term follow-up after atrioventricular nodal ablation and pacing: low incidence of sudden cardiac death.

Sudden cardiac death (SCD) has been reported in patients with drug refractory AF who underwent AV nodal ablation and pacing. However, whether SCD in these patients is related to the underlying heart disease or to the ablating and pacing procedure remains uncertain. Between May 1987 and January 1997, AV nodal ablation was performed in 585 patients (mean age 66 +/- 11 years) with drug-resistant, paroxysmal (n = 308) or chronic (n = 277) AF in 12 Italian centers. Lone AF was present in 133 patients. After AV junction ablation, patients underwent VVIR (454 patients) or DDDR (131 patients) pacemaker implantation. At a follow-up of 33.6 +/- 24.2 months, 80 (13.7%) deaths were recorded: 40 noncardiac, 23 nonsudden, and 17 sudden cardiac death (3%, 1.04% per year). Among five variables, including age. NYHA functional class, presence of heart disease, paroxysmal or chronic AF, previous embolic events, and LVEF, the presence of heart disease (P = 0.007) and a LVEF < 0.45, (P = 0.003) were associated with a higher risk of SCD. Analysis of SCD-free survival by log-rank test showed a higher incidence of SCD in patients with LVEF < 0.45 (P = 0.0001) and with coronary artery disease (P = 0.005). In this large cohort, a low incidence of long-term SCD after AV nodal ablation and pacing for drug-refractory AF was observed. The presence of underlying heart disease and the extent of baseline LV dysfunction were associated with an increased likelihood of SCD.

Aged↗
PubMed1999

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↗
PubMed1999

Linguistic impairment after right cerebellar stroke: a case report.

Increasing evidence suggests the involvement of the cerebellum in non-motor functions. We describe a patient who presented speech deficits after a right cerebellar infarction without other cognitive impairments. 99mTc-HMPAO single-photon emission computed tomography showed a marked hypoperfusion in the right cerebellar hemisphere, but did not show crossed cerebellar- cerebral diaschisis. The absence of neuroradiological evidence of structural supratentorial lesions supports the cerebellar role in modulating not only the motor system, but also higher order functions.

Cerebellum↗
PubMed1999

Prospective, randomized study of atrioventricular ablation and mode-switching, dual chamber pacemaker implantation versus medical therapy in drug-resistant paroxysmal atrial fibrillation. The PAF study. Paroxysmal Atrial Fibrillation.

We performed a prospective randomized 6-month evaluation of the clinical effects of atrioventricular junctional ablation together with placement of a DDDR mode-switching pacemaker vs pharmacological treatment in 43 patients with intolerable paroxysmal atrial fibrillation not controlled with antiarrhythmic drugs. Ablation and pacemaker treatment were highly effective and superior to drug therapy in controlling symptoms and improving quality of life. However, discontinuation of drug therapy exposed patients to further recurrences of paroxysmal atrial fibrillation and the risk of developing permanent atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed1999

Indium-111 pentetreotide lung uptake in infectious lung disease.

Bilateral diffuse lung uptake of In-111 pentetreotide (OCT) was observed during a whole-body scan performed in a 68-year-old woman with Cushing's syndrome and suspected ectopic adrenocorticotropic hormone secretion. A few days later, she was found to have bilateral bacterial pneumonia (of mixed anaerobic origin). Cushing's syndrome was finally proved to be of pituitary origin. The OCT lung uptake in pneumonia probably resulted from tracer binding by somatostatin receptors on the inflammatory leukocytes. Although the rapid wash-out from experimentally induced abscesses does not make OCT a suitable tracer for detecting acute infections, the images and data here reported suggest that infectious lung disease should be excluded before diagnosing lung involvement by neuroendocrine tumors.

ACTH Syndrome, Ectopic↗
PubMed1999

Congestive heart failure induced by recipient atrial tachycardia conducted to the donor atrium after orthotopic heart transplantation: complete regression after successful radiofrequency ablation.

We describe the case of a 30-year-old female patient who developed an interatrial tachycardia from the recipient to the donor atrium associated with signs of congestive heart failure 5 years after orthotopic heart transplantation. The patient underwent catheter mapping followed by successful radiofrequency (RF) ablation at the site of the presumed electrical connection between the recipient and the donor atria, through the interatrial surgical suture line, with stable recovery of sinus rhythm and disappearance of signs of left ventricular dysfunction. RF catheter ablation is confirmed to be feasible and safe in the treatment of heart transplant patients even in the presence of rare forms of arrhythmias, thus offering a cure for tachycardia to these patients.

Adult↗
PubMed1999

Thromboembolism after atrioventricular node ablation and pacing: long term follow up.

OBJECTIVE: To assess the incidence of arterial embolic events in patients with high rate, drug resistant, severely symptomatic paroxysmal and chronic atrial fibrillation who have undergone atrioventricular (AV) node ablation and permanent pacing. DESIGN: Multicentre retrospective cohort study. PATIENTS AND MANAGEMENT: From May 1987 to January 1997, AV node ablation was performed in 585 severely symptomatic patients (mean (SD) age 66 (11) years) with high rate, drug resistant paroxysmal atrial fibrillation (308) or chronic atrial fibrillation (277). Lone atrial fibrillation was present in 133 patients, while the remaining 452 suffered from dilated, ischaemic, or valvar heart disease. Patients underwent VVIR (454) or DDDR (131) pacemaker implantation, after AV node ablation. Antiplatelet agents were given to 202 patients, warfarin to 187 patients. RESULTS: During a follow up of 33.6 (24.2) months, thromboembolic events were observed in 17 patients (3%); the actuarial occurrence rates of thromboembolism were 1.1%, 3%, 4.2%, and 7.4% after one, three, five, and seven years, respectively. Among five variables, univariate analysis showed that only the presence of chronic atrial fibrillation at the time of ablation (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.02 to 3. 20, p = 0.04) and the need for warfarin treatment (RR = 1.6, 95% CI 1.00 to 2.71, p = 0.048) were associated with a significantly higher risk of occurrence of thromboembolic events. On multivariate analysis the only predictor of embolic events during the follow up was the presence of chronic atrial fibrillation. CONCLUSIONS: Data from this large cohort of patients indicate a fairly low incidence (1.04% per year) of thromboembolic events after AV node ablation and pacing for drug refractory, high rate atrial fibrillation.

Aged↗
PubMed1998

Gallium-67 scintigraphy evaluation of therapy in non-Hodgkin's lymphoma.

UNLABELLED: Patients with diffuse large cell lymphoma may achieve complete remission (CR) after chemotherapy, and the time to reach CR may be predictive of treatment outcome. Partial remission, or recurrence from CR, is associated with poor survival. Gallium-67 imaging has proven to be useful in evaluating lymphoma patients. In tumor models, this radiotracer is an indicator of tumor viability. Gallium-67 uptake is seen only in avid and viable lymphoma tissue, not in fibrotic or necrotic tissue. In this study, we prospectively assessed the ability of this radiotracer to define residual disease. In addition, we evaluated the possibility of predicting the clinical outcome in patients with diffuse cell lymphoma on the basis of scan positivity during chemotherapy. METHODS: Thirty-three consecutive patients with histologically proven diffuse large cell lymphoma were investigated with 67Ga scintigraphy 48-72 hr after injection of 185-259 MBq 67Ga-citrate for staging and during follow-up after four to six cycles of intensive chemotherapy. Patients were monitored for a mean of 56.0 mo (range 7-90 mo), and they were restaged using physical examination, CT and all necessary imaging modalities. RESULTS: Patients were divided into two groups according to the positivity or negativity of 67Ga scan after four to six cycles of chemotherapy. Of the 33 patients studied, 14 (42.4%) showed persistent abnormal uptake of 67Ga-citrate after four to six cycles of chemotherapy. In this group, 9 patients (64.2%) died of lymphoma at a mean of 24.3 mo from presentation with the diagnosis (range 7-71 mo). Four patients had no evidence of disease at an average of 71.7 mo after diagnosis, and 1 patient was considered to be in partial remission. In the second group of 19 67Ga-negative patients, after four to six cycles of chemotherapy, 4 died and 15 are alive and considered to be in CR. A statistical analysis of the association between 67Ga scan results after four to six cycles of chemotherapy and survival was performed using the log-rank test; there was a statistically significant association between scan results and survival (p=0.00125). CONCLUSION: We conclude that 67Ga scintigraphy is an excellent predictor of residual tumor viability in lymphoma patients and that persistent positivity of the scan predicts poor outcome and may justify a change in treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation: a randomized controlled study.

BACKGROUND: The purpose of the study was to evaluate the effect of AV junction ablation and pacemaker implantation on quality of life and specific symptoms in patients with paroxysmal atrial fibrillation (AF) not controlled by drugs. METHODS AND RESULTS: We performed a multicenter, randomized, 6-month evaluation of the clinical effects of AV junction ablation and DDDR mode-switching pacemaker (Abl+Pm) versus pharmacological treatment in 43 patients with intolerable, recurrent paroxysmal AF of three or more episodes in the previous 6 months not controlled with three or more antiarrhythmic drugs. Before completion of the study, 3 patients in the drug group withdrew because of the severity of their symptoms and 1 patient assigned to the Abl+Pm group in whom the ablation procedure failed. At the end of the 6 months, the 21 patients of the Abl+Pm group who completed the study showed, in comparison with the 18 of the drug group, lower scores in the Living with Heart Failure Questionnaire (-51%, P=.0006), palpitations (-71%, P=.0000), effort dyspnea (-36%, P=.04), exercise intolerance score (-46%, P=.001), and easy fatigue (-51%, P=.02). The scores for rest dyspnea, chest discomfort, and NYHA functional classification were also lower (-56%, -50%, and -17%, respectively) in the Abl+Pm group, although not significantly. At the end of the study, palpitations were no longer present in 81% of the Abl+Pm group and in 11% of the drug group (P=.0000). AF was documented in 31 of 122 visits (25%) in the Abl+Pm group and in 9 of 107 examinations (8%) in the drug group (P=.0005); chronic AF developed in 5 (24%) and 0 (0%) in the two groups, respectively (P=.04). CONCLUSIONS: In patients with paroxysmal AF not controlled by pharmacological therapy, Abl+Pm treatment is highly effective and superior to drug therapy in controlling symptoms and improving quality of life. The discontinuation of drug therapy exposes patients to further recurrences of paroxysmal AF and the risk of developing permanent AF.

Aged↗
PubMed1997

Cognitive improvement during Tolcapone treatment in Parkinson's disease.

The aim of this study was to evaluate the effects of Tolcapone, a reversible, selective inhibitor of catechol-O-methyltransferase, on the cognitive function of eight patients with advanced Parkinson's disease. They underwent neuropsychological and motor assessment at baseline and were re-evaluated after 6 months. During this period, they received Tolcapone three times daily, while the L-dopa dosage was progressively reduced. Significant improvements were observed in the attentional task, auditory verbal short-term memory, visuo-spatial recall, constructional praxia and motor symptoms. These data suggest that treatment with Tolcapone, in combination with L-dopa therapy, may determine a significant improvement in cognitive resources of patients with advanced Parkinson's disease.

Aged↗
PubMed1997

Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects.

OBJECTIVE: Pharmacokinetics, pharmacodynamic effects and tolerability of 200 mg valsartan, once-daily for 8 days, were investigated in 16 healthy, normotensive volunteers on a normal sodium diet. METHODS: This was a double-blind, placebo-controlled, randomized crossover study. Drug concentrations in plasma and urine, angiotensin II (Ang II) concentrations in plasma, systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) in the supine position and 3 min after passive head-up tilting, as well as safety parameters (ECG, clinical chemistry and hematology, renal water and electrolyte excretion) were measured over 24 h after the first dose (day 1) and at steady state on day 8. RESULTS: Absorption and distribution of valsartan were rapid (Cmax, 2 h; t1/2 lambda 1 < 1 h), followed by a slower terminal elimination phase (t1/2 lambda 2, 6 h) on days 1 and 8, with little accumulation in plasma (increase of 20% on day 8). Less than 10% of the dose was excreted unchanged in urine. The increase in plasma Ang II (Cmax, 6 h) was significantly enhanced at steady state. Supine SBP and DBP significantly decreased on day 8 only, by an average of -3.6 and -2.4 mmHg, respectively, versus placebo, without a concomitant increase in HR. Upon passive tilting, the increase in DBP, normally reinforced by sympathetic renin release, was slightly but significantly blunted on day 1 (-2.0 mmHg) and day 8 (-4.0 mmHg) of treatment with valsartan versus placebo. The orthostatic reflex increase in HR was slightly enhanced compared with placebo by an average of 2.8 beats min-1 on day 1 and by 2.9 beats.min-1 on day 8. Valsartan was well tolerated and had no influence on ECG, clinical laboratory parameters, and water, electrolyte and uric acid excretion. CONCLUSIONS: Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200 mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT1 blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200 mg per day in healthy normotensive volunteers.

Adult↗
PubMed1997

Comparison of gallium scan, computed tomography, and magnetic resonance in patients with mediastinal Hodgkin's disease.

BACKGROUND: In patients with Hodgkin's disease, the use of gallium-67 scintigraphy (Ga-67) compared to conventional staging and restaging techniques is still controversial. In particular, in a combined modality treatment with chemotherapy and radiotherapy given in sequence, its role in detecting active disease after chemotherapy may be useful in planning the subsequent radiotherapeutic strategy. PATIENTS AND METHODS: From March 1990 to September 1994, 125 patients with previously untreated histologically proven Hodgkin's disease were enrolled in two different prospective trials according to clinical stage. Staging procedures included Ga-67, chest-abdominal computed tomography (CT), and/or magnetic resonance (MR). All three tests were performed in 53 patients at staging and in 47 at restaging. Results of Ga-67 at staging were compared to conventional procedures or pathological findings. Results of Ga-67, CT scan, and MR at restaging were compared to disease outcome during the follow-up. Finally a cost/benefit ratio for each test was determined. RESULTS: At staging, Ga-67 showed lower sensitivity than CT and MR (90 vs. 96 and 100%, respectively) because of the number of false-negative images. Nevertheless, by using both CT and Ga-67 scan, the sensitivity is equal to that observed with MR (100%). At restaging, Ga-67 is superior to CT scan and equivalent to MR in detecting true negative patients (specificity: 98% vs. 45% vs. 92%). CONCLUSIONS: As a single technique, Ga-67 scan cannot substitute for CT scan or MR in staging patients with Hodgkin's disease. Nevertheless, Ga-67 scan has an important role in defining complete remission after treatment and therefore in planning subsequent treatment. Considering the lower costs of CT scan plus Ga-67 ($320) versus MR alone ($810), the two tests may be considered procedures of choice in staging as well as in restaging patients with Hodgkin's disease.

Adult↗
PubMed1996

Clinical role of technetium-99m sestamibi single-photon emission tomography in evaluating pretreated patients with brain tumours.

One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with 99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.

Adolescent↗
PubMed1996

Attentional functions in multiple system atrophy and Parkinson's disease.

OBJECTIVE: To assess cognitive performances of patients with striatonigral degeneration type multiple system atrophy compared with those of patients with Parkinson's disease. METHODS: The cognitive performances of a group of patients with multiple system atrophy of the striatonigral type were compared with those of matched patients with Parkinson's disease and controls, using tests sensitive to frontal lobe dysfunction. RESULTS: The multiple system atrophy group, when compared with the Parkinson's disease group, showed significant deficits in attention tasks, particularly in the Stroop test. CONCLUSION: There was a consistently greater impairment in attention resources in patients with multiple system atrophy than in patients with Parkinson's disease.

Aged↗